1 Introduction to Pharmacology

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

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.”

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

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

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

Drug Metabolization Animation Click here to view an animation showing drug metabolization. Back to Directory

Figure 1-1 The four processes of pharmacokinetics (that is, movement) are absorption, metabolism, distribution, and excretion.

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)

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

Figure 1-2A The dose-effect relationship 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.

Figure 1-2B (B) These curves show drug efficacy (or effectiveness) 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.

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.

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

Agonist and Antagonist Animation Click here to view an animation showing an agonist and antagonist. Back to Directory

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.

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

Figure 1-3 Plasma concentration of a drug versus time 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.

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

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

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

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

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

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.

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.

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.

Figure 1-4 First-pass effect 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.

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

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

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

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

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

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.

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

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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

Table 1-1 Allergic Drug Reactions

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

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

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