Drugs for Coronary Heart Disease (CHD)

Question 1

Definitions (NICE guidance):

Answer 1

Cardiovascular disease (CVD): disease of the heart & blood vessels.

• most common manifestation of CVD: coronary heart disease (CHD)
• also known as coronary artery disease and ischaemic heart disease.

Question 2

CHD is caused by

Answer 2

the narrowing of the arteries that supply the heart and is due to a gradual build-up of fatty material called atheroma.”

Question 3

Angina pectoris

Answer 3

Crushing pain in chest that may radiate to arm, neck or jaw
- Most commonly on exertion
The pain results from cardiac ischaemia

Question 4

CVD stats:

Answer 4

CVD single most common cause of death in the UK
(238,000 in 2002: 50% CHD, 25% stroke).

• approx. 30% of deaths “premature” (

Question 5

What are the pathophysiological problems in CHD?

Answer 5

narrowing of coronary arteries by atheroma (fatty gunge)
- so… not enough oxygen reaches heart muscle
- so… Oxygen DEMAND exceeds SUPPLY
- So… Heart muscle is HYPOXIC
Artery BLOCKED –> HEART CELLS DIE
CONSEQUENCES:
Anaerobic metabolism – cells don’t work well (less blood pumped);
- may “misbehave” electrically (conduction problems & arrhythmias)
Pain: ? Metabolites ? Mediators

Question 6

HEART ATTACK (MI)

Answer 6

Myocardial infarction – coronary artery completely blocked, typically by blood clot on ruptured plaque
Drugs as per previous slide (Beta blocker, ACE inhibitor) plus:
More) anti-platelet therapies
Make blood less likely to clot
Death of infarcted tissue
Clot-busting” drugs (thrombolytics)
Speed is critical - “Door-to-needle” time
Injured cells “misbehave” – e.g. arrhythmias
Anti-arrhythmia drugs
Severe pain
Major painkillers (e.g. morphine, diamorphine)

Question 7

Nitrates - (nitrovasodilators)

Answer 7

Commonest: Glyceryl Trinitrate (GTN)
Used for > 100 yrs for angina pain
Fast-acting
Sublingual tablet, nasal spray, transdermal patch
Unwanted effects common
Tolerance develops
Preparations differ in “shelf-life” (tablets go off quickest)
Short- and longer-acting nitrates used
Rapidly metabolized by liver (esp. GTN)

Question 8

Nitrates – Common unwanted effects

Answer 8

Throbbing headache - cerebral vasodilatation
Dizziness (esp. on getting up) – lowered blood pressure

Caution with:
Other BP-lowering drugs (BP can be too low!)
Other drugs acting on NO pathway eg Sildenafil

Question 9

STATINS: (developed as HMG-CoA reductase
inhibitors BUT may work via other
mechanisms)

Answer 9

HMG-CoA red‘ase is rate-limiting step in cholesterol synthesis
dose-dep. reduction total [cholesterol] AND [LDL cholesterol]
latter via upregulation of LDL receptors
first available on prescription 1987
(relatively) few side-effects
GI upset (usually wears off)
abnormal liver tests (usually mild)
muscle problems (myopathy – rare but serious)
Trials show effective in 2o AND 1o prevention of heart attacks
2o – existing CHD 1o – no CHD yet but high future risk
works any age, + diabetes, ♂ / ♀