Antihypertensive Drugs

Question 0

What is the renin-angiotensin-aldosterone system?

Answer 0

A system that senses the need to increase blood pressure and responding by constricting arterioles and preventing Na+ excretion.
Liver - angiotensin precursor (circulating) or renin circulating from sensor in kidney - angiotensin I - angiotensin II - AT1 receptor - aldosterone from adrenal cortex - Na+ retention and K+ excretion And vasoconstriction.

Question 1

How blood volume regulates cardiac stroke volume?

Answer 1

Increased blood volume is accommodated in distensible venous circulation, increasing venous pressure (filling pressure).
Atrium and ventricle are distensible so increased filling pressure lead to increased cardiac filling which leads to increased volume ejected with each contraction (stroke volume).

Question 2

What are the antihypertensive drug strategies?

Answer 2

Reduce cardiac output 
- B-adrenergic antagonist 
- Ca2+ channel blockers
Dilate resistance vessels 
- Ca2+ channel blockers
- Renin-angiotensin system blockers
- a1 adrenoceptor blocker
- nitrates
Reduce vascular volume
- diuretics

Question 3

Effects of cardiac B1 adrenoceptor stimulation or blockade?

Answer 3

Stimulation:
Increase heart rate
Increase contractility
Increase blood pressure
Increase heart work

Blockade:
Decrease heart rate
Decrease contractility
Decrease blood pressure
Decrease heart work

Question 4

What are metoprolol and atenolol?

Answer 4

Cardiac B1 adrenoceptor antagonist.
Clinically used as:
Antiarrythmic - slows some abnormal fast rhythms
Antihypertensive - not first line, usually as an add on
Antiangina - via reduced heart work

Question 5

What do angiotensin converting enzyme (ACE) inhibitors end in?

Answer 5

-pril

Examples: captopril, enalapril

Question 6

What do angiotensin1 receptor blockers end in?

Answer 6

-sartan

Examples: cardesartan, irbesartan

Question 7

What are the clinical uses of ACE inhibitors and AT1 blockers?

Answer 7

Reduced vascular resistance
Reduce aldosterone which reduces salt and water retention
Antihypertensive
Heart failure

Question 8

What is prazosin?

Answer 8

a1 adrenoceptor blocker.

Causes peripheral vasodilation which leads to reduced vascular resistance.

Question 9

In cardiac muscle, where is calcium stored?

Answer 9

Sarcoplasmic reticulum.

Question 10

How does calcium channel blocking drugs that act in the heart reduce blood pressure?

Answer 10

An influx of calcium can cause muscle cell contraction as the concentration of calcium extracellularly is greater than that intracellularly thus when the channels are stimulated to open they can cause contractions that lead to myocardial or vascular complications.
A calcium channel blocker like verapamil that is myocardial selective can reduce cardial contractability, reduce heart rate, blood pressure and heart work as it prevents the influx of calcium ions in the calcium channels,
On the other hand, vascular selective calcium channel blockers can reduce vascular resistance, blood pressure and heart work.

Question 11

Cardio selective calcium channel blocker?

Answer 11

Verapamil

Question 12

Vascular selective calcium channel blocker?

Answer 12

Anything that ends in "-dipine"
Dihydropyidines
- nifedipine
- felodipine
- amlodipine

Question 13

What are the clinical uses of antihypertensives?

Answer 13

Consequences of chronic high blood pressure.
Heart failure
Arterial disease
Kidney failure
Strokes
Myocardial infarction
Aim of treatment: prevent consequences of high blood pressure.

Question 14

What are nitrates used for in cardiovascular?

Answer 14

Rapid, short lived vasodilators.
Lower vascular resistance means less heart work, heart needs less oxygen.
This can be used to treat patients with coronary artery obstruction as increased heart work in them can lead to cardiac muscle hypoxia and angina.
Not used for managing high blood pressure.

Question 15

Examples of nitrates?

Answer 15

Glyceryl trinitrate (GTN)
Isosorbide (di) nitrate

Question 16

Pathway of nitrates in vascular smooth muscle cells?

Answer 16

GTN 
Organic nitrate ester reductase
NO
Guanylate cyclase
GTP
or cGMP
Protein kinase G
Relaxation

Question 17

Describe how digoxin increases cardiac contractility?

Answer 17

Digoxin is therapeutically used as a cardiac glycoside.
It’s mechanism if action increases the force of contraction by the inhibition of the Na+/K+ pump in the cardiac monocytes. Increased Na+ concentration slows extrusion of Ca+2. Increased calcium concentration is stored in the sarcoplasmic reticulum and this increases the amount of calcium released by each action potential.
Increased cardiac contractile strength in heart failure. Increase vagus nerve activity which leads to slower heart rate, slower AV conduction.
Digoxin can be toxic as various abnormal rhythms are dangerous.