Drugs and the

Body
SHIRLYNNE MC
• To understand what happens when a drug is administered, the nurse
must understand pharmacodynamics—how the drug affects the body—
and pharmacokinetics—how the body acts on the drug.
• These processes form the basis for the guidelines that have been
established regarding drug administration—for example, why certain
agents are given intramuscularly (IM) and not intravenously (IV), why
some drugs are taken with food and others are not, and the standard
dose that should be used to achieve the desired effect
• Knowing the basic principles of pharmacodynamics and
pharmacokinetics helps the nurse to anticipate therapeutic and adverse
drug effects and to intervene in ways that ensure the most effective drug
regimen for the patient.
 a. Pharmacodynamics
1. This is the process by which drugs influence the cell physiology to achieve the
desired result.
2. Drugs can inhibit or activate a process or replace a missing element.
3. All but a small number of drugs interact with specific sites called receptors.
4. Receptors are cellular proteins or nucleic acids that regulate the physiologic
and metabolic activities of the cell in either of two ways:
• AGONISTS- bind to the receptor on the cell membrane and act on the cell
through the receptor to produce a pharmacologic effect.
• ANTAGONISTS- bind to the receptor and prevent the cell from producing
an effect. Antagonists may also block the action of another drug.
 .
• Oxycodone
• Oxycodone is a semisynthetic opioid
which has agonistic properties on mu,
kappa, and delta-type opioid receptors,
with the strongest affinity being for
mu-type receptors. Upon binding to • Naloxone is an opioid antagonist.
these G-protein coupled receptors,
oxycodone stimulates the exchange of
GDP on the G-alpha subunit for GTP, • That means naloxone binds to the same
receptors as the opioid, displacing the
resulting in the inhibition of adenylate
opioid in the process and temporarily
cyclase and thus a decrease in undoing its harmful effects.
intracellular cAMP.
 a. Pharmacodynamics
5. Drug–Enzyme Interactions- Drugs also can cause their effects by
interfering with the enzyme systems that act as catalysts for various chemical
reactions. Enzyme systems work in a cascade fashion, with one enzyme activating
another, and then that enzyme activating another, until a cellular reaction
eventually occurs. If a single step in one of the many enzyme systems is blocked,
normal cell function is disrupted.
6. Selective Toxicity- The ability of a drug to attack only those systems
found in foreign cells is known as selective toxicity.
7. Potency is the drug activity measured in terms of the dose required to
produce a particular effect. A highly potent drug evokes a given response at low
concentrations, while a drug of lower potency evokes the same response only at
higher concentrations.
8. Efficacy is the maximal effect produced by a drug.
 b. Pharmacokinetics
1. Pharmacokinetics is the process by which the body absorbs the drug
into the bloodstream, distributes it to its site of action, metabolizes it, and
excretes it. The therapeutic action of the drug depends on the
pharmacokinetic actions.
2. Onset of action is the time it takes for the drug to reach its minimum
effective concentration.
3. Peak effect occurs when the drug is exerting its maximum effect and is at
highest concentration.
4. Duration of action is the length of time that the drug remains above its
minimum effective concentration.
 b. Pharmacokinetics
5. The amount of a drug that is needed to cause a therapeutic effect is
called the critical concentration. The recommended dose of a drug is
based on the amount that must be given to eventually reach the critical
concentration. Too much of a drug will produce toxic (poisonous) effects,
and too little will not produce the desired therapeutic effects.
6. Some drugs may take a prolonged period to reach a critical concentration.
If their effects are needed quickly, a loading dose is recommended. (a
higher dose than that usually used for treatment).
Digoxin Amiodarone
Loading dose: 0.75–1.5 mg over 24 hours in Loading dose 200mg tid for 1 week, then 200mg bid for 1
divided doses. (750mcg-1500mcg) week
Maintenance dose: 62.5 – 250 mcg daily, reduced
in elderly, usual max 125 mcg daily Maintenance dose:100 – 200mg daily
 b. Pharmacokinetics
7. Dynamic Equilibrium The actual
concentration that a drug reaches in the
body results from a dynamic equilibrium
involving several processes:
• Absorption from the site of entry
• Distribution to the active site
• Biotransformation (metabolism) in
the liver
• Excretion from the body
 b. Pharmacokinetics
Absorption- involves the transfer of the drug across biological membranes to the
target tissue. A biological membrane may be the skin, mucous membranes of the eye or
ear, vagina or rectum, stomach or intestinal lining, or subcutaneous or muscle tissue.
Drug absorption is influenced by the route of administration. Generally,
drugs given by the oral route are absorbed more slowly than those given
parenterally. Of the parenteral route, IV administered drugs are absorbed
the fastest.
a. With oral medications, absorption occurs from the GI tract by
diffusion across the mucosal barrier.
The acidic environment of the stomach is one of the first barriers to foreign
chemicals. The acid breaks down many compounds and inactivates others.
To decrease the effects of this acid barrier and the direct effects of certain
foods, oral drugs ideally are to be given 1 hour before or 2 hours after a meal.
 b. Pharmacokinetics
b. With parenteral medications, the absorption rate is more raid and
predictable because IV administration places the drug directly in the plasma.
- These drugs are more likely to cause toxic effects because the margin for
error in dose is much smaller
- Drugs that are injected IM are absorbed directly into the capillaries in the muscle
and sent into circulation. This takes time because the drug must be picked up by the
capillary and taken into the veins.
- Subcutaneous injections deposit the drug just under the skin, where it is slowly
absorbed into circulation. Timing of absorption varies with subcutaneous injection,
depending on the fat content of the injection site and the state of local circulation.
toxic effect will be felt quickly since it joined the systemic circulation, effects will be felt quickly, keep monitoring patients

c. The slowest form of absorption is through the skin and mucous membrane.
 b. Pharmacokinetics
Factors That Affect Absorption of Drugs
ROUTE FACTORS AFFECTING ABSORPTION
Intravenous None: direct entry into the venous system
Intramuscular Perfusion or blood flow to the muscle; Fat content of the muscle; Temperature of the muscle:
cold causes vasoconstriction and decreases absorption; heat causes vasodilation and increases absorption

Subcutaneous (same with IM)

PO (oral) Acidity of stomach; Length of time in stomach; Blood flow to gastrointestinal tract
Presence of interacting foods or drugs
PR (rectal) Perfusion or blood flow to the rectum; Lesions in the rectum; Length of time retained for
absorption
Mucous Perfusion or blood flow to the area; Integrity of the mucous membranes
membranes Presence of food or smoking
(sublingual, Length of time retained in area
buccal)

Topical (skin) Perfusion or blood flow to the area; Integrity of skin

Inhalation Perfusion or blood flow to the area; Integrity of lung lining Ability to administer drug properly
 b. Pharmacokinetics
Distribution is the process by which drugs are transported by blood or other body fluids to
the site of action. It depends on protein binding, lipid solubility and circulation.
a) Protein binding means that a percentage of the drug has bound to the plasma
proteins, leaving only the amount not bound free in the circulation to produce the
drug action. This makes protein binding an important aspect of drug distribution.
b) Lipid solubility is important because the cell membrane has a high concentration of
lipids; therefore if the drug is soluble, it can pass through cell membrane to exert its
action.
c) The amount of drug present in our tissues help determine how effective the drug will
be.
d) Initial distribution of the drug depends on cardiac output and blood flow to local
tissue.
e) Drug concentration at specific sites depends on the density of blood vessels in tissue,
the local vasodilatation or constriction, and the rate of blood circulation. Certain drugs
tend to concentrate in specific tissues.
 b. Pharmacokinetics
Distribution
f) The placental barrier and blood-brain barrier are the body’s defense mechanism. Some
drugs pass through these barriers, whereas others do not.
Blood–Brain Barrier
The blood–brain barrier is a protective system of cellular activity that keeps many
things away from the CNS. Drugs that are highly lipid soluble are more likely to pass
through the blood–brain barrier and reach the CNS.
Placenta and Breast Milk
Many drugs readily pass through the placenta and affect the developing fetus in
pregnant women. As stated earlier, it is best not to administer any drugs to
pregnant women because of the possible risk to the fetus. Drugs should be
given only when the benefit t clearly outweighs any risk. Many other drugs are
secreted into breast milk and therefore have the potential to affect the neonate.
 b. Pharmacokinetics
Biotransformation is the process by which drug is enzymatically converted or
conjugated from its original form to a simpler compound.
a. This means that a drug is reduced to smaller substances known as metabolites.
The metabolites often exert pharmacologic, and sometimes, toxic actions.
b. Biotransformation occurs in two phases. The initial phase produces chemical
change in the drug molecule. In the second phase, known as conjugation, the
altered molecule binds to another chemical group in the bloodstream, resulting
in the formation of a more water-soluble product that is more readily excreted.
c. Biotransformation occurs in the liver, so that persons with liver disease will
have difficulty metabolizing drugs. A client who has any disorder that prolongs
metabolism or excretion will have excess amounts of the drug in the
bloodstream and is more likely to have increased, and possibly toxic, effects of
the medications.
 b. Pharmacokinetics
Biotransformation
d. Biotransformation may be facilitated through enzyme systems found
elsewhere in the body such as the kidneys, lungs, and intestines.
e. Some metabolites are inactive and exert no effect, some are active and
continue to exert effects, and others become toxic metabolites as their
accumulation causes that clients to experience toxic effects of the drugs.
f. some drugs are partially metabolized in the liver before reaching the
bloodstream because drugs absorbed across the gastrointestinal (GI) tract enter
the hepatic portal circulation. This is known as the first-pass effect. This is
why oral doses must be higher than intravenous (IV) doses, which will directly
enter the bloodstream without entering the liver.
g. Factors that influence biotransformation include age and renal, liver, and
cardiovascular (CV) disease.
 b. Pharmacokinetics
Excretion, or elimination , is the process by which a drug is removed from the body
along with its metabolite.

a. The routes by which drugs are excreted include the kidneys, lungs, intestines, and in lesser
degrees the sweat, salivary, and mammary glands.
b. Most drugs are eliminated in the kidney, so elimination is highly influenced by renal function.
Consequently, renal function should be assessed when administering drugs, especially to
diabetic clients or to any others who may have some degree of renal insufficiency. If the
kidneys are not eliminating properly, the parent drug and metabolites accumulate and can cause
prolonged action or toxicity. The nurse must carefully assess the renal effect of ALL drugs and
check with the physician before administering two nephrotoxic drugs together.
c. the amount required for half of the drug to leave the system is known as drug half-life.
d. the rate at which the drug is eliminated by the body is known as drug clearance. This process is
influenced greatly by renal function, which is often measured by creatinine clearance ( which
reflects the glomerular filtration rate).
 Half-Life
• The half-life of a drug is the time it takes for the amount of drug in the
body to decrease to one half of the peak level it previously achieved.
• For instance, if a patient takes 20 mg of a drug with a half-life of 2 hours, 10
mg of the drug will remain 2 hours after administration.
• Two hours later, 5 mg will be left (one half of the previous level); in 2 more
hours, only 2.5 mg will remain. This information is important in determining
the appropriate timing for a drug dose or determining the duration of a
drug’s effect on the body
• For example, if 100mg of a drug with a half-life of 60 minutes is taken, the
following is estimated:
• 60 minutes after administration, 50mg remains
• 120 minutes after administration, 25mg remains
• 180 minutes after administration, 12.5mg remains
• 240 minutes after administration, 6.25mg remains
• 300 minutes after administration, 3.125mg remains.
• In theory, we can see that after 300 minutes, almost 97% of this drug is
expected to have been eliminated. Most drugs are considered to have a
negligible effect after four-to-five half-lives. However, this does not mean
that won’t be detectable, for example, during a drug test. Just that they
will have no effect.
Generic Name Brand Name Half-life (T1/2*)
Examples
Alprazolam Xanax 6-12 hours
Amiodarone Pacerone 15-142 days
Amphetamine Adderall, Dexedrine 10-12 hours
Atenolol
Clonazepam
Tenormin
Klonopin
6-7 hours
18-50 hours
List of
Cocaine
Diazepam
-
Valium
50 minutes
20-100 hours Common
Donepezil Aricept 70 hours
Dutasteride
Erenumab
Avodart
Aimovig
5 weeks
28 days
Substances
Fluoxetine
Heroin
Prozac
-
2-4 days
2-6 minutes
and Their
Lead
Mercury
-
-
28-36 days
65 days Half-Lives
Methamphetamine Desoxyn 6.4-15 hours
Methylphenidate Concerta, Ritalin 2-3 hours
Plutonium - 40 years (liver), 100 years (bone)

Phenytoin Dilantin, Phenytek 7-42 hours

Tetrahydrocannabinol (cannabis/marijuan - Infrequent users: 1.3 days
a) Regular users: 13 days
Warfarin Coumadin, Jantoven 1 week
 b. Pharmacokinetics
Factors affecting pharmacokinetics
1. Age
a. Elderly clients may have different outcomes from drug therapy for several reasons:
The liver is older, so biotransformation and metabolism may be slowed. The liver may be more
fragile, and the drug can accumulate there longer, causing toxicity.
Because circulation is slower, the kidneys are affected, reducing elimination and increasing the build
up of metabolites, some of which are toxic.
The CV system may slow down, resulting in slower distribution and removal of metabolites.
b. Pediatric clients have varying reactions to medications because of immaturity in the immune system,
liver, and kidneys. Pediatric clients also have paradoxical reactions to some drugs, such as
diphenhydramine (Benadryl), which usually causes sleep but can produce an amphetamine-like
reaction in children.
2. Diseases
a. Diseases that tend to slow down body processes alter drug effect by slowing down the absorption,
distribution, and elimination.
b. disease that speed up any of the body’s processes increase drug absorption.
 b. Pharmacokinetics
Factors affecting pharmacokinetics
3. Individual differences
a. Body size, weight, and muscle mass affect drug responses. For example, the
greater the client’s weight, the more drug can be diluted in the body. Conversely, the
lower the client’s body weight, the more likely the drug will accumulate and become
toxic. Persons with lower body weights such as infants, children, and the elderly may
require lower doses.
b. Adequate hydration is necessary to flush the metabolites from the system. In a
dehydrated client, the blood will have more concentrated levels of the drug. This
can occur in clients receiving diuretics or in clients who are not ingesting sufficient
fluids. A dehydrated person is also likely to accumulate a drug in kidneys, resulting
in renal toxicity.
c. Genetic factors are important because genetically determined enzyme systems
may change the metabolism of certain drugs. This is known as pharmacogenetic
reaction.
 b. Pharmacokinetics
Factors affecting pharmacokinetics
4. Psychological Factors
a. A client is more likely to have a positive outcome if he or she believes that the drugs will work. If the
client is convinced that a drug will be harmful or ineffective, noncompliance may occur.
b. The placebo reaction occurs when a client is given an inactive substance and it exerts a therapeutic
effect.
5. Type and amount of drug prescribed.
a. A cumulative effect is progressively increasing response that occurs when the rate of drug
administration exceeds the rate of elimination.
b. Tolerance is a decreased response to a drug, which occurs when the dose is repeated. This means that
the client may need to have the doses increase in time.
c. Drug resistance occurs when drug fails to exert its intended effect.
d. Dependence occurs when a client needs the drug to function. Drug dependence is often associated
with narcotics, but clients can become dependent on cardiac medication (e.g., digoxin), so that
discontinuing the drug would cause heart failure.
6. Social Factors: Smoking and alcohol use influence the metabolism of drugs.
 Activity: Seatwork
Determining the Impact of Half-Life on Drug
Levels

• A patient is taking a drug that has a half-life of 12 hours.

You are trying to determine when a 50-mg dose of the
drug will be gone from the body
• In 12 hours, half of the 50 mg (25 mg) would be in the body.
• In another 12 hours (24 hours), half of 25 mg (12.5 mg) would remain in the body.
• After 36 hours, half of 12.5 mg (6.25 mg) would remain.
• After 48 hours, half of 6.25 mg (3.125 mg) would remain.
• After 60 hours, half of 3.125 (1.56 mg) would remain.
• After 72 hours, half of 1.56 (0.78 mg) would remain.
• After 84 hours, half of 0.78 (0.39 mg) would remain.
• Twelve more hours (for a total of 96 hours) would reduce the drug amount to 0.195
mg.
• Finally, 12 more hours (108 hours) would reduce the amount of the drug in the
body to 0.097 mg, which would be quite negligible.
• Therefore, it would take 4½ to 5 days to clear the drug from the body.