Autonomic Pharmacology

At the end of this course, students should be able to: 1. describe the anatomy of the ANS and its two divisions; 2. outline the major neurotransmitters involved in each division of the ANS, synthesis of the neurotransmitters; 3. list sympathetic and parasympathetic effects; 4. describe the physiological and pathophysiological role of 5HT and histamine; 5. outline the mechanism of release of 5HT and histamine; 6. explain the various types and subtypes of receptors, with examples of antagonists; 7. discuss basic and clinical pharmacology of antagonists at the 5HT-and histamine receptors; 8. describe other autacoids; 9. list the various modes of action of drugs and explain dose-effect relation of drugs; and 10. explain concept of variability in individual response to drugs.

Review of autonomic nervous system anatomy, sympathetic (thoracolumbar) and parasympathetic (craniosacral) divisions. Review of neurohumoral transmission. Neurotransmitters of the ANS, cholinergic and adrenergic transmission–evidence for acetylcholine and noradrenaline, synthesis of the neurotransmitters. Parasympathetic system, cholinergic receptors, muscarinic and nicotinic stimulants, uses, pharmacodynamics, SAR, organ system effects. Indirectly acting cholinergic stimulants-anticholinesterases, chemistry and pharmacokinetics. Clinical pharmacology of cholinergic stimulants. Cholinergic receptor antagonists–muscarinic and nicotinic, chemistry, pharmacokinetics and pharmacodynamics of atropine and related drugs, organ system effects (CNS, eye, CVS, respiratory system, GIT, Genito–urinary tract and sweat glands), including their clinical pharmacology. Basic and clinical pharmacology of ganglion blockers. Somatic motor nerves. Neuromuscular junction transmission, effect of drugs, end–plate nicotinic receptor and neuromuscular blockers, types of blockers and their interaction with anti-cholinesterase, lack of Pseudo-cholinesterase and 212 anaesthesia. Sympathetic system, basic pharmacology of adrenergic receptor stimulants. Identification of adrenergic receptors, molecular mechanisms of adrenergic action, chemistry, pharmacokinetics and pharmacodynamics of sympathomimetic drugs. Organ system effects. CVS, blood vessels, heart, blood pressure, eye, respiratory tract, exocrine glands, metabolic effects on endocrine function (use of noradrenaline, adrenaline, isoprenaline dopamine, dobutamine, salbutamol, fenoterol, terbutaline, phenylephrine, ephedrine and amphetamine as examples). Direct and indirect acting sympathomimetics such as tyramine. Clinical pharmacology of adrenergic receptor acting drugs. Cardiovascular application, condition in which blood flow or blood pressure is to be enhanced, hypotension, shock, carcinogenic shock, condition in which the blood flow is to be reduced, hypertension, and cardiac applications, paroxysmal atrial tachycardia, complete heart block and cardiac arrest, congestive heart failure. Respiratory application, Bronchitis, bronchial asthma. Anaphylaxis, Ophthalmic, genitourinary, use of β2 antagonists (terbutaline, ritodrine, salbutamol) to suppress premature labour. CNS applications Toxicity of sympathomimetics. Adrenergic receptor blocking drugs - Alpha receptor blockers, types (reversible and irreversible), receptor–selective antagonists (phenoxybenzamine, phentolamine, yohimbine, prazosin, indoramin, idazoxan), pharmacological effects (cardiovascular and others), Beta-receptor blockers, types, B1- and B2-specificity (propranolol, metoprolol, timolol, atenolol, pindolol, labetalol), pharmacokinetics, (absorption, bioavailability, distribution and clearance), pharmacodynamics (CVS, respiratory tract, eyes, metabolic and endocrine effects), effects unrelated to beta receptor blockade. Clinical pharmacology of alpha- and beta-receptor blockers. Application of alpha-blockers, phaeochromocytoma, hypertensive emergencies and hypertensive chronic treatment, peripheral vascular disease and local vasoconstrictor excess. Application of beta-blockers, hypertension, ischaemic heart disease, cardiac arrhythmias, other cardiovascular disorders, glaucoma, hyperthyroidism, neurological disease (migraine headache, tremors, anxiety, alcohol withdrawal), choice of beta blockers, clinical toxicity. Autacoids, Histamine and its antagonists. Physiological and pathophysiological role of histamine, pharmacology of histamine receptors, mechanism of histamine release, H1-antagonists (ethanolamine, ethylenediamines, phenothiazines), H2-antagonists (burimamide, metiamide, cimetidine.), H3-antagonists (bronchioles, methylhistamine), basic pharmacology, chemistry, pharmacokinetics and pharmacodynamics, clinical pharmacology. 5HT and its antagonists. Methysergide. Cyproheptadine, cyclooxygenase inhibitors, vasoactive polypeptides, vasopressin, angiotensin, kinins, kallikrein, substance P, prostaglandins, leukotrienes, cyclic nucleotides and other mediators.