9: SNS Antagonists

Question 1

Alpha 1 receptor stimulateion

Answer 1

vasoconstriction, relaxation of GIT

Question 2

Alpha 2 receptor stimulation

Answer 2

inhibition of transmitter release, contraction of vascular smooth muscle (respond to NA), CNS actions

Question 3

Beta 1 receptor stimulation

Answer 3

increased cardiac rate and force, relaxation of GIT, renin release from kidney

Question 4

Beta 2 receptor stimulation

Answer 4

bronchodilation,
vasodilation,
relaxation of visceral smooth muscle,
hepatic glycogenolysis

these respond to circulating adrenaline levels- no direct input from SNS.

Question 5

Beta 3 receptor stimulation

Answer 5

lipolysis

Question 6

Which receptor does labetalol target

Answer 6

alpha 1 + beta1

Question 7

SNS antagonist targeting alpha 1 + 2

Answer 7

phentolamine

Question 8

SNS antagonist targeting alpha 1

Answer 8

prazosin

Question 9

Which receptors does propanolol target

Answer 9

beta 1+2

Question 10

atentolol targets

Answer 10

beta 1

Question 11

Main clinical uses of SNS antagonists and false transmitters

Answer 11

• Hypertension
• Cardiac Arrhythmias
• Angina
• Glaucoma

Question 12

Where do beta adrenoreceptor antagonist sgenerally work as antihypertensives

Answer 12

• Act in the CNS to reduce sympathetic tone
• Act on the beta 1 receptors in the heart to reduce HR + CO but this effect disappears with chronic treatment - the heart resets itself
• Acts on the kidneys: beta 1 receptors to reduce renin production. Blocking this kidney response is the primary anti-hypertensive effect. Reduced renin production results in reduced total peripheral resistance

Question 13

Unwanted effects of beta antagonists

Answer 13

Most effects come from beta 2 blockade

• Bronchoconstriction: b2 in bronchial SM.
• Cardiac failure
• Hypoglycaemia: can mask symptoms of hypoglycaemia. Dangerous for diabetics bc blocks b2 breakdown of glycogen in liver.
• Fatigue: reduced CO + muscle perfusion
• Cold extremities: loss of beta receptor emdiated vasodilation of cutaenous vessels

Question 14

Conditions in which you wouldnt give nonselective beta blocker

Answer 14

o ASTHMA
o COPD
o CARDIAC FAILURE
o DIABETES

Question 15

How does propanolol work

Answer 15

blocks b1 and b2.
At rest, propranolol causes very little change in HR, CO or arterial pressure.
At exercise you see the effects of propranolol on these variables. As it is non-selective, it produces all the typical adverse effects, mainly caused by beta 2 antagonism

Question 16

How does atenolol work

Answer 16

Beta-1 selective
. It mainly antagonises the effects of NA in the heart but will also affect any tissue with beta 1 receptor e.g. kidneys. This has less effect on the airways than non-selective drugs, but it’s still not safe with asthmatic patients

Question 17

How does labetalol work

Answer 17

alpha1 + Beta 2 selective

Acts more on beta-1
This lowers BP by reducing TPR. Like beta-blockers, labetalol induces a change in HR/CO but this effect wanes with chronic use as the heart resets itself

Question 18

Main cause of arrythmia

Answer 18

myocardial ischaemia. Damage to the heart muscle can result in re-entry of impulses that messes up the heart rhythm. Exercise increases the chance of arrhythmia.

Question 19

How do class 2 anti-arrythmics work

Answer 19

• The refractory period of the AV node is increased by beta antagonists. This interferes with AV conduction in atrial tachycardias and slows down ventricular rate
• So, even if you have strange re-entry type electrical activity in the damaged tissue, it won’t stimulate another heart beat because it’s still in the refractory period  decrease the chance of developing arrhythmias.

Question 20

What is angina

Answer 20

PAIN OCCURRING WHEN O2 SUPPLY TO MYOCARDIUM IS INSUFFICIENT

Question 21

3 types of angina

Answer 21

• Stable
• Unstable
• Variable

Question 22

when feel pain in the 3 types of angina

Answer 22

Stable: on exertion
Unstable: less and less exertion
Variable: rest

Question 23

Cause of stable angina

Answer 23

Due to a fixed narrowing of the coronary vessels e.g. atheroma
There is increased demand on the heart

Question 24

Cause of unstable angina

Answer 24

The atheromatous plaque is starting to rupture and breaks away.
You get a platelet-fibrin thrombus associated with the ruptured atheromatous plaque but without complete occlusion of the vessel
High risk of infarction

Question 25

Cause of variable angina

Answer 25

Caused by coronary artery spasm | It is associated with atheromatous disease

Question 26

How do Beta adrenoceptor antagonists reduce myocardial oxygen demand

Answer 26

• Decrease HR + SBP + cardiac contractile activity. This loweres O2 demand. Decreases chance of angina attack

Question 27

How is aq humour produced in eye

Answer 27

Aqueous humour is produced by the blood vessels in the ciliary body via the actions of carbonic anhydrase. The amount of humour produced is directly related to the blood flow in the ciliary body The production is indirectly linked to the BP and blood flow in the ciliary body

Question 28

How do beta antagonists work to treat glaucoma

Answer 28

beta-1 receptors regulates the action of carbonic anhydrase. | It reduce the rate of aqueous humour formation by blocking the receptors on the ciliary body reducing OP

Question 29

How do alpha adrenoreceptor antagonism work

Answer 29

Alpha-1 is the main mediator of TPR. If you block the alpha adrenoceptors you get a fall in TPR and hence a fall in BP. • CO and HR will increase as a reflex response to the fall in arterial blood pressure - this is a baroreceptor mediated tachycardia

Question 30

Why do u get postural hypotension if on alpha antagonist

Answer 30

When you stand up, the SNS kicks in to give a quick boost to your blood pressure and prevent you from fainting and falling over. , this sympathetic drive is blocked and you get postural hypotension.

Question 31

How does phenotolamine work

Answer 31

Non-selective alpha antagonist. Causes vasodilation and a fall in BP due to blockade of alpha-1 adrenoceptors. However, blockade of presynaptic alpha-2 receptors removes the inhibitory effect of the alpha-2 receptors on NA release and so you get an increase in NA release. This enhances the reflex tachycardia that you get with any BP lowering agent

Question 32

How does prazosin work

Answer 32

Highly selective ALPHA-1 antagonist. This leads to vasodilation and a fall in BP. There is less tachycardia than non-selective antagonists since they don’t increase NA release from nerve terminals (no alpha-2 actions). You still get some reflex tachycardia because of the fall in BP.

Question 33

Unlike other anti-hypertensives, alpha-1 antagonists cause a ....

Answer 33

decrease in LDL and an increase in HDL cholesterol.

Question 34

Example of false transmitter

Answer 34

methyldopa

Question 35

How is methyldopa use

Answer 35

Methyldopa is taken up by the noradrenergic neurons. It’s decarboxylated and hydroxylated to form the false transmitter: alpha-methyl noradrenaline. It is not deaminated within the neuron by MAO and tends to accumulate in larger quantities than NA. It displaces NA from the synaptic vesicles when taken up.

Question 36

Mechanism of action of methyldope

Answer 36

alpha-methyl noradrenaline) is released in the same way as NA into the synapse etc. • It is less active than NA on alpha-1 receptors. This means that it is less effective at causing vasoconstriction so there will be a fall in BP. * Also it is more active on presynaptic alpha-2 receptors (the ones that mediate the negative feedback and release of NA shut down the synthesis and release). * This means that the auto-inhibitory feedback mechanism operates more strongly and reduces noradrenaline release below normal levels • It also has some CNS effects, it stimulates the vasopressor centre in the brainstem to inhibit sympathetic outflow