18. Pharmacological Treatment of CDV Disorders

Question 1

What are the UK 3 stages of hypertension?

List some causes of hypertension.

Answer 1

1: > or equal to 140/90 (ambulatory BP monitoring if more than or 135/85)
2. > or equal to 160/100 (ABPM if more than or 150/95)
3. > or equal to 180/110

Idiopathic, genetic, environmental, secondary e.g. kidney disese, renal artery stenosis

Question 2

What are the four main treatments for hypertension? Give drug examples and SEs.

Answer 2

1. Lifestyle/environmental factors e.g. salt decrease.

Then drugs, 3 classes A,C,D:

A: ACEI : interrupt RAA system, e.g. ramipril, enalapril, SE: cough, K⁺ retention, angioedema

C: CCBs: block Ca²⁺ entry to vascular SM and myocardial cells, 2 types:

Dihydropiridine e.g. amylodapine, vasodilation, SE: oedema, flushing Non-dihydropiridine e.g. diltiazem, decease HR, contractility, conduction, SE: SM in gut - constipation

D: diuretics: decrease intravascular volume -> Na+ and H2O loss -> decreased C.O., works in DCT, e.g. thiazide type = first line e.g. indapamide, also loop e.g. furosemide - mainly used in heart failure, works on LoH

Question 3

Apart from the main 4, list some other agents used to treat hypertension.

Answer 3

Alpha adrenergic blockers (doxazocin, prazocin) vasodilation

Aldosterone blockers (spironolactone)

Beta blockers (metaprolol, bisoprolol, atenolol) vasodilation but bronchospasm SE

Central alpha adrenergic agonists (methyldopa, clonidine)

Question 4

Define heart failure.

What are the 3 main causes?

Answer 4

C.O. insufficient to deliver necessary blood flow to tissues. Get pulmonary congestion, difficulty breathing and pulmonary oedema.

Mainly ischemic heart disease, also valve defects and dysrhythmias.

Question 5

How can heart disease lead to heart failure that gradually gets worse?

Answer 5

Heart disease -> heart failure then either:

decrease in renal blood flow -> RAAS -> oedema -> increased preload -> heart failure

or

decrease in tissue perfusion -> increased sympathetic nerve activity -> vasoconstriction -> increased afterload -> heart failure

So compensatory mechanisms can worsen heart failure.

Question 6

Define preload and afterload.

What is Sterling’s law of the heart?

Answer 6

Preload: end diastolic volume Afterload: end systole ventricular pressure

Increased venous return = heart beats stronger, stretched myocytes = increased overlap so more shortening per contraction thus stretch ventricles and they’ll contract more but this fails in heart failure.

Question 7

How is heart failure treated? 4 main drugs.

Answer 7

ACEIs, Beta blockers, Diuretics (furosemide, spironolactone). These 3 = heart uses less O₂ = decreases risk of dangerous rhythms.

Main goals: decrease preload and afterload, improve stroke vol (and increase C.O), increase tissue perfusion, control fluid intake, decrease salt intake.

Also positive ionotropes increase strength of muscular contractions e.g. digoxin: selectively inhibits monocyte Na⁺ pump (Na⁺/K⁺ ATPase) -> increased intracellular Na⁺ -> Na⁺/Ca²⁺ exchange means increased intracellular Ca²⁺ -> increased cardiac AP -> decreased HR

Also direct action on conduction at AVN = decreases automacity and slows heart.

Question 8

What is angina?

Where are the common sites and arteries affected?

What is the main cause of angina

Answer 8

Pain at characteristic workloads from ischaemia of myocardial muscle generally owing to artherosclerotic obstruction (plaque) of coronary BVs.

Site: chest, neck, L.arm. Arteries: L. and R. coronary (myocardial muscle O₂ demand > supply, lactic acid -> stim nerve endings = pain!) and circumflex

Atherosclerosis

Question 9

What are the 3 main treatments for angina?

Answer 9

Nitrates e.g. glyceryl trinitrate, isosorbide mononitrate - vasodilators = reduce preload, vasospasm, and platelet aggregation. SE: headaches, reduced BP

Beta-blockers e.g. bisoprolol, decreases HR and O₂ demand, SE: bronchoconstriction

CCBs: decrease SM contractility and O² demand e.g amilodipine

Question 10

How are lipids transported?

Excess of which lipoproteins are associated with cardiovascular disease?

List 3 causes.

Answer 10

Packed in lipoproteins.

LDL

Diet, environment, genetics

Question 11

What are the 3 main treatments for lowering cholesterol/lipid? Give examples and SEs.

Answer 11

1. environment/diet alteration
2. statins: inhibit rate limiting step in cholestrol synthesis e.g. simvastatin, atorvastatin, SE: myositis, rhabdomyolysis, interactions with e.g. amylodapine
3. ezetimibe: blocks cholestrol absorption from small intestine, used with statins