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autonomic and cardiovascular drugs


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botulinum toxin mechanism
blocks ACh release
choline acetyltransferase action
synthesizes ACh
breaksdown ACh
rate-limiting step in NE synthesis
Tyrosine hydroxylase (tyrosine to dopa)
metyrosine action
inhibits tyrosine hydroxylase
uptake I
norepinephrine transporter into neuron
uptake II
uptake by extraneuronal tissue
Monoamine oxidase action
makes catecholamine aldehydes
Catechol-o-methyltransferase (COMT) action
makes (nor)metanephrine
physostigmine action
inhibits cholinesterase
carbidopa action
dopa decarboxylase inhibition
receptor type which stimulates adenylyl cyclase
Beta 1,2
Gi receptor types
a2, M2
receptor types stimulating PKC
phenylephrine mechanism
a1 agonist
methoxamine mechanism
a1 agonist
dilated pupil
Phentolamine mechanism
competitive a1 antagonist

**short half life
phentolamine uses
dx pheochromocytoma
pphenoxybenzamine mechanism
noncompetitive a1 antagonist
*long acting
phenoxybenzamine use
treat pheochromocytoma
prazosin mechanism
alpha1 antagonist
prazosin use
tx of hypertension and CHF
prazosin risks
syncope after first oral dose
reduced efficacy with chronic use
clonidine mechanism
a2 agonist--> reduced symp outflow
clonidine use
tx of hypertension
methyldopa mechanism
metabolite a-methyl*norepinephrine* is a2 agonist
methyldopa use
tx of hypertension
yohimbe mechanism
alpha 2 antagonist
Isoproterenol mechanism
stimulates b1 and b2
dobutamine mechanism
b1 agonist
uses of dobutamine
tx of pulmonary edema, coronary bypass post op
Propranolol mechanism
competitive inhibitor of b1 and b2
uses of propranolol
tx of angina
ventricular arrhythmia
htn *dec renin*
post myocardial infarction
propranolol side efx
worse heart failure
reduced AV conduction
cold extremities
Metoprolol mechanism
b1 blocker
atenolol mechanism
b1 selective blocker
atenolol uses
htn (one a day)
bromocriptine mechanism
dopanergic agonist
tyramine mechanism
displaces NE into synaptic cleft
population vulnerable to tyramine related hypertension
pts on monoamine oxidase inhibitors
Phenylpropanolamine mechanism
indirect sympathetic stim
methacholine mechanism
bethanachol mechanism
muscarinic agonist
pilocarpine mechanism
muscarinic agonist
bethanachol uses
improved gastric emptying
tx of urinary retension (if no physical obstruction)
pilocarpine uses
induce salivation
open angle glaucoma--constricts iris sphincter (miosis)
methacholine use
provoke bronchoconstriction for dx testing
(methacholine challenge)
atropine mechanism
muscarinic antagonist
atropine use
raising heart rate when vagal activity is pronounced **vasovagal syncope

decreased respiratory secretions for intubation
Bezold-Jarisch reflex
bradyardia, hypotension, nausea from high nicotine dose
ganglionic blocking agents mechanism
block Nn receptors
insectiside mechanism
physostigmine mechansim
"reversible" short acting cholinesterase inhibitor

enters CNS
neostigmine mechanism
"reversible" short acting cholinesterase inhibitor

does not enter CNS
physostigmine side effects
enters cns, restlessness, apprehension, hypertension

typical muscarinic/nicotinic efx
why neostigmine no enter cns?
quaternary amine (charged)
uses of neostigmine
myasthenia gravis
propranolol "traditional" frequency of dosing
4 times a day
metroprolol mechanism
b1 blocker
metabolism of propranolol
heavily liver metabolized
protein bound
interindividual variability
atenolol metabilism
reduced hepatic metabolization (vis a vis propranolol)
metroprolol metabolism
less hepaticlly metabolized (vis a vis propranolol)
esmolol clinical use
b blocker for critical care
esmolol metabolism
short half life, IV use only
labetolol mechanism
b blocker with a1 effect
carvedilol clinical use
carvedilol mechanism
beta blocker with a1 blocking
type of b blocker for treatment of portal hypertensive bleeding
non selective (propranolol in US)
betablocker type for essential tremor
non selective
vascular headache prophylaxis betablocker type
propranolol (non selective and more lipophilic)
methyldopa side effects
sedation, depression, dry mouth
special situations in which methyldopa is particularly safe
for htn in pts with ischemic heart disease (no efx on CO)

does not block baroreceper rflx
--safe for anti-htn in elective surgery
dosing of methyldopa
delayed onset of effect (needs to be metabolized to methyel-NE)

twice a day for maintanence
drug of choice for hypertensive pregnant pts
why clonidine is poor choice in pts with *severe* HTN?
clonidine rebound. withdrawal syndrome w/ massive symp discharge
pharmacokinetics of prazosin
hepatic metabolism
pharmacokinetics of terazosin and doxazosin
longer lasting than prazosin
labetolol R R stereoisomer mechanism
b1 antagonist and partial b2 agonist
labetalol SR stereoisomer mechanism
a1 antagonist
S isomer of Carvedilol
b blocker (both isomers a1 blockers)
The critical factor affecting the therapeutic utility of nitrates
what is given along with nitroprusside?
Na2S2O3 (Na thiosulfate)
the antidote to CN
pharmacokinetics of nitroprusside
infusion only--dissolved immediately prior to use in glucose/water

rapid/potent/fast half life
nitroprusside clinical use
acute hypertensive crisis
mechanism of hydralazine
who the fuck knows
clinical utility of hydralazine
hypertension--use with beta blocker and diuretic

heart failure
metabolism of hydralazine
acetylated (pt variability)
hydralazine side effects
Na retention, coronary steal
minoxidil mechanism
sulfate metabolite opens atp sensitive k channel
--hyperpolarizes cell
--arterial vasodilation
chemical class: nifedipine
1,4 dihydropyridines
chemical class: verapamil
chemical class: diltiazem
verapamil mechanism
L type calcium channel blocker
cardiac selective
diltiazem mechanism
L type calcium channel blocker
intermediate cardiac/vascular selective
nifedipine mechanism
L type calcium channel blocker
vascular selective
diltiazem and verapamil tx for what arrythmia
supraventricular tachycardia
CCB metabolism
protein bound and big first pass effect

low bioavailability
CCBs inhibit what entity important for drug interactinos
interaction of CCBs and beta blockers
profound conduction and contractile depression

decreased liver flow (betas) less clearance of CCBs
chemistry of captopril
contains a sulfhydryl group at zinc ligand site.
--other ACE inhibs do not
hyperkalemia in ace inhibitors???
decrease in aldosterone
**beware in pts with bad kidneys
he "diluting segment" of the nephron.
thick ascending limb
mannitol site of action
proximal tubule
mannitol characteristics of diuresis
loss of H2O in excess of Na and Cl
Acetazolamide site of action
proximal tubule, inhibits carbonic anhydrase
acetazolamide characteristics of diuresis
loss of Na, HCO3, Cl, and K
Furosemide site of action
thck ascending loop of henle
furosemide characteristics of diuresis
loss of Na, Cl, K
Lose Mg and Ca
potentially loss of 50% filtered Na
Thiazide like diuretics site of action
distal tubule +/- proximal tubule inner medullary collecting tubule
thiazide like diuretics characteristics of diuresis
loss of Na, Cl and K
increase blood Ca and uric acid

**prevent kidney stones
**inhibit osteoporosis
chemistry of carbonic anhydrase inhibitors
contain sulfamyl moiety
i.e. are sulfonamides
acetazolamide mechanism
noncompetitive carbonic anhydrase inhibitor
pharmacokinetics of acetazolamide
absorbed from GI
eliminated by kidney
actively secreted by organic acid transport system
clinical uses of carbonic anhydrase inhibitors
toxicity of carbonic anhydrase inhibitors
metabolic acidosis
renal stone formation (renal stones from alkaline pH)
K+ wasting
decreased NH3 secretion
furosemide mechanism
Na-K-Cl2 symport inhibitor
ethacrynic acid mechanism
Na-K-Cl2 symport inhibitor
ethacrynic acid chemistry
not a sulfonamide
furosamide chemistry
contains sulfamyl moiety
loop diuretics and mg++, ca++
substantial urinary loss of these divalent cations
**abolishes lumen positive potential
pharmacokinetics of loop diuretics
absorved in GI
secretion via organic acid secretion
threshold effect--once at effective dosage, more wont help
**can increase frequency for more urination
toxicity of furosemide
K+ loss
H loss with metabolic alkalosis
hydrochlorothiazide chemistry
sulonamide (sulfamyl moiety)
hydrochlorothiazide mechanism
inhibit Na trnasport in distal convoluted tubule
pharmacokinetics of hydrochlorothiazide
rapidly absorbed from GI
filterd and secreted in proximal tubule

binds to plasma proteins
thiazide diuretics and calcium
increase Ca++ reabsorption
triamterene chemistry
organic base, not sulfonamide
amiloride chemistry
organic base, not sulfonamide
triamterene mechanism
inhibition of Na+ channel in collecting tubule

k sparing
amiloride mechanism
inhibition of Na+ channel in collecting tubule

k sparing
amiloride pharmacokinetics
partially absorbed from GI
completely eliminated in kidney
triamterene pharmacokinetics
well absorbed from GI

elimenated by renal excretiona and metabolism
toxicity of amiloride and triamterene
do not combine with spironolactone

caution with ace inhibitors

do not combine with K+ supplements
spironolactone mechanism
competitive aldosterone inhibitor
Na+ channel blocking drugs terminate and prevent arrhythmias by
· 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)
Tx of atrial flutter/fibrillation to slow ventricular response
AV nodal blockers:
beta blockers
tx of atrial flutter/fibrillation to maintain normal rythm
(increase refractoriness in fast respone tissue)
class Ia
Class Ic
Class III
tx of supraventricular reentrant tachycardias: Acute (IV)

***(Almost always, the reentrant loop involves the AV node)
adenosine (drug of choice)
verapamil or beta blocker
maneuvers to increase vagal tone: vasalva, carotid massage
txt of svt reentrant (assuming AV node) tachycardia: oral (chronic)
verapamil or diltiazem
beta blocker
class Ic
tx of svt using a bypass tract
(fast response tissue)
Class Ia
Class Ic
Class III

**avoid empiric tx with AV node blockers
tx of ventricular arrhythmias: acute (IV)

**(slow condux, increase refractoriness in fast response tissue->ventricles)
tx of ventricular arrhythmia: chronic
class Ia
Class Ib
Class Ic
class III
tx of undiagnosed wide complex tachycardia
could be PSVT or VT. "all bets are off"

**avoid verapamil
tx for narrow complex tachycardia
usually slow response=av node

tx of unstable rhythm causing hemodynamic compromise
shock the muthafucka
QUINIDINE class and mechanism
blocks Na+ and multiple K+ currents
a-receptor block and vagal inhibition
Quinidine antiarrhythmic use
chronic therapy of atrial fib/flutter (and VT)
Quinidine problems

more death in pts with a-fib?

torsade de pointes 2-5%
procainamide class and mechanism

blocks Na and K+

metabolite N-acetylprocainamide blocks K+ channels
procainamide use
IV for SVT adn ventricular arrhythmia
procainamide things to look out for
dose adjustment in renal disease
lupus syndrome w/ chronic therapy
LIDOCAINE class and use

decrease incidence of V fib

**mortality increase
lidocaine dosage issues
rapid distribution half life

slow elimination half life

clearance reduced in CHF and liver disease
Flecainide Class Ic use
effective at surpressing isolated PVC and reentrant SVT

*BUT INCREASED mortality in patients following myocaridal infarction. wtf
esmolol class and usage
Class II, beta blocker

short half life=9 min

useful for reckless beta blockade
why does bretylium (class III) suck?
due to hypotensive effect, bretylium can cause hemodynamic collapse during previously well-tolerated VT (therefore use lidocaine, procainamide first)
amiodarone useage, but sucks b/c?

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
verapamil: NEVER USE WHEN
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*)
DILTIAZEM usefulness
· intravenous form: useful AV nodal blocker usually without hypotension (especially for rate control of atrial fibrillation)
ADENOSINE good for?
Acute therapy of choice for: supraventricular tachycardias, undiagnosed wide-complex tachycardia

**short acting--seconds
Quinidine, Verapamil, Amiodarone, (? Flecainide)

interactinos with

inc digitalis concentration and toxicity
amiodarone interactions with

warfarin, digoxin, procainamide, quinidine
decreased drug metabolism and excretion

increased drug effects
renal disease interaction wtih

procainamide (Ia) and dofetilide (III)
decreased clearance
liver disease interaction with lidocaine
decreased clearance
heart failure interaction with lidocaine
decreased clearance

decreased central volume (lidocaine) whatever the fuck that means
disopyramide, flecainide, beta blockers, verapamil interaction with

heart failure
worsen heart failure
dofetilide interaction with cimetidine and ketoconazole
increased dofetilide concentrations
plasmin, enzyme type
serum protease
enzyme that dissolves clots
what do kringle domains on plasminogen activators bind
Streptokinase mechanism
indirect activator of plasminogen...helps one plasminogen activate another
streptokinase problems
allergic rx's
bleeding, hypotension
urokinase mechanism
direct activator of plasminogen
urokinase metabolism
liver, short half life 15 min
urokinase inactivation
inactivated by PAI-1
second generation thrombolytic with long half life
APSAC....60 mins. given by bolus
APSAC, what is it?
complex of streptokinase and plasminogen
t-PA mechanism
binds to fibrin and activates plasmin **clot specific**
pharmacokinetics of t-PA
PAI-1 irreversibly inhibits

cleared in liver

short half life, 6 mins
Reteplase, what is it?
genetically engineered derivative of t-PA

just the kringle and protease, not glycosylated
TNK-t-PA (tenecteplase), wtf is it?
t-PA with no glycosylation site
the two antifibrinolytics?
Amicar (e-aminocaproic acid) or tranexamic acid
digoxin effects at AV node
increased ERP, and decreased conduction

slower ventricular rate during atrial flutter/fib
Digoxin effects at His-Purkinje fibers
increased automaticity

premature ectopic beats
digitalis effect on PR interval
digitalis effect on ST segment
digitalis effect on amplituted of T waves

may invert
digitalis effect on QT interval
aspirin mechanism
blocks cyclooxegenase--> no thromboxane A2
Dipyridamole action
Inhibits cyclic nucleotide phosphodiesterase to increase intraplatelet accumulation of cAMP

¨ Blocks the uptake of adenosine
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
pharmacokinetics of ticlodipine and Clopidogrel
delay in onset

effects persist several days
ticlodipine and Clopidogrel interactions
activated by CYP3A4
inhibitors of CYP3A4 may reduce activation
Adverse effects of Ticlodipine and Clopidogrel
neutropenia in 3% of pts. ticlodipine problem
(Abciximab mechanism
antibody to the IIb/IIIa receptor,
factors inactivated by heparin
thrombin (II)
activated IX, X, XI, and XII

**inactivates free thrombin, thus best for preventing clots
administration of heparin
IV, not absorbed thru GI
never ever administer heparin this way
intra muscular
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
what to do if in case of severe bleeding from heparin overdose
discontinue infusion

protamine administration
protamine mechanism
binds to and inactivates heparin

**possible allergic toxicity
mechanism of low molecular weight heparin
bind antithrombin/factor Xa
b/c very little binds to AT-III/thrombin, little effect on PTT

advantages of LMWH over regular heparin
less frequent administration
sub-q administration
more predictable response to dose
Direct Thrombin Inhibitors?
lepirudin, agatroban
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
adverse effects of warfarin
bleeding, yo
paradoxical thrombis
--pretein C and S fucked up first
beta blockers and hepatic metabolism
atenolol only beta blocker not metabolized in liver

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