7. Vasodilators (1)

Question 1

Describe the proposed mechanisms of action of organic nitrates?

Answer 1

Nitrates bind to receptor in vascular smooth muscle

A NO group is formed which stimulates guanylate cyclase to produce cGMP

Calcium entry is inhibited or calcium exit enhanced and vasodilation occurs

Process requires SH groups

Question 2

What us meant by pharmacodynamics?

Answer 2

What drugs do to you

Question 3

What is meant by Pharmacokinetics?

Answer 3

What you do to drugs

Question 4

How does the pharmacodynamic effect of organic nitrates benefit the treatment of angina and heart failure?

Answer 4

Dilate arteries and veins

Venous dilation- reduction of preload which can reduce cardiac work in angina and relieve symptoms in heart failure

Dilate the normal coronary arteries and reduce coronary spasm
Redistribute blood from epicardial to endocardial regions

Question 5

What are the features of sublingual GTN?

Answer 5

Poor oral bioavailability 
Good buccal absportion 
Rapid effect 
ideal for acute phrophylaxis and diagnosis of angina 
Short angina

Question 6

What are the features of nitrate patches?

Answer 6

Absorption variable and is dependent on skin area contact
Sustained effect or no effect
Tolerance is a major problem for preparations which have 24 hr duration
Care when defibrilating

Question 7

What are the features of isoorbide dinitrate?

Answer 7

Satisfactory gut absorption
Relatively large first pass effect
Longer duration

Question 8

What are the features of isoorbide mononitrate?

Answer 8

Same as dinitrate but oral bioavailability is better due to reduced liver metabolism during first pass

Question 9

What is the combination therapy for angina?

Answer 9

1. Nitrates+ calcium antagonists
2. Nitrates+ beta adrenoceptor agonists
3. Nitrates + calcium antagonists + beta blockers

Question 10

What are adverse effects of organic nitrates?

Answer 10

Headache 
Flushing 
Hypotension with syncope 
Tachycardia 
Methaemoglobinaemia

Question 11

What are adverse side effects of all vasodilators?

Answer 11

Flushing
Headache
Tachycardia
Hypotension

Question 12

What are the different types of vasodilators?

Answer 12

Nitrates
Calcium channel antagonists
Angiotensin converting enzyme inhibitors
Alpha adrenoceptor antagonists
Centrally acting vasodilators
Direct acting vasodilators

Question 13

How do calcium antagonists work?

Answer 13

Calcium antagonists block the entry of calcium channel in vascular smooth muscle and myocardium

Less Ca available for the contractile apparatus meaning

• vasodilation
• -ve inotropic effect

Question 14

What are dihydropyridine calcium antagonists?

Answer 14

Similar to nifedipine but

-longer acting and fewer adverse effects

Question 15

Why are dihydropyridines important?

Answer 15

Favour depolarised closed Ca++ channels most commonly found in the vascular smooth cells

Question 16

Look at slide 35

Answer 16

for pharmodynamics

Question 17

What are contraindications of nifedipine?

Answer 17

Aortic stenosis

Severe myocardial depression

Question 18

What are the contraindications of diltiazem?

Answer 18

Myocardial depression

Impaired cardiac coduction

Question 19

What are the contraindications of verapamil?

Answer 19

Sick sinus syndrome
Impaired cardaic conduction
Combinations with large doses of beta blockers or digoxin

Question 20

What are major adverse effects of nifedipine?

Answer 20

Rare but can cause heart failure in patients with poor left ventricular function

Question 21

What are the major adverse effects of diltiazem?

Answer 21

May cause heart block in at risk patients and those on digoxin and beta blockers

Question 22

What are the major adverse effects of verapamil?

Answer 22

increase in agina chest pain

Question 23

What does an interaction of verapamil and diltazem cause?

Answer 23

Increase in digoxin levels

Question 24

How do you enhance the effects of verapamil?

Answer 24

Digoxin

Beta blockers