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211 Cards in this Set
- Front
- Back
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botulinum toxin mechanism
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blocks ACh release
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choline acetyltransferase action
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synthesizes ACh
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acetylcholinesterase
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breaksdown ACh
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rate-limiting step in NE synthesis
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Tyrosine hydroxylase (tyrosine to dopa)
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metyrosine action
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inhibits tyrosine hydroxylase
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uptake I
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norepinephrine transporter into neuron
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uptake II
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uptake by extraneuronal tissue
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Monoamine oxidase action
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makes catecholamine aldehydes
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Catechol-o-methyltransferase (COMT) action
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makes (nor)metanephrine
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physostigmine action
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inhibits cholinesterase
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carbidopa action
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dopa decarboxylase inhibition
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receptor type which stimulates adenylyl cyclase
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Beta 1,2
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Gi receptor types
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a2, M2
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receptor types stimulating PKC
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a1
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phenylephrine mechanism
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a1 agonist
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methoxamine mechanism
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a1 agonist
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mydriasis
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dilated pupil
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Phentolamine mechanism
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competitive a1 antagonist
**short half life |
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phentolamine uses
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dx pheochromocytoma
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pphenoxybenzamine mechanism
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noncompetitive a1 antagonist
*long acting |
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phenoxybenzamine use
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treat pheochromocytoma
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prazosin mechanism
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alpha1 antagonist
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prazosin use
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tx of hypertension and CHF
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prazosin risks
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syncope after first oral dose
reduced efficacy with chronic use |
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clonidine mechanism
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a2 agonist--> reduced symp outflow
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clonidine use
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tx of hypertension
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methyldopa mechanism
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metabolite a-methyl*norepinephrine* is a2 agonist
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methyldopa use
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tx of hypertension
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yohimbe mechanism
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alpha 2 antagonist
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Isoproterenol mechanism
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stimulates b1 and b2
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dobutamine mechanism
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b1 agonist
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uses of dobutamine
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tx of pulmonary edema, coronary bypass post op
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Propranolol mechanism
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competitive inhibitor of b1 and b2
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uses of propranolol
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tx of angina
ventricular arrhythmia htn *dec renin* post myocardial infarction |
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propranolol side efx
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worse heart failure
reduced AV conduction nightmares fatigue cold extremities |
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Metoprolol mechanism
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b1 blocker
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atenolol mechanism
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b1 blocker, does not cross blood brain barrier.slow
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atenolol uses
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htn (one a day)
glaucoma |
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bromocriptine mechanism
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dopanergic agonist
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tyramine mechanism
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displaces NE into synaptic cleft
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population vulnerable to tyramine related hypertension
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pts on monoamine oxidase inhibitors
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Phenylpropanolamine mechanism
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indirect sympathetic stim
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methacholine mechanism
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cholinergic
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bethanachol mechanism
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muscarinic agonist
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pilocarpine mechanism
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muscarinic agonist
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bethanachol uses
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improved gastric emptying
tx of urinary retension (if no physical obstruction) |
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pilocarpine uses
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induce salivation
open angle glaucoma--constricts iris sphincter (miosis) |
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methacholine use
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provoke bronchoconstriction for dx testing
(methacholine challenge) |
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atropine mechanism
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muscarinic antagonist
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atropine use
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raising heart rate when vagal activity is pronounced **vasovagal syncope
decreased respiratory secretions for intubation |
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Bezold-Jarisch reflex
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bradyardia, hypotension, nausea from high nicotine dose
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ganglionic blocking agents mechanism
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block Nn receptors
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insectiside mechanism
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anticholinesterase
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physostigmine mechansim
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"reversible" short acting cholinesterase inhibitor
enters CNS |
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neostigmine mechanism
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"reversible" short acting cholinesterase inhibitor
does not enter CNS |
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physostigmine side effects
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enters cns, restlessness, apprehension, hypertension
typical muscarinic/nicotinic efx |
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why neostigmine no enter cns?
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quaternary amine (charged)
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uses of neostigmine
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myasthenia gravis
glaucoma |
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propranolol "traditional" frequency of dosing
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4 times a day
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atenolol mechanism
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b1 selective blocker
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metroprolol mechanism
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b1 blocker
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metabolism of propranolol
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heavily liver metabolized
protein bound interindividual variability |
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atenolol metabilism
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reduced hepatic metabolization (vis a vis propranolol)
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metroprolol metabolism
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less hepaticlly metabolized (vis a vis propranolol)
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esmolol clinical use
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b blocker for critical care
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esmolol metabolism
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short half life, IV use only
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labetolol mechanism
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b blocker with a1 effect
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carvedilol clinical use
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CHF
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carvedilol mechanism
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beta blocker with a1 blocking
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type of b blocker for treatment of portal hypertensive bleeding
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non selective (propranolol in US)
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betablocker type for essential tremor
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non selective
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vascular headache prophylaxis betablocker type
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propranolol (non selective and more lipophilic)
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methyldopa side effects
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sedation, depression, dry mouth
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special situations in which methyldopa is particularly safe
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for htn in pts with ischemic heart disease (no efx on CO)
does not block baroreceper rflx --safe for anti-htn in elective surgery |
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dosing of methyldopa
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delayed onset of effect (needs to be metabolized to methyel-NE)
twice a day for maintanence |
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drug of choice for hypertensive pregnant pts
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methyldopa
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why clonidine is poor choice in pts with *severe* HTN?
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clonidine rebound. withdrawal syndrome w/ massive symp discharge
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pharmacokinetics of prazosin
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hepatic metabolism
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pharmacokinetics of terazosin and doxazosin
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longer lasting than prazosin
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labetolol R R stereoisomer mechanism
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b1 antagonist and partial b2 agonist
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labetalol SR stereoisomer mechanism
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a1 antagonist
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S isomer of Carvedilol
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b blocker (both isomers a1 blockers)
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The critical factor affecting the therapeutic utility of nitrates
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tolerance
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what is given along with nitroprusside?
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Na2S2O3 (Na thiosulfate)
the antidote to CN |
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pharmacokinetics of nitroprusside
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infusion only--dissolved immediately prior to use in glucose/water
rapid/potent/fast half life |
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nitroprusside clinical use
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acute hypertensive crisis
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mechanism of hydralazine
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who the fuck knows
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clinical utility of hydralazine
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hypertension--use with beta blocker and diuretic
heart failure |
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metabolism of hydralazine
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acetylated (pt variability)
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hydralazine side effects
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Na retention, coronary steal
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minoxidil mechanism
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sulfate metabolite opens atp sensitive k channel
--hyperpolarizes cell --arterial vasodilation |
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chemical class: nifedipine
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1,4 dihydropyridines
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chemical class: verapamil
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phenylalkamines
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chemical class: diltiazem
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benzothiazepines
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verapamil mechanism
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L type calcium channel blocker
cardiac selective |
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diltiazem mechanism
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L type calcium channel blocker
intermediate cardiac/vascular selective |
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nifedipine mechanism
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L type calcium channel blocker
vascular selective |
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diltiazem and verapamil tx for what arrythmia
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supraventricular tachycardia
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CCB metabolism
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protein bound and big first pass effect
low bioavailability |
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CCBs inhibit what entity important for drug interactinos
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CYP 3A4
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interaction of CCBs and beta blockers
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profound conduction and contractile depression
decreased liver flow (betas) less clearance of CCBs |
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chemistry of captopril
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contains a sulfhydryl group at zinc ligand site.
--other ACE inhibs do not |
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hyperkalemia in ace inhibitors???
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decrease in aldosterone
**beware in pts with bad kidneys |
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he "diluting segment" of the nephron.
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thick ascending limb
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mannitol site of action
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proximal tubule
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mannitol characteristics of diuresis
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loss of H2O in excess of Na and Cl
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Acetazolamide site of action
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proximal tubule, inhibits carbonic anhydrase
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acetazolamide characteristics of diuresis
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loss of Na, HCO3, Cl, and K
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Furosemide site of action
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thck ascending loop of henle
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furosemide characteristics of diuresis
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loss of Na, Cl, K
Lose Mg and Ca potentially loss of 50% filtered Na |
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Thiazide like diuretics site of action
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distal tubule +/- proximal tubule inner medullary collecting tubule
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thiazide like diuretics characteristics of diuresis
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loss of Na, Cl and K
increase blood Ca and uric acid **prevent kidney stones **inhibit osteoporosis |
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chemistry of carbonic anhydrase inhibitors
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contain sulfamyl moiety
i.e. are sulfonamides |
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acetazolamide mechanism
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noncompetitive carbonic anhydrase inhibitor
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pharmacokinetics of acetazolamide
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absorbed from GI
eliminated by kidney actively secreted by organic acid transport system |
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clinical uses of carbonic anhydrase inhibitors
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glaucoma
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toxicity of carbonic anhydrase inhibitors
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metabolic acidosis
renal stone formation (renal stones from alkaline pH) K+ wasting decreased NH3 secretion |
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furosemide mechanism
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Na-K-Cl2 symport inhibitor
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ethacrynic acid mechanism
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Na-K-Cl2 symport inhibitor
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ethacrynic acid chemistry
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not a sulfonamide
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furosamide chemistry
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contains sulfamyl moiety
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loop diuretics and mg++, ca++
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substantial urinary loss of these divalent cations
**abolishes lumen positive potential |
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pharmacokinetics of loop diuretics
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absorved in GI
secretion via organic acid secretion threshold effect--once at effective dosage, more wont help **can increase frequency for more urination |
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toxicity of furosemide
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K+ loss
ototoxicity H loss with metabolic alkalosis |
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hydrochlorothiazide chemistry
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sulonamide (sulfamyl moiety)
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hydrochlorothiazide mechanism
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inhibit Na trnasport in distal convoluted tubule
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pharmacokinetics of hydrochlorothiazide
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rapidly absorbed from GI
filterd and secreted in proximal tubule binds to plasma proteins |
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thiazide diuretics and calcium
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increase Ca++ reabsorption
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triamterene chemistry
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organic base, not sulfonamide
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amiloride chemistry
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organic base, not sulfonamide
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triamterene mechanism
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inhibition of Na+ channel in collecting tubule
k sparing |
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amiloride mechanism
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inhibition of Na+ channel in collecting tubule
k sparing |
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amiloride pharmacokinetics
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partially absorbed from GI
completely eliminated in kidney |
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triamterene pharmacokinetics
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well absorbed from GI
elimenated by renal excretiona and metabolism |
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toxicity of amiloride and triamterene
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do not combine with spironolactone
caution with ace inhibitors do not combine with K+ supplements |
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spironolactone mechanism
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competitive aldosterone inhibitor
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Na+ channel blocking drugs terminate and prevent arrhythmias by
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· slowing conduction to interrupt a reentrant circuit
· increasing refractoriness to terminate functional reentry and so that there is "less room" for premature beats (which cause slowed conduction Þ reentry to occur) |
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Tx of atrial flutter/fibrillation to slow ventricular response
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AV nodal blockers:
verapamil/diltiazem beta blockers digitalis |
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tx of atrial flutter/fibrillation to maintain normal rythm
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(increase refractoriness in fast respone tissue)
class Ia Class Ic Class III |
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tx of supraventricular reentrant tachycardias: Acute (IV)
***(Almost always, the reentrant loop involves the AV node) |
adenosine (drug of choice)
verapamil or beta blocker digitalis maneuvers to increase vagal tone: vasalva, carotid massage |
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txt of svt reentrant (assuming AV node) tachycardia: oral (chronic)
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verapamil or diltiazem
beta blocker digitalis class Ic |
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tx of svt using a bypass tract
(fast response tissue) |
Class Ia
Class Ic Class III **avoid empiric tx with AV node blockers |
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tx of ventricular arrhythmias: acute (IV)
**(slow condux, increase refractoriness in fast response tissue->ventricles) |
lidocaine--Ib
procainamide--Ia amiodarone--III |
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tx of ventricular arrhythmia: chronic
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class Ia
Class Ib Class Ic class III |
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tx of undiagnosed wide complex tachycardia
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could be PSVT or VT. "all bets are off"
**avoid verapamil |
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tx for narrow complex tachycardia
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usually slow response=av node
adenosine verapamil esmolol |
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tx of unstable rhythm causing hemodynamic compromise
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shock the muthafucka
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QUINIDINE class and mechanism
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Ia
blocks Na+ and multiple K+ currents a-receptor block and vagal inhibition |
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Quinidine antiarrhythmic use
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chronic therapy of atrial fib/flutter (and VT)
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Quinidine problems
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diarrhea
more death in pts with a-fib? torsade de pointes 2-5% |
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procainamide class and mechanism
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Ia
blocks Na and K+ metabolite N-acetylprocainamide blocks K+ channels |
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procainamide use
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IV for SVT adn ventricular arrhythmia
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procainamide things to look out for
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dose adjustment in renal disease
lupus syndrome w/ chronic therapy |
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LIDOCAINE class and use
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Ib
decrease incidence of V fib **mortality increase |
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lidocaine dosage issues
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rapid distribution half life
slow elimination half life clearance reduced in CHF and liver disease |
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Flecainide Class Ic use
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effective at surpressing isolated PVC and reentrant SVT
*BUT INCREASED mortality in patients following myocaridal infarction. wtf |
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esmolol class and usage
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Class II, beta blocker
short half life=9 min useful for reckless beta blockade |
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why does bretylium (class III) suck?
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due to hypotensive effect, bretylium can cause hemodynamic collapse during previously well-tolerated VT (therefore use lidocaine, procainamide first)
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amiodarone useage, but sucks b/c?
class? |
Class I + II + III + IV action
· very effective for most arrhythmias, but NOT first-line oral therapy because . . · multiple toxicities: eye, *lungs*, liver, skin, thyroid during chronic treatment |
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verapamil: NEVER USE WHEN
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undiagnosed, wide complex tachycardia (Ë hemodynamic collapse)
· "preexcited" atrial fibrillation over an accessory pathway in the Wolff-Parkinson-White syndrome (may cause È heart rate, VF) · heart failure · sinus node dysfunction, AV block (*caution: Class I + IV*) |
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DILTIAZEM usefulness
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· intravenous form: useful AV nodal blocker usually without hypotension (especially for rate control of atrial fibrillation)
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ADENOSINE good for?
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Acute therapy of choice for: supraventricular tachycardias, undiagnosed wide-complex tachycardia
**short acting--seconds |
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Quinidine, Verapamil, Amiodarone, (? Flecainide)
interactinos with Digitalis |
inc digitalis concentration and toxicity
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amiodarone interactions with
warfarin, digoxin, procainamide, quinidine |
decreased drug metabolism and excretion
increased drug effects |
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renal disease interaction wtih
procainamide (Ia) and dofetilide (III) |
decreased clearance
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liver disease interaction with lidocaine
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decreased clearance
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heart failure interaction with lidocaine
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decreased clearance
decreased central volume (lidocaine) whatever the fuck that means |
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disopyramide, flecainide, beta blockers, verapamil interaction with
heart failure |
worsen heart failure
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dofetilide interaction with cimetidine and ketoconazole
|
increased dofetilide concentrations
|
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plasmin, enzyme type
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serum protease
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enzyme that dissolves clots
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plasmin
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what do kringle domains on plasminogen activators bind
|
fibrin
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Streptokinase mechanism
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indirect activator of plasminogen...helps one plasminogen activate another
|
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streptokinase problems
|
allergic rx's
bleeding, hypotension |
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urokinase mechanism
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direct activator of plasminogen
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urokinase metabolism
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liver, short half life 15 min
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urokinase inactivation
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inactivated by PAI-1
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second generation thrombolytic with long half life
|
APSAC....60 mins. given by bolus
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APSAC, what is it?
|
complex of streptokinase and plasminogen
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t-PA mechanism
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binds to fibrin and activates plasmin **clot specific**
|
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pharmacokinetics of t-PA
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PAI-1 irreversibly inhibits
cleared in liver short half life, 6 mins |
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Reteplase, what is it?
|
genetically engineered derivative of t-PA
just the kringle and protease, not glycosylated |
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TNK-t-PA (tenecteplase), wtf is it?
|
t-PA with no glycosylation site
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the two antifibrinolytics?
|
Amicar (e-aminocaproic acid) or tranexamic acid
|
|
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digoxin effects at AV node
|
increased ERP, and decreased conduction
slower ventricular rate during atrial flutter/fib |
|
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Digoxin effects at His-Purkinje fibers
|
increased automaticity
premature ectopic beats |
|
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digitalis effect on PR interval
|
increased
|
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digitalis effect on ST segment
|
depressed
|
|
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digitalis effect on amplituted of T waves
|
decreased
may invert |
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digitalis effect on QT interval
|
decreased
|
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aspirin mechanism
|
blocks cyclooxegenase--> no thromboxane A2
|
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Dipyridamole action
|
Inhibits cyclic nucleotide phosphodiesterase to increase intraplatelet accumulation of cAMP
¨ Blocks the uptake of adenosine |
|
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Ticlopidine and Clopidogrel mechanism
|
Metabolites Inhibit platelet activity via effects on
· Inhibition of ADP induced platelet activation (primary) · Glycoprotein IIb/IIIa receptor · von Willebrand factor |
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pharmacokinetics of ticlodipine and Clopidogrel
|
delay in onset
effects persist several days |
|
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ticlodipine and Clopidogrel interactions
|
activated by CYP3A4
inhibitors of CYP3A4 may reduce activation |
|
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Adverse effects of Ticlodipine and Clopidogrel
|
neutropenia in 3% of pts. ticlodipine problem
|
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(Abciximab mechanism
|
antibody to the IIb/IIIa receptor,
|
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factors inactivated by heparin
|
thrombin (II)
activated IX, X, XI, and XII **inactivates free thrombin, thus best for preventing clots |
|
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administration of heparin
|
IV, not absorbed thru GI
|
|
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never ever administer heparin this way
|
intra muscular
|
|
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Two forms of heparin-induced thrombocytopenia (HIT)
|
1 heparin induced platelet aggregation leading to decreased platelets
2 Rarer. b/t 7 and 11 days. immune response with thrombotic complications |
|
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what to do if in case of severe bleeding from heparin overdose
|
discontinue infusion
protamine administration |
|
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protamine mechanism
|
binds to and inactivates heparin
**possible allergic toxicity |
|
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mechanism of low molecular weight heparin
|
bind antithrombin/factor Xa
|
|
|
LMWH and PTT
|
b/c very little binds to AT-III/thrombin, little effect on PTT
NOT USED FOR MONITORING |
|
|
advantages of LMWH over regular heparin
|
less frequent administration
sub-q administration more predictable response to dose |
|
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Direct Thrombin Inhibitors?
|
lepirudin, agatroban
|
|
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lepirudin, agatroban mechanism
|
directly inhibit binding of thrombin to fibrinogen
|
|
|
warfarin action
which factors affected? |
antagonist of vitamin K
affects synthesis of II, VII, IX, X, protein C, and protein S |
|
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adverse effects of warfarin
|
bleeding, yo
paradoxical thrombis --pretein C and S fucked up first |
|
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beta blockers and hepatic metabolism
|
atenolol only beta blocker not metabolized in liver
|
