ACEI. dosed BID/TID on empty stomach, is not a prodrug (hepatic impairment). Additional SE rash.
monitor K and SrCr as they begin or increase dose
blocks binding of angiotensin II to AT1 receptor (less vasoconstriction)
ARB kinetics (DOA)
intermediate (12-24 hr) duration of action
HTN, CHF, pts who require an ACEI but cannot tolerate cough
absolute pregnancy (cat D). caution with volume depletion.
dizziness, hypotension, hyperkalemia, renal failure. [cough/angioedema less frequent]
ARB, 80-320mg PO qd (lower with diuretic)
ARB, 20-40mg PO qd
Direct Renin Inhibitor drugs
inhibit renin, less angiotensin I produced, less angiotensin II produced (less vasoconstriction), less aldosterone secretion (less reabsorption), more bradykinin (vasodilation).
DRI kinetics (T1/2)
long (40 hr) half life
absolute pregnancy (cat D). caution with volume depletion, hyponatremia.
diarrhea, GERD, hyperkalemia.
renin concentrations will likely increase during administration (ATII negative feedback loop)
Sodium Channel Blockers class
class 1a - procainamide, disopyramide, quinidine. Class 1b - lidocaine, mexitetene. Class 1c - propafenone, flecainide.
SCB - Class 1a
moderate Na+ channel blockers, increased ERP
SCB - Class 1b
weak Na+ channel blockers, decreased ERB
SCB - Class 1c
strong Na+ channel blockers, no ERB effect
block sodium channels, decreasing ion mvmt during phase 0. results in slower conduction, wider QRS. Phase 3 (and therefore QT interval) can be longer or shorter. also helps prevent after-depolarizations.
pt does not have a life-threatening arrhythmia. lots of drug interactions (leading to QT prolongation, arrhythmias, other toxicities).
cardiac arrhythmias, including torsades de pointes
SCB class 1a. SE drug-induced lupis.
SCB class 1a. SE anticholinergic.
SCB class 1a. SE GI, bitter taste, cinchonism (vertigo, headache, tinnitus, psychosis)
SCB class 1b. orally active form of lidocaine (lidocaine is IV due to short half life).
SCB class 1c
SCB class 1c
Beta Blockers class/drugs
class 2, "lols"
competitively antagonize the action of chatecholamines at beta receptors (beta-1 stimulation at SA/AV nodes leads to an increase in sodium currents/chronotropy/ionotropy). this reduces HR, contractility, and prevents after-depolarizations. can also block any compensatory increases in sympathetic activity.
BB cardioselective (beta-1 only)
atenolol, metoprolol selectivity
BB non-cardioselective (beta-1 and beta-2)
BB mixed alpha/beta
labetalol, carvedilol selectivity
BB least lipophilic, most water soluble, least CNS side effects
atenolol, (labetalol) distribution
BB most lipophilic, easily cross membranes, most CNS side effects (anhedonia, but could also help calm hyperenergetic brain)
class 4 = verapamil, diltiazem. also in this category are the "pines"(dihydropyridines)
binds to various sites on L-type calcium channels (V, D, or N) blocking Ca influx. non-DHPs are cardiac depressants (chronotropy/ionotropy) with some vasodilator activity. DHPs are primarily vasodilators, which can lead to a potential reflex increased chronotropy/ionotropy.
amlodipine kinetics (T1/2/info)
much longer (40 hr) half life than nifedipine (4 hr), helping to mitigate reflex tachycardia.
felodipine kinetics (info)
has the highest affinity of the dipines, therefore causes the most dilation but also the most side effects
block activity of ACh on parasympathetic muscaric receptors. in heart, SA/AV nodes increase pacemaker rate, sometimes increase conduction through blocks
SB with hypotension, 2 degree heart block with bradycardia (can be tried in 3 degree).
symptomatic bradycardia, slow PEA, asystole
caution in situations where tachycardia can be dangerous
anticholinergic side effects
tachycardia, hyperthermia, delirium, other decreased parasympathetic issues
anticholinergic, 0.5mg IV q5min max 3mg
quartet: red, hot, dry, confused
stimulates A1 receptors in AV note, decreasing K efflux, Ca influx, and Na influx. Hyperpolarization renders the cell refractory (essentially causing a 3 degree heart block for a few seconds).
1) reentry circuits terminated and NSR resumes, 2) QRS eliminated so atrial tachycardias can be more easily diagnosed
adenosine kinetics (T1/2)
half life of 10 seconds, so double-push.
caffiene acts on the same receptors and can block its action.
short-lived angina/extreme discomfort (endogenous adenosine is typically released with ischemia: decreased o2 --> decreased ADP change to ATP --> increased adenosine levels)
6-12 mg IV q1-2min, max 3 doses. pts taking carbamazepine, dipyridamole, heart transplant, central line initial dose is 3mg.
Cardiac Glycoside drugs
digoxin, digitalis (foxglove plant, longer T1/2)
decreased Na/K pump action. Increased intracellular Na decreases electrochemical gradient for Na-Ca exchanger, less Ca exits cell and intracellular levels rise. Net result is increased contractility. Indirectly decreases need for sympathetic compensation.
direct increase in parasympathetic tone via baroreceptors/brainstem vagal nuclei. net result is a decrease in HR (also useful in pts with a-fib due to increased PNS tone at AV node)
digoxin kinetics (T1/2)
half-life is 30 hrs
therapeutic index 0.8-2ng/mL, 2.6 probable toxicity, 3 guaranteed toxicity (higher in children). Draw levels away from dose administration. 20% will experience toxicity, especially those with hypokalemia/electrolyte imbalances.
absolute in pts with VF. relative in pt with ventricular arrhythmias/PVCs (exacerbate them).
long PR interval, AV block, scooping of ST-segment, upslope into R wave
inhibit HMG-CoA reductase, mediator in the first step in the biosynthesis of cholesterol. reduced synthesis increases number of LDL receptors (via SREBPs), increasing catabolic rate of LDL and liver extraction of LDL precursors.
major LDL. minor HDL/trigs.
statin kinetics (prodrugs)
lovastatin/simvastatin/atorvastatin/rosuvastatin have active metabolites
cyclosporine, macrolides, anti-fungals. pravastatin is the only one not metabolized by CYP450 enzymes (reduced risk of interactions)
absolute pregnancy (cat X), liver disease
generally well tolerated. myalgia 10%. rare include myositis/rhabdomyolysis, hepatotoxicity. possibly increase glucose.
10-80mg PO qd
10-80mg PO qd
10-80mg PO qd
20-80mg PO qd
5-40mg PO qd
simbastatin/ezetimibe (Vytorin) dose
20-40mg/10mg PO qd
monitor liver enzymes, blood sugar
gemfibrozil, fenofibrate, clofibrate
activate transcription factors (PPARs). reduces production of VLDL and speeds up removal of triglycerides, increases HDL levels (apo A1/A2 expression increased).
major HDL/trigs. minor LDL.
gemfibrozil inhibits glucoronidation of statins (increased liklihood of muscle breakdown/pain with coadministration). Interact with warfarin (potentiate anticoag - monitor INR).
bile acids facilitate fat digestion/absorption, and are normally enterohepatically recycled. sequestrants are large and carry a positive charge, so they bind negatively charged bile acids and are excreeted together. the body needs to create more bile acids (which takes cholesterol) and less fat is absorbed.
major LDL. no HDL. hurt trigs.
never leave GI tract, so are OK to use in disease/pregnancy. reduce absorption of fat-soluble vitamins (A,D,E,K)
hypertriglyceridemia (interruption of enterohepatic recycling increases enzyme activity of phospatidic acid phosphatase, which is involved in triglyceride formation)
bind to negatively charged molecules, so interfere with absorption of thiazides, furosimide, propranolol, digoxin, warfarin, OCPs (can be overcome simply by seperating administration)
GI. rare hyperchloremic acidosis (bile acid resins are chloride salts, can result in increased chloride/decreased bicarb levels)
BAS, 8g powder dissolved in liquid PO TID
most often used in combo with statins because their use alone results in upregulation of HMG-CoA reductase
Nicotinic Acid (a B-complex vitamin)
unknown. does reduce liver synthesis of VLDL.
major HDL/trigs. moderate LDL.
arterial bleeding (can cause slight decrease in platelets/increased prothrombin times), hepatic issues (increased LFTs dose related)
skin flushing, itching, dryness, rash (offset with ASA/ibuprofin 30 min prior). hyperglycemia, hyperuricemia, upper GI distress (offset by taking with food).
nicotinic acid, 0.5-2g PO TID
Cholesterol Absorption Inhibitors drugs
selectively inhibit absorption of cholesterol by small intestine (NPC1L1 transporter) by up to 50%
act on adrinergic receptors. alpha-1 receptors increase IP3 which increases vascular tone (vasoconstriction). beta-1 receptors activate G proteins that increase cAMP levels, resulting in increased myocardial contractile force.
dobutamine (also a vasodilator)
norepinephrine, phenylephrine (pure)
combo pressors and ionotropes (alpha and beta)
I/P kinetics (T1/2)
very short half lives, so IV infusions (or boluses in ACLS)
PDE breaks down cAMP/cGMP. Inhibitors increase cAMP/cGMP, causing increased intracellular Ca. Cardiac tissue = stronger contraction, smooth muscle = decreased afterload due to smooth muscle relaxation. Also theoretically improves diastolic functioning (decreased end diastolic pressure).
PDE-3 kinetics (T1/2)
long half life even though administered IV, can make it tricky to find correct dose (often levels get too high) -- Swang Ganz monitoring of CO can help titrate to correct dose
CHF (increased risk of mortality)
hypotension secondary to vasodilation (can last for hours due to long half life), thrombocytopenia (much less often with milrinone).
PDE-3 vs. beta agonists
PDE-3 not direct positive chronotropes (better for tachy pts/CAD). In CHF b-receptors are frequently down-regulated to to high endogenous chatecholamine compensatory mechanisms, so PDE-3 inhibitors are clinically much stronger.