Treatments Quiz 4

Question 1

Statins

Answer 1

MOA: HMG CoA reductase inhibitors (rate limiting step of cholesterol synthesis. Blocks the production of mevalonate (cholesteral precursor)

Lipid effects: — LDL, +HDL, -TG

Adverse effects: Hepatoxicity (ncrease in LFTs), rhabdomyolysis

Question 2

Niacin

Answer 2

MOA: Inhibit lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation.

Lipid effects: –LDL, ++HDL, -TG

Adverse effects: Red, flushed face, which is decreased by aspirin or long-term use. Hyperglycemia (acanthosis nigrans) Hyperuricemia (exacerbates gout)

Question 3

Cholestyramine

Answer 3

Bile Acid Resins

MOA: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more.

Lipid effects: – LDL, +HDL, +TG

Adverse effects: Patients hate it - tastes bad and causes GI discomfort, decreased absorption of fat-soluble vitamins. Cholesterol gallstones.

Question 4

Ezetimibe

Answer 4

Class: Cholesterol absorption blockers

MOA: Prevent cholesterol reabsorption at small intestine brush border.

Lipid effects: –LDL

Question 5

Colestipol

Answer 5

Bile Acid Resins

MOA: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more.

Lipid effects: – LDL, +HDL, +TG

Adverse effects: Patients hate it - tastes bad and causes GI discomfort, decreased absorption of fat-soluble vitamins. Cholesterol gallstones.

Question 6

Colesevelam

Answer 6

Bile Acid Resins

MOA: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more.

Lipid effects: – LDL, +HDL, +TG

Adverse effects: Patients hate it - tastes bad and causes GI discomfort, decreased absorption of fat-soluble vitamins. Cholesterol gallstones.

Question 7

Gemfibrozil

Answer 7

Class: Fibrates

MOA: Upregulate LPL –> increased TG clearance.

Lipid effets: -LDL, +HDL, —TG

Adverse effects: myositis, hepatoxicity, cholesterol gallstones.

Question 8

Procainamide

Answer 8

Class: IA

MOA: Blocks Na+ channel. Slow or block conduction (especially in depolorized cells).

State Dependent (selectively depresses tissue that is frequently depolarized)

Cardiac effects: Increases AP duration. Increase ERP.

Extra Cardiac Effects: Ganglionic blocking properties reduces peripheral vascular resistance causing hypotension.

PK: Metabolite (N-acetylprofainamide) has class II activity. Hepatic metabolism to NAPA (excreted by kidneys).

Toxicity: Excessive prolongation –> TDP. Long term usage can cause SLE like syndromes.

Uses - most atrial and ventricular arrhythmias. 2nd/3rd choice drug for sustained ventricular arrhythmias w/ acute MI.

Question 9

Quinidine

Answer 9

Class: IA

MOA: Blocks Na+ channel. Slow or block conduction (especially in depolorized cells).

State Dependent (selectively depresses tissue that is frequently depolarized)

Cardiac effects: Increases AP duration. Increase ERP.

Extracardiac effects: Antimuscarinic effects. Cinchonism (headache, dizziness, tinnitus)

PK: Readily absorbed in GI.

Toxicity: TDP.

Uses: rarely used due to toxicity.

Question 10

Disopryamide

Answer 10

Class: IA

MOA: Blocks Na+ channel. Slow or block conduction (especially in depolorized cells). State Dependent (selectively depresses tissue that is frequently depolarized)

Cardiac effects: Increases AP duration. Increase ERP. Increase QTI. Slows upstroke of AP. Slows conduction of impulse. Prolongs QRS.

Extra cardiac effects: Antimuscarinic effects.

PK: Loading dose not reccommended.

Toxicity: TDP

Uses: Ventricular arrhythmias

Question 11

Lidocaine

Answer 11

Class: IB

MOA: Blocks Na+ channel. Slow or block conduction

State Dependent (preferentially affects ischemic/depolarized purkinje and ventricular tissue)

Cardiac effects: Decreased AP duration. Little effect seen on EKG in normal sinus.

Extra cardiac effects: Block generation and conduction of nerve impulses, increasing the threshold excitation –> slows propagation = no pain.

PK: Must be given parenterally.

Toxicity: Minimal, paresthesias, tremor, nausea, light headedness, hearing disturbances, slurred speech and convulsions.

Uses: Terminating V-tach after cardioversion. Prophylactic use may INCREASE mortality.

Question 12

Mexiletine

Answer 12

Class: IB

MOA: Blocks Na+ channel. Slow or block conduction (especially in depolorized cells).

State Dependent (preferentially affects ischemic/depolarized purkinje and ventricular tissue)

Cardiac effects: Decreased AP duration. Decreased ERP. Little effect seen on EKG in normal sinus.

Extra cardiac effects: significantly effective at relieving chronic pain, especially due to DM neuropathy and nerve injury.

PK: 90% oral absorption w/ low first pass metabolism.

Toxicity: possible development/excacerbation of arrhythmias (monitor before/during use). Possible excacerbation of hypotension and CHF.

Uses: Sustained V-Tach. Not for less severe arrhythmias.

Question 13

Flecainide

Answer 13

Class: IC

MOA: Potent Na+ and K+ channel blocker. Slow unblocking kinetics (does not prolong AP or QT.

Cardiac effects: Significantly prolongs refractory period in AV node. Minimal effect on AP duration. Slows upstroke of AP. Slows conduction.

PK: Rapidly and completely absorbed by GI w/o first pass metab.

Toxicity: potential for new/more severe arrhytmias. Potential to excacerbate CHF.

Uses: Prevention of PSVT (AV nodal reentrant tachy and WPW syndrome)

Question 14

Propafenone

Answer 14

Class IC

MOA: Na+ channel blocker with weak B-blocking activity

Cardiac effects: Slows conduction. Significantly prolongs refractory period in AV node. Minimal effects on AP duration.

Extra cardiac effects: Bradycardia and bronchospasm.

PK: GI absorbed w/ extensive first pass metabolism.

Toxicity: New or worsened CHF. Reversible granulocytopenia or agranulocytosis. Blocking of bronchodilation (dont use in asthmatics).

Uses: Prolong time to recurrence of PSVT.

Question 15

Propanolol

Answer 15

Class II (non-selective B-blocker)

MOA: Decrease SA and AV nodal activity via decreasing cAMP, decreasing CA++.

Cardiac effects: Suppress normal pacemakers by decreasing slope of phase 4 (AV node particularly sensitive –> increased PRI)

PK: oral absorption w/ wide distribution

Toxicity: Inhibits bronchodilation, Possible intensification of AV block.

Question 16

Acebutolol

Answer 16

Class II (B1-blocker)

MOA: Decrease SA and AV nodal activity via decreasing cAMP, decreasing CA++.

Cardiac effects: Suppress normal pacemakers by decreasing slope of phase 4 (AV node particularly sensitive –> increased PRI)

Toxicity: Avoid use in patients w/ decompensated HF. Possible decreased signs and sx of hypoglycemia.

Uses: frequent PVCs and HTN

Question 17

Esmolol

Answer 17

Class II (B1-blocker)

MOA: Short acting. Decrease SA and AV nodal activity via decreasing cAMP, decreasing CA++.

PK: rapid onset and remission.

Toxicity: hypotesnion, dizziness, diaphoresis, headache, somnolence, confusion, agitation, nausea

Rx: SVT (intraoperative), HTN, Acute MI, unstable angina, NSTEMI

Question 18

Sotalol

Answer 18

Class II (non-selective B-blocker)

MOA: Decrease SA and AV nodal activity via decreasing cAMP, decreasing CA++. 2 isomers (L=beta blocker; D = antiarrhythmetic).

Beta blocker at 25mg and antiarrhythmetic at 160mg.

Cardiac effects: Suppress normal pacemakers by decreasing slope of phase 4 (AV node particularly sensitive –> increased PRI).

Antiarrhythmetic effect lengthens repolarization or plateau)

Toxicity: Sinus brady, ches pain, palpitations, hypotension, fatigue, dizziness, asthenia, lightheadedness, dsypnea, nausea, and vomiting.

Uses: Vent arrhytmias and SVTs.

Question 19

Amiodarone

Answer 19

Class III

MOA: K channel blocker; also potent Na channel blocker, weak B-blocker and Ca++ blocker.

Cardiac effects: slows repol, lengthens QT. prolongs AP. Slows SA and AV nodal conduction.

Extracardiac effects: peripheral vasodilation.

PK: CYP3A4 metab, metabolite is bioactive, half life is complex –> effects 1-3 months post cessation. Can inhibit CYPs.

Toxicity: Brady and heart block in patients w/ SA or AV nodal disease. Drug accumulates in tissues. Blocks peripheral conversion of T4 and T3 (hypo and hyper thyroidism). Dose related pulmonary toxicity. Abnormal LFT and hypersensitivty. Photodematitis. Corneal microdeposits.

Uses: VTACH, VFIB, AFIB, A flutter.

Question 20

Dofelitide

Answer 20

Class III

MOA: Very selective K+ channel blocker.

Cardiac effects: Slows repol, lengthens QT, prolongs AP, increases QTI

Extra cardiac effects: Hypokalemia or hypomagnesia.

PK: 100%bioavailable. CYP3A4 Metab.

Toxicity: TDP (don’t use in Long QT, bradycardia, or hypokalemia)

Uses: AFIB

Question 21

Ibutilide

Answer 21

Class III

MOA: K channel blocker (and also inward NA+ activators which increases NA+ inactivation and increases ERP.

Cardiac effects: Prolongs AP

Toxicity: TDP

Uses: A flutter

Question 22

Dihydrophyridines (i.e. amlodiPINE)

Answer 22

Class IV:

MOA: Blocks L-type Ca++ channels specifically in peripheral smooth muscle. Causes vasodilation and decreased in TPR.

Toxicity: flushing, headache, excessive hypotension, reflex tachy. Poor choice for angina due to lack of cardiac effects.

Uses: HTN

Question 23

Verapamil

Answer 23

MOA: blocks activated and inactivated L type Ca++ channels. (greater effect in tissues that fire frequently, less polarized, or nodal tissues).

Causes both shortened phase 2 of AP and peripheral vasodilation.

Largest cardiac suppression of Ca++ blockers.

PK: Significant first pass metab.

Toxicity: AV block in large doses. constipation, lassitude, nervousness, peripheral edema, hypotension, VFIB.

Don’t use w/ B-blockers (synergistic mechanims)

Uses: Angina. SVT, AFIB, Aflutter. Reduces ventricular rate, does not convert back to sinus.

** Do NOT use in WPW.

Question 24

Diltiazem

Answer 24

Class IV

MOA: blocks activated and inactivated L type Ca++ channels. (greater effect in tissues that fire frequently, less polarized, or nodal tissues).

Causes both shortened phase 2 (less than vermapil) of AP and peripheral vasodilation (more than vermapil).

PK: significant first pass metabolism.

Toxicity: hypotension and VFIB.

Don’t use w/ B-blockers (synergistic mechanisms).

Uses: SVT, and AFIB

Question 25

Adenosine

Answer 25

“Class V”

MOA: Activation of K+ channels and inhibition of L type Ca++ channels. Results in hyperpolariztion and suppression of Ca++ dependent APs (nodal tissue).

Extracardiac effects - Vasodilation

Toxicity: Flushing and headache, rapid arterial hypotenison, caffeine competitively antagonizes binding site.

Uses: conversion of PSVT

Question 26

Digoxin

Answer 26

“Class V”

MOA: Blocks Na/K/ATPAse which increases intracellular Na+. This inhibits Na/Ca anitporter which increases intracellular Ca –> improved contractility.

Extracardiac effects: activates vagal efferents to heart –> slows SA rate and AV conduction increasing ERP.

PK: Renally excreted.

Toxicities: AV block. WPW, monitor dose if renally impaired, GI distress, hyperkalemia, arryhtmias, increased PRI

Uses: refractory HF.

Question 27

Cilostazol

Answer 27

MOA: cAMP phosphodiesterase III inhibitor. Causes a decrease in platelet aggregation and increase in vasodilation (preferentially in femoral capillary beds)