9: SNS Antagonists

Question 1

Explain the role of alopha 2 adrenoreceptors in Noradrenaline release

Answer 1

As soon as Noradrenaline is released into the synapse it binds to alpha 1+2 receptors

1. Alpha 1: effect of Noradrenaline (vasoconstriction)
2. Alpha 2: negative feedback on Noradrenaline release in presynaptic neuron to ensure short acting action of Noradrenaline

Question 2

Explain the effects and mechanisms of action in the clinical use of ß-Blockers

Answer 2

ß Blockers

• Reduce blood volume (ß1 on kidney Via less Renin–> Aldosterone production)
• Reduce TPR (less Renin –> less Vasocontriction as AGTII response)
• Reduce CO (ß1 on heart: reduced cAMP leading to redcued HR+ Force of Contraction)
• Minor effect: blockage of presynaptic ß receptors leading to a reduced NA release

Question 3

Which drug class of SNS antagonists is commonly used in the chronical treatment of hypertension?

Answer 3

ß-Blockers

Question 4

What is Propanolol?

Answer 4

It is a non-selective ß antagonist (equal afinity for ß1+2 receptors)

Question 5

What is Atenolol?

Answer 5

It is a ß1 “selective” antagonist

Question 6

What is Carvedilol?

Answer 6

Mixed b and a blockers

•a1 blockade gives additional vasodilator properties

Question 7

Which different ß Blocker classes are there?

Name examples for each class

Answer 7

1. Non selective (ß1+2)
   
   • Propanolol
2. Cardio-selective
   
   • Atenolol
3. Mixed ß-a- blockers
   
   • Cervedilol
4. Other
   
   • Nebivolol: also potentiates NO
   • Sotalol: also inhibits K+ channels

Question 8

What are the side effects of Beta-blockers

Answer 8

1+2 are the major concerns

1. Bronchoconstriction (no pure slectivity for ß1)–> might not be tolerated by astmathics (ß2 activity)
2. Hypoglycaemia –> might not be toleareated by Diabetics
   
   • masking of hypoglycaemic symptoms
   • Inhibits glycogen break down in liver (ß2)
3. Cardiac failure (some SNS activity required for heart)
4. Cold extremitis (no cutaneous ß2 mediated vasodilation)
5. Fatigue (reduced CO+ reduced muscle blood flow (ß2 antagonism))
6. Bad dreams

Question 9

Which group of patients might not tolerate ß-blockers?

Answer 9

1. Astmatics (inhibitionof ß2-mediated bronchiodilation)
2. Diabetics (risk of hypoglycaemia –> inhibition ß-2 mediated glycogen break down and release)
3. Cardiac failure –> loss of SNS innervation to the heart which keeps the heart running

Question 10

What is the clinical use for alpha blockers?

Answer 10

Limited use in treament of hypertension

Question 11

Name 2 alpha-blockers and explain their mechanism of action, effect and use

Answer 11

1. Phenotolamine
   
   • used in reduceing phaeochomocytoma-induced hypertension
   • alpha-non selective antagonist
2. Prazosin
   
   • limited BP lowering effect
   • only used in combination with other hypertensive drugs

Question 12

What is Phenotolamine?

When is it used?

Answer 12

It is a non-selective adrenergic alpha antagonist

Used in management of phaechromycytoma-induced hypertension

Question 13

What is prazosin?

What is its clinical use?

Answer 13

It is a alpha1 selective adrenergic antagonist

• used in hypertension treatment (in combination with other hpyertensive drugs due to limited effects)

Question 14

What are the side-effects of alpha-blocker?

Answer 14

Side effect mainly GI tracts

• reduces SNS innervation to gut –> leading to increased gut activity
• diarreah etc.

Question 15

Explain the mechnism of action of Methyldopa

Answer 15

It is a false substrate for DOPA-methyltransferase that gets converted into alpha-methylnoradrenaline

Alpha-methylnoradrenaline is a false transmitter resulting in

• Increased selectivity for alpha2 receptors
• Decreased sensitivity for alpha1+ß receptors
• Decreased break down by MAO

​–> Higher concentration of alpha-methylnoradrenaline in synapse with high A2 affinity

–> Decreased SNS activtity–> hypotension

Question 16

Which drug can be used as a false transmitter in the treatment of hypertensoion?

Answer 16

Methyldopa

• Mmimics DOPA
• Gets transfered to the false transmitter alpha-methylnoradrenaline

Question 17

What is the clinical use of Methyldopa?

Answer 17

Used to treat Hypertension

• linked to Kidney disease
• linked to CNS + cerebrovascular disease

Question 18

What are the (main) side effects of the use of Methyldopa?

Answer 18

Many side effects because it interferes with almost whole SNS

–> Mainly

• Hypotension: Very potent anti-hypertensive drug
• Dry mouth

Question 19

Ich which clinical conditions could you use SNS antagonists as a treatment?

Answer 19

1. In Hypertension
2. In Arrythmias
3. In Angina
4. In Glaucoma

Question 20

Explain the use of SNS antagonists in the treatment of Arrythmias

Answer 20

Mainly Propanolol

• blocks the ß1 receptors in heart
• –> slows heart rate –> giving heart more time to fill

Question 21

Explain the use of SNS antagonists in Angina Pectoris

Answer 21

There are two ways of treating Angina:

1. Increasing the Oxygen availibility to the Myocardium
2. Decreasing the Oxygen demand of the Myocardium –> ß Blockers (less work for heart muscles)

Question 22

Explain the use of SNS antagonists in the treatment of Glaucoma

Answer 22

Target: ß1 receptors on cliary body –> reduction in production of aqueous humor (ß-blockers)