Vasodilators

Question 1

HOw does clonidine work?

Answer 1

A2 agonis ( minimal a1 action)
Indirect- decreases NA release, lessens a1 simulation and so reduces sympathetic tone

Question 2

SIde effects of clonidine?

Answer 2

Diuresis as inhibits ADH
Inhibits insulin release
Rebound hypertension following abrupt cessation

Question 3

Selective a2 agonist?

Answer 3

Dexmedetomidine

Question 4

WHat is trimetaphan and how does it work?

Answer 4

Ganglion blocking agent-
Non depolarising competitive antagonist of nicotinic receptor of autonomic ganglia
REduces sympathetic input to peripheral vasculature + so vasodilates

Question 5

What is guanethidine and how does it work?

Answer 5

Adrenergic neurone blocking agent
Enters the neurone via uptake 1 NA pathway
Displaces NA and prevents further release
Decreased a1 stimulation

Question 6

How does hydralazine work?

Answer 6

MAINLY ON ARTERIOLES
Both through direct activation of guanylyl cyclase and by acting as a possible NO donor (that activates guanylyl cyclase)
INcreases levels of cGMP (from GTP)
DEcreases sensitivity to calcium and decreases calcium entry into smooth muscle cells

Question 7

SIde effects of hydralazine?

Answer 7

tachycardia (reflex)
Fluid retention
INcreases cerebral blood flow
GI
Long term use can cause a lupus type syndrome

Availability dependes on acelator status

Question 8

HOw do nitrates work?

Answer 8

Nitrate converts to NO which activates guanulul cyclase
More CGMP

Question 9

WHere does GTN work ?

Answer 9

Lower doses on veins
Higher doses on arterioles

Question 10

WHy can GTN be given transdermally?

Answer 10

V lipid solubleSi

Question 11

side effects of GTN

Answer 11

HEadache, flushing, post. hypotension

Question 12

Misc facts about GTN

Answer 12

Can get tolerance due to depletion of sulphydryl groups, can cause methaemoglobin
GTN is absorbed by PVC

Question 13

HOw does sodium nitroprusside work?

Answer 13

SImilarly, converts to NO which activates guanylyl cyclase -> increased cGMP

Question 14

Sodium nitroprusside kinets/dynamics

Answer 14

Only parenteral
Rapid on/off
Acts on both arterioles and venules
INcreases ICP
Activates RASS and increases plasma catecholamines
Hypoxic pulmonary vasoconstictino can be inhibited causing shunt

Question 15

Side effects of SNP?

Answer 15

Can react with oxyhaemoglobin in RBC to form cyanide- high infusion rates can cause cyanide accumulation
Is also broken down into cyanide on exposure to light so kept in foil

Question 16

How does magnesium work?

Answer 16

Blocks catecholamine receptors such as a1 and decreases response of vessels to catecholamines
Also blocks L type calcium channels and prevents entry
MAgnesium is also a cofactor in the generation of cAMP

Question 17

CAlcium channel blockers MOA

Answer 17

Reduces ca entry into cells and results in vasodilation
REduced myocardial contractility
reduced propogation of cardiac depolarisation

Question 18

Subgroups of calcium channel blockers?

Answer 18

-Phenylalkylamines- eg verpamil- antiarrhythmic
-Dihydropyridines- nifedipine, amlodipine - mainly arteriolar vasodilation. ANtiHTN + anginal
- Benzothiazepines- DiltiazemAffects peripheral and myocardial channels, mostly used as antianginals

Question 19

How do thiazide diuretics lower BP?

Answer 19

At lower doses, activates potassium channels causing hyperpolarisation and relaxation
HIgher doses inhibit sodium + chloride reabsorption in DCT

Question 20

ACEi subgroups?

Answer 20

Active drug, metabolized to active metabolites- captopril
-Pro drug activated in the liver- ramipril
-Active drug excreted unchanged in urine- lisinopril

Question 21

SIde effects of ACEi

Answer 21

Transient hypotrnsion
renal failure if RAS
REduced aldosterone- hyperkalaemia + hyponatraemia
Dry cough (accumulation of bradykinin)
Prteinuria