Dyslipidemia

Mech: bind bile acids -> Stool -> More synth from liver -> Liver cholesterol depletion -> Stimulate LDL receptors -> More LDL taken from blood

Causes: decrease LDL, increase TG and HDL

Use: Adjuvant  w/statin b/c high LDL

SE: bloating, dyspepsia, constipation

Other: Good offset by increase in chol synth, use statin, can also interfere w/absorption of other oral drugs

Dyslipidemia

Mech: Inhib hepatic HMG-CoA reductase (needed for chol synth) -> more LDL receptors expressed -> more LDL removed from blood

Response: Decrease LDL and TG, increase HDL

Use: Primary and secondary prevention of CAD, use in combo

SE: Myopathy (dose related, drugs interactions involved), hepatotoxic

Other: More than just effects on decrease cholesterol (CAD): improve endothelial cell function, enhance plaque stability, reduce inflamm

Dyslipidemia

Ezetimibe

Mech: Inhibit traporter in jejunum via NPC1L1 protein -> decrease cholesterol uptake -> more synth in liver -> more LDL receptors on hepatocytses -> more LDL removed from blood

Response: Decrease LDL and TGs, Increase HDL

Use: Adjuvant to statins

SE: RARE allergic rxn

Other: Bile acid binding resinds inhib absorpt of ezetimibe (use other or other w/a statin)

Mech: Inhib lypolysis of TG via hormone sensitive lipase in fatty tissue -> less FFA transport to liver and hepatic TG synth -> less TG synth via inhibition of esterification of FA in liver

Increase HDL-C via decrease clearance of apoA-1

Response: Decrease LDL, TGs and VDLD, Increase HDL

Use: High triglycerides, high LDL, and low HDL-C levels

SE: Flushing, hepatotoxic, insulin-resistnace, gout, GI

Other: Using niacin + statin = increase in statin-induced myopathy. Uses sustaines-release niacin (Niaspan)

Dyslipidimia

Mech: Binds PPARalpha (nuclear receptor that normally turns on fatty acid synth to make TGs in liver and brown adipose tissue) -> decrease TGs via stim of FA oxidation, increased liporpotein lipase synthesis and decreased apoC-III

Increase HDL-C b/c of PPARalpha stim of apoA-I and apoA-II expression

Response: Decrease LDL and TG, increase HDL

Use: Severe high TGs and low HDLs like in metabolic syndromes (Type II Diabetes)

SE: GI, urticaria (hives), hair loss

Other: Fibrates + Statin = increased statin-induced myopathy (heart disease), LDL increase in some, use is combo but has same SE for myopathy as the niacin/statin combo, good @ decreasing TGs

Angina, Heart Failure (acute decomp)

Mech: Enter cell -> release NO -> activate gualylate cyclase -> cGMP -> vascular smooth M -> vasorelaxation (ESP VEINS RELAX TO PULL BLOOD AWAY FROM HEART)

Plates -> Inhibition of aggregation

Response: DECREASE SYSTEMIC VENOUS CONTRACTION (decrease work, decrease O2 needed, decrease filling P, decrease preload), systemic arterial contraction (decrease work, decrease O2 needed, decrease filling pressure, decrease afterload),  and pulmonary/systemic edema (decrease work), large coronary aretery contraction (increase O2 supply)

Use: under tongue or IV to terminate angina episode OR oral, patch or ointment for prophylaxis (angina)

HF: IV or sublingual for acute decomp, limited w/hydalazine or in acute decomp (because decrease preload)

SE: headache (everyone gets, will go away), flushing, hypotension

Other: Tolerance = major problem thus use intermittantly. Sildenafil and other ED drugs last longer b/c blockage of cGMP metabolism

In Stable angina = veins relax

In Varient angina = reverses spasms

Stable Angina, Hypertension

Mech: competitively block B-ad receptors

Response: decrease HR and contractility, arterial blood pressure (decrease O2 demand), increase coronary flow via increase time in diastole (increase O2 supply)

HT: decrease CO, renin release and SNS to decrease BP (not sure how or why but it does)

Use: orally for chronic prophylaxis of stable, unpredictable in variant

HT: low and high dose works same, younger and middle-age HT's (non-blacks) respond best

SE: cardiac effects, bronchoconstriction, lethargy, fatigue, metnal depression, nightmares, hypoglycemia

Other: use w/caustion in people w/conduction disorders or obstructive lung disease, abrupt withdrawls can cause attacks or other ishemic symptoms (very dangerous rebound effect)

Chronic Stable or Variant Angina, HT

Two classes: dihydropyridine type ("pines": mainly on BV's, little effect on heart) and D,V (strong effect on heart, weak effect on BV's)

Mech: non-comp inhibit Ca++ thru V-sensitive L-type membrane Ca channels, DV also slows channel recovery time

Response: DV: decrease HR and contractility (decrease O2 demand), All: decrease systemic arterial contraction (decrease O2 demand) and coronary artery contraction (increase O2 supply)

Use: Chronic prophylaxis of stable or variant angina

SE: headache, dizzy, flushing, hypotension, leg edema, V = constipation and nausea

Other: careful in conduction issues and in combo w/B-blockers b/c can cause heart failure (VD, but can use dihydro + b-blockers), lots of drug interactions

Stable: decrease work

Variant: coronary A spasm

Chronic prophylaxis of Stable Angina

Mech: 1. Block "late" Na current -> stop increased intracellular Na and Ca caused by ishchemia

2. Block FA oxidation -> use glucose (more efficent) instead

Response: No affect on BP or HR, increase exercise tolerance, decrease anginal attacks

Use: Alone as oral prophylaxis of chronic stable angina OR combo w/nitrates, b-blocks, or Ca channel blocks

SE (rare): dizzy, headache, constipation, nausea

Other: efficacy and tolerability NOT change elderly and comorbid (preexisting) conditions (diabetes, heart fail)

ALMOST ALL PTS CAN TAKE SAFELY!!! (b-block have issues in diabetes and heart fail)

Ischemia -> Na/K ATPase + NHE + increase late Na current -> Na overload -> NCX -> Ca overload -> Mechanical dysfucntion (increase diastolic tension and decrease contractility) electrical issues (arryth) and O2 issue (increase ATP consumption and decreased ATP production)

Ranol: blocks the late Na current which stops the Na overload....YAY!

Ivabradine: block pacemaker current -> decrease HR

Nicorandil: open ATP-sensitive K channels -> coronary dilation

Trimetazidine: inhibit mitochondrial 3-ketoAcyl CoA thiolase -> FA use to carb use for E (more efficient)

Perhexilene: inhib mitochondrial carnitine-palmitoyl-transferase -> FA use to carb use for E

Unstable Angina Thrombosis

Anti-platelet drug

Mech: Irreversibly acetylates COX-I -> blocks TxA2 synth -> less platelet aggregation (lasts 7-10 days b/c need to make more platelets)

Response: PHENOMENAL decrease in risk of death or MI, can see benefits in 1st day of treat!

Use: oral, use low dose to minimize bleeding potential

SE: risk of bleeding, allergy in some

Other: 5-8% show resistance to x-plate effects (have increase risk of SE's)

Unstable Angina Thrombosis

Anti-platelet drug

Mech: inhib ADP binding to receptor -> decrease plate agg and activation

Response: decrease risk of death or MI, early is better

Use: Oral, slow onset (b/c pro-drug), long duration (4-8 days), combo w/aspirin

SE: neutropenia, thrombotic thrombocytopenic purpura, GI bleed (less than aspirin)

Other: Clopidogrel = rapidly replacing ticlopidine b/c quicker onset and less neutropenia.  Some people resistant to clopidogrel.

Unstable Angina Thrombosis (percutaenous coronary interventions)

Anti-Platelet

Mech: prevent fibrinogen mediated cross-liknage via GP IIb/IIIa receptors -> less aggregation

Response: Decrease in risk of death or MI, early is better

Use: IV, short duration of action (use in surg), oral doesn't work, combo w/aspirin and hep

SE: thrombocytopenia, bleeding

Other: best used prior to percutaneous coronary interventions than in unstable angina

Anticoag

Mech: catalyzes inhib of several coag proteases by antithrombin

X-thrombin -> inhib coag factors of intrinsic and common paths (Xa, IXa).  LMWH act on Xa mainly

Response: LMWH > Hepapin @ reducing death or MI in combo w/aspirin in unstable angina

Use: IV (hep) SC (LMWH - more reliable absportion and plasma 1/2 life)

SE: bleeding, thrombocytopenia (less is LMWH)

Other: Resistance forms b/c of differences in concentrations of heparin-binding proteins in plasma or b/c accel clearence

Anti-coags have increased risk of bleeding than x-plates, don't use in pts w/bleeding disorders

X-coag

Mech: synthetic, sulfated pentasaccharide -> binds antithrombin -> selective inhib of Factor Xa

Response: reduce death or MI in ACS (acute coronary syndromes like acute myocardial ischemia) similar to heparins

Use: specific and selective, long 1/2 life, 100% bioavalable (sq) = once-daily x-coat w/out needing to monitor clotting time (unlike close monitor in heparin)

SE: bleeding (less than Heprin)

Other: overall more favorable long-term outcomes than heparin, limited data on cost effectivness (enoxaparin: heparin may still cost less)

X-Coag

Mech: bind catalytic site of thrombin -> stop substrate access

Response: stable levels of x-coag (not yet proven beneficial in unstable angina)

Use: IV, combo w/aspirin or other x-plates

SE: bleeding, unlikly to cause thrombocytopenia (low platelet #)

Other: trials underway to determine efficacy in unstable angina and other ischemic syndromes

Fibrinolytic in MI

Mech: binds fibrin -> activate BOUND plasminogen -> plasmin -> lysis of PREFORMED clot

Response: recanalize (reallow flow) thombotic occlusion, restore coronary flow, reduce infart size, improve myocardial function and survival over short and long terms

Use: IV w/in 2 hrs of MI symptoms

SE: bleeding, stroke (esp w/heparin)

Other: less benefit in old or high BP post MI, more benefits in diabetes post MI

Life saving in acute MI, serious issues if not careful

MI

Mech: stim mu-type opiod receptor in brain and SC

Response: decrease pain, anxiety, restlessness, ANS, venous and artial contraction (all decrease O2 demand)

Use: IV till pain relieved or toxic, some need LARGE cumulative doses but can tolerate them

SE: hypotension, resp depression, vomiting

Other: Also in Unstable angina, pain relief is a primary goal in the setting of acute chest pain due to MI

Acute MI, HT

Ace Ininhibs, ARBs (angiotensin receptor blockers)

Mech: inhibit ACE -> block angiotensin formation  (ACEI)

OR block access of angiotensin to AT-1 type tissue receptor (ARB)

Response: decrease venous and arterial contraction, SNS, and ventricular remodeling (for 2nd prevention), TPR (HT), increase renal Na/H2O excretion

Use: post aspirin, b-blockers and reperfusion therapy (w/in 24 hrs of event)

HT: less effective in blacks and old, use w/diuretic, use ARBs (BEST SE PROFILE OR ALL HT DRUGS, but costs), excellent in protecting against nephropathy (esp diabetics), CAD and HF

SE: hypotension, cough (ACEI), angioedema (ACEI, rare)

Other: benefits clear in old, prior MI, congestive heart failure or other reduced ventricular function pts

HT: no benefic to combining ARB and ACEI in HT but happens alot

2nd prevention of MI

Warfarin and coumadin

Mech: block synth of reduced vit K (needed for synth of factors II, VII, IX and X)

Response: decrease growth of existing thrombi, prevent new thrombi formation

Use: takes days for optimal onset, monitor dose via prothrombin time

SE: bleeding, skin necrosis, MANY drug interactions

Other: lots vit K = less effective, liver diease increase effect

Heparin is too risky in the long term, and this doesn't x-coag in test tube like heparin does.

Chronic and Acute Decompensated Heart Failure, Hypertension

Lasiks

Mech: Reversibly inhibit Na/K/2Cl- cotranport on luminal membrane of epi cells of thick acending limb

Response: increase renal exrection of Na, H2O, K, Ca, Mg, CI and H, relax systemic veins (increase venous capacitance): both cause decrease preload (decreased energy needs), diuretic effect causes decrease in edema (decrease in dyspnea, like in congetive heart failure)

Use: No survival, both chronic heart failure (oral) and acute decomp (IV). Most effective diuretic

HT: pts w/renal insufficiency or resistant HT

SE: volume and K (can get lethal arythmias) depletion, metabolic alkalosis

Other: resistance to diuretic effect happens lots in HF pts, overcome w/higher dose or adding thiazide.  Combo w/K-sparing diuretic (prevent K loss), action potentiated (increased) by renin-angiotensin inhibs (ACEI or ARB), also put on low sodium, high potassium diets, ONLY diuetic used for acute decomp, less effective than thiazide in hypertenseion, use in chronic renal failure w/high BP

Chronic HF, Hypertension

Mech: reversibly inhib Na/Cl cotransport on luminal membraine of distal convoluted tubule

Response: increase renal excretion of Na, H2O, K+, Mg++, Cl- and H+ BUT decrease Ca excretion.  Diuretic effect causes decrease in edema (decrease in dyspnea) and proload (decrease E need).  Lower efficacy than loop diuretics, activation of renin-angiotensin-aldosterone system (limits use in hypertension)

Use: No survival, only chronic stable heart failure (oral), combo w/loop diuretics, wide use as 1st line monotherapy for hypertension (esp blacks and old), low Na diet

SE: volume depletion, K depletion, increase uric acid and glucose (make gout and diabetes worse, not cause them)

Other: combo w/K-sparing diuretic (prevent xs K loss), actions potentiated (increased) w/angiotensin inhib (ACEI or ARB), choice in hypertense w/out comorbid dx, not strong enough in hypertense w/chronic renal fail, second in heart fail to loop diuretics

Chronic Heart Failure (?), Hypertension

Block up pore

Mech: block luminal epithelial cell Na channels in late distal tubule and collecting ducts (don't act on K+ channel or transport but Na and K linked in dist tubule, block Na uptake -> block K+ secretion...Na to urine, K stays in plasma)

Response: increase Na, H2O excretion, decrease Ca, K, Mg and H excretion.  Low efficacy alone.

Use: No survival.  Combo w/loop and/or thiazide diuretics to prevent K loss.

SE: Hyperkalemia (good @ stopping loss of K), GI

Other: Aldosterone antagonists (also K sparing) block insertion of channel into membrane..the two are not the same

 Use in heart fail w/high BP

Heart Failure, Hypertension

"Stop making channels"

Mech: block expression of luminal epithelial cell Na channel in late distal tubule and collecting ducts.  Competitive ant of aldosterone receptor in kidney and other tissues (heart).

Response: increase excretion of Na, H20, Cl, decrease exrection of Ca, K, Mg and H.  Low efficacy alone.  Inhibit ventricular remodeling (slows progression of disease b/c aldosterone stimulate mineralcorticoids in heart and promote fibrous laydown)

HT: monotherapy as eplerone

Use: Yes survival in combo w/standard tx for SEVERE chronic HF (independent of diuretic effects of drug)

HT: comb w/thiazide or loop diuretics to prevent hypokalemia, benefit in HF indicate potential use in HT + HF

SE: hyperkalemia, gynecomastia, impotence (spironolactone) and mestrual irregularities(spironolactone)

Other: why it's help still being worked out, use in people that don't response to other BP drugs (main use in hypertension, more SE's than other K sparing)

Chronic Heart Failure, Hypertense and Ischemia

ACEI's and ARBs (angiotensin receptor blockers)

Mech: Block angiotensin formation via ACEI OR block angiotensin binding to AT-1 type tissue receptor via ARB

Response: decrease venous and arterial contraction, VENTRICULAR REMODELING, SNS, preload and afterload, increase excretion of Na and H2O

Use: yes survival, important in current tx of systolic dysfunction, not as efficient as aldosterone inhib, decrease sx and hospitalizations

SE: hypotension, cough (ACEI) and angioedema (ACEI, rare) ARB have less SE

Other: no benefit to combo ACEI w/ARB, combo w/diuretic

Minor for heart fail

Hydalazine

Mech: unknown (selevite arterial dilator)

Response: decrease arterolar contration -> decrease afterload -> decrease O2 demand (work)

Use: Yes survival in combo w/isosorbide dinitriate in chronic HF, most vasodilators (unless also neurohormonal inhibs) NO to survival

SE: headache, dizzy, tachy, edema 

Other: use w/inability to tolerate ACEI/AR or blacks

Severe Heart Fail, Arryths

Mech: bind alpha subunit of Na/K ATP-ase -> less Na pushed out -> decrease Na/Ca exchanger -> less Ca pumped out during myocyte repol -> more contractility (unique!)

Response: decrease SNS, filling presure, edema, AV conduction, increase CO, PNS, exercise tolerance and PR (b/c slower conduction @ AV node)

Use: low theraputic index (esp in hypokalemia), restrict to serever HF or pts w/A fib, decrease sx and hospital, no survival, ventricular rate control in pts w/heart fail and A fib

SE: anorexia, nausea, vomit, blurry, arryths 

Other: lots interactions, K+ or digoxin x-ab's to tx OD (hard to use), clinical use decrease b/c cause arryth (b/c increase Ca inside myocardial cells)

Acute Decomp HF

Dopamine, Dobutamine

Mech: activatge b-receptors in heart -> increase contractility (inotropic)

ALSO: Dope activated kids -> increase renal blood flow

High dose: stimulate alpha receptors

Response: Increase CO, decrease filling P

Use: Restricted to acute decomp, decrease Sx, maintain circulatory stability, no survival

SE: tachy, aryth

Other: Dobutamin continuous IV several days in severe clinical decomp, pharm tolerance limit efficacy in long term

Acute Decomp HF

Mech: inhib phosphodiesterase type IIIa (SR of cardiac myocytes and vasc smooth M, not ED ones) -> increase cAMP in SR -> increase Ca in cells (similar to digoxin)

Response: increase contractility, rate of relax, CO, decrease venous and arterial contraction (DILATE ARTERIOLES), filling pressure and pulmonary arterial contraction

Use: Acute decomp HF only, decrease Sx, maintain circulatory stability, no survival

SE: hypotense, arrhyth (less so than digoxin)

Other: DRUG OF CHOICE in pts w/b-blockers that need ionotrpic support (like in decomp), chronic consistant therapy decrease survival

Acute Decomb HF

Mech: recomb form of human B-type natriuretic peptide (BNP)

Response: decrease venous (STRONG) and arterial contraction, and filling pressure, increase CO

Use: restricted to acute decomp HF, decrease Sx, maintain circulatory stability, NO survival

SE: hypotense, increased plasma creatine

Other: may be associated w/ risk of xs mortailty and worsening of renal insufficiency

Tachyarrhythmias (Supraventricular and Ventricular)

MEch: Block Na and K channels

Resposne: decrease conduction and automaticity (b/c Na block), increase refractoriness (b/c K block), QRS (slower conduction, b/c Na channel block) and QT (increased refractoriness b/c K channel block)

Use: wide-specturm for both supraventricular and ventricular arrythmias due to re-entry or ectopic automaticity, term A fib or flutter, comb w/stuff to tx serious ventricular arrhyth

Other: decrease ventricular contractility, musc ant, decrease clinical use b/c causes aryths

Ventricular Aryths

Mech: block Na channels (esp w/high HR or in ischemic heart damage)

Response: decrease conduction, automaticity (only in abnormal, not in normal) and QT (NOT BIG CHANGE IN EKG)

Use: Ventricualr aryth b/c re-entry or ectopic automaticity, use against digoxin-induced arryth and long Q-T syndome (mexiletine and phenytoin), good at suppring aryth caused by ischemia (MI)

Other: lidocane MUST be parenterally (not oral), little effect on EKG

Serious ventricualr arryth

Strongest Na Channel Blockers

Mech: block Na channels (slow onset and offset)

Response: decrease CONDUCTION, automaticity, increase QRS (VERY marked)

Use: SERIOUS VENTRICULAR ARRYTHS b/c re-entry, A fib and flutter, AV nodal re-entry tachy

Other: prone to cause arryth, decrease ventricular contractility

Arrhythmias

Nodal Tissue

Mech: Beta blockers

Response: decrease conduction, automaticity (normal and abnormal), increase PR (delay @ AV node)

Use: Arryth w/surg, anastersia, exercise, coke or other xs SNS states, vetnricuar rate control (so vent can slow when atria going nuts) in A fib and flutter, long Q-T syndrome

 Other: decrease sudden cardiac death post MI

Broad specturm anti-arryth

Mech: block K channels

Response: increase refractoriness, QT (*), decrease automaticity and PR (minor)

Use: broad supraventriculoar and ventricular aryths b/c of re-entry or ectopic automaticity, term A fib/flutter, combo w/devices for tx serious ventricualr arryth, DRUG OF CHOICE fo ventricual arryth in cardiac resuscitation, good @ tx arryth in pts w/heart fail (cause less arryths than other drugs)

Other: Amiodarone blocks alpha and beta receptors, Ca and Na channels.  Ibutilide, dofetilide and azimilide for term A fib/flut

Arrythmias

Nodal Tissue, Like Class II

Mech: block L-type Ca channel

Response: Decrease AV conduction, and automaticity, increase PR (delay @ AV node)

Use: AV nodal re-entry tachy, VENTRICULAR RATE CONTROL in A fib/flutter

Other: on EKG look liek B-blocker

 Aryth

Mech: Open K channels -> decrease intracellular cAMP via inhib adenylate cyclase

Response: Decrease AV conduction and sinus node rate, increase PR (longer conduction @ AV node)

Use: AV nodal re-entry tachy (can mistake for anxiety attack)

Other: SHORT DURATION (acute), IV only

Renin Angiotensin Inhibitor for HT

Mech: block renin enzyme -> no formation of angiotensin I or II

Response: decrease angiotensin II actions, venous and arterial contraction, SNS, TPR

Increase renal Na/H2O excretion

Use: less in blacks, STRONGLY better w/diuretic, additive w/ACEI or ARB but alone has same efficacy as either of the other two alone

SE: mild, short lived, diarrhea in some, allergic rx rare but need withdrawl, Not in preggers

Other: Expensive and new/unproven