Pharmacokinetics

1. Pharmacokinetics Absorption & Interaction of Medications 2012/2013

2. Student Learning Outcomes See outline for SLO's

3. Overview • This week we will start by tracing the path a medication takes to enter the body, how it travels to the site of action, is broken down and excreted • Then how the medication produces its effects at the site of action • How to safely administer medications following the 8 (10 rights) • Conclude with Surgical Asepsis ( safe delivery of parental medications)

4. Introduction • Over 11,000 brand name and generic medications available • Each medication requires distinct • Application • Indications • Observation for adverse effects • Mechanism of actions • Some are prescribed for more then one illness • The RN must have an understanding of each medication prior to its administration

5. Introduction Pharmacology – is the study of medication Pharmacotherapy - / Pharmacothetreputics -application of a drug for the purpose of diagnosis, prevention or treatment of suffering (Adams & Urban) Pharmacokinetics – absorption, distribution, metabolism, (biotransformation), excretion

7. What Are the Benefits of This Info? Assists us to: 1. 2. 3. 4. 5. 6.

8. Introduction • Passage of drugs across membranes • Medications must get into the body • Diffusion • Takes into account • Membrane structure • Drugs must pass thru cells vs. between

9. Drugs Cross Membranes By: • Traveling via channels and pores • Must have small ions • Sodium & potassium are examples • Transport systems – carriers that move drugs from one side of the cell membrane to the other • Transportation depends on the structure of the drug molecule

10. Diffusion

11. Drugs Cross Membranes By: • Direct penetration of the membrane • Most drug use this route • These drugs must be lipid soluble • Remember cell membrane walls consist of lipids • Other • Polar molecules – uneven distribution of electrical charges therefore do not penetrate cells • Kanamycin (antibiotic)

12. Ions • Molecules that have a net electrical charge pH dependent ionization • Many drugs weak acids or weak bases • Acid may give up (H+) ions • Bases may take up (H+) ion

13. Note • Acids tend to ionize in basic solutions • Bases tend to ionize in acidic media • Ionization – any process by which a neutral atom gains or loses electrons thus developing a net charge • ASA (acidic) is absorbed better in stomach acid then in base lower GI environment • Remaining non ionized and therefore absorption is increased

14. Ion Trapping • Drugs will be trapped on the side that favors their ionization • Acidic drugs will accumulate on the alkaline side • Alkaline drugs will accumulate on the acidic side • Treatment for poisoning an example we can change the pH of urine thus enhancing excretion

15. Factors That Affect Absorption • Absorption – “movement of medication from its site of administration into the blood stream ” • Rate of dissolution • Drug must first dissolve before it can be absorbed • Drugs that dissolve faster are absorbed faster • Repository

16. Factors That Affect Absorption • Absorption dependent on the properties of the drug and on the physiological & anatomical attributes of the surface • Surface area • The larger the surface area the faster the absorption • Anesthesia delivered via the lungs

17. Factors That Affect Absorption • Blood flow • Drugs absorbed most rapidly from sites with the most blood flow • IV – directly into the blood stream • IM – muscles have a good blood supply • Any thing that impedes or enhances blood supply can impact absorption • Heating pad vs. ice pack

18. Factors That Affect Absorption • Drug Solubility • Lipid soluble drugs can readily cross the cell membranes • pH Partitioning • Just addressed

19. Routes • IV • no barriers to absorption • Immediate & complete absorption • Disadvantages • Incontinent, costly, medication irretrievable • Fluid overload • Infection • Emboli

20. Routes • IM • Only barrier – capillary wall • Drug can easily pass thru tissue • Absorption depends on • Water soluble will be absorbed more rapidly • Blood flow • Disadvantages • Discomfort • Nerve damage

21. Routes • Subcutaneous • Nearly identical to IM

22. Oral • Barriers • Lining of GI tract • Capillary wall 3. Absorption pattern • solubility stability gastric & intestinal ph. gastric emptying food in GI Other meds special medication coatings

23. Oral • Absorption takes place along the GI mucosa either in the stomach or lower GI tract • Absorbed meds enter blood stream and go directly to the liver • Hepatic first pass effect • Hepatic microsomal enzymes • Advantages • Easy & inexpensive (relatively) • Safer – potentially reversible • Good choice for senior citizens

24. Oral • Disadvantages • Variable absorption rate • Inactivation of certain medications • Requires a conscious & cooperative client • Age • Change in gastric pH can affect medication absorption

25. Pharmaceutical Preparation • Tablets • Enteric coating (do not crush) • Sustained release preparations

26. Additional Routes • Topical • Skin, eyes, ears, nose, mouth, & vagina • Inhalation • Rectal suppositories – cut in half length wise

27. Distribution “Movement of drugs throughout the body’’ Affected by • Blood flow to the tissues - Exiting the vascular tissue - to site of action • Drug Solubility • Lipid soluble drugs are not limited by the barriers that normally limit water soluble drugs (Adams & Urban)

28. Distribution • Tissue storage • Some tissues have a greater ability to accumulate and store drugs • Bone marrow • Teeth • Eyes • Adipose tissue

29. Distribution • Determined: • Protein binding • Bonds reversible • Albumin – large molecule that remains in the blood stream & therefore amount of med available to the site of action may be limited • Only a few molecules will bind at any one time • Multiple Meds may compete at binding sites – resulting in Over dose • Special Barriers • Blood brain & placental barriers

30. Distribution

31. Distribution • Entering the cells. • Ph., lipid solubility etc. • Drugs may produce effects by. • Binding with receptors.

32. Metabolism • Also known as “Biotransformation” • “Enzymatic alteration of the drug structure • Most often takes place in the liver • Multiple enzymes • Hepatic microsomal enzymes – • Latest research is focusing on identifying individual characteristics and specific function of these enzymes

33. Consequences of Metabolism • Accelerated renal excretion • Drug inactivation • Increased therapeutic action • Activation of “prodrugs” (inactive substance changed to active substance) • Increased toxicity • Decreased toxicity

34. Factors Impacting Drug Metabolism • Age • Induction of drug metabolizing enzymes • Stimulates liver to breakdown itself faster or this change may affect other medications • Hepatic First pass effect • Nutritional status • Competition between drugs

35. Question? • List three problems you would see for a client with decreased liver function when it comes to metabolizing drugs ? • 1. • 2. • 3.

36. Excretion • “Removal of drugs from the body.” • Options • glomerular filtration • Drugs removed from blood & discarded into the urine • Passive tubular reabsorption • Frequently occurs with lipid soluble drugs • Active tubular secretion – active pumping of drug into tubular urine

37. Modifiers of Renal Excretion • pH – dependent ionization • > excretion rate • Competition for active tubular transport • Competition between drugs for active transport • Age 1. 2. 3. Lab test

38. Nonrenal Routes of Drug Excretion • Breast milk • Bile • Lungs • Sweat • Saliva

39. Plasma Drug Levels • Minimum effective concentration • Below MEC therapeutic effects of med will not occur • Toxic concentration • Therapeutic Range • Drug half life (t5) • Loading & maintenance doses • Peak & Trough

40. Time Response

41. Pharmacodynamics • Drug receptor interactions • Functional macromolecule in a cell to which a drug binds to produce its effects

42. Pharmacodynamics • Receptors are normal points of control • Receptor function regulated by body • Meds only Mimic, block, normal functions • Can not confer new functions

43. Pharmacodynamics • Meds Therapeutic effects due to body’s preexisting capabilities. • Research – ongoing

44. 2 Agonists

45. Medication Interactions • Agonist - medication that produces the same response as the endogenous substance – (actual molecule in the body that produces the desired effect) (some times these substances produce a great erect then the endogenous substance) • partial agonist - medication that produces a weaker effect • Antagonist - drug that prevents the agonist from producing the desired effect

46. Medication Interactions • Drug may enhance or inhibit drug action • Additive - 1+1 + 2 • Two drugs from a similar therapeutic class produce a combined summative effect • Synergistic effect - medications acting together produce a greater effect them each of them alone 1+1 += 3 • Medication manufactured as a combination drug • Synercid – comb antibiotic – effective against “Staph infections ”

47. Remember • Medication interactions : • Meds • Enhance absorption • Decrease absorption • Reverse the effects • Foods • All of the above • OJ + Iron

48. Determinants that Affect Drug Therapy • Clinical Factors • Age, weight • Present health disorder • Other disease entities • Client drug compliance • Pharmacokinetics • Absorption • Distribution • Metabolism (t1/2) • Excretion • Administration • Drug form • Route of administration • Multiple drug therapy. • Drug interactions • Pharmacodynamics • Onset, peak , & duration • Therapeutic range • Side effects and adverse effects • Pharmacogenitics

49. Practice Question • Mr. T has liver and kidney disease he is administered a medication that is manufactured to have a 30 hour half life. You expect the duration of this mediation for him to: • A. • B. • C. • D.

50. Answer