Alpha, Beta and Calcium Channel Blockers Flashcards
Arterial blood pressure directly proportional to the product of what?
Cardiac output (CO) and Peripheral vascular resistance (PVR)
What regulates blood pressure?
Sympathetic nervous system, the kidneys and vasoactive motors on the endothelium
What is cardiac output and how is it increased?
Stroke volume x Heart rate, increased by sympathetic Beta 1 receptor stimulation in the heart
What is peripheral vascular resistance (PVR)?
Resistance to blood flow through the arteries
How does the sympathetic nervous system regulate blood pressure?
- Short term control though baroreceptor reflex
- Modules sympathetic stimulation of CO and PVR
How do the kidneys regulate blood pressure?
- Long Term Control through Modulation of the renin-angiotensin-aldosterone system
What classes of drugs are diuretics?
- Thiazides
- Loop diuretics
- Potassium-sparing diuretics
What classes of drugs are sympathoplegic agents?
- Non-specific adrenoreceptor antagonists
- alpha blockers
- beta blockers
- CNS acting agents
What classes of drugs are direct vasodilators?
- CCBs
- Organic nitrates
What classes of drugs act on the renin-angiotensin-aldosterone system?
- ACE inhibitors
- ARBs
- Direct renin inhibitors
What compensatory mechanisms can antihypertensives be susceptible to?
- Reflex tachycardia
- Fluid retention by kidneys
- Activation of the renin-angiotensin-aldosterone system
What are examples of centrally acting sympathoplegic agents?
Clonidine and Methyldopa
What is the mechanism of action and clinical effects of sympathoplegic agents?
Increases baroreceptor influence on vasomotors
Leads to reduced SNS activation and increased parasympathetic nervous system activation
Reduces PVR, blood pressure and tachycardia
What are the adverse drug reactions of centrally acting sympathoplegic agents?
- Severe rebound hypertension if discontinued abruptly
- nightmares, sedation, diminished mental acuity
What are examples of alpha blockers?
Doxazosin, prazosin, terazosin (all alpha-1 selective)
Why are non selective and alpha-2 selective antagonists not clinically useful?
Lead to a continued release of norepinephrine which causes beta-1 stimulation in heart = tachycardia
What is the mechanism of action and clinical effects of alpha blockers?
Prevents SNS stimulation of arteriolar smooth muscle contraction.
Vasodilation, decreased PVR
What are is the general mechanism of action and side effects of beta blockers?
Lowers blood pressure by blocking Beta-1 receptors in heart.
Fatigue, depression, vivid dreams, reduced exercise capacity.
Name a non-selective beta blocker and give their mechanism of action
Propranolol
Blocks beta-1 and 2 receptors, causing a reduction in HR and contractility, reducing cardiac output and arterial pressure.
What are the adverse drug reactions of non selective beta blockers?
- Cardiac bronchospasm risk to asthmatics and COPD patients
- can reduce hypoglycaemia response in diabetics
- Nightmares, fatigue, cold extremities
What is the mechanism of action of beta-1 blockers?
Block beta-1 receptors selectively, reduces HR and contractility = reduces cardiac output and arterial pressure, and inhibits renin secretion
What are lipid soluble variants of beta-1 blockers (Metoprolol, nebivolol and bisoprolol) more likely to cause?
CNS effects (nightmares, etc) due to BBB passage
What are the clinical effects of alpha/beta receptor blockers? (Labetalol, carvedilol)
Block alpha-1 and beta-1 receptors, reduce renin release, decrease CO and BP, lowers PVR
What are the adverse effects of non-selective alpha/beta receptor blockers? (Labetalol)
Orthostatic hypertension, Sleep disturbances, fatigue, reduced exercise capacity.
How does calcium affect cardiac muscle contraction?
- Ca2+ enters cell and binds to troponin C
- transforms myosin from a low-actin-binding state to a strongly actin-bound state
- Force of contraction depends on influx of Ca2+ into cell during an action potential
How does calcium channel blockers affect cardiac action potential?
- CCBs block L-type calcium channels (Phase 2 of action potential) and so slow Ca2+ influx into cell
- Shortens AP depolarisation -> reduces amount of intracellular calcium available for contraction
- Decreases force generated during contraction -> reduced HR
How does the effects of CCBs on cardiac tissue differ between Dihydropyridines (Amlodipine, Felodipine, Nicardipine and Nifedipine) and Non-dihydropyridines?
Dihydropyridines - MORE effect on vasodilation, LESS effect on heart function
Non-Dihydropyridines - LESS effect on vasodilation, MORE effect on heart function
Why is caution needed in giving Non-Dihydropyridines (Such as Diltiazem and Verapamil) to patients with heart failure?
They both significantly reduce cardiac output
