Lect 18

• Alpha- and beta-adrenergic antagonists can be classified into different categories.
• Some beta-blockers have intrinsic sympathetic activity (ISA), resulting in a partial agonist effect at β1 and β2, or both types of adrenergic receptors.
• Agonists favor the inactive conformation of an enzyme.
• This results in a smaller reduction in cardiac output and less bradycardia.
• Alpha-adrenergic antagonists have cardiovascular and noncardiovascular effects.
• Cholinesterase Inhibitors (Indirect - Acting) produce skeletal muscle fasciculations, twitching, and subsequently muscle paralysis occurs.
• Typical parasympathomimetic actions include profuse salivation, vomiting, defecation, hypermotility of GI tract, urination, bradycardia, hypotension, severe bronchoconstriction, and excess bronchial secretion.
• Endogenous ACh is not inactivated.
• Organophosphate poisoning produces diffuse cholinomimetic effects.
• Nonselective alpha1 and alpha2 receptor antagonists are also a part of alpha-adrenergic antagonists.
• Selective alpha1 and alpha2 receptor antagonists are also a part of alpha-adrenergic antagonists.
• Selective beta-adrenergic antagonists work by inhibiting the interaction of NE, EPI, and other sympathomimetics with beta-adrenergic receptors.
• Drugs that inhibit the interaction of NE, EPI, and other sympathomimetics with alpha- and beta-adrenergic receptors are termed adrenergic receptor antagonists, also known as sympatholytics.
• Alpha-adrenergic receptor antagonists include beta-haloethylamine alkylating agents such as Phenoxybenzamine, imidazoline analogs like Phentolamine, and piperazinyl quinozolines like Prazosin.
• Alpha-adrrenoceptor antagonists are a chemically heterogenous and structurally diverse group, predominantly competitive antagonists.
• Atenolol is a second generation β-blocker that decreases heart rate, cardiac output, and systolic and diastolic pressures.
• Cholinesterase inhibitors work by inhibiting the breakdown of acetylcholine, which increases the duration of cholinergic receptor stimulation.
• Muscarinic receptor antagonists work by binding to these receptors and blocking their effects.
• Carvedilol is a third generation β-blocker that demonstrates modest α1-adrenergic receptor antagonist properties, membrane stabilizing activity, and no intrinsic sympathetic activity.
• Cholinergic receptor stimulants work by binding to these receptors and have clinical uses such as treating asthma and controlling heart rate.
• Cholinergic receptors are found in the brain, heart, and peripheral tissues and have physiological effects such as increasing heart rate, constricting blood vessels, and increasing glandular secretion.
• Esmolol is a second generation β-blocker with no intrinsic sympathomimetic activity or membrane-stabilizing properties and is an ultra-short-acting β1-selective receptor antagonist (half-life < 10 min).
• Metoprolol is a second generation β-blocker that does not have intrinsic sympathetic activity (ISA) and decreases heart rate, cardiac output, and systolic and diastolic pressures.
• Tenth edition of Veterinary Pharmacology and Therapeutics is edited by Jim E. Riviere and Mark G. Papich.
• Pilocarpine, Muscarine, and Arecoline are examples of cholinomimetic alkaloids.
• Bethanechol is resistant to hydrolysis by cholinesterase and has been used to promote bladder contraction in paraplegic dogs and cats.
• There are few clinical indications for the use of cholinergic agonists in veterinary medicine.
• Carbachol (Miostat®) is used topically to produce miosis.
• Direct-acting agonists contain structural groupings that allow interaction with the receptor.
• Direct-acting parasympathomimetic agonists act directly on receptors and do not depend upon endogenous ACh for their effects.
• ACh is not used therapeutically because it is inactive at the target organ.
• Bethanechol is used to promote detrusor muscle contraction for treatment of detrusor sphincter dyssynergia.
• Nicotinic receptors are found in autonomic ganglia, the adrenal medulla, and the endplate of the NMJ.
• The pharmacological effects of the primary choline derivates are similar to the parasympathomimetic effects produced by ACh administration.
• ACh is the neurotransmitter released at sympathetic and parasympathetic ganglia.
• The physiological response profiles produced by different choline esters are not identical and vary in relative selectivity for one organ system to another.
• Choline esters are a type of cholinomimetic alkaloid.
• Muscarinic receptors are found at postsynaptic target sites in the heart, glands, urinary bladder, and GI tract.
• Acetylcholine is a prototypical cholinergic agonist.
• Metoprolol inhibits the β-agonist-induced tachycardia.