antihypertensive drugs

Question 1

what blood pressure is considered to be hypertensive?

Answer 1

equal to or greater than 160/95 mmHg

Question 2

what is the level of vascular smooth muscle tone dependent on

Answer 2

alpha 1 activity

Question 3

what other physiological factors contribute to blood pressure (equation)

Answer 3

blood pressure= cardiac output x peripheral resistance

Question 4

what are symptoms of hypertension

Answer 4

hypertension is asymptomatic but leads to increased risk of heart disease

Question 5

what is treatment for mild hypertension

Answer 5

weight loss, give up smoking if a smoker, reduced alcohol intake

Question 6

what is further treatment (drugs) of hypertension

Answer 6

diuretics, beta blockers, calcium channel blockers, ACE inhibitors

if^ inadequate then vasodilators may be given

Question 7

what is mechanism of diuretics in reducing blood pressure

Answer 7

reduce blood volume by increasing sodium excretion

associated water loss then reduces blood volume and so cardiac output, reducing pressure

in long term cardiac output and plasma volumes return to original value however pressure remains lower due to reduced peripheral resistance (mechanism unclear, some relax vascular smooth muscle)

Question 8

what is mechanism of vasodilators in blood pressure

Answer 8

they are K+ (atp) channel openers:

channels close when ATP binds, vasodilators block ATP binding to these ATP sensitive potassium channels

hyperpolarisation caused by their opening of vascular smooth muscle causes voltage gated L type calcium channels to close

this reduces calcium concentration in smooth muscle, causing relaxation

relaxation of vascular smooth muscle causes decrease in peripheral resistence

Question 9

give examples of vasodilators used to treat hypertension and under what circumstances are they used

Answer 9

diazoxide: potent vasodilator, only used in hypertensive emergencies
minoxidil: only given in severe hypertension, causes hypertrichosis

Question 10

what is mechanism of calcium channel blockers in reduction of blood pressure

Answer 10

reduce calcium influx into arterial smooth muscle and to an extent in myocardial cells

causes both vasodilator effect and reduction in strength of contraction of myocardial cells

Question 11

give examples of calcium channel blocker drugs and their effect

Answer 11

nifedipine: selective for L-type calcium channels so targets vascular smooth muscle

verapamil used to decrease cardiac output

Question 12

what is mechanism of nitrovasodilators in reduction of blood pressure, name a drug and when it is used

Answer 12

used to break down nitric oxide, relaxes smooth muscle

not for day to day treatment of hypertension

sodium nitroprusside is given via IV to control severe hypertensive crisis

Question 13

give some examples of indirect vasodilators

Answer 13

alpha adrenoceptor antagonists: lower blood pressure by blocking effects of sympathetic stimulation on vasculature, e.g prazosin

adrenergic blocking agents: block release of NA from postganglionic sympathetic neurones, rarely used today, blocks sympathetic activity, not specific to vasculature, e.g guanethidine

ganglion blocking drugs: not used any more, formerly used in hypertensive crisis, side effects would be blockade of both sympathetic and parasympathetic systems

Question 14

what do all antihypertensive drugs cause (aside from reduced blood pressure)

Answer 14

will cause baroreceptor reflex to be activated since beta 1 receptors are not blocked

this causes reflex tachycardia and activation of renin angiontensin system

Question 15

give some examples of centrally acting antihypertensives

Answer 15

clonidine and alpha-methyl DOPA: have effects in CNS to cause decrease in sympathetic outflow, their action is on alpha 2 receptors in medulla

clonidine is alpha 2 selective agonist

alpha methyl DOPA is prodrug which is converted into alpha methyl noradrenaline which is highly selective for alpha 2 over alpha 1

there may be rebound hypertension if a patient is withdrawn abruptly from clonidine

Question 16

what is mechanism of beta adrenoceptor antagonists, give examples used

Answer 16

block of beta 1 adrenoceptors causes reduction in cardiac output however alpha receptors are not blocked so baroreceptor reflex compensates

fall in pressure is believed to be due to lack of peripheral resistance since cardiac output returns to normal values

examples are propranolol (crosses blood brain barrier) and atenolol (does not cross blood brain barrier)

beta blockers also block beta 1 receptors on juxtaglomerular cells in kidney which secrete renin, also lowering blood pressure

Question 17

what is mechanism of ACE inhibitors in reducing hypertension

Answer 17

renin is released from renal cortex

renin acts on angiotensin to cause inactive angiotensin 1 to split off, remainder is substrate which is converted by angiotensin converting enzyme (ACE) to angiotensin 2

angiotensin is then metabolised to angiotensin 3

angiotensin 2 is a vasoconstrictor

angiotensin 2 and 3 stimulate aldosterone secretion which causes retention of sodium and water

Question 18

give examples of ACE inhibitors used, and side effects

Answer 18

examples: captopril and enalpril

ACE inhibitors block breakdown of bradykinin, a vasodilator but bradykinin also causes coughing, so coughing is a side effect

other side effects: hypotension, hyperkalaemia and renal impairment