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86 Cards in this Set

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M2 receptor
G-protein target:
effect (s):
results:
G-protein target:1.adenylyl cyclase 2. GIRK-aK+ channel subtype
effect (s):1.inhibition- decreased cyclic AMP. 2. activation of GIRK
results:1.deacreased Ca2+ influx. 2.increased K+ outflow. Combined 1 and 2 effects result in decreased heart rate, conduction, and contractility
M3 receptor
G-protein target:
effect (s):
results:
G-protein target:phospholipase C
effect (s):Activation
results: 1.increased IP3 and increased Ca2+ influx= smooth muscle contraction 2. endothelial cells- increased production of NO= vascular smooth muscle relaxation
alpha1 receptor
G-protein target:
effect (s):
results:
G-protein target:phospholipase C
effect (s):activation
results:Increased IP3 and increased Ca2+ influx = smooth muscle contraction
alpha2 presynaptic receptor
G-protein target:
effect (s):
results:
G-protein target:voltage-gated Ca2+ channel
effect (s):inhibition- decreased Ca2+ influx into nerve terminals
results:decreased neurotransmitter release
alpha2-postsynaptic receptor
G-protein target:
effect (s):
results:
G-protein target:phospholipase C
effect (s):activation
results:increased IP3 and increased Ca2+ influx = smooth muscle contraction
beta1 receptor
G-protein target:
effect (s):
results:
G-protein target:adenylyl cyclase
effect (s):Activation, increased cyclic AMP
results:increased Ca2+ influx = increased heart rate, conduction, and contractility
beta2 receptor
G-protein target:
effect (s):
results:
G-protein target:adenylyl cyclase
effect (s):activation, increased cyclic AMP
results:inhibits myosin light chain kinase in certain cell types = smooth muscle relaxation
cholinergic agonsists:
(parasympathomimetics)- mimic the effects of ACH at muscarinic receptors
Are cholinergic agonsits specific for any receptor subtype?
No
Bethanechol (urecholine)
type:
target(s):
effect(s):
adverse effects:
Clinical Use:
type:cholinergic agonist direct acting choline ester
target(s):Post-synaptic muscarinic receptors
effect(s):chlinergic agonsit
Clinical Use:Used primarily in small animals to increase bladder contraction (M3)
adverse effects:increased GI motility, abdominal discomfort, diarrhea. don't use in patients with suspected GI or urinary tract obstruction
pilocarpine (piloptic)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):Muscarinic receptors (M3 eye)
Mechanisms of action:cholinergic agonist
Clinical use:open angle glaucoma. used in conjunction with hyperosmotic agents, carbonic anhydrase inhibitors and beta blockers. (eye ointment or drops)
Adverse effects:minimal, may be contraindicated in closed-angle glaucoma
are cholinergic antagonsists specific for any receptor subtype?
no
atropine
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):muscarinic recptors (M2 in the sinus node)
Mechanisms of action:cholinergic antagonist
Clinical use:used primarily to increase heart rate, either as an adjunct to anesthesia or in cardiovascular emergencies. also used to decrease respiratory and GI secretion, and as an antidote for organophosphate poisoning. used topically in the eye for long term pupil dilation
Adverse effects:tachycrdia, ileus (especially in large animals) urine retention. CNS stimulatory effects at high doses (restlessness, delirium) Do not use in patients with pre-existing tachycardia, intestinal ileus, or glaucoma
glycopyrrolate (robinul-V)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):muscarinic (M2 in the sinus node)
Mechanisms of action:cholinergic antagonist
Clinical use:used primarily to increase heart rate, typically as an adjunct to anesthesia (it is longer acting than atropine) also used to decrease respiratory and GI secretion
Adverse effects:tachycardia, ileus, urine retention. No CNS effects since it doesn't cross the blood brain barrier. do not use in patients with pre-existing tachycardia, intestinal ileus, or glaucoma
propantheline (pro-banthine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):muscarinic (M3 bladder)
Mechanisms of action:cholinergic antagonist
Clinical use:antidiarrheal in small animals, used to decrease smooth muscle contraction and GI secretions. also used to treat vagally mediated bradycardia and heart block. drug of choice for oral therapy when an anicholinergic is indicated
Adverse effects:tachycardia, ileus, urine retention, behavior changes. do not use in patients with pre existing tachycardia, intestinal ileus, or glaucoma
tropicamide
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):muscarinic (M3 eye)
Mechanisms of action:cholinergic antoagonist
Clinical use:produce mydriasis (necessary for thorough examination of the retina) and cycloplegia (paralysis of the ciliary muscle for treatment of iridocyclitis)
Adverse effects:do not use in patients with pre existing glaucoma
ipratropium (atrovent)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):muscarinic
Mechanisms of action:cholinergic antagonist
Clinical use:used primarily in horses as a bronchodilator (treatment of recurrent airway obstruction HEAVES) given as an inhalant in aersol form
Adverse effects:minimal when administered by aerosal/ not effective in acute bronchospasm
are adrenergic agonists specific for any receptor subtype?
yes, sort of drugs have distinct binding profiles for adrenergic receptor subtypes
epinephrine/adrenaline
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s): a1,a2,b1,b2
Mechanisms of action:potent alpha and beta adrenergic agonist
Clinical use:used in emergency situations such as cardiac arrest and anaphylactic shock
Adverse effects:vasoconstriction, hypertension, very arryhthmogenic. used primarily for emergencies because dose is difficult to titrate
Norepinephrine (levophed)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1,a1,a2 some b2
Mechanisms of action:potent b1,a1,a2 agonist, little effect on b2 receptors
Clinical use:used as a vasoconstrictor in specific clinical circumstances-pheochromocytectomy, spinal anesthesia, septicemia
Adverse effects:very potent vasoconstrictor, increased total peripheral resistance, reduced blood flow to kidneys, liver, and skeletal muscle- do not administer to hypovolemic patients
dopamine (intropin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):dopamine, a1, b1
Mechanisms of action:adrenergic agonist. dose-dependent effects on dopamine receptors, and a1 and b1 adrenergic receptors
Clinical use:used primarily as a positive inotropic agent (5ug/kg/min);used at lower doses (1ug/kg/min) to improve renal perfusion; used at higher doses (10ug/kg/min) for both ionotropic and vasoconstrictive effects
Adverse effects:tachycardia and arrhythmias at high doses- must be administered very carefully as a constant rate infusion; short term therapy
inotropic
Affecting the force or energy of muscular contractions
dobutamine (dobutrex)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1
Mechanisms of action:adrenergic agonist primarily on b1
Clinical use:often the drug of choice (especially in horses) to manage cardiac contractility in low coontractility states (anesthesia, heart failure, post-cardiac arrest)
Adverse effects:tachycardia and arrhythmias at high doses - must be administered very carefully as a constant rate infusion; short term therapy
phenylephrine (neo-synephrine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a1
Mechanisms of action:a1 adrenergic receptor agonist
Clinical use:used in critical care situations often as a last ditch effort to increase; also used topically to reduce nasal edema in the horse (in recovery)
Adverse effects:excessive vasoconstriction resulting in compensatory bradycardia- do not use in patients with cardiovascular disease
ephedrine (ephedra)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):non selective alpha and b1
Mechanisms of action:non selective alpha and b1 adrenergic agonist
Clinical use:used primarily to manage cardiac contractility in low contractility states and as a vasopressor; can be given as a single injection rather than a constant rate infusion
Adverse effects:tachycardia and hypertension- no do use in patients with cardiovascular disease
terbutaline (brethine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b2
Mechanisms of action:b2 adrenergic agonist
Clinical use:bronchial smooth muscle relaxant;used to treat bronchoconstriction (cats with bronchial asthma)
Adverse effects:tachycrdia and tremors at high doses- use with caution in animals with cardiac disease
Medetomidine (domitor)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a2
Mechanisms of action: a2 adrengeric agonist- recptors located presynaptically block release of neurotransmitter; receptors located postsynaptically cause vasoconstriction
Clinical use:very potent, reversible, sedative-analgesic agent; used widely in veterinary medicine
Adverse effects: profound compensatory bradycardia- use only in normal, healthy dogs; avoid concurrent use of anticholinergic drugs; causes vomiting in cats
are adrenergic antagonists specific for any receptor subtype?
yes, sort of. drugs have distinct binding profiles for adrenergic receptor subtypes
phentolamine (regitine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a1 and a2
Mechanisms of action:alpha adrenergic antagonist. block alpha receptors on vascular smooth muscle
Clinical use:vasodilator used to treat acute hypertension
Adverse effects:excess hypotension with alarming compensatory tachycardia; stimulatory GI effects (abdominal pain)-used in short term to mange pheochromocytoma patients; do not use in dehydrated animals or in those with poor perfusion (decreased cardiac output)
pheochromocytoma
small chromaffin cell tumor, usually located in the adrenal medulla but occasionally occuring in chromaffin tissue of the sympathetic paraganglia. Occurs most often in dogs and cattle; in bulls it developes concurrently with c-cell tumors of the thyriod gland. functional tumors secrete catecholamines, causing arteriolar sclerosis and medial hyperplasia and clinical signs of hypertension; tachycardia, edema and cardiac hypertrophy
phenoxybenzamine (dibenzyline)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a1
Mechanisms of action:somewhat selective a1 adrenergic receptor antagonist (block is irreversible; recovery requires synthesis of new receptors)
Clinical use:vasodilator used to treat hypertension. used routinely for 10-14 days prior to sx in patients with pheochromocytoma(works well in cats prior to adrenalectomy). also used for urethral relaxation
Adverse effects:postural hypotension and compensatory tachycardia
atipamezole (antisedan)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a2
Mechanisms of action:highly selective a2 antagonist
Clinical use:medetomidine reversal agent
Adverse effects:may cause transient hypotension especially when given rapidly IV (recommend giving IM)
propranolol (inderal)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1 and b2
Mechanisms of action:beta adrenergic receptor antagonist
Clinical use:used to treat tachycardia and other arrhythmias (class II antiarrhythmic agent)
Adverse effects:bradycardia, decreased cardiac output, hypotension, bronchoconstriction-contraindicated in patients with respiratory problems
timolol
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1 and b2
Mechanisms of action:beta adrenergic antagonist
Clinical use:opthalmic formulations used to in treatment of glaucoma(used widely in people, used in veterinary patients, but effectivness has yet to be established
Adverse effects:even eye drops capable of causing bradycardia, decreased cardiac output, hypotension, bronchoconstriction
atenolol (tenormin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1
Mechanisms of action:highly selective b1 adrenergic receptor antagonist
Clinical use:currently the drug of choice for decreasing heart rate and contractility in cats with hypertrophic cardiomyopathy
Adverse effects:bradycardia, decreased cardiac output. though highly selective, it still may cause bronchospasm in susceptible patients- may cause severe hypotension in patients with myocardial failure (decreased contractility)
esmolol (breviblock)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):b1
Mechanisms of action:highly selective b1 receptor antagonist
Clinical use:very short acting. drug of choice for critical care situations such as sudden intraoperative hypertension
Adverse effects:similar to other beta blockers, but half-life is only 8 min.
succinylocholine (anectine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):nACH
Mechanisms of action:nACH receptor agonist; depolarizing neuromuscular blocker
Clinical use:used primarily for rapid sequence enodtracheal intubation (has the fastest onset of all neuromuscualar blockers)
Adverse effects:may cause histamine release, hyperkalemia, may trigger malignant hypertermia in susceptible species (especially if anesthetized with halothane) will increase intraocular and intracranial pressure, therefore avoid in patients with penetrating eye injuries, glaucoma, intracranial tumors
atracurium (tracurium)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):nACH
Mechanisms of action:nACH antagonist;non-depolarizing neuromuscular blocker
Clinical use:one of the most widely used NMB's in veterinary medicine; used routinely for ophthamological surgery in the dog where relaxtion of the extrinsic muscles of the eyeball is required (cataract removal)
Adverse effects:histamine release only at high doses-very safe drug except for rare cases of anaphylaxis; doesn't require liver or renal function for termination of effect; intermediate duration of action generally dosen't require reversal; monitor wit nerve stimulator
pancuronium (pavulon)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):nACH
Mechanisms of action:nACH recpetor antagonist; nondepolarzing neuromuscular blocker
Clinical use:long procedures requiring nueromuscular blockade
Adverse effects:vagolytic properties, may cause mild tachycardia and increased blood pressure- one of the oldest neuromuscular blockers, still preferred by many ophthalmologists; primary route of elimination is kidney ( a factor to consider in patients with renal disease)
physostigmine (antilirium)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):binds Acetylcholinesterase
Mechanisms of action:reversible carbamate inhibitors cholinesterase inhibitor
Clinical use:primarily used for treatment of anticholinergic intoxication
Adverse effects:crosses the blood brain barrier, associated with more side effects than other ACHE inhibitors
neostigmine (prostigmin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):):binds Acetylcholinesterase

Mechanisms of action:reversible carbamate inhibitors cholinesterase inhibitor
Clinical use:treatment of myasthenia gravis. Neuromuscular muscle blocker reversal. treatment of ileus, urinary retention.
Adverse effects:widely used, fewer side effects than physotigmine. onset of action is 7-10min
edrophonium (tensilon)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):binds Acetylcholinesterase

Mechanisms of action:reversible carbamate inhibitors cholinesterase inhibitor

Clinical use:test for myasthenia gravis (ie patients show a rapid but short lived improvement) neuromuscular muscular blocker reversal. treatment of ileus, urinary retention
Adverse effects:least potent, fewer side effects. rapid onset of action 1-2min
gusifensin (glyceryl guaiacolate = GG)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):not clear
Mechanisms of action:centrally acting muscle relaxant; disrupts impulse transmission in connecting (internuncial) neurons of the spinal cord (not a NMB)
Clinical use:anesthetic induction agent for horses and cows when combined with either thiopental or ketamine; provides muscle relaxation without respiratory paralysis
Adverse effects:cardiovacular and repiratory effects are minimal at recommended dosages, however lethal dose is 3 times clinical dose. administered as a 5% solution, higher concentration may cause hemolysis
digoxin (lanoxin, cardoxin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):Na+/K+ ATPase
Mechanisms of action:inibits Na+/K ATPase results in an indirect effect on Na+/Ca2+ exchanger- increases Ca2+ in the cell
Clinical use:postive inotropic agent
1.systolic dysfunction/congestive heart failure- esp dilated cardiomopathy and latter stages of valvular disease. The benefits are: a)decreased heart rate b) increased contractility without increasing myocardial O2 consumption c) improved cardiac output
2.superventricular tachyarrythmias (SVT) i.e. atrial fibrillation (especially when associated with congestive heart failure. by slowing AV conduction, digoxin decreases the ventricular rate response to the fibrillating atria. Some SVT are associated with re-enrty pathways that involve the AV node; by slowing conduction and increaseing the refractoriness of the AV node, digoxin may interrupt the re-entrant pathway and abolish the arrhythmia
Adverse effects:very low saftey margin. theraprutic plasma concentration .9-3.0ng/ml toxicities begins above 3.5ng/ml. not fat soluble- be sure to calculate dose based on lean body weight
milrinone (primacore)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):cyclic AMP phosphodiesterase
Mechanisms of action:cyclic AMP phosphodiesterase inhibitor- increase Ca2+
Clinical use:short term support of the circulation in advanced heart failure. termed an inodilator- causes vasodilation and decreased in systemic vascular resistance; also increases contractility
Adverse effects:arrhythmias, hypotension, GI effects (nausea vomiting), hepatotoxicity, thromocytopenia, has greater selectivity for PDE, shorter half-life, and fewer side effects when compared to amrinone
pimobendan (vetmedin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):troponin C
Mechanisms of action: Calcium sensitizing inodilator: 1.stabilzes troponin C in the conformation that triggers and maintains contraction in the presence of Ca2+ 2. phosphodiesterase inhibitor at concentrations above therapeutic levels
Clinical use:available in europe- congestive heart failure, valvular insufficentce
Adverse effects:
hydralazine (apresoline)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):unknown
Mechanisms of action:causes direct relaxation of arteriolar smooth muscle. mechansim unknown but appears to be independent of endothelium and is not related to guanylate cyclase activation (as is true for nitrates)
Clinical use:antihypertension- used to decrease aferload in the management of mitral regurgitation and congestive heart failure
Adverse effects:lethargy, weakness, and depression (signs of hypotension). reflex tachycardia. renal hypotension may cause an increase in BUN. acute severe hypotension is a common problem. It is often recommended that dosing start at 1/3 the calculated dose for 4-5 days, then 2/3 for 4-5 days, then full dose. may be given along with digoxin
amlodipine (norvasc)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):a vessel selective Ca2+ channel blocker
Mechanisms of action:3rd generation dihydropyridine class L-type voltage-gated Ca2+ channel blocker. decreases calcium influx in heart cells and vascular smooth muscle (arteries primarily)
Clinical use:used primarily to treat systemic hypertension but has been used as a vasodilator in treatment of congestive heart failure.
Adverse effects:hypotension and bradycardia- reduces afterload more gradually than hydralazine and, as a result, is less likely to increase heart rate
nitroglycerin (nitrostat)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):
Mechanisms of action:converted to NO in the endothelial cells lining blood vessels
Clinical use:used primarily in heart failure to reduce preload and to decrease pulmonary hypertension. (used to treat angina in people) venodilator therapy reduces preload by shifting blood form the central circulation (heart and lungs) into the peripheral circulation. this may also reduce preload, depending on severity of congestive heart failure. drugs are tricky and often resvered for acute care situations to relieve pulmonary edema
Adverse effects:hypotension
captopril (capoten)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):ACE
Mechanisms of action:sulfhydral containing ACE inibitor
Clinical use:direct acting, inhibit converstion of angiotension I to angiotensionII, treatment of hypertenison and congestive heart failure
Adverse effects:may cause azotemia in some cases, especially patients receiving high doses of diuretics; crosses the placenta and may cause fetal malformations
enalapril (vasotec)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):ACE
Mechanisms of action:dicarboxyl ACE inhibitor
Clinical use:inhibit converstion of angiotension I to angiotensionII, treatment of hypertenison and congestive heart failure

Adverse effects:may cause azotemia in some cases, especially patients receiving high doses of diuretics; crosses the placenta and may cause fetal malformations
lisinopril (prinivil, zestril)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):ACE
Mechanisms of action:dicarboxyl ACE inhibitor

Clinical use:inhibit converstion of angiotension I to angiotensionII, treatment of hypertenison and congestive heart failure
Adverse effects:may cause azotemia in some cases, especially patients receiving high doses of diuretics; crosses the placenta and may cause fetal malformations
mannitol (osmitrol)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):H2O
Mechanisms of action:osmotic diuretic, works in the proximal tubule. small molecular weight compound that is freely filtered at the glomerulus, not transported by renal tubules, and not metabolized to any extent by any organ. tends to retain fluid within vessels when given intravenously
Clinical use:oliguric renal failure, cerebral edema, acute glaucoma
Adverse effects:fluid overload if urine flow is not enhanced, intracranial hemorrhage
acetazolamide (diamox)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):Carbonic Anhydrase
Mechanisms of action:Carbonic Anhydrase Inhibitors Prevent reabsorption of HCO3- in proximal tubule
Clinical use:lower intraocular pressure in animals with glaucoma
Adverse effects:may cause hypokalemia(enhances effects of digoxin). do not use in patients with known sensitivity to sulfonamides
furosemide (lasix)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):cotransporter in loop of henle
Mechanisms of action:inhibits sodium and water transport in ascending loop of henle
Clinical use:acute oliguric renal failure, congestive heart failure, acute pulmonary hypertension. administer conservativelly in animals receiving ACE inhibitors to decrease risk of azotemia
Adverse effects: hypokalemia, dehydration. concurrent use with anitbiotics may potentiate toxicities
_______ diuretics have a paradoxical effect on urine flow rate in patients with diabetes insipidus
thiazide
spironolactone (aldactone)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):aldosterone recptors in distal tubule
Mechanisms of action:competitive antagonist of aldosterone. mechansim of action responsible for delayed onset of action and delayed loss of effect after discontinuation of diuretics. Max effect delayed up to 3-5 days
Clinical use:used for mild diuresis with reduced potential for potassium loss. Often used in combination with other diuretics (loop diuretics) to reduce potential for inappropriate loss of K
Adverse effects: hyperkalemia in some patients NSAIDS may inhibit action
two types of K sparing diuretics
1.aldosterone antagonists
2.Na+ transport blockers
amiloride (midamor)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):Na+ channel in luminal membrane of principal cells in collecting duct
Mechanisms of action:blocks Na+ channel
Clinical use:used for mild diuresis with reduced potentail for K loss. often used in combination with other diuretics (loop and thiazide diuretics) to reduce potential fot inappropriate K loss
Adverse effects: hyperkalemia in some patients- do not use alone due to its potential to cause hyperkalemia
quinidine (cardioquin)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):Class 1a antiarrhythmic
Mechanisms of action:Na channel blocking- decreased slope of phase 4 depolarization(decreased automaticity); increased firing threshold. K channel blocking effects-prolonged action potential duration. vagolytic effect may increase heart rate. might block Ca channel
Clinical use:treatment of ventricular arrhythmias (not as commonly as other antiarrhythmics) and occasionally to try to convert atrial fibrillation to normal sinus rhythm. is the drug of choice to treat atrail fibrillation in the horse
Adverse effects:side effects are very common. hypotension and tachycardia esp if given rapidly IV. GI effects such as nausea and vomiting. do not use in patients receiving digoxin- displaces digoxin form protein binding sites, increasing free digoxin concentrations
procainamide (pronestyl)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):class 1a antiarrhythmic
Mechanisms of action: Na channel blocking effects- decreased slope of phase 4 depolarization (decreased automaticity); increased firing threshold. K channel blocking effects- prolonged action potential duration.
Clinical use:treatment of ventricular arrhythmias. used very commonly in veterinary medicine
Adverse effects: fewer than quinidine- hypotension and tachycardia
lidocaine (xylocaine)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):class 1b antiarrhythmic
Mechanisms of action:Na channel blocking effects- lidocaine binds with higher affinity to inactivated Na channels. thus it binds preferably to abnormal tissue (ischemic, depolarized) its effects are thus different form quinidine and procainamide. it shortens the action potential and duration of refractoriness
Clinical use:treatment of ventricular arrhythmias. it is the most commonly used drug for treatment of acute ventricular arrhytmias. not effective against atrial arrhythmias.rapidly metabolized and therofore must be given in repeated doses every 20 min or as a constant rate infusion
Adverse effects: high doses cause CNS effects (tremors, twitches, seizures) and vomiting. cats are very sensitive to lidocaine. use lower dose
sotalol (betapace)
Receptor target (s):
Mechanisms of action:
Clinical use:
Adverse effects:
Receptor target (s):class II and III antiarrhythmic (has specific beta adrenergic blocking)
Mechanisms of action:beta blocking effects-decreased slope of phase 4 depolarization (decreased automaticity); increased AV conduction time; reduce ventricular rates. K channel blocking effect-blocks the fast component of the outward rectfier current, therefore prolongs action potential duration
Clinical use:treatment of chronic ventricular arrhythmias primarily, also used to prevent the recurrence of atrial fibrillation
Adverse effects:like all beta blockers, can cause worsening of congestive heart failure, lethargy and bradycardia. like other class III drugs, it is proarrhythmic at higher doses. hypokalemia may increase the possibility of generating the arrhythmia
torsade de pointes
a tachycardia that is associated with prolongation of the QT interval and can be acquired (high doses of sotalol)or congenital.
propranolol
class II antiarrhythmic. beta 1 and beta 2 blockade
amiodarone (cordarone)
receptor (s):
mechanism of action:
clinical use:
adverse effects:
receptor (s):class III antiarrhymic, and Na channel blocker, automonic effects
mechanism of action:classified as class III antiarrhythmic but also has Na channel blocking and autonomic effects
clinical use:reserved for treatment of life threatening ventricular arrhythmias when all else has failed
adverse effects:dose related effects include GI, pulmonary fibrosis(possibly related to release of free radicals in the lungs), hypo or hyperthyroidism ( drug is structurally similar to thyroxine) ocular opacities and hepatic failure. can be arrhythmogenic and may cause sudden death. has delayed and highly variable onset when given orally. it is very lipophilic and is highly protein bound
diltiazem (cardiazem)
receptor (s):
mechanism of action:
clinical use:
adverse effects:
receptor (s):class IV antiarrhythmic
mechanism of action:highly selective benzodiazepine L-type voltage gated Ca+2 channel blocker. primary effect is to slow sinus rate and decrease AV nodal conduction. also has negative inotropic and vasodilatory effect
clinical use:used primarily for control of supraventricular arrhythmias, systemic hypertenision, and hypertrophic cardiomyopathy in cats (to decrease contractility)
adverse effects:hypotension, myocardial depression, bradycardia, AV block. of the Ca channel blockers available it causes less cardiovascular depression
Parasympathetic stimulation causes:
Eye:
Glands:
Heart:
Blood Vessels:
Lungs:
Liver:
GI Tract:
Bladder:
Eye: Miosis
Glands: Salivation, Lacrimation
Heart: decreased heart rate
Blood Vessels:Dilation, decreased blood pressure
Lungs: Bronchoconstriction
Liver: Glycogen synthesis
GI Tract:Peristalsis
Bladder:Detrusor contraction
Sympathetic stimulation causes:
Eye:
Glands:
Heart:
Blood Vessels:
Lungs:
Liver:
GI Tract:
Bladder:
Eye: Mydriasis
Glands: Decreased secretion
Heart: Increased heart rate
Blood Vessels:Vasoconstriction, increased blood pressure
Lungs: Bronchodilation
Liver: Glycogenolysis
GI Tract: Decreased motility
Bladder:Sphincter contraction
Dual innervation with reciprocal effects
–Heart
___- Increased HR, Contractility, and Conduction
___- Decreased HR
–Vessels
___ – Constriction (peripheral)
___- Dilation (skeletal muscle)
___- Dilation (abdominal viscera)
Dual innervation with reciprocal effects
–Heart
b1 - Increased HR, Contractility, and Conduction
M2- Decreased HR
–Vessels
a1, a2 – Constriction (peripheral)
b2 - Dilation (skeletal muscle)
M3- Dilation (abdominal viscera)
Dual innervation with reciprocal effects
–Lung
___– Bronchial dilation
___- Bronchial constriction, Increased secretions
–Eye
___- Pupil dilation
___ - Pupil constriction
Dual innervation with reciprocal effects
–Lung
b2 – Bronchial dilation
M3- Bronchial constriction, Increased secretions
–Eye
a1- Pupil dilation
M3 - Pupil constriction
Dual innervation may allow for dual therapeutic approach
Increase heart rate
__ agonist
__ antagonist
Bronchodilation
__ agonist
__ antagonist
Dual innervation may allow for dual therapeutic approach
Increase heart rate
b1 agonist
M2 antagonist
Bronchodilation
b2 agonist
M3 antagonist
1. Synthesis of acetylcholine (ACH) from _______________
2. Storage of ACH in ______________
3. Release of ACH ___________
4. ACH binding to post-synaptic __________receptors
5. Inactivation of ACH by _____________ (breakdown to ___________________________)
1. Synthesis of acetylcholine (ACH) from acetyl CoA and choline
2. Storage of ACH in synaptic vesicles
3. Release of ACH vesicle fusion
4. ACH binding to post-synapatic muscarinic recptors
5. Inactivation of ACH by acetylcholinesterase (breakdown to acetate and choline; choline gets recycled)
1. Synthesis of norepinephrine (NE)
2. Storage of NE in _____________
3. Release of NE _________________
4. NE binding to post-synaptic ______________receptors generates agonist responses 5. NE binding to presynaptic ______ receptors inhibits further NE release.
6. Metabolism by ______________________________________
1. Synthesis of norepinephrine (NE)
2. Storage of NE in synaptic vesicles
3. Release of NE (vesicle fusion)
4. NE binding to post-synaptic receptors (a and b) generates agonist responses 5. NE binding to presynaptic a2 receptors inhibits further NE release.
6. Metabolism by monoamine oxidase (MAO) and catechol-O-methyltransferease (COMT)
1. Nerve action potential: pharmacology?
2. Vesicular acetylcholine (ACH) release (pre-synaptic):pharmacology?
3. ACH binding to post-synaptic nACH receptor (N2); increased Na+ permeability, depolarization:pharmacology?
4. Hydrolysis of acetylcholine by acetyl-cholinesterase (ACHE):pharmacology?
5. Muscle action potential and spread of excitation through muscle:pharmacology?
6. Release of Ca2+ from sarcoplasmic reticulum; muscle contraction:pharmacology?
1.Inhibited by Na+ channel blockers- tetrodotoxin, batrachotoxin, local anesthetics
2.Inhibited by botulinum toxin, 4-aminopyridine, Mg2+, hypocalcemia- MILK FEVER
3.Inhibited by curare alkaloids, depolarizing and non-depolarizing neuromuscular blockers
4.Inhibited by acetylcholinesterase inhibitors
5.Inhibited by Na+ channel blockers
6.Inhibited by dantrolene, hypocalcemia MILK FEVER
Neuromuscular Blockers Clinical Use
– Balanced anesthesia –Muscle relaxation for specific surgeries (cataract removal) and procedures (external electrical pacing) –Muscle relaxation for external pacing –IPPV – intermittent positive pressure ventilation –Rapid sequence induction/intubation (RSI)
The ideal neuromuscular blocker
– Ultra fast acting –No cardiovascular or respiratory side effects –Doesn’t require liver or kidney function for termination of effect –Rapidly reversible
Neuromuscular Blockers:
_____________ and ______________ are fastest acting
____________, ____________ and _________ cause histamine release
All but ______________ require some form of liver metabolism or renal excretion
All but __________________ are reversible
Neuromuscular Blockers
Succinylcholine and rocuronium are fastest acting
Succinylcholine, mivacurium and rocuronium cause histamine release
All but atracurium require some form of liver metabolism or renal excretion
All but succinylcholine are reversible
Cholinesterase inhibitors
Clinical Use
–atony of the smooth muscle of the intestinal tract and urinary bladder –glaucoma –myasthenia gravis (acetylcholine receptor deficiency) –reversing effects of neuromuscular blocking drugs.
Cholinesterase inhibitors
Side Effects
–Bradycardia –Increased GI motility, diarrhea –Increased secretion from salivary glands –Bronchoconstriction –Miosis
class 1a
drugs have moderate potency at blocking sodium channels and also usually prolong repolarization (increase width of QRS). Thus, they slow the rate of rise of phase 0 and prolong the effective refractory period
class 1b
drugs have the lowest potency as sodium channel blockers, produce little if any change in action potenial duration, and usually shorten repolarizaton
class 1c
drugs are the most potent sodium channel blocking agents, and have little effect on repolarization
class II
drugs act indirectly on electrophysiological parameters by blocking beta adrenergic receptors (increasing PR) They decrease the slope of phase 4, depress automaticity, and slow conduction through the AV node
class III
drugs act by mechanisms that are not well understood (interference with potassium conductance is one possible mechanism) but act to prolong repolarization (thus prolong the action potential and increase refractoriness), with little effect on the rate of depolarization.
class IV
drugs are relatively selective AV nodal calcium channel blockers, primarily L-type channels (increase PR)