6. Clinical Pharmacology of Adrenoceptor Antagonists

Question 1

What is the effect of adrenoceptors on the rate of contraction and what is the primary receptor?

Answer 1

Increase

Beta 1

Question 2

What is the effect of adrenoceptors on cardiac conductivity and what is the primary receptor?

Answer 2

Increase

Beta 1

Question 3

What is the effect of adrenoceptors on the force of contraction and what is the primary receptor?

Answer 3

Increase

Beta 1

Question 4

What is the effect of adrenoceptors on the arteries and what is the primary receptor?

Answer 4

Constriction

alpha 1

Question 5

What is the effect of adrenoceptors on the skeletal muscleand what is the primary receptor?

Answer 5

dilation

beta 2

Question 6

What is the effect of adrenoceptors on the veins and what is the primary receptor?

Answer 6

constriction

alpha 1

Question 7

What is the effect of adrenoceptors on the aiways and what is the primary receptor?

Answer 7

relax

Beta 2

Question 8

What is the effect of adrenoceptors on the kidney and what is the primary receptor?

Answer 8

increased renin secretion

Beta 1

Question 9

What is the effect of adrenoceptors on the peripheral sympathetic nerves and what is the primary receptor?

Answer 9

Increased release beta 2

Decreased release alpha 2

Question 10

What is the effect of adrenoceptors on the decreased sympathetic outflow and what is the primary receptor?

Answer 10

Alpha 2

Question 11

What is an adrenoceptor antagonist?

Answer 11

Drugs which occupy adrenoceptors and prevent the action of adrenaline and noradrenaline

Question 12

What are examples of adrenoceptor antagonists?

Answer 12

Beta blockers (-lol)
Alpha1 blockers (-osin)

Question 13

What are the pharmacodynamic properties of beta adrenoceptor anatgonists?

Answer 13

Selectivity
Partial agonist activity
Additional actions

Question 14

What are the pharmacokinetic properties of beta adrenoceptor anatgonists?

Answer 14

Solubility in water vs lipid
Ability to enter CNS
Route of elimination

Question 15

What does a partial agaonist do?

Answer 15

Counter sympathetic hyperactivity

Question 16

Why are partial agonists useful?

Answer 16

Advantageous in situations where some cardiac stimulation beneficial

Question 17

Why are partial agonists useful?

Answer 17

Advantageous in situations where some cardiac stimulation beneficial

Question 18

What is the molecular mechanism of action of beta 1 adrenoceptor antagonists?

Answer 18

Stimulation of beta 1 adrenoceptors by adrenaline leads to activation of adenyalte cyclase and elevation of cAMP resulting in >contraction of heart muscle

This process is inhibited by beta1 adrenoceptor antagonists

Question 19

What is the action of cardiovascular blockers?

Answer 19

Reduce the heart rate, cardiac conductivity and force of contraction
Decrease cardiac work and oxygen demand
reduce blood pressure

Question 20

Why do beta- blockers lower blood pressure?

Answer 20

Initial fall in cardiac output then delayed indirect fall in peripheral vascular resistance and lead to a blood pressure decrease

Question 21

What are the uses of beta blockers?

Answer 21

Arhythmias 
angina pectoris 
post MI 
heart failure 
Migraine 
glaucoma 
physical effects of anxiety

Question 22

What is the use of beta blockers and hypertension?

Answer 22

Less widely used now just for hypertension in absence of other compelling indications

Question 23

What are the anti-arrythymic affects of beta-blockers?

Answer 23

Sympathtetic effects on automaticity and conductivity
-periods of abnormally fast heart beat arising in upper chambers of the heart

Management of atrial fibirilation
-chaotic electrical activity in atria resulting in irregularly irregular rhythm, pumonig of the heart is less sufficient

Useful for rate control : AV node to decrease the number of impulses that conduct into ventricles

Question 24

How are beta blockers used in angina pectoris?

Answer 24

Used in prophylaxis of stable angina

Blunt sympathetic response to excersize
Reduce myocardial oxygen demand by reducing heart rate and contracitilty
Prolonged diastole also imprves perfusion of sub-endocardial myocardium and oxygen supply

Question 25

What are the reasons for benefits post MI?

Answer 25

Decrease in cardiac work and oxygen demand Attenuate ventricular remodelling Decrease in incidence of supra ventricular tachycardias Decrease in incidence of ventricular dysrrhythmias

Question 26

Why are beta beta blockers useful in heart failure?

Answer 26

Reduce mortaility in all grades of heart failure Reduce morbidity Improve symptoms, excersize tolerance, cardiac function

Question 27

What is the benefits of reduced heart rate?

Answer 27

Prolong diastole, improve chamber filling | Reduce ischaemia

Question 28

What are further additional uses of beta blockers?

Answer 28

Prophylaxis of migraine attack Topically in glaucoma Symptomatic relief in anxiety

Question 29

What are adverse effects of beta blockers?

Answer 29

``` Bradycardia Heart block Central effects Beta 2 adrenoceptor antagonism Adverse metabolic effects ```

Question 30

What is bradycardia?

Answer 30

- lowered HR leading to reduced CO - hypotension- fainting/weak/dizzy - less marked with partial agonists

Question 31

What is meant by heart block?

Answer 31

impaired conduction of electrical impulse from atria to ventricles resulting in dropped beats

Question 32

What are adverse central effects of beta blockers?

Answer 32

fatigue nightmares etc less lipid soluble

Question 33

What is mean by beta 2 adrenoceptor antagonism?

Answer 33

Poor tissue perfusion in PVD IC exacerbation of Raynauds COld hands and feet Bronchospasm in asthmatics

Question 34

What are adverse metabolic effects of beta-blockers?

Answer 34

Prolonged hypoglycaemia Interfere with autonomic and metabolic repsonses to hypoglycaemia, worsening glycaemic control Tendency to dyslipidaemia

Question 35

What are contra-indications of beta blocker use?

Answer 35

``` Bradycardia and heart block asthma Acute decompensated heart failure Type 1 diabetes mellitus Claudication ```

Question 36

What are some side effects of beta blockers?

Answer 36

Hypertension Angina pectoris/ myocardial ischaemia acute MI

Question 37

What is the explanation of the adverse side effects of beta blockers?

Answer 37

Rebound sympathetic stimulation of heart following prolonged beta receptor blockade

Question 38

What are other drugs which slow the heart/ depress cardiac function?

Answer 38

Rate-limiting calcium channel modulators

Question 39

What is the cardiovascular effects of alpha adrenoceptor antagonists?

Answer 39

Reduce peripheral vascular resistance -antagonise postsynaptic adrenoceptors BUT cause rebound increase in HR, cardiac output and oxygen demand

Question 40

What are the clinical uses of alpha adrenoceptor antagonists?

Answer 40

Management of resistant hypertension Hypertension secondary to phaeochromocytoma Relieve urinary retention in prostate hyperplasia