Cardiac & Vascular

Question 1

Congestive Heart Failure characteristics

Answer 1

Disease of cardiac muscle:

• CO below normal range
• breathless on minor exercise
• left ankle oedema

Question 2

Hypertension

Answer 2

High bp -> VSM issues

• no symptoms with stroke/angine
• increase arterial vascular resistance

Question 3

BP =

Answer 3

BP = CO x TPR (total peripheral resistance)

Question 4

Angina

Answer 4

VSM

• pain running down left arm + chest on exercise
• coronary arterial - partial occlusion

Question 5

Indirect treatment of CHF

Answer 5

Reduce work load

• > decrease vascular resistance
• ACE inhibitors
• vasodilators
• diuretics

Question 6

What do after load and preload relate to?

Answer 6

arterial and venous pressure respectively

Question 7

Direct treatment of CHF

Answer 7

Inotropes

• cardiac glycosides
• beta 1 adrenoreceptor agonists e.g. dobutamine

Question 8

An example of a cardiac glycoside and its mech. of action

Answer 8

Digitoxin increases force of contraction by

1. inhibiting Na+/K+ ATPase
2. causing [Na+] i accumulation
3. Slowing of Ca2+ - Na+ pump
4. Ca2+ accumulation by S.R.

Question 9

Risks of using digitoxin

Answer 9

1. non-pacemaker cells can develop pacemaker activity

2. Ectopic beats + dystrhythmia from competition between glycoside and K+ which is enhanced by hypokalaemia

Question 10

What does it mean to have a low therapeutic index?

Answer 10

Therapeutic dose is near toxic dose

Question 11

Vagal tone differences with digitoxin

Answer 11

Increase vagal tone by slow A-V conduction -> longer P-R increases refractory period -> prevents fibrillation/ flutter

Question 12

Overall effects of digitoxin:

Answer 12

1. Increase CO then decrease
2. Cardiac area decrease
3. HR decrease
4. body weight decrease
5. urine output increase

Question 13

Examples of beta 1 adrenoreceptor antagonists

Answer 13

Carvedilol (also a1 antagonist) and bisoprolol

Question 14

Beta 1 adrenoreceptor antagonist uses and mech of action

Answer 14

First line therapy with ACE inhibitors decreasing mortality by 65%
- decrease sympathetic stimulation of heart (indirect)

Question 15

Hypertension is defined as

Answer 15

> 160/95 mmHg - increase peripheral resistance

Question 16

General solution for hypertension

Answer 16

Switch of NA release from SNS/ relax VSM

Question 17

Types of drugs that target hypertension:

Answer 17

1. Ganglion blockers e.g. hexamethonium
2. Alpha adrenoreceptor antagonists e.g. prazosin whibh blocks sympathetic stimulation -> decrease peripheral resistance
3. A2 agonist e.g. clonidine/ alpha-methyl DOPA (pro-drug - false transmitter) -> act centrally

Question 18

Example of a direct vasodilator

Answer 18

Minoxidil

Question 19

Minoxidil mech. of action

Answer 19

Block ATP action on KATP (which normally closes channel ) -> hyperpolarisation -> close L-type Ca2+ channels -> vasodilation

Question 20

L-type Ca2+ channels can also be blocked by

Answer 20

antagonists e.g. nifedipine

-> blocks coronary arterial spasm

Question 21

Possible angina treatments:

Answer 21

• Beta adrenoreceptor antagonists -> decrease O2 demand by decrease symp. response and increase in HR
• nitrates -> improve coronary flow
• ca2+ antagonists

Question 22

Organic nitrate mech of action

Answer 22

1. nitrite (NO2) anion, liberated within cells when organic nitrates react with tissue sulfhydryl (-SH) groups.
2. Within the cell nitrite anions are converted to nitric oxide (NO) which
3. activates cytosolic form of the enzyme guanylate cyclase causing an increase in cGMP formation.
4. cGMP activates protein kinase G and leads to a cascade of effects in the smooth muscle culminating in
5. 5/6 dephosphorylation of myosin light chains and
6. sequestration of intracellular Ca2+,with consequent
   relaxation.

Question 23

Main mechanism of anti-anginal drugs:

Answer 23

1. Reduce cardiac work due to peripheral arteriole and vein dilation
2. dilation of collateral vessels

Question 24

Glyceral trinitrate

Answer 24

Absorbed rapidly from oral mucosa
- 10 -20 min action -> metabolised rapidly by liver
-> hepatic first pass -> little escapes into systemic circulation
side effects: headache, hypotension risk of fainting

Question 25

Atenolol

Answer 25

Beta adrenoreceptor antagonist
- blocks sympathetic resp. -> adrenaline circulates on myocardium -> decrease cardiac work during exercise/ stress -> Increase O2 demand -> longer diastole so longer perfusion of coronary arteries

Question 26

Aspirin

Answer 26

Anti-platelet agent -> changes balance TBA2 between platelet aggregation + PGI2 which inhibits it
-> COX inhibition -> decrease TBA2 without drastically reducing PGI2
Low doses: prophylaxis against thrombosis

Question 27

Statins e.g. simvastatin

Answer 27

Administered orally
Used for underlying atheromatous disease
inhibits HMG-CoA reductase which is the rate limiting
step in cholesterol synthesis.

Question 28

Heparins

Answer 28

Inhibits coagulation by activating antithrombin III which inhibits thrombin formation and therefore thrombus formation.
Administered IV or subcutaneously (Low molecular weight heparin).
Side effects: haemorrhage and thrombocyopaenia.

Question 29

Glycoprotein IIb/IIIa inhibitors e.g. abciximab, tirofiban

Answer 29

IV anti-platelet agents:

- antagonise glycoprotein IIb/IIIa receptor

Question 30

Why wouldn’t I use diprymidine for a atheromous plaque?

Answer 30

Steal: blood flow to normal increase and to ischemic decrease since collateral between not dilated -> use a nitrate to dilate collateral instead

Question 31

Why would I use a diuretic or AT1 receptor antagonist instead of an ACE inhibitor for CHF and hypertension?

Answer 31

Diuretics just decrease H20 and Na+. Both diuretics and AT1 e.g. losarten doesn’t affect bradykinin (-> vasoD -> cough) unlike ACE inhibitors