Pharm - Drugs for hypertension & heart failure
Terms
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- Heart Failure
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- abnormal heart function
- signs of low CO and/or pulmonary or systemic congestion
- incomplete emptying of ventricle
- increased atrial/ventricular/pulmonary capillary pressure
- edema
- left or right sided heart failure - left-sided heart failure
- pulmonary edema
- right-sided heart failure
- systemic/pedal edema
- S&S of heart failure
-
- dyspnea
- fatigue (may limit exercise tolerance)
- fluid retention (may lead to pulmonary & peripheral edema) - Most used therapies for heart failure?
-
1. Diuretics
2. Beta-Blocker
3. ACE Inhibitor
4. Digoxin
5. ARB - Cardiac Output?
- CO = HR x SV
- Cardiac Preload?
- pressure in right side of the heart as blood returns to the heart
- Cardiac Afterload?
- pressure the heart must pump against within the arterial system to eject blood (PVR)
- Ischemic Heart Disease?
-
- SYSTOLIC heart failure
- reduced blood supply of the heart due to CAD - Chronic hypertension or volume overload?
- - DIASTOLIC heart failure
- Myocardial injury (Pathophysiology):
-
- causes a fall in LEFT ventricular performance
- RAAS & SNS activated causing:
- vasoconstriction - increased BP, HR
- Na+ & H20 retention
- vascular remodelling & worsening of LEFT ventricle function
- myocardial toxicity --> morbidity/mortality - RAAS (renin-agiotensin-aldosterone system)
-
Regulates:
- BP
- VOL
- fluid/electrolyte balance (aldosterone) - What causes activation of RAAS?
-
- low BP
- low blood volume
- decreased renal perfusion
- beta 1 stimulation by SNS - What is the RAAS process?
- renin released --> angiotensin I (inactive) ---converted by ACE (lung) to---Angiotensin II (active) --> aldosterone (adrenals) --> Na+ retention/H20 retention & increased K+ excretion (kidneys)
- What are the effects of angiotensin II (active)?
-
- stimulate aldosterone release
- most potent vasoconstriction (increases cardiac pumping & O2 demand)
- vascular remodelling - Heart Failure Medications:
-
BAADDA
B - Beta Blockers
A - Ace Inhibitors
A - Angiotensin II Receptor Blockers (ARBS)
D - Diuretics
D - Digoxin
A - Aldosterone inhibitors -
Ace-inhibitor drugs:
(Angiotensin Converting Enzyme Inhibitors) -
- Catopril (Capoten)
- Enalapril (Vasotec)
- Lisinopril (Zestril)
- Ramipril (Altace)
- Who should take ACE inhibitors?
-
- all patients with heart failure symptoms
- symptoms of ejection fraction (EF) less than 40% or asymptomatic EF of less than 35%
- myocardial infarction (obstruction of blood supply)
***should take maximum tolerated dose - What are some precautions for ACE inhibitors?
-
- DIURETICS increase effects
- taking with BETA BLOCKERS & DIURETICS can cause hypotension
- NSAIDS increases Na+ reabsorption (decrease effects of ACE inhibitors)
- ACE inhibitors cause retention of K+. K+ supplements should be avoided (could cause hyperkalemia)
- cause dry, hacking cough
- angioedema - edema in blood vessels (rare but life threatening) - Captopril (Capoten) - ACE inhibitor
-
- 3 times per day (TID)
- well-absorbed (less when taken with food)
- Peak: 1-2 hrs
- Half-life: 1-2 hrs
- Duration: 6-12 hrs
- Dose: 12.5-50 mg tid - Enalapril (Vasotec) & Lisinopril (Zestril) - ACE inhibitors
-
- 10-20 times MORE POTENT than captopril (capoten) with LONGER EFFECTS
- similar side effects as captopril (capoten)
- enhanced compliance
- reduced cost
- less pills/day
Enalapril (Vasotec) --> bid
Lisinopril (Zestril) --> daily - ARB Drugs (Angiotensin II Receptor Blockers)
-
Atacand (Candesartan)
Diovan (Valsartan)
Cozaar (Losartan)
Avapro (Irbesartan) - Who should take ARBs (Angiotensin II Receptor Blockers)?
-
- heart failure
- if intolerant to ACE inhibitors (because of cough)
- used in conjunction with ACE inhibitors (if persistent heart failure symptoms) OR if beta blocker is not tolerated or contraindicated - What are the functions of the kidney?
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- cleansing/maintenance of extracellular fluid (ECF)
- acid-base balance
- excretion of metabolic wastes & foreign substances
- Who should take diuretics?
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- heart failure patients with congestive symptoms (pulmonary/peripheral edema)
- supervised self-adjustment based on weight & symptoms
- volume overload
***lowest dose once congestion clears - What additional drug should be taken if persistent volume overload?
-
- Thiazide diuretic
OR
- low dose Metolazone (prototype: Furosemide (Lasix) - high ceiling loop diuretic)
**monitor weight, renal function, & K+ levels - What risks are associated with Diuretics?
-
1. dehydration/hypovolemia
2. hypotension
3. electrolyte depletion (hyponatremia/hypokalemia)
4. Azotemia (increased blood urea nitrogen)
5. Ototoxicity (ear)
6. Hyperglycemia (high blood sugar levels)
7. Hyperuricemia
8. Neurohormonal activation (RAAS) - Classification of Diuretics:
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1. Mannitol - Osmotic (Proximal Convoluted Tubule)
2. Furosemide (Lasix) - high ceiling ascending loop of hence (decreased Na+ & Cl- reabsorption)
3. Thiazide (Hydrochlorothiazide/Hydrodiuril) - early distal convoluted tubule
4. Spironolactone/Adactone - K+ retention (aldosterone antagonist) - late distal convoluted tubule
- What percentages of Na+ & Cl- is excreted for various diuretics and where?
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1. Mannitol (65%) - PCT
2. Furosemide (20%) - ascending loop
3. Thiazide (10%) - EDCT
4. Spironolactone (5%) - LDCT - Which diuretic is common, safe, and effective?
- Loop diuretics Furosemide (Lasix), ethacrynic acid
- Which diuretic is the 1st choice for hypertension & is mild?
-
Thiazide diuretics:
- Diuril (hydrochlorothiazide) - Which diuretics have additive value?
-
Thiazide analogs:
Zaroxolyn (metolazone) - Which diuretics should be taken for people with hypokalemia?
-
potassium-sparing diuretics:
Aldactone (Spironolactone) - What are Thiazide Diuretics?
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Hydrochlorothiazide (hydrodiuril)
- most widely used for mild hypertension
- less potent than loop diuretics
- bind at early distal convoluted tubule
- dependant on good renal function
- peak: 4-6 hrs - Adverse effects of Thiazide diuretics:
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SAME AS LOOP DIURETICS (except NOT ototoxic!! - relating to ear)
1. dehydration/hypovolemia
2. hypotension
3. electrolyte depletion (hyponatremia/hypokalemia)
4. Azotemia (increased blood urea nitrogen)
5. Hyperglycemia (high blood sugar levels)
6. Hyperuricemia
7. Neurohormonal activation (RAAS) -
Potassium Sparing Diuretics
(Aldosterone Inhibitors) MOA: -
Spironolactone (Aldactone):
- binds to aldosterone receptors in late DCT
- K+ is retained and 5% of Na+ is excreted - Who should take potassium-sparing diuretics (aldosterone inhibitors)?
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People with:
- hypertension
- edema
- severe heart failure (WITH hypokalemia) - low K+
- primary hyperaldosteronism (too much aldosterone produced by adrenal glands) - What is the main osmotic diuretic?
-
Mannitol (osmitrol)
- receptor site: proximal convoluted tubule - Who should take osmotic diuretics such as mannitol (osmitrol)?
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- people who have renal failure
- increased intracranial pressure (ICP)
- increased intraocular pressure (IOP) - What are the adverse effects of osmotic diuretics? Mannitol (Osmitrol)
- - very potent (should be used in ICU (intensive care units)
- Who should take Digoxin (Lanoxin) - Inotropic drugs?
-
- moderate to severe heart failure with symptoms, in sinus rhythm
- little or no effect on survival but may increase exercise tolerance
- for chronic atrial fibrillation (too many contractions & poor cardiac output) & rate control despite beta blocker
- limited affect when used alone to treat heart failure - Digoxin (Lanoxin) - Inotropic drug MOA?
-
- inhibits Na+K+ ATPase in cardiac cell membranes (inhibits Na+ release and K+entry)
- intracellular Na+ & Ca++ increases
causing:
1. increased actin-myosin coupling --> increases FOC --> increases CO
2. slows SA node depolarization/conduction --> decreases HR --> increased filling & CO
***overall - stronger contraction but less often - What are digoxin (Lanoxin) precautions?
-
- long half-life
- easily retained in small people, elderly, women, renal impairment and can cause toxicity
- hypokalemia increases effects of Digoxin & worsens risk of toxicity
- TOXICITY:
- N/V
- visual changes
- dysrhythmias
- anorexia
- headache
- confusion
- antacids increase absorption & effect
- check pulse: if less than 50 (don't give) - What is the onset, half-life, duration and therapeutic range for digoxin (lanoxin)?
-
- Onset: 0.5 hrs IV, 3 hrs PO
- Half-life: 32-48 hrs
- Duration: 6 days
- Therapeutic Range: 0.5 - 1.1 mg/ml (VERY NARROW)
**monitor serum levels carefully! - What is Inotropic?
- modifying the force or speed of muscle contraction
- What are some inotropic drugs for heart failure?
-
Cardiac glycosides:
Digoxin (Lanoxin) - What are drug interactions with Digoxin (Lanoxin)?
-
1. Antacids - increase absorption & effect of digoxin
2. Quinidine, Verapamil
- displaces digoxin from tissue binding sites
- decreases renal excretion of digoxin - What are some non-pharm measures for heart failure?
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- moderate aerobic exercise
- Na+ restriction
- daily weights
- flu/pneumonia vaccine
- 1.5-2L of fluids/day