Prelab lab report

Question 1

Myocardial oxygen supply and demand

Pg 1

Answer 1

The coronary arteries supply blood flow to the heart.
When functioning normally, they ensure adequate oxygenation of the myocardium at all levels of cardiac activity.
Constriction and dilation of the coronary arteries regulate the amount of blood flow to the myocardium.
The amount of oxygen delivered to the myocardium matches the myocardial demand for oxygen.

Question 2

Angina

Angina is chest pain associated with transient myocardial ischaemia.
Angina is common, affecting 3.8% of people in New Zealand.
About half of patients with ischaemic heart disease initially present with symptoms consistent with angina.

Pg2

Answer 2

Angina symptoms occur when there is insufficient blood supply to the heart at times of increased oxygen demand, e.g. during exercise. This is most often due to coronary artery disease where atherosclerotic plaques in the coronary arteries cause narrowing of the lumen, reducing blood flow to the myocardium.

Angina occurs when the oxygen supply to the myocardium is insufficient for its needs. The pain has a characteristic distribution in the chest, arm, and neck and is brought on by exertion, cold or excitement

Question 3

Types of angina

One of the main groups of drugs used to treat angina are organic nitrates.

An example of an organic nitrate is glyceryl trinitrate (GTN). GTN is one of the oldest synthetic drugs still in widespread use. GTN has been used for over a century to prevent and provide relief from angina pectoris.

Pg 3

Answer 3

• Stable Angina

- Unstable Angina

Question 4

Mechanism of action

Organic nitrates are vasodilators that relax vascular smooth muscle by mimicking the effects of endogenous nitric oxide (NO).

Enzymatic degradation of organic nitrates leads to formation of nitrosothiol groups which can activate guanylate cyclase to generate the second messenger cyclic GMP (cGMP).

cGMP activates protein kinase G which reduces the availability of intracellular calcium required for muscle contraction.

• pg 5

Answer 4

This causes relaxation and vasodilation of:

Venous capacitance vessels (leading to decreased venous return)
Arterial resistance vessels (leading to reduced resistance to left ventricular emptying)
which lowers BP and decreases cardiac work

Question 5

Unwanted actions

The main adverse effects of GTN are a direct consequence of its pharmacological action and include decreased blood pressure and headache

Answer 5

Pharmacokinetics
GTN is unstable at gastric pH and is rapidly inactivated by hepatic enzymes. If swallowed, GTN is ineffective because of first pass metabolism by enzymes in the gut wall and liver.

GTN is well absorbed from the mouth and is taken as a tablet under the tongue or as a sublingual spray. It produces effects within a few minutes and its effective duration of action is approximately 30 minutes.

GTN is also quite well absorbed through the skin and a longer lasting effect can be achieved by applying it as a transdermal patch.

Stability
Once a bottle of tablets has been opened, its shelf-life is quite short because the volatile active substance evaporates. Spray formulations avoid this chemical degradation.