Antianginal / Heart Failure Drugs Flashcards
Isosorbide Dinitrate
Nitrate
Isosorbide Mononitrate
Nitrate
Available as oral
Isosorbide mononitrate
Available as sublingual (TABLET AND SPRAY), oral, IV, transdermal patch, and topical ointment
Nitroglycerine
Nitrate: MOA
- releases nitric oxide (NO) in vascular smooth muscle
- relaxes venous smooth muscle
- increases coronary blood flow
- reduces preload and BP (reflex tachycardia)
Nitrate: indications
Angina
Continuous use leads to tolerance
Nitrates
Do not use in HF
- Diltiazem
- Verapamil
(Nondihydropyridines)
Nitrates: adverse effects
- headache
- dizziness
- hypotension
- reflex tachycardia
Nitrates: interactions
- 5-PDE inhibitors (contraindicated if using nitrates daily)
- do not use within 24 or 72 hours of 5-PDE inhibitors use
Nitroglycerine
Nitrate
NifeDIPINE
Calcium channel blocker
Dihydropyridine
3A4 inhibitors
- Diltiazem
- Verapamil
(Nondihydropyridines)
NicarDIPINE
Calcium channel blocker
Dihydropyridine
FeloDIPINE
Calcium channel blocker
Dihydropyridine
Diltiazem
Calcium channel blocker
Nondihydropyridine
Verapamil
Calcium channel blocker
Nondihydropyridine
Calcium channel blockers: MOA
- prevent entry of Ca into cells
- peripheral vasodilation, decreased afterload
- coronary vasodilation
Decrease mycocardial contractility, heart rate, and AV node conduction
Nondihydropyridine CCBs
Adverse effects of all calcium channel blockers
Gingival hyperplasia
Adverse effects of dihydropyridines
- dizziness, headache
- peripheral edema
- reflex tachycardia
Adverse effects of nondihydropyridines
constipation
Indicated for atrial arrhythmias
- Diltiazem
- Verapamil
(Nondihydropyridines)
AmloDIPINE
Calcium channel blocker
Dihydropyridine
Increases Digoxin levels
Verapamil
B-Blockers
- decreases heart rate and contractility therefore DECREASES OXYGEN DEMAND
- INCREASES DIASTOLIC FILLING therefore better coronary perfusion increases oxygen supply
Selective B-blockers
Atenolol
Metoprolol
Nonselective B-blockers
Propranolol
Ranolazine
B-blocker
Ranolazine: pharmacokinetics
Metabolized by 3A4
Indicated for treatment of CHONIC ANGINA
Ranolazine
Should not be used w/ 3A4 inducers or strong 3A4 inhibitors
Ranolazine
Warning: QT prolongation (caution w/ other drugs that can cause QT prolongation
Ranolazine
Ranolazine: adverse effects
- constipation
- dizziness
- headache
How do we treat acute angina?
- sit or lie down
- NTG under the tongue (do not swallow)
- wait 5 minutes for pain releif
- if no pain relief, call 911
- may repeat 2 more times
Definition of HF
Complex CLINICAL SYNDROME that results from any structural or functional impairment of ventricular filling or eject blood
Cardinal manifestations of HF
- dyspnea
- fatigue
- may limit exercise tolerance and fluid retention
- may lead to pulmonary or splanchnic congestion and/or peripheral edema
When is the term “heart failure” preferred over “congestive heart failure?”
when patient presents w/o signs/symptoms of volume overload
Pathophysiology of heart failure
Reduction in tissue perfusion activates neurohumoral system response
- Renin-angiotensin-aldosterone system (RAAS)
- Sympathetic nervous system
Pathophysiology of heart failure: RAAS
- vasoconstriction (angiotensin II)
- Angiotensin II stimulates secretion of aldosterone (causes remodeling and fibrosis) and antidiuretic hormone
- Angiotensin II causes Na and water retention
- Angiotensin II leads to cardiac remodeling and fibrosis
Pathophysiology of heart failure: SNS
- Vasoconstriction
- cardiac remodeling leading to myocyte death
Digoxin
Digitalis glycoside
Adrenergic agonists
Dobutamine
Phosphodiesterase inhibitor
Milrinone
Increase Carbamezapine levels
- Diltiazem
- Verapamil
(Nondihydropyridines)
What drugs have a positive inotropic effect?
- Digoxin
- Phosphodiesterase inhibitors (Milrinone)
- Dobutamine
What drugs have a negative inotropic effect?
- Diltiazem
- Verapamil
(Nondihydropyridines)
DO NOT USE IN HEART FAILURE
Positive inotropic definition
Increase cardiac CONTRACTILITY
Digoxin antidote
Digoxin immune Fab
Digoxin: pharmacokinetics
- Renally excreted
- Very low therapeutic index (monitor for toxicity)
Indicated for HF (reduces morbidity but NOT MORTALITY) and Atrial Fib
Digoxin
Blurred vision, yellow, green, or blue colors
Digoxin
Adverse effect includes anorexia, N&V
Digoxin
Adverse effect includes arrhythmias (most common AV block)
Digoxin
Digoxin MOA/pharmacologic effect
HF: POSITIVE INOTROPIC and NEGATIVE CHRONOTROPIC AND DROMOTROPIC EFFECT
- inhibits Na pump and increases intracellular Na causing more Ca to enter the myocyte, thus INCREASING CONTRACTILITY
Atrial Fib: INCREASES PARASYMPATHETIC TONE and REDUCES SYMPATHETIC TONE
- slows heart rate
- slows AV node conduction velocity
Can cause seizures
Digoxin
Amiodarone
Propafenone
Verpamil and diltiazem
can increase Digoxin serum levels
Used for short term management of acute HF and cardiogenic shock
Dobutamine
Aluminum and Magnesium containing antacids
Cholestyramine/Colestipol
can decrease Digoxin serum levels
Precipitate Digoxin toxicity by enhancing pharmacodynamics effects
Diuretic induced hypokalemia
Can also cause ventricular arrhythmias and hypokalemia can precipitate arrhythmias
Digoxin
Dobutamine adverse reactions
- tachycardia
- arrhythmias
Milrinone indication
Short term management of acute HF (usually less than 48 hours)
Inhibits type III phosphodiesterase
Milrinone
Milrinone MOA
increases cardiac contractility and relax vascular smooth muscle (vasodilation) by inhibiting type III phospodiesterase
Nesiritide adverse effects
- Hypotension
- Renal impairment
Nesiritide
Vasodilator
Form of human b-type natriuretic peptide; causes vasodilation of vascular smooth muscle and vasodilation
Nesiritide
Indicated for acute DECOMPENSATED HF
Nesiritide
Dobutamine MOA
increases cardiac contractility and hear rate, small effect of preload and decreased afterload
Shown to decrease morbidity and mortality in HF patients
ACEI
Contraindicated in patients w/ a systolic blood pressure of less than 90 mm Hg
Nesiritide
ACEI w/ NSAIDs
Decreases effect of ACEI and may result in decreased renal function, hyperkalemia
ACEI w/ Lithium
increases lithium levels (leads to toxicity)
Thiazolidinediones (Rosiglitazone and Pioglitazone)
Should generally be avoided in patients w/ HF
Valsartan
Angiotensin II Receptor Blocker (ARB)
ACEI w/ Spironolactone, Eplerenone, Potassium supplements, ARBs, Trimethoprim
Increase potassium levels (hyperkalemia)
What should be considered in patients who are intolerant to ACEI such as cough (do not inhibit bradykinin)?
ARBs
When should you use caution when using ARBs?
In people who have developed angioedema while on ACEI.
ARB drug interactions
same as ACEI drug interactions
Hydralazine/Isosorbide Dinitrate
Vasodilator
What does isosorbide do?
relaxes VENOUS smooth muscle
When may you use Hydralazine and Isosorbide Dinitrate (Nitrates)?
if intolerante to ACEIs or ARBs; can be used as an alternative
What does hydralazine do?
relaxes ARTERIAL smooth muscle
Candesartan
Angiotensin II Receptor Blocker (ARB)
Indicated in African Americans on optimal therapy w/ ACEIs, B-blockers, and diuretics.
Hydralazine and Isosorbide Dinitrate
What do B-blockers do?
Reduce excessive sympathetic stimulation of the heart
- sympathetic activation also increases activation of RAAS
- chronic stimulation of sympathetic nervous system leads to hypertrophy and apoptosis
- increases cytokines
REDUCES MORTALITY AND MORBIDITY
B-blockers and NSAIDs
decrease effect of B-blockers
Metformin
Should generally be avoided in patients w/ HF (in “acute congestive heart failure”)
Effects on morbidity and mortality are not known
Loop diuretics
Antiarrhythmics (except Amiodarone)
Should generally be avoided in patients w/ HF
Non-DHP CCBs
Should generally be avoided in patients w/ HF
NSAIDs and COX2 inhibitors
Should generally be avoided in patients w/ HF
Nondihydropyridines: Indications
- HTN
- Angina
- Atrial arrhythmias
Strong 3A4 inhibitor/s (e.g. Azole antifungals and clarithromycin) increase levels of…
calcium channel blockers (Dihydropyridines and Nondihydropyridines)
