Pharm autonomic drugs Flashcards
Number of neurons in sequence in the sympathetic versus parasymp versus somatic nervous systems
For sympathetic, it is two neurons in sequence (Ach, then norepi). For parasymp, it is two neurons in seq (Ach, then Ach), and somatic is a single neuron (Ach) to skeletal muscle
How is sympathetic to the sweat glands and sympathetic to the renal vasculature different from normal sympathetic innervation?
With normal, it is Ach then norepi; with sweat glands, it is Ach then Ach; for renal it is Ach then Dopamine receptor
Ach receptors
Nicotinic Ach receptors are the first ones; muscarinic Ach receptors are the second ones
Nicotinic Ach receptors
ligand-gated Na+/K+ channels
Muscarinic Ach receptors
G-protein coupled receptors that usually act through second messengers; 5 subtypes are M1, M2, M3, M4, and M5
alpha 1 receptors
G protein class q; increase vascular smooth muscle contraction, increase pupillary dilator muscle contraction, increase intestinal and bladder sphincter muscle contraction
alpha 2 receptors
G protein class I; decreased sympathetic outflow, decrease insulin release, decrease lipolysis, increase platelet aggregation, decrease acqueous humor production
beta 1 receptors
G protein class s; increase HR, increase contractiliy, increae renin release, increase lipolysis
beta 2 receptor
G protein class s; vasodilation, bronchodilation, increase lipolysis, increase insulin release, decreaes uterine tone (tocolysis), ciliary muscle relaxation, increase acqueous humor production
M1 parasymp receptor
G protein class q; CNS, enteric NS
M2 parasymp receptor
G protein class I; decrease HR and contractility of atria
M3 parasymp receptor
G protein class q; increase exocrine gland secretions, increase gut peristalsis, increase bladder contraction, bronchoconstriction, increase pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accomodation)
D1 dopamine receptor
G protein class s; relaxes renal vascular smooth muscle
D2 dopamine receptor
G protein class I; modulates transmitter release, esp in brain
H1 histamine receptor
G protein class q; increase nasal and bronchial mucus production, increase vascular permeability, contraction of bronchioles, pruritis, pain
H2 histamine receptors
G protein class s; increase gastric acid secretion
Vasopressin V1
G protein class q; increase vascular smooth muscle contraction
Vasopressin V2
G protein class s; increase water permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)
Way to remember the G protein class
Qiss and qiq until you’re siq of sqs
How is Gq involved in the receptor pway?
Receptor activates Gq, which turns on phospholipase C, which leads to conversion of PIP2 into DAG and IP3; IP3 leads to increase in calcium into the cell and contraction of the smooth muscle; DAG activates protein kinase C
How are Gs and Gi involved in the receptor pway?
Gs turns on adenylate cyclase, whereas Gi inhib adenylyl cyclase; adenylyl cyclase converts ATP into cAMP, which activates protein kinase A, which increases calcium in the heart and inhibits myosin LCK in smooth muscle cells
How do cholinergic neurons work?
The choline needs to get into the cell, get aceylated by Acetyl-co-A, which turns it into Ach, which gets packaged into the vesicle; Then when calcium gets into the cell, the vesicle can be released; Achesterase chomps up the Ach back into choline and acetate and the cycle continues
Hemicholinum
inhibits the choline from getting into the neuron so that it cannot be made into Ach
Vesamicol
inhibits the Ach from being taken up into the vesicle in the cell
Botulinum
inhibits the release of the vesicle into the nerve terminal
How do noradrenergic neurons work?
Tyrosine gets taken up into the cell, then converted to DOPA, which is converted to dopamine; dopamine gets into the vesicle, where it is converted to norepi; the norepi is released when release-modulating receptors on the surface of the cell (ATII,pro, and alpha 2, inhib) signal it to be released by the intake of calcium into the cell
metyrosine
inhibits convesion of tyrosine into DOPA
Reserpine
inhibits the uptake of dopamine into the vesicle
Bretylium, guanethidine
inhibits release of vesicle into the post-synaptic area
Cocaine, TCAs, amphetamine
inhibit the reuptake of norepi in the presynaptic neuron
AT II receptor on the surface of the neuron
signals that the norepi vesicle should be released into the synapstic space
alpha 2 recepotr
norepi acting on the alpha 2 receptor inhibits the release of the norepi into the synapse (negative feedback)
Bethanecol
cholinomimetic direct agonist; used for post-op ileus, neurogenic ileus, urinary retention; activates bowel and bladder smooth muscle; resistant to Achesterase
Carbachol
cholimimetic direct agonist; constricts pupil and relieves intraocular pressure in glaucoma; this is just like acetycholine
Methacholine
cholimimetic direct agonist; used for challenge test for diagnosis of asthma; stimulates muscarinnic receptors in the airway when inhaled
Pilocarpine
cholimimetic direct agonist; potent stumulator fo sweat, tears, and saliva; open angle and closed angle glaucoma; contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed angle glaucoma), resistant to AChE
donepezil, galantamine, rivastigmine
acetylcholinesterase inhib; used for alzheimer’s disease
edrophonium
increase Ach; ued for dx of myasthenia gravis in the past; now MG is dx by anti-AChR Ab test
neostigmine
increases Ach; postop and neurogenic ileus and urinary retention, MG, reversal f NMJ blockade post-op; no CNS penetration; Neo=no
physostigmine
used to treat anticholinergic toxicity, crosses BBB; “phyxes” atropine overdose
pyridostigmine
used to treate MG (long acting); does not penetrate CNS
what to be careful with the cholinergic agents
Exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients
cholinesterase inhib poisoning
results in too much Ach; often due to organophosphates, such as parathion that irreversibly inhibit AChE; causes DUMBBELSS diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating, and salivation
antidote for organophosphate poisoning
atropine (competitive inhib) with pralidoxime (regenerates AChEsterase if given early)
atropine, homatropine, tropicamide
muscarinic antags that produce mydriasis and cycloplegia (i.e. affect the eye)
benztropine
muscarinic antag that is used to treat parkinsons disease and acute dystonia
glycopyrrolate
muscarinic antag that is used IV often pre-op to reduce airway secretions
hyoscyamine, dicyclomine
muscarinic antag used as antispasmodic for IBS
ipratropriu, tiotroprium
muscarinic antag used for COPD and asthma
oxybutinin, solifenacin, tolterodine
muscarinic antag used to reduce bladder spasms and urge incontinence (overactive bladder)
scopolamine
muscarinic antag used for motion sickness
atropine
used to treat bradycardia and for opthalmic applications
atropine’s effect on eye, airway, stomach, gut, bladder
increae pupil dilaton, cycloplegia, decrease airway secretions, decrease stomach acid, decrease motility in the gut, decrease urgency in cystitis
Toxicity of atropine
increase body temp (due to decrease sweating), rapid pulse, dry mouth, dry, flushed skin, cycloplegia, constipation, disorientation; can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia and hyperthermia in infants
tetrodotoxin
Muscarinic antag; highly potent toxin that binds fast voltage gated Na channels in cardac and nerve tissue, preventing depol; causes nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes, treatment is supportive; poisoning can result from poorly prepared puffer fish (Japan)
Ciguatoxin
muscarinic antag; causes ciguatera fish poisoning; opens Na channels causing depol. Sx are like cholinergic poisoning: temp dyasthesia (cold feels hot and vice versa) is a spec finding; treatment is supportive
scombroid poisoning
muscarinc antag; acute onset burning sensation in the mouth, flushing of face, erythema, urticaria, pruritis, HA. May cause anaphylaxis-like presentation; treat supportively with antihistamines or anti-anaphylactics; caused by eating dark meat fish improperly stored at room temp
albuterol, salmeterol
B2 greater than B1 agonist; used for asthma or COPD control
dobutamine
B1 greater than B2 and alpha; used in HF as an ionotrope more often then a chronotrope and in cardiac stress testing
dopamine
D1 and D2, greater than beta, greater than alpha; used for unstable bradycardia, HF, shock; ionotropic and chronotropic alpha (?) effects predominate at high doses
epinephrine
beta greater than alpha; used to treat anaphylaxis, asthma, open angle glaucoma; alpha effects predominate at high doses. Significantly stonger effect at beta 2 recepotr than norepi
isopreterenol
b1 and b2; used for the electrophysiologic eval of tachyarrhythmias. Can worsen ischemia
norepi
alpha 1 greater than alpha 2 greater than beta 1; used to treat hypotension (but decreases renal perfusion); signif weaker effect at beta 2 receptor than epi
phenylephrine
alpha 1 greater than alpha 2; used to treat hypotension, used for ocular procedure (bc it is mydriatic), used to treat rhinitis
amphetamine
indirect general sympathetic agonist bc it is a reuptake inhib, aso releases stored catecholamines; used to treat narcolepsy, obesity, ADHD
cocaine
inidrect general sympathetic agonist; reuptake inhib; causes vasoconstriction and local anesthesia; never give beta blockers if cocaine intox is suspected because it can lead to unopposed alpha 1 activation and extreme HTN
ephedrine
indirect general sympathetic agonist; releases stored catecholamines; used for nasal congestion, urinary incont, hypotension
norepi versus isopreteronol
norepi increases systolic and diastolic pressures as a result of alpha 1 mediated vasoconstriction leading to incr mean arterial presure leading to relex bradycardia; isoproterenol has little allpha effect but causes b2 mediated vasodilation, resulting in decreased MAP and increased HR through B1 and reflex activity
clonidine
alpha 2 agonist; used to hypertensive urgency, does nor decreae renal blood flow; also used for ADHD and Tourette’s; toxicity is CNS depression, bradycardia, hypotension, resp depression, miosis
alpha methyldopa
alpha 2 agonist; used for HTN in pregnancy; toxicity has direct Coomb’s pos hemolysis, SLE-like syndrome
phenoxybenzamine
irreversible nonselective alpha blockers; used to treat pheochromocytoma preop to prevent catecholamine crisis; can cause orthostatic hypotension, and reflex tachycardia
Phentolamine
reversible non-selective alpha blocker used for patients on MAOis who eat tyramine containing foods; can, again, cause orthostatic hypotension, relfex tachycardia
Prazosin, terazosin, doxazosin, tamsulosin
selective alpha 1 blocker; used for urinary sx of BPH, PTSD (prazosin), hypertension (except tamsulosin); side effects are orthostatic hypotension, dizziness, HA
mirtazapine
selective alpha 2 blocker; used to treat depression; side effects are sedation, increased serum cholesterol, increase appetiite
Effect of beta blockers (what are they used for clinically?)
used for angina to decrease HR and contractility, resulting in decreased oxygen consumption; used in SVT to decrease AV condution velocity (class II antiarrhythmics), HTN (decrease CO, decrease renin secretion), glaucoma (decr secretion of acqueous humor)
toxicity of beta blockers
impotence, CV adverse effects (bradycardia, AV bock, HF), CNS adverse efffects (seizures, sedation, sleep alterations), dyslipidemia (metop), and asthma/COPD exacerbations
Beta 1 selective antags
Acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol; mostly A-M (first half of alphabet)
Nonselective beta antags
nadolol, pindolol, propranolol, timolol; mostly go from N to Z
Nonselective alpha and beta antags
carvedilol, labetolol; “olol”
