S1M3 Introduction to Cardiovascular Pharmacology

Diuretics, Thiazide-type,

Hydrochlorothiazide

Inhibits sodium reabsorbtion in the distal tubules leading to Na and water lost (as well as K+ and H++)

• Therapeutic use: For
• mild to moderate hypertension or in combination with other drugs if hypertension is severe

• Potassium depletion i.e. hypokalemia.
• Dangerous in patients taking digitalis (increases contractility), in patients with chronic arrhythmias, and in acute MI

• Onset
• of action (i.e. diuresis) ~ 2
• hours

• Peak
• effect: 4-6 hours

• Duration
• of action: 6-12 hours

Absorption: ~ 50% - 60%

Distribution: 3.6 – 7.8 L / Kg

• Protein
• binding: 68%

Metabolism: Not metabolized

Bioavailability: 70%

• Half-life
• of elimination: 5.6 – 14.8 hours

• Time
• to peak effect: 1 – 2.5 hours

Excretion; Urine (as unchanged drug)

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)

Captopril

• Inhibits angiotensin converting enzyme (a peptidyl dipeptidase)
• Prevents formation of angiotensin II and prevents breakdown of bradykinin

Hypertension,heart failure, myocardial infarction, LV dysfunction, Diabetic nephropathy

Adverse effects: 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!)

It is an Angiotensin 2 Receptor Blocker (ARBs)

• 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)

• Hypertension
• Heart Failure
• LV dysfunction after MI
• Unstable angina

Adverse effects: hyperkalemia, hypotension, renal damage, dizziness (17%)

Contraindications: PREGNANCY!

A beta blocker duh.

Non-selective beta-adrenergic receptor blocker (both B1 and B2 receptors)

• Hypertension,
• angina,
• pheochromocytoma,
• benighessential tremor,
• supra-ventricular arrhythmias,
• prevention of myocardial infarction,
• prophylaxis of migraine,
• anxiety,
• thyrotoxicosis.

• Adverse effects:
• Bradycardia,
• hypotension,
• Insomnia
• Hypoglycemia
• Hyperlipidemia
• Bronchospasm
• Sexual dysfunction :(

• Contraindications:
• Don’t withdraw abruptly,
• asthma,
• COPD,
• uncompensated congestive heart failure,
• bradycardia,
• higher than 1st
• degree heart block

pts of African descent and older than 60yrs

Inhibits calcium entry from L-type calcium channels in vascular smooth muscle and myocardium

Calcium Channel Blockers, CCBs

• Chronic stable or vasospastic angina,
• hypertension (sustained release
• tablets only – it has a short half-life (2 hours),
• premature labor

• Adverse Effects:
• flushing
• othostatic hypotension
• headache
• nausea
• sexual dysfunction

• Hypersensitivity
• Cardiogenic Shock
• Unstable angina
• Hypertensive emergencies (immediate release formula)
• Acute MI

• 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.

• 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.

• results from coronary vasospasm, which temporarily reduces coronary blood flow.
• Caused by emotional stress (increased sympathetic activity), dysfunctional coronary endothelium)

• decrease Mycardia O2 need, increase O2 to myocardium
• Vasospastic angina? reverse vaso-spasm!

• 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.

• 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.

At higher doeses: nitroglycerine decreases arterial blood pressure (ie afterload and myocardial workload)

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 doeses: nitroglycerine decreases arterial blood pressure (ie afterload and myocardial workload)

• Chronic stable, unstable or vasospastic angina
• IV for congestive heart failure CHF especially associated with myocardial infarction,
• pulmonary hypertension
• hypertension during heart surgery.

• Hypotension
• flushing
• headache (very common)
• tachycardia (with high doses)
• Contraindications: concurrent use with viagra (also a vasodilator---can get serious hypotension)!

• 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 progressive
• Patients can be stabilized and myocardial dysfunction and remodeling may improve as consequence of therapy.

• TREATMENT of HF includes treatments of all these comorbidities:
• Hypertension
• Diabetes
• Metabolic Syndrom
• Hyperlipidemia
• Ischemic heart disease
• Any other conditions (COPD, obestiy)

• Diuretics
• Digoxin (cardiac glycoside)
• ACEIs (angiotensin converting enzyme inhibitors)
• Beta Blockers (metoprolol, carvedilol, bisoprolol)
• Aldosterone antagonist
• Many more!