Factors Affecting Drug Activity

1. Factors Affecting Drug Activity Chapter 11 Pages 252-264

2. Bell work 4/27 • Can you think of three things that might influence an individuals response to medication?

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

4. 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.

5. 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.

6. Age • Adult • Adults experience a decrease in many physiological function after age 30. • Decreases in affects on drug activity are gradual.

7. Age • The elderly • Elderly typically consume more drugs than any other age group due to chronic illness and disease.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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?

13. 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.

14. 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

15. 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

16. 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

17. 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?

18. 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.

19. 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

20. 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

21. 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.

22. 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

23. 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