CVPR drugs

• Prototye: Captopril, lisinopril,
• Uses: Congestive HF (w/ or w/o hypertension), hypertension and diabetes, cardioprotective after acute MI
• Primary mechanism: Inhibiting ACE, preventing conversion of AI -> AII
• Secondary mechanism: Inhibits ACE inactivation of bradykinin, leading to increased vasodilation
• Side effects: Cough, angioedema, proteinuria/increased potassium, taste, hypertension, pregnancy, rash, increased renin, lower levels of AII
• *Note that the cough and angioedema are due to increased levels of bradykinin
• Contraindications: Potassium sparing diuretics, potassium supplements/potassium iodide (risk of hyperkalemia), renal failure, pregnancy
• Other med interactions: NSAIDS reduce vasodilatory effects of bradykinin; mitigates the hypokalemia caused by thiazide diuretics

• Angiotensin II Receptor antagonist
• Uses: Congestive HF; used when patients are intolerant to ACE inhibitors
• Mechanism: blocks the angiotensin II receptor (has no effect on the inactivation of bradykinin)
• Side effects: hyperkalemia, angioneurotic edema

• A loop diuretic
• Use: Acute and chronic heart failure
• Mechanism: Acts on the ascending limb of the loop of Henle to decrease NaCl and KCl reabsorption (20% of sodium is absorbed here)
• Major effects: increases excretion of salt and water, reduces cardiac preload/afterload, and reduces pulmonary/peripheral edema

• Thiazide diurectic
• Use: Mild chronic heart failure
• Mechanism: Acts on the distal convoluted tubule to decrease sodium reabsorption (normally responsible for 10% of sodium reabsorption)

• Potassium-sparing diuretic
• Use: Chronic heart failure
• Mechanism: Blocks aldosterone receptors in the cytoplasm of cells in the collecting tubules of the nephron (responsible for 2% of sodium reabsorption)
• Toxicity: Hyperkalemia (and so contraindicated in patients on ACE inhibitors, AII receptor antagonists/blockers, and beta blockers), gynecomastia
• Reduces mortality

• Potassium-sparing diuretic used for heart failure
• Mechanism is similar to spironolactone
• ***Does not cause gynecomastia
• Reduces mortality

• Beta1 selective antagonist used in chronic heart failure to slow progression
• Mechanism: blocks beta1 receptor, slowing the heart rate and reduces blood pressure
• Toxicity: Bronchospasm, bradycardia, AV block, acute cardiac decompensation
• Reduces mortality

• Beta1 selective antagonist used in chronic heart failure to slow progression
• Mechanism: blocks beta1 receptor, slowing the heart rate and reduces blood pressure
• Toxicity: Bronchospasm, bradycardia, AV block, acute cardiac decompensation
• Reduces mortality

• Alpha1, beta1, beta2 antagonist used in heart failure to slow progression
• Mechanism: blocks beta1 receptor, slowing the heart rate and reduces blood pressure
• Toxicity: Bronchospasm, bradycardia, AV block, acute cardiac decompensation
• Reduces mortality

• Mechanism: Inhibits Na+/K+ ATPase, causing increased intracellular sodium, and preventing sodium calcium exchanger (NXS) from pumping calcium out, thereby increasing intracellular calcium and increasing contraction
• Use: Reentrant arrhythmias involving the AV node and control of ventricular response to a-fib in HF
• Effect: Shortens duration of action potential
• Toxicities: diarrhea/vomitting (due to blocking ATPase in GI tract), visual disturbances/disorientation, arrhythmias
• Contraindication: Do not use with thiazide or loop diuretics as they cause hypokalemia and increase incidence of toxicity
• Does NOT reduce mortality
• Use anti-digoxin antibodies to treat toxicity

• Bipyridines that inhibit phosphodiesterases (break down cAMP), increasing cAMP levels and potentiating calcium channels
• Milrinone used only in refractory acute heart failure
• Inamrinone causes bone marrow and liver toxicity

• Beta-1 selective agonist that increases cAMP synthesis
• Used for stimulating the heart in CHF or acute MI
• Increases cardiac output but has little effect on heart rate or vascular effects

Atrial vasodilator used in refractory cases

Arterial and venous vasodilator used in refractory cases

• Sodium channel blockers
• Three Groups

Combo of hydralazine and isosorbide dinitrate useful in reducing the mortality in African Americans

• Prolong AP duration
• Dissociate with intermediate kinetics
• Include procainamide, dysopyramide, and quinidine

• Class IA anti-arrhythmic agent
• Use: Atrial and ventricular arrhythmias (typically as short term)
• Primary mechanism: Blocks activated voltage-gated sodium channels and remained bound to the inactivated channels
• Secondary mechanism: Inhibition of voltage-gated potassium channels involved in repolarization
• Side effects: Torsades de pointes, lupus-like syndrome (malar rash, arthralgia, arthritis)
• Drug interactions: Hypokalemia with diuretics, steroids, amphotericin-B; contraindicated in drugs that increase the QT interval (macrolide/quinolone antibiotics, chloroquine, antidepressants/psychotics, ondansetron, Group III anti-arrhythmic agents)

• Class IA anti-arrhythmic agent
• Use: Ventricular arrhythmias
• Primary mechanism: Blocks voltage-gated sodium channels and remains bound to the inactivated channels
• Secondary mechanism: Inhibition of voltage-gated potassium channels involved in repolarization
• Side effects: Significant antimuscarinic effects
• Never used as a first line of treatment because can cause/aggravate heart failure

• Class IA anti-arrhythmic agent
• Use:
• Primary mechanism: Blocks voltage-gated sodium channels and remains bound to the inactivated channels
• Secondary mechanism: Inhibition of voltage-gated potassium channels involved in repolarization
• Side effects: Diarrhea (cause hypokalemia), nausea, vomiting, cinchonism (headache, dizziness, tinnitus)

• Have no effect on AP duration
• Dissociate with rapid kinetics
• Includes lidocaine and mexiletine

• Group 1B anti-arrhythmic agent
• Use: To terminate ventricular tachycardia and other ventricular arrythmias (ONLY for ventricular stuff)
• Mechanism: Blocks activated and inactivated sodium channels from inside the cell by diffusing across (pH mediated->requires uncharged base to cross membrane but charged base to bind)
• Little to no effect on QRS and QT interval
• Side effects: Restlessness, tremor, convulsions, respiratory depression, nystagmus, arteriolar dilation, CV collapse
• Drug interactions: increases risk of seizure, watch with drugs that lower seizure threshold

Not to be used prophylactically

• Group 1B Anti-arrhythmic
• Has little effect on AP duration but dissociates with rapid kinetics
• Oral administration only
• Resistant to liver first pass metabolism
• Used to treat pain

• Have minimal effect on AP duratoin
• Dissociate with slow kinetics
• Includes flecainide, propafenone, moricizine

• Group 1C Anti-arrhythmia agent
• Use: supraventricular arrhythmias
• Mechanism: Blocks activated sodium channels and remains bound to inactivated channels; also blocks delayed rectifier potassium channels
• Side effects: cause heart failure (esp in conjunction with calcium blockers)
• BIG KEY: use to treat young patients who present with sudden onset of supraventricular arrythmia and no history of heart disease/problems

• Beta-receptor blockers
• Includes propalol, esmolol, metoprolol, atenolol, timolol

• Nonselective beta antagonist
• MoA: blocks B1 receptor activation, preventing stimulation of sodium If channel during phase 4, preventing T-type Ca channel activation during phase 4, preventing L-type channel activation in phase 0
• Effects: Decreases SA nodal firing frequencing, increases AV node conduction time, prolongs AV refractoriness, and decresaes AV node automaticity
• Use: Terminating re-entrant AV node arrhythmias, reducing post-MI arrhythmias (reduces mortality), v-tach, SVT, slowing ventricular rate during a-fib and a-flutter
• SE: bronchospasm, impotense, bradycardia/AV block/CHF, sedation, sleep alterations, may mask hypoglycemia, dyslipidemia
• Treat OD with glucagon

• B1 selective antagonist used IV that is ultra short acting
• MoA: blocks B1 activation of heart, leading to decreased SA firing frequency, decreased AV node automaticity, increased AV conduction time, and prolonged AV refractoriness
• Use: Terminating re-entrant AV node arrhythmias, reducing post-MI arrhythmias (reduces mortality), v-tach, SVT, slowing ventricular rate during a-fib and a-flutterSE: bronchospasm, impotense, bradycardia/AV block/CHF, sedation, sleep alterations, may mask hypoglycemia, dyslipidemiaTreat OD with glucagon

• Potassium channel blockers
• Includes Ibutilide, sotalol, bretylium, amiodarone, and dofetilide
• "K IS BAD"

• Potassium channel blocker that has secondary effects of beta, sodium, and calcium channel blocker
• Effects: Increases PR interval and slightly prolongs QRS and QT interval
• Used when other antiarrhythmics fail
• Use: V-tach/v-fib resistant to other drugs, maintaining sinus rhythm in a-fib, and as an arrythmia prophylaxis post-MI (decreases mortality)
• SE: Pulmonary fibrosis, bradycardia, hypotension, torsades, hyperthyroidism/hypothyroidism (is 40% iodine by weight), corneal microdeposits, gray-blue skin discoloration (from deposits that lead to photodermatitis)

• L-type calcium channel blockers (phase 0)
• Includes verapamil and diltiazem

• L-type calcium channel blockers that affect phase 0 of the action potential, cuasing decreased SA firing frequency, increased AV conduction time, and prolonged AV refractoriness
• See increased PR interval on EKG
• Use: SVT arrhythmias an in pt with comorbidities (htn, angina, or Reynaud's syndrome)
• SE: exacerbates HF, bradycardia, and constipation
• Combining it with beta blocker can cause asystole
• Use with digitalis can lead to toxicity and heart block

• MoA: Stimulates vagal ACh release (leading to activation of potassium channels [hyperpolarizing the cells] and inhibition of voltage-gated Ca channels)
• Use: Dx and abolishing re-entrant SVT arrhythmias (SVT tachycardia)
• SE: flushing, hypotension, chest pain
• Effects blocked by theophylline

Effective in treating torsades de pointes and arrhythmias caused by digoxin toxicity

• Cardiac glycoside
• MoA: Inhibits the Na/K ATPase, leading to inhibition of the Na/Ca exchanger/antiport, causing increased intracellular calcium and positive inotropy; also stimulates the vagus nerve
• Use: Re-entrant arrhythmias involving the AV node, controlling ventricular response to a-fib, CHF (because it increases contractility)
• SE: cholinergic (nausea, vomiting, diarrhea, blurry yellow vision), hyperkalemia
• Worsened by: renal failure, hypokalemia, and quinidine (blocks digoxin clearance)
• Antidoe: slowly normalize K+, lidocaine, cardiac pacer, anti-digoxin Fab fragments, and Mg2+

• Short acting B2 agonist used for acute bronchospasm asthma treatment
• Mechanism: Stimulates B2 receptor, stimulating AC to produce more cAMP, leading to bronchodilation of the airway muscle
• Perferred route: Inhaled
• Side effects: Skeletal muscle tremor, cardiac tachycardia, hypokalemia, nausea, vomiting, headache, paradoxical bronchospasm

• Long acting B2 agonists (LABA) used for moderate/severe persistant asthma in conjunction with corticosteroids
• Mechanism: Stimulates B2 receptor -> adenylyl cyclase stimulation (AC) -> increased cAMP -> bronchodilation
• Perferred route: Inhaled
• Side effects: Skeletal muscle tremor, tachycardia, hypokalemia, vomiting, nausea, headache, higher risk of asthma related death
• Salmeterol should NOT be used for monotherapy or for acute rescue
• Fomoterol can be used as both a controller and a reliever

• Muscarinic antagonists used for inhalation therapy for COPD or in asthma (either as adjuvant or for patients intolerant of B2 agonists)
• Mechanism: Blocks M3 receptor on airway smooth muscle and submucusal glands (preventing constriction and mucus production)
• Preferred route: inhalation
• Side effects: Anti-muscarinic effects (dry mouth, constipation, palpitations, blurred vision, urinary retention); high doses can hallucinations, tachycardia, and narrow-angle glaucoma

• Leukotriene receptor antagonists used for mild to moderate asthma, especially for exercise or aspirin induced asthma
• Mechanism: Block the leukotriene receptor (CysLT) in the cell, prevnting binding of LD4, LE4, and LC4, preventing smooth muscle contraction, eosinophil migration, and edema
• Preferred route: Oral
• Toxicities: Eosiniphilia, vasculitis, hepatotoxicity
• Safety/efficacy not est in pt <5 yr

• 5-lipoxygenase inhibitor that prevents leukotriene production
• Used in mild or moderate asthma as an alternative to corticosteroid therapy
• Mechanism: Inhibits 5-lipoxygenase enzyme (reducing leukotriene synthesis)
• Preferred route: Oral?
• Toxicities: hepatotoxicity
• Safety/efficacy not est in pt <12 yr

• Corticosteroids used in asthma control
• Mechanism: Inhibits production of leukotrienes, prostaglandins, and platelet activating factor, NOSi, COX-2, cytokine receptors (reducing the mediators of inflammation)
• Preferred route: ?
• Toxicities: suppression of adrenal-pituitary axis if taken orally; throat thrush and hoarseness with inhalation
• Does NOT prevent or cure asthma

• Used for antigen and exercise induced asthma
• Mechanism: Blocks chloride channel functions, leading to inhibition of calcium influx; on mast cells, this results in prevention of release of histamine/LTX; may inhibit other inflammatory cells
• Side effects: throat irritation, cough, bronchospasm, mouth dryness
• Only valuable if used prophylactically as cannot reverse bronchospasm (no effect on airway smooth muscle)

• Anti-IgE antibody used for severe asthma that is inadequately controlled by other agents
• Mechanism: inhibits IgE binding to mast cells (preventing degranulation)
• Side effects: anaphylaxis, malignancies, helminth infections

• Used as a lipid lowering agent
• Mechanism: inhibits HMG CoA reductase, the rate limiting step of cholesterol synthesis
• Results in increased hepatic LDL receptor uptake and icnreased conversion/export of cholesterol to bile acids
• Contraindicated: pregnancy/lactation, major liver disease, with cyclosporine, erythromycin, fibrates, and niacin
• SE: Incr serum transaminases and CK, myopathies, ab pain, diarrhea, constipation, headaches

• Lipid lowering agent
• Mechanism: Inhibits lipolysis in the periphery and synthesis/esterification of fatty acids in liver (impairs hepatic synthesis of VLDL); also promotes secretion of tPA and lowers fibrinogen levels
• Has largest impact on HDL and only agent that lower Lp(a)
• SE: flushing (prostaglandin mediated), skin drying, and GI intolerance

• Lipid lower agent
• Mechanism: Acts at PPAR-alpha ligands to block hepatic production of VLDL (liver responds by increasing HDL to transport more TG to the liver)
• SE: GI intolerance and incr incidence of gallstones
• Interactions: incr myostitis risk on statin, dose reduction if pt is on warfarin

• Lipid lowering agent
• Mechanism: Binds bile acids in the GI tract and blocks re-absorption (causes liver to increase cholesterol conversion to bile acids for secretion)
• SE: GI issues

• Lipid lowering agent
• Prototype: ezetimibe
• Mechanism: Blocks initial absorption of cholesterol (causing incr hepatic uptake of cholesterol and reductions in LDL)

• Med for Angina
• Mechanism: Nitrates are converted to NO by aldehyde dehydrogenase, stimulating GC to increased cGMP, which activates PKG and leads to smooth muscle cell relaxation by potentiating potassium channel opening, decreasing intracellular calcium, and activating MCCP
• Oral administration is not effective
• VASODILATES VEINS MORE THAN ARTERIES (decreases preload and therefore demand)
• Drug effects: decreases ventricular volume, atrial pressure, and ejection time (decr oxygen requirement), decreases platelet aggregatoin to control thrombosis formation
• Side effects: Reflex tachycardia (leading to increased oxygen requirement and decreased coronary perfusion), reflex incr in contractility (increases oxygen deman), orthostatic htn/syncope, headache, and incr cranial pressure
• Interactions: causes hypotension w/ sildenafil and anti hypertensives/anesthetics, syncope with depressants; monitor BP with MONA

• Primary mechanism: Decreases heart rate, contractility, and cardiact output
• Secondary mechanism: renin secretion
• 1st line therapy for chronic stable angina as it decr the frequency and threshold
• Pros: It decr oxygen consuption and diastolic coronary perfusion
• Cons: It incr end diastolic volume and ejection time
• Nonselective antagonists cause bronchospasm, while B1 have less?
• SE: Asthma, AV block, acute heart failure, and sedation

• Mechanism: Verapamil and diltazem blocks L-type calcium channels (affects cardium > vascular); nifedipine blocks L type channels more (affects vascular > cardium) never use nifedipine for angina
• Mechanism in angina: decreases contractility, cardiac output, peripheral resistance, and coronary tone
• Amlodipine: Good for LV dysfunction as it has minimal inotropic effects
• Pros: Decreases oxygen consumption, increases perfusion time of the coronary arteries, and dilates the coronary arteries
• Cons: Nifedipine increases heart rate and decr blood pressure
• SE: Exacerbate CHF (not amlodipine), fluid retention, SA/AV nodal depression, increased MI risk due to reflex tachycardia and incr oxygen demand, and asystole when used with Beta blockers