Pharmacology for Nursing Introduction DrugBody Interactions The interactions
Pharmacology for Nursing Introduction
Drug-Body Interactions The interactions between a drug and the body are conveniently divided into two classes. The actions of the drug on the body are termed pharmacodynamic processes. These properties determine the group in which the drug is classified, and they play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease. The actions of the body on the drug are called pharmacokinetic processes. These processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient, e. g. , a 2 patient with impaired renal function.
Drug Receptors & Pharmacodynamics Therapeutic and toxic effects of drugs result from their interactions with molecules in the patient. Most drugs act by associating with specific macromolecules in ways that alter the macromolecules' biochemical or biophysical activities. Receptors are the components of the cell or organism that interact with a drug to initiate chain of events leading to the drug's observed effects. 3
Drug Receptors & Pharmacodynamics Many drug receptors have been isolated and characterized in detail, thus opening the way to precise understanding of the molecular basis of drug action. The receptor concept has important practical consequences for the development of drugs and for arriving at therapeutic decisions in clinical practice. These consequences form the basis for understanding the actions and clinical uses of drugs. 4
Drug Receptors & Pharmacodynamics Receptors largely determine the quantitative relations between dose (or concentration) of the drug and pharmacologic effects. The receptor's affinity for binding a drug determines the concentration of drug required to form a significant number of drug-receptor complexes, The total number of receptors limits the maximal effect a drug can produce. 5
Relations between drug concentration and drug effect 6
Relations between drug concentration and receptor-bound drug 7
Drug Receptors & Pharmacodynamics Receptors are responsible for selectivity of drug action. The molecular size, shape, and electrical charge of a drug determine how it will bind to a particular receptor. Accordingly, modifications in the chemical structure of a drug can dramatically increase or decrease a drug's affinities for different classes of receptors, with resulting alterations in therapeutic and toxic effects. 8
Drug Receptor Interactions Agonists act at the agonist binding site(Receptors) to initiate an action. Competitive inhibitors act at the agonist binding site, to produce no action, but can inhibit the binding and action of the agonist. Allosteric activators act at separate sites to increase the efficacy of the agonist or its binding affinity. Allosteric Inhibitors act at separate sites to decrease the efficacy of the agonist or its binding affinity 9
Drug Receptor Interactions 10
Drug Receptors & Pharmacodynamics Receptors mediate the actions of pharmacologic agonists and antagonists. 11
Agonist-Antagonist Relationships Competitive antagonist, higher concentrations of agonist are required to produce a given effect. High agonist concentrations can overcome inhibition by a competitive antagonist. Irreversible (or noncompetitive) antagonist, reduces the maximal effect the agonist can achieve, although it may not change its EC 50. 12
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Transmembrane Signaling Mechanisms 1. Lipid-soluble drug crosses the plasma membrane and acts on an intracellular receptor (which may be an enzyme or a regulator of gene transcription. 2. The drug binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain 3. The drug binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activats 4. The drug binds to and directly regulates the opening of an ion channel 5. The drug binds to a cell-surface receptor linked to an effector enzyme by a G protein. 14
Nicotinic Receptor 15
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Therapeutic and Toxic Effects of Drugs Three posssibilities: Both mediated by the same receptoreffector mechanism. – i. e. toxicity is a direct pharmacologic extension of therapeutic action of the drug. Mediated by identical receptors but in different tissues or by different pathways. Each mediated by different types of receptors. 17
Possibilities of Drug Combinations Antagonistic Effects Additive Effects. Synergistic Effects. No effect. 18
Drug Antagonism Pharmacologic Antagonism: – Drugs work on the same receptor. – Competitive Antagonism. – Noncompetitive antagonism. Physiologic Antagonism: – Drugs work on opposite physiological processes. – E. g. Epinephrine in Anaphylaxis. Chemical Antagonism: – A drug chemically neutralizes the other drug. – Antacid in heartburn. 19
Pharmacologic Antagonism Competitive Antagonism: Antagonist binds to the same site of agonist binding and prevents agonist binding. Noncompetitive antagonism: Antagonist binds to a site on the receptor separate from the agonist binding site and prevents receptor activation without blocking agonist binding. 20
the agonist concentration (C') required for a given effect in the presence of concentration [I] of an antagonist is shifted to the right, as shown. High agonist concentrations can overcome inhibition by a competitive antagonist. Agonist concentration required for a given effect in the presence of concentration of an antagonist is shifted to the right. High agonist concentrations can overcome inhibition by a 21 competitive antagonist.
Irreversible (or noncompetitive) antagonist, which reduces the maximal effect the agonist can achieve. High agonist concentrations can not overcome inhibition by a competitive antagonist. 22
Variations in Drug Resposiveness Hporeactive. Hyperreactive or hypersensitivity. Tolerance. Tachyphylaxis. Idiosyncrasy reactions: – Unusual, or rare, or unexpected responses. – Infrequently observed in most patients. – Might be due to genetic differences or immunologic factors. 23
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