S1M3 Introduction to Cardiovascular Pharmacology
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What is the first line of therapy for hypertension?
What is the MOA of hydrochlorothiazide (a thiazide diuretic)?
Inhibits sodium reabsorbtion in the distal tubules leading to Na and water lost (as well as K+ and H++)
What is the Therapeutic use of Hydrochlorothiazide(a thiazide diuretic)?
- Therapeutic use: For
- mild to moderate hypertension or in combination with other drugs if hypertension is severe
What is the most common adverse effect of the use of Hydrochlorothiazide(a thiazide diuretic)?
- Potassium depletion i.e. hypokalemia.
- Dangerous in patients taking digitalis (increases contractility), in patients with chronic arrhythmias, and in acute MI
What are the pharmacokinetics of Hydrochlorothiazide (a thiazide diuretic)?
- of action (i.e. diuresis) ~ 2
- of action: 6-12 hours
Absorption: ~ 50% - 60%
Distribution: 3.6 – 7.8 L / Kg
Metabolism: Not metabolized
- of elimination: 5.6 – 14.8 hours
- to peak effect: 1 – 2.5 hours
(as unchanged drug)
A patient of African descent tends to retain sodium---would it be ok to give them Hydrochlorothiazide?
Yes, because it inhibits sodium reabsorption in the distal tubules leading to Na and water loss (and K+ and H+ loss, which is why you don't want to give this thiazide diuretic to anyone who has hypokalemia or is taking digitalis)
What is one example of an Angiotensin Converting Enzyme Inhibitor (ACEIs)?
What is the MOA of Captopril (ACE inhibitor)
- Inhibits angiotensin converting enzyme (a peptidyl dipeptidase)
- Prevents formation of angiotensin II and prevents breakdown of bradykinin
What is the therapeutic use of Captoril (ACE inhibitor)?
Hypertension,heart failure, myocardial infarction, LV dysfunction, Diabetic nephropathy
What are the Adverse effects and Contraindications of Captopril (ACE inhibitor)?
Hypotension in patients with hypovolemia, Dry cough, Hyperkalemia, Angioedema (rapid swelling)
- Contraindications: Pregnancy: 1st
- trimester teratogenicity,
- 2nd and 3rd trimesters (fetal hypotension) and malformations
- Interactions: Potassium supplements, Potassium sparing diuretics
- NSAIDs block the vasodilating effects of bradykinin (bradykinin causes dry cough!)
What is Valsartan?
It is an Angiotensin 2 Receptor Blocker (ARBs)
What is the MOA of Valsartan (Angiotensin 2 receptor blocker)
- Blockage of angiotensin II receptor 1
- By blocking AT receptor 1, it prevents vasoconstriction, and aldosterone release
- Does NOT produce a dry cough. (Captopril does)
What are the therapeutic uses of Valsartan (Angiotensin 2 receptor blocker)?
- Heart Failure
- LV dysfunction after MI
- Unstable angina
What are the adverse effects and contraindications of Valsartan (Angiotensin 2 receptor blocker)?
Adverse effects: hyperkalemia, hypotension, renal damage, dizziness (17%)
What is Propranolol?
A beta blocker duh.
What is the MOA of Propranolol (Beta Blocker)?
Non-selective beta-adrenergic receptor blocker (both B1 and B2 receptors)
What are the Therapeutic uses of Propranolol (Beta Blocker?)
- benighessential tremor,
- supra-ventricular arrhythmias,
- prevention of myocardial infarction,
- prophylaxis of migraine,
What are the adverse effects and contraindications of Propranolol (Beta blocker)?
- Adverse effects:
- Sexual dysfunction :(
- Don’t withdraw abruptly,
- uncompensated congestive heart failure,
- higher than 1st
- degree heart block
Beta blockers don't work well in?
pts of African descent and older than 60yrs
What is the MOA of Nifedipine (Calcium Channel Blockers CCBs)
Inhibits calcium entry from L-type calcium channels in vascular smooth muscle and myocardium
Calcium Channel Blockers, CCBs
What are the therapeutic uses of Nifedipine (CCBs)?
- Chronic stable or vasospastic angina,
- hypertension (sustained release
- tablets only – it has a short half-life (2 hours),
- premature labor
What are the adverse effects of Nifedipine (Ca2+ blocker)?
- Adverse Effects:flushing
- othostatic hypotension
- sexual dysfunction
What are the contraindications of Nifedipine (Ca2+ blocker)?
- Cardiogenic Shock
- Unstable angina
- Hypertensive emergencies (immediate release formula)
- Acute MI
What is Chronic Stable Angina?
- the most common type of angina. It is caused by a chronic narrowing of coronary arteries due to atherosclerosis.
- This narrowing is readily observed in the large epicardial arteries by coronary angiography.
What is Unstable Angina?
- Avery dangerous type of angina that predisposes the individual to a high risk of myocardial infarction.
- Unstable angina is caused by transient formation and dissolution of a blood clot within a coronary artery.
- The clots often form in response to plaque rupture in atherosclerotic coronary arteries; however, the clot may also form because diseased coronary artery endothelium is unable to produce nitric oxide and prostacyclin that inhibit platelet aggregation and clot formation.
What is Vasospastic Angina (or Variant or Prinzmetal's Angina)?
- results from coronary vasospasm, which temporarily reduces coronary blood flow.
- Caused by emotional stress (increased sympathetic activity), dysfunctional coronary endothelium)
How do you treat angina?
- decrease Mycardia O2 need, increase O2 to myocardium
- Vasospastic angina? reverse vaso-spasm!
What is the MOA of Nitroglycerine? [sublingual,
IV, oral (controlled release), transdermal, topical]
- Converted to Nitric Oxide (NO) by aldehyde dehydrogenase in mitochondria.
- NO activates guanylyl cyclase increasing cGMP.
- cGMP inactivates myosin light chain kinase leading to smooth muscle relaxation. Sulfhydryl (SH) groups suppled by cysteine are required for formation of NO.
The effect of Nitoglycerine is dependent upon what?
At higher doeses
- effect on blood vessels is does dependent!
- At lower doses: nitroglycerine decreases preload by dilating systemic and pulmonary veins. Decrease end-end diastolic pressure, heart size, wall tension and myocardial O2 deman, Also deacreases pulmonary vascular resistance.
: nitroglycerine decreases arterial blood pressure (ie afterload and myocardial workload)
At lower does what is Nitroglycerine's effect?
At lower doses: nitroglycerine decreases preload by dilating systemic and pulmonary veins. Decrease end-end diastolic pressure, heart size, wall tension and myocardial O2 deman, Also deacreases pulmonary vascular resistance.
At higher doses what is Nitroglycerine's effect?
At higher doeses: nitroglycerine decreases arterial blood pressure (ie afterload and myocardial workload)
What are the Therapeutic uses of Nitroglycerine?
- Chronic stable, unstable or vasospastic angina
- IV for congestive heart failure CHF especially associated with myocardial infarction,
- pulmonary hypertension
- hypertension during heart surgery.
What are the adverse effects and contraidications of Nitroglycerine?
- headache (very common)
- tachycardia (with high doses)
- Contraindications: concurrent use with viagra (also a vasodilator---can get serious hypotension)!
What is heart failure?
- reduced pumping efficiency of the heart resulting from myocardial weakness or loss.
- Can be with left ventricular dilation or hypertrophy or both
- This leads to either or both pulmonary and systemic venous congestion and or inadequate peripheral oxygen delivery at rest or during stress.In the absence of appropriate therapeutic intervention, HF is progressivePatients can be stabilized and myocardial dysfunction and remodeling may improve as consequence of therapy.
Treatment of heart failure?
- TREATMENT of HF includes treatments of all these comorbidities:
- Metabolic Syndrom
- Ischemic heart disease
- Any other conditions (COPD, obestiy)
Drugs used in the treatment of Heart Failure?
- Digoxin (cardiac glycoside)
- ACEIs (angiotensin converting enzyme inhibitors)
- Beta Blockers (metoprolol, carvedilol, bisoprolol)
- Aldosterone antagonist
- Many more!
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