M2 Pharmacology Cardiology

Thiazide

diuretic (thiazide)

• Diabetes mellitus & Proteinuria: ACE inhibitors (help delay diabetic nephropathy)
• Angina: β-blockers, Ca channel blockers (help reduce work of heart)
• Benign prostatic hyperplasia: α1-blockers (help with BPH too)
• Heart failure: diuretics, ACE inhibitors, AT receptor blockers, β-blockers
• African Americans: respond better to diuretics, Ca channel blockers (higher sensitivity to sodium)

Nitroprusside, fenoldopam, labetalol

contributes to resistance (↑vessel stiffness & neural reactivity); ↑Na/Ca exchange, with increased intracellular Ca2+, and fluid retention

Loop

azotemia and hypotension

In the morning. They are only symptomatic treatment, so they are wasted at night.

Reduced renal function: avoid thiazide diuretics
Gut edema- use IV
NSAIDS
SALT

dopamine or dobutamine

• Body weight (self monitor), edema Sx
• Electrolytes (K+ >4 minimize arrhythmias)
• BP
• Renal function (Cr)
• Dehydration/postural hypotension

increase force of contraction by ↑ intracellular Ca2+, ↓central sympathetic outflow (baroreceptors), and ↓renal absorption of sodium

fatigue, visual, confusion, ↓strength, anorexia, arrhythmia, conduction block, bradycardia (worse in hypokalemia, hypomagnesium, and hypothyroidism)

Symptomatic: Exercise tolerance
atrial fibrillation

ACE-I

ACE-I

ACE-I

ACE-I

small rise in SeCr (normal and should just be monitored if 0.5), low bp (ACE-I don’t lower bp much in normotensive), cough (okay if patient can tolerate).

symptomatic takes weeks –months, improves survival, cough, angioedema

less cough

ACE-I and B-Blocker

nitrate- venous
hydralazine- arterial

Hydralazine + Isosorbide dinitrate

Alt for ACE-I: several renal insufficiency (no effect on renal function), hyperkalemia, angioedema, & pregnancy.

Downsides: AE, cumbersome dosing, not as good as ACE-I.

HA, dizziness, hypotension, rash, drug-induced lupus, reflex tachycardia, don’t take PDE inhibitor.

metoprolol and bisoprolol

Carvedilol

B-blocker

B-blocker

fatigue, edema, sexual dysfunction (start slow, takes > 2 months, don’t raise dose unless lower dose is well tolerated)

symptomatic improvement not seen for 1-3 months (exercise fatigue), keep taking drugs even if symptoms improve, helps survival even if symptoms don’t improve

ACE-I

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Each element can contain any number of sub elements.

Aldosterone antagonists

CAD (nitrates, hydralazine, amlodipine), hyperlipidemia (statins), A-fib (amiodarone, warfarin, HTN (SHEP & STOP)

Non-DHP CCP in systolic HF (too inotropic and ald ant stop catecholamines + neurohormonal activation), class I & III antiarrhythmics (- ionotropic effects), sympathomimetics (counteracts), alpha blockers (HF), glitazones (fluid retention), NSAIDS(promote Na/H2O retention, inhibit diuretics, decrease renal perfusion by prostaglandins, use other pain relievers), corticosteroids (Na/fluid retention)

carbonic anhydrase inhibitors

carbonic anhydrase inhibitors

loop diuretics

loop diuretics

-iliopsoas sign

-patient is asked to extend the right thigh against resistance with the knee flexed; the test is positive if the patient experiences pain as a result of stretching of the iliacus fascia

Loop diuretic, allergic to sulfa

thiazides

thiazides

Spironolactone, Eplerenone

Triamterene

methyldopa, hydralazine, and labetolol

methyldopa

ACE-I, B-blockers

ACE, CCB, thiazide

thiazide w/ ACE-I
B-blocker CI for asthma and bradycardia

thiazide/CCB

give B-blockers, handles HTN/angina/tachycardia.
reflex tachycardia

diet/exercise or fenofibrate

rhabdomyolysis

hypotension --> syncope

tachyphylaxis and rebound tachycardia --> angina

pancreatitis (>500)

decreased CO and shunting

metolozone

III CHF

carvedilol and metoprolol

hydralazine + isosorbide dinitrate

digoxin
BB and verapamil contraindicated

hemodynamically unstable, tx = cardioversion.
hemodynamically stable, tx = adenosine, verapamil, diltiazem, class I AA's, digoxin.

mechanical cardioversion, quinidine/procainaide cardioversion. Control rate with diltiazem, verapamil. Warfarin b/c stasis.

Acute tx: lidocaine --> procainamide. Cordarone. Adenosine. Chronic: amiodarone, pacemaker.

Ia

Tx: atrial, ventricular, paroxysmal ventricular contraction. Class II effect. AE: hypotension, QT prolongation [torsades], GI, bitter taste, bradycardia, asystole. Narrow therpeutic window, increases digoxin level.

Tx: atrial, ventricular, PVCs. AE: QT prolongation, GI, rash, hypotension. NAPA is a renally cleared active metabolite that affects K channels.

Tx: supraventricular & ventricular arrythmias. Good ventricular function require b/c (-) inotrope. AE: anticholinergic

Ib

Tx: short tern of ventricular arrythmias, local anesthetic. AE: cardiac depression, asystole, CNS stimulation/ depression, seizures, coma. Kinetics: Short T1/2, change dose in hepatic dysfunction

profoundly slows conduction velocity, no change on AP duration. TX: last resort for ventricular arrythmias.

B-blockers

MO: pure class II at low doses, class II at higher. Tx: Life threatening v. tachycardia, a. flutter, a. fib. CI: asthmatics, COPD, CHF, abrupt withdrawl. Use in hospital only. Increases mortality post-MI, short acting,, eliminated by kidneys.

MO: increases ERP but characteristics of all 4 classes. TX: tachycardias. AE: pulmonary fibrosis, cirrhosis, AV block, hypotension, bradycardia, cataracts, hypo/hyperthyroid. Check PFTs, LFTS, TFTs. T1/2 = 30-100 days. Least likely to be proarrythmic.

ibutilide
dofetilide

IV

Class II, B-blockers

IV or subQ

bleeding from GPIIb/IIIa antagonism (platelet receptors), dose dependent bleeding
Thrombocytopenia (HIT vs HIT)
LFTs
osteoporosis

venous thrombosis, PE, early in unstable angina and acute MI,

prophylaxis in surgery, blood transfusions, dialysis,

warfarin, statins, and ACE-I/ARB

decreased HIT (decreased platelet bindings), decreased osteoporosis (decreased osteoblast binding), and longer T1/2 (decreased macrophage binding)

low molecular weight heparins

hirudin, argatroban, lepirudin, bivalirubin

Less HIT

Direct Xa: Reversible binds and accelerates Antithrombin III --> inhibition of factor Xa

Less HIT

Bleeding & Coumadin induced skin necrosis

Permanent action on platelet (irreversible), lasting for life of platelet (7-10 days)

Increased dose normally only increases toxicity

Inhibit phosphodiesterase (degrades cAMP) --> ↑cAMP in platelets --> ↓ aggregation
Stimulates prostacyclin anti-platelet effects

Prevent embolization from prosthetic heart valves (given with Warfarin)
reduces thrombosis w/ aspirin

Bleeding, GI problems
Severe neutropenia: must monitor CBC closely; therefore, drug not commonly used

clopidogrel

Glycoprotein IIb/IIIa receptor antagonists

Acute coronary syndrome at high risk for further MI; Ischemia

Bleeding risks: surgery within past 10 days; serious GI bleed within past 3 months; active bleeding disorder
Cardiac: aortic dissection, acute pericarditis
Previous stroke or other active intracranial problem

• hyperchloremic metabolic acidosis (lose HCO3- in urine)
• Renal stones: calcium salts insoluble at alkaline pH
• Potassium wasting: increases load for Na/K/2Cl cotransport, increasing load for K+ secretion
• Drowsiness, paresthesias
• Cross allergenicity with sulfa derivatives

• Liver failure: alkalization = ↓ ammonium excretion = hyperammonemia -> hepatic encephalopathy
• Na+, K+ depletion

• Glaucoma: ↓aqueous humor production = ↓intraocular pressure
• Acute mountain sickness: ↓pH in CNS, which increases ventilation to reduce symptoms
• Urinary alkalization
• Metabolic alkalosis: correction of alkalosis that occurs when using loop diuretics

Loop diuretics
Thiazide

• Ototoxicity: (endolymph electrolyte alteration)
• Ion dysregulation: hypokalemia, hyperglycemia (rare), hypocalcemia, hypomagnesemia, hyperuricemia (gout)
• Lipids: ↑LDL/triglycerides, ↓HDL (cholesterol problems = hypertension)

osteoporosis (mineral loss) and sulfa allergy (use ethacrynic acid instead)

• Edema: acute pulmonary edema, edema of nephritic syndrome, edema/ascites of cirrhosis, chronic renal failure
• Hypertension: reduced renal function states (increases urine flow), alt to thiazides (symptomatic tx only)
• Drug overdose: forces excretion of Br, F, I
• Hypercalcemia tx
• Acute renal failure (increases urine flow = prevent oliguria)

Indapamide
Metolazone

uric acid (gout), NSAIDs, probenecid

• ↓glucose tolerance: important if diabetic
• Hyperlipidemia: ↑LDL, triglycerides
• Hyponatremia: Na excretion
• Allergic reactions (skin rash): associated with sulfas
• Rare weakness, fatigue, impotence

• Hypertension: DOC
• Edema
• Osteoporosis
• Nephrolithiasis from hypercalciuria: ↓ Ca2+ in urine = ↓stone formation)
• Nephrogenic diabetes insipidus (block dilute urine)

• Combined w/ diuretics to prevent hypokalemia
• Mineralocorticoid excess or hyperaldosteronisms
• Spironolactone: DOC for hepatic cirrhosis

• Renal failure, hyperkalemic
• Never used in combo with other K+ sparing diuretics or ACE inhibitors (except CHF)

• Life threatening hyperkalemia
• Metabolic acidosis in cirrhotic patients (↓ H+ excretion)
• Steroid symptoms: gynecomastia, impotence, decreased libido, hirsuitism, menstrual irregularities
• Peptic ulcers
• Triamterene: drug containing renal stones

• Spironolactone, Eplerenone (bind Ald receptors in CD)
• Amiloride, Triamterene (Interfere w/ Na+ entry in CD)

• CNS effects: sedation, depression, nightmares, vertigo
• Lactation: ↑prolactin secretion
• *Positive Coombs: hemolytic anemia, hepatitis, drug fever

• Rash at site of patch
• CNS: severe dry mouth, severe sedation, risk of depression (tricyclic)
• Rebound hypertension: abrupt withdrawal --> tachycardia, nervousness, sweating
• Wean slowly or treat with α/β blockers to blunt effects of NE

• displaces NE in nerve ending vesicles = ↓release of NE from sympathetic endings
• ↓CO (bradycardia & relaxation of capacitance vessels), ↓PVR
• Other drugs, similar effects: cocaine, amphetamine, tricyclic antidepressants, phenothiazines, phenoxybenzamine

Sympathectomy (cuts off sympathetic effects): postural hypotension, diarrhea, delayed/retrograde ejaculation, • Severe reflex sodium and water retention (RAAS)

• ↓ uptake of biogenic amines into transmitter vesicles, depleting stores
• Throughout body, affecting NE, DA, 5HT
• Hypotensive effects (↓CO, ↓PVR)

Naldolol, carteolol, atenolol

Betaxolol, bisoprolol

Pindolol, acebutolol, penbutolol

carvedilol, labetolol

• ↑risk of HF if monotherapy
• Postural hypotension (vasodilation)
• Salt and water retention (RAAS reflex)
• 1st dose phenomenon: rapid ↓ BP when standing, start w/ low dose at bedtime
• Infrequently: dizziness, palpitations, headache, lassitude

• Lupus like syndrome: rash, myalgia, arthralgia, fever (seen with slow acetylators & at high doses, reversible)
• MC: HA, nausea, anorexia, palpitations, sweating/flushing, edema
• Angina (ischemic heart disease -> tachycardia)

Minoxidil & Diazoxide

• Reflex responses: tachycardia and angina; fluid retention, with possible pericardial effusion
• Hirsuitism
• Postural hypotension

Renal failure: thiocyanate accumulates over several days à weak, disoriented, psychosis, spasms, convulsions

D1 (dopamine) agonist: causes dilation of peripheral arteries & natriuresis

glaucoma

Verapamil: constipation, due to effects on non vascular smooth muscle
• Nifedipine: reflex tachycardia & gum hypertrophy  not a good choice for DHP-CCB (best is Amlodipine)

digoxin

diltiazem and verapamil

Captopril/Lisinopril

• Hypotension: volume contraction
• Renal failure: efferent glomerular arteriolar constriction
• Hyperkalemia: ↓aldosterone, ↓GFR
• Cough & Angioedema (bradykinin): more severe at night, when lying down
• Generally well tolerated
• Sulfydral allergy: rash & fever

• Pregnancy (For pregnancy, use methyldopa, labetolol, hydralazine), bilateral renal stenosis, hyperkalemia, angioedema; marrow suppression in CRF& SLE

cough

Aliskiren ↓ plasma renin activity (thus entire RAAS);
Clonidine ↓ renin secretion by affecting renal sympathetic activity, centrally
Propranolol β-blocker, affects JG cells renin secretion

NTG

NTG

PDE5-I

decrease HR and contractility

↑Obstructive airway disease (asthma > COPD)
Heart block
Peripheral vascular disease (vasospastic): Raynaud’s
Diabetes: masks hypoglycemia symptoms, by blocking tremors; hyperglycemia in type 2 (blocks insulin release)
Rebound angina
CNS (lipophilic drugs): dizziness, fatigue, depression, lethargy, drowsiness, unusual dreams
Other: impotence, wheezing, dyspnea

Cardiac: ↓contractility (negative inotropism), ↓AV conduction, SA node depression
Vasculature: vasodilation (coronary & arterioles) = ↓afterload

CCB

Heart failure (very negative inotropic)
Heart block & Bradycardia (affects AV conduction & SA node)
Drug int: β-blockers: negative inotropy, digoxin: increases plasma concentration of digoxin  toxicity

Monitor CK levels and LFTs

no effect on carotid inter-media thickness

Lovastatin, Simvastatin, Atorvastatin (ALS)

Kidney metabolism: Pravastatin, via sulfonation (no hepatotoxicity)
Liver metabolism: CYP3A4 (Lovastatin, Simvastatin, Atorvastatin) & CYP3C9 (Fluvastatin, Rosuvastatin)

fenofibrate

Dyspepsia (associated with peptic ulcer disease), myopathy

LDL

directly reduces hepatic production of VLDL and inhibits hepatic synthesis of Apo

Prevent bile acid reabsorption (thus recycling) --> divert cholesterol to bile acid synthesis
↑cholesterol 7-α hydroxylase
↑ LDL receptors

TG

GI distress/constipation
Decreased GI absorption of other drugs (don’t give at the same time) affects lipophilic drugs (ie statin)

Cause release of prostaglandins from endothelium [flushing/itching, hypotension, transient HA]
Often need to pretreat with prostaglandin inhibitor (aspirin) or give extended release form
Hyperglycemia (↓glucose tolerance)
Upper GI distress (peptic ulcers)
Hepatotoxicity (LFTs)
Hyperuricemia (interferes with renal excretion of uric acid)
Myopathy (don’t use with fibric acids, or additive myopathy)

↓lipogenesis in liver
↑lipoprotein lipase activity

CI: Hx of Torsades, QTc > 440, K< 4.0 mEq/L, Concomitant Type 1 or III drug, HR <60, Severe LV dysfunction (EF < 30%)