Introduction to Pharmacology

1. 1 Introduction to Pharmacology

2. Multimedia Directory Slide 7 Drug Metabolization Animation Slide 15 Agonist and Antagonist Animation Slide 34 EpiPen Video 1 Slide 35 EpiPen Video 2

3. General Principles “To administer a drug safely, one must know its usual dose frequency, route of administration, indications, contraindications, significant adverse reactions, and major drug interactions.”

4. Pharmacology • Pharmacology: the study of drugs and their actions and effects in body systems • Pharmacodynamics: the study of biochemical and physiologic drug effects, and the mechanisms of drug action • Pharmacokinetics: the study of drug absorption, distribution, metabolism, and excretion

5. Other Pharmacologic Terms • Pharmacognosy: the study of drugs derived from herbal or natural sources • Pharmacotherapeutics: the study of how drugs are best used and which drug is appropriate for a specific disease • Toxicology: the study of poisons and poisonings

6. A Drug’s Journey • Enter the body • Absorption • Bioavailability • Distribution • Metabolism • Elimination

7. Pharmacokinetics • Absorption, distribution, metabolism, and excretion of drugs are related to: • Concentration of drug • Drug’s chemical by-products in various body sites • Time required for drug concentrations to develop or change

8. Figure 1-1 The four processes of pharmacokinetics (that is, movement) are absorption, metabolism, distribution, and excretion. Many drugs are carried through the bloodstream bound to the protein albumin. First - Pass Effect: Many drugs are metabolized in the liver before reaching their target tissue. This metabolism may lead to inactivation or activation of the drug. The class of enzymes most involved are cytochrome oxidases, notably, Cytochrome P450

9. Drug Metabolization Animation Click on the screenshot to view an animation showing drug metabolization. Back to Directory

10. Pharmacodynamics • Describes all matters concerned with pharmacologic actions of a drug, including: • Therapeutic effects (effects that are meant to treat a disease or disorder) • Adverse effects(harmful effects)

11. Dose-Effect Relationship • Pharmacokinetics and pharmacodynamics determine the dose-effect relationship: • Relationship between dose of a drug that produces harmful effects and severity of effects on client • Body’s response to a drug or toxic agent increases as overall exposure to substance increases

12. Figure 1-2A The dose-effect relationship. Along the x-axis is the drug dose, which increases from left to right. Along the y-axis is the maximum response for each drug (%). (A) These curves show drug potency. Drug A’s curve is to the left of drug B’s curve, which indicates that drug A has a higher potency. This means that a smaller dose of drug A will produce the same effect as a larger dose of drug B.

13. Figure 1-2B (B) These curves show drug efficacy (or effectiveness). Drug A reaches a maximum response of 100% at the same dose as drug B, which reaches a maximum response of about 60%. Therefore, drug A’s efficacy (or effectiveness) is greater than that of drug B.

14. Mechanisms of Drug Action • Drugs work by altering normal cell and tissue function. • Specific groups of drugs have affinity (attractive force) for specific target cells, known as receptors. • Binding of drugs to a particular receptor type produces pharmacologic effect—either agonist or antagonist actions.

15. Agonists and Antagonists • Two types of chemical substances bind to receptors: • Agonists: drugs that bind to receptors and produce stimulatory responses that are similar to that produced by endogenous chemicals • Antagonists: drugs that prevent agonists from binding to receptors, thus blocking their effects

16. Agonist and Antagonist Animation Click on the screenshot to view an animation showing an agonist and antagonist. Back to Directory

17. Receptor Selectivity • Some receptors have subtypes, for which certain chemicals have some selectivity. • For example, beta (β)-adrenoreceptors have two subtypes, β1 and β2. • The drug propranolol (Inderal) is an antagonist at both β1 and β2, whereas atenolol (Tenormin) is selective for β1.

18. Drug Half-Life • Half-life (t1/2): time taken for the drug’s blood or plasma concentration to decrease from full to one-half (50%) • The longer the half-life, the longer the drug remains in the body

19. Figure 1-3 Plasma concentration of a drug versus time. The onset of action occurs at 2 hours; the duration of action is 6 hours; peak plasma concentration is 10 mcg/mL; and the time to reach peak drug effect is 5 hours.

20. Factors Affecting Drug Action • Age • Affects metabolic rates, requiring dosage adjustments • Gender • Responses to drugs sometimes differ • Body weight • Dosages may require adjusting for body weight and body surface area

21. Factors Affecting Drug Action • Diurnal rhythms • Intensity of response to drug may be affected by when it is given • Disease • Dosages may need to be adjusted in persons with kidney or liver disease • (kidneys excrete drugs, liver metabolizes drugs)

22. Drug Elimination in Elderly Patients • Acute or chronic diseases that affect liver architecture or function also affect hepatic metabolism of some drugs • Elderly patients may therefore have markedly affected drug elimination and require dosage adjustment

23. Pharmacokinetics: Absorption • Absorption: movement of drug into systemic circulation • Depends on drug’s ability to cross cell membranes and resist presystemic metabolism (enzymes in GI tract begin to break down drug before it is absorbed) • Presystemic metabolism affects drug’s bioavailability—amount of drug that reaches systemic circulation intact and its speed

24. Factors That Affect Absorption • Acidity of the stomach • Physiochemical properties: dissolution, solubility, thermodynamics • Presence of food in stomach or intestine • Routes of administration: PO, IV, IM, subcutaneous, transdermal, sublingual, buccal, rectal, vaginal

25. Pharmacokinetics: Distribution • Distribution: passage of agent through blood or lymph to various body sites • Many drugs are bound to circulating proteins, affecting their ability to bind to receptors; cross tissue membranes; and be distributed, metabolized, and excreted. • Example: many drugs do not cross the blood-brain barrier

26. Pharmacokinetics: Metabolism • Most drug metabolism occurs in the liver. • First-pass effect (metabolism of drug by liver enzymes before it reaches systemic circulation) influences metabolism.

27. Pharmacokinetics: Metabolism • Substances that are absorbed across the intestinal wall enter blood vessels and are carried directly to the liver (hepatic portal circulation). • End-products of metabolism are metabolites.

28. Figure 1-4 First-pass effect. Oral drugs are absorbed through the intestinal wall and enter the hepatic portal circulation. They are taken directly to the liver for metabolism before reaching the heart and circulating throughout the body.

29. Biotransformation • Biotransformation is the conversion of drugs in four stages: • Oxidation: combining with oxygen • Reduction: gaining electrons • Hydrolysis: cleaving into simpler compounds • Conjugation: combining with glucuronic or sulfuric acid, terminating biologic activity

30. Pharmacokinetics: Excretion • The main route of excretion is via the kidneys. • Kidney diseases can prolong the duration of drug action.

31. Pharmacokinetics: Excretion • Other routes of excretion include: • Lungs • Breast milk • Sweat, tears, urine, feces • Bile • Saliva

32. Other Pharmacologic Principles • Toxicity: refers to drug’s ability to poison the body • Overdose: dose of drug that causes harm • Adverse drug reaction (ADR): any response to drug that is noxious, unintended, and occurs at doses normally used for prophylaxis, diagnosis, or therapy

33. Other Pharmacologic Principles • Side effect: an unintended drug effect; this can be beneficial

34. Drug Interactions • Occur when the effects of one drug are altered by those of another drug • Occasionally, the effects of both drugs are altered. • Drug interactions usually result in an adverse drug reaction, though some interactions may be beneficial.

35. Idiosyncratic Reactions • Idiosyncratic reaction: a unique, strange, or unpredicted reaction to a drug • Allergic reaction: hypersensitivity to drug that occurs after previous exposure to similar or same drug, and develops rapidly after reexposure • Anaphylactic shock: idiosyncratic, sudden, and life-threatening allergic reaction

36. EpiPen Video 1 Click on the screenshot to view a video on the topic of the EpiPen. Back to Directory

37. EpiPen Video 2 Click on the screenshot to view a video on the topic of the EpiPen. Back to Directory

38. Allergy History • Ask all patients if they have a history of allergies, such as hay fever, rashes or asthma, or have had unusual reactions to any drugs taken orally or by injection

39. Table 1-1 Allergic Drug Reactions

40. Tolerance • Tolerance: development of resistance to drug’s effects, such that dose must be continually raised to elicit desired response • Drugs that commonly produce tolerance are: • Opiates • Barbiturates • Tobacco • Nitrates • Alcohol

41. Other Drug Effects • Cumulative effect: occurs when body cannot completely metabolize and excrete one drug dose before next dose is given • Synergism: occurs when combined action of two or more agents produces a greater effect than expected from agents acting separately

42. Other Drug Effects • Potentiation: a greater effect than expected caused from additive properties of two or more drugs