Cardiology

Question 1

Atropine

Answer 1

Blockade of muscarinic receptors.

Minimal stimulant effects on CNS.

Cardiovascular: SA node is very sensitive. Can cause tachycardia by blockade of vagal slowing. Reduced PR interval by AV node muscarinic receptors.

MI causes refelex vagal discharge which depresses SA or AV node to impair cardiac output. Atropine can be used.

Adverse: mydriasis, cycloplegia, others from muscarinic blockade

Question 2

Ganglion-blocking drugs

Answer 2

Tetraethylammonium, Hexamethonium, Mecamylamine, Trimethaphan.

Trimethaphan and hexamethonium impair transmission by competing with ACh for nicotinic sites, or blocks channel.

Use of ganglionic antagonists in treating hypertension/ autonomic hyperreflexia: Blood vessels have sympathetic innervation causing them to constric and cause a decrease in arteriolar and vasomotor tone. Using these drugs, this constriction is inhibited and so blood pressure will be lowered.

Diminished contractility and b/c SA node is dominated by parasympathetic system, tachycardia.

Question 3

Epinephrine

Answer 3

(α1=α2=β1=β2) Adrenergic Receptor agonist

Effects: increases BP (α1), increases HR (β1 direct effect, β2 blocks vegal reflex), relative decrease in diastolic BP (β2 on skeletal muscle causing vasodilation)

CI: acute angle glaucoma, pregnancy

Kinetics: metabolize by COMT and MAO

Epinephrine Reversal: Pretreatment with α antagonist converts an epinephrine infusion from a pressor response to a depressor response. (ie, β2 dilation predominates)

Note: all direct adrenergic agonists can cause angina, MI, and arrhythmias; Released from adrenal medulla endogenously

Question 4

Norepinephrine

Answer 4

(α1=α2=β1>>β2) Adrenergic Receptor agonist

Uses: emergency hypotension; eg: to maintain coronary or cerebral flow (NOT C/I in closed angle glaucoma)

Effects: increases BP (α1), decrease HR (net effect of β1and vagal reflex); increase contractility (β1)

Kinetics: metabolized by COMT and MAO
C/I: pregnancy

α1: vascular SM (Gq; increase IP3/DAG, [Ca]i)
α2: presynaptic and in CNS (Gi; decrease cAMP)
β1: heart and juxtaglomerular cells (Gs; increase cAMP)
β2: vascular SM (in skeletal muscle & heart) and bronchial SM (Gs; increase cAMP)

Question 5

Isoproterenol

Answer 5

(β1=β2>>α) Adrenergic Receptor agonist

Uses: cardiogenic shock; asthma; AV block

CI: heart disease

Effects: increase HR, increase Contractility, decrease BP (marked increase CO)
 Potent vasodilation (β2), increase pulse pressure (contractility) despite decrease BP

Question 6

Beta selective adrenergic agonists

Answer 6

Isoproterenol (B₁=B₂), albuterol (B₂), salmeterol, dobutamine (B₁₎

Isoproterenol’s net effect is to maintain or slightly increase systolic pressure and to lower diastolic pressure, decreasing mean blood pressure. It has positive chronotropic and inotropic actions.

Dobutamine is used for a cardiac stress test. It augments cardiac contractility and promotes coronary and systemic vasodilation, increasing HR.

Question 7

Treatment of Hypertension (alpha antagonists/ beta antagonists)

Answer 7

Using a pure alpha₁ antagonist like Prazosin is better treatment for hypertension. alpha₂ antagonist cause net release of NE which causes tachycardia.

Beta-blocking drugs chronically lower blood pressure in hypertensive patients, treatment of angina and chronic heart failure, and following MI.

Causes a rise in peripheral resistance acutely in nonhypertensive patients.

Beta antagonists can treat ischemicheart disease, cardiac arrhythmias (supraventricular, ventricular, atrial flutter, A fib), and heart failure

Question 8

Labetalol

Answer 8

Mixed antagonist for adrenoceptor

alpha₁-selective and B-antagonistic effects.

Used for hypertensive emergencies and treating hypertension of pheochromacytoma

Less tachycardia seen compared with phentolamine

Question 9

Propanolol, Metoprolol, Atenolol

Answer 9

Propanolol (B₁=B₂), Metoprolol/ Atenolol (B₁>>>B₂) (CI in asthmatics)

Metoprolol is an inverse agonist. Metoprolol has shown a reduction in mortality in patients with stable severe heart failure.

Propanolol is the prototype but comes with toxicities: sedation, vivid dreams, depression, worsening of asthma, bradycardia, fatigue, cold hands; has been replaced by Metoprolog and Atenolol

Propanolol can treat Hypertension: less reflex tachycardia in comparison to direct vasodilators. MOA mainly from depression the renin-angiotensin-aldosterone system.

Toxicity of propanolol: withdrawal causes nervousness, tachycardia, increase intensity of angina, increase BP.

Metoprolol is as effective as propanolol in inhibiting beta 1, but way less potent in beta 2. Better agent in treating those with asthma, diabetes, peripheral vascular disease.

Atenolol is less effective in treating hypertension due to the lack of maintaining adequate blood levels of the drug.

Beta-Blockers reduce mortality following an MI

Question 10

Sildenafil and more NO info

Answer 10

Sildenafil – enhances c-GMP from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum.

NO – elevates cGMP in vascular smooth muscle; vasodilator; decrease pulm. resist. when inhaled; Tx for pulmonary HTN; SE: methemoglobinemia.
L-NMMA – comp. inhibitor binding to arginine-binding site in NO synthase
Superoxide Dismutase – NO scavenger prolonging DOA by protecting against NO inactivation from superoxide.
Methylene Blue – soluble guanylate cyclase inhibitor that prevents the action of NO and can reverse NO induced hypotension.
L-Arginine is substrate for eNOS (activated by Ca-Calmodulin complex) that forms NO and L-Citrulline.

Question 11

Nitric Oxide

Answer 11

Synthesis: made from 3 isoenzymes of NO synthase

1. nNOS (neuronal) 2. iNOS (inducible) 3. eNOS (endothelial)

NO made from arginine into citrulline using O₂ and NADPH dependent rxn. Unlike the other isoenzymes, iNOS is not regulated by calcium. the others are constitutively active.

vasodilator of vascular smooth muscle tone, antithrombotic

ACh and bradykinin cause NO production through the release of intracellular calcium, activiating calmodulin and eNOS.

cGMP gets made from GTP via guanylyl cyclase

In CNS, NO made when NMDA receptors are stimulated causing influx of calcium. Too much is deleterious and NOS inhibitors are frequently used to prevent damage.

Noradrenergic, noncholinergic (NANC) neurons are widely distributed in peripheral tissues. NO is a mediator of these neurons actions, and some even seem to release NO.

NO promotes relaxation of smooth muscle in corpora cavernosa of penile tissue causing erection.

Question 12

Hydrochlorothiazide

Answer 12

Diuretic (thiazide)

Uses: anti-HTN, heart failure, nephrolithiasis, nephrogenic diabetes insipidus

Effects: acts on distal tubule to inhibit NaCl reabsorption (NCC block); enhances Ca reabsorption; decrease volume (decrease BP)

SE: hyperlipidemia, hyponatremia, hypokalemia (most common adverse effect of diuretics), allergic reaction (sulfonamide), weakness, fatigue, paresthesias, gout, alkalosis

CI: hepatic cirrhosis, borderline renal failure, NSAIDs
Better than loops for chronic HTN

Diuretics are often combined with beta blockers

Question 13

Furosemide

Answer 13

*Via study guide: diuretic agents are included in this phase to introduce their use for hypertension, details will be covered in Renal phase.

Diuretic (Loop)
Uses: severe HTN in presence of other drugs causing Na retention, acute pulmonary edema, acute hypercalcemia, hyperkalemia, edema, acute renal failure, anion overdose, acute and chronic heart failure in combo with ACE inhibitors and other therapies, cirrhosis

Effects: inhibition of NKCC2 (Na/K/2Cl transporter); inhibits NaCl reabsorption in TAL; induces renal synthesis of PG

SE: hypokalemia (most common adverse effect of diuretics), ototoxicity, hyperuricemia, hypomagnesemia, gout; [not for chronic use]; hypovolemia

CI: sulfonamide allergy, hepatic cirrhosis, borderline renal failure, NSAIDs
Kinetics: 4-6 hrs DOA

Question 14

Methyldopa

Answer 14

(α2>α1>>β) Adrenergic Receptor agonist

Uses: Central acting HTN; HTN (mainly used for treatment during pregnancy)

MOA: decreases sympathetic outflow from vasopressor centers in brainstem; Stimulates presynaptic α2 receptors to decreases NE release. (also it replaces NE in vesicles; long DOA)

Effects: decreases BP (lowers peripheral vascular resistance), decreases HR, decreases Renal vascular resistance, reflexes intact

SE: orthostatic hypotension very rare, sedation (most common undesireable effect), nightmares, impaired concentration, lactation, + Coombs, EPS, vertigo

CI: tricyclics, depression

L-Dopa analog converted to α-Methyl NE and α-Methyl DA

Kinetics: Action begins 4-6 hrs after dose and works until 24 hrs after dose.

Question 15

Clonidine

Answer 15

(α2>α1>>β) Adrenergic Receptor agonist

Uses: Central acting HTN; treat opioid withdrawal; HTN; neuropathic pain; opiod detox; sleep hyperhidrosis; anesthetic use

MOA: decreases sympathetic outflow from vasopressor centers in brainstem; Stimulates presynaptic α2 receptors to decrease NE release. Lowers HR and CO more than methyldopa.

Effects: after brief increase in BP, there is a decrease in BP (especially when high sympathetic tone was present), decreases HR (more than methyldopa), decreases renal vascular resistance; venodilation

SE: withdrawal causes life-threatening HTN; dry mouth, sedation; postural hypotension very rare

CI: tricyclics, depression

Question 16

Guanethidine

Answer 16

Adrenergic Neuron Blocker

Uses: HTN

Effects: Blocks NE release from SNS by displacing NE in vesicles resulting in a gradual depletion. (Doesn’t enter CNS but causes sympathoplegia); decreases HR, CO, BP. compensatory Na+ and H2O retention. No CNS effects (too polar)

SE: pharmacologic sympathectomy: postural hypotension, diarrhea, impaired ejaculation; exercise hypotension
In high doses can cause profound sympathoplegia

CI: cocaine, amphetamine, tricyclics, phenoxybenzamine; pheochromocytoma
Similar to Guanadrel
Kinetics: half-life 5 days

Question 17

Reserpine

Answer 17

Adrenergic Neuron Blocker

Uses: moderate HTN, but not used due to adverse effects

Effects: irreversible VMAT inhibitor; enters CNS and depletes NE, E, DA, 5-HT

decreases BP (decreases CO/PVR but reflexes intact)

SE: sedation, mental depression, EPS, diarrhea, cramps, parkinsonism; depletion of cerebral amines
Low doses: orthostatic hypotension

CI: PUD, mental depression

Question 18

Pindolol

Answer 18

(β1=β2) Adrenergic Receptor Antagonist

Uses: HTN (especially patients with PVD or bradyarrhythmias)

Effects: partial agonists actually; less of decrease HR/CO than other β blockers; decrease BP (TPR); potentiate antidepressants
SE: fatigue, vivid dreams, cold hands

Question 19

Prazosin

Answer 19

(α1>>α2) Adrenergic Receptor Antagonist

Uses: HTN (especially in combo w/ β blocker), benign prostatic hyperplasia

Effects: decreases BP (dilation of resistance and capacitance vessels; more pronounced when in the upright position); some reflex tachycardia (less than nonselective α antagonists (phentolamine) because NE negative feedback on α2)

SE: Orthostatic hypotension(less than nonselective α antagonists), increases HDLs, salt and water retention, dizziness, headache, ANA development

Kinetics: half-life= 3 hours; extensive 1st pass hepatic metabolism; oral bioavailability = 50%

Question 20

Terazosin

Answer 20

(α1>>α2) Adrenergic Receptor Antagonist
Reversible blocker

Uses: HTN, benign prostatic hyperplasia

Effects: not much reflex tachycardia; decreases BP (dilation of resistance and capacitance vessels; more pronounced when in the upright position)

SE: Orthostatic hypotension upon first dose

Kinetics: half-life= longer than Prazosin; extensive 1st pass hepatic metabolism
High bioavailability
Half life 9-12 hrs

Question 21

Hydralazine

Answer 21

Vasodilator

Uses: Anti-HTN; Heart failure (used with nitrates); fatigue due to low LV output

Effects: arteriolar dilation (not veins); decreases TPR (lowers BP), but compensatory tachycardia and water retention may counteract this (usually given with diuretic and β blocker); lots of NO release

SE: headache, nausea, anorexia, palpitations, sweating, flushing; no renal toxicity

Kinetics: metabolized by acetylation (acetylators are C/I and there is an increase incidence of SLE-like syndrome in pt’s who slowly acetylate hydralazine); rapid liver metabolism
CI: IHD (since drug causes tach)

effective in heart failure by reducing preload (venodilation) or afterload (arteriolar dilation); reduces damaging remodeling of the heart.

Question 22

Minoxidil

Answer 22

Vasodilator

Uses: Anti-HTN (good for pt’s w/ renal failure & severe HTN); stimulate hair growth (Rogaine)

Effects: dilates arterioles but not veins. increase K+ permeability (effects SM of arterioles only); lowers TPR (&BP) with increase HR and Na+ retention (reflex)

SE: Tachycardia, palpitations, angina, edema (must be given with diuretic and β blocker); headache; sweating; hypertrichosis

Half life of 4 hours
Taken orally

Question 23

Sodium Nitroprusside

Answer 23

Vasodilator

Uses: hypertensive emergency; Severe heart failure (decreased afterload)

Effects: activates guanylyl cyclase (arterial and venous dilation); lowers PVR, VR, BP (increase CO in heart failure); dilates arterioles and veins;

SE: methemoglobinemia, metabolic acidosis, CNS Sx’s (cyanide accumulation); excessive hypotension; arrhythmias; death; defect in cyanide metabolism → give cyanocobalamin to facilitate breakdown; thiocynate toxicity → weakness, disorientation, psychosis, muscle spasms, and convulsions

Kinetics: rapid effects; kidney excretion
Sensitive to light; must be made fresh; given IV continuously

Question 24

Diazoxide

Answer 24

Vasodilator

Uses: Anti-HTN; hypoglycemia secondary to insulinoma

Effects: prevents vascular SM contractions (opens K+ channels); arteriolar dilator; lowers TPR (&BP) with reflex increase HR, CO and tachycardia
Effects greater if pretreated with β blocker to prevent reflex tachycardia
Long lasting parenterally; administered for HTN emergencies
Therapeutic effect within 5 min and injection lasts for 4-12 hours

SE: excessive hypotension (stroke, MI), angina, ECG ischemia, cardiac failure, hyperglycemia (inhibits insulin release); severe hypotension in renal fail patients

Question 25

Calcium Channel Blockers

Answer 25

antianginal, antiarrhymia, decreases peripheral resistance and blood pressure. MOA: inhibits calcium influx into arterial smooth muscle cells. Verapamil, ditiazem, dihydropyridine family are all equally effective in lowering blood pressure. Clevidipine is newer and IV use only. Dihydropyridine agents are more selective as vasodilators and less cardiac depressants. Verapamil has greates cardiac depressant effects and may decrease HR and CO. SE: may increase risk of MI

Question 26

Catopril

Answer 26

ACE Inhibitor Uses: HTN [especially w/ comorbidities: IHD, renal failure (decreases proteinuria), DM]; Heart failure, post-MI Effects: lowers BP (&PVR); no effect on CO/HR; effectiveness independent of Renin levels; no reflex sympathetics (ie, it resets baroreceptors); vasodilation (bradykinin) SE: neutropenia, proteinuria (pts w/ renal insufficiency); hypotension (esp. with low volume), acute renal failure (pt’s with bilateral renal artery stenosis), hyperkalemia, **dry cough (bradykinin; most common SE and not associated with ARBs)**, taste change, drug fever, angioedema, skin rash CI: pregnancy Kinetics: excretion by kidneys; monitor K+

Question 27

Angiotensin Receptor-blocking agents

Answer 27

Losartan, valsartan: blocks AT₁ receptor for angiotensin ll No effect on bradykinin metabolism CI: pregancy SE: similar to ACE inhibitors

Question 28

Aliskiren

Answer 28

Renin cleaves angiotensinogen into angiotensin l (rate limiting step) Renin Inhibitor Uses: HTN (diuretics often used in combination;No feedback inhibition from ANG ll; both of these results in increase renin levels); arteriolar dilation; decreased aldosterone secretion; increased Na+ and water secretion Effects: Blocks enzymatic conversion of ANG to ANG I Dose dependent Overcome Renin feedback loop CI: pregnancy

Question 29

Drugs affecting Kallikrein-Kinin system

Answer 29

**Icatibant:** beta 2 receptor antagonist (similar affinity as bradykinin) Use: treatment of hereditary angiodema, airway disease, thermal injury, ascites, pancreatitis **Aprotinin, Ecallantide**: blocks synthesis of Kinin Use: hereditary angioedema \*Actions of kinins can be enhanced with ACE inhibitors

Question 30

Inhibitors of Endothelin synthesis and action

Answer 30

ET_A and ET_B can be blocked **Bosentan** is a nonselective receptor blocker. More selective blockers have been made: **ambrisentan, sitaxsentan** Formation of endothelins can be blocked by inhibiting endothelin converting enzyme with phosphoramidon effects: vasodilation and decreases arterial pressure

Question 31

Procainamide

Answer 31

Class 1A Antiarrhythmic Uses: Atrial and ventricular arrhythmias; Long Term therapy avoided ; 2nd choice after lidocaine for treatment of sustained ventricular arrhythmias associated with acute MI MOA: Blocks **active** Na+ channels; Nonspecific K+ channel blockade; Ganglion blocking properties Renal excretion (C/I with renal failure) Effects: Slows AP upstroke (Na+); Slows conduction(Na+); Prolongs QRS (Na+); Prolongs QT interval; Prolongs AP duration (K+) therefore acting like a class 3 drug; Directly depressant effect on SA/AV node (only slightly countered by drug-induced vagal block); decreases PVR (Gang-Block); raises refractory period in normal & depolarized cells S.E: Hypotension due to lowered PVR (primarily w/ IV infusion), excessive AP prolongation, QT interval prolongation, torsade de pointes(from elevated NAPA w/ renal failure), syncope, new arrhythmias, SLE-like syndrome(1/3 dev.), serological abnormalities

Question 32

Quinidine

Answer 32

Class 1A Antiarrhythmic Uses: Used occasionally to maintain normal sinus rhythm w/ atrial fib / flutter; restricted to patients with normal (but arrhythmic) hearts MOA: Blocks Na+ channels; Nonspecific K+ channel blockade; More pronounced cardiac anti-muscarinic effects; hepatic metabolism Effects: Prolongs AP upstroke (Na+); Slows conduction (Na+); Prolongs QRS (Na+); Prolongs QT interval; Prolongs AP duration (K+); increases refractory period in normal & depolarized cells; blocks ganglionic cells via anticholinergic activity (more than procainamide) S.E: Excessive QT interval prolongation, torsade de pointes, excessive Na+ block = slowed conduction throughout the heart; GI side effects (1/3) Toxicities: headache, dizziness, tinnitus (cinchonism); “terrible rash”

Question 33

Disopyramide

Answer 33

Class 1A Antiarrhythmic Uses: Given with a drug that slows AV conduction (due to ↑antimuscarinic activity); used to treat ventricular arrhythmias (although can treat SV arrhythmias, not approved in US) MOA: Blocks Na+ channels; Nonspecific K+ channel blockade; Very pronounced cardiac anti-muscarinic effects (atropine-like); longer duration of action than procainamide Effects: Slows AP upstroke (Na+); Slows conduction(Na+); Prolongs QRS (Na+); Prolongs QT interval; Prolongs AP duration (K+); increases refractory period in normal & depolarized cells; prevent reentry; S.E: DUMBELSS CI: patients with heart failure; glaucoma

Question 34

Lidocaine

Answer 34

Class 1B Antiarrhythmic Uses: Arrhythmias associated with MI; agent of choice for ventricular tach to prevent vfib after cardioversion in the setting of ischemia; local anesthetic Extensive 1st pass hepatic metabolism (must be given parenterally) (t1/2= 1-2hrs). Class B have rapid dissociation kinetics MOA: Blocks activated & inactivated (ensures block on Purkinje / ventricular cells w/ long AP) Na+ channels; shortens AP Effects: Selective depression of conduction in depolarized cells; decrease refrac period in normal; increase refrac period in depolarized; decreases pacemaker activity; use dependent S.E: Least cardiotoxic; may worsen impaired conduction, cause SA node arrest; neuro side effects (parasthesia, tremor, slurred speech, convulsions)

Question 35

Mexiletine

Answer 35

Class 1B Antiarrhythmic Uses: Ventricular arrhythmias; chronic pain (due to diabetic neuropathy, nerve injury) MOA: Orally active form of lidocaine; Blocks activated & inactivated (ensures block on Purkinje / ventricular cells w/ long AP) Na+ channels; shortens AP due to blocking window currents T1/2= 8-20 hours Effects: Selective depression of conduction in depolarized cells; decreases refrac period in normal; increases refrac period in depol; decreases pacemaker activity; use dependent S.E: Neurologic SE (tremor, blurred vision, lethargy); nausea

Question 36

Flecainide

Answer 36

Class 1C Antiarrhythmic Uses: Use in refractory ventricular tachyarrhythmias (very effective at suppressing PVCs); supraventricular arrhythmias (Afib); Paroxysmal Atril Fib (pill in the pocket) MOA: Potent Na+ and K+ channel blocker w/ slow unblock kinetics; don’t affect AP duration; blocks Na channel in any state; no muscarinic effects Half-life of 20 hours; hepatic and liver metabolism Effects: increases refractory period in depolarized cells; decreases pacemaker activity; lessens PR interval; Prolongs QRS; does not prolong QT S.E: May exacerbate arrhythmias in patients w/ preexist vent tachyarrhythmias. (proarrhythmic in 15% of cases) CI: post MI & ventricular ectopy

Question 37

Propafenone

Answer 37

Class 1C Antiarrhythmic Uses: Supraventricular arrhythmias MOA: Potent Na+ and K+ channel blocker w/ slow unblock kinetics; Weak β blocker (similar structurally to propanol); no change in AP duration Hepatic metabolism T1/2 = 5-7hr Effects: increase refractory period in normal & depol cells; decrease pacemaker activity; increase AV node refrac period; Prolongs QRS; increase PR interval S.E: Metallic taste, constipation, arrhythmia exacerbation

Question 38

Moricizine

Answer 38

Class 1C Antiarrhythmic Uses: Was used for Ventricular arrhythmias MOA: Potent Na+ channel blocker; Multiple metabolites (may be active); don’t affect AP duration Effects: lowers refrac period in normal and depolarized cells; lowers pacemaker activity; Prolongs PT interval; Prolongs QR; decrease upstroke of AP; increases refractory period of AV node S.E: Dizziness & nausea

Question 39

Beta-adrenoceptor-blocking drugs (class 2 antiarrhythmia)

Answer 39

Propanolol: prolong cardiac action potential. Can prevent recurrent infarction and sudden death in patients recovering from acute MI Esmolol: short-acting beta blocker used for introperative and other acute arrhythmias Sotalol: nonselective beta blocker; prolongs action potential.

Question 40

Amiodarone

Answer 40

Class 3 Antiarrhythmic Uses: Serious ventricular arrhythmias; also effective for supraventricular arrhythmias (Afib); not associated with an increase in mortality for patients with CAD or heart failure IV = QT prolonging, bradycardia, AV block MOA: Blocks I_Kr; Blocks I_Ks with chronic admin; Blocks inactivated Na channels increases upstroke duration; Weak adrenergic & calcium channel blocking actions; CYP3A4 substrate; Beta-receptor blocker Effects: Markedly prolongs AP duration; Prolongs QT interval; decreases HR, AV node conduction; Peripheral vasodilation; No reverse use-dependent action; suppress automaticity; interrupt reentry circuits S.E: Bradycardia, heart block(in pts w/ preexisting SA/AV node issues); pulm fibrosis, abnormal liver func. tests, hepatitis, skin discoloration (gray/blue), hypo/hyperthyroidism, optic neuritis; lowered incidence Torsades de pointes; Very long t1/2

Question 41

Dronedarone

Answer 41

structural analog of amiodarone; designed to eliminate action of parent drug on thyroxine metabolism and to modify the half life of the drug (24 hours) Better absorption with food Toxicities: liver toxicity, increased risk of death, stroke, heart failure, increase mortality in those with advanced heart failure. Restores sinus rhythm in some patients with atrial fibrillation. Reduces ventricular rate. MOA: blocks potassium, Na, Ca currents. Beta blocker

Question 42

Vernakalant

Answer 42

Class 3 antiarrhythmic Multi-ion channel blocker developed for treating atrial fibrillation. MOA: prolongs atrial effective refractory period and slows conduction over AV node. Ventricular refractory period is unchanged; APD prolonging effect is atrial specific fast recovery from block; half life of 2 hours; CYP2D6 metabolism Toxicity: dysgeusia (taste disturbance), sneezing, paresthesia, cough, hypotension

Question 43

Sotalol

Answer 43

(β) Adrenergic Receptor Antagonist Class 2 and Class 3 Antiarrhythmic Uses: Life threatening ventricular arrhythmias, maintenance of sinus rhythm in afib; SV and ventricular arrhythmias in kids MOA: blocks K+ channels and beta receptors; AP prolonged Kidney excretion; Duration: 7 hours Effects: decreases Contractility , CO,BP; HR S.E: Dose related Torsades de Pointes; Cardiac depression

Question 44

Dofetilide

Answer 44

Class 3 Use: maintenance of normal sinus rhythm in those with A fib MOA: APD prolonged; blockade of rapid component of delayed rectifier K current. Blockade increases in hypokalemia 100% bioavailable QT prolonging effects are related to plasma concentration so this needs to be monitored carefully. **Ibutiide:** similar drug used more so for atrial flutter. adverse: prolong QT interval and tosades de pointes

Question 45

Verapamil

Answer 45

(L-type) Ca Channel Blocker (Non-Dihydropyridine) class 4 antiarrhythmia Uses: Angina, HTN, antiarrythmic (SV reentry tachycardia, atrial fib/flutter), migraine Effects: decrease BP, contractility, HR (nonspecific anti-adrenergic), decrease AV nodal conduction; modest Na+ channel block; blocks P-glycoprotein; peripheral dilation SE: serious cardiac depression (cardiac arrest, bradycardia, AV block, heart failure); flushing, dizziness, nausea; constipation edema; hypotension CI: β blockers 3-6 hour half life 6 hour duration

Question 46

Diltiazem

Answer 46

Ca2+ Channel Blocker Uses: Class 4 Antiarrhythmic; management of supraventricular arrhythmias; rate control in Afib MOA: Non-dihydropyridine; Blocks L-type Ca2+ channel (binds diltiazem receptor); Slight Na+ channel block; Nonspecific antiadrenergic effect Effects: decrease Contractility (dose-dependent) = may lower CO, HR (nonspecific adrenergic effect); prolonged AV nodal conduction (moderate effect) and prolonged effective refractory period; slow SA node but hypotensive reflex causes small increase in SA rate S.E: Hypotension (women more susceptible), serious cardiac depression Rate control in AFib; Angina, HTN, Raynaud’s phenomenon, arrhythmias (SV tachyarrhythmias) C/I: β blockers (can cause AV block)

Question 47

Adenosine

Answer 47

Antiarrhythmic Uses: Drug of choice for conversion of Paroxysmal SVT to sinus rhythm; Used for drug-induced stress test (used for atrial arrhythmias); good for reentry tachycardia; acute nodal tachycardia MOA: Naturally occurring nucleoside; activates inward rectifier K+ currents; inhibits Ca2+ current; given IV bolus → directly inhibits AV node conduction Half-life of 10 sec Effects: Marked hyperpolarization; Suppression of calcium-dependent AP; Inhibits AV node conduction; increases AV node refractory period; Little SA node effect S.E: Flushing, SOB, high-grade AV block, atrial fib, headache, hypotension, nausea, parasthesia; Not as effective in presence of caffeine/theophylline

Question 48

Magnesium

Answer 48

antiarrhythmic effects in some patients with normal serum Mg levels. MOA unknown but may influence Na/ K ATPase, Na channels, K channels, Ca channels. Indicated in patients with digitalis induced arrhythmias if hypomagnesia is present; used for torsades de pointes IV

Question 49

Potassium

Answer 49

Increasing serum K: 1. resting potential depolarizing action 2. Membrane potential stabilizing action (increasing K permeability) Hypokalemia results in an increased risk of early and delayed afterdepolarizations. Hyperkalemia depress ectopic pacemakers and slows down conduction

Question 50

Statins- General

Answer 50

Structural analogs of HMG-CoA **which are most effective in reducing LDL**. Works through inhibition of HMG-CoA reductase, the first committed step of sterol biosynthesis. This leads to an increase in high-affinity LDL receptors, and increased extraction and catabolism of LDL Also decrease oxidative stress and vascular inflammation with increased stability of atherosclerotic lesions. All have high first-pass extraction by the liver; also the major effect is on the liver **Obj15.112**: statins reduce prenylation of Rho and Rab proteins. Prenylated Rho activates Rho kinase, which mediates a number of mechanisms in vascular biology. These **pleiotropic effects** of statins have been linked to a reduction in coronary events that is more rapid than changes in arterial plaque morphology. Likewise, decreased prenylation of Rab reduces accumulation of AB proteins in neurons, potentially helping with Alzheimer's.

Question 51

Statins- Therapeutic Uses and Toxicity

Answer 51

Should **not** be used in pregnant women. Use in children is restricted to patients with familial hypercholesterolemia or familial combined hyperlipidemia. Should be given at night, as most cholesterol synthesis occurs at night. Food enhances absorption Can increase serum aminotransferase activity. Make sure activity doesn't consistently stay elevated to three times normal. CK elevation and myopathy occur in some patients. Some are broken down by CYP3A4, avoid drugs that interact with this

Question 52

Statins- Specific Drugs

Answer 52

**Lovastatin** is an inactive lactone prodrug hydrolyzed in the GI tract to the active form. **Pravastatin** has an open, active lactone ring. Nearly as potent as lovastatin on a mass basis. Absorption is ***not*** enhanced by food. The dose-response curve tends to level off in the upper part of the dosage range. Broken down by "other pathways" including sulfation. **Atorvastatin and rosuvastatin** are fluorine-containing congeners that are active as given. Neither are given at night, probably due to their longer half lives (14 and 19 hrs, respectively)

Question 53

Niacin (Nicotinic Acid)

Answer 53

Decreases VLDL, LDL, and Lp(a) *(the only agent to do so)* in most patients, as well as an increases HDL. Inhibits VLDL secretion, and therefore production of LDL. Has no effect on bile acid production. It does decrease catabolism of HDL, reduce fibrinogen levels, and increase tPA levels. Often given in combination with a resin or reductase inhibitor. A harmless flushing redness and warmth occurs after each dose. Should be avoided with patients with severe peptic disease. Hyperuricemia occurs in some patients (allopurinol can be given to avoid gout precipitation) Liver functions should be monitored; reversible elevations of aminotransferases can occur. May increase insulin resistance in some diabetic patients

Question 54

Fibric Acid Derivatives

Answer 54

**Gemfibrozil and Fenofibrate** (differences between them are pretty vague) Decrease levels of VLDL. Fibrates serve as ligands for nuclear transcription receptor PPAR-alpha, causing up-regulation of lipoprotein lipase (LPL), apo A-I, and apo A-II, as well as down-regulating apo C-III (inhibitor of lipolysis) Only modest reductions of LDL occur in most patients. Useful in hypertriglyceridemias in which VLDLs predominate and in dysbetalipoporteinemia Fibrates should be avoided in patients with hepatic or renal disfuntion. They increase risk of cholesterol gallstones. Fenofibrate is the fibrate of choice for use in combination with a statin Gemfibrozil: absorption improved with food.

Question 55

Bile Acid-Binding Resins

Answer 55

**Colestipol** and **Cholestyramine** (literally almost no differentiation in Katzung) Useful only for isolated increases in LDL. In patients who also have hypertriglyceridemia, VLDL levels may be further increased during treatment with resins. Insoluble, bind bile acids in the intestine and prevent resportion (they aren't absorbed at all). This leads to increase cholesterol use in bile production via an upregulation of LDL receptors (useless in patients with homozygous familial hypercholesterolemia who have no functioning receptors) Used to treat primary hypercholesterolemia (20% maximal reduction). May also be used to relieve pruritus in patients with cholestasis and bile salt accumulation. Could also be used to block digitalis absorption in cases of digitalis toxicity. Taken with meals. Can lead to constipation and bloating. Should be avoided with diverticulitis. Malabsorption of vitamin K can occur, leading to the need to measure prothrombin time frequently in patients taking resins and anticoagulants. Binds to a ton of drugs in the intestines. Give other drugs an hour before or two hours after the resins

Question 56

Ezetimibe

Answer 56

Inhibits intestinal absorption of phytosterols and cholesterol. Used primarily to reduce LDL levels. 80% of the drug is excreted in the poop (Matt Pearce) Affects intestinal absorption of both ingested sterols as well as bile salts by targetting NPC1L1, a transport protein. Minimal increases in HDL Synergistic with reductase inhibitors, producing 25% greater decrements in LDL cholesterol than with a reductase inhibitor alone.

Question 57

When to Treat with Drug Combinations

Answer 57

1. when VLDL levels are significantly increased during treatment of hypercholesterolemia with a resin 2. when LDL and VLDL levels are both elevated initially 3. when LDL or VLDL levels are not normalized with a single agent 4. when an elevated level of Lp (a) or an HDL deficiency coexsits with other hyperlipidemias.

Question 58

Coronary Artery Disease

Answer 58

Most common cause of angina is atheromatous obstruction of large coronary vessels (CAD). Inadequate blood flow with CAD results in effort angina, aka classic angina. Transient spasms of portions of these vessels, with underlying atheromas, causes myocardial ischemia and pain (vasospastic or variant angina). Variant angina is also called **Prinzmetal** angina

Question 59

Nitroglycerin

Answer 59

Nitrates and Nitrites Uses: angina, myocardial ischemia Effects: Denitrated to NO which raises levels of cGMP (increased PGE2 or PGI2 and platelet aggregation) which dephosphorylates myosin light chain → relaxation Venodilation (lower VR), some depression of TPR, coronary artery vasodilation; depressed LV pressure and wall stress and O2 demand (works on smooth muscle, practically no direct dilatory effect on heart or skeletal muscle). SE: Orthostatic hypotension, tachycardia, headache; salt and water retention; methemaglobinemia CI: high intracranial pressure; sildenafil Tolerance develops: caused by decrease in needed tissue sulfhydryl groups, increased generation of oxygen free radicals, and diminished availability of calcitonin gene-related peptide (CGRP) taken IV/sublingual (10-20min); low oral bioavailability (4-6hrs); onset within minutes; transdermal (24hrs) High first pass effect for oral (which is why sublingual is preferred) → metabolized to dinitrate (high vasodilation) then mononitrate (low vasodilation) Decrease in platelet aggregation Nitroglycerin requires glutathione S-transferase in smooth muscle to be activated (and also aldehyde dehyrdogenase from mitochondria), unlike nitroprusside. These enzymes releases NO from nitroglycerin. NO combines with guanylyl cyclase, forming cGMP and decreasing myosin light chain activty in VSMC. Reduces vasospasm in variant angina Arteries respond at higher doses; veins at lower doses weak negative inotropic effect on the heart

Question 60

Drugs used in Angina

Answer 60

Organic nitrates, calcium channel blockers, and Beta blockers- all of these decrease myocardial oxygen requirement by lowering oxygen demand: HR, ventricular volume, BP, contractility vasospastic angina: nitrates and calcium channel blockers Angina of effort; Nitrates, calcium blockers, beta blockers chosen for maintenance therapy of chronic stable angina. Unstable angina and acute coronary syndromes: antiplatelet therapy of aspirin and clopidogrel.

Question 61

Isosorbide Dinitrate

Answer 61

Nitrates and Nitrites Vasodilator Uses: angina, myocardial ischemia Effects: Denitrated to NO which increases cGMP Venodilation (depressed VR and symptoms of pulmonary congestion), coronary artery vasodilation; lower LV pressure and wall stress and overall O2 demand. SE: Orthostatic hypotension, tachycardia, headache CI: increased intracranial pressure High first pass metabolism Tolerance develops; taken IV/sublingual; low oral bioavailability; onset 10-60 minutes. Main excretion is kidneys A metabolite of the drug, 5-mononitrate, is available as isosorbide mononitrate: oral and 100% bioavailable. effective in heart failure by reducing preload (venodilation) or afterload (arteriolar dilation); reduces damaging remodeling of the heart.

Question 62

Beta antagonist (Propanolol)

Answer 62

management of effort angina. Benefits due to hemodynamic effects- decreased heart rate, BP, contractility-ultimately decreasing oxygen requirement at rest and excercise May be useful in treating silent or ambulatory ischemia (which causes no pain). It's detected by ECG signs of ischemia. Increase survival and prevent stroke in patients with hypertension, and reduce mortality in those with recent MI. Undesirable: increase end diastolic volume and increase in ejection time; increases myocardial oxygen requirement. This can be balanced by concominant use of nitrates. CI: asthma and brochospasm, bradycardia, AV blockade, bradycardia-tachycardia syndrome, unstable left ventricular failure SE: insomnia, bad dreams :( , ED, worsening claudication.

Question 63

Mechanism of effect: Nitrates

Answer 63

Decreases venous return to heart, reducing preload and decreasing overall Oxygen consumption. Sometimes, an increase in oxygen required can result from reflex tachycardia. Nitrates dont increase the caliber of large cornoary arteries that are blocked by concentric atheromas. Nitrates in variant angina: beneficial by relaxing the smooth muscle of epicardial coronary arteries and relieving coronary artery spasm. Nitrates in unstable angina: useful but MOA unknown. Dilates epicardial coronary arteries and reduces myocardial oxygen demand, and **decreases platelet aggregation** **Benefits**: decreased ventricular volume, arterial pressure, ejection time all cause decrease in myocardial oxygen requirement. Improved perfusion. **Deleterious:** Reflex tachycardia and reflex increase in contractility causes increase in oxygen requirement. Also decreased coronary perfusion

Question 64

Calcium channel blockers (Nifedipine)

Answer 64

(L-type) Ca Channel Blocker (Dihydropyridine) Uses: Angina, HTN (severe HTN), Raynaud’s phenomenon, supraventricular tachyarrythmias; AV node conduction abnormalities More selective as vasodilators Effects: decreases BP, contractility, O2 demand of heart; reflex sympathetic activation with slight tachycardia maintains or increases CO Slow release options; 6-8 hour duration. Does not effect skeletal muscle due to SM intracellular calcium stores. SE: less cardiac depression (cardiac arrest, bradycardia, AV block, heart failure); flushing, dizziness, nausea CI: heart failure, β blockers Oral Short-acting (increased risk of adverse cardiac events [MI])

Question 65

Ranolazine

Answer 65

New antianginal drug MOA: reduces late sodium current that facilitates calcium entry via the sodium-calcium exchanger. Reduction in intracellular calciun reduces cardiac contractility and work.

Question 66

Ivabradine

Answer 66

I_f Sodium channel blocker "bradycardic drug" reduces cardiac rate by inhibiting the hyperpolarization activated sodium channel in the SA node Reduced anginal attacks with similar efficacy of calcium channel blockers/ beta blcokers No GI and bronchial side effects, so it is advantageous

Question 67

Trimetazidine

Answer 67

pFOX Inhibitor Uses: prophylaxis of angina Effects: partially inhibits fatty acid oxidation; blocks late Na+ current that facilitates Ca entry Shift to carbohydrate metabolism (decreased O2 demand) SE: prolonged QT, nausea, dizziness, constipation

Question 68

Verapamil

Answer 68

(L-type) Ca Channel Blocker (Non-Dihydropyridine) Uses: Angina, HTN, antiarrythmic (SV reentry tachycardia, atrial fib/flutter), migraine Effects: decreases BP, contractility, HR (nonspecific anti-adrenergic), decreases AV nodal conduction; modest Na+ channel block; blocks P-glycoprotein; peripheral dilation SE: serious cardiac depression (cardiac arrest, bradycardia, AV block, heart failure); flushing, dizziness, nausea; constipation edema; hypotension CI: β blockers 3-6 hour half life

Question 69

Digoxin

Answer 69

Cardiac Glycosides (prototype) Uses: Heart failure; Atrial fibrillation. Only used when diuretics and ACE inhibitors have failed to control symtoms Effects: inhibition of Na/K/ATPase; increases intracellular Na which inhibits Na/Ca exchanger; increases [Ca] intracellularly; increases contractility, CO; decreases the AP duration (short plateau; due to increased potassium conductance) decreases SA conduction, atrial refractory period, AV node conduction rate; increased AV node refractory period; increased PR interval, shorter QT interval 65-80% orally absorbed. Wide distribution gets into CNS; excreted by kidney Low doses: parasympathetic cardiac tone Toxic doses: sympathetic cardiac tone SE: Anorexia, nausea, vomiting, diarrhea, disorientation, visual disturbances (yellow halo), hyperkalemia, digitalis induced arrhythmias CI: potassium and digitalis inhibit each others binding to Na/K ATPAse

Question 70

Digibind

Answer 70

Cardiac Glycoside Antibody Digitalis antibody (FAB) – directed toward Na/K ATPase pump Directed toward digitoxin and cardiac glycosides Used to reverse digitalis toxicity Caution w/ renal impairment

Question 71

Digitoxin

Answer 71

Cardiac Glycosides Uses: Heart failure; antiarrythmic, dilated heart and third heart sounds MOA: inhibits Na/K ATPase Effects: same as digoxin SE: Anorexia, nausea, vomiting, diarrhea, disorientation, visual disturbances (yellow halo), gynecomastia, arrhythmias, hypercalcemia, hypomagnesemia; increased EC K+ decreases effects Kinetics: longer acting than Digoxin

Question 72

Diuretics for Heart Failure

Answer 72

Furosemide No direct effect on cardiac contractility MOA: reduce venous pressure and ventricular preload. This results in reduction of salt and water retention and edema. Improved pump efficiency in systolic failure Spironolactone and eplerenone, aldosterone antagonist diuretics, have additional benefits in decreasing morbidity and mortality in patients with severe heart failure who also take ACE inhibitors.

Question 73

Enalapril

Answer 73

ACE Inhibitor Uses: HTN, **Heart failure**, post-MI; given IV in HTN emergency decreases BP (PVR); no effect on CO/HR; effectiveness independent of Renin levels; no reflex sympathetics (ie, it resets baroreceptors); vasodilation SE: hypotension (esp. with low volume), acute renal failure (pt’s with bilateral renal artery stenosis), hyperkalemia, dry cough (bradykinin), taste change, drug fever, angioedema, skin rash CI: pregnancy Kinetics: oral prodrug (liver activated to enalaprilat) Monitor K+

Question 74

Spironolactone

Answer 74

Diuretic Aldosterone receptor antagonist Uses: hyperaldosteronism (primary: Conn’s syndrome, ectopic ACTH production; secondary: chronic heart failure. Hepatic cirrhosis, nephrotic syndrome, decreases intravascular volume) Effects: lower total volume (K+ sparing) can use with digoxin ⇒ decreases BP (slow onset of action; increased Na+ excretion); decrease venous pressure and ventricular preload long acting (24-48hrs) SE: Hyperkalemia, hyperchloremic, metabolic acidosis, gynecomastia, acute renal failure, menstrual irregularities CI: chronic renal insufficiency, ACE inhibitors, liver disease, NSAIDs, β blocker

Question 75

Losartan

Answer 75

Angiotensin Receptor Antagonist HTN (in pt’s with IHD or chronic renal disease), **Heart failure (reduces afterload),** post-MI AT₁ receptor of ang II block (no effect on bradykinin, but more complete ang II block; decreases BP (PVR); no change in HR SE: hypotension (esp. with low volume), acute renal failure (pt’s with bilateral renal artery stenosis), hyperkalemia, dry cough not common, taste change, drug fever, angioedema less common, skin rash CI: pregnancy Monitor K+

Question 76

Carvedilol

Answer 76

(β1=β2\>α1\>α2) Adrenergic Receptor Antagonist Uses: HTN; chronic **heart failure** Decreases BP; little or no reflex increase in HR (differs from α blockers); attenuates oxygen free radical lipid peroxidation; inhibits vascular SM mitogenesis Kinetics: half-life 6-8 hours; extensive hepatic metabolism CI: quinidine due to metabolism

Question 77

Dobutamine

Answer 77

(β1\>β2\>\>α) Adrenergic Receptor agonist Uses: **Heart failure**, cardiogenic shock, drug-induced stress test Effects: increase contractility; increase CO (not so much reflex bradycardia [from β2]); lowers ventricular filling Pressure Tolerance builds quickly SE: tachycardia, angina, arrhythmias in pt’s with CAD. **Dopamine** has also been used in acute heart failure and can raise blood pressure.

Question 78

Milrinone

Answer 78

Phosphodiesterase Inhibitors (Bipyridine) Uses: Acute Heart failure (exacerbates CHF) Prevents inactivation of cAMP and cGMP (inhibits PDE-3), increasing contractility and vasodilation. Increase calcium influx (also influences SR Ca levels) SE: Arrhythmia, otherwise less toxic then **amrinone** Given IV only

Question 79

Nesiritide

Answer 79

Vasodilator Uses: Acute Heart failure Effects: synthetic form of BNP; increases cGMP in SM; decreases arteriolar and venous tone; lower preload; Diuresis Parenteral application lasts minutes. Short half-life of 18min SE: Excessive hypotension, renal damage, death

Question 80

What two conditions are successfully treated with diuretics?

Answer 80

- Heart failure and hypertension (Diuretics eliminate excess Na+ and H2O through renal excretion and are therefore useful when in heart failure there is enhanced renal absorption of Na+ and H2O leading to peripheral edema and pulmonary congestion) (In treatment of HTN, diuretics similarly reduce intravascular volume and in some cases promote vascular dilatation).

Question 81

What are the three groups of diuretics?

Answer 81

Loop diuretics, thiazide diuretics, and potassium-sparing diuretics

Question 82

Loop Diuretics

Answer 82

- Loop diuretics act principally on the thick asceding limb of the Loop of Henle. Powerful diuretics that result in excretion of 20% - 25% of filtered Na+ load through inhibition of Sodium - 2Chloride - Potassium cotransport system. Because inhibtion at this site impairs the generation of a hypertonic interstitium, the gradient for passive water movement out of the collecting duct is diminished and water diuresis results. OF GREAT IMPORTANCE IN PULMONARY EDEMA (IV) and in the treatment of CHRONIC HEART FAILURE (ORAL) or PERIPHERAL EDEMA (ORAL). Effective in the setting of impaired renal function (unlike other diuretics). May enduce venous vasodilation via drug-induced prostaglandin and NO generation. MOST COMMON SIDE-EFFECT: Intravascular volume depletion, hypokalemia, and metabolic acidosis. MOST COMMONLY USED Loop Diuretic: Furosemide. Bemetanide is also good and has limited ototoxicity. Ethacrynic acid is the only nonsulfonamide loop diuretic, so can be prescribed to patients with sulfonamide intolerance.

Question 83

Thiazide Diuretics

Answer 83

- Commonly used diuretics becuase they demonstrate excellent GI absorption and well tolerated. Less potent than loop diuretics, however sustained action makes them more useful in chronic conditions such as HTN and mild CHF. Act at the distal tubule, where they block reabsorption of 3% - 5% of filtered sodium (mediated through the Na - Cl cotransporter on the luminal membrane. Cardiac output can initially be reduced due to reduction of intravascular volume with unchanged peripheral resistance (this corrects via vasodilation over time). Indapamide is unique as it displays a particularly prominent vasodilating effect. Clorothiazide has low bioavail and therefore not used as often as hydroclorothiazide. Chlorthalidone is slowly absorbed and has LONG DURATION of action. Metolazone is unique as it is effective in patients with reduced renal function (none of the other thiazides are). Used for anti-HTN therapy. Adverse effects are Hypokalemia, metabolic acidosis, hyponatremia with prolonged treatment, and increased LDL lipid profiles.

Question 84

Potassium-Sparing Diuretics

Answer 84

- Relatively weak diuretics that antagonize Na+ reabsorption at the distal convoluted tubule and cortical collecting tubule. Potassium-sparing agents reduce K+ excretion (duh) and therefore hypokalemia is not a side-effect. Used when maintenance of serum potassium levels is crucial and in states characterized by aldosterone excess. Two types of drugs for this group: 1) Aldosterone antagonists (**Spironolactone** and eplerenone) 2) Direct inhibitors of Na+ permeability in the collecting duct, which act independently of aldosterone (triamterene and amiloride). Often used in combination with Loop diuretics or Thiazide classes since these have mild diuretic effects and prevent hypokalemia. Spironolactone also displays beneficial cardiac antiremodeling effects in pts with heart failure (although hyperkalemia and gynecomastia can occur). Eplerenone is more specific inhibitor of aldosterone receptor that does not have the systematic antiandrogenic effects seen with Spironolactone. Triamterene is metabolized by the liver and Amiloride is secreted unchanged in urine (hyperkalemia also occurs with these).

Question 85

Difference between STEMI and UA and NSTEMI

Answer 85

- STEMI are patients who present with ST segment elevation whereas UA and NSTEMI are patients that do NOT present with ST segment elevation. STEMI typically indicates TOTAL OCCLUSION of a coronary artery and benefit from immediate reperfusion therapies, while patients without ST elevation do not.

Question 86

Management of UA and NSTEMI

Answer 86

Primary focus of treatment for UA and NSTEMI consists of anti-ischemic medications to restore the balance between myocardial O2 supply and demand and anti-thrombotic therapy aimed at preventing further growth, and facilitating resolution of, the underlying partially occlusive coronary thrombus. B-Blockers slow the sympathetic stimulation and therefore decrease O2 demand. Nitrates (nitroglycerin) relieve angina via venodilation. Calcium channel antagonists (verapamil and diltiazem) exert anti-ischemic effects by decreasing heart rate and contractility and through their vasodilatory properties (Only give if B-blockers are contraindicated or don't give the full effect). NEVER GIVE if patient has LV systolic dysfunction.

Question 87

Aspirin

Answer 87

- Inhibits platelet synthesis of thromboxane A2, a potent mediator of platelet activation. IMPORTANT intervention to reduce mortality in patients with all forms of Acute Coronary Syndrome (ACS). Administer immediately upon presentation and continued indefinitely in patients without contraindications to its use (allergy or underlying bleeding disorder). Other antithrombotics: Clopidogrel (if allergy to aspirin), Prasugrel (metabolized more effectively), and Glycoprotein (GP) IIb/IIIa receptor antagonists (those at highest risk).

Question 88

Unfractionated Heparin (UFH) & Low Molecular Weight Heparin (LMWHs)

Answer 88

- Unfractionated heparin (UFH) has long been standard anticoagulant therapy for UA and NSTEMI. Binds antithrombin, which greatly increases the potency of that plasma protein in the inactivation fo clot-forming thrombin (also inhibits factor Xa). High degree of pharmacodynamic variability and thus must be monitored often (least expensive drug though). - Low molecular weight heparins (LMWHs) interact with antithrombin but preferentially inhibit coagulation factor Xa. They provide more predictable pharmacologic response and thus don't have to monitored as often. Fondaparinux is similar to LMWH at reducing cardiac adverse event but with LESS bleeding complications.

Question 89

Fibrinolytic Therapy

Answer 89

- Fibrinolytic drugs accelerate lysis of the occlusive intracoronary thrombus in STEMI, thereby restoring blood flow and limiting myocardial damage. Patients with UA and NSTEMI DO NOT BENEFIT FROM THIS THERAPY.

Question 90

Alteplase, Reteplase, Tenecteplase

Answer 90

- Each drug functions by stimulating the natural fibrinolytic system, transforming the inactive precursor plasminogen into the active protease plasmin, which lyses fibrin clots. Bleeding is the most common complication/side-effect. rPA (reteplase) and TNK-tPA (Tenecteplase) are derivatives of tPA with LONGER half-lives; their main advantage is that they can be administered as IV boluses, which is more convenient and less prone to incorrect administration than the continuous intravenous infusion necessary for tPA. Patients who receive therapy within 2 hours of the onset of symptoms of STEMI have HALF the mortality rate of those who receive it after 6 hours. Obviously contraindicated in patients with peptic ulcer disease or who have had a recent stroke (need clotting factors). Ideal to administer these drugs within 30 min of patient's presentation to hospital.

Question 91

Alternate to fibrinolytic therapy for Acute Coronary Syndromes

Answer 91

- Primary Percutaneous Coronary Intervention, an alternative to fibrinolytic therapy. Immediate catherization and PCI of the lesion responsible for the infarction. Involves angioplast and stenting of the culprit vessel. Greater survival rates with lower rates of reinfarction or bleeding (therefore PREFERRED reperfusion approach in acute STEMI). In patients where fibrinolytics are contraindicated, PCI is obviously more preferred.

Question 92

Dilated Cardiomyopathy

Answer 92

- Approaches for the relief of vascular congestion and improvement in forward cardiac output are the same as standard therapies for heart failure. Initial therapy typically includes salt restriction and diuretics, vasodilator therapy with an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), and a B-blocker.

Question 93

Arrhythmias in DCM

Answer 93

- Arrhythmias are common in advanced DCM, and approximately 40% of deaths in this condition are casued by ventricular tachycardia or fibrillation. Important to keep electrolytes within normal ranges. Important to note in patients with LV function, many antiarrhythmic drugs may worsen the rhythm disturbance. Implantable cardioverter-defibrillator (ICD) does reduce arrhythmic deaths in patients with DCM (recommended therapy).

Question 94

Thromboembolic Event Prevention in DCM

Answer 94

- Pts with DCM are at increased risk of thromboembolic complications for reasons that include: 1) stasis in the ventricles resulting from poor systolic function, 2) stasis in the atria due to chamber enlargement or atrial fibrillation, 3) venous stasis becasue of poor circulatory flow. Chronic oral anticoagulation therapy (i.e. Warfarin) is often administered to DCM patients who have severe depression of ventricular function to prevent thromboembolism.

Question 95

Cardiac Transplantation in DCM

Answer 95

- In suitable patients, cardiac transplantation offers a substantially better 5-year prognosis than the standard therapies for DCM previously described. The scarcity of donor hearts greatly limits the availability of this technique.

Question 96

Prognosis of DCM

Answer 96

- Up to 1/3 of patients will experience spontaneous improvement of heart function after the diagnosis of DCM is made. However, the pronosis for patients with persistent DCM who do not undergo cardiac transplantation is poor - the avg. 5-yr survival rate is \<50%.

Question 97

Treatment for Hypertrophic Cardiomyopathy (HCM)

Answer 97

- B-Blockers are standard therapy for HCM because they 1) reduce myocardial oxygen demand by slowing the heart rate and the force of contraction (and therefore diminish angina and dyspnea); 2) lessen any LV outflow gradient during exercise by reducing the force of contraction (allowing the chamber size to increase, thus separating the anterior leaflet of the mitral valve from the ventricular septum); 3) Increase passive diastolic ventricular filling time owing to the decreased heart rate; and 4) decrease the frequency of ventricular ectopic beats. Calcium channel antagonists can reduce ventricular stiffness and are sometimes useful in improving excercise capacity in patients who fail to respond to B-blockers. AVOID vasodilators that reduce LV size (Nitrates!!!)

Question 98

A-fib and V-fib in HCM

Answer 98

- Poorly tolerated and should be controlled aggressively, most commonly with antiarrhythmic drugs. (Amiodarone and disopyramide). ICD therapy is life saving in for both primary prevention in such patients, and for HCM patients who have already survived a cardiac arrest. Surgical therapy (myomectomy) is considered for patients whose symptoms do not respond adequately to pharmacologic therapy. This procedure involves excision of portions of the hypertrophied septal muscle mass and usually improves outflow tract obstruction, symptoms, and exercise capacity. Less invasive alternative is percutaneous septal ablation (not as good though).

Question 99

Treatment for Restrictive Cardiomyopathy

Answer 99

- Restrictive Cardiomyopathy typically has a VERY poor prognosis, except when treatment can target an UNDERLYING CAUSE. Ex: Phlebotomy and Iron Chelation therapy may be helpful in the early stages of hemochromatosis. Symptomatic therapy for all etiologies includes salt restriction and cautious use of diuretics to improve symptoms of systemic and pulmonary congestion. Unlike dilated cardiomyopathies, vasodilators are not helpful becuase systolic function is usually preserved. In the case of primary amyloidosis, chemotherapy followed by autologous bone marrow stem cell transplantation has proved effective in selected patients with early cardiac involvement.

Question 100

Aortic Dissection Treatment

Answer 100

- The goal of acute treatment is to arrest progression of the dissecting channel. Suspicion of acute aortic dissection warrants immediate medical therapy to reduce systolic blood pressure and to decrease the force of left ventricular contraction and thus minimize aortic wall shear stress. Therefore, B-blockers are useful as they reduce the force of contraction and heart rate as well as lower BP. Vasodilators such as **sodium nitroprusside** (to rapidly reduce BP). Type A gets surgical treatment, whereas Type B dissection gets ONLY aggressive medical treatment.

Question 101

Peripheral Artery Disease (PAD)

Answer 101

- For all patients with PAD, antiplatelet therapy and risk factor modification (including smoking cessation, lipid lowering, and control of diabetes and HTN) are important in reducing the likelihood of coronary events. Platelet inhibitors -\> Aspirin. Excercise, particularly walking, improves endurance in part by increasing metabolic efficiency. A formal exercise program is considered first-line therapy in the management of PAD. Cilostazol (selective phosphodiesterase inhibitor that increased cAMP and has vasodilator and platelet-inhibiting properties) Pentoxifylline is a drug purported to improve the deformability of red and white blood cells and may improve claudication symptoms in some patients.

Question 102

Deep Veinous Thrombosis Treatment

Answer 102

- Elevation of the affected extremity above the level of the heart helps reduce edema and tenderness, and anticoagulation prevents extension of the thrombus and PE. Initial anticoagulation usually ocnsists of subcutaneous low molecular weight heparin (LMWH). Warfarin can also be used for long-term oral therapy. In patients who cannot be treated with anticoagulants (because of bleeding disorder), an intravascular filter can be percutaneously inserted into the inferior vena cava to prevent emboli from reaching the lungs. Prophylaxis against DVT is mandatory in high-risk patients (bed rest following surgery). Use subcutaneous LMWH, fondaparinux, low-dose oral warfarin, compression stockings, and/or intermittent external pneumatic compression of the legs to prevent venous stasis. For superficial thrombophlebitis (benign disorder) use heat, relaxation, and possibly aspirin.