Drug Actions and Interactions Chapter 10 Drug Actions and Interactions MAKE SURE TO UPDATE ALL REFERENCES TO THE CORRECT EDITION, AS WELL AS COPYRIGHT DATA

Overview Two or more drugs can alter the effect of each other Complete, current medication records must be maintained for patients Many problems occur from drug interactions

Pharmacokinetics Pharmacokinetics is the study of drugs within the body It includes the mechanisms of: Drug absorption Drug distribution Drug metabolism Drug excretion

Pharmacokinetics

Drug Absorption Absorption - movement of a drug from site administration into the bloodstream Diffusion – moving from areas of higher concentration to areas of lower concentration First-pass effect - oral drugs mostly absorbed in small intestine, partly metabolized in liver

Drug Distribution Process by which drug molecules leave the bloodstream and enter the tissues of the body Rate of distribution is highly dependent on the blood flow to various organs

Drug Metabolism Most drugs undergo metabolism, and are converted to metabolic derivatives (biotransformation) The enzyme called cytochrome P-450 is very important in drug metabolism

Drug Excretion Process by which drugs are eliminated from the body The kidney is the major site of excretion Drugs are mostly excreted in the urine, followed by the feces, saliva, sweat, breast milk, breath, and tears

Pharmacodynamics Pharmacodynamics – the study of biochemical and physiological effects of drugs It is also the study of the mechanism of action of drugs

Drug Action Specific affinity – a drug “chooses” a certain cell and exerts its effects Receptor – the specific cell recipient Agonist – the drug that has specific affinity for this cell, which it functionally changes

Drug Action

Drug Half-Life Half-life – the time needed for plasma concentration of a drug to be reduced by 50% Bioavailability – measurement of drug absorption and total amount of drug reaching systemic blood circulation after administration

Diurnal Body Rhythms Diurnal – “during the day” Important in the effects of certain drugs Example – sedatives should be given before bedtime, not in the morning

Psychological Factors People respond to prescribed drugs differently, based on how they feel about them Placebo – a simulated medication that contains no active ingredients A patient who believes in a placebo may report actual beneficial drug effects

Drug Toxicity Therapeutic index – the range between a drug’s therapeutic and toxic doses This is expressed in a ratio: LD50 / ED50 LD50 = lethal dose that will kill 50% of animals tested ED50 = effective dose that will produce a specific therapeutic effect in 50% of animals tested

Drug Effects Side effects – mild, annoying responses to a drug Adverse effects – more severe symptoms in response to a drug Idiosyncratic reaction – a unique, strange, or unpredicted reaction to a drug

Hypersensitivity or Allergy Hypersensitivity reactions – unpredictable reactions, usually after a patient has received a drug and developed antibodies against it Antigen-antibody reaction produces itching, hives, rash, or skin swelling

Anaphylactic Reaction Anaphylactic reaction – a severe form of allergic reaction that is life-threatening Signified by shortness of breath and sometimes, cardiac collapse It is a true medical emergency

Drug Interaction An interference of a drug with the effect of another drug, nutrient, or laboratory test Usually from taking more than one drug concurrently Can occur during liberation, absorption, distribution, biotransformation, or excretion

Synergism “Working together” of two or more drugs to produce a stronger effect than for each drug taken alone Example: the combination of warfarin sodium with aspirin, which causes excessive risk of blood hemorrhage

Potentiation One drug prolongs the effects of another drug Is often desirable in order to build up a sufficient drug level or to prolong its effect Example: when cimetidine is combined with asthma medications containing theophylline

Antagonism Two drugs decrease the effects of each other Example: when ibuprofen and aspirin are taken together, they stop each other’s action Tetracycline and antacids should not be used together since tetracycline must be absorbed in the stomach and antacids inhibit this

Multiple Pharmacological Effects Many current drugs can influence many physiological systems Example: combining antipsychotics, antidepressants, and antiparkinsonian drugs causing unanticipated additive anticholinergic effect

Multiple Prescribers Seeing multiple physicians makes it difficult for each to be aware of all drugs prescribed to the patient Example: antihistamines from one physician mixed with antianxiety drugs from another may cause an excessive depressant effect

Nonprescription Drug Use Patients may not mention nonprescription medications to their physicians Interactions with prescription drugs can occur Purchase both prescription and nonprescription medications at the same pharmacy

Patient Noncompliance Many patients do not take medication in the manner intended by the prescriber because of: Confusion about dosage instructions Forgetting to take all of their various medications After forgetting to take a dose, many patients double the next dose

Drug Abuse Drug abuse or deliberate misuse drugs may cause increased drug interactions Opioids, barbiturates, analgesics, and amphetamines are drugs most often abused

Patient Variables Affecting Drug Interaction Age Genetic factors Diseases and conditions Diet Alcohol consumption Smoking

Age Young and elderly patients have increased incidence of adverse drug reactions Cytochrome P-450 (enzymes) contribute to many drug interactions in newborns Elderly patients’ illnesses and slowing of renal function increases interactions

Genetic Factors Control rate of metabolism for isoniazid, which may cause peripheral neuritis Isoniazid may inhibit metabolism of phenytoin, causing nystagmus, ataxia, and lethargy

Diseases and Conditions Impaired renal and hepatic function are the most important conditions that alter drug activity Renal and hepatic diseases influence patient responses to certain drugs

Diet Food can affect drug absorption from the GI tract Many antibiotics must be given one hour before, or two hours after meals Grapefruit juice interacts with estrogens, cyclosporine, midazolam, triazolam, and all calcium channel blockers (continues)

Diet Toxicity of some drugs (such as MAO inhibitors) increases with wine, cheese, or yogurt CNS-stimulating drugs may cause toxicity if combined with caffeine Potassium-sparing diuretics and salt substitutes can cause dangerous blood potassium levels

Alcohol Consumption Chronic use may affect metabolism of drugs such as warfarin, phenytoin, and tolbutamide If used concurrently with sedatives and depressants, can cause excessive depressant response

Smoking Increases activity of drug-metabolizing liver enzymes This can decrease effects of diazepam, theophylline, chlorpromazine, and amitriptyline

Reducing Risk of Drug Interactions Patient risk factors: age, medical condition, diet, smoking, alcohol use Accurate patient drug history required Knowledge of drug actions is essential in assessing drug interactions Use therapeutic alternatives instead of drugs that can interact (continues)

Reducing Risks of Drug Interactions Avoid complex therapeutic regimens; keep number of medications to a minimum Educate patients about their illnesses and benefits and risks of their drug therapy