Block B Lecture 3 - Therapeutic Uses of Adrenoceptor Drugs

Question 1

What are 2 scenarios where you would want to manually activate the fight or flight response?

Answer 1

If the patient is experiencing anaphylactic shock or cardiac arrest
(Slide 3)

Question 2

Why would you want to try and manually activate the fight or flight response in a patient who is experiencing anaphylactic shock?

Answer 2

To maintain blood pressure (as blood pressure drops rapidly during anaphylactic shock) and to open airways so the patient can breathe easier as anaphylactic shock causes bronchoconstriction
(Slide 3)

Question 3

Why would you want to try and manually activate the fight or flight response in a patient who is experiencing cardiac arrest?

Answer 3

To constrict peripheral blood vessels to maintain flow to vital organs and to stimulate the heart
(Slide 3)

Question 4

What is xylazine?

Answer 4

An anaesthetic used in veterinary medicine, which is usually used as an adjunct, which reduces the amount of other anaesthetics needed. It also increases the effects of opioids and other drugs
(Slide 5)

Question 5

What harmful effect can xylazine cause when used by humans in illicit drug mixtures?

Answer 5

Necrotic skin ulcers
(Slide 5)

Question 6

What 3 uses do α1-adrenoceptor agonists have?

Answer 6

Nasal decongestants - constrict blood vessels in nasal passages to clear up the airway

Management of shock-associated hypotension - increase blood pressure by constricting blood vessels

Pupil Dilation - constricts the dilator muscle of the iris, allowing optometrists to examine the interior of the eye

(Slide 10)

Question 7

What are the primary use of α2-adrenoceptor agonists?

Answer 7

To reduce blood pressure by inhibiting noradrenaline release or via central mechanisms (processes or actions that occur within the CNS)
(Slide 12)

Question 8

Is methyldopa active as soon as it is adminestrated?

Answer 8

No it has to be metabolised by the body to become α-methyldopamine and then to α-methylnoradrenaline
(Slide 14)

Question 9

What are 2 reasons that non-selective α-antagonists are not widely used?

Answer 9

In recent years the availability of more specific treatments have phased them out.

They can produce varying, sometimes even opposing effects, such as:

α1-antagonism in arteries leading to vasodilation and reflex tachycardia, and α2-antagonism in vascular nerves leading to vasoconstriction and reflex bradycardia. α2-antagonism in cardiac sympathetic nerves also just causes reflex tachycardia and leads to heart dysthymia and that’s probably bad.
(Slide 16)

Question 10

How do α1-antagonists lower blood pressure?

Answer 10

Although α1-antagonism actually causes vasodilation in arteries, this can lead to reflex tachycardia which contributes to a higher blood pressure, but this is offset by them vasodilating veins resulting in a decreased venous return and stroke volume

REMEMBER: BP = CO X PVR
CO = HR X STROKE VOLUME

(Slide 19)

Question 11

What were α1-antagonists used to treat and what is their recommended use now?

Answer 11

They were used to treat high blood pressure (they are antihypertensives) but are now only recommended to be used for resistant hypertension or to treat benign prostatic hyperplasia
(Slides 20 and 21)

Question 12

What are 3 examples of α1-antagonists prescribed for high blood pressure and how long do they act for?

Answer 12

Doxazosin (long acting)
Terazosin (long acting)
Prazosin (short acting)
Indoramin (short acting)
(Slide 20)

Question 13

What is benign prostatic hyperplasia (BPH)?

Answer 13

A common disorder in aging men where the prostate gland becomes enlarged but it isn’t cancerous, which can result in increased frequency of urination, urgency to urinate or struggling to urinate
(Slide 21)

Question 14

What are 2 α1-antagonists prescribed to treat benign prostatic hyperplasia (BPH)?

Answer 14

Alfuzosin
Doxazosin
Tamsulosin
Terazosin
(Slide 22)

Question 15

How do α1-antagonists treat benign prostatic hyperplasia (BPH)?

Answer 15

They relax smooth muscle in the prostate gland and neck of the bladder to reduce obstruction of the urethra and reduce restriction of urine flow
(Slide 22)

Question 16

What is postural hypotension?

Answer 16

A decrease in blood pressure when you stand up after sitting or lying down
(Slide 23)

Question 17

What are 4 side effects of clonidine (α2-agonist)?

Answer 17

Postural hypotension
Erectile dysfunction / failure to ejaculate
Drowsiness
Rebound hypotension
(Slide 23)

Question 18

What are 4 side effects of methyldopa (α2 agonist) and α1-antagonists?

Answer 18

Postural hypotension
Diarrhoea
Erectile dysfunction / failure to ejaculate
Drowsiness
(Slide 23)

Question 19

What effect do β1-adenoceptor agonists have?

Answer 19

They increase heart rate and force of contraction
(Slide 26)

Question 20

What are 5 conditions which β1-agonists can treat?

Answer 20

Bradycardia
Heart failure (where the heart is unable to pump blood effectively)
Myocardial infarction (heart attack)
Heart block (slowed heart rate due to electrical conduction)
Cardiogenic shock (heart failing to pump enough blood)
Cardiac arrest (sudden loss of heart function)
(Slide 26)

Question 21

What is an example of a selective β1 agonist?

Answer 21

Dobutamine
(Slide 26)

Question 22

What is an example of a non-selective β receptor agonist?

Answer 22

Isoproterenol
(Slide 26)

Question 23

What type of drug are adrenaline and noradrenaline classified as?

Answer 23

Non-selective α and β agonists
(Slide 26)

Question 24

What effect do β2 agonists have?

Answer 24

They relax smooth muscle of the respiratory tract and blood vessels
(Slide 27)

Question 25

What 2 conditions are β2 agonists used to treat?

Answer 25

Asthma (by relaxing respiratory tract smooth muscle)
Obstructive Pulmonary Disease (COPD) - a progressive lung disease characterised by obstructed airflow in lungs
(Slide 27)

Question 26

What are 4 examples of β2 agonists and their properities?

Answer 26

Salbutamol
Terbutaline (both are rapidly onsetting and short-acting)
Salmeterol (a long acting drug used for maintenance therapy)
Bambuterol (a prodrug which is metabolised to terbutaline)
(Slide 27)

Question 27

What is maintenance therapy?

Answer 27

A long-term treatment strategy aimed at managing a chronic condition or preventing relapse or worsening of a disease
(Slide 27)

Question 28

What is 1 potential side effect of β2 agonists which is still hotly debated?

Answer 28

That they increase the risk of the patient developing Parkinson’s disease
(Slide 28)

Question 29

Who developed the first beta blocker?

Answer 29

James black
(Slide 29)

Question 30

What are 3 uses of beta blockers (nonselective β receptor antagonists)?

Answer 30

Used to treat angina and they are class II antidysrhymic therapy drugs (treat heart dysrhymia). They also treat glaucoma and anxiety
(Slides 31, 32 and 33)

Question 31

What is Angina pectoris?

Answer 31

Chest pain or discomfort that occurs when the heart muscle does not receive enough oxygenated blood (Ischaemia)
(Slide 31)

Question 32

How do beta blockers treat angina?

Answer 32

β1 antagonism in the heart:
Decreases heart rate and force
Reduces the hearts workload
Decreases myocardial O2 demand
Relieves symptomatic relief
(Slide 31)

Question 33

What leads heart dysthymia caused by?

Answer 33

Excessive catecholamine response after a myocardial infarction
(Slide 32)

Question 34

How do beta blockers help with heart dysrhymia?

Answer 34

β1 antagonism in the heart:
Decreases heart rate and force
Reduces myocardial contractability (workload)
Restores regular heart beat
(Slide 32)

Question 35

What is glaucoma?

Answer 35

Increased ocular pressure which leads to optic nerve damage, which is caused by the excess production of aqueous humour, regulated by the sympathetic nervous system
(Slide 33)

Question 36

What specific beta blockers are used to treat glaucoma?

Answer 36

Betaxolol - a “cardioselective “ drug
Timolol
(Slide 33)

Question 37

What is a “cardioselective” beta blocker?

Answer 37

A type of beta-blocker that preferentially blocks beta-1 receptors in the heart, and has less effect on vascular smooth muscle and bronchial beta-2 receptors
(Slide 33)

Question 38

What causes many anxiety symptoms?

Answer 38

Increased sympathetic nervous system activity
(Slide 33)

Question 39

What 2 beta-blockers are used to treat anxiety?

Answer 39

Propranolol and Timolol
(Slide 33)

Question 40

What are 4 potential side effects of beta blockers?

Answer 40

Fatigue and dizziness (due to slowed HR)
Cold extremities (due to vasoconstriction of peripheral blood vessels)
Erectile dysfunction (due to decreased β2-mediated vasodilation of corpora cavernosum)
Masks signs of hypoglycaemia (tachycardia, sweating)
Prevents epinephrine from working in anaphylaxis cases
(Slide 34)

Question 41

What patients SHOULD NOT be prescribed beta blockers?

Answer 41

Anyone with:
Heart Failure
Low Blood Pressure
Heart Arrythmias
Asthma
Lung Disease

Care is also required in diabetic patients
(Slide 34)

Question 42

What are 4 functions of β3-adrenoceptors and where do these occur?

Answer 42

Answers Include:
Brain - Increases Trp and Serotonin (5-HT) levels

Myocardium - can increase or decrease cardiac contractability

Adipose tissue - increases lipolysis and thermogenesis

Retina - Increases cell growth, migration and elongation

Kidney - Increases activation of water-soluble transporters

Bladder - Triggers detrusor muscle relaxation (the smooth muscle in the bladder wall)

(Slide 36)

Question 43

What are the 2 conditions which β3-agonists have entered clinical trial for?

Answer 43

Urinary incontinence (Overactive bladder)

Antidepressant
(Slide 37)