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Cholinergic receptors

Response, activates PLC->IP3,DAG=>Ca++ Similar to M1 mechanism. Sm. Muscles, secretory Agonists Action Bethanechol Stimulates GI and urinary bladder Carbachol + Increases ureteral peristalsis, contraction of detrusor muscle, and decreases Betanechol capacity of urinary bladder (increase in micturation) M3 agonist for salivary gland activation Induces marked salivation and diaphoresis (sweating) Tx of glaucoma by inducing papillary constriction, spasm of accommodation = fall in IOP myasthenia Gravis (also w/ neostigmine and pyridostigmine) anatagonists, Tx of organophosphate toxcitiy echothiophate Tx of glaucoma. The only organophosphate used clinically Short acting ChE inhibitor. Dx of Myasthenia gravis Metabolized to malaoxon. Mammals rapidly detoxify by plasma carboxylesterases. (Organophosphate) Insecticide. Quaternary reversible carbamate inhibitor Tx paralytic ileus and atony of urinary bladder -An oxine = an nuc agent that reactivates phospharylated ChE more rapidly than spontaneous hydrolysis -Not effective against cabamoyl esters such as Neostigmine and physostigmine. -Most effective reversal of NMJ paralysis -Used for Tx of organophostphate toxicity Tx of myasthenia gravis Prophylactic Tx of organophosphate war gas exposure • Quaternary compounds have no CNS activity, but can directly stimulate (direct agonists) nicotinic receptors on NMJ. (even in denervated tissue) • Choline subsite: Edophonium, Tacrine, Donepezil • Acyl subsite: Neostigmine, Pyridostigmine, Physostigmine, Rivastigmine 2. little CNS effect 3. Toxicity associated with exciation, restlessness, irritability, disorientation, hallucinations or delirium 4. Atropine suppression of mucous secretion and mucociliary clearance is good for general anesthesia, but bad for airway dis. 5. inhibits GI activity induced by choline esters or by anti-ChE agents 6. Only partially inhibits vagal activation of intestine Pirenzepine 1. Selective activity for M1 receptor in ganglia to reduce vagal activation 2. at therapeutic doses, we see depression, drowsiness, amnesia, fatigue. Anticholinergic/antimuscarinic Toxicity from other drugs Diphenhydramine H1-histamine antagonists (Benadryl®) Atypical antipyschotics, thienobenzodiazepine Neuromuscular (nicotinic cholinergic receptors) Blockers [paralytic agents]
Nicotinic Antagonists

Drug Action Atracurium 1. Intermediate acting 2. More selective because of little vagolytic or ganglionic activity even though releases histamine (also w/ mivacurium).
3. Elimination not dependent on renal function. (It gets hydrolyzed 2. Classic antagonist though not selective for NMJ 3. Ganglionic blockade (nicotinic AG) which induces tachycardia 4. Vagolytic (muscurinic antagonist) which induces tachycardia 5. Acts on mast cells to release histamine which induces bronchospasm, hypotension and airway secretions. (vagal hyperactivity!) Dantrolene 1. A ryanodine R (RYR-1) agonist that prevents Ca++ release. Mivacurium 1. short acting (same with succiylcholine)
2. Competitive (Phase II)
3. Hydrolysis by ChE
4. Selective because of little vagolytic or ganglionic activity even
though histamine is released. (same deal with Atracurium) Pancuronium 1. Long Acting (like curare) 2. No histamine release but induces tachycardia by vagolytic action. 2. Depolarizing
3. Effects of a single 10-30 mg iv dose
4. induces HYPERKALEMIA (contraindication for patients on
digitalis, diuretics and in burn patients) 5. Triggers Malignant Hyperthermia along with halogenated
Short acting – Mivacurium Intermediate Acting – Atarcurium, Succinylcholine Long acting – pancuronium, curare 1. Blocks slow EPSP of ganglionic transmission 1. Ganglionic blocking agents. Antagonists only (no
stimulation).
2. Block rapid depolarization by inward Na+ current
3. Interacts with Nicotinic sites. Competitive antagonists (no
2. PNS effects:
a. transient stimulation and subsequent persistent depression of autonomic ganglia. Stimulation and depression of adrenal medulla and NMJ 3. CV effects:
a. tachycardia (↑ HR) and ↑ BP. Stimulates sympathetic ganglia , adrenal medulla. Releases catecholamines
from nerve terminals Æ increases Sympathetic effects.
Activates chemoreceptors of aortic and carotid bodies.
4. CNS effects:
a. N/V. Psychostimulant. Tx for psychological i. Gum, transdermal patch, nasal spray, vapor tetramethylammonium 1. other ganglionic stimulant 1) Bethanechol (1st choice)
2) Carbechol
3) Pilocarpine
4) Cevimeline
1) atropine
2) piroenzipine
3) Scopolamine
1) Curare
2) Succinylcholine
3) dantrolene

Source: http://www.johndang.net/rxnotes/PS1/s/Exam%20III%20notes.pdf

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