NRSG-114: General Pharmacology

LO1: Discuss pharmacotherapeutics, pharmacokinetics, and pharmacodynamics

Land Acknowledgement
 Pharmacology Definitions
• Pharm: Drug/medication
• Pharmacology: Study of drugs

• Pharmacotherapeutics – use of drugs to treat disorders; the emphasis on

clinical management.

• Pharmacoepidemiology – study of the effect of drugs on populations,

questions dealing with the influence of genetics are particularly important.

• Pharmacoeconomics – study of the economics impacting drug costs.

(Mosby dictionary, 8th edition, 2009; Professor Nassiri , Director Institute of International health Michigan State University)
 Pharmacology Definitions
Pharmacokinetics – The study of how the body
absorbs, distributes, metabolizes and excretes
drugs. Includes the onset of action, duration of
effect, biotransformation, and effects and routes
of excretion of the metabolites of the drugs.

(Mosby dictionary, 8th edition, 2009; Professor Nassiri , Director Institute of International health Michigan State
University)
 Pharmacology Definitions
Pharmacodynamics – study of how a drug acts
on a living organism, including the
pharmacologic response and the duration and
magnitude of response observed relative to the
concentration of the drug at an active site in the
organism.

(Mosby dictionary, 8th edition, 2009; Professor Nassiri , Director Institute of International health Michigan State
University)
 How They Work
Medications generally work to
stimulate or inhibit normal cellular
functions and activities; however, they
cannot add functions and activities.

(Lilley, 2021)
Drugs Are Chemical Structures
• All body functions, disease processes, and most drug
actions occur at the cellular level.

• Drugs are essentially chemicals that alter or change

basic processes in the body cells.

• Some medications you want to stay local: e.g., some

eye drops can cause serious anticholinergic effects if
allowed to go systemic, so you occlude the puncta.

(Lilley, 2021)
 On the Hunt
Medications are looking for specific sites of
actions known as target cells. Meds travel
through the blood stream or are absorbed
locally.

(Lilley, 2021)
 Examples
• Acetylsalicylic acid (ASA) also known as aspirin can reduce
inflammation, pain, and fever: it inhibits the action of a human
cell membrane enzyme known as cyclooxygenase, which is
responsible for the synthesis of a number of inflammatory
mediators.

• Penicillin cures certain bacterial infections. It works by

disrupting the synthesis of cell walls in susceptible bacterial
strains by inhibiting a key enzyme.
(Professor Nassiri , Director Institute of International health Michigan State University).
(Lilley, 2021)
Drug Actions
 Non-Receptor Drug Action
Only a few drugs act by mechanisms other than combining with
receptor sites on cells.
Alteration of chemical composition of specific body fluids
(e.g., antacids).
Increase the osmolarity of plasma to pull water out of tissues
(e.g., mannitol).
Metal chelating agents combine with toxic metals (e.g., lead) to
form a complex that can be more readily excreted.
Antacids use a base to neutralize an acid.

(Lilley, 2021)
 Systemic
• Systemic Medications – dosage forms
are liquids, tablets, intravenous,
transdermal, etc.

• These medications travel from site of

administration through the blood stream
to affect cells in the body (widespread).

(Lilley, 2021)
 Localized
• Topical Medications - ointments, creams, local
anesthetics, eye drops
• Will act only where applied to body (local effects)
(depending on medication, can have systemic effects).

(Lilley, 2021)
Local Effects Example

(Lilley, 2021)
Pharmacokinetics
 Pharmacokinetics
• The study of what the body does to the drug.

• Pharmacokinetics looks at 4 phases:

• Absorption
• Distribution
• Metabolism
• Excretion

(Lilley, 2021)
 Absorption
• Transfer of a drug from its entry site to
circulation.
• Onset of drug action is largely determined by the
rate of absorption.
• Drugs are absorbed from skin, mucous
membranes, by oral ingestion & by injection.
• Oral medications are absorbed in the stomach,
small intestine, and large intestine.
(Lilley, 2021)
 Absorption Continued
Factors that affect absorption:
• Dosage form
• Route of administration
• Blood flow to site of administration
• GI function
• Age of the client
• Presence of food or other drugs

(Lilley, 2021)
 Absorption Continued
• Oral drugs: must be swallowed, dissolved in
gastric fluid & delivered to small intestine before
they are absorbed.
• Liquid meds are absorbed faster than tablets or
capsules because they don’t have to be dissolved.
• Rapid movement through the stomach & small
intestine may increase drug absorption by
promoting contact with mucous membranes; may
also decrease absorption because some drugs
move too rapidly to be absorbed.

(Lilley, 2021)
 Absorption Continued
• Food in the stomach may enhance absorption of fat-
soluble drugs.
• Drugs given by SC & IM routes are usually absorbed
more rapidly than oral drugs because they move directly
from injection site to the bloodstream.
• Absorption is rapid from IM sites because muscle has a
rich blood supply.
• IV drugs do not need to be absorbed because they are
placed directly into the bloodstream – effectively
bypassing the “first-pass” metabolism of drugs in the
liver.

(Lilley, 2021)
 Absorption Continued
Most drugs applied to skin are given for local
effects.
Systemic absorption is minimal from intact skin
but may be considerable when skin is inflamed or
damaged – topicals such as clobetasol state “do
not apply to areas of broken skin” to avoid the
medication going systemic.
Adhesive Patches – specifically formulated for
absorption through the skin (fentanyl, nitro).

(Lilley, 2021)
 Absorption Continued
Systemic absorption occurs from mucosa of
oral cavity, nose, eye, vagina & rectum.
Drugs absorbed from mucous membranes pass
directly into the bloodstream.
Lungs have a large surface area for absorption of
anesthetic gases & other drugs – absorption
through the lungs is one of the fastest routes of
administration. For this reason, “huffing” is
incredibly dangerous!

(Lilley, 2021)
Absorption Chart

(Lilley, 2021)
 Bioavailability
• The portion of a dose that reaches systemic circulation &
is available to act on the body’s cells.
• Dosage form is a major determinant of a drug’s
bioavailability.
• An IV drug is almost 100% bioavailable – remember it
bypasses the first-pass metabolism in the liver!
• An oral drug is almost always less than 100%
bioavailable because some of it is not absorbed from the
GI tract & some goes to the liver & is partially
metabolized before reaching systemic circulation (first-
pass effect).

(Lilley, 2021)
 Bioavailability
************************************************
Differences in bioavailability between generic and
brand name drugs can result in poor therapeutic
outcomes for individuals that have already
stabilized on a certain medication. When possible,
advocate for medication orders to not switch out
generic and name brand medications when patients
come into your care.
************************************************

(Lilley, 2021)
 Question
Drugs administered via the oral route have 100%
bioavailability.

A. True
B. False
 Distribution
• Transportation of drug molecules into
circulating fluids, particularly blood, which
carries them through the body.
• Depends largely on adequacy of blood
circulation.
• Rapid distribution to organs with large blood
supply (heart, liver, kidneys, brain).
• Distribution to other internal organs, muscle,
fat & skin is slower.
(Lilley, 2021)
 Distribution Continued
An important factor in drug distribution is protein binding.
Most drugs form a compound with plasma proteins (albumin)
which act as carriers.
Drug molecules bound to plasma proteins are
pharmacologically inactive because their large size prevents
them from leaving the bloodstream through small openings in
capillary walls.
Only the free unbound portions of a drug can act on body cells
(target tissue).
Drugs highly bound to plasma proteins or stored in other
tissues have a long duration of action.

(Lilley, 2021)
 Albumin Carriers

Copyright © 2017 Elsevier Canada, a division of Reed Elsevier Canada, Ltd.

 Distribution Continued
• Drug distribution into the central nervous system (CNS)
is limited because of the blood-brain barrier.
• This barrier acts as a selectively permeable membrane to
protect the CNS.
• It can make drug therapy for CNS disorders more
difficult.
• Only drugs that are lipid soluble or have a transport
system can cross the blood-brain barrier & reach
therapeutic concentrations in brain tissue.

(Lilley, 2021)
 Distribution Continued
• Pregnancy - most drugs will cross the placenta & may
affect the fetus.
• During lactation, many drugs enter breast milk & may
affect the nursing infant – always check the drug’s
directions for use!
• Check drug references for teratogenic effects.
• Elderly & children have hypoalbuminemia (low
protein) so have higher levels of free drug; therefore,
requiring smaller doses for a therapeutic effect.
• Other pediatric considerations: more drugs enter brain
because of an immature blood-brain barrier.
(Lilley, 2021)
 Metabolism
Process by which drug molecules are broken down into
metabolites.
Active Metabolites cause pharmacological effects.
Inactive Metabolites – no pharmacological effects.
Most drugs are lipid soluble (this aids their movement across
cell membranes).
Kidneys can excrete only water-soluble substances.
Hepatic drug metabolism or clearance is a major mechanism
for stopping drug action & eliminating the drug from the body
– liver turns drugs into water-soluble molecules so the kidneys
can get rid of them.
(Lilley, 2021)
 Metabolism Continued
Most drugs are metabolized by a liver
enzyme known as cytochrome P450 (CYP).

With chronic administration, some drugs

stimulate liver cells to produce larger amounts
of drug-metabolizing enzymes – thus larger
doses of the drug may be required to produce
and maintain the desired therapeutic effect.

(Lilley, 2021)
 Metabolism Continued
Pediatrics: levels of microsomal enzymes are
decreased so rate of drug metabolism is
decreased.

Geriatrics: levels of microsomal enzymes are

decreased & liver blood flow is reduced so
rate of metabolism is decreased.

(Lilley, 2021)
 First-Pass Effect
• When meds are given orally, they are absorbed
into the GI tract & carried to the liver through
portal circulation.

• Some drugs are extensively metabolized in

liver; therefore, initially only part of the drug
dose reaches systemic circulation for
distribution to sites of action (i.e., the first-pass
effect)
(Lilley, 2021)
 First-Pass Effect Continued
• Some drugs must undergo first-pass metabolism in order to
become active prior to reaching circulation. E.g., Buspar
(for treatment of anxiety), and codeine (a form of morphine).

• Some drugs will become immediately inactive by stomach

acid and first-pass metabolism.

• A phase II metabolism causes drugs to undergo another

biotransformation into a water-soluble byproduct
(conjugation reaction).
(Lilley, 2021)
 Question
Drugs administered sublingually, and via inhalation bypass
the first-pass effect of drug metabolization.

A. True
B. False
 Excretion
The process of drug elimination from the body.
Primary site of excretion is the kidneys.
Other sites: bowel, lungs, skin – think of the cytotoxic
precautions in clinical (also consider bile, sweat, saliva,
breast milk).
Pediatrics: Glomerular filtration rate (GFR) & tubular
secretion & resorption are all decreased due to kidney
immaturity; perfusion to kidneys may be decreased which
results in reduced renal function, concentrating ability &
excretion of drugs.
Factors impairing excretion such as severe renal disease
will lead to accumulation of drugs which can cause severe
adverse effects if dosage is not decreased. (Lilley, 2021)
 Excretion
Most drugs undergo liver
metabolism but some bypass the
liver and go directly to the kidneys

Lungs – EtOH (alcohol), some

anesthetics

Skin – aspirin – converted to

salycilic acid, crystal meth,
chemotherapy drugs

(Lilley, 2021)
 Factors Influencing Medication
Excretion
• Decreased hepatic/renal function
• Age:
• very young have immature kidney
function so will have decreased
function
• elderly may have decreased kidney
function
(Lilley, 2021)
 Serum Half-Life
• Also called elimination half-life.
• Time required for serum concentration of a
drug to decrease by 50%.
• Determined by drug’s rate of metabolism &
excretion.
• E.g., 500 mg tab given – half-life 3 hr.
• So, 250 mg will remain in body after 3 hr.
• 125 mg will remain in body after 6 hr., etc.
(Lilley, 2021)
 Real Life Examples
• Meds with short half-life need to be
given frequently (e.g., heparin).
• Meds with a long half-life (such as 24
or even 36 hr.) can be given once
daily (e.g., digoxin).
• The time it takes for a drug to reach
its maximum therapeutic effect varies.
(Lilley, 2021)
 Question
You administer 800 mg of ibuprofen. The half-life of this
drug is 2 hours. How many mg of ibuprofen is left in the
patient’s blood after 8 hours?

A. 200 mg
B. 100 mg
C. 400 mg
D. 50 mg
Pharmacokinetics: How Drugs Move Through
the Body
Pharmacokinetics and
Pharmacodynamics in Action
Variables Affecting Drug Actions
Variables Affecting Drug Actions
• Drug-Related Variables
• Dosage
• Route of Administration
• Drug-Diet Interactions
• Drug-Drug Interactions
Client-Related Variables
Age
Body Weight
Genetic & Ethnic Characteristics
Gender
Pathologic conditions
Psychological considerations
Tolerance & Cross-Tolerance

(Lilley, 2021)
 Question
Medications are absorbed, distributed, metabolized, and
excreted from the body once their therapeutic effect has run its
course. Which of the following options are viable forms of
excretion? (Select all that apply)

A. Stool
B. Saliva
C. Sweat
D. Urine
E. Exhalation
 Dosage
• Refers to frequency, size & # of doses
• A major determinant of drug actions & responses
• If amount is too small or too infrequent, no pharmacologic
action occurs (therapeutic effect is not reached)
• If amount is too large or given too often, toxicity may occur
• Overdosage can occur
• Toxic doses produce S&S of toxicity
• Lethal doses cause death…

(Lilley, 2021)
 Dosage

• Dosage is dependent on the client characteristics

(pathophysiology, age, how long they’ve been on a med,
weight, genetic background, desired effect (e.g., sedation vs
anxiolytic) and the drug (half-life, and safety margins).

(Lilley, 2021)
Route of Administration
• Route of medication administration affects
drug actions & response largely by influencing
absorption & distribution.
• Intravenous & inhalation are very rapidly
absorbed so they act quickly.
• The oral route usually produces slower drug
action than parenteral routes (oral drugs
typically take at least 20+ minutes to take
effect).
(Lilley, 2021)
Route of Administration
• Try the least invasive route (Oral)

• Some meds cannot be given orally (e.g., Insulin)

• Local effects – topical

• Quick effects through parenteral admin

• Avoid first-pass metabolism for drugs that would become

inactive
(Lilley, 2021)
 Route of Administration

What are some reasons you may give drugs

using other routes?

(Lilley, 2021)
 Question
Which route of medication administration is typically the
slowest to absorb?

A. Oral
B. Transdermal
C. IV
D. IM
E. SC
 Drug – Diet Interactions
• Food slows absorption of drugs by slowing gastric
emptying time, altering gastric acid secretions &
motility.
• Food may also decrease absorption of a drug by
combining with it to form an insoluble drug-food
complex.
• Interactions can be minimized by ensuring space
(time) between consumption of food & administering
medications.
• Some foods contain substances that react with certain
meds. (Lilley, 2021)
 Drug – Diet Interactions
• Check the drug you are giving. Some meds are to be
given with food (e.g., NSAIDs, and opioids) while
others are to be given on an empty stomach (e.g.,
captopril and ampicillin).

• Avoid giving meds with grapefruit as grapefruit can

decrease a person’s ability to metabolize meds by
inhibiting CYP3A4 enzyme

• Monoamine oxidase inhibitors (MAOI) and tyramine

(Lilley, 2021)
 Drug – Diet Interactions
Foods containing Tyramine:
• Strong cheeses such as aged cheddar, Swiss, and parmesan,
blue cheese. As well as cheeses made from pasteurized milk:
cottage cheese, ricotta, and cream cheese.
• Cured meats such as sausages, pepperoni, and salami.
• Smoked or processed meats such as hot dogs, bologna, bacon,
corned beef or smoked fish.
• Pickled foods such as sauerkraut, kimchi, caviar, tofu, and
pickles.
• Sauces such as soy sauce, fish sauce, miso, and teriyaki sauce.
• Alcoholic beverages such as beer (especially homebrewed), red
wine, sherry, and liqueurs.
(Hall-Flavin, 2018)
 Drug – Drug Interactions
• Action of a drug may be increased or decreased
by its interaction with another drug in the body
– altering metabolization.
• E.g., drugs metabolized by same enzymes
compete for enzyme binding sites & there may
not be enough binding sites for 2 or more drugs.
• Some drugs induce or inhibit the metabolism of
other drugs.
• Protein binding can also interfere.
(Lilley, 2021)
 Increased Drug Effects
Interactions that increase the therapeutic or
adverse effects of drugs:

1. Additive/synergistic effects (agonistic)

2. Inhibitory effects

(Lilley, 2021)
 Increased Drug Effects
• Additive/synergistic – alcohol and benzodiazepines
• Inhibitory – a food or drug inhibits enzymes breaking
down the medication, so medications have a longer, more
powerful action (e.g., grapefruit juice)
• Competitive inhibition of enzymes – too many substances
for the enzyme to break down (MAOIs and tyramine)
• Interference – Ativan and Ritalin
• Metabolic – Carbamazipine and birth control – taking
both decreases effectiveness of birth control

(Lilley, 2021)
 Decreased Drug Effects
• These interactions are grouped under the term
antagonism.
• E.g., a drug that is a specific antidote is given
to antagonize the toxic effects of another drug.
Naloxone is given to relieve opioid-induced
(morphine) respiratory depression.
• Decreased intestinal absorption of oral drugs
occurs when drugs combine to produce
nonabsorbable compounds (e.g., antacids +
tetracycline [an antibiotic]). (Lilley, 2021)
 Incompatibility
Some drugs are incompatible with others…

Usually applies to parenteral drugs – look for changes in

the tubing and medication. Precipitates, color change,
and/or haziness are common with incompatibilities.

E.g., furosemide and heparin sodium

Always consult your pharmacist and unit CPS if unsure!

(Lilley, 2021)
Client Related Variables
 Age
• Especially in neonates, infants & older adults.
• During pregnancy drugs may cross the placenta &
harm the fetus. Fetuses have no effective
mechanism for metabolizing or eliminating drugs
due to immature kidneys & liver.
• Infant organ systems are not fully developed.
• Children have a period of increased activity of drug
metabolizing enzymes so may clear some drugs
faster than adults.
• Older adults: all pharmacokinetics altered by
physiological changes.
(Lilley, 2021)
 Body Weight
• Affects drug action mainly in relation to dose.

• In general, heavier people may need larger doses,

so long as their renal, CV & hepatic function is
normal.

• Many drugs have recommended doses based on

grams or mg per kg of body weight.

(Lilley, 2021)
Genetic & Ethnic Characteristics
• Genes determine types & amounts of proteins; most
drugs interact with proteins; genetic characteristics that
alter any proteins can alter drug pharmacokinetics or
pharmacodynamics.
• Ethnicity: most drug information has come from clinical
trials involving white males; there are ethnic variations –
e.g., people of African decent are less responsive to ACE
inhibitors & beta blockers as single-drug therapy for
HTN. Asians often require smaller doses of psychotropic
drugs.

(Lilley, 2021)
 Gender
• There are differences in the way that men & women
respond to drug therapy.
• Hormonal fluctuations may be one of the causes.
• E.g., lithium, phenytoin.
• Some disease processes have increased S&S
premenstrually, so clients may need dosage adjustment.
• Women with schizophrenia require lower doses of
antipsychotic meds than men – if given same doses as
men, women more likely to have adverse effects.

(Lilley, 2021)
 Pathologic Conditions
• May alter pharmacokinetic processes.
• All pharmacokinetic processes are decreased in
cardiovascular (CV) disorders characterized by decreased
blood flow to tissues, such as heart failure.
• Absorption of drugs is decreases with GI disorders.
• Distribution is altered in liver or kidney disease.
• Metabolism is decreased in malnutrition & severe liver
disease.
• Excretion is decreased in kidney disease.

(Lilley, 2021)
Psychological Considerations
• Influence an individual’s response to drug
administration.
• E.g., placebo response.
• Attitudes & expectations r/t drugs
influence the client’s response to
medications; this also influences adherence
or willingness to carry out prescribed
regimen.
(Lilley, 2021)
Tolerance & Cross-Tolerance
• Drug tolerance occurs when the body
becomes accustomed to a particular drug
over time so that larger doses must be
given to produce the same effect.
• E.g., common with opioid analgesics,
alcohol & other CNS depressants.
• Tolerance to pharmacologically related
drugs is called cross-tolerance.
(Lilley, 2021)
 Allergy
• An immune response to a foreign
antigen that results in inflammation
and organ dysfunction.
• Range form life threatening to
annoying.

(Lilley, 2021)
 Allergy Reactions
• Urticaria (hives)
• Systemic anaphylaxis
• Eczematous dermatitis
• Laryngeal edema
(itchy, scaly, rash)
• Transfusion reactions
• Allergic Rhinitis (hay
• Bronchospasms (tightening of
the muscles that line the fever)
airways) • Conjunctivitis
• Vasculitis (inflammation of the (inflammation of the
blood vessels) conjunctiva)
• Angioedema (swelling of the
neck [including the larynx],
tongue, lips, and eyes)
(Lilley, 2021)
Anaphylaxis
Name That Allergic Reaction!
Eczematous Dermatitis
Allergic Rhinitis
Conjunctivitis
Urticaria
Angioedema
Angioedema
Angioedema
Urticaria
Adverse and Unexpected
Drug Effects
 Adverse Drug Effects
• Adverse effects are any undesired responses to drug
administration.
• Most drugs produce a mixture of therapeutic & adverse
effects.
• All drugs can produce adverse effects.
• May be common or rare, mild or severe, localized or
widespread – depending on the drug & client.
• E.g., CNS effects, GI effects, hematologic effects, hepatic
effects, nephrotoxicity, hypersensitivity, and drug fever.

(Lilley, 2021)
 Idiosyncrasy
• An unexpected or unusual reaction to a drug that
occurs usually the first time it is given.

• It is where a reaction is different than that of others.

• These reactions are usually attributed to genetic

characteristics that alter client’s drug-metabolizing
enzymes.

(Lilley, 2021)
 Paradoxical Effect
• A paradoxical effect is an effect of a
drug that is the opposite to what
would usually be expected.

Example: Tylenol causing a headache.

(Lilley, 2021)
 Terminology
Side effects are results of taking a medication that are not the reason you
are taking the drug. For example, Rogaine (monoxidil) was originally
investigated as a blood pressure medication that was found to cause hair
growth. For people taking it for blood pressure, the hair growth would be
an (unwanted) side effect. For people taking it to grow hair, a drop in blood
pressure (possibly causing dizziness) would be a side effect.

Toxic effects are any outcomes of taking a medication that are harmful to
the body. Generally, they result from taking a medication at doses above
the recommended level.

Drug allergy is a hypersensitivity of a particular individual person to a

drug that causes an allergic reaction, typically a rash or swelling, when the
drug is taken. Penicillin is one of the most common causes of drug allergy.

(Lilley, 2021)
 Drug Dependence
• May occur with mind-altering
drugs, sedative-hypnotics,
antianxiety agents & CNS
stimulants
• May be physiologic or
psychological

(Lilley, 2021)
 Important Definitions
ONSET OF ACTION – time it takes to reach MEC
(minimum effective concentration). MEC must be present
before a drug exerts its pharmacologic action on body cells.
PEAK ACTION – when drugs reach their highest blood
concentration. Max therapeutic response.
DURATION OF ACTION – length of time the drug causes
its therapeutic effect.
SERUM DRUG LEVEL – a lab measurement of the amount
of a certain drug in the bloodstream at a particular time.

(Lilley, 2021)
 Question

Pharmacodynamics is the study of what the body does to

the drug.

A. True
B. False
 Tricks to Remember
1. Onset: restaurant opens to first customer.
2. Peak: busiest time rush hour (lunch).
3. Duration: When restaurant closes.
These pills will help you to stay asleep. They change
your dreams into General Pharmacology PowerPoint
presentations!
Please identify five things you have learned today!
 References

Hall-Flavin, D. (2018). MAOIs and diet: Is it necessary to restrict

tyramine?
https://www.mayoclinic.org/diseases-conditions/depression/expert-ans
wers/maois/faq-20058035

Sealock, K., Seneviratne, C., Lilley, L., Rainforth, S., & Collins, J.
(2021). Pharmacology for Canadian health care practice (4th ed.).
Elsevier Canada. ISBN 978-0-323-52949-5.