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81 Cards in this Set
- Front
- Back
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Cholinergic neurotrasmitter is not used in clinical therapeutics because |
1. Can cause a generalized but transient effect 2. It is readily hydrolized by plasma cholinesterases that it cannot be detected in the plasma following absorption |
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Muscarinic effect of heart |
Decreased cardiac output Depression of SA node and AV node Increased automaticity of ventricles |
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Muscarinic effect of vascular smooth muscle |
Vasodilation |
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Muscarinic effect of gut |
Increase peristalsis Decrease sphincter tone |
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Muscarinic effect of urinary bladder |
Stimulate contraction Facilitate urination |
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Muscarinic effect of bronchioles |
Bronchoconstriction Dyspnea |
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Muscarinic effect of eyes |
Papillary constriction Ciliary muscle stimulation Drainage of intraocular fluid |
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Muscarinic effect of exocrine glands |
Increased secretion |
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Nicotinic effects are mediated at the |
Autonomic ganglia Adrenal medulla Motor end plate |
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produces a hypertensive effect by acting on sympathetic ganglia and adrenal medulla to discharge norepi and epi |
Nicotinic effect |
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Acts on cholinergic receptors at motor end plate to cause muscle contraction, tremors and fasciculation |
ACETYLCHOLINE |
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Sustained stimulation of ach may cause |
Muscle fatigue Paralysis |
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Drugs acting on cholinergic domain |
Cholinergic stimulants (Parasympathomimetics) Anticholinergics (Parasympatholitics) |
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It directly stimulates cholinergic receptors |
Directly acting |
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Cholinesterase inhibitors |
Indirectly acting |
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Examples of directly acting |
Choline esters -methacholine -carbachol -betanechol Alkaloids -muscarine -pilocarpine -arecholine |
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Examples of irreversible cholinesterase inhibitors |
Organophosphate -malathion -parathion -dichlorvos Carbamates -carbaryl -propoxur |
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Examples of reversible cholinesterase inhibitors |
Natural alkaloid -physostigmine Synthetic alkaloids -neostigmine -edrophonium -ambenonium -pyridostigmine |
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Categories of anticholinergics |
Cholinergic blockers Ganglionic blocking agent |
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Examples of cholinergic blockers |
Atropine Atropine-like drugs |
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Examples of ganglionic blocking agent |
Non-depolarizing blocking agents Depolarizing blocking agents |
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Have direct action on the receptor for acetylcholine. some are muscarinic or nicotinic |
Direct acting cholinomimetics |
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Derivative of acetylcholine Binds directly to muscarinic receptors |
Choline esters |
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Resist degradation by cholinesterase Produce typical muscarinic effects Used in ergot poisoning |
Methacholine |
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Active on both muscarinic and nicotinic receptors Potent GI stimulant Treatment of gut hypomotility and bladder paralysis, and glaucoma Used in colic and impactions Not used in pregnant animals Can be given at the middle of farrowing Should not be given IV or IM |
Carbachol |
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Most resistant to cholinesterase More on muscarinic effects Treat neurogenic urinary bladder paralysis Used in esophageal achalasia |
Bethanechol |
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Active principleof poisonous mushroom Has selective excitatory effect CS: profuse salivation, lacrimation, dyspnea, colic, diarrhea, CV collapse |
Muscarinic |
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Has marked effects on the muscarinic receptors in the eye, exocrine glands, and GI muscles Potent constrictor effect on pupils Used as potent pupillary constrictor Treat glaucoma |
Pilocarpine (Pilocarpus jaborandi) |
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Activates muscarinic receptors Mote potent than pilocarpine Once used as purgative to remove intestinal worms |
Arecholine (Areca catechu) |
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Toxicology of cholinomimetic alkaloids |
Severe colic and diarrhea Dyspnea Hypotension ad extreme cardiac slowing |
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Act by blocking the metabolism of acetycholine by cholinesterases Effectively increase concentration of acetylcholine |
Indirect-acting cholinomimetics |
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3 categories of cholinesterase inhibitors |
Organophosphates Carbamates Short-acting cholinesterase inhibitors |
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What are 2 types of cholinesterase |
Acetylcholinesterase Butyrylcholinesterase |
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Substrate of true and pseudo cholinesterases |
Acetylcholine Acetylcholine, esters of choline, some local anesthetics |
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Location of acetylcholinesterases |
Nerve terminals Neuromuscular junction CNS gray matter |
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Location of butyrylcholinesterase |
Plasma CNS white matter |
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Clinical signs of cholinesterase inhibition |
Muscarinic- colic, dyspnea, diarrhea, hypotension, miosis, excessive excretion Nicotinic- muscle tremors, paralysis, convulsion, coma |
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How can cholinesterase be inhibited |
Acetylation Carbamylation Phosphorylation |
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Includes OP and carbamates |
Irreversible cholinesterase inhibitors |
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Used as insecticide Cause carbamylation of the estaratic site |
Carbamates |
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Used as insecticide or pesticide, anthelmintics |
Organophosphates |
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OP deadly gases |
Diisopropylfluorophosphate Triorthocresylphosphate Sarin Others: malathion, dichlorvos, coumaphos, ronnel |
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Strong covalent linkage between OP and cholinesterase which can be permanent |
Stage 1: Phosphorylation of the enzyme |
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OPs with more complex R groups takesnlonger to recover |
Stage 2 : Spontaneous recovery/dephosphorylation |
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Dephosphorylation can sometimes be induced by |
Hydroxylamine Pralidoxime |
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Stge at which enzyme cannot be reactivated |
Stage 3: Aging |
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After OP poisoning, it takes weeks or months to restore normal cholinesterase level |
Stage 4: Biosynthesis of new cholinesterase |
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CNS effects of OP |
Excitation and mania - convulsion and coma Usual cause of death is respiratory failure |
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Is the most important antidote Blocks muscarinic effects but not nicotinic Given by IV |
Atropine |
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Atropine is counteracted by |
Pentobarbital |
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Dose of atropine |
0.2-2mg/kg give 1/4 dose IV and the rest SC or IM |
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Useful during early stages of poisoning |
Pralidoxime |
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Dose of 2-PAM |
Horse - 20mg/kg Cattle - 10-40mg/kg IM IV q12h Dog- 10-20 mg/kg by slow IV |
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Derived from calabar bean or ordeal bean (Physostigma venenosum) Blocks esteratic site of Che Mainly muscarinic effects Used exclusively in ophthalmology |
Physostigmine |
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Quaternary amine analogue of physostigmine Has dual action Has potent anticurare action |
Neostigmine |
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Dual action of neostigmine |
Inhibit cholinesterase Directly stimulate cholinergic receptors |
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Clinical uses of neostigmine |
Treatment of gut hypomotility Urinary bladder paralysis Myasthenia gravis Counteract effects of non-depolarizing muscle relaxants |
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Condition in which the number of cholinergic receptors in skeletal muscle end plates is reduced May be congenital or autoimmune |
Myasthenia gravis |
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Increase the available acetylcholine in the motor end plate to increase chances of stimulating whatever normal receptors left Also directly stimulate cholinergic receptors |
Neostigmine |
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Used to differentiate between muscle wekaness due to myasthenia gravis and muscle weakness by overstimulation |
Edrophonium |
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Long acting |
Ambenonium Pyridostigmine |
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Antagonist of acetylcholine at the muscarinic receptors Have little or no action on the nicotinic sites |
Anticholinergics |
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Prototype cholinergic blocker Effects are opposite of acetylcholine Well absorved orally parenterally and from the eye |
Atropine |
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Active poisons of atropine |
Atropa belladona - deadly night shade Datura stramonium - jimson weed Hyocayamus niger - henbane |
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Most resistant species to atropine |
Rabbit |
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Most sensitive sensitive species to atropine |
Pig Dog Cat |
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Pharmacological effects of atropine |
Tachycardia Relaxation of smooth muscles Decreased exocrine secretions Relaxation of ciliary muscle - mydriasis and cyloplegia Hyperthermia - large doses |
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Signs of atropine poisoning |
Dry mouth Thirst Dysphagia Constipation Mydriasis Tachycardia Restlesness Delirium Convulsion Respiratory depression and failure |
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Clinical uses of atropine |
Pre-anesthetic medication Antispasmodic In ophthalmology - produce mydriasis Treatment of OP or carbamate poisoning |
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Has more CNS effects than atropine Used to produce twilight sleep in human |
Scopolamine |
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Has only 10% of atropine's effect Ocular effect |
Homatropine |
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Has greater CNS effect Unique anti emetic effect in dogs |
Hyocine |
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Used as preanesthetic medication 5x more potent than atropine as sialogogue |
Glycopyrrolate |
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Used as a gastrointestinal antispamodic drug |
Propantheline |
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Used in ophthalmology as a mydriatic |
Eucatropine |
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Enumerate atropine-like drugs |
Scopolamine Homatropine Hyocine Glycopyrrolate Propantheline Eucatropine |
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Block cholinergic receptors in the autonomic ganglia in both para and sympa divisions |
Ganglionic blocking agents |
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Have no intrinsic activity Fall in blood pressure, decreased gut motility, constipation |
Non depolarizing blockers |
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Examples of non depolarizing blockers |
Tetraethylammonium Hexamethonium Pentolinium Mecamylamine |
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Cause powerful and persistent stimulation of cholinergic receptors leading to receptor blockade and fatigue |
Depolarizing blockers |
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Wildlife capture drug and insecticide Poisoninf is characterized by hypertension and tachycardia |
Nicotine |
