blood pressure drugs

Question 1

what is defined as clinical hypertension?

Answer 1

clinic blood pressure 140/90 mmHg (other definitions are considered depending on method of blood pressure measurement or in those who are frail or multi-morbid)

Question 2

what are therapeutic options for hypertension?

Answer 2

→angiotensin converting enzyme inhibitors (ACE)
→angiotensin II receptor blocker
→calcium channel blocker
→thiazide like diuretic

Question 3

normally what happens with RAAS (renin-angiotensin-aldosterone system)?

Answer 3

starts with kidney detecting drop in blood pressure or reduced flow → renin being produced in kidney →through bloodstream & goes to liver where acts on plasma protein angiotensinogen to convert renin to angiotensin I →travels to lungs angiotensin converting enzyme (ACE) converts to angiotensin II which leads to:

• thirst and AVP secretion (makes you drink more fluid - AVP reduces water loss by kidneys)
• aldosterone secretion (promotes reabsorption of Na+ and water by kidneys)
• renal haemodynamics →increase circulating blood volume and increase blood pressure

Question 4

what does ACE inhibitor do?

Answer 4

angiotensin converting enzyme (ACE) inhibitors prevent angiotensin I →angiotensin II therefore reduces all the effects of angiotensin II and means decreased circulating blood volume and decreased blood pressure

Question 5

what is an example of ACE inhibitor drug?

Answer 5

perindopril

→Inhibits the action of angiotensin converting enzyme (ACE)
→Important in the treatment of hypertension AND heart failure

Question 6

what is effects of angiotensin II?

Answer 6

• Angiotensin II acts on the kidneys to increase Na+ and water reabsorption (by thirst and AVP secretion and aldosterone secretion)
• Angiotensin II is also a vasoconstrictor

Question 7

what is the first line of treatment in hypertension with type 2 diabetes?

Answer 7

• ACE inhibitors
• angiotensin II receptor blocker

Question 8

what is side effect of ACE inhibitor?

Answer 8

dry cough (excess bradykinin)

Question 9

what are some effects of the ACE inhibitor?

Answer 9

• Very valuable in treatment of heart failure (Chronic failure of the heart to provide sufficient output to meet the body’s requirements – can lead to both peripheral and pulmonary oedema)
• ACEi → decrease vasomotor tone (↓blood pressure)
• Reduce afterload of the heart
• ALSO Decrease fluid retention (↓blood volume)
• Reduce preload of the heart (volume blood return to ventricles)
• BOTH effects reduce work load of the heart

Question 10

what is alternative to ACE inhibitor? (as some people can’t tolerate ACEi)

Answer 10

angiotensin II receptor blocker

Question 11

what is an example of angiotensin II receptor blocker?

Answer 11

losartan
= used in treatment of heart failure & hypertension

Question 12

what is effect of angiotensin II receptor blocker?

Answer 12

decreased veno/arterioconstriction and so decreased blood pressure

Question 13

what is an example of a loop diuretic?

Answer 13

furosemide

= reduces pulmonary and peripheral oedema
- used to treat conditions where excessive fluid retention or edema is a concern

Question 14

what are diuretics used to treat?

Answer 14

used in treatment of heart failure & hypertension

Question 15

what are some examples of calcium channel blockers?

Answer 15

Amlodipine, nicardipine

Question 16

what do calcium channel blockers do?

Answer 16

• stop smooth muscle cells from contracting so decrease arterial blood pressure
• Decrease peripheral resistance
• Decrease arterial BP
• Reduce workload of the heart by reducing afterload

Question 17

when are calcium channel blockers used?

Answer 17

useful in hypertension, angina, coronary artery spasm, supraventricular tachycardias

Question 18

what is an example of a calcium channel blocker that isn’t effective in preventing arrhythmias but can act on vascular smooth muscle?

Answer 18

Dihydropyridine Ca2+ channel blockers

Question 19

what drugs do you use if main therapeutic treatments for hypertension don’t work?

Answer 19

antihypertensive drugs:

• Vasodilator antihypertensives
• Centrally acting antihypertensives
• Adrenergic neurone blocking drugs
• Alpha adrenoreceptor blocking drugs

Question 20

what are vasodilators antihypertensives?

Answer 20

= potent hypotensives (especially when they are given in combination with beta blocker and a thiazide diuretic)
- used for resistant hypertension (when other drugs don’t work)

Question 21

what are examples of Vasodilator antihypertensives?

Answer 21

Hydralazine and minoxidil

Question 22

what are centrally acting hypertensives and examples?

Answer 22

• used for resistant hypertension (when other drugs don’t work)

= Methyldopa and clonidine (usually very far down the line)

Question 23

what are Alpha adrenoreceptor blocker drugs and examples?

Answer 23

• used for resistant hypertension (when other drugs don’t work)

Prazosin and terazosin (usually very far down the line)

Question 24

what are positive inotropes drugs and examples?

Answer 24

= increase contractility & thus cardiac output

cardiac glycosides →example = digoxin

beta adrenergic agonist →example = dobutamine

Question 25

what is dobutamine mechanism?

Answer 25

- funny current due to hypepolarisation cyclic nucleotide gated channel (HCN) - opens to drive funny current - gated by cyclic nucleotides (cAMP) which are activated by beta adrenoceptors →PKA allows phosphorylation of channel which increases open probability = increase funny current = decrease time to get to threshold (threshold faster) - dobutamine increases the open probability = decreased time to get to threshold, also increase force of contraction

Question 26

what is problem with cardiac glycosides?

Answer 26

they improve symptoms but have no long term outcome (digoxin is example of cardiac glycoside drug)

Question 27

what is mechanism of digoxin?

Answer 27

Primary mode of action is to block Na+/K+ ATPase →Increases [Ca2+]i - after action potential Na+ out and K+ in (SOPI) by Na/K ATPase - digoxin inhibits sodium potassium pump which means rise in intracellular Na+ concentration - due to increase in intracellular Na+ concentration,the Na+, Ca2+ exchanger in membrane (usually Na+ in and Ca2+ out) = reversed so Ca2+ in, Ca2+ stored in SR (sarcoplasmic reticulum), more Ca2+ available, more Ca2+ means more cross bridges = more contraction

Question 28

what is effect of cardiac glycosides?

Answer 28

- increased heart contraction Cardiac glycosides also cause increased vagal activity - action via central nervous system to increase vagal activity - slows AV conduction - slows the heart rate Cardiac glycosides may be used in heart failure when there is an arrhythmia such as atrial fibrillation

Question 29

what is angina?

Answer 29

generally transient ischaemia (Can be stable or unstable) Angina occurs when O2 supply to the heart does not meet its need - But for limited duration and does not result in death of myocytes, Ischaemia of heart tissue - Chest pain (Usually pain with exertion like exercise)

Question 30

what are organic nitrates purpose?

Answer 30

essentially allow us to release NO which is potent vasodilator which means systematic relief between oxygen = treatment of angina - Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO to be released - NO2- is reduced to NO (Nitric Oxide) - Nitric oxide is released endogenously from endothelial cells NO →activates guanylate cyclase →increase in cGMP →lower intracellular Ca2+ conc →Causes relaxation of vascular smooth muscle

Question 31

what are examples of organic nitrates for treatment?

Answer 31

- GTN spray (quick, short acting) - Isosorbide dinitrate (longer acting)

Question 32

what does organic nitrates act on?

Answer 32

- At normal therapeutic doses it is most effective on veins  - less of an effect on arteries - Very little effect on arterioles

Question 33

how does organic nitrates alleviate synptoms? a) primary action b) secondary action

Answer 33

a) primary action: - action on venous system - venodilation lowers preload - reduces workload of the heart - heart fills less therefore force of contraction reduced (Starling’s Law) - this lowers O2 demand b) secondary action - action on coronary collateral arteries improves O2 delivery to the ischaemic myocardium - acts on collateral arteries NOT arterioles

Question 34

for treatment of angina: a) what reduces workload of the heart? b) what improves the blood supply to the heart?

Answer 34

a) - organic nitrates (via venodialtion) - beta adrenoceptors blockers - calcium channel antagonists b) - Ca2+ channel antagonists - Minor effect of organic nitrates

Question 35

when are anti-thrombotic drugs prescribed?

Answer 35

Certain heart conditions carry an increased risk of thrombus formation - Atrial fibrillation - Acute myocardial infarction - Mechanical prosthetic heart valves

Question 36

what are examples of anti-platelet drugs?

Answer 36

- Aspirin - Clopidogrel = following acute MI or high risk of MI

Question 37

what are examples of anticoagulant drugs?

Answer 37

= Prevention of venous thromboembolism - Heparin (given intravenously) - inhibits thrombin - used acutely for short term action - Fractionated heparin (subcutaneous injection) - Warfarin (given orally) - antagonises action of vitamin K - Direct acting oral thrombin inhibitors such as dabigatran