Factors Affecting Drug Activity

Chapter 11

Pages 252-264

Bell work 4/27

Can you think of three things that might influence an individuals response to medication?

Human Variability

Differences in age, weight, genetics, and gender are factors that influence the differences in response to medication among people.

Age

Infants and Neonates Drug distribution is different in a neonate and

infant because their organ systems are not fully developed. They do not eliminate drugs as efficiently as adults.

Age

Children Children metabolize certain drugs more rapidly

than adults. Metabolism rates increases between 1 year and

12 years (depends on age and drug). After age 12 metabolism rates decline with age to

a normal adult level.

Age

Adult Adults experience a decrease in many

physiological function after age 30. Decreases in affects on drug activity are gradual.

Age

The elderly Elderly typically consume more drugs than any

other age group due to chronic illness and disease.

Gender

Women used to be excluded from drug studies. In 1993 the FDA stated that women will be included in clinical drug trials.

Since then many studies have been completed and show that men and women do show differences in absorption, distribution, metabolism, and excretion (ADME).

Gender based differences in drug response appear to be related to hormonal fluctuations.

Gender differences may also be due to differences in body composition.

Genetics

The field of study, pharmacogenetics, defines the hereditary basis of individual differences in absorption, distribution, metabolism, and excretion (ADME) processes.

The largest contributing factor to variability is metabolism.

Body Weight

Dosage adjustments based on weight are generally not made for adults who are slightly overweight.

Weight is a factor in determining drug dosage for infants, children, or obese patients.

Psychological Factors

Psychological factors can influence individual responses to drugs.

When placebo drugs are given patients receiving them can report therapeutic and adverse effects.

Another factor can be patient’s willingness to follow prescribed dosage regimens.

Bell work 4/30

Name two groups of people that need to have adjustments in drug dosages?

What group of people metabolism drugs the fastest?

Adverse Drug Reactions

Drugs generally produce a mixture of either therapeutic (desired) or adverse (undesired) effects.

An adverse effect is an unintended side effect of a medication that is negative or in some way injures a patient’s health.

Reactions may be rare or common, localized or wide-spread, mild or severe depending on the drug and the patient.

Common Adverse Reactions

Hypersensitivity or Allergy Almost any drug, in any dose, can produce an

allergic or hypersensitive reaction in a patient. The drug will interact with antibodies, releasing

histamine and other substances that produce reactions that can range from mild rashes to potentially fatal anaphylactic shock.

Allergic reactions can occur within minutes or weeks after drug administration

Adverse Drug Reactions Central nervous system (CNS):

Stimulation – agitation, confusion, disoriented Depression – dizziness, drowsiness, sedation

Hepatotoxicity: Hepititis Necrosis

Hepatotoxic drugs include: acetaminophen, aspirin.

Gastrointestinal effects: Anorexia, nausea, diarrhea Ulcers, colitis

Adverse Drug Reactions Nephrotoxicity:

Kidney failure - Gentamicin and ibuprofen Idiosyncrasy:

Unexpected reaction the first time a drug is given Hematological effects:

Coagulation, bleeding, bone marrow disorders Drug dependence:

Chronic use of analgesics, sedatives, hypnotics,etc Teratogenicity:

Ability of a substance to cause abnormal fetal development

Carcinogenicity: Ability of a substance to cause cancer

Bell Work 5/1, 5/2

What is a potentially fatal hypersensitivity reaction that produces respiratory distress and cardiovascular collapse?

What is an unexpected reaction the first time a drug is given?

Drug – Drug Interactions Taking more than one drug at a time can

cause a drug-drug interaction. Drug – drug interactions can affect the

disposition (all processes of the ADME) of any drug.

Therapeutic effects and side effects can be decreased or increased when more than one drug is taken.

Drug – Drug Interactions See examples of drug-drug interactions on page 256-257

Common drug-drug interactions Additive effects – when two drugs effects equal

to the sum of the individual effects Synergism – two drugs produce greater effect

than the sum of the individual effects Potentiation – one drug increases the activity of

another drug Antidote – a drug given to block or reduce toxic

effects

Drug – Drug Interactions Complex – decreased intestinal absorption of oral

drugs occurs when drugs complex to produce nonabsorbable compounds

Displacement – a drug bound to a plasma protein is removed when another drug of greater binding potential binds to the same protein.

Inhibition – one drug with the elimination of a second drug may intensify the effects of the second drug

Induction – a drug causes more metabolic enzymes to be produced, increasing metabolic activity

Urinary excretion – some drugs are altered by raising urinary pH and decrease renal absorption

Drug – Diet Interactions Dietary intake may affect disposition of drugs.

Absorption - increased or decreased when food is in the stomach. Generally absorption is decreased.

Distribution – a previously bound drug is displaced and this increases the concentration of the drug in the blood and this leads to an increased effect

Metabolism – high protein diets are associated with increased drug metabolism and high carbohydrate diets are associated with decreased metabolism. Malnourished adults have a decreased metabolism

Excretion – high protein diet increases kidney function.

Disease States The disposition (ADME process) and effect of some

drugs can be influenced by diseases other than the one that the drug is intended for.

Hepatic Cirrhosis and obstructive jaundice decrease hepatic

metabolism and will diminish drug elimination Viral hepatitis little change in disposition

Circulatory Changes in blood flow can influence ADME and therefore

will have the potential to alter the effect of the drug

Disease States

Renal Reduced renal function can effect the elimination of many

drugs and affect the plasma protein binding of drugs Thyroid

Changes in thyroid function can effect many aspects of absorption excretion and metabolism