Do I Have Anger Issues?

How to Identify and Treat

an Angry Outlook
 Causes

 Symptoms

 Types

 Diagnosis

 Treatment

 Summary

Anger issues definition

Anger is a natural, instinctive response to threats. Some anger is necessary for our
survival.

Anger becomes a problem when you have trouble controlling it, causing you to say
or do things you regret.

A 2010 study Trusted Source found that uncontrolled anger is bad for your
physical and emotional health. It can also quickly escalate to verbal or physical
violence, harming you and those around you.

Learn more about identifying your triggers and managing your anger below.
What causes anger issues?
Many things can trigger anger, including stress, family problems, and financial
issues.

For some people, anger is caused by an underlying disorder, such

as alcoholism or depression. Anger itself isn’t considered a disorder, but anger is a
known symptom of several mental health conditions.

The following are some of the possible causes of anger issues.

Depression

Anger can be a symptom of depression, which is characterized as ongoing feelings

of sadness and loss of interest lasting at least two weeks.

Anger can be suppressed or overtly expressed. The intensity of the anger and how
it’s expressed varies from person to person.

If you have depression, you may experience other symptoms. These include:

 irritability

 loss of energy

 feelings of hopelessness

 thoughts of self-harm or suicide

Obsessive compulsive disorder

Obsessive compulsive disorder (OCD) is an anxiety disorder that’s characterized

by obsessive thoughts and compulsive behaviour. A person with OCD has
unwanted, disturbing thoughts, urges, or images that drive them to do something
repetitively.

For example, they may perform certain rituals, such as counting to a number or
repeating a word or phrase, because of an irrational belief that something bad will
happen if they don’t.

A 2011 study Trusted Source found that anger is a common symptom of OCD. It

affects approximately half of people with OCD.

Anger may result from frustration with your inability to prevent obsessive thoughts
and compulsive behaviours, or from having someone or something interfere with
your ability to carry out a ritual.

Alcohol abuse

Research shows that drinking alcohol increases aggression. Alcohol is a

contributing factor in approximately half of all violent crimes committed in the
United States.

Alcohol abuse, or alcoholism, refers to consuming too much alcohol at once or

regularly.
Alcohol impairs your ability to think clearly and make rational decisions. It affects
your impulse control and can make it harder for you to control your emotions.

Attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder

marked by symptoms such as inattention, hyperactivity, and or impulsivity.

Symptoms usually start in early childhood and continue throughout a person’s life.
Some people are not diagnosed until adulthood, which is sometimes referred to
as adult ADHD.

Anger and short temper can also occur in people of all ages with ADHD. Other
symptoms include:

 restlessness

 problems focusing

 poor time management or planning skills

Oppositional defiant disorder

Oppositional defiant disorder (ODD) is a behavioural disorder that affects 1 to 16

percent of school-age children. Common symptoms of ODD include:

 anger

 hot temper

 irritability
Children with ODD are often easily annoyed by others. They may be defiant and
argumentative.

Bipolar disorder

Bipolar disorder is a brain disorder that causes dramatic shifts in your mood.

These intense mood shifts can range from mania to depression, although not
everyone with bipolar disorder will experience depression. Many people with
bipolar disorder may experience periods of anger, irritability, and rage.

During a manic episode, you may:

 be easily agitated

 feel euphoric

 have racing thoughts

 engage in impulsive or reckless behaviour

During a depressive episode, you may:

 feel sad, hopeless, or tearful

 lose interest in things once enjoyed

 have thoughts of suicide

Intermittent explosive disorder

A person with intermittent explosive disorder (IED) has repeated episodes of
aggressive, impulsive, or violent behaviour. They may overreact to situations with
angry outbursts that are out of proportion to the situation.

Episodes last less than 30 minutes and come on without warning. People with the
disorder may feel irritable and angry most of the time.

Some common behaviours include:

 temper tantrums

 arguments

 fighting

 physical violence

 throwing things

People with IED may feel remorseful or embarrassed after an episode.

Grief

Anger is one of the stages of grief. Grief can come from the death of a loved one, a
divorce or breakup, or from losing a job. The anger may be directed at the person
who died, anyone else involved in the event, or inanimate objects.

Other symptoms of grief include:

 shock

 numbness
  guilt

 sadness

 loneliness

 fear

Anger issues symptoms

Anger causes physical and emotional symptoms. While it’s normal to experience
these symptoms on occasion, a person with anger issues tends to experience them
more often and to a more severe degree.

Physical symptoms

Anger affects different parts of your body, including your heart, brain, and
muscles. A 2011 study found that anger also causes an increase
in testosterone levels and decrease in cortisol levels.

The physical signs and symptoms of anger include:

 increased blood pressure

 increased heart rate

 tingling sensation

 muscle tension

Emotional
There are several emotions that go hand in hand with anger. You may notice the
following emotional symptoms before, during, or after an episode of anger:

 irritability

 frustration

 anxiety

 rage

 stress

 feeling overwhelmed

 guilt

Anger issues types

Anger can manifest itself in several different ways. Not all anger is expressed in
the same way. Anger and aggression can be outward, inward, or passive.

 Outward. This involves expressing your anger and aggression in an obvious

way. This can include behaviour such as shouting, cursing, throwing or
breaking things, or being verbally or physically abusive toward others.

 Inward. This type of anger is directed at yourself. It involves negative self-

talk, denying yourself things that make you happy or even basic needs, such
as food. Self-harm and isolating yourself from people are other ways anger
can be directed inward.

 Passive. This involves using subtle and indirect ways to express your anger.
Examples of this passive aggressive behaviour include giving someone the
silent treatment, sulking, being sarcastic, and making snide remarks.

Do I have anger issues?

You may have anger issues if:

 you feel angry often

 you feel that your anger seems out of control

 your anger is impacting your relationships

 your anger is hurting others

 your anger causes you to say or do things you regret

 you’re verbally or physically abusive

Anger issues management

If you believe your anger is out of control or if it’s negatively affecting your life or
relationships, consider seeking help from a mental health professional.

A mental health professional can help determine if you have an underlying mental
health condition that’s causing your anger issues and requires treatment.

Anger management can also include one or more of the following:

 relaxation techniques

 behavioural therapy

 depression, anxiety, or ADHD medications, if you’re diagnosed with any of

these conditions

 anger management classes, which can be taken in person, by phone, or

online

 anger management exercises at home

  support groups

About HIV & AIDS

1. What Are HIV and AIDS?
2. How Is HIV Transmitted?
3. Who Is at Risk for HIV?
4. Symptoms of HIV
What Is HIV?
HIV (human immunodeficiency virus) is a virus that attacks cells that help the body
fight infection, making a person more vulnerable to other infections and diseases. It is
spread by contact with certain bodily fluids of a person with HIV, most commonly
during unprotected sex (sex without a condom or HIV medicine to prevent or treat
HIV), or through sharing injection drug equipment.

If left untreated, HIV can lead to the disease AIDS (acquired immunodeficiency
syndrome).

The human body can’t get rid of HIV and no effective HIV cure exists. So, once you
have HIV, you have it for life.

However, by taking HIV medicine (called antiretroviral therapy or ART), people with
HIV can live long and healthy lives and prevent transmitting HIV to their sexual
partners. In addition, there are effective methods to prevent getting HIV through sex
or drug use, including pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis
(PEP).

First identified in 1981, HIV is the cause of one of humanity’s deadliest and most
persistent epidemics.

What Is AIDS?
AIDS is the late stage of HIV infection that occurs when the body’s immune system is
badly damaged because of the virus.

In the U.S., most people with HIV do not develop AIDS because taking HIV medicine
every day as prescribed stops the progression of the disease.

A person with HIV is considered to have progressed to AIDS when:

 the number of their CD4 cells falls below 200 cells per cubic millimetres of
blood (200 cells/mm3). (In someone with a healthy immune system, CD4
counts are between 500 and 1,600 cells/mm3.) OR
 they develop one or more opportunistic infections regardless of their CD4
count.
Without HIV medicine, people with AIDS typically survive about 3 years. Once
someone has a dangerous opportunistic illness, life expectancy without treatment falls
to about 1 year. HIV medicine can still help people at this stage of HIV infection, and
it can even be lifesaving. But people who start ART soon after they get HIV
experience more benefits—that’s why HIV testing is so important.

How Do I Know If I Have HIV?

The only way to know for sure if you have HIV is to get tested. Testing is
relatively simple. You can ask your health care provider for an HIV test. Many
medical clinics, substance abuse programs, community health centres, and hospitals
offer them too. You can also buy a home testing kit at a pharmacy or online.

To find an HIV testing location near you, use the HIV Services Locator.

HIV self-testing is also an option. Self-testing allows people to take an HIV test and
find out their result in their own home or other private location. You can buy a self-
test kit at a pharmacy or online. Some health departments or community-based
organizations also provide self-test kits for free.

Read the U.S. Food and Drug Administration’s (FDA) fact sheet on the OraQuick In-
Home HIV Test, the only FDA-approved in-home HIV test.
INFORMATION: The coronavirus (COVID-19) pandemic has made it more difficult for some people
to access traditional places where HIV testing is provided. Self-testing allows people to get tested for HIV
while still following stay-at-home orders and social distancing practices. Ask your local health department
or HIV service organization if they offer self-testing kits.

How Do You Get or Transmit HIV?

You can only get HIV by coming into direct contact with certain body fluids from a
person with HIV who has a detectable viral load. These fluids are:

 Blood
 Semen (cum) and pre-seminal fluid
 Rectal fluids
 Vaginal fluids
 Breast milk
For transmission to occur, the HIV in these fluids must get into the bloodstream of an
HIV-negative person through a mucous membrane (found in the rectum, vagina,
mouth, or tip of the penis); open cuts or sores; or by direct injection.

People with HIV who take HIV medicine daily as prescribed and get and keep an
undetectable viral load have effectively no risk of sexually transmitting HIV to their
HIV-negative partners.
How Is HIV Spread from Person to Person?
HIV can only be spread through specific activities. In the United States, the most
common ways are:

 Having vaginal or anal sex with someone who has HIV without using a
condom or taking medicines to prevent or treat HIV. Anal sex is riskier than
vaginal sex.
 Sharing injection drug equipment (“works”), such as needles, with
someone who has HIV.
Less common ways are:

 From mother to child during pregnancy, birth, or breastfeeding. However,

the use of HIV medicines and other strategies have helped lower the risk of
mother-to-child transmission of HIV to 1% or less in the United States.
 Getting stuck with an HIV-contaminated needle or other sharp object. This
is a risk mainly for health care workers. The risk is very low.
HIV is spread only in extremely rare cases by:

 Having oral sex. But in general, the chance that an HIV-negative person will
get HIV from oral sex with an HIV-positive partner is extremely low.
 Receiving blood transfusions, blood products, or organ/tissue transplants
that are contaminated with HIV. The risk is extremely small these days
because of rigorous testing of the U.S. blood supply and donated organs and
tissues.
 Being bitten by a person with HIV. Each of the very small number of
documented cases has involved severe trauma with extensive tissue damage
and the presence of blood. There is no risk of transmission if the skin is not
broken.
 Contact between broken skin, wounds, or mucous membranes and HIV-
infected blood or blood-contaminated body fluids.
 Deep, open-mouth kissing if both partners have sores or bleeding gums
and blood from the HIV-positive partner gets into the bloodstream of the
HIV-negative partner. HIV is not spread through saliva.
 Eating food that has been pre-chewed by a person with HIV. The
contamination occurs when infected blood from a caregiver’s mouth mixes
with food while chewing. The only known cases are among infants.
Does HIV Viral Load Affect Getting or
Transmitting HIV?
Yes. Viral load is the amount of HIV in the blood of someone who has HIV. Taking
HIV medicine (called antiretroviral therapy or ART) daily as prescribed can make the
viral load very low—so low that a test can’t detect it (this is called an undetectable
viral load).

People with HIV who take HIV medicine daily as prescribed and get and keep an
undetectable viral load have effectively no risk of transmitting HIV to an HIV-
negative partner through sex.

HIV medicine is a powerful tool for preventing sexual transmission of HIV. But it
works only as long as the HIV-positive partner gets and keeps an undetectable viral
load. Not everyone taking HIV medicine has an undetectable viral load. To stay
undetectable, people with HIV must take HIV medicine every day as prescribed and
visit their healthcare provider regularly to get a viral load test. Learn more.

Ways HIV Cannot Be Spread

HIV is not spread by:

 Air or water
 Mosquitoes, ticks or other insects
 Saliva, tears, or sweat that is not mixed with the blood of a person with HIV
 Shaking hands; hugging; sharing toilets; sharing dishes, silverware, or drinking
glasses; or engaging in closed-mouth or “social” kissing with a person with
HIV
 Drinking fountains
 Other sexual activities that don’t involve the exchange of body fluids (for
example, touching).
HIV can’t be passed through healthy, unbroken skin.

How Do You Get AIDS?

You can’t “catch” AIDS.

AIDS is the most advanced stage of HIV infection. If you have HIV and you are not
on HIV treatment, eventually your body’s immune system will weaken and you will
progress to AIDS.
People with AIDS have such badly damaged immune systems that they get a number
of severe illnesses, called opportunistic infections.

INFORMATION: People who are HIV-negative can prevent getting HIV by using PrEP (pre-
exposure prophylaxis). Post-exposure prophylaxis (PEP) is a way to prevent HIV infection after a
recent possible exposure to the virus. There are other ways to prevent getting or transmitting HIV
through injection drug use and sexual activity.

Is the Risk of HIV Different for Different

Groups?
HIV can affect anyone regardless of sexual orientation, race, ethnicity, gender, age, or
where they live. However, certain groups of people in the United States are more
likely to get HIV than others because of particular factors, including the communities
in which they live, what subpopulations they belong to, and their risk behaviours.

Communities. When you live in a community where many people have HIV

infection, the chance of being exposed to HIV by having sex or sharing needles or
other injection equipment with someone who has HIV is higher. You can use
CDC’s HIV, STD, hepatitis, and tuberculosis Atlas Plus to see the percentage of
people with HIV (“prevalence”) in different U.S. counties and states, as well as other
data. Within any community, the prevalence of HIV can vary among different
subpopulations.

Subpopulations. In the United States, gay, bisexual, and other men who have sex
with men are the population most affected by HIV. According to CDC, in 2018, gay
and bisexual men accounted for 69% of new HIV diagnoses. By race/ethnicity,
Blacks/African Americans and Hispanics/Latinos are disproportionately affected by
HIV compared to other racial and ethnic groups. Also, transgender women who have
sex with men are among the groups at highest risk for HIV infection, and injection
drug users remain at significant risk for getting HIV.

Risk behaviours. In the United States, HIV is spread mainly through having anal or
vaginal sex or sharing needles or syringes with an HIV-positive partner. Anal sex is
the highest-risk behaviour. Fortunately, there are more HIV prevention tools available
today than ever before. These include using condoms correctly, every time you have
sex; pre-exposure prophylaxis (PrEP), a prevention method in which the HIV-negative
partner takes daily HIV medicine to prevent HIV; and treatment as prevention, a
method in which the HIV-positive partner takes daily HIV medicine to achieve and
maintain an undetectable viral load. If a person with HIV takes HIV treatment every
day exactly as prescribed and gets and keeps an undetectable viral load, they have
effectively no risk of transmitting HIV to their partners through sex.

Visit our U.S. Statistics page for more information on how HIV affects different
populations.

What Should I Do If I Think I’m At Risk for

HIV?
If you think you’re at risk for getting HIV, or that you might already have HIV, get
tested and learn about the effective HIV prevention and treatment options
available today.

Testing is the only way to know for sure if you have HIV. Find out whether testing is
recommended for you.

Many HIV tests are now quick, free, and painless. Ask your health care provider for
an HIV test or use the HIV Services Locator to find a testing site near you. You can
also buy an FDA-approved home testing kit at a pharmacy or online.

Knowing your HIV status gives you powerful information to help you take steps to
keep you and your partner(s) healthy:

 If you test positive, you can start HIV treatment to stay healthy and prevent
transmitting HIV to others.
 If you test negative, you can use HIV prevention tools to reduce your risk of
getting HIV in the future.
Learn More about Groups at Higher Risk for
HIV
The CDC fact sheets listed below provide in-depth information about groups at greater
risk for HIV. More links are provided under Additional Resources.

Risk by sexual orientation

 HIV and Gay and Bisexual Men
 HIV and African American Gay and Bisexual Men
 HIV and Hispanic/Latino Gay and Bisexual Men

Risk by gender
 HIV and Men
 HIV and Pregnant Women, Children and Infants
 HIV and Transgender People
 HIV and Women

Risk by race/ethnicity
 HIV and African Americans
 HIV and American Indians and Alaska Natives
 HIV and Asians
 HIV and Hispanics/Latinos
 HIV and Native Hawaiians and Other Pacific Islanders

Risk by age
 HIV and People Aged 50 and Older
 HIV and Youth

Risk by region
 HIV in the United States by Region
 HIV in the Southern United States
Risk and substance use
 HIV and People Who Inject Drugs
 HIV and Substance Use in the United States

How Can You Tell If You Have HIV?

The only way to know for sure if you have HIV is to get tested. You can’t rely on
symptoms to tell whether you have HIV.

Knowing your HIV status gives you powerful information so you can take steps to
keep yourself and your partner(s) healthy:

 If you test positive, you can take medicine to treat HIV. By taking HIV
medicine daily as prescribed, you can make the amount of HIV in your blood
(your viral load) very low—so low that a test can’t detect it (called an
undetectable viral load). Getting and keeping an undetectable viral load is the
best thing you can do to stay healthy. If your viral load stays undetectable, you
have effectively no risk of transmitting HIV to an HIV-negative partner
through sex.
  If you test negative, there are more HIV prevention tools available today than
ever before.
 If you are pregnant, you should be tested for HIV so that you can begin
treatment if you're HIV-positive. If an HIV-positive woman is treated for HIV
early in her pregnancy, the risk of transmitting HIV to her baby can be very
low.
Use the HIV Services Locator to find an HIV testing site near you.

HIV self-testing is also an option. Self-testing allows people to take an HIV test and find out
their result in their own home or other private location. You can buy a self-test kit at a
pharmacy or online, or your health care provider may be able to order one for you. Some
health departments or community-based organizations also provide self-test kits for free.

What Are the Symptoms of HIV?

There are several symptoms of HIV. Not everyone will have the same symptoms. It
depends on the person and what stage of the disease they are in.

Below are the three stages of HIV and some of the symptoms people may experience.

Stage 1: Acute HIV Infection

Within 2 to 4 weeks after infection with HIV, about two-thirds of people will have a
flu-like illness. This is the body’s natural response to HIV infection. 

Flu-like symptoms can include:

 Fever
 Chills
 Rash
 Night sweats
 Muscle aches
 Sore throat
 Fatigue
 Swollen lymph nodes
 Mouth ulcers
These symptoms can last anywhere from a few days to several weeks. But some
people do not have any symptoms at all during this early stage of HIV.
Don’t assume you have HIV just because you have any of these symptoms—they can
be similar to those caused by other illnesses. But if you think you may have been
exposed to HIV, get an HIV test.

Here’s what to do:

 Find an HIV testing site near you—You can get an HIV test at your primary
care provider’s office, your local health department, a health clinic, or many
other places. Use the HIV Services Locator to find an HIV testing site near
you.
 Request an HIV test for recent infection—Most HIV tests detect antibodies
(proteins your body makes as a reaction to HIV), not HIV itself. But it can take
a few weeks after you’re infected for your body to produce them. There are
other types of tests that can detect HIV infection sooner. Tell your doctor or
clinic if you think you were recently exposed to HIV, and ask if their tests can
detect early infection.
 Know your status—After you get tested, be sure to learn your test results. If
you’re HIV-positive, see a doctor as soon as possible so you can start treatment
with HIV medicine. And be aware: when you are in the early stage of
infection, you are at very high risk of transmitting HIV to others. It is
important to take steps to reduce your risk of transmission. If you are HIV-
negative, there are prevention tools like pre-exposure prophylaxis (PrEP) that
can help you stay negative.

Stage 2: Clinical Latency

In this stage, the virus still multiplies, but at very low levels. People in this stage may
not feel sick or have any symptoms. This stage is also called chronic HIV infection.

Without HIV treatment, people can stay in this stage for 10 or 15 years, but some
move through this stage faster.

If you take HIV medicine every day, exactly as prescribed and get and keep an
undetectable viral load, you can protect your health and have effectively no risk of
transmitting HIV to your sexual partner(s).
But if your viral load is detectable, you can transmit HIV during this stage, even when
you have no symptoms. It’s important to see your health care provider regularly to get
your viral load checked.

Stage 3: AIDS
If you have HIV and you are not on HIV treatment, eventually the virus will weaken
your body’s immune system and you will progress to AIDS (acquired
immunodeficiency syndrome). This is the late stage of HIV infection.

Symptoms of AIDS can include:

 Rapid weight loss

 Recurring fever or profuse night sweats
 Extreme and unexplained tiredness
 Prolonged swelling of the lymph glands in the armpits, groin, or neck
 Diarrhea that lasts for more than a week
 Sores of the mouth, anus, or genitals
 Pneumonia
 Red, brown, pink, or purplish blotches on or under the skin or inside the mouth,
nose, or eyelids
 Memory loss, depression, and other neurologic disorders
Each of these symptoms can also be related to other illnesses. The only way to know
for sure if you have HIV is to get tested. If you are HIV-positive, a health care
provider will diagnose if your HIV has progressed to stage 3 (AIDS) based on certain
medical criteria.

Many of the severe symptoms and illnesses of HIV disease come from
the opportunistic infections that occur because your body’s immune system has been
damaged. See your health care provider if you are experiencing any of these
symptoms.

Read more about the difference between HIV and AIDS.

Food poisoning
 Symptoms & causes
Print

Overview

Food poisoning, also called foodborne illness, is illness caused by eating

contaminated food. Infectious organisms — including bacteria, viruses and parasites
— or their toxins are the most common causes of food poisoning.

Infectious organisms or their toxins can contaminate food at any point of processing
or production. Contamination can also occur at home if food is incorrectly handled or
cooked.

Food poisoning symptoms, which can start within hours of eating contaminated food,
often include nausea, vomiting or diarrhea. Most often, food poisoning is mild and
resolves without treatment. But some people need to go to the hospital.

Products & Services

 Book: Mayo Clinic Book of Home Remedies

Symptoms

Food poisoning symptoms vary with the source of contamination. Most types of food
poisoning cause one or more of the following signs and symptoms:

 Nausea

 Vomiting

 Watery or bloody diarrhea

  Abdominal pain and cramps

 Fever

Signs and symptoms may start within hours after eating the contaminated food, or
they may begin days or even weeks later. Sickness caused by food poisoning
generally lasts from a few hours to several days.

When to see a doctor

If you experience any of the following signs or symptoms, seek medical attention.

 Frequent episodes of vomiting and inability to keep liquids down

 Bloody vomit or stools

 Diarrhea for more than three days

 Extreme pain or severe abdominal cramping

 An oral temperature higher than 100.4 F (38 C)

 Signs or symptoms of dehydration — excessive thirst, dry mouth,

little or no urination, severe weakness, dizziness, or light-headedness’

 Neurological symptoms such as blurry vision, muscle weakness

and tingling in the arms
Request an Appointment at Mayo Clinic

Causes

Contamination of food can happen at any point of production: growing, harvesting,

processing, storing, shipping or preparing. Cross-contamination — the transfer of
harmful organisms from one surface to another — is often the cause. This is
especially troublesome for raw, ready-to-eat foods, such as salads or other produce.
Because these foods aren't cooked, harmful organisms aren't destroyed before
eating and can cause food poisoning.

Many bacterial, viral or parasitic agents cause food poisoning. The following table
shows some of the possible contaminants, when you might start to feel symptoms
and common ways the organism is spread.
Contaminant Onset of Foods affected and means of transmission
symptom
s

Campylobacter 2 to 5 Meat and poultry. Contamination occurs during

days processing if animal faces contact meat surfaces.
Other sources include unpasteurized milk and
contaminated water.

Clostridium 12 to 72 Home-canned foods with low acidity, improperly

botulinum hours canned commercial foods, smoked or salted fish,
potatoes baked in aluminium foil, and other foods
kept at warm temperatures for too long.

Clostridium 8 to 16 Meats, stews and gravies. Commonly spread when

perfringens hours serving dishes don't keep food hot enough or food
is chilled too slowly.

Escherichia coli 1 to 8 Beef contaminated with faces during slaughter.

(E. coli) days Spread mainly by undercooked ground beef. Other
sources include unpasteurized milk and apple cider,
alfalfa sprouts, and contaminated water.

Giardia lamblia 1 to 2 Raw, ready-to-eat produce and contaminated water.

weeks Can be spread by an infected food handler.

Hepatitis A 28 days Raw, ready-to-eat produce and shellfish from

contaminated water. Can be spread by an infected
food handler.

Listeria 9 to 48 Hot dogs, luncheon meats, unpasteurized milk and

hours cheeses, and unwashed raw produce. Can be
spread through contaminated soil and water.

Noroviruses 12 to 48 Raw, ready-to-eat produce and shellfish from

 Contaminant Onset of Foods affected and means of transmission
symptom
s

(Norwalk-like hours contaminated water. Can be spread by an infected

viruses) food handler.

Rotavirus 1 to 3 Raw, ready-to-eat produce. Can be spread by an

days infected food handler.

Salmonella 1 to 3 Raw or contaminated meat, poultry, milk, or egg

days yolks. Survives inadequate cooking. Can be spread
by knives, cutting surfaces or an infected food
handler.

Shigella 24 to 48 Seafood and raw, ready-to-eat produce. Can be

hours spread by an infected food handler.

Staphylococcus 1 to 6 Meats and prepared salads, cream sauces, and

aureus hours cream-filled pastries. Can be spread by hand
contact, coughing and sneezing.

Vibrio vulnificus 1 to 7 Raw oysters and raw or undercooked mussels,

days clams, and whole scallops. Can be spread through
contaminated seawater.

Risk factors

Whether you become ill after eating contaminated food depends on the organism,
the amount of exposure, your age and your health. High-risk groups include:

 Older adults. As you get older, your immune system may not
respond as quickly and as effectively to infectious organisms as when
you were younger.
  Pregnant women. During pregnancy, changes in metabolism and
circulation may increase the risk of food poisoning. Your reaction may be
more severe during pregnancy. Rarely, your baby may get sick, too.

 Infants and young children. Their immune systems haven't fully

developed.

 People with chronic disease. Having a chronic condition — such

as diabetes, liver disease or AIDS — or receiving chemotherapy or
radiation therapy for cancer reduces your immune response.

Complications

The most common serious complication of food poisoning is dehydration — a severe

loss of water and essential salts and minerals. If you're a healthy adult and drink
enough to replace fluids you lose from vomiting and diarrhea, dehydration shouldn't
be a problem.

Infants, older adults and people with suppressed immune systems or chronic
illnesses may become severely dehydrated when they lose more fluids than they can
replace. In that case, they may need to be hospitalized and receive intravenous
fluids. In extreme cases, dehydration can be fatal.

Some types of food poisoning have potentially serious complications for certain
people. These include:

 Listeria infection. Complications of a listeria food poisoning may

be most severe for an unborn baby. Early in pregnancy, a listeria
infection may lead to miscarriage. Later in pregnancy, a listeria infection
may lead to stillbirth, premature birth or a potentially fatal infection in the
baby after birth — even if the mother was only mildly ill. Infants who
survive a listeria infection may experience long-term neurological
damage and delayed development.

 Escherichia coli (E. coli). Certain E. coli strains can cause a

serious complication called haemolytic uremic syndrome. This syndrome
damages the lining of the tiny blood vessels in the kidneys, sometimes
leading to kidney failure. Older adults, children younger than 5 and
people with weakened immune systems have a higher risk of developing
 this complication. If you're in one of these risk categories, see your
doctor at the first sign of profuse or bloody diarrhea.

Prevention

To prevent food poisoning at home:

 Wash your hands, utensils and food surfaces often. Wash

your hands well with warm, soapy water before and after handling or
preparing food. Use hot, soapy water to wash utensils, cutting boards
and other surfaces you use.

 Keep raw foods separate from ready-to-eat foods. When

shopping, preparing food or storing food, keep raw meat, poultry, fish
and shellfish away from other foods. This prevents cross-contamination.

 Cook foods to a safe temperature. The best way to tell if foods

are cooked to a safe temperature is to use a food thermometer. You can
kill harmful organisms in most foods by cooking them to the right
temperature.

Cook ground beef to 160 F (71.1 C); steaks, roasts and chops, such as
lamb, pork and veal, to at least 145 F (62.8 C). Cook chicken and turkey
to 165 F (73.9 C). Make sure fish and shellfish are cooked thoroughly.

 Refrigerate or freeze perishable foods promptly — within two

hours of purchasing or preparing them. If the room temperature is above
90 F (32.2 C), refrigerate perishable foods within one hour.

 Defrost food safely. Don't thaw food at room temperature. The

safest way to thaw food is to defrost it in the refrigerator. If you
microwave frozen food using the "defrost" or "50% power" setting, be
sure to cook it immediately.

 Throw it out when in doubt. If you aren't sure if a food has been
prepared, served or stored safely, discard it. Food left at room
temperature too long may contain bacteria or toxins that can't be
destroyed by cooking. Don't taste food that you're unsure about — just
throw it out. Even if it looks and smells fine, it may not be safe to eat.

Food poisoning is especially serious and potentially life-threatening for young

children, pregnant women and their fetuses, older adults, and people with weakened
immune systems. These individuals should take extra precautions by avoiding the
following foods:

 Raw or rare meat and poultry

 Raw or undercooked fish or shellfish, including oysters, clams,

mussels and scallops

 Raw or undercooked eggs or foods that may contain them, such

as cookie dough and homemade ice cream

 Raw sprouts, such as alfalfa, bean, clover and radish sprouts

 Unpasteurized juices and ciders

 Unpasteurized milk and milk products

 Soft cheeses, such as feta, Brie and Camembert; blue-veined

cheese; and unpasteurized cheese

 Refrigerated pates and meat spreads

 Uncooked hot dogs, luncheon meats and deli meats

Diagnosis & treatment

Diagnosis

Food poisoning is often diagnosed based on a detailed history, including how long
you've been sick, your symptoms and specific foods you've eaten. Your doctor will
also perform a physical exam, looking for signs of dehydration.

Depending on your symptoms and health history, your doctor may conduct
diagnostic tests, such as a blood test, stool culture or examination for parasites, to
identify the cause and confirm the diagnosis.

For a stool test, your doctor will send a sample of your stool to a lab, where a
technician will try to identify the infectious organism. If an organism is found, your
doctor likely will notify your local health department to determine if the food poisoning
is linked to an outbreak.

In some cases, the cause of food poisoning can't be identified.

Treatment
Treatment for food poisoning typically depends on the source of the illness, if known,
and the severity of your symptoms. For most people, the illness resolves without
treatment within a few days, though some types of food poisoning may last longer.

Treatment of food poisoning may include:

 Replacement of lost fluids. Fluids and electrolytes — minerals

such as sodium, potassium and calcium that maintain the balance of
fluids in your body — lost to persistent diarrhea need to be replaced.
Some children and adults with persistent diarrhea or vomiting may need
hospitalization, where they can receive salts and fluids through a vein
(intravenously), to prevent or treat dehydration.

 Antibiotics. Your doctor may prescribe antibiotics if you have a

certain kind of bacterial food poisoning and your symptoms are severe.
Food poisoning caused by listeria needs to be treated with intravenous
antibiotics during hospitalization. The sooner treatment begins, the
better. During pregnancy, prompt antibiotic treatment may help keep the
infection from affecting the baby.

Antibiotics will not help food poisoning caused by viruses. Antibiotics

may actually worsen symptoms in certain kinds of viral or bacterial food
poisoning. Talk to your doctor about your options.

Adults with diarrhea that isn't bloody and who have no fever may get relief from
taking the medication loperamide (Imodium A-D) or bismuth subsalicylate (Pepto-
Bismol). Ask your doctor about these options.

Food poisoning often improves without treatment within 48 hours. To help keep
yourself more comfortable and prevent dehydration while you recover, try the
following:

 Let your stomach settle. Stop eating and drinking for a few

hours.

 Try sucking on ice chips or taking small sips of water. You

might also try drinking clear soda, clear broth or noncaffeinated sports
drinks. You might also try oral rehydration solutions if you have severe
dehydration symptoms or diarrhea. You're getting enough fluid when
you're urinating normally and your urine is clear and not dark.
  Probiotics. Your doctor may recommend trying probiotics. Ask
your doctor before trying probiotics.

 Ease back into eating. Gradually begin to eat bland, low-fat,

easy-to-digest foods, such as soda crackers, toast, gelatine, bananas
and rice. Stop eating if your nausea returns.

 Avoid certain foods and substances until you're feeling

better. These include dairy products, caffeine, alcohol, nicotine, and fatty
or highly seasoned foods.

 Rest. The illness and dehydration can weaken and tire you.

Preparing for your appointment

If you or your child needs to see a doctor, you'll likely see your primary care provider
first. If there are questions about the diagnosis, your doctor may refer you to an
infectious disease specialist.

What you can do

Preparing a list of questions will help you make the most of your time with your
doctor. Some questions to ask include:

 What's the likely cause of the symptoms? Are there other possible
causes?

 Is there a need for tests?

 What's the best treatment approach? Are there alternatives?

 Is there a need for medication? If yes, is there a generic

alternative to the medicine you're prescribing?

 How can I ease the symptoms?

What to expect from your doctor?

Some questions the doctor may ask include:

 Has anyone in your family or otherwise close to you developed

similar symptoms? If so, did you eat the same things?
  Have you travelled anywhere where the water or food might not
be safe?

 Are you having bloody bowel movements?

 Do you have a fever?

 Had you taken antibiotics in the days or weeks before your

symptoms started?

 When did symptoms begin?

 Have the symptoms been continuous, or do they come and go?

 What foods have you eaten in the past few days?

What you can do in the meantime

Drink plenty of fluids. Stick with bland foods to reduce stress on your digestive
system. If your child is sick, follow the same approach — offer plenty of fluids and
bland food. If you're breast-feeding or using formula, continue to feed your child as
usual.

Ask your child's doctor if giving your child an oral rehydration fluid (Pedialyte,
Enfalyte, others) is appropriate. Older adults and people with weakened immune
systems might also benefit from oral rehydration solutions. Medications that help
ease diarrhea generally aren't recommended for children.
Your Anxiety Loves
Sugar. Eat These 3
Things Instead
 Highs and lows

 Worsen anxiety

 Depression risk

 Withdrawal

 Brain zapper

 Eat this
We include products we think are useful for our readers. If you buy through links on this page, we
may earn a small commission. Here’s our process.

Is it time to ditch sugar?

It’s no secret that sugar can cause issues if you’re indulging in a little too
much of the sweet stuff. Still, most Americans are eating too much sugar.

The harmful effects it can have on your physical health are well studied,
which is why we talk so much about reducing sugar intake to lower the risk
of these effects, like chronic disease.

While ditching the sweet stuff can result in a physically healthier you, it’s
the effect sugar has on our mental health that’s worth taking a second look.

1. Sugar can affect your mood

You’ve probably heard of the term “sugar rush” — and have maybe even
turned to a doughnut or soda for an extra boost during a long day.

Yet sugar may not be such a positive pick-me-up after all.

Recent research indicates that sugary treats have no positive effect on
mood.

In fact, sugar may have the opposite effect over time.

One study published in 2017Trusted Source found that consuming a diet

high in sugar can increase the chances of incident mood disorders in men,
and recurrent mood disorders in both men and women.
A more recent 2019 study Trusted Source found that regular consumption
of saturated fats and added sugars were related to higher feelings of
anxiety in adults over age 60.

Although more studies are needed to solidify the relationship between

mood and sugar consumption, it’s important to consider how diet and
lifestyle choices Trusted Source can affect your psychological well-being.

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2. It can weaken your ability to

deal with stress
If your idea of coping with stress involves a pint of Ben and Jerry’s, you’re
not alone. Lots of people turn to sugary sweets when they feel anxious.

That’s because sugary foods can weaken Trusted Source the body’s ability

to respond to stress.

Sugar can help you feel less frazzled by suppressing the hypothalamic

pituitary adrenal (HPA) axis in your brain, which controls your response to
stress.

Researchers Trusted Source at the University of California, Davis found

that sugar inhibited stress-induced cortisol secretion in healthy female
participants, minimizing feelings of anxiety and tension. Cortisol is known
as the stress hormone.

Yet the temporary relief sweets provide may make you more reliant on
sugar, and raise the risk of obesity and its related diseases.
The study was limited to just 19 female participants, but results were
consistent with other studies Trusted Source that have looked at the
connection between sugar and anxiety in rats.

While findings show a definite link between sugar intake and anxiety,
researchers would like to see more studies done on humans.

3. Sugar can increase your risk

for developing depression
It’s hard to avoid reaching for comfort foods, especially after a difficult day.

But the cycle of consuming sugar to manage your emotions may only make
your feelings of sadness, fatigue, or hopelessness worse.

Multiple studies have found a link between diets high in sugar and

depression.

Overconsumption of sugar triggers imbalances in certain brain chemicals.

These imbalances can lead to depression and may even increase the long-
term risk of developing a mental health disorder in some people.

In fact, a 2017 study Trusted Source found that men who consumed a high
amount of sugar (67 grams or more each day) were 23 percent more likely
to receive a diagnosis of clinical depression within 5 years.
Even though the study just involved men, the link between sugar and
depression is also found in women Trusted Source.

4. Withdrawing from sweets can

feel like a panic attack
Quitting processed sugar might not be as simple as you think.

Withdrawing from sugar can actually cause side effects, such as:

 anxiety

 irritability

 confusion

 fatigue

This has led experts Trusted Source to look at how the withdrawal

symptoms from sugar can resemble those of certain addictive substances.

“Evidence Trusted Source in the literature shows substantial parallels and

overlap between drugs of abuse and sugar,” explains Dr. Uma Naidoo,
who’s considered the mood-food expert at Harvard Medical School.

When someone misuses a substance for a period of time, like cocaine,

their body goes into a physiological state of withdrawal when they stop
using it.
Naidoo says that people who are consuming high amounts of sugar in their
diets can similarly experience the physiological sensation of withdrawal if
they suddenly stop consuming sugar.

That’s why going cold turkey from sugar may not be the best solution for
someone who also has anxiety.

“Suddenly stopping sugar intake can mimic withdrawal and feel like a panic
attack,” Naidoo says. And if you have an anxiety disorder, this experience
of withdrawal can be heightened.

5. Sugar zaps your brain power

Your stomach may be telling you to dive in and drink your way out of that
jumbo cherry Icee, but your brain has a different idea.

Emerging research has found that diets high in sugar can impair cognitive
functioning, even in the absence of extreme weight gain or excessive
energy intake.

A 2015 study Trusted Source found that consuming high levels of sugar-

sweetened beverages impaired neurocognitive functions like decision
making and memory.

Granted, the research was done on rats.

But a more recent study found that healthy volunteers in their 20s scored
worse on memory tests and had poorer appetite control after just 7 days of
eating a diet high in saturated fat and added sugars.

While more studies are necessary to establish a clearer link between sugar
and cognition, it’s worth noting that your diet can affect your brain health.

If you’re craving sweets, here’s

what to eat instead
Just because you’re ditching or limiting processed sugar doesn’t mean you
have to deny yourself the pleasure of sweet-tasting food.

In addition to being a doctor known as an expert on food and mood, Naidoo

is also a chef and the author of the forthcoming book “This Is Your Brain on
Food.”

Here are a few of her favourite low- or no-sugar recipes.

Chef Uma’s Chai Tea Smoothie

Ingredients

 1 serving vanilla protein powder of your choice

 1/4 avocado

 1 tbsp. almond butter

 1 cup almond milk

 1/8 tsp. each of ground cinnamon, nutmeg, clove, and cardamom

spice

 1/4 tsp. organic vanilla essence

 ice

 a small bit of organic honey to sweeten, if needed

Optional

 brewed chai tea instead of spices

  avocado for creaminess

Directions

1. Add all ingredients to your blender.

2. Blend until smooth.

Chef Uma’s tips

 If you don’t have the spices, brew a cup of chai tea using tea bags or
whole leaf tea. Use it instead of the almond milk.

 For a thinner smoothie, add more almond milk.

 For creaminess, add avocado. It’s also a healthy fat to boot!

Chef Uma’s Watermelon Pops

Ingredients

 4 cups chopped watermelon

 1 tablespoon honey

 juice of 1 lime

 zest of 1 lime

Optional

 1 cup whole blueberries

Directions

1. Puree the watermelon, honey, lime juice, and lime zest in a blender.
 2. Pour into square ice cube trays or popsicle molds.

3. Before fully frozen, add ice cream stick to each ice cube or mold.

4. If desired, add whole blueberries to ice cube trays or popsicle molds.

Chef Uma’s tips

 You can omit the honey, as a ripe watermelon can be very sweet.

 Blueberries can incorporate a fun pop of colour and add an

antioxidant boost.

Chef Uma’s Oven-Roasted Sweet Potatoes with

Red Miso Paste

Ingredients

 1/4 cup olive oil

  1/4 to 1/2 cup red miso paste

 salt and pepper to taste

 4 medium sweet potatoes

Directions

1. Preheat oven to 425ºF (218ºC).

2. Create a marinade by mixing the olive oil, red miso paste, and salt
and pepper.

3. Peel and cut sweet potatoes into equal-sized pieces or discs.

4. Toss the sweet potatoes in the marinade.

5. Place sweet potatoes on a sheet pan in a single layer.

6. Roast for about 20 to 25 minutes, or until potatoes are tender.

Chef Uma’s tips

 You can substitute white miso paste for less of an umami flavour.

 It may be easier to coat all the potatoes with the marinade if you put
both in a Ziploc bag, then toss around.

 Sweet potatoes are a healthy source of fibre and phytonutrients.

What is sepsis?
On this Page
 What causes sepsis?
 Who is at risk?
 What are the signs & symptoms?
 I think I might have sepsis. What should I do?
 Fact Sheets
Know the Risks.  Spot the Signs.  Act Fast.
Sepsis is the body’s extreme response to an infection. It is a life-threatening medical
emergency.  Sepsis happens when an infection you already have triggers a chain reaction
throughout your body.  Without timely treatment, sepsis can rapidly lead to tissue damage,
organ failure, and death.
Almost any type of infection can lead to sepsis. Infections that lead to sepsis most often start
in the lung, urinary tract, skin, or gastrointestinal tract.
You can’t spread sepsis to other people. However, an infection can lead to sepsis, and you
can spread some infections to other people. Bacterial infections cause most cases of sepsis.
Sepsis can also be a result of other infections, including viral infections, such as COVID-19
or influenza.

 
Sepsis happens when…image icon
Transcript: Sepsis happens when txt icon[TXT 1 1 KB]
What causes sepsis?
When germs get into a person’s body, they can cause an infection. If you don’t stop that
infection, it can cause sepsis.
Top of Page
Who is at risk?
Anyone can get an infection, and almost any infection can lead to sepsis. Some people are at
higher risk:

Adults 65 or older

People with chronic medical conditions, such as diabetes, lung disease, cancer, and kidney
disease

People with weakened immune systems

Sepsis survivors

Children younger than one

Top of Page
What are the signs & symptoms?
A patient with sepsis might have one or more of the following signs or symptoms:

High heart rate or low blood pressure

Confusion or disorientation

Extreme pain or discomfort

Fever, shivering, or feeling very cold

Shortness of breath

Clammy or sweaty skin

Top of Page
I think I might have sepsis. What should I do?
Sepsis is a medical emergency. If you or your loved one has an infection
that’s not getting better or is getting worse, ACT FAST. Get medical care
IMMEDIATELY either in-person, or at minimum, through telehealth
services. Ask your healthcare professional, “Could this infection be leading
to sepsis?” and if you should go to the emergency room for medical
assessment.
If you have a medical emergency, call 911. If you have or think you have
sepsis, tell the operator. If you have or think you have COVID-19, tell the
operator this as well. If possible, put on a mask before medical help
arrives.

How can I get ahead of sepsis?

As a patient, specific steps can be taken to reduce your risk of sepsis, such as:

1 Prevent infections
Talk to your healthcare professional about steps you can take to prevent infections that can
lead to sepsis. Some steps include:

Take good care of chronic conditions

Get recommended vaccines

Top of Page
2 Practice good hygiene

Wash your hands

Keep cuts clean and covered until healed

Top of Page
3 Know the signs and symptoms of sepsis
A patient with sepsis might have one or more of the following signs or symptoms:

High heart rate or low blood pressure

Fever, shivering, or feeling very cold

Confusion or disorientation

Shortness of breath

Extreme pain or discomfort

Clammy or sweaty skin

Top of Page
4 Act fast
Sepsis is a medical emergency. If you or your loved one has an infection
that’s not getting better or is getting worse, ACT FAST. Get medical care
IMMEDIATELY either in-person, or at minimum, through telehealth
services. Ask your healthcare professional, “Could this infection be leading
to sepsis?” and if you should go to the emergency room for medical
assessment.
Does cancer put me at risk for sepsis?
On this Page
 When am I more likely to get an infection?
 How will I know if I have neutropenia?
 How can I prevent an infection?
Yes. Having cancer and undergoing certain treatments for cancer, such as
chemotherapy, can put you at higher risk of developing an infection, and
infections can lead to sepsis.
Chemotherapy works by killing the fastest-growing cells in your body—
both good and bad. This means that along with killing cancer cells, chemo
also kills your infection-fighting white blood cells.

When am I more likely to get an infection?

An infection or sepsis can happen at any time. However, when your body
has very low levels of a certain type of white blood cell (neutrophils) that
increases your risk of getting an infection. This condition is a common side
effect of chemo called neutropenia.

How will I know if I have neutropenia?

Your doctor will routinely test for neutropenia by checking the level of
your white blood cells.

How can I prevent an infection?

 Wash your hands often and ask others around you to do the same.

 Avoid crowded places and people who are sick.

 Talk to your doctor about getting a flu shot or other vaccinations.

 Take a bath or shower every day (unless told otherwise).

 Use an unscented lotion to try to keep your skin from getting dry or
cracked.

 Clean your teeth and gums with a soft toothbrush.

 Use a mouthwash to prevent mouth sores (if your doctor

recommends one).
  Do not share food, drink cups, utensils or other personal items, such
as toothbrushes.

 Cook meat and eggs all the way through to kill any germs.

 Carefully wash raw fruits and vegetables.

 Protect your skin from direct contact with pet bodily waste (urine or
feces).

 Wash your hands immediately after touching an animal or removing

its waste, even after wearing gloves.

 Use gloves for gardening.

How is sepsis diagnosed and treated?

Diagnosis
Doctors diagnose sepsis using a number of physical findings such as:

 Fever

 Low blood pressure

 Increased heart rate

 Difficulty breathing
Doctors also perform lab tests that check for signs of infection or organ
damage.  Doctors also perform specific tests to identify the germ that
caused the infection that led to sepsis. This testing might include blood
cultures looking for bacterial infections, or tests for viral infections, like
COVID-19 or influenza.

Treatment
Research shows that rapid, effective sepsis treatment includes:
  Giving appropriate treatment, including antibiotics

 Maintaining blood flow to organs

Sometimes surgery is required to remove tissue damaged by the infection.
Doctors and nurses should treat sepsis with antibiotics as soon as
possible. Antibiotics are critical tools for treating life-threatening
infections, like those that can lead to sepsis. However, as antibiotic
resistance grows, infections are becoming more difficult to treat. 
Antibiotic side effects range from minor, such as rash, dizziness, nausea,
diarrhea, and yeast infections, to very severe health problems, such as life-
threatening allergic reactions or C. difficile (also called C. diff) infection,
which causes severe diarrhea that can lead to severe colon damage or
death. However, when you need antibiotics, the benefits outweigh the
risks of side effects or antibiotic resistance. Improving the way healthcare
professionals prescribe antibiotics, and the way we take antibiotics, helps
keep us healthy now, helps fight antibiotic resistance, and ensures that
these lifesaving drugs will work for you or others when they are needed
most, like for treating infections associated with sepsis.

I survived sepsis. What’s next?

On this Page
 How will I feel when I get home?
 What can I do to help myself recover?
 What if I think I need more help?
What are the long-term effects of sepsis?
Recovery takes time.
After you have had sepsis, rehabilitation usually starts in the hospital. You
will begin by slowly building up strength. You will be helped with  bathing,
sitting up, standing, walking, and taking yourself to the restroom.
The purpose of rehabilitation is to restore you back to your previous level
of health or as close to it as possible. You will begin your rehabilitation by
building up your activities slowly and resting when you are tired.

How will I feel when I get home?

You have been seriously ill, and your body and mind need time to get
better. You may experience the following physical symptoms upon
returning home:

 General to extreme weakness and fatigue

 Breathlessness

 General body pains or aches

 Difficulty moving around

 Difficulty sleeping

 Weight loss, lack of appetite, food not tasting normal

 Dry and itchy skin that may peel

 Brittle nails

 Hair loss
It is also not unusual to experience the following once you’re home:

 Feel unsure of yourself

 Not care about your appearance

 Want to be alone, avoiding friends and family

 Have flashbacks, bad memories

 Be confused about what is real and what isn’t

 Feel anxious, more worried than usual

 Experience poor concentration

 Be depressed, angry, unmotivated

 Feel frustration at not being able to do everyday tasks

Top of Page
Fact Sheet

What sepsis survivors need to know (Print Only) pdf icon[PDF – 2 pages]

What can I do to help myself recover?
Set small, achievable goals for yourself each week, such as taking a bath,
dressing yourself, or walking up the stairs. Here are some things you can
do:

 Rest and rebuild your strength

 Talk about what you are feeling with family and friends

 Record your thoughts, struggles, and milestones in a journal

 Learn about sepsis to understand what happened

 Ask your family to fill in any gaps you may have in your memory
about what happened to you

 Eat a balanced diet

 Exercise if you feel up to it

Make a list of questions to ask your doctor when you go for a check
up
Top of Page
What if I think I need more help?
Some hospitals have follow-up clinics or staff to help patients and families
once they have been discharged. Find out if yours does or if there are local
resources available to help you while you get better.
However, if you feel that you are not getting better, finding it difficult to
cope, or continue to be exhausted, call your doctor or nurse.
Top of Page
What are the long-term effects of sepsis?
As with other illnesses requiring intensive medical care, some patients
have long-term effects. These problems might not become apparent for
several weeks after treatment is completed  and might include such
consequences as:

 Insomnia, difficulty getting to or staying asleep

 Nightmares, vivid hallucinations, panic attacks

 Disabling muscle and joint pains

 Decreased mental (cognitive) function

 Loss of self-esteem and self-belief

 Organ dysfunction (kidney failure, lung problems, etc.)

 Loss of hands, arms, legs, or feet (limb amputation)

What is CDC Doing?

CDC’s Division of Healthcare Quality Promotion’s sepsis-related work
includes:

 Understanding the epidemiology of sepsis by assessing the adult

sepsis burden and identifying factors that put people at higher risk
for sepsis. See Incidence and Trends of Sepsis in US Hospitals Using
Clinical vs Claims Data, 2009-2014external icon.
o Working with pediatric and critical care specialists to develop
ways to assess sepsis burden in children and identify factors
that put children at higher risk.
 Developing tools for tracking sepsis, such as the Hospital Toolkit
for Adult Sepsis Surveillance pdf icon[PDF – 32 pages], to help
healthcare facilities assess adult sepsis incidence within their
facilities.
  Working with partners, including the CDC Prevention
Epicenters, and other Federal agencies, to develop innovative
ways to improve sepsis early detection and treatment.

 Promoting early recognition and timely treatment of

sepsis through:

o Get Ahead of Sepsis, CDC’s educational effort for patients,

healthcare professionals, and the general public—information
available on the Educational Information page of this website.

o Collaboration with partners, clinical organizations, and

consumer groups to implement sepsis awareness efforts and
improve antibiotic prescribing and use.

 Preventing infections in health care settings and in the community

so that infections that can lead to sepsis can be stopped before they
happen. See Infection Control.

Clinical Information
On this Page
 Surveillance and Epidemiology
 Prevention
 Treatment
Clinical Guidelines

Each year, at least 1.7 million adults in America develop sepsis.
Nearly 270,000 Americans die as a result of sepsis.
1 in 3 patients who dies in a hospital has sepsis.
Surveillance and Epidemiology
Tools
Hospital Toolkit for Adult Sepsis Surveillancepdf icon  [PDF – 32
pages]
Centers for Disease Control and Prevention
August 2018
Presentations and Media Interviews
A Matter of Life and Death: How States Are Tackling Sepsis as Public
Policyexternal icon
 Association of State and Territorial Health Officials Public Health
Review podcast
November 25, 2019
 Hospital Toolkit for Adult Sepsis Surveillance Webinar
Society of Critical Care Medicine Critical Care Quality Summit
September 25, 2018
Publications
 Assessment of Health Care Exposures and Outcomes in Adult
Patients With Sepsis and Septic Shockexternal icon
JAMA Network Open
July 7, 2020
 Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis,
2012–2018*external icon
Critical Care Medicine
March 2020
 A National Approach to Pediatric Sepsis Surveillanceexternal icon
Pediatrics
December 2019
 Epidemiology of Hospital-Onset Versus Community-Onset Sepsis in
U.S. Hospitals and Association With Mortality: A Retrospective Analysis
Using Electronic Clinical Dataexternal icon
Critical Care Medicine
May 24, 2019
 Variation in Identifying Sepsis and Organ Dysfunction Using
Administrative Versus Electronic Clinical Data and Impact on Hospital
Outcome Comparisonsexternal icon
Critical Care Medicine
April 2019
 Using Objective Clinical Data to Track Progress on Preventing and
Treating Sepsis — CDC’s New ‘Adult Sepsis Event’ Surveillance
Strategy external icon
BMJ Quality & Safety
April 2019
 Assessing Variability in Hospital-Level Mortality Among U.S.
Medicare Beneficiaries With Hospitalizations for Severe Sepsis and
Septic Shockexternal icon
Critical Care Medicine
November 2018
  Combined Biomarkers Predict Acute Mortality Among Critically Ill
Patients With Suspected Sepsisexternal icon
Critical Care Medicine
July 2018
 Variability in Determining Sepsis Time Zero and Bundle Compliance
Rates for the Centers for Medicare and Medicaid Services SEP-1
Measureexternal icon
Infection Control & Hospital Epidemiology
June 22, 2018
 Risk of Subsequent Sepsis Within 90 Days After a Hospital Stay by
Type of Antibiotic Exposure.external icon
Clinical Infectious Diseases
March 10, 2018
 Enhancing Recovery from Sepsis: A Reviewexternal icon
JAMA
January 2, 2018
 Incidence and Trends of Sepsis in US Hospitals Using Clinical vs
Claims Data, 2009-2014 external icon
JAMA
October 3, 2017
 Varying Estimates of Sepsis Mortality Using Death Certificates and
Administrative Codes — United States, 1999–2014external icon
Morbidity and Mortality Weekly Report
April 8, 2016

TYPES OF DRUGS AND MEANINGS OF IT

Types of drugs
Drugs can be grouped together in different ways — by the way they affect the body or by
how or where they are used. Find out which drugs we are focused on reducing in Australia.
 Listen
 Print
  Share
On this page
 Drug categories
 Common groups of drugs
 Our priorities

Drug categories
Drugs can be categorised by the way in which they affect our bodies:

 depressants — slow down the function of the central nervous system

hallucinogens — affect your senses and change the way you see, hear, taste,
smell or feel things

 stimulants — speed up the function of the central nervous system

Some drugs affect the body in many ways and can fall into more than one category.
For example, cannabis appears in all 3 categories.

Depressants
Depressants slow down the messages between the brain and the body — they don’t
necessarily make you feel depressed. The slower messages affect:

 your concentration and coordination

 your ability to respond to what’s happening around you

Small doses of depressants can make you feel relaxed, calm and less inhibited.

Larger doses can cause sleepiness, vomiting and nausea, unconsciousness and even
death.

Examples include:

 alcohol

 benzodiazepines (minor tranquillisers such as Valium)

 cannabis

 GHB (gamma-hydroxybutyrate)

 ketamine

 opioids (heroin, morphine, codeine)

Hallucinogens
Hallucinogens change your sense of reality — you can have hallucinations. Your
senses are distorted and the way you see, hear, taste, smell or feel things is different.
For example, you may see or hear things that are not really there, or you may have
unusual thoughts or feelings.

Small doses can cause a feeling of floating, numbness, confusion, disorientation, or

dizziness.

Larger doses may cause hallucinations, memory loss, distress, anxiety, increased heart
rate, paranoia, panic and aggression.

Examples include:

 cannabis

 ketamine

 LSD (lysergic acid diethylamide)

 psilocybin (magic mushrooms)

 PCP (phencyclidine)

Stimulants
Stimulants speed up the messages between the brain and the body. This can cause:

 your heart to beat faster

 your blood pressure to go up

 your body temperature to go up — leading to heat exhaustion or even heat

stroke

 reduced appetite

 agitation

 sleeplessness

You can feel more awake, alert, confident or energetic.

Larger doses can cause anxiety, panic, seizures, stomach cramps and paranoia.

Examples include:

 amphetamines (speed and ice)

 caffeine

 cocaine
  ecstasy (MDMA — methylenedioxymethamphetamine)

 nicotine (tobacco)

Common groups of drugs

Drugs can also be grouped by how or where they are commonly used.

Analgesics
Analgesics – or painkillers – relieve the symptoms of pain. Some people take more
than the recommended dose to get high, or to self-harm. They can also be overused
by people who have chronic pain.

Some are available over the counter, such as:

 aspirin

 paracetamol

 ibuprofen

Others require a prescription from a doctor, such as:

 codeine and paracetamol combination products

 fentanyl

 morphine

 oxycodone

 pethidine

Inhalants
Inhalants are substances that you breathe in through the nose (sniffing) or mouth.
They are absorbed into the bloodstream very quickly, giving the user an immediate
high.

There are 4 main types of inhalants:

volatile solvents — liquids that turn into a gas at room temperatures — for
example, paint thinners and removers, glues, petrol and correction fluid (liquid
paper)

 aerosol sprays — for example, spray paints, deodorants and hairsprays, fly
sprays and vegetable oil sprays
  gases — for example, nitrous oxide (laughing gas), propane, butane (cigarette
lighters), helium

 nitrites — for example, room deodorisers and leather cleaners

Most of these are depressants, except for nitrites.

Opioids
Opioids are a type of painkiller that can be made from poppy plants (heroin) or
produced synthetically (fentanyl). Also called opiates or narcotics, they are addictive
as they can give you a feeling of wellbeing or euphoria.

Examples include:

 codeine

 heroin

 methadone

 oxycodone

Party drugs
Party drugs are a group of stimulants and hallucinogens. They are often used by
young people in an attempt to enhance a party, festival or concert experience.
However, dozens of Australians become seriously ill or die after using party drugs
each year.

The most common party drug is ecstasy (MDMA), but the pills/tablets/capsules are
of variable purity or don’t actually contain any MDMA and may contain a wide range
of other substances. You cannot be sure what you’re taking and the risks to your
health are high.

Performance and image enhancing drugs

Performance and image enhancing drugs are substances used by people to change
their physical appearance or boost their sporting ability, for example, weightlifters
and athletes.

There are 3 main types of performance and image enhancing drugs:

 anabolic steroids — synthetic hormones that help grow and repair muscles

 peptides — stimulate the release of human growth hormone, which is

involved in muscle and bone growth
  hormones — both natural and artificial — for example, growth hormones,
selective androgen receptor modules, insulin-like growth factors, mechanical
growth factor

Read more about performance and image enhancing drugs.

Prescription drugs
Medicines prescribed by a doctor — also known as pharmaceuticals — that are not
being used appropriately can cause harm, both short and long-term. People assume
that all prescribed medicines are safe, but not following instructions or combining
them with other medicines, drugs and/or alcohol can be dangerous.
Did you know?
Drug-related deaths from prescribed drugs are more common than those for illegal
drugs.

Examples include:

 painkillers — codeine, oxycodone

 sedatives and sleeping pills — benzodiazepines

Read more about medicines and prescribed drugs.

Psychoactive drugs
Psychoactive drugs affect the way you think, feel and behave. They act mainly on the
central nervous system, changing brain functions and temporarily changing your
consciousness.

Examples include:

 caffeine

 cannabis

 psilocybin (magic mushrooms)

 LSD

Synthetic drugs
Synthetics drugs are a range of drugs that have been developed to create similar
effects to banned drugs. These new psychoactive substances are being developed
quickly, trying to stay ahead of the law. They are also called ‘legal highs’, although in
most cases they are not legal.
Because they are not regulated or tested and change constantly there is not a lot of
information about their effects and side-effects. You cannot be sure what you are
taking or how it will affect you.

Examples include:

 synthetic cannabis

 NBOMe (N-methoxybenzyl) — similar effects to LSD

Our priorities
Our National Drug Strategy identifies a number of drug types that cause the most
harm in Australia. These include:

 alcohol

 tobacco

 cannabis

 methamphetamines (e.g., MDMA) and other stimulants such as cocaine

 new psychoactive substances — synthetic drugs

 opioids, including heroin

 the non-medical use of prescription drugs

Gamma-hydroxybutyrate
Drug

Description
Description
gamma-Hydroxybutyric acid or γ-Hydroxybutyric acid, also known as 4-hydroxybutanoic acid, is a
naturally occurring neurotransmitter and a psychoactive drug. It is a precursor to GABA,
glutamate, and glycine in certain brain areas. It acts on the GHB receptor and is a weak agonist
at the GABAB receptor. Wikipedia

Formula: C4H8O3
Molar mass: 104.1 g/mol
CAS ID: 591-81-1
Classification: Hydroxybutyrates
IUPAC ID: 4-Hydroxybutanoic acid, Sodium 4-hydroxybutanoate
Soluble in: Alcohol, Water
Diazepam
Medicinal

Description
Description
Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an
anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol
withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, insomnia, and
restless legs syndrome. Wikipedia

Formula: C16H13ClN2O

Boiling point: 497.4 °C

Molar mass: 284.7 g/mol

CAS ID: 439-14-5

Bioavailability: 76% (64–97%) by mouth, 81% (62–98%) rectal

Elimination half-life: (50 hours); 20–100 hours (36–200 hours for main active
metabolite desmethyldiazepam)

People also search for: Lorazepam, Alprazolam, Clonazepam, MORE

VALIUM
 Generic Name: diazepam tablets
 Brand Name: Valium
Last reviewed on RxList: 2/22/2021
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PROFESSIONAL
Drug Description

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What is Valium and how is it used?
Valium is a prescription medicine used to treat symptoms of anxiety, muscle spasm, alcohol
withdrawal and as a sedative before surgery or to treat seizures. Valium may be used alone or
with other medications.
Valium belongs to a class of drugs called Antianxiety Agents; Anxiolytics,
Benzodiazepines; Skeletal Muscle Relaxants; Anticonvulsants, Benzodiazepine.
It is not known if Valium is safe and effective in children younger than 6 months of age.
What are the possible side effects of Valium?
Valium may cause serious side effects including:
 weak or shallow breathing,
 severe drowsiness,
 lightheadedness,
 depressed mood,
 thoughts of suicide or hurting yourself,
 confusion,
 hallucinations,
 anxiety,
 panic attacks,
 trouble sleeping,
 hyperactivity,
 agitation,
 aggression,
 hostility,
 unusual risk-taking behavior, and
 new or worsening seizures
Get medical help right away, if you have any of the symptoms listed above.
The most common side effects of Valium include:
 drowsiness,
 tiredness,
 muscle weakness, and
 loss of coordination
Tell the doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Valium. For more information, ask your doctor
or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.

DESCRIPTION
Valium (diazepam) is a benzodiazepine derivative. The chemical name of diazepam is 7-
chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin- 2-one. It is a colorless to light
yellow crystalline compound, insoluble in water. The empirical formula is C16H13ClN2O and
the molecular weight is 284.75. The structural formula is as follows:

Valium is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg

diazepam. In addition to the active ingredient diazepam, each tablet contains the following
inactive ingredients: anhydrous lactose, corn starch, pregelatinized starch and calcium
stearate with the following dyes: 5-mg tablets contain FD&C Yellow No. 6 and D&C Yellow
No. 10; 10-mg tablets contain FD&C Blue No. 1. Valium 2-mg tablets contain no dye.
Indications

INDICATIONS
Valium is indicated for the management of anxiety disorders or for the shortterm relief of the
symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually
does not require treatment with an anxiolytic. In acute alcohol withdrawal, Valium may be
useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium
tremens and hallucinosis.
Valium is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to
local pathology (such as inflammation of the muscles or joints, or secondary
to trauma), spasticity caused by upper motor neuron disorders (such as cerebral
palsy and paraplegia), athetosis, and stiff-man syndrome.
Oral Valium may be used adjunctively in convulsive disorders, although it has not proved
useful as the sole therapy.
The effectiveness of Valium in long-term use, that is, more than 4 months, has not been
assessed by systematic clinical studies. The physician should periodically reassess the
usefulness of the drug for the individual patient.
Dosage
 DOSAGE AND ADMINISTRATION
Dosage should be individualized for maximum beneficial effect. While the usual daily
dosages given below will meet the needs of most patients, there will be some who may
require higher doses. In such cases dosage should be increased cautiously to avoid adverse
effects.
ADULTS: USUAL DAILY DOSE:

Management of Anxiety Disorders and Relief of Symptoms of Depending upon severity of symptoms—2 mg to 10 mg, 2 to 4
Anxiety. times daily

10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg,

Symptomatic Relief in Acute Alcohol Withdrawal.
3 or 4 times daily as needed

Adjunctively for Relief of Skeletal Muscle Spasm. 2 mg to 10 mg, 3 or 4 times daily

Adjunctively in Convulsive Disorders. 2 mg to 10 mg, 2 to 4 times daily

2 mg to 2.5 mg, 1 or 2 times daily initially; increase gradually as

Geriatric Patients, or in the presence of debilitating disease.
needed and tolerated

PEDIATRIC PATIENTS:  

Because of varied responses to CNS-acting drugs, initiate

1 mg to 2.5 mg, 3 or 4 times daily initially; increase gradually as
therapy with lowest dose and increase as required. Not for use
needed and tolerated
in pediatric patients under 6 months.

HOW SUPPLIED
For oral administration, Valium is supplied as round, flat-faced scored tablets with V-shaped
perforation and beveled edges. Valium is available as follows: 2 mg, white - bottles of 100
(NDC 0140-0004-01); 5 mg, yellow - bottles of 100 (NDC 0140-0005-01) and 500
(NDC 0140-0005-14); 10 mg, blue - bottles of 100 (NDC 0140-0006-01) and 500
(NDC 0140-0006-14).
Engraved on tablets:
2 mg - 2 VALIUM® (front) ROCHE (twice on scored side)
5 mg - 5 VALIUM® (front) ROCHE (twice on scored side)
10 mg - 10 VALIUM® (front) ROCHE (twice on scored side)
Storage
Store at room temperature 59° to 86°F (15° to 30°C). Dispense in tight, lightresistant
containers as defined in USP/NF.
Distributed by:  Genentech USA, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990.
Revised: August 2015

Side Effects

SIDE EFFECTS
Side effects most commonly reported were drowsiness, fatigue, muscle weakness, and ataxia.
The following have also been reported:
Central Nervous System: confusion, depression, dysarthria, headache, slurred
speech, tremor, vertigo
Gastrointestinal System: constipation, nausea, gastrointestinal disturbances
Special Senses: blurred vision, diplopia, dizziness
Cardiovascular System: hypotension
Psychiatric and Paradoxical Reactions: stimulation, restlessness, acute hyperexcited states,
anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, delusions,
increased muscle spasticity, insomnia, sleep disturbances, and nightmares. Inappropriate
behavior and other adverse behavioral effects have been reported when
using benzodiazepines. Should these occur, use of the drug should be discontinued. They are
more likely to occur in children and in the elderly.
Urogenital System: incontinence, changes in libido, urinary retention
Skin and Appendages: skin reactions
Laboratories: elevated transaminases and alkaline phosphatase
Other: changes in salivation, including dry mouth, hypersalivation
Antegrade amnesia may occur using therapeutic dosages, the risk increasing at higher
dosages. Amnestic effects may be associated with inappropriate behavior.
Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in
patients during and after Valium therapy and are of no known significance.
Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver
function tests are advisable during long-term therapy.
Postmarketing Experience
Injury, Poisoning and Procedural Complications: There have been reports of falls and
fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives
(including alcohol), and in the elderly.
Drug Abuse And Dependence
Diazepam is subject to Schedule IV control under the Controlled Substances Act of 1970.
Abuse and dependence of benzodiazepines have been reported. Addiction-prone individuals
(such as drug addicts or alcoholics) should be under careful surveillance when receiving
diazepam or other psychotropic agents because of the predisposition of such patients to
habituation and dependence. Once physical dependence to benzodiazepines has developed,
termination of treatment will be accompanied by withdrawal symptoms. The risk is more
pronounced in patients on long-term therapy.
Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol have
occurred following abrupt discontinuance of diazepam. These withdrawal symptoms may
consist of tremor, abdominal and muscle cramps, vomiting, sweating, headache, muscle pain,
extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the
following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and
tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations
or epileptic seizures. The more severe withdrawal symptoms have usually been limited to
those patients who had received excessive doses over an extended period of time. Generally
milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following
abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several
months. Consequently, after extended therapy, abrupt discontinuation should generally be
avoided and a gradual dosage tapering schedule followed.
Chronic use (even at therapeutic doses) may lead to the development of physical dependence:
discontinuation of the therapy may result in withdrawal or rebound phenomena.
Rebound Anxiety: A transient syndrome whereby the symptoms that led to treatment with
Valium recur in an enhanced form. This may occur upon discontinuation of treatment. It may
be accompanied by other reactions including mood changes, anxiety, and restlessness. Since
the risk of withdrawal phenomena and rebound phenomena is greater after abrupt
discontinuation of treatment, it is recommended that the dosage be decreased gradually.
Drug Interactions

DRUG INTERACTIONS
Centrally Acting Agents
If Valium is to be combined with other centrally acting agents, careful consideration should
be given to the pharmacology of the agents employed particularly with compounds that may
potentiate or be potentiated by the action of Valium, such as phenothiazines, antipsychotics,
anxiolytics/sedatives, hypnotics, anticonvulsants, narcotic analgesics,
anesthetics, sedative antihistamines, narcotics, barbiturates, MAO inhibitors and
other antidepressants.
Alcohol
Concomitant use with alcohol is not recommended due to enhancement of the sedative effect.
Antacids
Diazepam peak concentrations are 30% lower when antacids are administered concurrently.
However, there is no effect on the extent of absorption. The lower peak concentrations appear
due to a slower rate of absorption, with the time required to achieve peak concentrations on
average 20 - 25 minutes greater in the presence of antacids. However, this difference was not
statistically significant.
Compounds Which Inhibit Certain Hepatic Enzymes
There is a potentially relevant interaction between diazepam and compounds which inhibit
certain hepatic enzymes (particularly cytochrome P450 3A and 2C19). Data indicate that
these compounds influence the pharmacokinetics of diazepam and may lead to increased and
prolonged sedation. At present, this reaction is known to occur with cimetidine, ketoconazole,
fluvoxamine, fluoxetine, and omeprazole.
Phenytoin
There have also been reports that the metabolic elimination of phenytoin is decreased by
diazepam.
Warnings

WARNINGS
Valium is not recommended in the treatment of psychotic patients and should not be
employed instead of appropriate treatment.
Since Valium has a central nervous system depressant effect, patients should be advised
against the simultaneous ingestion of alcohol and other CNSdepressant drugs during Valium
therapy.
As with other agents that have anticonvulsant activity, when Valium is used as an adjunct in
treating convulsive disorders, the possibility of an increase in the frequency and/or severity
of grand mal seizures may require an increase in the dosage of standard anticonvulsant
medication. Abrupt withdrawal of Valium in such cases may also be associated with a
temporary increase in the frequency and/or severity of seizures.
Pregnancy
An increased risk of congenital malformations and other developmental abnormalities
associated with the use of benzodiazepine drugs during pregnancy has been suggested. There
may also be non-teratogenic risks associated with the use of benzodiazepines during
pregnancy. There have been reports of neonatal flaccidity, respiratory and feeding
difficulties, and hypothermia in children born to mothers who have been receiving
benzodiazepines late in pregnancy. In addition, children born to mothers receiving
benzodiazepines on a regular basis late in pregnancy may be at some risk of experiencing
withdrawal symptoms during the postnatal period.
Diazepam has been shown to be teratogenic in mice and hamsters when given orally at daily
doses of 100 mg/kg or greater (approximately eight times the maximum recommended
human dose [MRHD=1 mg/kg/day] or greater on a mg/m² basis). Cleft
palate and encephalopathy are the most common and consistently reported malformations
produced in these species by administration of high, maternally toxic doses of diazepam
during organogenesis. Rodent studies have indicated that prenatal exposure to diazepam
doses similar to those used clinically can produce long-term changes in cellular immune
responses, brain neurochemistry, and behavior.
In general, the use of diazepam in women of childbearing potential, and more specifically
during known pregnancy, should be considered only when the clinical situation warrants the
risk to the fetus. The possibility that a woman of childbearing potential may be pregnant at
the time of institution of therapy should be considered. If this drug is used during pregnancy,
or if the patient becomes pregnant while taking this drug, the patient should be apprised of
the potential hazard to the fetus. Patients should also be advised that if they become pregnant
during therapy or intend to become pregnant they should communicate with their physician
about the desirability of discontinuing the drug.
Labor And Delivery
Special care must be taken when Valium is used during labor and delivery, as high single
doses may produce irregularities in the fetal heart rate and hypotonia, poor sucking,
hypothermia, and moderate respiratory depression in the neonates. With newborn infants it
must be remembered that the enzyme system involved in the breakdown of the drug is not yet
fully developed (especially in premature infants).
Nursing Mothers
Diazepam passes into breast milk. Breastfeeding is therefore not recommended in patients
receiving Valium.
Precautions

PRECAUTIONS
General
If Valium is to be combined with other psychotropic agents or anticonvulsant drugs, careful
consideration should be given to the pharmacology of the agents to be employed -
particularly with known compounds that may potentiate the action of diazepam, such as
phenothiazines, narcotics, barbiturates, MAO inhibitors and
other antidepressants (see DRUG INTERACTIONS).
The usual precautions are indicated for severely depressed patients or those in whom there is
any evidence of latent depression or anxiety associated with depression, particularly the
recognition that suicidal tendencies may be present and protective measures may be
necessary.
Psychiatric and paradoxical reactions are known to occur when using benzodiazepines
(see ADVERSE REACTIONS). Should this occur, use of the drug should be discontinued.
These reactions are more likely to occur in children and the elderly.
A lower dose is recommended for patients with chronic respiratory insufficiency, due to the
risk of respiratory depression.
Benzodiazepines should be used with extreme caution in patients with a history of alcohol or
drug abuse (see Drug Abuse And Dependence).
In debilitated patients, it is recommended that the dosage be limited to the smallest effective
amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice
daily, initially, to be increased gradually as needed and tolerated).
Some loss of response to the effects of benzodiazepines may develop after repeated use of
Valium for a prolonged time.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In studies in which mice and rats were administered diazepam in the diet at a dose of 75
mg/kg/day (approximately 6 and 12 times, respectively, the maximum recommended human
dose [MRHD=1 mg/kg/day] on a mg/m² basis) for 80 and 104 weeks, respectively, an
increased incidence of liver tumors was observed in males of both species. The data currently
available are inadequate to determine the mutagenic potential of diazepam. Reproduction
studies in rats showed decreases in the number of pregnancies and in the number of surviving
offspring following administration of an oral dose of 100 mg/kg/day (approximately 16 times
the MRHD on a mg/m² basis) prior to and during mating and throughout gestation and
lactation. No adverse effects on fertility or offspring viability were noted at a dose of 80
mg/kg/day (approximately 13 times the MRHD on a mg/m² basis).
Pregnancy
Category D (see WARNINGS: Pregnancy).
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 6 months have not been
established.
Geriatric Use
In elderly patients, it is recommended that the dosage be limited to the smallest effective
amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice
daily, initially to be increased gradually as needed and tolerated).
Extensive accumulation of diazepam and its major metabolite, desmethyldiazepam, has been
noted following chronic administration of diazepam in healthy elderly male subjects.
Metabolites of this drug are known to be substantially excreted by the kidney, and the risk of
toxic reactions may be greater in patients with impaired renal function. Because elderly
patients are more likely to have decreased renal function, care should be taken in dose
selection, and it may be useful to monitor renal function.
Hepatic Insufficiency
Decreases in clearance and protein binding, and increases in volume of distribution and half-
life have been reported in patients with cirrhosis. In such patients, a 2- to 5- fold increase in
mean half-life has been reported. Delayed elimination has also been reported for the active
metabolite desmethyldiazepam. Benzodiazepines are commonly implicated in hepatic
encephalopathy. Increases in half-life have also been reported in hepatic fibrosis and in both
acute and chronic hepatitis (see CLINICAL PHARMACOLOGY: Pharmacokinetics in
Special Populations: Hepatic Insufficiency).
Overdosage & Contraindications

OVERDOSE
Overdose of benzodiazepines is usually manifested by central nervous system depression
ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, confusion,
and lethargy. In more serious cases, symptoms may include ataxia, diminished
reflexes, hypotonia, hypotension, respiratory depression, coma (rarely), and death (very
rarely). Overdose of benzodiazepines in combination with other CNS depressants (including
alcohol) may be fatal and should be closely monitored.
Management Of Overdosage
Following overdose with oral benzodiazepines, general supportive measures should be
employed including the monitoring of respiration, pulse, and blood pressure. Vomiting
should be induced (within 1 hour) if the patient is conscious. Gastric lavage should be
undertaken with the airway protected if the patient is unconscious. Intravenous fluids should
be administered. If there is no advantage in emptying the stomach, activated charcoal should
be given to reduce absorption. Special attention should be paid to respiratory and cardiac
function in intensive care. General supportive measures should be employed, along with
intravenous fluids, and an adequate airway maintained. Should hypotension develop,
treatment may include intravenous fluid therapy, repositioning, judicious use of vasopressors
appropriate to the clinical situation, if indicated, and other appropriate
countermeasures. Dialysis is of limited value.
As with the management of intentional overdosage with any drug, it should be considered
that multiple agents may have been ingested.
Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or
partial reversal of the sedative effects of benzodiazepines and may be used in situations when
an overdose with a benzodiazepine is known or suspected. Prior to the administration of
flumazenil, necessary measures should be instituted to secure airway, ventilation and
intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper
management of benzodiazepine overdose. Patients treated with flumazenil should be
monitored for resedation, respiratory depression and other residual benzodiazepine effects for
an appropriate period after treatment. The prescriber should be aware of a risk of seizure
in association with flumazenil treatment, particularly in long-term benzodiazepine users
and in cyclic antidepressant overdose. Caution should be observed in the use of flumazenil
in epileptic patients treated with benzodiazepines. The complete flumazenil package insert,
including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, should be
consulted prior to use.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of
benzodiazepines (see Drug Abuse And Dependence).

CONTRAINDICATIONS
Valium is contraindicated in patients with a known hypersensitivity to diazepam and, because
of lack of sufficient clinical experience, in pediatric patients under 6 months of age. Valium
is also contraindicated in patients with myasthenia gravis, severe respiratory insufficiency,
severe hepatic insufficiency, and sleep apnea syndrome. It may be used in patients with open-
angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute
narrow-angle glaucoma.
Clinical Pharmacology

CLINICAL PHARMACOLOGY
Diazepam is a benzodiazepine that exerts anxiolytic, sedative,
musclerelaxant, anticonvulsant and amnestic effects. Most of these effects are thought to
result from a facilitation of the action of gamma aminobutyric acid (GABA), an
inhibitory neurotransmitter in the central nervous system.
Pharmacokinetics
Absorption

After oral administration > 90% of diazepam is absorbed and the average time to achieve
peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours. Absorption is
delayed and decreased when administered with a moderate fat meal. In the presence of food
mean lag times are approximately 45 minutes as compared with 15 minutes when fasting.
There is also an increase in the average time to achieve peak concentrations to about 2.5
hours in the presence of food as compared with 1.25 hours when fasting. This results in an
average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%)
when administered with food.
Distribution

Diazepam and its metabolites are highly bound to plasma proteins (diazepam 98%).
Diazepam and its metabolites cross the blood-brain and placental barriers and are also found
in breast milk in concentrations approximately one tenth of those in maternal plasma (days 3
to 9 post-partum). In young healthy males, the volume of distribution at steady-state is 0.8 to
1.0 L/kg. The decline in the plasma concentration-time profile after oral administration is
biphasic. The initial distribution phase has a half-life of approximately 1 hour, although it
may range up to > 3 hours.
Metabolism

Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-

desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-
desmethyldiazepam and temazepam are both further metabolized to oxazepam. Temazepam
and oxazepam are largely eliminated by glucuronidation.
Elimination

The initial distribution phase is followed by a prolonged terminal elimination phase (half-life
up to 48 hours). The terminal elimination half-life of the active metabolite N-
desmethyldiazepam is up to 100 hours. Diazepam and its metabolites are excreted mainly in
the urine, predominantly as their glucuronide conjugates. The clearance of diazepam is 20 to
30 mL/min in young adults. Diazepam accumulates upon multiple dosing and there is some
evidence that the terminal elimination half-life is slightly prolonged.
Pharmacokinetics in Special Populations
Children

In children 3 - 8 years old the mean half-life of diazepam has been reported to be 18 hours.
Newborns

In full term infants, elimination half-lives around 30 hours have been reported, with a longer
average half-life of 54 hours reported in premature infants of 28 - 34 weeks gestational age
and 8 - 81 days post-partum. In both premature and full term infants the active metabolite
desmethyldiazepam shows evidence of continued accumulation compared to children. Longer
half-lives in infants may be due to incomplete maturation of metabolic pathways.
Geriatric

Elimination half-life increases by approximately 1 hour for each year of age beginning with a
half-life of 20 hours at 20 years of age. This appears to be due to an increase in volume of
distribution with age and a decrease in clearance. Consequently, the elderly may have lower
peak concentrations, and on multiple dosing higher trough concentrations. It will also take
longer to reach steady-state. Conflicting information has been published on changes of
plasma protein binding in the elderly. Reported changes in free drug may be due to
significant decreases in plasma proteins due to causes other than simply aging.
Hepatic Insufficiency
In mild and moderate cirrhosis, average half-life is increased. The average increase has been
variously reported from 2-fold to 5-fold, with individual half-lives over 500 hours reported.
There is also an increase in volume of distribution, and average clearance decreases by
almost half. Mean half-life is also prolonged with hepatic fibrosis to 90 hours (range 66 - 104
hours), with chronic active hepatitis to 60 hours (range 26 - 76 hours), and with acute viral
hepatitis to 74 hours (range 49 - 129). In chronic active hepatitis, clearance is decreased by
almost half.
Medication Guide

PATIENT INFORMATION
Diazepam
(dye-AZ-e-pam) 10 mg Tablets
What is the most important information I should know about diazepam tablets?
Diazepam tablets are a benzodiazepine medicine. Taking benzodiazepines
with opioid medicines, alcohol, or other central nervous system depressants (including street
drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and
death.
Diazepam tablets can make you sleepy or dizzy, and can slow your thinking and motor skills.
Do not drive, operate heavy machinery, or do other dangerous activities until you know how
diazepam tablets affect you.
Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking
diazepam tablets without first talking to your healthcare provider. When taken with alcohol or
drugs that cause sleepiness or dizziness, diazepam tablets may make your sleepiness or
dizziness much worse.
Do not take more diazepam tablets than prescribed.
What are diazepam tablets?
 Diazepam tablets are a prescription medicine used:
 to treat anxiety disorders
 for the short-term relief of the symptoms of anxiety
 to relieve the symptoms of alcohol withdrawal including agitation, shakiness (tremor),
sudden and severe mental or nervous system changes (delirium tremens) and seeing or
hearing things that others do not see or hear (hallucinations)
 along with other medicines for the relief of muscle spasms
 along with other medicines to treat seizure disorders
Diazepam tablets are a federal controlled substance (C-IV) because it can be abused or lead
to dependence. Keep diazepam tablets in a safe place to prevent misuse and abuse. Selling or
giving away diazepam tablets may harm others, and is against the law. Tell your healthcare
provider if you have abused or been dependent on alcohol, prescription medicines or street
drugs.
It is not known if diazepam tablets are safe and effective in children under 6 months of age.
It is not known if diazepam tablets are safe and effective for use longer than 4 months.
Do not take diazepam tablets if you:
 are allergic to diazepam or any of the ingredients in diazepam tablets. See the end of
this Medication Guide for a complete list of ingredients in diazepam tablets.
 have a disease that can cause muscle weakness called myasthenia gravis
 have severe breathing problems (severe respiratory insufficiency)
 have severe liver problems
 have a sleep problem called sleep apnea syndrome
Before you take diazepam tablets, tell your healthcare provider about all of your
medical conditions, including if you:
 have or have had depression, mood problems, or suicidal thoughts or behavior
 have lung disease or breathing problems
 have liver or kidney problems
 are pregnant or plan to become pregnant. Diazepam tablets may harm your unborn
baby. You and your healthcare provider should decide if you should take diazepam
tablets while you are pregnant.
 are breastfeeding or plan to breastfeed. Diazepam passes into your breast milk and
may harm your baby. Talk to your healthcare provider about the best way to feed your
baby if you take diazepam tablets. Do not breastfeed while taking diazepam tablets.
Tell your healthcare provider about all the medicines you take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements. Taking diazepam tablets with
certain other medicines can cause side effects or affect how well diazepam tablets or the other
medicines work. Do not start or stop other medicines without talking to your healthcare
provider.
How should I take diazepam tablets?
Take diazepam tablets exactly as your healthcare provider tells you to take them. Your
healthcare provider will tell you how many diazepam tablets to take and when to take them.
Talk to your healthcare provider about slowly stopping diazepam tablets to avoid withdrawal
symptoms.
If you take too many diazepam tablets, call your healthcare provider or go to the nearest
hospital emergency room right away.
What should I avoid while taking diazepam tablets?
Diazepam tablets can cause you to be drowsy. Do not drive a car or operate heavy machinery
until you know how diazepam tablets affect you.
You should not drink alcohol while taking diazepam tablets. Drinking alcohol can increase
your chances of having serious side effects.
What are the possible side effects of diazepam tablets?
 Diazepam tablets may cause serious side effects, including:
 See “What is the most important information I should know about diazepam
tablets?”
 Seizures. Taking diazepam tablets with other medicines used to treat epilepsy can
cause an increase in the number or severity of grand mal seizures.
 Withdrawal symptoms. You may have withdrawal symptoms if you stop taking
diazepam tablets suddenly. Withdrawal symptoms can be serious and include
seizures. Mild withdrawal symptoms include a depressed mood and trouble sleeping.
Talk to your healthcare provider about slowly stopping diazepam tablets to avoid
withdrawal symptoms.
 Like other antiepileptic drugs, diazepam tablets may cause suicidal thoughts or
actions in a very small number of people, about 1 in 500.
Call your healthcare provider right away if you have any of these symptoms, especially
if they are new, worse, or worry you:
 thoughts about suicide or dying
 new or worse anxiety
 trouble sleeping (insomnia)
 acting on dangerous impulses
 attempts to commit suicide
 feeling agitated or restless
 new or worse irritability
 an extreme increase in activity and talking (mania)
 new or worse depression
 panic attacks
 acting aggressive, being angry, or violent
 other unusual changes in behavior or mood
How can I watch for early symptoms of suicidal thoughts and actions?
Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or
feelings.
Keep all follow-up visits with your healthcare provider as scheduled.
Call your healthcare provider between visits as needed, especially if you are worried about
symptoms. Suicidal thoughts or actions can be caused by things other than medicines. If you
have suicidal thoughts or actions, your healthcare provider may check for other causes.
Abuse and dependence. Taking diazepam tablets can cause physical and psychological
dependence. Physical and psychological dependence is not the same as drug addiction. Your
healthcare provider can tell you more about the differences between physical and
psychological dependence and drug addiction.
The most common side effects of diazepam tablets include:
 drowsiness
 muscle weakness
 fatigue
 loss of control of body movements (ataxia)
These are not all the possible side effects of diazepam tablets. Call your doctor for medical
advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may
also report side effects to Teva Pharmaceuticals USA, Inc. at 1-866-832-8537.
How should I store diazepam tablets?
Store diazepam tablets in a tightly closed container between 68°F to 77°F (20°C to
25°C) and out of the light.
Keep diazepam tablets and all medicines out of the reach of children.
General information about the safe and effective use of diazepam tablets.
Medicines are sometimes prescribed for purposes other than those listed in a Medication
Guide. Do not use diazepam tablets for a condition for which they were not prescribed. Do
not give diazepam tablets to other people, even if they have the same symptoms that you
have. They may harm them. You can ask your pharmacist or healthcare provider for
information about diazepam tablets that is written for health professionals.
What are the ingredients in diazepam tablets?
Active ingredient: diazepam
Inactive ingredients: anhydrous lactose, colloidal silicon dioxide; colorants: 5 mg only
(D&C Yellow No. 10 aluminum lake and FD&C Yellow No. 6); 10 mg only (FD&C Blue
No. 1 aluminum lake); magnesium stearate, microcrystalline cellulose, pregelatinized corn
starch, and sodium starch glycolate

WHAT IS DIAZEPAM?
Diazepam is a benzodiazepine (ben-zoe-dye-AZE-eh-peen) that is used to treat anxiety
disorders, alcohol withdrawal symptoms, or muscle spasms. Diazepam is sometimes used
with other medications to treat seizures.
Diazepam may also be used for purposes not listed in this medication guide.

WHAT ARE THE POSSIBLE SIDE EFFECTS OF DIAZEPAM?

Get emergency medical help if you have signs of an allergic reaction: hives; difficult
breathing; swelling of your face, lips, tongue, or throat.
Diazepam can slow or stop your breathing, and death may occur. A person caring for you
should seek emergency medical attention if you have slow breathing with long pauses, blue
colored lips, or if you are hard to wake up.
Call your doctor at once if you have:
 weak or shallow breathing;
 severe drowsiness or feeling like you might pass out;
 depressed mood, thoughts of suicide or hurting yourself;
 confusion, hallucinations;
 anxiety, panic attacks, trouble sleeping;
 hyperactivity, agitation, aggression, hostility;
 unusual risk-taking behavior; or
 new or worsening seizures.
The sedative effects of diazepam may last longer in older adults. Accidental falls are common
in elderly patients who take benzodiazepines. Use caution to avoid falling or accidental injury
while you are taking diazepam.
Common side effects may include:
 drowsiness;
 tired feeling;
 muscle weakness; or
 loss of coordination.
This is not a complete list of side effects and others may occur. Call your doctor for medical
advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW

ABOUT DIAZEPAM?
You should not use this medicine if you are allergic to diazepam or similar medicines
(Klonopin, Xanax, and others), or if you have myasthenia gravis, severe liver disease,
narrow-angle glaucoma, a severe breathing problem, or sleep apnea.
MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR
DEATH, especially in a child or other person using the medicine without a prescription.
Fatal side effects can occur if you use this medicine with opioid medicine, alcohol, or
other drugs that cause drowsiness or slow your breathing.
Do not give this medication to a child younger than 6 months old.
 Valium Patient Information including How Should I Take

WHAT SHOULD I DISCUSS WITH MY HEALTHCARE PROVIDER

BEFORE TAKING DIAZEPAM?
You should not use this medicine if you are allergic to diazepam or similar drugs (Klonopin,
Xanax, and others), or if you have:
 myasthenia gravis (a muscle weakness disorder);
 severe liver disease;
 a severe breathing problem;
 sleep apnea (breathing stops during sleep); or
 alcoholism, or addiction to drugs similar to diazepam.
Tell your doctor if you have ever had:
 glaucoma;
 asthma, emphysema, bronchitis, chronic obstructive pulmonary disorder (COPD), or
other breathing problems;
 kidney or liver disease;
 epilepsy or other seizure disorder;
 a drug or alcohol addiction; or
 mental illness, depression, or suicidal thoughts or behavior.
When treating seizures, do not start or stop taking diazepam during pregnancy without
your doctor's advice. Diazepam may cause harm to an unborn baby, but having a seizure
during pregnancy could harm both the mother and the baby. Tell your doctor right away if
you become pregnant while taking diazepam for seizures.
When treating anxiety, alcohol withdrawal, or muscle spasms: If you take diazepam
while you are pregnant, your baby could become dependent on the drug. This can cause
life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on
habit-forming medicine may need medical treatment for several weeks. Tell your doctor if
you are pregnant or plan to become pregnant.
You should not breast-feed while using this medicine.
Diazepam is not approved for use by anyone younger than 6 months old. Do not give this
medicine to a child without a doctor's advice.

HOW SHOULD I TAKE DIAZEPAM?

Follow all directions on your prescription label and read all medication guides or instruction
sheets. Your doctor may occasionally change your dose. Use the medicine exactly as
directed.
Diazepam may be habit-forming. Misuse can cause addiction, overdose, or death. Keep the
medication in a place where others cannot get to it. Selling or giving away this medicine is
against the law.
Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-
measuring device (not a kitchen spoon).
Diazepam should be used for only a short time. Do not take this medicine for longer than 4
months without your doctor's advice.
Do not stop using diazepam suddenly, even if you feel fine. Stopping suddenly may cause
increased seizures. Follow your doctor's instructions about tapering your dose.
Call your doctor at once if you feel that this medicine is not working as well as usual, or if
you think you need to use more than usual.
You will need frequent medical tests.
Store at room temperature away from moisture, heat, and light. Keep track of your medicine.
Diazepam is a drug of abuse and you should be aware if anyone is using your medicine
improperly or without a prescription.
Do not keep leftover diazepam. Just one dose can cause death in someone using this
medicine accidentally or improperly. Ask your pharmacist where to locate a drug take-back
disposal program. If there is no take-back program, flush the unused medicine down the
toilet.
Valium Patient Information including If I Miss a Dose

WHAT HAPPENS IF I MISS A DOSE?

Take the medicine as soon as you can, but skip the missed dose if it is almost
time for your next dose. Do not take two doses at one time.

WHAT HAPPENS IF I OVERDOSE?

Seek emergency medical attention or call the Poison Help line at 1-800-222-
1222. An overdose of diazepam can be fatal.

Overdose symptoms may include extreme drowsiness, loss of balance or

coordination, limp or weak muscles, or fainting.

WHAT SHOULD I AVOID WHILE TAKING DIAZEPAM?

Do not drink alcohol. Dangerous side effects could occur.

Avoid driving or hazardous activity until you know how this medicine will affect
you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Grapefruit may interact with diazepam and lead to unwanted side effects. Avoid

the use of grapefruit products.
WHAT OTHER DRUGS WILL AFFECT DIAZEPAM?
Taking diazepam with other drugs that make you sleepy or slow your
breathing can cause dangerous side effects or death. Ask your doctor before
taking a sleeping pill, opioid pain medicine, prescription cough medicine, a
muscle relaxer, or medicine for anxiety, depression, or seizures.

Other drugs may affect diazepam, including prescription and over-the-counter

medicines, vitamins, and herbal products. Tell your doctor about all your current
medicines and any medicine you start or stop using.

Methamphetamine
Drug

Description
Description
Methamphetamine is a potent central nervous system stimulant that is mainly used as a
recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity
disorder and obesity. Wikipedia

Formula: C10H15N

IUPAC ID: N-methyl-1-phenylpropan-2-amine

Melting point: 170 °C

Other names: N-methylamphetamine, N,α-dimethylphenethylamine, desoxyephedrine

Duration of action: 10–20 hours

Onset of action: Rapid

Methamphetamine[note 1] (contracted from N-methylamphetamine) is a potent central nervous

system (CNS) stimulant that is mainly used as a recreational drug and less commonly as
a second-line treatment for attention deficit hyperactivity disorder and obesity.
[15]
 Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-
methamphetamine and dextro-methamphetamine.[note 2] Methamphetamine properly refers to a
specific chemical, the racemic free base, which is an equal mixture of levomethamphetamine and
dextromethamphetamine in their pure amine forms. It is rarely prescribed over concerns involving
human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among
other concerns, as well as the availability of safer substitute drugs with comparable treatment
efficacy. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine.

Both methamphetamine and dextromethamphetamine are illicitly trafficked and sold owing to
their potential for recreational use. The highest prevalence of illegal methamphetamine use
occurs in parts of Asia, Oceania, and in the United States, where racemic methamphetamine and
dextromethamphetamine are classified as schedule II controlled substances.
Levomethamphetamine is available as an over-the-counter (OTC) drug for use as an
inhaled nasal decongestant in the United States.[note 3] Internationally, the production, distribution,
sale, and possession of methamphetamine is restricted or banned in many countries, due to its
placement in schedule II of the United Nations Convention on Psychotropic Substances treaty.
While dextromethamphetamine is a more potent drug, racemic methamphetamine is sometimes
illicitly produced due to the relative ease of synthesis and limited availability of chemical
precursors.

In low to moderate doses, methamphetamine can elevate mood, increase alertness,

concentration and energy in fatigued individuals, reduce appetite, and promote weight loss. At
very high doses, it can induce psychosis, breakdown of skeletal muscle, seizures and bleeding in
the brain. Chronic high-dose use can precipitate unpredictable and rapid mood swings, stimulant
psychosis (e.g., paranoia, hallucinations, delirium, and delusions) and violent behavior.
Recreationally, methamphetamine's ability to increase energy has been reported to lift
mood and increase sexual desire to such an extent that users are able to engage in sexual
activity continuously for several days.[19] Methamphetamine is known to possess a
high addiction liability (i.e., a high likelihood that long-term or high dose use will lead to
compulsive drug use) and high dependence liability (i.e. a high likelihood
that withdrawal symptoms will occur when methamphetamine use ceases). Withdrawal off of
methamphetamine after heavy use may lead to a post-acute-withdrawal syndrome, which can
persist for months beyond the typical withdrawal period. Methamphetamine is neurotoxic to
human midbrain dopaminergic neurons at high doses. Methamphetamine has been shown to
have a higher affinity and, as a result, higher toxicity toward serotonergic neurons
than amphetamine.[20][21] Methamphetamine neurotoxicity causes adverse changes in brain
structure and function, such as reductions in grey matter volume in several brain regions, as well
as adverse changes in markers of metabolic integrity.[21]

Methamphetamine belongs to the substituted phenethylamine and substituted

amphetamine chemical classes. It is related to the other dimethylphenethylamines as a positional
isomer of these compounds, which share the common chemical formula: C10H15N1.

Contents

 1Uses
o 1.1Medical
o 1.2Recreational
 2Contraindications
 3Adverse effects
o 3.1Physical
o 3.2Fatal
o 3.3Psychological
o 3.4Neurotoxic and neuroimmunological
o 3.5Addictive
o 3.6Neonatal
 4Overdose
o 4.1Psychosis
o 4.2Emergency treatment
 5Interactions
  6Pharmacology
o 6.1Pharmacodynamics
o 6.2Pharmacokinetics
 7Chemistry
o 7.1Degradation
o 7.2Synthesis
 8History, society, and culture
 9Trafficking
 10Legal status
 11Research
 12See also
 13Explanatory notes
 14Reference notes
 15References
 16Further reading
 17External links

Uses
Medical

Desoxyn (Methamphetamine Hydrochloride) 100 tablets.

In the United States, dextromethamphetamine hydrochloride, under the trade name Desoxyn,

has been approved by the FDA for treating ADHD and obesity in both adults and children;[22]
[23]
 however, the FDA also indicates that the limited therapeutic usefulness of methamphetamine
should be weighed against the inherent risks associated with its use.[22] Methamphetamine is
sometimes prescribed off label for narcolepsy and idiopathic hypersomnia.[24][25] In the United
States, methamphetamine's levorotary form is available in some over-the-counter (OTC) nasal
decongestant products.[note 3]

As methamphetamine is associated with a high potential for misuse, the drug is regulated under
the Controlled Substances Act and is listed under Schedule II in the United States.
[22]
 Methamphetamine hydrochloride dispensed in the United States is required to include a boxed
warning regarding its potential for recreational misuse and addiction liability.[22]
Recreational
See also: Party and play and the Recreational routes of methamphetamine administration

Methamphetamine is often used recreationally for its effects as a potent euphoriant and stimulant

as well as aphrodisiac qualities.[26]

According to a National Geographic TV documentary on methamphetamine, an entire subculture

known as party and play is based around sexual activity and methamphetamine use.
[26]
 Participants in this subculture, which consists almost entirely of homosexual male
methamphetamine users, will typically meet up through internet dating sites and have sex.[26] Due
to its strong stimulant and aphrodisiac effects and inhibitory effect on ejaculation, with repeated
use, these sexual encounters will sometimes occur continuously for several days on end.[26] The
crash following the use of methamphetamine in this manner is very often severe, with
marked hypersomnia (excessive daytime sleepiness).[26] The party and play subculture is
prevalent in major US cities such as San Francisco and New York City.[26][27]

Desoxyn tablets – pharmaceutical methamphetamine hydrochloride

Crystal meth – illicit methamphetamine hydrochloride

Contraindications
Methamphetamine is contraindicated in individuals with a history of substance use
disorder, heart disease, or severe agitation or anxiety, or in individuals currently
experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension.[22] The FDA
states that individuals who have experienced hypersensitivity reactions to other stimulants in the
past or are currently taking monoamine oxidase inhibitors should not take methamphetamine.
  The FDA also advises individuals with bipolar disorder, depression, elevated blood pressure,
[22]

liver or kidney problems, mania, psychosis, Raynaud's

phenomenon, seizures, thyroid problems, tics, or Tourette syndrome to monitor their symptoms
while taking methamphetamine.[22] Due to the potential for stunted growth, the FDA advises
monitoring the height and weight of growing children and adolescents during treatment.[22]

Adverse effects

A 2010 study ranking various illegal and legal drugs based on statements by drug-harm experts.
Methamphetamine was found to be the fourth most damaging to society.[28]

Physical
The physical effects of methamphetamine can include loss of appetite, hyperactivity, dilated
pupils, flushed skin, excessive sweating, increased movement, dry mouth and teeth
grinding (leading to "meth mouth"), headache, irregular heartbeat (usually as accelerated
heartbeat or slowed heartbeat), rapid breathing, high blood pressure, low blood pressure, high
body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, numbness, tremors,
dry skin, acne, and pale appearance.[22][29] Long-term meth users may have sores on their skin;[30]
[31][32]
 these may be caused by scratching due to itchiness[31] or the belief that insects are crawling
under their skin,[30] and the damage is compounded by poor diet and hygiene.[32] Numerous
deaths related to methamphetamine overdoses have also been reported as well.[33][34]

Meth mouth
Main article: Meth mouth

A suspected case of meth mouth

Methamphetamine users and addicts may lose their teeth abnormally quickly, regardless of the
route of administration, from a condition informally known as meth mouth.[35] The condition is
generally most severe in users who inject the drug, rather than swallow, smoke, or inhale it.
[35]
 According to the American Dental Association, meth mouth "is probably caused by a
combination of drug-induced psychological and physiological changes resulting
in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high-
calorie, carbonated beverages and bruxism (teeth grinding and clenching)".[35][36] As dry mouth is
also a common side effect of other stimulants, which are not known to contribute severe tooth
decay, many researchers suggest that methamphetamine associated tooth decay is more due to
users' other choices. They suggest the side effect has been exaggerated and stylized to create a
stereotype of current users as a deterrence for new ones.[23]

Sexually transmitted infection

Methamphetamine use was found to be related to higher frequencies of unprotected sexual
intercourse in both HIV-positive and unknown casual partners, an association more pronounced
in HIV-positive participants.[37] These findings suggest that methamphetamine use and
engagement in unprotected anal intercourse are co-occurring risk behaviors, behaviors that
potentially heighten the risk of HIV transmission among gay and bisexual men.
[37]
 Methamphetamine use allows users of both sexes to engage in prolonged sexual activity,
which may cause genital sores and abrasions as well as priapism in men.[22][38] Methamphetamine
may also cause sores and abrasions in the mouth via bruxism, increasing the risk of sexually
transmitted infection.[22][38]

Besides the sexual transmission of HIV, it may also be transmitted between users who share a
common needle.[39] The level of needle sharing among methamphetamine users is similar to that
among other drug injection users.[39]

Fatal
Doses of 200 mg or more of methamphetamine are considered fatal.[40]

Psychological
The psychological effects of methamphetamine can include euphoria, dysphoria, changes
in libido, alertness, apprehension and concentration, decreased sense of
fatigue, insomnia or wakefulness, self-confidence, sociability, irritability,
restlessness, grandiosity and repetitive and obsessive behaviors.[22][29][41] Peculiar to
methamphetamine and related stimulants is "punding", persistent non-goal-directed repetitive
activity.[42] Methamphetamine use also has a high association
with anxiety, depression, amphetamine psychosis, suicide, and violent behaviors.[43]

Neurotoxic and neuroimmunological

This diagram depicts the neuroimmune mechanisms that mediate methamphetamine-induced

neurodegeneration in the human brain.[44] The NF-κB-mediated neuroimmune response to
methamphetamine use which results in the increased permeability of the blood–brain barrier arises through
its binding at and activation of sigma receptors, the increased production of reactive oxygen
species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern
molecules (DAMPs), the dysregulation of glutamate transporters (specifically, EAAT1 and EAAT2)
and glucose metabolism, and excessive Ca2+ ion influx in glial cells and dopamine neurons.[44][45][46]

Methamphetamine is directly neurotoxic to dopaminergic neurons in both lab animals and

humans.[20][21] Excitotoxicity, oxidative stress, metabolic compromise, UPS dysfunction, protein
nitration, endoplasmic reticulum stress, p53 expression and other processes contributed to this
neurotoxicity.[47][48][49] In line with its dopaminergic neurotoxicity, methamphetamine use is
associated with a higher risk of Parkinson's disease.[50] In addition to its dopaminergic
neurotoxicity, a review of evidence in humans indicated that high-dose methamphetamine use
can also be neurotoxic to serotonergic neurons.[21] It has been demonstrated that a high core
temperature is correlated with an increase in the neurotoxic effects of methamphetamine.
[51]
 Withdrawal of methamphetamine in dependent persons may lead to post-acute
withdrawal which persists months beyond the typical withdrawal period.[49]

Magnetic resonance imaging studies on human methamphetamine users have also found

evidence of neurodegeneration, or adverse neuroplastic changes in brain structure and function.
[21]
 In particular, methamphetamine appears to cause hyperintensity and hypertrophy of white
matter, marked shrinkage of hippocampi, and reduced gray matter in the cingulate cortex, limbic
cortex, and paralimbic cortex in recreational methamphetamine users.[21] Moreover, evidence
suggests that adverse changes in the level of biomarkers of metabolic integrity and synthesis
occur in recreational users, such as a reduction in N-acetylaspartate and creatine levels and
elevated levels of choline and myoinositol.[21]

Methamphetamine has been shown to activate TAAR1 in human astrocytes and

generate cAMP as a result.[50] Activation of astrocyte-localized TAAR1 appears to function as a
mechanism by which methamphetamine attenuates membrane-bound EAAT2 (SLC1A2) levels
and function in these cells.[50]

Methamphetamine binds to and activates both sigma receptor subtypes, σ1 and σ2, with

micromolar affinity.[46][52] Sigma receptor activation may promote methamphetamine-induced
neurotoxicity by facilitating hyperthermia, increasing dopamine synthesis and release, influencing
microglial activation, and modulating apoptotic signaling cascades and the formation of reactive
oxygen species.[46][52]

Addictive

showAddiction and dependence glossary[53][54][55][56]

Signaling cascade in the nucleus accumbens that results in psychostimulant addiction

 v
 t
 e
Note: colored text contains article links.
Nuclear pore
Nuclear membrane
Plasma membrane
Cav1.2
NMDAR
AMPAR
DRD1
DRD5
DRD2
DRD3
DRD4
Gs
Gi/o
AC
cAMP
cAMP
PKA
CaM
 CaMKII
DARPP-32
PP1
PP2B
CREB
ΔFosB
JunD
c-Fos
SIRT1
HDAC1
[Color legend 1]

This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-
dose exposure to psychostimulants that increase the concentration of synaptic dopamine,
like amphetamine, methamphetamine, and phenethylamine. Following
presynaptic dopamine and glutamate co-release by such psychostimulants,[57][58] postsynaptic receptors for
these neurotransmitters trigger internal signaling events through a cAMP-dependent pathway and
a calcium-dependent pathway that ultimately result in increased CREB phosphorylation.[57][59]
[60]
 Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help
of corepressors;[57][61][62] c-Fos repression acts as a molecular switch that enables the accumulation of ΔFosB
in the neuron.[63] A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for 1–
2 months, slowly accumulates following repeated high-dose exposure to stimulants through this process.[61]
[62]
 ΔFosB functions as "one of the master control proteins" that produces addiction-related structural
changes in the brain, and upon sufficient accumulation, with the help of its downstream targets
(e.g., nuclear factor kappa B), it induces an addictive state.[61][62]

Current models of addiction from chronic drug use involve alterations in gene expression in
certain parts of the brain, particularly the nucleus accumbens.[64][65] The most
important transcription factors[note 4] that produce these alterations are ΔFosB, cAMP response
element binding protein (CREB), and nuclear factor kappa B (NFκB).[65] ΔFosB plays a crucial
role in the development of drug addictions, since its overexpression in D1-type medium spiny
neurons in the nucleus accumbens is necessary and sufficient[note 5] for most of the behavioral and
neural adaptations that arise from addiction.[54][65][67] Once ΔFosB is sufficiently overexpressed, it
induces an addictive state that becomes increasingly more severe with further increases in
ΔFosB expression.[54][67] It has been implicated in addictions
to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol,
and substituted amphetamines, among others.[65][67][68][69][70]

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both directly

oppose the induction of ΔFosB in the nucleus accumbens (i.e., they oppose increases in its
expression).[54][65][71] Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral
vectors can completely block many of the neural and behavioral alterations seen in chronic drug
use (i.e., the alterations mediated by ΔFosB).[65] ΔFosB also plays an important role in regulating
behavioral responses to natural rewards, such as palatable food, sex, and exercise.[65][68][72] Since
both natural rewards and addictive drugs induce expression of ΔFosB (i.e., they cause the brain
to produce more of it), chronic acquisition of these rewards can result in a similar pathological
state of addiction.[65][68] ΔFosB is the most significant factor involved in both amphetamine
addiction and amphetamine-induced sex addictions, which are compulsive sexual behaviors that
result from excessive sexual activity and amphetamine use.[note 6][68][73] These sex addictions (i.e.,
drug-induced compulsive sexual behaviors) are associated with a dopamine dysregulation
syndrome which occurs in some patients taking dopaminergic drugs, such as amphetamine or
methamphetamine.[68][72][73]

Epigenetic factors
Methamphetamine addiction is persistent for many individuals, with 61% of individuals treated for
addiction relapsing within one year.[74] About half of those with methamphetamine addiction
continue with use over a ten-year period, while the other half reduce use starting at about one to
four years after initial use.[75]

The frequent persistence of addiction suggests that long-lasting changes in gene

expression may occur in particular regions of the brain, and may contribute importantly to the
addiction phenotype. Recently a crucial role has been found for epigenetic mechanisms in driving
lasting changes in gene expression in the brain.[76]

A review in 2015[77] summarized a number of studies involving chronic methamphetamine use in

rodents. Epigenetic alterations were observed in the brain reward pathways, including areas
like ventral tegmental area, nucleus accumbens, and dorsal striatum, the hippocampus, and
the prefrontal cortex. Chronic methamphetamine use caused gene-specific histone acetylations,
deacetylations and methylations. Gene-specific DNA methylations in particular regions of the
brain were also observed. The various epigenetic alterations caused downregulations or
upregulations of specific genes important in addiction. For instance, chronic methamphetamine
use caused methylation of the lysine in position 4 of histone 3 located at the promoters of the c-
fos and the C-C chemokine receptor 2 (ccr2) genes, activating those genes in the nucleus
accumbens (NAc).[77] c-fos is well known to be important in addiction.[78] The ccr2 gene is also
important in addiction, since mutational inactivation of this gene impairs addiction.[77]

In methamphetamine addicted rats, epigenetic regulation through reduced acetylation of

histones, in brain striatal neurons, caused reduced transcription of glutamate receptors.
[79]
 Glutamate receptors play an important role in regulating the reinforcing effects of misused illicit
drugs.[80]

Treatment and management

Further information: Addiction §  Research

A 2018 systematic review and network meta-analysis of 50 trials involving 12 different

psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found
that combination therapy with both contingency management and community reinforcement
approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout
rate).[81] Other treatment modalities examined in the analysis included monotherapy with
contingency management or community reinforcement approach, cognitive behavioral
therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy,
and other combination therapies involving these.[81]

As of December 2019, there is no effective pharmacotherapy for methamphetamine addiction.[82]

[83][84]
 A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different
pharmacotherapies used in RCTs for amphetamine and methamphetamine addiction; [83] it found
only low-strength evidence that methylphenidate might reduce amphetamine or
methamphetamine self-administration.[83] There was low- to moderate-strength evidence of no
benefit for most of the other medications used in RCTs, which included antidepressants
(bupropion, mirtazapine, sertraline), antipsychotics (aripiprazole), anticonvulsants
(topiramate, baclofen, gabapentin), naltrexone, varenicline, citicoline, ondansetron, prometa, riluz
ole, atomoxetine, dextroamphetamine, and modafinil.[83]

Dependence and withdrawal

Tolerance is expected to develop with regular methamphetamine use and, when used
recreationally, this tolerance develops rapidly.[85][86] In dependent users, withdrawal symptoms are
positively correlated with the level of drug tolerance.[87] Depression from methamphetamine
withdrawal lasts longer and is more severe than that of cocaine withdrawal.[88]

According to the current Cochrane review on drug dependence and withdrawal in recreational

users of methamphetamine, "when chronic heavy users abruptly discontinue [methamphetamine]
use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last
dose".[87] Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6%
of cases, and persist for three to four weeks with a marked "crash" phase occurring during the
first week.[87] Methamphetamine withdrawal symptoms can include anxiety, drug
craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased
movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.[87]

Methamphetamine that is present in a mother's bloodstream can pass through the placenta to

a fetus and be secreted into breast milk.[88] Infants born to methamphetamine-abusing mothers
may experience a neonatal withdrawal syndrome, with symptoms involving of abnormal sleep
patterns, poor feeding, tremors, and hypertonia.[88] This withdrawal syndrome is relatively mild
and only requires medical intervention in approximately 4% of cases.[88]

Neonatal
Unlike other drugs, babies with prenatal exposure to methamphetamines don't show immediate
signs of withdrawal. Instead, cognitive and behavioral problems start emerging when the children
reach school age.[89]

A prospective cohort study of 330 children showed that at the age of 3, children with
methamphetamine exposure showed increased emotional reactivity, as well as more signs of
anxiety and depression; and at the age of 5, children showed higher rates
of externalizing and attention deficit/hyperactivity disorders.[90]

Overdose
See also: Aimo Koivunen

A methamphetamine overdose may result in a wide range of symptoms.[4][22] A moderate

overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm,
confusion, difficult and/or painful urination, high or low blood pressure, high body
temperature, over-active and/or over-responsive reflexes, muscle aches, severe agitation, rapid
breathing, tremor, urinary hesitancy, and an inability to pass urine.[4][29] An extremely large
overdose may produce symptoms such as adrenergic storm, methamphetamine
psychosis, substantially reduced or no urine output, cardiogenic shock, bleeding in the
brain, circulatory collapse, hyperpyrexia (i.e., dangerously high body temperature), pulmonary
hypertension, kidney failure, rapid muscle breakdown, serotonin syndrome, and a form
of stereotypy ("tweaking").[sources 1] A methamphetamine overdose will likely also result in mild brain
damage due to dopaminergic and serotonergic neurotoxicity.[94][21] Death from methamphetamine
poisoning is typically preceded by convulsions and coma.[22]

Psychosis
Main section: Stimulant psychosis §  Substituted amphetamines

Use of methamphetamine can result in a stimulant psychosis which may present with a variety of
symptoms (e.g., paranoia, hallucinations, delirium, and delusions).[4][95] A Cochrane
Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine
use-induced psychosis states that about 5–15% of users fail to recover completely.[95][96] The
same review asserts that, based upon at least one trial, antipsychotic medications effectively
resolve the symptoms of acute amphetamine psychosis.[95] Amphetamine psychosis may also
develop occasionally as a treatment-emergent side effect.[97]
Emergency treatment
Acute methamphetamine intoxication is largely managed by treating the symptoms and
treatments may initially include administration of activated charcoal and sedation.[4] There is not
enough evidence on hemodialysis or peritoneal dialysis in cases of methamphetamine
intoxication to determine their usefulness.[22] Forced acid diuresis (e.g., with vitamin C) will
increase methamphetamine excretion but is not recommended as it may increase the risk of
aggravating acidosis, or cause seizures or rhabdomyolysis.[4] Hypertension presents a risk
for intracranial hemorrhage (i.e., bleeding in the brain) and, if severe, is typically treated with
intravenous phentolamine or nitroprusside.[4] Blood pressure often drops gradually following
sufficient sedation with a benzodiazepine and providing a calming environment.[4]

Antipsychotics such as haloperidol are useful in treating agitation and psychosis from

methamphetamine overdose.[98][99] Beta blockers with lipophilic properties and CNS penetration
such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity.
[100]
 The mixed alpha- and beta-blocker labetalol is especially useful for treatment of concomitant
tachycardia and hypertension induced by methamphetamine.[98] The phenomenon of "unopposed
alpha stimulation" has not been reported with the use of beta-blockers for treatment of
methamphetamine toxicity.[98]

Interactions
Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6 inhibitors will
prolong the elimination half-life of methamphetamine.[101] Methamphetamine also interacts
with monoamine oxidase inhibitors (MAOIs), since both MAOIs and methamphetamine increase
plasma catecholamines; therefore, concurrent use of both is dangerous.[22] Methamphetamine
may decrease the effects of sedatives and depressants and increase the effects
of antidepressants and other stimulants as well.[22] Methamphetamine may counteract the effects
of antihypertensives and antipsychotics due to its effects on the cardiovascular system and
cognition respectively.[22] The pH of gastrointestinal content and urine affects the absorption and
excretion of methamphetamine.[22] Specifically, acidic substances will reduce the absorption of
methamphetamine and increase urinary excretion, while alkaline substances do the opposite.
[22]
 Due to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are
known to interact with methamphetamine.[22]

Pharmacology

This illustration depicts the normal operation of the dopaminergic terminal to the left, and the dopaminergic
terminal in the presence of methamphetamine to the right. Methamphetamine reverses the action of the
dopamine transporter (DAT) by activating TAAR1 (not shown). TAAR1 activation also causes some of the
dopamine transporters to move into the presynaptic neuron and cease transport (not shown). At VMAT2
(labeled VMAT), methamphetamine causes dopamine efflux (release).
Pharmacodynamics
Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor
1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems.[102]
[103]
 Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and
either completely inhibits or reverses the transport direction of the dopamine
transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT).[102]
[104]
 When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein
kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or
reverse function of monoamine transporters.[102][105] Methamphetamine is also known to increase
intracellular calcium, an effect which is associated with DAT phosphorylation through
a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn
producing dopamine efflux.[106][107][108] TAAR1 has been shown to reduce the firing rate of neurons
through direct activation of G protein-coupled inwardly-rectifying potassium channels.[109][110]
[111]
 TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the
membrane expression and function of EAAT2, a type of glutamate transporter.[50]

In addition to its effect on the plasma membrane monoamine transporters, methamphetamine

inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the
vesicles and promotes their release.[112] This results in the outflow of monoamines from synaptic
vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent
release into the synaptic cleft by the phosphorylated transporters.[113] Other transporters that
methamphetamine is known to inhibit are SLC22A3 and SLC22A5.[112] SLC22A3 is an
extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-
affinity carnitine transporter.[103][114]

Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma

receptors with a greater affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A)
and monoamine oxidase B (MAO-B).[46][103][52] Sigma receptor activation by methamphetamine may
facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain.[46]
[52]
 Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has
stronger peripheral effects, a longer half-life, and longer perceived effects among addicts.[115][116]
[117]
 At high doses, both enantiomers of methamphetamine can induce
similar stereotypy and methamphetamine psychosis,[116] but levomethamphetamine has shorter
psychodynamic effects.[117]

Pharmacokinetics
Following oral administration, methamphetamine is well-absorbed into the bloodstream, with
peak plasma methamphetamine concentrations achieved in approximately 3.13–6.3 hours post
ingestion.[118] Methamphetamine is also well absorbed following inhalation and following
intranasal administration.[4] Due to the high lipophilicity of methamphetamine, it can readily move
through the blood–brain barrier faster than other stimulants, where it is more resistant to
degradation by monoamine oxidase.[4][118] The amphetamine metabolite peaks at 10–24 hours.
[4 ]
 Methamphetamine is excreted by the kidneys, with the rate of excretion into the urine heavily
influenced by urinary pH.[22][118] When taken orally, 30–54% of the dose is excreted in urine as
methamphetamine and 10–23% as amphetamine.[118] Following IV doses, about 45% is excreted
as methamphetamine and 7% as amphetamine.[118] The half-life of methamphetamine is variable
with a range of 5–30 hours.[4]

CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, butyrate-CoA ligase,

and glycine N-acyltransferase are the enzymes known to metabolize methamphetamine or its
metabolites in humans.[sources 2] The primary metabolites are amphetamine and 4-
hydroxymethamphetamine;[118] other minor metabolites include: 4-hydroxyamphetamine, 4-
hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine,
and phenylacetone, the metabolites of amphetamine.[6][118][119] Among these metabolites, the
active sympathomimetics are amphetamine, 4-hydroxyamphetamine,[125] 4-hydroxynorephedrine,
  4-hydroxymethamphetamine,[118] and norephedrine.[127] Methamphetamine is a CYP2D6
[126]

inhibitor.[101]

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-
hydroxylation, N-oxidation, N-dealkylation, and deamination.[6][118][128] The known metabolic
pathways include:
Metabolic pathways of methamphetamine in humans[sources 2]

Methamphetamine
4-Hydroxymethamphetamine
4-Hydroxyphenylacetone
Phenylacetone
Benzoic acid
Hippuric acid
Amphetamine
Norephedrine
4-Hydroxyamphetamine
4-Hydroxynorephedrine

The primary metabolites of methamphetamine are amphetamine and 4-hydroxymethamphetamine.

[118]
 Human microbiota, particularly Lactobacillus, Enterococcus, and Clostridium species, contribute to the
metabolism of methamphetamine via an enzyme which N-demethylates methamphetamine and 4-
hydroxymethamphetamine into amphetamine and 4-hydroxyamphetamine respectively.[129][130]

Detection in biological fluids

Methamphetamine and amphetamine are often measured in urine or blood as part of a drug
test for sports, employment, poisoning diagnostics, and forensics.[131][132][133][134] Chiral techniques
may be employed to help distinguish the source of the drug to determine whether it was obtained
illicitly or legally via prescription or prodrug.[135] Chiral separation is needed to assess the possible
contribution of levomethamphetamine, which is an active ingredients in some OTC nasal
decongestants,[note 3] toward a positive test result.[135][136][137] Dietary zinc supplements can mask the
presence of methamphetamine and other drugs in urine.[138]

Chemistry

Shards of pure methamphetamine hydrochloride, also known as crystal meth

Methamphetamine is a chiral compound with two enantiomers, dextromethamphetamine and

levomethamphetamine. At room temperature, the free base of methamphetamine is a clear and
colorless liquid with an odor characteristic of geranium leaves.[9] It is soluble in diethyl
ether and ethanol as well as miscible with chloroform.[9] In contrast, the methamphetamine
hydrochloride salt is odorless with a bitter taste.[9] It has a melting point between 170 and 175 °C
(338 and 347 °F) and, at room temperature, occurs as white crystals or a
white crystalline powder.[9] The hydrochloride salt is also freely soluble in ethanol and water.[9]

Degradation
A 2011 study into the destruction of methamphetamine using bleach showed that effectiveness is
correlated with exposure time and concentration.[139] A year-long study (also from 2011) showed
that methamphetamine in soils is a persistent pollutant.[140] In a 2013 study of bioreactors
in wastewater, methamphetamine was found to be largely degraded within 30 days under
exposure to light.[141]

Synthesis
Further information on illicit amphetamine synthesis: History and culture of substituted
amphetamines §  Illegal synthesis

Racemic methamphetamine may be prepared starting from phenylacetone by either

the Leuckart[142] or reductive amination methods.[143] In the Leuckart reaction, one equivalent of
phenylacetone is reacted with two equivalents of N-methylformamide to produce the
formyl amide of methamphetamine plus carbon dioxide and methylamine as side products.[143] In
this reaction, an iminium cation is formed as an intermediate which is reduced by the second
equivalent of N-methylformamide.[143] The intermediate formyl amide is then hydrolyzed under
acidic aqueous conditions to yield methamphetamine as the final product.[143] Alternatively,
phenylacetone can be reacted with methylamine under reducing conditions to yield
methamphetamine.[143]
 Methamphetamine synthesis

Method of methamphetamine synthesis of methamphetamine via reductive amination

Methods of methamphetamine synthesis via the Leuckart reaction

History, society, and culture

Main article: History and culture of substituted amphetamines

Pervitin, a methamphetamine brand used by German soldiers during World War II, was dispensed in these
tablet containers.
U.S. drug overdose related fatalities in 2017 were 70,200, including 10,333 of those related to
psychostimulants (including methamphetamine).[144][145]

Amphetamine, discovered before methamphetamine, was first synthesized in 1887 in Germany

by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.[146][147] Shortly after,
methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai
Nagayoshi.[148] Three decades later, in 1919, methamphetamine hydrochloride was synthesized
by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.[149]

During World War II, methamphetamine was sold in tablet form under the brand
name Pervitin (not to be confused with Perviton, which is a synonym for Phenatine), produced by
the Berlin-based Temmler pharmaceutical company. It was used by all branches of the
combined Wehrmacht armed forces of the Third Reich, for its stimulant effects and to induce
extended wakefulness.[150][151] Pervitin became colloquially known among the German troops as
"Stuka-Tablets" (Stuka-Tabletten) and "Herman-Göring-Pills" (Hermann-Göring-Pillen). Side
effects were so serious that the army sharply cut back its usage in 1940.[152] By 1941, usage was
restricted to a doctor's prescription, and the military tightly controlled its distribution. Soldiers
would only receive a couple tablets at a time, and were discouraged from using them in combat.
Historian Lukasz Kamienski says "A soldier going to battle on Pervitin usually found himself
unable to perform effectively for the next day or two. Suffering from a drug hangover and looking
more like a zombie than a great warrior, he had to recover from the side effects." Some soldiers
turned very violent, committing war crimes against civilians; others attacked their own officers.[152]

At the end of the war, it was used as part of a new drug: D-IX.

Obetrol, patented by Obetrol Pharmaceuticals in the 1950s and indicated for treatment
of obesity, was one of the first brands of pharmaceutical methamphetamine products.[153] Due to
the psychological and stimulant effects of methamphetamine, Obetrol became a popular diet pill
in America in the 1950s and 1960s.[153] Eventually, as the addictive properties of the drug became
known, governments began to strictly regulate the production and distribution of
methamphetamine.[147] For example, during the early 1970s in the United States,
methamphetamine became a schedule II controlled substance under the Controlled Substances
Act.[154] Currently, methamphetamine is sold under the trade name Desoxyn, trademarked by the
Danish pharmaceutical company Lundbeck.[155] As of January 2013, the Desoxyn trademark had
been sold to Italian pharmaceutical company Recordati.[156]

Trafficking
The Golden Triangle (Southeast Asia), specifically Shan State, Myanmar, is the world's leading
producer of methamphetamine as production has shifted to Yaba and crystalline
methamphetamine, including for export to the United States and across East and Southeast Asia
and the Pacific.[157]

Concerning the accelerating synthetic drug production in the region, the Cantonese Chinese
syndicate Sam Gor, also known as The Company, is understood to be the main international
crime syndicate responsible for this shift.[158] It is made up of members of five different triads. Sam
Gor is primarily involved in drug trafficking, earning at least $8 billion per year.[159] Sam Gor is
alleged to control 40% of the Asia-Pacific methamphetamine market, while also
trafficking heroin and ketamine. The organization is active in a variety of countries, including
Myanmar, Thailand, New Zealand, Australia, Japan, China, and Taiwan. Sam Gor previously
produced meth in Southern China and is now believed to manufacture mainly in the Golden
Triangle, specifically Shan State, Myanmar, responsible for much of the massive surge of crystal
meth in recent years.[160] The group is understood to be headed by Tse Chi Lop, a gangster born
in Guangzhou, China who also holds a Canadian passport.
Legal status
Main article: Legal status of methamphetamine

The production, distribution, sale, and possession of methamphetamine is restricted or illegal in

many jurisdictions.[161][162] Methamphetamine has been placed in schedule II of the United
Nations Convention on Psychotropic Substances treaty.[162]

Research
It has been suggested, based on animal research, that calcitriol, the active metabolite of vitamin
D, can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic
doses of methamphetamine.[163]

See also
 18-MC
 Breaking Bad, a TV series centered on illicit methamphetamine synthesis
 Faces of Meth, a drug prevention project
 Methamphetamine in Australia
 Methamphetamine in Bangladesh
 Methamphetamine in the Philippines
 Methamphetamine in the United States
 Montana Meth Project, a Montana-based organization aiming to reduce meth
use among teenagers
 Rolling meth lab, a transportable laboratory that is used to illegally produce
methamphetamine
 Ya ba, Southeast Asian tablets containing a mixture of methamphetamine
and caffeine

Explanatory notes
1. ^ Synonyms and alternate spellings include: N-methylamphetamine,
desoxyephedrine, Syndrox, Methedrine, and Desoxyn.[10][11][12] Common slang terms for
methamphetamine include: speed, meth, crystal, crystal meth, glass, shards, ice,
and tic[13] and, in New Zealand, "P".[14]
2. ^ Enantiomers are molecules that are mirror images of one another; they are
structurally identical, but of the opposite orientation.
Levomethamphetamine and dextromethamphetamine are also known as L-
methamphetamine, (R)-methamphetamine, or levmetamfetamine (International
Nonproprietary Name [INN]) and D-methamphetamine, (S)-methamphetamine, or
metamfetamine (INN), respectively.[10][16]
3. ^ Jump up to:a b c The active ingredient in some OTC inhalers in the United
States is listed as levmetamfetamine, the INN and USAN of levomethamphetamine.[17][18]
4. ^ Transcription factors are proteins that increase or decrease the expression of
specific genes.[66]
5. ^ In simpler terms, this necessary and sufficient relationship means that ΔFosB
overexpression in the nucleus accumbens and addiction-related behavioral and neural
adaptations always occur together and never occur alone.
6. ^ The associated research only involved amphetamine, not methamphetamine;
however, this statement is included here due to the similarity between the
pharmacodynamics and aphrodisiac effects of amphetamine and methamphetamine.