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192 Cards in this Set
- Front
- Back
|
what are representative agents of CCB's?
|
verapamil
diltiazem dihydrophyridines |
|
|
what are examples of dihydropyridines?
|
-amlodipine (norvasc)
-felodipine (Plendil) -isradipine (DynaCirc) -nicardipine (Cardene) -nifedipine (procardia, adalat -nimodipine (Nimotop) -nisoldipine (Sular) |
|
|
All CCB's undergo what metabolism?
|
all undergo hepatic metabolism except verapamil
|
|
|
where do CCB's bind to?
|
-voltage gated L-type calcium channels in heart and vascular sm muscle and block transmembrane Ca++ flux
|
|
|
CCB's interfere w/ what?
|
-phase O depolarization of SA and AV nodal cells
-phase 2 depolarization of ventricular muscle -depolarization of vascular sm muscle cells |
|
|
what agents mainly affect the heart of the CCB's?
|
verapamil
diltiazem |
|
|
relaxation of vascular sm muscle results from what?
|
arteriolar vasodilatation and reduced SVR
|
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what agents have greater affect on arteriolar vasodilatation?
|
dihydropyridines
|
|
|
what are CV actions of CCB's?
|
-depression of myocardial contractility
-decrease in HR -decreased automaticity -decreased rate of impulse conduction through the AV node -relaxatio of vasc. sm muscle -decrease in MvO2 -relief/prevention of coronary artery vasospasm -decrease in BP |
|
|
what agent has high affinity for cerebral blood vessels and can prevent/relieve cerbral vasospams assoc w/ SAH?
|
nimodipine
|
|
|
what are adverse effects of CCB's?
|
-flushing
-dizziness -nausea -constipation -myocardial depression -AV block -CHF -conduction abnormalities -bradydysrhythmias |
|
|
what CCB can cause torsades?
|
bepridil (prolongs repolarization and increases QT interval)
|
|
|
what are clinical uses of CCB's?
|
-mngmt of angina pectoris
-nifedipine-increased coronary blood flow and myocardial oxygen delivery -tx of narrow complex tachycardia -class IV antidysrhythmic -essential HTN -hypertrophic cardiomyopathy -Raynaud's syndrome |
|
|
what can CCB's do to muslce relaxants?
|
potentiate the effects of depolarizing and nondepolarizing muscle relaxants
|
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what agent should be avoided in combination w/ a beta blocker?
|
verapamil (particularily in pts w/ conduction degects or poor ventricular function)
|
|
|
what is most frequent cause of artery obstruction?
|
atherosclerosis
|
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when does angina result?
|
when myocardial oxygen demand exceeds oxygen supply
|
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what occurs predictably at a particular level of exertion or during emotional stress?
|
stable angina
|
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unstable angina usually occur when?
|
at rest
|
|
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what is variant angina (Prinzimetal's angina)?
|
coronary artery vasospasm cause transient ischemia episodes
|
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|
how do nitrates/nitrites work?
|
to prevent or relieve imbalance btwn myocardial O2 demand and O2 supply
|
|
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what agents are nitrates/nitrites?
|
-NTG
-isosorbide dinitrate (isordil) -isosorbide monotitrate (ismo) -amyl nitrite (aspirols) |
|
|
what is packaged as a cloth-covered glass ampules and crushing the ampule releases volatile drug to be inhaled?
|
Amyl nitrite
|
|
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what is MOA of antianginals?
|
agents release NO--activation of guanylyl cyclase in vasc. sm muscle--increased cGMP--sm muscle relaxation
|
|
|
what are effects of antianginals on vascular sm muscle?
|
-veins and arteries dilate
-venodilation reduces preload -dilation of coronary arteries and increase in coronary blood flow |
|
|
venodilation and arterial dilation reduce what ?
|
ventricular wall tension, afterload, MVO2
|
|
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what is effect of antianginal on variant angina?
|
nitrates relieves vasospasm of epicardial coronary arteries
|
|
|
what are adverse effects of antianginals?
|
-orthostatic hypotension
-reflex tachycardia -throbbing HA |
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|
what are effects on heart of blockade of beta-1 adrenergic receptors?
|
-reduces HR, contractility, CO and BP
-slows AV conduction -reduces myocardial Oxygen demand |
|
|
what types of pts should you use with caution or not all w/ beta blockers?
|
-CHF, heart block
-PVD -asthma -diabetes |
|
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what CCB is best combined with beta blocker?
|
nifedipine
|
|
|
what cobination of meds is generally effective and well tolerated?
|
beta blockers plus nitrate
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what may be useful in pts with significant ventricular dysfunction?
|
nifedipine and nitrate
|
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why is CCB beneficial w/ nitrates?
|
verapamil and dilt. reduce reflex tachycardia produced by nitrates
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|
what are pharmacological effects of diuretics?
|
-diuresis (increased urine flow rate)
-natriuresis (increased sodium excretion) |
|
|
what are principal clinical uses of diuretics?
|
-mobilization of peripheral or pulm edema fluid
-tx of essential HTN -tx of increased ICP -prophylaxis/tx of ARF |
|
|
what agents are true thiazides?
|
-chlorothiazide (Diuril)
-HCTZ -hydroflumethiazide |
|
|
what agents are thiazide like cmpds?
|
-chlorothalidone (Thalitone)
-metolazone (zaroxolyn) -indapamide (lozol) |
|
|
what are principle uses of thiazides?
|
-CHF
-essential HTN -hypercalciuria -nephrogenic DI |
|
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do thiazides affect CMOG?
|
No
|
|
|
what is MOA of thiazides?
|
-inhibition of Na and CL reabsorption in the distal tubule
-reduced H2O reabsorption in collecting tubules secondary to impaired distal tubule NaCl reabsorption |
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|
what are S/S of hypokalemia?
|
-cardiac dysrhtyhmias
-skeletal muscle weakness -enhanced digital toxicity |
|
|
what are adverse effects of thiazides?
|
increased K+ secretion in CCT-kaliuresis; hypokalemia can result
-hypokalemic metabolic acidosis -hyperglycemia -hyponatremia -volume depletion |
|
|
what are the loop diuretics?
|
-furosemide (lasix)
-ethacrynic acid (Edecrin) -bumetanide (Bumex) -torsemide (demadex) |
|
|
what are principle uses of loop diuretics?
|
-mngt edema in pts w/ CHF or RF
-tx of acute pulm edema -tx of acute hypercalcemia -ARF |
|
|
what is MOA of loop diuretics?
|
-inhibit Na+ and Cl absorption in the thick ascending loop of H
-washout CMOG -reduced H2O reabsorption in collecting tubules -FEna can reach 20-25% |
|
|
what are adverse effects of loop diuretics?
|
-volume depletion
-kaliuresis -hypokalemic metabolic acidosis -deafness -hypomagnesemia |
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|
what agents are osmotic diuretics?
|
-mannitol
-urea |
|
|
what are clinical uses for osmotic diuretics?
|
-prophylaxis against ARF
-conversion of oliguric ARF to nonoliguric ARF -reduction in ICP |
|
|
what is MOA of osmotic diuretics?
|
-inhibition of waer and Na+ reabsorption in the PCT--accelerates flow out of PCT
-accelerated flow leads to reduced Na+ reabsorption in LofH -washout of CMOG -water lost in excess of Na+ |
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|
what are adverse effects of osmotic diuresis?
|
-initial ECF expansion may complicate CHF and cause pulm edema
-volume depletion and hypernatremia |
|
|
what are potassium sparing diuretics?
|
-amiloride (Midamor)
-spironalactone (Aldactone) -triamterene (Dyrenium) |
|
|
what agent is used in tx of primary Conn's syndrome or secondary hyperaldosteronism?
|
spironolactone
|
|
|
what may be used to tx polyuria due to lithium induced nephrogenic DI?
|
amiloride
|
|
|
what is principle use of potassium sparing diuretics?
|
combination therapy w. a loop or thiazide diuretic to diminish K+ loss
|
|
|
what is MOA of potassium sparing diuretics?
|
-act to inhibit Na+ reabsorption in the CCT
-FEna reaches only 1-2% |
|
|
what agents block Na+ channels in luminal cell membranes?
|
-amiloride
-triamtrene |
|
|
what does spironolactone and eplerenone do?
|
antagonize aldosterone action; reduce Na+ and K+ channels in luminal cell membranes
|
|
|
what are adverse effects of potassium sparing diuretics?
|
-reduction in K+ secretion can lead to hyperkalemia
-hypercholermic metabolic acidosis |
|
|
what agent is representative of carbonic anhydrase inhibitors?
|
acetazolamide (Diamox)
|
|
|
what are carbonic anhydrase inhibitors used for?
|
-reduction in IOP
-adjunct therapy for epilepsy -prophylaxis/tx of high-altitude sickness (decrease is CSF formation and pH) - |
|
|
what is MOA of carbonic anhydrase inhibitors?
|
inhibtion of carbonic anhydrase and reabsorption of HCO3 and Na+ in the PCT
-diuresis and natriuresis are very mild -FEna-1% |
|
|
what is most common cause of CHF?
|
CAD
|
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systolic dysfunction represents what?
|
impaired contractility
|
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what type of ventricular dysfunction is d/t acute heart failure d/t MI?
|
systolic dysfunction-reduced CO and EF <45%
|
|
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what agents is systolic dysfunction usually responsive to initially?
|
inotropic agents
|
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what is diastolic dysfunction?
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inadequate ventricular relaxation during diastole and filling
|
|
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what happens to CO and EF during diastolic dysfunction?
|
CO reduced but EF normal
|
|
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what is diastolic dysfunction often due to?
|
ventricular hypertrophy and stiffening
|
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what may occur when body oxygen demands overwhelm an already increased CO ?
|
high-output failure
|
|
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what is therapy for high-output failure?
|
direct therapy at cause, poorly responds to inotropic agents
|
|
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what are s/s of heart failure?
|
-decreased exercise tolerance
-tachycardia -SOB -peripheral and pulm edema |
|
|
what are compensatory responses to heart failure?
|
-increased SNS activity
-activiation of renin-angiotensin-aldosterone system -myocardial hypertrophy and remodeling |
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|
what is the only glcoside used in the U.S?
|
Digoxin
|
|
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what are clinical uses of digoxin?
|
-tx of CHF
-contorl of ventricular rate in pts w/ SVT |
|
|
what is the Aglycone portion?
|
lactone ring attached to a steroid nucleus
|
|
|
what is glycone portion?
|
-seriesof sugar attached to the steroid nucleus; determine pharmacokinetic behavior
|
|
|
effects on myocardium from glycosides?
|
-inhibition of Na+, K+ ATPase in cardiac cell membranes
-cardiac glycosides inhibit Na+ extrusion from cell -increase Na+ reduces Na+-Ca+ exchange allowing Ca+ to increase inside cell -increase intracellular Ca+ causes positive inotropic effect |
|
|
what are cardiovascular responses to glycosides?
|
-incresae in myocardial contactility (positive inotropic effect)
-delayed conduction of cardiac impulse through the AV node -prolonged PR interval -Shortened QT interval |
|
|
what does a decrease in myocadial contracililty from glycosides cause?
|
-increased SV
-decreased LVEDP -decreased heart size -shift in vent. fxn curve upward and to left |
|
|
what does the delayed conduction of cardiac impulse through AV node from glycosides cause?
|
-enhanced parasympathetic discharge
-reduction in HR adn MVO2 |
|
|
what is another important effect of cardiac glycosides?
|
-decreased peripheral vascular resistance (decrease afterload)
|
|
|
where is digoxin taken up?
|
extensively in tissues; at equilibrium cong of dig in heart muscle is 10-50x the plasma drug conc
|
|
|
what is T1/2 of dig?
|
40h
|
|
|
where is 2/3 of dig dose excreted?
|
unchanged in the kidneys; therefore reduce dose in pts w. renal insuff
|
|
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main tissue reservoir of dig is what?
|
skeletal muscle
|
|
|
what is TI of dig?
|
1.2 (narrow margin of safety)
|
|
|
what are GI adverse effects of dig?
|
-anorexia
-N/V |
|
|
what is another adverse effect of dig?
|
heart block due to impulse delay at AV node
|
|
|
ventricular dysrhythmias can occur w/ dig d/t what?
|
increased automaticity
|
|
|
what is most common cause of death from cardiac glycoside toxicity?
|
v-fib
|
|
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what are some possible contributors to toxicity?
|
-hypokalemia
-hypercalcemia;hypomagnesemia -increased SNS activity -renal insuff -decreased skeletal muscle mass |
|
|
how does hypokalemia contribute to dig toxicity?
|
-enhances binding of dig to cardiac muscle and increased drug effect
-concurrent use of diuretics that cause K+ loss -hyperventilation (during anesthesia) |
|
|
what are agents that have + inotropic effect but are not glycosides?
|
-glucagon
-Bipyridines |
|
|
how does glucagon have + inotropic effect?
|
-increases cAMP
-increased SV and HR -enhanced automaticity in SA and AV nodes but not in ventricles |
|
|
what are uses of glucagon?
|
-reersal of depressed HR and myocardial contracitility d/t OD of beta adrenergic antagonists
|
|
|
by which routes is glucagon administered?
|
IV or IM (ineffective orally b/c is hyrolyzed in GI tract)
|
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what is another use of glucagon?
|
releive opioid induced contraction of sphincter of Oddi
|
|
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what are adverse effects of glucagon?
|
-hyperglycemia
-hypoglycemia (d/t glucagon mediated insulin release) -hypokalemia -N/V |
|
|
what are the Bipyridines that can be used acutely?
|
-Inamrinone (Inocor)
-Milrinone (Primacor) |
|
|
what are pharmacodynamics of bipyridines?
|
-positive inotropic effect--increased CO
-decreased LVEDP |
|
|
what is the mechanism of inotropic action?
|
inhibition of phosphodiesterase--elevation of intracellular cAMP--calcium mobilization
|
|
|
perihperal vasodilation does what?
|
reduces SVR and afterload
|
|
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what is T1/2 of dypryidines?
|
3-6h
|
|
|
what are SE of inamrinone?
|
N/V; thrombocytopenia
|
|
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what are SE of milrinone?
|
dysrhythmias; long term use has increased moratality in pts w/ CHF
|
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what are other inotropic agents can be used as + inotropic agents?
|
-beta adrenergic agonists ex isoproterenol, dobutamine, epi
-dopamine |
|
|
LA are classified as what?
|
either esters or amides
|
|
|
what are the esters of LA?
|
-procaine
-chloroprocaine -tetracaine -cocaine |
|
|
what aer the amides of LA?
|
-lidocaine
-mepivacaine -prilocaine -etidocaine -bupivacaine -l-buprivacaine -ropivacaine |
|
|
modifications of LA structure can have significant effects on what?
|
-lipid solubility
-potency -duration of action -toxicity |
|
|
tetracaine has butyl substitution on amino grp so compared to procaine tetracaine is what?
|
-more lipid soluble
-more potent - longer DOA |
|
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what agent has less toxicity than bupivacaine?
|
ropivacaine
|
|
|
what is MOA of LA?
|
-prevent conduction of nerve impulses by blocking fast sodium channels in nerve cell membranes
|
|
|
bupivacaine is how many times more potent than what?
|
8x more potent than mepivacaine
|
|
|
substituting a butyl grp for the N-methyl grp on mepivacaine results in the cmpd what?
|
bupivacaine; more lipid soluble, more potent, longer DOA
|
|
|
where do LA bind?
|
to specific receptor sites near the internal gate of sodium channel, stabilizing the channel in the inactivated-closed state, and preventing return to the rested closed state
|
|
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inactivated sodium channels are impermeable to Na+ so what happens to AP?
|
AP propagation is blocked
|
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T or F LA do NOT affect either the resting membrane potential or the threshold potential for AP formation?
|
True
|
|
|
peripheral nerves are what kind of nerves and contain what?
|
compound nerves; contain numerous axon bundles, or fasicles
|
|
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what is the endoneurium?
|
the connective tissue coast around each axon fascicle
|
|
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each fascicle is surrounded by a layer of cells known as what/
|
perineurium
|
|
|
the entire peripheral nerve is surrounded by a collagen sheath known as what?
|
epineurium
|
|
|
Cm (minimum conc) is influenced by what?
|
-chemical properties of the drug
-physical properties of the nerve -local pH -electrolyte disturbances |
|
|
what is more susceptible to blockade a nerve w/ high freq firing or or low freq firing?
|
nerve w/ high freq firing more susceptible to blockade
|
|
|
what affect does pH have on block?
|
acidosis can antagonize the block
|
|
|
what electrolyte disturbances can antagonize the block?
|
hypokalemia
hypercalcemia |
|
|
what is sensitivity to LA of fiber type?
|
Type B>type C=TypeAdelta>type Abeta>type Aalpha
|
|
|
why are preganglionic autonomic nerve fibers most readily blocked?
|
combination of myelin and relatively small diameter
|
|
|
axons in the mantle or core are anesthetized first?
|
axons in nerve mantle are anesthetized before axons in core
|
|
|
LA are weak ________and are readily protonated at what?
|
bases, physiologic pH
|
|
|
what is the form that diffuses into the nerve cell membrane the ionized or nonionized form?
|
nonionized form diffuses into the nerve cell membrane
|
|
|
what is the active form of the drug the ionized or nonionized form?
|
ionized form; form that actually blocks sodium channels
|
|
|
the percent of drug in the nonionized form depends on what?
|
the pKa of the drug and the local pH
|
|
|
the pka of local anesthetics is somewhat higher than physiologic pH thus?
|
less than 50% of the drug exists in the nonionized form at physiologic pH
|
|
|
increasing the drug dose will do what to onset of action?
|
increase onset of action
|
|
|
what terminates LA action?
|
absorption
|
|
|
what aer the four factors that infuence the absoprtion of LA?
|
1-blood flow to inj. site
2-physiochemical characteristics of the drugs 3-dose of drug 4-presence or absence of vasoconstrictor |
|
|
what is flow of absorption from highest to lowest?
|
trachea>intercostal>caudal>paracervical>epidural>brachial plexus>sciatic>subq
|
|
|
agents like etidocaine have longest DOA b/c have whta phsiochemical characteristics?
|
-high lipid solubility
-highly bound to tissue protein |
|
|
what do vasoconstrictors do?
|
reduce local blood flow, slow the rate of systemic absorption
|
|
|
what is dose of epi that can be added as vasoconstrictor?
|
1:200,000; 5micrograms/ml
|
|
|
in sp anesthesia epi also does what?
|
activate alpha2 adrenorecetors in substantia gelatinosa of sp cord--inhibits substance P release
|
|
|
following absorption amide LA distribute where first
|
to highly perfused tissues like brain, heart, lung; then to more slowly perfused tissues such as muscle and gut
|
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ester LA are rapidly metabolized where?
|
in the blood and thus do not undergo significant tissue distribution
|
|
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clearance of LA from circulation is primarily via what?
|
metabolism
|
|
|
what hydrolyzes the amide bond?
|
microsomal enzymes
|
|
|
of the amide LA what is order of metabolism from fastest to slowest?
|
prilocaine>etidocaine>lidocaine>mepivacaine>bupivacaine
|
|
|
the amides undergo what metabolism?
|
hepatic
|
|
|
what may reduce amide LA clearance and increase risk of systemic toxicity?
|
liver disease (cirrhosis) or reduction in hepatic blood flow (ex anesthetsia)
|
|
|
prilocaine is metabolized to what?
|
ortho-toluidine; an oxidizing cmpd that can convert Hgb to methgb
|
|
|
when prilocaine dose exceed what can methgb be present and pt appears what?
|
exceeds 600mg (8mg/Kg) and pt appears cyanotic
|
|
|
what is clinical uses of prilocaine?
|
low doses can be used in Bier block and its a component of EMLA
|
|
|
metabolism of esters is via what?
|
plasma pseudocholinestersase to derivatives of para-aminobenzoic acid (PABA)
|
|
|
what can PABA cause?
|
allergic reactions
|
|
|
what are comparative rates of metabolism of esters (fastest to slowest)?
|
chloroprocaine>procaine>tetracaine
|
|
|
spinal block w/ tetracaine is terminated by what?
|
drug absorption into circulation; b/c CSF contains very littel pseudocholinesterase activity
|
|
|
what does systemic toxicity of LA result from?
|
exces plasma levels of the drug; most commonly caused by inadvertent intravascular inj of LA during epidural or peripheral nerve block
|
|
|
what is first sign of toxicity of LA?
|
numbness of tongue and mouth; "metallic" taste
|
|
|
what are CNS s/s of LA systemic toxicity?
|
-vertigo, tinnitus, visual blurring
-restlessness,skeletal muscle twitching, seizures -slurred speech, coma, resp arrest, cardiac arrest |
|
|
what are the toxic plasma levels of lidocaine, mepivacaine,prilocaine?
|
5-10ug/ml
|
|
|
what is toxic levels of bupivacaine, etidocaine?
|
1.5ug/ml
|
|
|
T or F CV system is more resistant to local toxicity than CNS.
|
TrUe
|
|
|
what is cv effect from toxic levels of LA?
|
-hypotension (d/t depression of myocardial contracility)
-can block myocardial fast sodium channels |
|
|
what LA has highest likely hood of cardiotoxicity?
|
Bupivacaine
|
|
|
cardiac dysrhythmias are less likely with what agents?
|
-l-bupivacaine or ropivacaine
|
|
|
what is used for tx of severe systemic LA toxicity?
|
Lipid rescue- iV administration of lipid emulsion
|
|
|
what do LA do to nondepolarizing muscle relaxants?
|
potentiate the effects of NDMR
|
|
|
what agents reduce liver blood flow and amide LA clearance?
|
-cimetidine
-propranolol |
|
|
what agents can be used as topical anesthetics?
|
Lidocaine
tetracaine |
|
|
what agent can be used as topical and is unique b/c it causes vasoconstriction?
|
cocaine
|
|
|
what agents do not readily cross epithelium and are not used for topical anesthesia?
|
procaine and chloroprocaine
|
|
|
what agents can be used for local infiltration?
|
lidocaine
mepivacaine bupivacaine ropivacaine |
|
|
for spinal block LA is injected into what space and acts on what?
|
subarachnoid space, acts on spinal nerve roots
|
|
|
what agents are used for spinal block?
|
-tetracaine
-lidocaine -bupivacaine -ropivacaine -chloroprocaine |
|
|
the sp gravity of a LA is important in determining the _________of the drug in subarachnoid space.
|
distribution
|
|
|
adding______increases solution density relative to CSF?
|
glucose
|
|
|
adding _______ _________ decreases solution density (hypobaric solution)
|
distilled water
|
|
|
what are complications from spinal block?
|
-venodilation--decreased venous return--fall in CO and BP (hypotension)
-spinal HA |
|
|
injection of LA for epidural block is where?
|
epidural space
|
|
|
agents used for epidural block include?
|
-chloroprocaine
-lidocaine -mepivacaine -bupivacaine -ropivacaine |
|
|
test dose of what is administered initially w/ epidural block and why?
|
3ml of LA containing 1:200,000 epi; to detect intrathecal or intravascular injection
|
|
|
what would you see w/ intravascular injection ?
|
20% or > increase in HR
|
|
|
what is peripheral nerve block?
|
inj of LA in proximity to individual peripheral nerves or nerve plexuses
|
|
|
agents used for peripheral nerve block are?
|
-chloroprocaine
lidocaine mepivacaine bupivacaine ropivacaine |
|
|
what is a Bier Block?
|
method of anesthetizing a limb by intravenous inj of a LA while blood flow to the extremety is occluded by a tourniquet
|
|
|
what is DOA of LA for bier block determined by?
|
time tourniquest is applied
|
|
|
why is chloroprocaine not recommended for bier block?
|
high incidence of thrombophlebitis
|
|
|
why is bupivacaine not recommended for bier block?
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potential cardiotoxic effects when circulation is restored
|
|
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what agent is freq. used for bier blocks?
|
lidocaine-
low incidence of thrombophlebitis |
|
|
what LA can be used for tx of cardiac dysrhythmias?
|
lidocaine
|
|
|
what LA can be used for suppression of tonic-clonic seizures?
|
Lidocaine
mepivacaine |
