Drugs affecting blood pressure Flashcards
What are the factors causing primary hypertension?
Smoking Obesity Diet (e.g. salt) Exercise (lack of) Genetic
How many of the cases are primary hypertension?
Roughly 90%
How many of the cases are secondary hypertension?
<10%
What is an example of secondary hypertension?
Renal hypertension or pheochromocytoma
What does chronic hypertension lead to?
Further cardiovascular disease E.g. Atherosclerosis Stroke Myocardial infarction Heart failure Renal failure Retinopathy
What are the benefits of antihypertensive therapy?
40% reduction of stroke
25% reduction in myocardial infarction
>50% reduction in heart failure
What is the equation to calculate blood pressure?
BP= Total peripheral resistance x Cardiac output
How do you calculate cardiac output?
CO= Heart rate x Stroke volume
What are the ways of lowering blood pressure by drug action via the block of sympathetic nervous system
Reduce effects on heart (beta1-blockers)
Reduce effects on blood vessels (alpha1-blockers
Reduce renin release from kidney (beta1-blockers)
What are the ways of lowering blood pressure by drug action via the kidney?
Reduce blood volume (diuretics)
What are the ways of lowering blood pressure by drug action via hormones?
Inhibit renin-angiotensin-aldosterone system (angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers)
What are used to lower blood pressure by drug action?
Via: Block of sympathetic nervous system Kidney Hormones Vasodilation of peripheral resistance arterioles (Ca2+ channel blockers)
What are examples of beta-adrenoceptors?
Propranolol (beta1 and beta2) and atenolol (beta1 selective)
What do competitive reversible antagonists do?
Decreases pressure via blockade of beta1 sympathetic tone on heart and reduction in renin release from kidney
Decrease in heart rate and stroke volume
Decrease in cardiac output
What are the adverse effects of beta-adrenoceptor blockers?
Exacerbate asthma (block of beta2- abslute contraindication)
Intolerance to exercise
Hypoglycaemia
Vivid dreams
What are some examples of alpha-adrenoceptor blockers?
Phentolamine (alpha1 and alpha2)
Doxazosin, prazosin (alpha1 selective)
What are alpha-adrenoceptor blockers?
Competitive reversible antagonists
Decreases blood pressure via decreases in sympathetic tone in arterioles (alpha1 (decreases peripheral resistance)
What are the adverse effects of alpha-adrenoceptors?
Postural hypotension (loss of sympathetic venoconstriction) Reflex tachycardia (via baroreceptors)
What are some examples of ACE inhibitors?
Captopril and enalapril
What do ACE inhibitors do?
Angiotensin Converting Enzyme on vascular endothelial surface converts angiotensin I to the active angiotensin II
What effects do ACE inhibitors have?
Lower blood pressure
How do ACE inhibitors lower blood pressure?
Reduced formation of the vasoconstrictor angiotensin II (decrease in peripheral resistance)
Reduced blood volume (loss of angiotensin II- stimulated release of aldosterone, thus reduction of renal reabsorption of Na+ and water)
What are the adverse effects of ACE inhibitors?
Sudden fall in BP on 1st dose
Persistent irritant cough- due to reduced breakdown of bradykinin, a peptide that activates sensory nerves in lung tissue
What are the two receptor subtypes of angiotensin II receptor blockers?
AT1
AT2
What does AT1 receptor mediate?
Vasoconstrictor and aldosterone-releasing actions of angiotensin II
What are some examples of AT1 blockers?
Losartan and candesartan
What are AT1 blockers useful for?
Antihypertensive agents
Are side effects seen with AT1 blockers?
No
No irritant cough as seen with ACE inhibitors
What are some examples of diuretics?
Bendroflumethiazide (a thiazide)
What do diuretics do?
Lower blood pressure by reducing blood volume
What is the mechanism of diuretics?
Mechanism is through reduced renal reabsorption of Na+ and water
(additional vasodilator action may also contribute: decrease peripheral resistance)
What are the adverse effects of diuretics?
Decrease in plasma K+
What are examples of calcium channel blockers?
Verapamil, dlitiazem and nifedipine
What do L-type voltage operated calcium channel do?
Open upon membrane depolarisation
Calcium entry into cardiac and vascular smooth muscle
What do L-type voltage operated calcium channels reduce?
Ca2+ entry into vascular smooth muscle and cardiac muscle by blocking L-type voltage-operated calcium channels
What are the 3 mechanism of L-type channel blockers?
Open channel block
Allosteric modulation
Tissue selectivity
What drugs use open channel block mechanism?
Verapamil and diltiazem
What do allosteric modulation bind to?
Allosteric site and reduce channel opening
Nifedipine works this way
What is tissue selectivty in smooth muscle?
nifedipine > diltiazem > verapamil
What is tissue selectivity in cardiac muscle?
verapamil > diltiazem > nifedipine
How do calcium channel blockers lower blood pressure?
Reducing peripheral resistance (block of Ca2+ entry into vascular smooth muscle → vasodilation)
Reducing cardiac output (block of Ca2+ entry into cardiac muscle- heart rate and stroke volume both reduced)
1»2
What are the adverse effects of calcium channel blockers?
Headache
Constipation
Cardiac dysrhythmias (negative chronotropic effect and slowed conduction)
