Drug Action and Handling: Understanding Dose-Effect Curves and Mechanisms of Drug Receptors

1. Chapter 2 Drug Action and Handling

2. Characterization of Drug Action • Dose-Effect Curve • Intensity of the drug changes as the dose changes. • Intensity of the effect changes with time. • Desired therapeutic effect is related to dose. • Adverse and therapeutic effects are related to dose. 2

3. Figure 2-1 Dose-effect curve. 3

4. Figure 2-2 Log dose-effect curve. 4

5. Figure 2-3 Potency of agent. 5

6. Drug Mechanism of Action • Nerve Transmission • Normally, an impulse travels along the nerve and produces an action potential. • The action potential is triggered by the neurotransmitter released at the previous synapse. • Ultimately, the nerve transmission binds to a receptor on a cell and enters the cell. • Once inside the cell, the message is given to produce a response (i.e. increased heart rate). 6

7. Drug Receptors • When a drug combines with a receptor it either enhances cell function or inhibits cell function. • Drugs that enhance cell function are called agonists. • Drugs that inhibit cell function are call antagonists. 7

8. Drug Agonists • Have an affinity for a receptor • Combine with the receptor • Produce an effect • Naturally occurring neurotransmitters are agonists 8

9. Antagonists • Competitive Antagonists – These drugs have an affinity for the receptor, combine with the receptor, and produce no effect once attached to the receptor. • Noncompetitive Antagonists – These drugs bind to a receptor site that is different from the binding site of the neurotransmitter or agonist. This reduces the maximal response of the agonist. 9

10. Antagonists • Physiologic Antagonist – These drugs have an affinity for a different receptor site than the neurotransmitter or agonist. This decreases the maximal response of the agonist by producing an opposite effect by means of different receptors. 10

11. Routes of Drug Administration • Enteral – Drugs are placed directly into the gastrointestinal tract by oral or rectal administration. • Parenteral – This type of drug administration bypasses the gastrointestinal tract and includes various injection routes, inhalation, and topical preparations. 11

12. Oral Routes of Administration • Convenient, easy to use • Most widely accepted by Americans • Small intestine provides a large area for drug absorption • Slower onset of action • Gastrointestinal adverse effects • Blood levels are less predictable 12

13. Rectal Routes of Administration • Good for patients who are vomiting or unconscious • Can be used for local or systemic effects • Poor patient acceptance • Poor and irregular absorption of drugs 13

14. Intravenous Routes of Administration • Produces the most rapid drug response • Can produce an almost immediate onset of action • Bypasses the absorption phase of the pharmacokinetic process • Produces a more predictable drug response • Route of choice for an emergency situation • Disadvantages include phlebitis, local irritability, drug irretrievability in the face of an allergic reaction 14

15. Pharmacokinetics • Passage Across Body Membranes • In order for a drug to be absorbed into the body it must pass across different body membranes. • Drug passage across body membranes is facilitated by several different transport systems. • The transport systems include passive transfer, active transport, and facilitated diffusion. 15

16. Pharmacokinetics – Absorption • This is the process that transports drug molecules from the site of administration to the circulating blood. • Once in the circulating blood, drug molecules must then pass through or across biologic membranes. 16

17. Drug Absorption • Factors that Effect the Rate of Drug Absorption • Physicochemical factors • Site of administration • Drug’s solubility 17

18. Absorption from Oral Dose Forms • Dose form influences drug absorption. • Liquid dose forms are absorbed right away. • Tablets and capsules must be broken down so that the drug can be released into the gastrointestinal tract. 18

19. Drug Release from Solid, Oral Dose Forms • Disruption • The tablet coating or capsule shell begins to disintegrate. • Disintegration • Tablet or capsule contents break apart. • Dispersion • Concentrated drug particles are spread throughout the stomach or small intestine. • Dissolution • The drug is dissolved in the gastrointestinal fluid. 19

20. Drug Distribution • Distribution is the passage of drugs into target organs, non-target organs, plasma, interstitial fluids, intracellular fluids, brain, placenta, and enterohepatic circulation. • Distribution is determined by the size of the organ, drug solubility, plasma protein binding capacity, and the presence of barriers. • The proportion of drug distribution to site of action determines how quickly it will produce a response and the duration of that response. 20

21. Drug Metabolism • Active parent compound is converted to an inactive compound. • Active parent compound is converted to a second active compound that is then. converted to an inactive compound • Inactive parent compound is transformed into an active compound. 21

22. Drug Excretion • Routes of Excretion • Kidneys • Sweat • Saliva • Gingival crevicular fluid • Respiratory tract • Gastrointestinal tract • Breast milk 22

23. Factors that Effect Pharmacokinetics • Patient compliance • Age and weight • Sex • Pathologic state • Genetic variations • Placebo effect • Time or route of administration • Other drugs 23