L17. Drugs Influencing the CVS

Question 1

What is the clinical definition of hypertension?

Answer 1

Blood pressure > 140/90 mmHg

Question 2

Hypertension is a risk factor for…

Answer 2

Stroke
MI, Ischaemic heart disease, chronic heart failure
Aortic aneurysm, retinal haemorrhage
Renal Failure
Death

Question 3

What are the risk factors for developing hypertension?

Answer 3

A multifactorial disease:

Smoking, diet, weight, stress, family Hx

Question 4

What is the aim for hypertension therapies?

Answer 4

Reduce the blood pressure below 140/85
Or below 130/80 for diabetic for obese patients
Mainly achieved by reducing the risk factors

Question 5

For Homeostatic control of blood pressure:
Regulated variable is \_\_\_\_
Sensors \_\_\_\_
Controlled variables \_\_\_\_\_\_
Effectors \_\_\_\_\_ 
Effector Signals \_\_\_\_\_\_\_

Answer 5

Regulated variable is __Blood Pressure__
Sensors __Baroreceptors and Osmoreceptors__
Controlled variables __HR and SV (CO) and TPR____
Effectors __Blood vessels, Heart and Kidney___
Effector Signals __Neuronal and Hormonal__

Question 6

Which system (Para or symp) takes precedence in controlling BP?

Answer 6

Sympathetic is the major regulator for changing blood pressure (parasympathetic is for rest situations)

Question 7

What receptors to noradrenaline and adrenaline act on to control blood pressure?

Answer 7

alpha 1 adrenoreceptors in the blood vessels

beta 1 adrenoreceptors in the heart and in the kidneys

Question 8

What are the main results of adrenaline acting on these receptors in blood y
pressure regulation?

Answer 8

Vasoconstriction
Increased HR
Increased Contractility
Increased Blood Volume

Question 9

Describe the Renin-Angiotensin System

Answer 9

Noradrenaline binding to B1 receptors in the kidney
Stimulates secretion of renin by the kidney
Converts angiotensinogen into angiotensin I
ACE converts angiotensin I into angiotensin II
Angiotensin II

Question 10

What are the main actions of Angiontensin II?

Answer 10

Acts on AT1 receptors: Vasoconstriction of blood vessels
Acts on AT1 receptors: Release of aldosterone leading to salt and water retention
Cell growth (hypertrophy of the heart) 
Positive feedback to sympathetic nervous system (increase noradrenaline)

Question 11

Why would we use Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) in hypertension?

Answer 11

They prevent the conversion of AngI to AngII: reducing vascular tone, reducing aldosterone production (reduces water retention, reduces SV) and reduces cardiac hypertrophy

Question 12

What is another mechanism of ACE inhibitors (involving bradykinin)?

Answer 12

ACE works like Kininase II: breaks down bradykinin

ACE inhibitors prevent bradykinin breakdown allowing it to have longer potent vasodilatory effects

Question 13

What are the adverse effects of ACE inhibitors?

Answer 13

Dose Dependent:
First dose hypotension
dry cough
loss of taste
hyperkalaemia (often given in combination with diuretics)
Acute renal failure
Itching, rash, angio-oedema
Foetal malformations

Question 14

What are some contraindicators of ACE inhibitors?

Answer 14

Pregnancy
Bilateral renal stenosis
Angio-neurotic oedema

Question 15

What are some examples of ACE inhibitors?

Answer 15

The -PRILS
Captopril
Perindopril
Enalapril
Ramipril

Question 16

What are the antiotensin receptor antagonists?

Answer 16

The SARTANS
Losartan
Candesartan

Question 17

What happens with you block the AT receptors?

Answer 17

AT1 and AT2
Reduce vasoconstriction
Reduce aldosterone formation
Reduce cardiac hypertrophy
Reduce sympathetic activity (inhibits the positive feedback)

Question 18

What is the major difference between AT antagonists and ACE inhibitors (that it thought to make them safer)?

Answer 18

AT antagonists do not have an effect on bradykinin

Question 19

What are the adverse effects of AT antagonists?

Answer 19

Hyperkalaemia
Headache
Dizziness

Question 20

What are the contraindications for AT antagonists?

Answer 20

Contraindicators are the same for the ACE inhibitors:
Pregnancy
Bilateral renal stenosis
Angio-neurotic oedema

Question 21

What are the b1 adrenoreceptor antagonists?

Answer 21

The -OLOLS
Propanolol
Timolol (nonselective)
atenolol
metoprolol (b1 selective)
pindolol (partial agonist for b1 and b2)

Question 22

What is the aim of using B1 adrenoreceptor antagonists in hypertension?

Answer 22

Reduce the Cardiac Output and reduce renin release (decreases blood volume) by preventing sympathetic innervation

Question 23

How to the B blockers vary within the class? [3]

Answer 23

1. Vary with selectivity (for receptors)
2. With intrinsic sympathomimetic activity (eg. partial agonist activity)
3. Vary with lipid solubility (eg. ability to cross the blood brain barrier)

Question 24

What are the adverse effects of b adrenergic receptor antagonists?

Answer 24

Cold extremities: occurs acutely when CO is dropped by the drug, a reflex alpha 1 constriction occurs
Fatigue: puts a limit on the sympathetic nervous system to increase HR and blood vessel supply
Dreams and insomnia (CNS lipid solubility)
Bronchoconstriction (B2 adrenoreceptor blockage)

Question 25

What are some contraindications for b1 adrenergic receptor antagonists?

Answer 25

Asthma Diabetes AV conduction block Must take care with heart failure and metabolic syndrome

Question 26

What are the Calcium Channel Blockers?

Answer 26

Vermpamil Diltiazem Dihydropyridines: felodipine and nifeipine

Question 27

What is the mechanism of action of the Calcium channel blockers in hypertension?

Answer 27

Inhibit voltage gated L-type Calcium channels in the myocardium and the vasculature. = reduced cardiac and vascular contractility = Reduced vascular resistance

Question 28

What are the 2 types of calcium channel blockers?

Answer 28

1. reduce cardiac and vascular contractility | 2. Reduce vascular resistance

Question 29

What are the adverse effects of calcium channel blockers?

Answer 29

Oedema, flushing, headache Bradycardia (for reduced cardiac contractility) Reflex tachycardia (for reduced vascular resistance)

Question 30

What is the mechanism of action of thiazide diuretics in terms of hypertension?

Answer 30

Inhibit NaCl co-transporter in the distal convoluted tubule of the kidneys leading to decreased reabsorption: increases the Na and water excretion form the kidney Also has a loss of K from the collecting duct = lowers blood volume

Question 31

What is an example of a thiazide diuretic used in hypertension?

Answer 31

Hydrochlorothiazide

Question 32

What is an adverse effect of the thiazide diauretics?

Answer 32

Hypokalaemia: Loss of K leading to gout, hyperglycaemia and allergic reactions

Question 33

What are some other drugs used in hypertension (when the main ones don't work)?

Answer 33

Alpha 1 adrenoreceptor antagonists Vasodilators alpha 2 antagonists (CNS) New renin inhibtors

Question 34

What are the main drugs used to combat hypertension?

Answer 34

``` ABCD Angiotensin System Inhibitors B-adrenoreceptor antagonists Calcium channel blockers Diuretics ```

Question 35

Why do we have so many anti-hypertensive drugs?

Answer 35

Because it is a multifactorial disease with both neural and hormonal control Multiple target organs, signals and proteins Often use a combination of drugs