Factors affecting Drug Activity Chapter 11 Pages 313 - 331

Human Variability Age Gender Pregnancy Genetics Body Weight Psychological Factors

Age Neonate: up to one month old Infant: one month to 2 years Child: between the ages of 2-12 years Adolescent: between the ages of 13-19 years Adult: between the ages of 20-70 years Elder: older than 70 years

Neonates and Infants: drug distribution, metabolism, and excretion are different related to immature organ systems. Children: generally metabolize drugs more rapidly. Elderly: generally consume more drugs; leads to higher chance of drug interactions. Also experience more physiological changes which will affect drug actions.

Gender Pregnancy Rate of absorption decreases in late pregnancy. Plasma protein binding may be reduced with metabolism increased. Drugs easily transported to fetus; concentration levels higher in fetus than mom. Drug distribution may be affected by hormone levels and/ or body composition (males have more muscle, women have more fat).

Genetics Body Weight Determine type and amount of proteins in body. Dosage adjustments based on weight are generally not for adults. Considered in neonates, infants, children, obese, or small patients.

Disease States Hepatic Renal Circulatory Thyroid Disease can disrupt function of the organ involved with any part of the ADME process; which then alters the drug’s effect.

Hepatic Disease Loss of liver function Decrease hepatic metabolism; thereby diminish first-pass metabolism. Drugs with increased bioavailability with Cirrhosis: Verapamil, morphine, nifedipine, midazolam, and chlormethiazole. Drugs with decreased elimination with liver disease: Caffeine, diazepam, erythromycin, lidocaine, meperidine, metronidazole, theophylline, and verapamil.

Renal Disease Can affect elimination and plasma protein binding of drugs. As renal function declines, drug dosage should be reduced. Acidic drugs greatly reduces as kidneys fail. Albumin = major plasma and tissue protein responsible for binding. Monitor kidney function by following creatinine levels; levels decrease as kidneys fail. Selected drugs with decreased elimination in renal disease: Digoxin, gentamicin, lithium, ranitidine, Vancomycin

Circulatory Cause a decrease blood flow Decrease blood flow affects absorption, distribution, and elimination and therefore its effect. Changes in blood flow have less effect on renal system. High renal clearance drugs that may be effected by blood flow problems are: penicillin, lithium, and allopurinal.

Thyroid Diseases Can affect many aspects of absorption, excrement, and metabolism. In hypothyroidism, bioavailability of a few drugs increased while with hyperthyroidism they would be decreased related to GI motility. Thyroid function also effects renal blood flow and enzyme metabolism in the liver.

Adverse Drug Reactions Can be ANY undesired symptom and involve any organ. If they occur with usual doses of drugs then called side effects (i.e. Percocet – nausea, drowsiness).

Common Adverse Reactions CNS: stimulation ( confusion and hallucinations) or depression ( sedation and impaired respiration/ circulation). Hepatotoxicity: hepatitis, necrosis, biliary tract inflammation or obstruction. GI effects: anorexia, nausea, vomiting, constipation, and diarrhea Nephrotoxicity: renal toxicity can occur with gentamicin, ibuprofen, NSAIDS, and acyclovir. Hematological effects: bleeding, blood coagulation, and bone marrow disorders.

Teratogenicity: ability to cause abnormal fetal development Teratogenicity: ability to cause abnormal fetal development. All drugs have a pregnancy class (A-E). Carcinogenicity: ability of a drug to cause cancer. This includes some hormones and anticancer drugs. Drug Dependence: Chronic use of narcotics, anti-anxiety, hypnotic agents, and amphetamines can result in physiological or psychological dependence. Idiosyncrasy: unexpected reaction to a drug the FIRST time it is given; believed to be caused by genetics. Hypersensitivity or allergy: Almost any drug, in almost any dose can produce an allergic or hypersensitive reaction. This occurs because the patient has developed antibodies while taking the drug or a similar one. Allergic reactions can occur within minutes to weeks; while Anaphylactic Shock occurs within minutes and can lead to death.

Drug – Drug Interactions Probability of a drug-drug interaction increases with the number of medications a patient takes and certain disease states. Herbal supplements can also be involved in drug-drug interactions.