W3 Physiology and Pharmacology Workshop

Question 1

If you need to directly target stroke volume with drugs acting at heart muscle cells, suggest a receptor target and indicate how the drugs’ action on it may affect the stroke volume. (2)

Answer 1

• Beta-adrenoreceptor antagonists (beta blockers), block sympathetic activation and negative inotropy and lead to reduced stroke volume.
• Calcium channel blockers (CCBs) block the L type calcium channel on the cardiomyocytes and block the excitation contraction coupling and heart muscle contraction, leading to reduced stroke volume.

*negative inotropy- weakens force of heartbeat

Question 2

If you need to target peripheral resistance using a vasodilatory drug, suggest two drug classes. Among them, one class of drug directly acts as a vasodilator and the other one acts at a defined receptor subtype. Give drug examples.

Answer 2

Direct vasodilator= Nitrates
Receptor subtypes: alpha/beta blockers, CCBs and others

Question 3

What is stroke volume?

Answer 3

The volume of blood pumped out of the left ventricle
of the heart during each systolic cardiac contraction

Question 4

Which class of anti-hypertensive drug is an example of physiological antagonism* of blood pressure?

Answer 4

Diuretics (Loop diuretics, thiazide-like diuretics, K-sparing diuretics)

*A drug that produces the opposite physiological effect to that of an agonist will indirectly oppose the action of that agonist

Question 5

What are the 3 main types of diuretics?

Answer 5

Loop, Potassium sparing, thiazide-like
each act on a different part of the kidneys

Question 6

Nitric oxide (NO) released from the endothelial cells acts on the adjacent vascular smooth muscle cells to dilate. Briefly illustrate the mechanisms by which NO stimulate vascular smooth muscle dilation. (5)

Answer 6

1.NO stimulates CGC- Cytoplasmic guanylyl cyclase
2. Elevation of intracellular cGMP
3. Activates protein kinase G
4. Leads to Smooth muscle relaxation (vasodilation)
5. PDE isoform breaks down cGMP

Question 7

What are the types of nitrates used in clinics? Briefly describe the systemic, cardiac and coronary effects of nitrates.

Answer 7

Direct and Organic (requires enzymes)
Systemic effects
- Vasodilation
Cardiac effects
- Reduced preload and afterload
Coronary effects
- Prevents/reverses vasospasm

e.g. isosorbide dinitrate (organic)
nitroglycerin (direct)

Question 8

Why are patients over 55 years and of African Caribbean origin, not prescribed ACE inhibitors first line?

Answer 8

• Age-mediated natural loss of nephrons (compromised renal functions)
• Insufficiency of Renin-dependent blood regulation in African Caribbean ethnic background. (low renin levels)

Question 9

Why does ACE inhibition affect the following levels in the blood
a) Potassium level
b) Bradykinin

Answer 9

The ACE inhibitors block the production of angiotensin II and prevent the downstream secretion of aldosterone.
Consequently, the decreased aldosterone concentrations lead to reduced sodium reabsorption (hyponatremia) in the nephron and subsequent retention of excessive potassium (hyperkalaemia) and protons (metabolic acidosis) in the blood.

b) ACE inhibitors block the breakdown of bradykinin, and increase bradykinin levels, which can contribute to the vasodilator action. Accumulation bradykinin induces sensitisation of airway sensory nerves via rapidly adapting stretch receptors and C-fiber receptors that release neurokinin A and substance P. This causes airway smooth muscle to constrict leading to bronchoconstriction and persistent dry cough. (most common adverse effect, 10-20% of patients)