Pharmacokinetics

1. Pharmacokinetics Study of process of drug absorption, metabolism and excretion, distribution, biotransformation, excretion and half-life

2. Absorption • Process by which drug is made available for use in the body. • Transfer drug from the body fluids to the tissue sites-

3. Absorption (Cont) • Factors that influence the rate of absorption: • Route of administration • IV- most rapid- immediate onset • IM- short onset w/in minutes- about 20 min • SubQ- rapid- e.g. insulin • Oral- takes 30-60 minutes before absorption from GI tract… onset of drug action thus delayed

4. Absorption (Cont) • Solubility of drug • More soluble, more rapidly absorbed • Most drugs are Water-sol (most readily absorbed)- and partially lipid soluble • Law of Diffusion- drug molecules pass from an area of high concentration to an area of low concentration – • Concentration of drug on each side differs… so will equal out with transport

5. Absorption (Cont) • Drugs pass through cell membranes through • Filtration • Passive transport- most pass thisway • Active transport

6. Absorption (Cont) • Presence of certain body conditions: • Development of lipodystrophy • Orally, food delays drug absorption • Some drugs irritate stomach

7. Absorption (Cont) • Factors that influence distribution: • Systemic circulation distributes drugs to various body tissues or target sites (receptor sites) • Interact w/ specific receptors during distribution • Some bind to protein or albumin in the blood plasma

8. Absorption (Cont) • Blood levels must be maintained for drug to be effective… Therapeutic level • Blood flow needs to be adequate • Blood-brain barrier: lipid barrier • Blood-brain barrier: lipid barrier • Drugs need to be lipid soluble to get into brain cells.

9. Biotransformation • Metabolism • Process by which drug is converted to a substance that can be eliminated • Drug is converted by the liver to inactive compounds • DMMS- drug microsomal metabolizing system • Drugs such as barbiturates and sedatives stimulate the DMMS when taken frequently

10. Excretion • Inactive compounds of drugs excreted by the kidneys- must be water- soluble • Some drugs excreted w/o being changed by the liver • Caution for pts w/ kidney disease • lower doses in infants and children as immature kidney function…. And in older age pts w/ diminished kidney function

11. Half-life • Time required for body to eliminate 50% of drug or for the concentration in blood to fall to half of the original level. • Affects timing/frequency of drug dosage • Drug w/ short half-life of 2-4 hours need freq adm • Drug w/ long half-life (20-24 hrs) req less freq dosing. • Rate of metabolism and excretion affects half-life.

12. Drug Reactions / Interactions • Adverse drug reactions: • Undesirable drug effects which may be common or infrequently occurring • May be mild, severe or life threatening. • May occur after first dose, after several doses, or after many

13. Drug Reactions / Interactions(Cont) • Reporting adverse drug reactions: • Drugs used, studied for many yrs… and may take that long for adv rxns to become known. • Reporting mechanisms to help ID adv rxns

14. Allergic drug reactions • Allergic reaction • Hypersensitivity reaction • Allergy to drug begins to occur after more than one dose given. • Occ may occur the first time a drug is given e.g. penicillin so need to monitor pt carefully w/ first dose.

15. Allergic drug reactions(Cont) • immune system views drug as an antigen or foreign body which then stimulates the antigen-antibody response that prompts body to produce antibodies and release histamine from the cell against the drug. • Allergy SXS: itching, skin rashes, hives (urticaria), incr nasal secretions, diff breathing and wheezing due to bronco-constriction, cyanosis, sudden loss of consciousness, swelling of eyes, lips or tongue.

16. Allergic drug reactions(Cont) • Anaphylactic shock-extreme serious allergic drug rxn occurs shortly after adm of drug w sensitivity • TX raise BP, improve breathing, restore cardiac function, tx symptoms as arise.

17. Allergic drug reactions(Cont) • Angioedema – angioneurotic edema… collection of fluid in subq tissue. • Eyelids, mouth, lips, throat. • Dangerous when mouth affected. Swelling may block airway and result in asphyxia or difficult breathing or inability to breath

18. Drug idiosyncrasy • Any unusual or abnormal rxn to a drug different from the one expected. • Cause due to genetic deficiency making pt unable to tolerate certain drugs and chemicals.

19. Drug tolerance/ dependence • Body adapts to presence of certain drugs • Also sign of drug dependence • Some users experience discomfort when drug w/drawn- with physical or psychological symptoms

20. Drug Reactions / Interactions • Cumulative drug effect: • Seen most commonly w/ liver or kidney disease as organs are major sites of detox and excretion. • Body is unable to metabolize and excrete a normal dose of drug before next dose occurs. Serious as can lead to toxic effects.

21. Drug Reactions / Interactions(Cont) • Toxic reactions: • Levels build up to toxic when lgr doses given. • Some drugs such as digoxin have very, very narrow margin of safety before toxic

22. Drug Reactions / Interactions(Cont) • Can be reversible or irreversible • Liver damage reversible as liver cells can regenerate. • Hearing loss due to damage to 8th cranial nerve permanent- due to streptomycin or gentimicin. • Can reverse w/ administration of antidote, digitalis toxicity can give Digibind,Narcan for narcotic overdose. • monitor blood level for certain drugs: gentimicin, theophylline, digitalis

23. Drug Reactions / Interactions(Cont) • Drug Interactions • Drug-drug interactions and food-drug interactions. • Occurs when one drug interacts w/ action of another. • antacids interact w drugs like tetracycline • Know interactions: • oral anticoagulants • anti-infectives, antiarrhythmics, alcohol

24. Drug Reactions / Interactions(Cont) • Additive drug reaction= when combined effect of the two drugs equal to sum of each drug given alone • Synergistic drug reaction= drugs interact w/ each other and produce effect greater than sum of separate actions. • Antagonistic drug reaction= one drug interferes w/ action of another and neutralizes or decreases effects

25. Drug Reactions / Interactions(Cont) • Drug-food interaction= food impairs or enhances drug given orally. • Some req food • Some antibiotics

26. Factors influencing drug response • Age • Infants and children req smaller doses • Dose varies for age and wt. • Elderly also need lower doses • Polypharmacy- taking numerous drugs that can potentially react.

27. Factors influencing drug response(Cont) • Weight= based on wt of 150 # average wt • Gender= women in general require smaller dose of some drugs as smaller ratio of body fat and water • Genetic variations- some inherit protein or enzyme patterns that influence absorption • Emotional state • Patient expectations… placebo affect

28. Factors influencing drug response(Cont) • Disease = presence of disease may influence action • Liver disease= alters ability to metabolize or detoxify drugs. • Kidney disease = impairs excretion.

29. Route of administration • Local and systemic effects • LOCAL: topical application affects the skin, eye, ear, mucous membranes – creams, ointments, suppositories • SYSTEMIC: absorbed and distributed throughout system via blood stream

30. Route of administration (Cont) • Oral- slowest, and most convenient • Parenteral= any route that does not involve GI tract or inhalation • IV- most rapid drug absorption • IM- into muscles • SubQ- into the subcutaneous tissues of the skin

31. Nursing Implications • Many factors influence drug action: • Need to know routes, factors, dosages, other drugs, if oral can be give w/ or w/o food. • Observe reactions, responses, adv rxns drug tolerance. • Report and record observations. • Know when to w/hold drug and notify MD.

32. Drug legislation / regulations • Federal legislation- describes conditions under which certain meds may be given and distributed. • State legislation- describes who may prescribe, dispense and administer certain drugs and under what conditions.

33. Drug legislation / regulations (Cont) • Pure Food and Drug Act (FDA)= first act passed in 1906, • Harrison Narcotic Act= 1914 • Pure Food, Drug and Cosmetic Act= 1938 • Comprehensive Drug Abuse Prevention and Control Act= 1970 • Drug Enforcement Agency(DEA)

34. Pregnancy Categories • Drugs carry risk of causing birth defects • Teratogen= any substance that causes abnormal development of the fetus leading to a severely deformed fetus. • Five categories of potential for causing birth defects.

35. Drug Development • FDA approval required for use, monitoring for adverse or toxic reactions • Investigational new drugs/ release of drugs for use.