Hopkins Pharmacology: Autonomic Pharmacology I And Ii

Front 1

neurotransmitter and receptor type of parasympathetic ganglionic receptors

Back 1

acetylcholine and nicotinic Ach receptor

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neurotransmitter and receptor type of parasympathetic target receptors

Back 2

muscarinic

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classical parasympathetic actions

Back 3

pupil: constriction
lungs: constriction of bronchial muscle
heart rate: decreased
GI: increased digestion - 1) sphincters relax, 2) segmentation and longitudinal muscles construct
bladder: contract (except sphincter)

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role and inhibitor of choline acetyltransferase

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convert AcCoa + choline to Ach, NVP inhibits

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Ach muscarinic receptor agonist

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pilocarpine

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promotes Ca-dependent release of Ach

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beta-bungarotoxin and black widow spider venom

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blocks Ca-dependent release of Ach

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botulism toxin (cleaves SNARE: SNAP-25)

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Ach muscarinic receptor antagonist

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atropine

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blocks acetylcholinesterase

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neostigmine, soman

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blocks choline uptake

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hemicholinium

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two types of acetylcholinesterase

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neuronal and serum

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Ach muscarinic receptors that interact with Gq/11 and stimulate phospholipase C and IP3

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M1, M3, M5

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Ach muscarinic receptors that interact with Gi and stimulate K channels and inhibit adenylyl cyclase

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M2, M4

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cardiac selective muscarinic Ach receptor

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M2

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Bethanecol (urecholine)

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-choline carbamate that is resistant to cholinesterases
-increased GI and ureteral peristalsis, increased GI secretion, decrease bladder capacity, relaxes external sphincter
-used in post-op gastroparesis orally or subcutaneously

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pilocarpine

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-generalized muscarinic activation: ocular-pupillary contriction, spasm of accommodation, fall in intraocular pressure, miosis lasting several hours
-used as aqueous ophthalmic solution for glaucoma

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metoclopramide (reglan)

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-increases gastric emptying and anti-emetic (via dopamine receptor antagonism)
-firstline gastroparesis, anti-emetic, given orally

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atropine

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-competitive antagonist at Ach muscarinic receptors
-effects: dry mouth, constipation, urinary retention, dry skin, flush, bronchodilation, mydriasis (pupil dilation), tachycardia, delirum -- mad as a hatter, red as a beat, dry as a bone

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scopolamine (l-hyoscine)

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oral or transdermal admin for motion sickness

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ipratropium bromide (atrovent)

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bronchodilator for asthma and COPD, use inhaler

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benztropine (cogentin)

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oral treatment for parkinson-like side effects of anti-psychotics

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oxybutynin (ditropan)

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increases bladder capacity and anti-spasmodic used for incontinence, oral admin

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dephenhydramine (benedryl)

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antihistamine with anticholinergic properties, used as sedative

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tricyclic antidepressants

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blocks norepinephrine and serotonin reuptake but also has anticholinergic side effects

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huperzine A

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reversible competitive Ach-esterase inhibitor used in treatment of Alzheimer's

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reversible covalent modifiers of Ach-esterase

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neostigmine, pyridiostigmine, physostygmine

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irreversible inhibitor of Ach-esterase

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sarin nerve gas

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signs of Ach-esterase poisoning

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bronchial spasm, salivation, lacrimation, defecation, urination, bradycardia, hypotension, muscle weakness, death in minutes-hours

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pralidoxime

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drug that reactivates irreversibly blocked Ach-esterase (must occur before enzyme "aging")

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sympathetic ganglion receptor type

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nicotinic Ach receptor

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sympathetic target receptor type

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adrenergic (sweat glands are cholinergic)

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classical sympathetic actions

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lungs: dilation of bronchi
liver: increase in glucose
heart: increase in rate and stroke volume
skeletal muscle: increase in blood flow
GI: decreased motility, increased sphincter tone

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synthesis pathway of norepinephrine from dopamine

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tyrosine -[tyrosine hydroxylase]-> DOPA -[aromatic amino acid decarboxylase]-> dopamine -[dopamine hydroxylase]-> norepinephrine

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pargyline

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blocks monoamine oxidase

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rate-limiting enzyme of norepinephrine synthesis

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tyrosine hydroxylase

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alpha-methyltyrosine

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blocks tyrosine hydroxylase
treatment for pheochromacytoma

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alpha-methyldopa

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blocks aromatic amino acid decarboxylase

Front 38

act as false neurotransmitters and replace NE in vesicles

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alpha-methylnorepinephrine, bretylium, guanethidine

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enzyme in adrenal glands that converts norepinephrine to epineprhine

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phenylethanolamine N-methyltransferase

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sympathomimetics that increase secretion of NE

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tyramine, amphetamine, ephedrine

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turnoff mechanism of muscarinic Ach receptor

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Ach-esterase activity

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turnoff mechanism of adrenergic receptor

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NE reuptake

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adrenergic receptor coupled to adenylate cyclase activity

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beta adrenergic receptor

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adrenergic receptor that inhibits adenylate cyclase, Ca channels and activates K channels

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alpha 2 adrenergic receptor

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adrenergic receptor with mixed effects

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alpha 1 adrenergic receptor

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dopamine receptor present in vascular bed

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D1

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dopamine receptors present in CNS

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D1-D5

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adrenergic receptor that may be bound by dopamine

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alpha

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types of adrenergic receptors

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alpha 1A, 1B, 1C
alpha 2A, 2B, 2C
beta 1, 2, 3

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alpha receptor agonists

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epinephrine, norepinephrine, phenylephrine, dopamine

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alpha receptor non-selective antagonists

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phenoxybenzamine, phentolamine

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phenylephrine

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alpha 1 agonist used to treat hypotension via vasoconstriction
used as spray for nasal decongestant

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prazosin

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alpha 1 antagonist blocks smooth muscle constriction to treat high blood pressure and enhance urine flow

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clonidine

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alpha 2 agonist decreases NE release and acts to reduce BP and for treating substance withdrawal

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yohimbine

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alpha 2 antagonist used for ED and as aphrodisiac but of controversial utility

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beta receptor agonists

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isoproterenol, epinephrine
stimulate cardiac output, dilates bronchial smooth muscle

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propranolol

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non-selective beta antagonist used to treat HBP, angina, anxiety, fainting, arryhthmias

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dobutamine

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beta 1 agonist increase cardiac rate and force of contraction
given by IV drip for cardiomyopathy
helps dilate coronaries and reduce afterload

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metoprolol

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beta 1 antagonist that reduces cardiac output
used for hypertension and angina

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albuterol

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beta 2 agonist
dilates bronchial smooth muscle and uterine smooth muscle, few cardiac side effects, used for asthma and to prevent premature labor
promotes glycogenolysis in the liver

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beta 2 antagonists

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none clinically useful

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beta 3 agonists

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no examples, but may help reduce adipose in obesity

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action, effect, and use of epineprine

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action: predominantly beta agonist
effect: increases cardiac output and systolic arterial blood pressure, increases 02 consumption and blood glucose
use: stop anaphylactic response

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action, effect, and use of norepineprine

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action: predominantly alpha agonist
effect: increase systolic and diastolic bp with less effect on cardiac output and metabolism
use: treat hypotensive shock but replaced by phenylephrine

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action and use of dopamine

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action: IV infusion that acts on D1 receptor
use: used in renal failure patients with low perfusion, higher doses act on alpha and beta receptors, often used as first pressor in shock