Hypertension

Question 1

Hypertension

Answer 1

High blood pressure

<140/90mmHg

Question 2

Determinants of blood pressure

Answer 2

• Cardiac output = increased cardiac output causes an increase in blood pressure
• Vascular tone = increased peripheral resistance increased blood pressure
• Blood volume = increased blood volume increases blood pressure

Question 3

Sympathetic nervous system

Answer 3

The sympathetic nervous system works to increase blood pressure

• Increases contraction force
• Increases heart rate
• Reduces cardiac efficiency

Occurs via activation of B1-adrenoceptors by catecholamines

Question 4

Parasympathetic nervous system

Answer 4

Works to decrease blood pressure

• Cardiac slowing
• Inhibition of AV conduction

Occurs via activation of muscarinic (M2) receptors by acetylcholine

Question 5

Adrenergic receptors

Answer 5

Ligand is catecholamines

Key cardiac adrenergic receptor is the B1-adrenoceptor

A GPCR (Gs)- stimulation increases the probability that calcium channels will open, increasing inward calcium ion flow and the force of cardiac contraction

Question 6

Nicotinic receptors

Answer 6

Ligand is acetylcholine

Less important in cardiac pharmacology because they are non-specific and have CNS effects

Question 7

Muscarinic receptors

Answer 7

Ligand is acetylcholine

Key cardiac muscarinic receptor is M2

A GPCR (Gi) - stimulation inhibits the opening of L-type calcium channels, slowing the flow of calcium 
Also opens potassium channels, hyperpolarising the cell

Question 8

RAAS

Answer 8

1. Angiotensinogen is released from the liver
2. Renin is released from the kidney and converts angiotensinogen to angiotensin I
3. ACE is released from the pulmonary and renal endothelium and converts angiotensin I to angiotensin II

Question 9

Angiotensin II

Answer 9

Angiotensin II has several effects which raise blood pressure

• Stimulates release of noradrenaline from the sympathetic nervous system
• Stimulates release of aldosterone which increases salt reabsorption
• Causes arterial vasoconstriction
• Stimulates release of anti-diuretic hormone

Question 10

Beta blockers

Answer 10

B-adrenoceptor antagonists

Decrease output from the sympathetic nervous system to reduce cardiac output

Atenolol is specific for B1-adrenoceptors only

Propanolol targets B1 & B2 adrenoceptors

Propanolol tends to be more effective but has more side effects

Question 11

Beta blockers side effects

Answer 11

• Heart failure
• Bradycardia
• Fatigue
• Cold extremities
• Hypoglycaemia
• Sleep disturbances

Question 12

ACE inhibitors

Answer 12

Inhibitors of the ACE

Prevents conversion of angiotensin I to angiotensin II

Angiotensin I is biologically inactive, so the RAAS is prevented from increasing blood pressure

Question 13

ACE inhibitors side effects

Answer 13

-Dry cough

Due to the inhibition of the breakdown of bradykinin

Question 14

Angiotensin II receptor antagonists

Answer 14

AT1 receptor antagonists

AT1 is a GPCR (Gq)

Inhibits the action of angiotensin II, although without inhibiting the breakdown of bradykinin

Question 15

Angiotensin II receptor antagonists side effects

Answer 15

• Hypotension

- Dizziness

Question 16

Renin inhibitors

Answer 16

Used to treat hypertensin by inhibiting plasma renin activity

Side effects = diarrhoea, rash

Question 17

Diuretics

Answer 17

Diuretics encourage the excretion of water to reduce blood volume

There are several types of diuretic

Question 18

Loop diuretics

Answer 18

The most powerful

Act upon the ascending limb of the loop of Henle to inhibit water reabsorption by inhibiting the Na/K/Cl carrier

Side effects = gastric irritation, hypotension, hyperglycaemia

Question 19

Thiazide diuretics

Answer 19

Act upon distal convoluted tubules to inhibit sodium reabsorption

Achieved by inhibiting the action of the Na/Cl co-transport system

Side effects = postural hypotension, gastric irritation, hyperglycaemia

Question 20

K+ sparing diuretics

Answer 20

Act upon distal convoluted tubules to prevent sodium reabsorption only

Less effective, mostly used as an add-on therapy

Side effects = gastric irritation, dry mouth, rash

Question 21

Aldosterone antagonists

Answer 21

Act upon distal Na/K exchange

Have limited diuretic effects when used alone but can prolong survival in heart failure patients

Side effects = hyperkalaemia, gastric irritation

Question 22

Vasodilators

Answer 22

Vasodilators decrease peripheral resistance to decrease blood pressure

There are several types of vasodilator

Question 23

Nitrates

Answer 23

Cause acute, short-lived vasodilation by causing nitric oxide release

Nitric oxide activates guanylate cyclase, which produces cGMP

cGMP activates protein kinase C which leads to muscle relaxation

Not suitable to treat chronic hypertension

Question 24

Calcium channel blockers

Answer 24

Prevent influx of calcium, therefore inhibiting smooth muscle contraction

Side effects - abdominal pain, nausea, palpitations, oedema

Question 25

Potassium channel openers

Answer 25

Cause efflux of potassium, leading to hyperpolarisation of muscle cells

Therefore, muscle contraction is inhibited

Only used to treat extreme malignant hypertension

Side effects = hair growth

Question 26

Lifestyle changes

Answer 26

A key treatment for hypertension is lifestyle changes

• Weight-loss
• Decreased salt, alcohol and caffeine intake
• Smoking cessation
• Exercise