Beta Blockers

Question 1

What are beta-adrenoceptor blocking drugs and calcium channel blockers used to treat?

Answer 1

Angina
Hypertension
Cardiac arrhythmia

Question 2

Describe hypertension.

Answer 2

• when long-term force of blood against artery walls is high enough to cause damage.
• bp determined by amount of blood the heart pumps and the resistance to blood flow in arteries.
• build up of plaque in artery walls are going to narrow the lumen of arteries = more resistance to blood flow.
• narrower arteries = higher bp - leads to enlarged heart, blocks and blood clots.

Question 3

Describe angina.

Answer 3

• angina is discomfort or pain in the chest when not enough oxygen-rich blood reaches the muscle cells of the heart.
• CAD = main cause of angina.
• CAD is caused by atherosclerosis - condition where fatty deposits called plaque is deposited along inside of blood vessels.
• angina occurs when blood vessels become blocked due to plaque.

Question 4

Describe cardiac arrhythmia.

Answer 4

• these are heart rhythm problems which occur when electrical impulses that coordinate the heartbeats don’t wok properly, causing heart to beat too fast/too slow/irregularly.
• sometimes harmless sometimes fatal.

Question 5

What are adrenoceptors?

Answer 5

These are receptors which mediate the central and peripheral actions of the NT noradrenaline and adrenaline. The receptors are important in regulation of the autonomic nervous system (SNS and PNS).

Question 6

Where are adrenoceptors found?

Answer 6

In nearly all peripheral tissues.

Question 7

What does noradrenaline and adrenaline do?

Answer 7

They have important roles in the control of bp, myocardial contractile rate and force, airway reactivity and many metabolic and CNS functions.

Question 8

What types of adrenoceptors are there?

Answer 8

Alpha and Beta

subtypes = a1 and a2, B1, B2 and B3.

Question 9

What does activating alpha adrenoceptors result in?

Answer 9

Contracts smooth muscle except in the gut

Question 10

What does activating B2 adrenoceptors result in?

Answer 10

Relaxes smooth muscle

Question 11

What does activating B1 adrenoceptors result in?

Answer 11

Contracts cardiac muscle

Question 12

Which adrenoceptor predominates the airways?

Answer 12

B2

Question 13

Which adrenoceptor predominated the heart?

Answer 13

B1

Question 14

What are noradrenaline and adrenaline?

Answer 14

Both are catecholamines

NA and A are neurotransmitters. A is a hormone as well.

Question 15

What is the difference in structure of A and NA?

Answer 15

A contains a methyl group.

Question 16

What are the 7 drug targets for preventing the activation of adrenoceptors?

Answer 16

1. Enzymes in the biosynthesis of noradrenaline.
2. Vesicles carrying noradrenaline.
3. Exocytosis of vesicles with cell membrane.
4. Adrenergic receptor.
5. Transport protein for noradrenaline.
6. Metabolic enzymes.
7. Presynaptic receptors.

Question 17

What is the most effective drug target?

Answer 17

Blocking adrenoceptor/adrenergic receptors - to prevent NA/A from interacting with the receptor.

Question 18

How do beta blockers work (briefly)?

Answer 18

They prevent catecholamine, NA and A from accessing the beta adrenergic receptor sites in the heart, bronchi and other organs.

Question 19

Do the Beta and Alpha adrenoceptors have hydrophobic pockets?

Answer 19

Beta does alpha does not.

Question 20

How can selectivity to the B-adrenoceptor be achieved?

Answer 20

By having bulky groups on the amide of NA or A.

Question 21

How can you differentiate between 1st, 2nd and 3rd generation B blockers?

Answer 21

1st = double aromatic rings
2nd = para substituted aromatic ring
3rd = chain extension

Question 22

How do beta blockers treat hypertension?

Answer 22

Beta blockers decrease arterial bp by reducing cardiac output as bp is caused by increased blood volume and cardiac output.
Chronic treatment required to treat hypertension. Acute treatment not effective in reducing arterial pressure due to compensatory increase in systemic vascular resistance.

Question 23

How do beta blockers treat angina and prevent myocardial infarction?

Answer 23

Anti-anginal effects of beta blockers are attributed to their cardio-depressant and hypotensive actions.
By reducing heart rate, contractility and arterial pressure, beta-blockers reduce the work and oxygen demand of the heart.
Reducing oxygen demand improves oxygen supply/demand ratio - relieves patient of anginal pain caused by reduction in oxygen supply/demand ratio due to CAD.

Question 24

How do beta blockers treat arrhythmias?

Answer 24

Anti-arrhythmic properties of beta blockers - related to their ability to inhibit sympathetic signals on cardiac electrical activity.
Sympathetic nerves increase sinoatrial node automaticity by increasing the pacemaker currents which increase sinus rate. Sympathetic activation also increases conduction velocity and stimulates aberrant pacemaker activity.

Question 25

How do beta blockers treat heart failure?

Answer 25

By blockage of excessive chronic sympathetic influences on the heart which are known to be harmful to the failing heart.

Question 26

People taking beta blockers have no or very mild side effects that become less troublesome over time. List some of the side effects patients have.

Answer 26

Dizziness
Tiredness
Blurred vision
Cold extremities (cold hands and feet)
Slow heartbeat
Diarrhoea and nausea

Question 27

What is the problem with lipophilic beta blockers?

Answer 27

Can cross the BBB and cause CNS effects - leading to more harmful side effects

Question 28

In terms of antagonism, write what 1st, 2nd and 3rd gen will block.

Answer 28

1st - non-selective antagonist - blocks beta 1 and 2 receptors
2nd - more cardioselective - more B1 selective
3rd - highly B1 selective - B1 antagonist