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Sympathetic NS Pharmacology of the Autonomic Nervous System Indented = similar action to parent compound italic = less important agent [ ] = questionable therapeutic value I =drug interactions S = side effects T = toxicity CV = cardiovascular system CNS = central nervous system Agent (trade name®) Therapeutic Use Notes E. Ishac Adrenoceptor Agonists MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants Norepinephrine (Levarterenol) Hypotension, pressor agent α / β1 β3 (β2) neuronal, non-circulating, I: MAOI, TCA Epinephrine (generic) Allergic reactions, shock, CPR α / β1 β2 (β3) adrenal medulla, circulating; I: MAOI, TCA Dopamine (Intropin) Renal vasodilatation during shock α1 / β1 / D, precursor to NE, I: MAOI Isoproterenol (Isuprel) Asthma, cardiac stimulant β, synthetic, not endogenous; (↓, --) BP HR Phenylephrine (Neosynephrine) Nasal decongestant, hypotension not commonly used for hypotension; S: CV, reflex Methoxamine (Vasoxyl) Hypotension, pressor agent bradycardia Metaraminol (Aramine) Hypotension, pressor agent α, orally active; NE or DA better choice Clonidine (Catapres) Hypertension α2, ↓ cns sympathetic outflow, inhibit NE release, Guanfacine (Tenex) rebound HT; S: dry mouth, sedation, impotence. α-methyl-dopa is metabolized to α-methyl-NE (α - α 2 -methyl-dopa (Aldomet) agonist) Dobutamine (Dobutrex) CHF, cardiac stimulant β1, iv infusion, tolerance, desensitization Prenalterol Terbutaline (Brethaire) Asthma, premature labor β2-selective, Oral 1-2 hrs onset ! 4-6 hrs duration, Ritodrine (Yutopar) Premature labor Inhalation 5-10 min onset ! 3-4 hrs duration; S: cardiovascular; less via inhalation Metaproterenol (Alupent) Asthma - bronchodilator Albuterol (Proventil, Ventolin) Miscellaneous Adrenoceptor Agonists L-Dopa (Dopar, Larodopa) Parkinson’s disease precursor to DA, cross to CNS! DA Ephedrine (Vatronol, Efedron) Nasal decongestant, red eyes α /β, also indirect to release NE; I: MAOI, TCA Amphetamine (Dexedrine) Narcolepsy, hyperactivity, [obesity] release NE, CNS stimulant, tolerance Tyramine None, [high] in red wine & cheese interaction with MAO inhibitors Adrenoceptor Antagonists HT = Hypertension PHT = Postural hypotension LA = Local anaesthetic action Phenoxybenzamine (Dibenzyline) Pheochromocytoma, acute HT α1, irreversible, S: PHT Phentolamine (Regitine) Pheochromocytoma, acute HT, [impotence] α, competitive, S: PHT, reflex tachycardia Tolazoline (Priscoline) Prazosin (Minipres) Hypertension (HT), benign prostrate α1, competitive; no reflex tachycardia S: PHT, Terazosin (Hytrin) hypertrophy nausea, drowsiness Yohimbine (Yohimex) [Impotence] α2, currently not used as such Propranolol (Inderal) Hypertension, angina, arrhythmias, tremor, β, non-selective, LA-action, no ISA; A very useful migraine, hyperthyroidism (propranolol), group, Contraindications: heart failure (currently panic stress under FDA review), asthma, diabetes Pindolol (Visken) Hypertension, angina, arrhythmias β, LA-action, ISA, angina commonly Timolol (Blocadren) Glaucoma, decrease secretion; (HT) β, no LA-action, no ISA, glaucoma commonly Metoprolol (Lopressor) Hypertension, angina, arrhythmias β1, LA-action, no ISA, arrhythmia commonly Atenolol (Tenormin) Hypertension, angina β1, no LA-action, no ISA Nadolol (Corgard) β, no LA-action, no ISA, long acting Esmolol (Brevablock) Arrhythmias, [angina] β1, no LA-action, no ISA, very short acting Labetalol (Normadyne) Hypertensive crisis, hypertension, CHF β / α, some β-agonist action Miscellaneous Adrenergic Agents SSRI = Selective serotonin reuptake inhibitors α-methyl-p-tyrosine (Metyrosine) Pheochromocytoma (diffuse) inhibit tyrosine hydroxylase (rate limiting step) α-methyl-m-tyrosine (Metaraminol) Hypotension, pressor agent converted to metaraminol (α-agonist) Cocaine (generic) Drug of abuse, local anaesthetic inhibit neuronal uptake, cross CNS; I: CA's, amph. Imipramine (tricyclic’s) (Janimine) Depression, inhibit neuronal uptake; at toxicS: dry mouth, blurred vision, decrease urination; T: Amitriptylline (Amitril, Elavil) doses can block muscarinic, alpha, and severe anticholinergic effect, respiratory depression, histamine receptors PHT (alpha-block) Chlorpromazine (Thorazine) Schizophrenia, surgery premedication inhibit extra- & neuronal uptake; sedation Pargyline, Phenelzine (MAOAB) Depression: non-selective, accumulation of All MAO inhibitors have important interaction with → Tranylcypromine (Parnate) NE, TCAs or SSRIs preferred tyramine HT crisis, S: agitation, tremor, insomnia, Clorgiline (MAOA) Depression found in nerve terminals, liver, kidney, CNS Selegiline (MAOB) (Deprenyl) Parkinson’s Disease found in platelets, liver, kidney, CNS Pharmacology of the Autonomic Nervous System Reserpine (Sandril, Serpasil) Hypertension depletion of NE; S: depression Guanethidine (Ismelin) Hypertension, arrhythmias Inhibit NE release, initial transient HT; I: TCA's Bretylium (Bretylol) Arrhythmias, surgery premedication decrease effectiveness; S: PHT Cholinoceptor Agonists AchE = Acetylcholinesterase Acetylcholine (Miochol) No major use, minor ocular procedures for M / N, short acting (AchE); T/S: All M-agonists: brief miosis; muscarine found in certain salivation, lacrimation, urination, diarrhea, emesis, mushrooms (slude), miosis, bronchoconstriction, ↓HR Bethanechol (Urecholine) Atonic gut, urinary retention M, resistant to AchE Pilocarpine (Oscusert-Pilo) Open angle glaucoma M, resistant to AchE; alkaloid, increase outflow Carbachol (Carbacel) Glaucoma, if pilocarpine ineffective M / some N, resistant to AchE Methacholine (Provocholine) Ocular procedures M, resistant to AchE Indirect Cholinoceptor Agents Edrophonium (Tensilon) Diagnostic for myasthenia gravis competitive, short-acting (5-10min) Physostigmine (Eserine) Reverse atropine toxicity; glaucoma reversible, CNS action Neostigmine (Prostigmin) Myasthenia gravis, reverse nmj block reversible, no CNS, some direct agonist action Ambenonium (Mytelase) Myasthenia gravis AchE inhibitors occupy AchE and prevent Ach Pyridostigmine (Mestinon) degradation, T/S: same as for high Ach Demecarium (Humorsol) Glaucoma DFP (Isoflurophate) Organophosphate Organophosphates, irreversible inhibition of AchE. Echothiophate (Phospholine) Can use 2-PAM before ‘aging’ to regenerate enzyme, T: same as for high Ach, death due to sarin, soman (nerve gases) Military (classified) respiratory paralysis Malathion, (Chemathion) Insecticides Parathion (Folidol) Cholinoceptor Antagonists Atropine (Isopto-Atropine) Reverse AChE inhibition; GI-disorders, ↓GI activity, ↓secretions, relax lung, mydriasis (pupil Homatropine (generic) ocular (iritis), vagolysis dilation), cyclopegia (loss of accommodation), competitive M-antagonists, pirenzepine (M1- Ipratropium (Atrovent) Asthma – bronchodilator selective); T: mad as a hatter (unresponsive), red as Pirenzepine Peptic ulcer a beet (erythematous), blind as a bat (cycloplegia), dry as a bone (secretions), hot as hell Benztropine (Cogentin) Parkinson's disease, esp. drug induced (thermoregulation); Reverse toxic effects with AchE Scopolamine (Isopto-Hyoscine) Motion sickness, diarrhea, ↓secretions inhibitors eg. physostigmine or neostigmine Propantheline (Probanthine) GI-disorders ie. mild diarrhea, [peptic ulcer] Glycopyrolate, Dicyclomine Cyclopentolate (Cyclogyl) Ocular examination Miscellaneous Cholinergic Agents Hemicholinium None inhibit choline uptake (rate limiting step) Botulinus toxin Treat facial muscle spasms, strabismus prevent release of Ach Pralidoxime, (2-PAM) (Protopam) Regenerate AchE need to use before ‘aging’ occurs Ganglionic Agents Nicotine, Lobeline (Cigarettes) Insecticide, cigarettes N-agonist, (blocker) T: convulsions, vomiting, CV Mecamylamine (Inversine) ↓ BP during surgery, Nn-antagonists Nn-antagonist, active orally; S: PHT, mydriasis Trimethapan (Arfonad) (competitive) Nn-antagonist, not oral; S: PHT, mydriasis Neuromuscular Junction Agents Succinylcholine (Anectine) NMJ paralysis, depolarizing block short acting due to plasma AchE; fasciculations Tubocurarine (generic) NMJ paralysis, competitive blockers, Nm, some histamine release & ganglia block Gallamine (Flaxedil) Small/fast nerves first (face, hands), then Nm, some M-receptor block trunk, respiratory muscles last. Flaccid Mivacurium (Mivacron) paralysis. Can reverse block with AchE short acting 10-20 min, slight histamine release Pancuronium, Vecuronium inhibitors Atracurium & Mivacurium hydrolysed by AchE, other Metocurine, Atracurium competitive agents eliminated:kidney, liver Dantrolene (Dantrium) Malignant hyperthermia, cerebral palsy Inhibit calcium release from SR Diuretics - Acetazolamide, Methazolmide Glaucoma Oral, ↓ secretion due to lack of HCO3 - Dorzollamide, Brinzolamide Topical, ↓ secretion due to lack of HCO3 .
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