UMP2006 pharmacological basis of the treatment of high blood pressure Flashcards
what is hypertension defined as?
- systolic BP above 140mmHg and diastolic BP above 90mmHg
what are the 2 different types of causes of hypertension?
- essential/primary = no known cause/ many factors like environmental/genetics?
- secondary = hypertension with identifiable mechanism e.g. pheochromocytoma, primary aldosteronism, Cushing’s syndrome
what is the equation for blood pressure?
blood pressure = cardiac output x total peripheral resistance
cardiac output = stroke volume x heart rate
what is the equation for cardiac output?
- cardiac output = stroke volume x heart volume
give all the different drug classes used to treat hypertension
- alpha adrenoreceptor antagonist
- adrenergic neurone blockers
- beta blockers
- sympathetic ganglion blockers
- ACE inhibitors
- angiotensin receptor blockers
- diuretics
- nitrates
- Ca channel blockers
- K channel activators
how do Ca channel blockers treat hypertension?
- prevent Ca entry into cells which is needed for contraction, thus blood vessels relax and open more and for the heart muscle to contract less and less strongly
= decreasing total peripheral resistance and cardiac output
give some examples of Ca channel blockers (hypertension)
dihydropyridines (such as nifedipine and amlodipine) (bp only)
and the nondihydropyridines (diltiazem and verapamil) (bp and heart)
how do K channel openers treat hypertension?
- they let more K out of the cell
- this blocks the action of ATP on Katp channels which causes hyperpolarisation, preventing Ca channels from opening
- so low Ca = less contraction = relaxation
give some examples of K channel openers (hypertension)
minoxidil and diazoxide ( not used commonly)
how do nitrovasodilators treat hypertension?
- they cause the release of NO (nitric oxide) which activates guanylate cyclase which increases cGMP causing relaxation and vasodilation locally in endothelial and muscle tissue
(short term fix)
give some example of nitrovasodilators (hypertension)
Glyceryl trinitrate (nitroglycerin), sodium nitroprusside
(not used for chronic hypertension)
give some example of a smooth muscle vasodilator and how they lowers blood pressure
- thiazide diuretics e.g. bendroflumethiazide
- lowers bp but not through diuresis
- thought to cause vasodilation but mechanism unknown
- (might be due to reduced Ca entry caused by Na depletion or by synthesis of prostaglandins, or by opening K channels)
- hydralazine ( unknown - maybe activation of guanylate cyclase)
give examples of drug classes that effect the sympathetic nervous system that reduce blood pressure
- a1 antagonists
- a2 agonists
- beta blockers
- ganglion blockers
- drugs that block catecholmine synthesis
- drugs that block storage and release of NA from presynaptic terminal
how do alpha 1 adrenoreceptor antagonists lower blood pressure?
- block effect of noradrenaline on blood vessels which constricts them, causing relaxation and vasodilation
give some examples of alpha 1 antagonists (hypertension)
Doxazosin. Prazosin. Terazosin
how do sympathetic ganglion blockers lower blood pressure?
- they block sympathetic action potentials from being transmitted beyond the ganglion to the receptors = no neurotransmitters released = no effect = relaxation
give an example of a ganglion blocker drug (hypertension)
- hexamethonium ( not used anymore)
how do K sparing diuretics lower blood pressure?
- block ENaC or inhibit aldosterone receptor (which normally causes Na and thus water reabsoption in the kidneys)
- therefore they cause more Na and water to be excreted, decreasing blood volume and thus blood pressure
give some examples of K sparing diuretics (hypertension)
Spironolactone
Amiloride
Triamterene
Eplerenone
how do alpha 2 adrenoreceptors agonists lower blood pressure?
- they are similar to noradrenaline, so act as negative feedback in the vasomotor centre in the medulla, so reduce excitation to pre-ganglionic neurones, so no release of noradrenaline = relaxation
give some examples of alpha 2 agonists (hypertension)
clonidine and guanabenz, guanfacine
give some examples of drugs that lower blood pressure by inhibiting the synthesis of catecholamines
- a-methyltyrosine = inhibit tyrosine hydroxylase which converts L-tyrosine to L-DOPA
- disulfiram = inhibit dopamine Beta-hydroxylase which converts dopamine to noradrenaline
give some examples of drugs that act on the medulla to decrease blood pressure
- alpha 2 agonists
- a-methyl DOPA
- a-methyl Dopamine
- a-methyl Noradrenaline
= all similar to the precursor or noradrenaline, act as negative feedback in the medulla to reduce excitation to preganglionic neurons = prevent release of NA = relaxation
describe how beta blockers lower blood pressure
- block the effects of adrenaline/noradrenaline on Beta adrenoreceptors in the heart and blood vessels which causes both to contract less = heart beat less and vessels vasodilate and relax = decrease blood vessels
- they also reduce renin release, reduce sympathetic tone and reset baroreceptor reflex
give some examples of beta blockers used to treat hypertension
atenolol
bisoprolol
carvedilol.
metoprolol
nebivolol
propranolol
describe the renin-angiotensin-aldosterone system
- decreased Na concentration (low bp) of the juxtaglomerular apparatus in the kidneys causes renin secretion
- renin causes angiotensinogen (from the liver) to convert to angiotensin 1
- ACE from the lungs and renal endothelium converts angiotensin 1 to angiotensin 2
- angiotensin 2 = increases sympathetic activity, increases aldosterone which increases Na,Cl and water reabsorption and K excretion in kidneys, vasoconstriction of blood vessels, causes pituitary gland to secret more ADH which causes water reabsorption from kidneys
all = increased BP
give some examples of how the renin-angiotensin-aldosterone system can be targeted to lower bp
- the system increases bp, so blocking different parts of it will decrease bp
- renin blockers
- ACE inhibitors
- angiotensin 1 receptor blockers
- aldosterone receptor blockers
give an example of a renin blockers (hypertension)
- aliskiren
give some examples of ACE inhibitors (hypertension)
- Benazepril, Captopril, Enalapril, Quinapril, Ramipril
give some examples of angiotensin 1 receptor blockers (ARBs)
irbesartan, valsartan, losartan and candesartan