Antihypertensive Drugs

Question 1

Stages of hypertension SBP/DBP

Answer 1

Stage 1 - mild >/= 140/90
Stage 2 - moderate >/= 160/100
Stage 3 - severe >/= 180/110

Question 2

Primary vs secondary hypertension

Answer 2

Primary - cause unknown 90% cases

Secondary - identified cause e.g. Polycystic renal disease, renal artery stenosis, pheochromocytoma

Question 3

BP equation(s)

Answer 3

BP= CO x TPR
CO=HR x SV
Therefore
BP=HRxSVxTPR

Question 4

5 ACE inhibitors

Which is the worst adherence-wise?

Answer 4

• Captopril - short plasma half life so must be taken 2-3 tames a day, therefore bad for patient adherence
• Ramipril
• enalapril
• trandolapril
• lisinopril

Question 5

ACE Inhibitor mechanism

Answer 5

Blocks angiotensin-converting enzyme so angiotensin I can’t turn into angiotensin II which causes vasoconstriction
Blocking this hence causes vasodilation

Question 6

Explain ACE inhibitor side effects of oedema and cough

Answer 6

ACE normally inactivates bradykinin
Because we are inactivating ACE, this means bradykinin is not inactivated, so bradykinin is activated
Bradykinin produces spasmogen actions on bronchial smooth muscle, producing a cough
Also causes oedema

Question 7

ACE inhibitors dilate veins and arteries, what does this mean CVS wise?

Answer 7

Decrease cardiac workload
But doesn’t affect cardiac contractility
Therefore Increase in CO

Question 8

ACE inhibitor side effects

Answer 8

Rash/angiodema
Dry cough
Progressive renal failure if patient already has renal artery stenosis
DO NOT USE in pregnancy as can cause congenital abnormalities to fetus

Question 9

Advantages of using angiotensin receptor blocker

Answer 9

• well tolerated (no cough)
• reduced angiotensin II vasoconstriction
• reduced salt/water retention

Question 10

Disadvantages of using angiotensin receptor blockers

Answer 10

• Dizziness
• Hyperkalaemia
• Cost $$ (why they are not 1st line)

Question 11

Name 3 angiotensin receptor blocker drugs

Answer 11

Losartan
Valsartan
Candesartan

Question 12

Name 5 Calcium channel blockers and put a star* next to the two that are more effective in vascular smooth muscle compared to cardiac smooth muscle

Answer 12

Nifedipine*
Amlodipine*
Diltiazem 
Nicardipine 
Verapamil

Question 13

Side effects of calcium channel blockers

Warning to tell patients

Answer 13

Oedema, headache, constipation
React with grapefruit juice as also a CYP450 transporter - if taken with grapefruit juice this will increase the concentration of the drug in blood and may be harmful

Question 14

Why do calcium channel blockers cause oedema?

Answer 14

Dilation of resistance vessels, increased blood flow to capillaries
Which causes an increased hydrostatic pressure across the capillary wall at the arteriole end
Fluid loss occurs across the wall

Question 15

How Beta-1-antagonists have antihypertensive effect

Answer 15

Beta1 receptors increase HR/force of contraction and increase renin release
So if you block these
-CO reduced
-Renin release from juxta-glomerular apparatus reduced
so vasomotor centre in medulla oblongata is also reduced
Vasodilation!

Question 16

Name 5 B1-antagonists/blockers

Answer 16

Propranolol, atenolol, labetalol, bisoprolol, metaprolol

Question 17

Propranolol details

Answer 17

B1-blocker

• competitive antagonist
• non-selective beta blocker
• relatively lipid-soluble, so good CNS penetration

Question 18

Atenolol (also bisoprolol and metoprolol) details

Answer 18

Competitive antagonist
Relatively selective for B1 blockers
Relatively water-soluble - poor CNS penetration
-not 1st line as can worsen insulin resistance and other drugs are better at reducing blood pressure

Question 19

Labetalol details

Answer 19

Mixed alpha1/beta1 blocker

Can be used safely in pregnancy

Question 20

B1 blockers adverse effects

Answer 20

• Bronchoconstriction
• Precipitation of cardiac failure or heart block, but carveilol may be used in patients with heart disease
• hypoglycaemia, masks sympathetic sweating, tachycardia and tremor
• cold extremities
• vivid dreams

Question 21

Name 2 alpha blockers, which is best for adherence?

When are alpha blockers used?

Answer 21

Prozosin and Doxazosin
Doxazosin better for adherence as can be taken once daily as longer half life
Both used in antihypertensive treatment when other treatments have failed or are not acceptable

Question 22

Name 3 thiazide or thiazide-like diuretics

How do they work in the treatment of hypertension

Answer 22

Chlortalidone
Indaparmide
Bendoflumethiazide

Initially reduce blood volume, but then have a vasodilator effect

Question 23

Side effects of thiazide and thiazide-like diuretics

Answer 23

Hypokalaemia
Reduced insulin release
Increase in plasma lipid and urate
Erectile dysfunction

Question 24

Name a loop diuretic used for hypertension

What’s good about this one in particular? What is bad?

Answer 24

Furosemide
Good for resistant hypertension but
Short duration of action

Question 25

Loop diuretic side effects

Answer 25

E.g. Furosemide - can affect hearing - gout - hypokalaemia

Question 26

Name 3 potassium-sparing diuretics When are they used in treatment of hypertension? Why?

Answer 26

Amiloride, triamterene, spironolactone Used alongside thiazide diuretics Don't decrease K+, but can increase it (hyperkalamia) Can also decrease Na+ in blood (hyponatraemia)

Question 27

Name 5 vasodilator drugs

Answer 27

``` Hydralazine Minoxidil Sodium nitroprusside Methyldopa Sildenafil ```

Question 28

``` Hydralazine How it works Where it acts When it is used Side effects ```

Answer 28

Works by opening K+ATP channels Acts mainly on arteries/arterioles Used in moderate to severe hypertension and for short term treatment of hypertension in pregnancy IV in hypertensive emergencies Decrease in blood pressure causes reflex tachycardia SEs: Palpitations GI disturbance SLE-like syndrome (pain in joints and skin)

Question 29

``` Minoxidil When is it used Why is it good? How does it work? What is it given with? Side effects ```

Answer 29

``` Used in severe, resistant hypertension Very potent and long-acting Increases cardiac output and heart rate, this causes fluid retention Given with loop diuretics SEs: Peripheral oedema (see above) GI disturbance Hypertrichosis (abnormal hair growth) ```

Question 30

Methyldopa When is it used? How does it work? Side effects

Answer 30

Hypertension in pregnancy Blocks DOPA decarboxylase enzyme, hence less dopamine produced SEs: GI disturbance, dry mouth, bradycardia

Question 31

``` Sodium Nitroprusside How does it work? Bad side of it? How is it given? Side effects ```

Answer 31

NO donor, acts equally on arterial and venous smooth muscle In solution hydrolyses to cyanide Short half life so given as continuous infusion and only for short term (<72 hours) treatment SEs: Headache Dizziness Nausea

Question 32

Siledenafil Use(s) How it works Side effects

Answer 32

Pulmonary hypertension and erectile dysfunction (Trade name is Viagra) Works by blocking phosphodiesterase 5 enzyme (PDE V) SEs: GI disturbance