Drugs affecting vasculature and BP

Question 1

Nitric Oxide (NO)

Answer 1

eNOS catalyses the conversion of L-arginine -> NO.
NO moves from the endothelial cell to the smooth muscle cell and activates guanylate cyclase which converts GTP -> cGMP -> PKG and ultimately leads to relaxation.
Thus, NO is a potent vasodilator.

Question 2

Organic Nitrates (mechanism)

Answer 2

Relax all types of smooth muscle

Increase coronary blood flow - improved perfusion of ischaemic zone

Question 3

Organic Nitrates (examples)

Answer 3

GTN

• short acting, undergoes first pass metabolism
• administration: sublingually (tablet/spray) before exertion
• IV infusion in ACS

Isosorbide Mononitrate

• longer acting, resistant to first pass metabolism
• administration: oral

Question 4

Organic Nitrates (clinical uses)

Answer 4

Angina

ACS

Question 5

Organic Nitrates (adverse effects)

Answer 5

Tolerance
First dose hypotension
Headaches

Question 6

ACE inhibitors (mechanism)

Answer 6

End in -pril
Block the conversion of angiotensin 1-> angiotensin 2
ACE inactivates bradykinin, so ACEi activates bradykinin which causes vasodilation
Cause venous dilation, arteriolar dilation
Reduce aldosterone release

Question 7

ACE inhibitors (clinical uses)

Answer 7

Hypertension
Heart failure
Following MI
Diabetic nephropathy

Question 8

ACE inhibitors (adverse effects)

Answer 8

Dry cough
Hypotension
Not used in Renal artery stenosis
Contraindicated in pregnancy

Question 9

ARB’s (mechanism)

Answer 9

End in -sartan

Block the agonist action of angiotensin II at AT1 receptors in a competitive manner.

Question 10

ARB’s (clinical uses)

Answer 10

Hypertension
Heart failure
Following MI

Question 11

ARB’s (adverse effects)

Answer 11

Not used in renal artery stenosis

Contraindicated in pregnancy

Question 12

CCB’s (mechanism)

Answer 12

Prevent the opening of L-type Ca2+ channels and thus limit the Ca2+ influx
Decrease HR
Increase AVN delay
Decrease force of contraction

Question 13

Rate limiting CCB’s

Answer 13

Act on cardiac L-type channels
Verapamil
Diltiazem

Question 14

Dihydropyridine CCB’s

Answer 14

Act on smooth muscle L-type channels

Amlodipine

Question 15

CCB’s (clinical uses)

Answer 15

Hypertension (dihydropyridines preferred)
Angina
Dysrhhythmias (verapamil)

Question 16

CCB’s (adverse effects)

Answer 16

Don't use with beta-blockers (bradycardia due to both drugs having a -ve inotropic effect) 
Hypotension 
Flushing
Headaches
Ankle oedema

Question 17

K+ channel openers (mechanism)

Answer 17

Open ATP modulated K+ channels in VSM.

Cause hyper polarisation which switches off L-type Ca2+ channels

Question 18

K+ channel openers (clinical uses)

Answer 18

Minoxidil - severe last resort hypertension

Nicorandil - angina

Question 19

a1 adrenoceptor receptor antagonists (mechanism)

Answer 19

Block a1 adrenoceptors which cause vasodilation
This results in decreased MABP
eg: Doxazosin, Prazosin

Question 20

a1 adrenoceptor receptor antagonists (clinical uses)

Answer 20

Benign prostatic hyperplasia

Hypertension

Question 21

a1 adrenoceptor receptor antagonists (adverse effects)

Answer 21

Postural hypotension

Question 22

Diuretics (mechanism)

Answer 22

Act on the kidney to increase excretion of Na, Cl, H2O

Relax vasculature

Question 23

Thiazide diuretics

Answer 23

eg: bendroflumethiazide

Inhibit NaCl reabsorption at the distal end of the convoluted tubule

Question 24

Loop diuretics

Answer 24

eg: furosemide

Inhibit NaCl reabsorption at the thick ascending look of henle to reduce Na and H2O overload

Question 25

Diuretics (clinical uses)

Answer 25

Hypertension (mainly thiazide)
Heart failure (mainly loop) 
Pulmonary oedema (IV) (loop)

Question 26

Diuretics (adverse effects)

Answer 26

Hypokalaemia
Tiredness
Arrhythmias 
Gout
Impotence