Lecture 5 - pharmacology of the medicines used in Hypertension treatment

Question 1

what is the first and second line treatment of hypertension?

Answer 1

1. lifestyle modification
   - weight reduction, regular exercises, DASH eating plan, reduction of dietary sodium intake, moderation of alcohol intake
2. pharmacologic treatment

Question 2

what drugs are used in the pharmacologic treatment of HTN?

Answer 2

diuretics

sympatholytics - opposes downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system. they are indicated for various functions: for example they may be used as antihypertension

at on RAAS
- calcium channel blockers
- direct - acting vasodilators

Question 3

what drugs are recommended for initial therapy in heart failure?

Answer 3

diuretics

beta blockers

ace inhibitors

angiotensin receptor blockers

aldosterone antagonists

Question 4

what drugs are used for initial therapy in post MI ?

Answer 4

beta blocker

ace inhibitor

aldosterone antagonist

Question 5

what drugs are used in the itnitla treatment for coronary artery disease risk?

Answer 5

diuretic

beta blocker

ace inhibitor

arb

ccb

Question 6

what drugs are used in the initial therapy of diabetes?

Answer 6

diuretics

beta blockers

ace inhibitors

arb

ccb

Question 7

what drugs are used in initial therapy for chronic kidney disease?

Answer 7

ace inhibitor

arb

Question 8

what drugs are used in the initial treatment for recurrent stroke prevention?

Answer 8

diuretic

ace inhibitor

Question 9

what do diuretics do?

Answer 9

all diuretics indirectly prevents the reabsorption of water in kings, most of them by preventing sodium reabsorption

Question 10

what are the classes of diuretics?

Answer 10

loop diuretics - furosemide supplemented with spirinolactone or amiloride

thiazides - bendroflumethiazide

potassium sparing diuretics - not acting on sodium channels

Question 11

describe the mechanism of action of loop diuretics

Answer 11

Loop diuretics inhibit the Na+/ K+/ 2CL- co transporter. It prevents the reabsorption of Na+, K+ and 2Cl- from the lumen into the loop of hence

major problem associated with loop diuretics is hypokalaemia

Question 12

describe the mechanism of action of thiazides

Answer 12

thiazides work by inhibiting the sodium cotransporter in the distal tubule

because this transporter only reabsorbs 5% of the filtered sodium, the are less efficacious than loop diuretics which produces natriuresis and diuresis

Question 13

describe the mechanism of action of potassium sparing diuretics

Answer 13

potassium sparing diuretics act by inhibiting the Na+ channel in the distal tubule
–> tubule and collecting duct (distal nephron)

potassium sparing diuretics are also known as aldosterone receptor antagonists

Question 14

what drugs causes renin inhibition?

Answer 14

B1 antagonists she as Aliskiren

not deemed suitable use in the UK

Question 15

where do ace inhibitors work in the body and give example of ace inhibitor drugs

Answer 15

work primarily in the lung

examples are ramipril, captopril, lisinopril, and enalapril

Question 16

describe the mechanism of action of ace inhibitors and what effect this has in the body

Answer 16

ace inhibitors block the action of the ace, to prevent the concession form angiotensin I to angiotensin II

a vasoconstrictor and stimulates aldosterone secretion

blocking its action reduces peripheral vascular resistance (afterload), which lowers blood pressure

dilates the efferent glomerular arterial which reduces intra-glomerular pressure

Question 17

what effect does reducing aldosterone level in the body have?

Answer 17

reducing aldosterone level promotes sodium and water excretion. this can help to reduce venous return (preload), which has a beneficial effect in heart failure

Question 18

describe the mechanism of action of ARBs and give examples of them

Answer 18

ARBs have a similar effects of ACE inhibitors but instead of inhibiting the conversion of angiotensin I to angiotensin II, ARBs block the action of the AT1 receptor.

examples of ARBs candesartan, valsartan and losartan

Question 19

describe the mechanism of action of aldosterone antagonists and examples of them

Answer 19

aldosterone antagonists competitively inhibit the aldosterone receptor.
they promote the secretion of Na+ and water excretion from the collecting tubule and duct

also known as potassium sparing diuretics

examples are spironolactone and eplerenone

Question 20

give an outline of sympatholytics

Answer 20

beta blockers
alpha 1 blockers
alpha/ beta blockers
centrally acting alpha-2 agonists (inhibit the release of norepinephrine)
ganglionic verve

Question 21

what are beta blocker used in?

Answer 21

used mainly as hypertension treatment

Question 22

what are the actions of beta blockers in hypertension?

Answer 22

blockade of cardiac beta1 receptors which cause a decrease in heart rate and contractility, and so decrease in cardiac output

improve efficiency

suppress tachycardia causing vasoconstriction

blockade of beta1 receptors in JG cells in the kidney –> decrease in renin release and decrease in RAAS mediated vasoconstriction (angiotensin II) and decrease in volume expansion (aldosterone)

long term use leads to a decrease in peripheral vascular resistance

Question 23

Describe the beta blockers affinity for receptors

Answer 23

some block both beta 1 and beta 2 receptors - non selective

some have greater affinity for beta-1 than beta-2 - cardioselective - but selectivity is not absolute

some are partial agonists - the are said to have intrinsic sympathomimetic activity

Question 24

what are the calcium channel blocker dihydropeptides?

Answer 24

amlodipine and nifedipine

Question 25

describe the actions of nifedipine and amlodipine dihydropeptides

Answer 25

block ca2+ channels in the arterioles
- do not have the same effects that verampil does
- used mainly for hypertension
- dilation of peripheral vessels leads to a decrease in blood pressure
- decrease of coronary arteries leads to increased coronary perfusion

do NOT block cardiac ca2+ channels at therapeutic doses

Question 26

describe nifedipine and amlodipine indirect reflex effects

Answer 26

lower blood pressure leads to increased baroreceptor reflex which stimulates the medulla. there is increased firing of SNS to beta receptors in the heart, which leads to increase heart rate and contractility

stimulating the heart may not be desirable in somebody with heart disease

Question 27

what does nifedipine lack?

Answer 27

direct cardiosuppresant actions, cardiosuppresant in unopposed.This lead to increased heart rate and contractility

Question 28

what is the net effect ?

Answer 28

sum of direct effect (vasodilation) and indirect effect (reflex cardiac stimulation)

Question 29

what are calcium channel blockers nondihydropeptidases?

Answer 29

verampil and diltiziam

can also be used for hypertension
- reduce TPvR

also act on the heart to slow conduction and decrease contractility (arrhythmias)

Question 30

describe the actions of verampil

Answer 30

blocks Ca2+ channels in arterioles, heart
- dilation of peripheral vascular resistance leads to a decreased BP
- dilation of increased coronary arteries leads to increased perfusion (better blood flow)
- blockade at SA node leads to decreased heart rate
- blockade at AV node leads to decreased nodal conduction
- blockade in myocardium leads to decreased contractile force