1 Cardiovascular drugs

What is the common cause of hypertension?

→ systolic BP >130 mm Hg OR diastolic BP >80 mm Hg on at least 2 occasionS

• results from ↑ peripheral vascular arteriolar smooth muscle tone → ↑ arteriolar resistance

What are the 2 disorders that chronic hypertension can contribute to?

1. Heart disease

2. Stroke

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HTN an important risk factor for the development of…

1. Chronic kidney disease

2. Heart failure

What are the risk factors for HTN?

• Family hx

• Age

• Medical conditions: DM, obesity, or disability status.

• Environmental factors: stressful lifestyle, high Na⁺ intake & smoking

Name the 2 factors that have a direct influence on arterial BP.

1. CO

2. Peripheral resistance

How do antihypertensive drugs ↓BP?

↓ CO & ↓ Peripheral resistance

Name the 2 mechanisms for regulating BP.

1. Baroreflexes

2. Renin–angiotensin–aldosterone system (RAAS)

Briefly explain how baroreceptors regulate BP when the pressure drops.

1. When BP falls, baroreceptors in the aortic arch and carotid sinuses send fewer impulses to the spinal cord

2. This triggers ↑ sympathetic output reflex (↓ parasympathetic output) → vasoconstriction & ↑CO

3. This causes compensatory ↑BP

Briefly explain the steps involved in elevation of BP due to activation of RAAS.

1. ↓ arterial pressure or ↓ Na⁺ triggers the kidney to release renin

2. Renin converts angiotensinogen to Ang 1

3. ACE converts Ang 1 → Ang 2 (potent vasoconstrictor)

4. Ang 2 ↑ BP by:

   • constricting arterioles & veins

   • stimulating aldosterone secretion → Na⁺/H₂O retention

5. ↑BP

What is the goal of antihypertensive therapy?

↓ cardiovascular & renal morbidity and mortality

Name the 4 classes of drugs that can be commonly used as initiation therapy for treatment of hypertension.

1. Thiazide diuretic

2. ACE inhibitor

3. Angiotensin receptor blocker (ARB)

4. Ca²⁺ channel blocker

Why are β-blockers not preferred in treatment of diabetes patients with hypertension?

FIND ANSWER TO THIS

What are the 3 ways by which β-blockers reduce hypertension & HF?

1. ↓ CO (

2. ↓ sympathetic outflow from CNS (prevents NE from acting on the heart)

3. Inhibit renin release from kidneys (which ↓ Ang 2 & aldosterone formation)

What are Diuretics?

↓ blood volume → ↓BP

Name 3 side effects of thiazide diuretics.

1. Hypokalemia (↓K⁺)

2. Hyperuricemia (↑ uric acid)

3. Hyperglycemia (↑ blood sugar)

Why should non-selective β-blockers not be used in the treatment of hypertension in asthma patients?

block β-mediated bronchodilation → worsen asthma

What are the 3 contraindications for β-blockers use for hypertension?

1. Reversible bronchospastic disease (e.g., asthma)

2. 2^nd & 3^rd degree heart block

3. Severe peripheral vascular disease

What is the influence of nonselective β-blockers on lipid metabolism?

disturb lipid metabolism by ↓ HDL cholesterol & ↑TG

How does bradykinin influence BP?

↑ NO & prostacyclin production

• both are potent vasodilators that ↓BP

Give 2 main side effects of ACE inhibitors.

1. Dry cough

2. Hyperkalemia

Why should ARBs not be used with ACE inhibitors?

b/c they have similar mechanisms and adverse effects

What is the concern of using ARBs in pregnant women?

teratogenic

Name hypertensives approved for use in pregnant women.

Methyldopa (mainly used for management in pregnancy)

Labetalol (used for gestational hypertension)

Hydralazine (accepted for pregnancy-induced hypertension)

Of the 3 different Ca²⁺ channel blockers, which one has the greater affinity for vascular

Ca²⁺ channels than for Ca²⁺ channels in the heart?

Dihydropyridines (e.g., Nifedipine)

Why are α-adrenoreceptor blocking agents no longer used as initial HTN treatment?

Due to their side effect profile (but may be used for refractory cases)

What is hypertensive emergency?

severe BP elevation (systolic > 180 mm Hg or diastolic > 120 mm Hg) + impending or progressive target organ damage

What drugs are used for hypertensive emergency?

1. Ca²⁺ channel blockers (nicardipine & clevidipine)

2. NO vasodilators (nitroprusside & nitroglycerin)

3. Adrenergic receptor antagonists (phentolamine, esmolol, and labetalol)

4. Vasodilator (hydralazine)

5. Dopamine agonist (fenoldopam)

What is resistant HTN?

BP that remains elevated despite an optimal 3 drug regimen + diuretic

Name drugs that can lead to resistant hypertension.

1. Sympathomimetics

2. NSAIDs

3. Corticosteroid

What is Heart failure?

→ complex, progressive disorder where heart can’t pump enough blood to meet the needs of the body

• sx = dyspnea, fatigue & fluid retention

List the underlying causes of HF.

• Hypertensive heart disease

• Atherosclerotic heart disease

• Valvular heart disease

• Congenital heart disease

List the pharmacologic intervention provides the following benefits in HF.

• ↓ myocardial work load

• ↓ extracellular fluid volume

• ↓ cardiac remodeling rate

• Improved cardiac contractility

What are Cardiac myocytes?

→ electrically excitable cells

• have spontaneous, intrinsic rhythm generated by specialized “pacemaker” cells located in the SA & AV nodes

• have unusually long action potential, which can be divided into 5 phases (0 to 4)

What are the 5 phases involved in action potential of cardiac muscle? What are the changes involved in each phase in terms of ion movement?

Phase 0 (Fast Upstroke): Na⁺ channels ("fast channels") open → fast inward current of Na⁺

Phase 1 (Partial Repolarization): Na⁺ channels are inactivated, and K⁺ channels rapidly open and close → transient outward current

Phase 2 (Plateau): Voltage-sensitive Ca²⁺ channels open → slow inward current of Ca²⁺ that balances the slow outward K⁺ leak

Phase 3 (Repolarization): Ca2⁺ channels close and K⁺ channels open → outward current of K⁺ & membrane repolarization

Phase 4 (Forward Current): Gradual increase in Na⁺ permeability → spontaneous depolarization that eventually reaches the threshold for the next AP

How is Na⁺ and Ca²⁺ balance maintained during cardiac muscle contraction?

Ca²⁺ balance

• maintained through a cycle where Ca²⁺ entry from outside the cell triggers a much larger release of Ca²⁺ from SR

• Ca²⁺ is then removed via reuptake into SR + extrusion from the cell via a Ca²⁺/Na⁺ exchange

Na⁺ balance

• restored by the Na⁺/K⁺ ATPase

What are the 4 major compensatory mechanisms evoked by failing heart?

1. ↑ SNS activity

2. RAAS activation

3. Natriuretic peptide activation

4. Myocardial hypertrophy (thickening heart)

What are the 2 major side effects of spironolactone?

1. Gynecomastia

2. Dysmenorrhea