Pharmacology of the ANS 3

Question 1

Where are alpha 1 adrenoreceptors found and what do they do?

Answer 1

• Found in blood vessels and GI tract

- Cause vasoconstriction

Question 2

Where are alpha 2 adrenoreceptors found and what do they do?

Answer 2

• Found in pre-synaptic cells

- Inhibit release of neurotransmitters

Question 3

Where are beta 1 adrenoreceptors found and what do they do?

Answer 3

• Found in heart

- Increase rate and force of contraction

Question 4

Where are beta 2 adrenoreceptors found and what do they do?

Answer 4

• Found in bronchial and uterine smooth muscle
• Cause muscle relaxation
• Also found in blood vessels in skeletal muscle
• Cause vasodilation

Question 5

Describe the general effects of alpha 1 adrenoreceptors

Answer 5

• Activate phospholipase C to activate 2nd messengers

- Stimulation results in vasoconstriction and constriction of smooth muscle except in GI tract

Question 6

What is the effect of alpha 1 stimulation on vascular smooth muscle

Answer 6

• Constriction
• Leads to increased peripheral resistance, decreased vascular compliance and increased central venous pressure
• Increase in systolic and diastolic arterial pressure

Question 7

Describe alpha 1 adrenoreceptor antagonists and hypertension

Answer 7

• Selective alpha 1 adrenoreceptor antagonists such as doxazosin and prazosin cause vasodilation and fall in arterial pressure
• Used in treating resistant hypertension
• Have long plasma half-lives- can be taken once a day
• Side effects include postural hypertension and erectile dysfunction

Question 8

What is the use of doxazosin as an alpha 1 adrenoreceptor antagonist?

Answer 8

• Relax smooth muscle in benign protastic hyperplasia, improving urinary flow
• Also evidence that these receptors play a role in trophoc response in hypertension, may prevent these changes

Question 9

What is the use of alpha 1 adrenoreceptors in local anaesthetics?

Answer 9

• Injection of lidocaine- spreads out widely, numbness spread
• Lidocaine with adrenaline, greater focus of aneasthetic- constricted vessels in skin with adrenaline

Question 10

What is the use of alpha 1 adrenoreceptors in nasal decongestants?

Answer 10

• Parasympathetics nervous system controls glandular secretion and causes vasodilation
• Sympathetic nervous system causes vasoconstriction
• Alpha ar agonists such as pseudophedrine and oxymetazoline will decrease nasal secretions- vasocontstriction in nose
• Parasympathetic also involved in gland regulation

Question 11

What is the use of alpha 1 adrenoreceptors in other decongestants?

Answer 11

• Parasympathetic agents such as atropine will also reduce nasal secretions, but atropine is readily absorbed via nasal mucosa
• Can lead to many side effects but useful drug

Question 12

Describe the general action of alpha 2 adrenoreceptors

Answer 12

• Linked to adenylate cyclase (inhibit)

- Reducing cytosolic levels of cAMP helps preventing the release of noradrenaline

Question 13

Describe alpha 2 adrenoreceptor agonists and hypertension

Answer 13

• Selective alpha 2 AR agonists such as clonidine will inhibit the release of NA and can be used to treat resistant hypertension
• Methylnoradrenaline will also activate alpha 2 adrenoreceptors and its precursor methyl dopa (substitutes dopa in normal reaction)
• May also be used in resistant hypertension

Question 14

Describe the general action of beta adrenoreceptors

Answer 14

• Beta receptors activate adenylate cyclase and increase cAMP levels in cell
• Beta 1 and Beta 2 differ in their distribution and their agonist/antagonist profiles

Question 15

Describe the distribution of beta adrenoreceptors

Answer 15

• 1 in heart

- 2 in airway smooth muscle

Question 16

What are the effects of beta 1 adrenoreceptor agonists?

Answer 16

• Increase heart rate (chonotropic) and force of contraction (inotropic)
• Reduces cardiac efficiency (amount if work required to pump blood)
• Can help restore automaticity
• Can disturb cardiac rhythm and ischaemic heart more susceptible to dysrhythmias

Question 17

What are the uses and side effects of beta 1 adrenoreceptor agonist dobutamine?

Answer 17

• Stimulate failing heart
• Slightly more effective with inotropic than chronotropic
• High incidence of dysrhythmia
• Also reduces cardiac efficiency as oxygen consumption increases more than cardiac work

Question 18

What are the effects of beta 2 adrenoreceptor agonists?

Answer 18

• Relax airway smooth muscle by acting directly on receptors to increase intracellular cAMP levels
• Effective regardless of constricting stimulus
• Useful in asthma where more than one bronchoconstrictor substance may be present

Question 19

What are the uses of beta 2 adrenoreceptor salbutamol?

Answer 19

• Relieve symptoms of asthma
• Also used in COPD but are much less effective in chronic obstructive lung disease
• Agonists do not affect underlying airways inflammation inasthma and over-reliance on this form of therapy should be avoided

Question 20

What are the uses of beta agonists in premature labour?

Answer 20

• Beta agnoists such as salbutamol relax uterine smooth muscle and can be given as an infusion to delay delivery
• Allows mother to receive steroid therapy to mature baby’s lungs

Question 21

What are the effects of beta-blockers?

Answer 21

• Like propranolol, depend on levels of sympathetic activity
• Beta blockers have little effect on restoring heart rate, CO or arterial pressure normally but will blunt effects of exercise on these variables
• Exercise tolerance reduced because of effects on heart and loss of vasodilation in skeletal muscles

Question 22

How do beta blockers reduce hypertension?

Answer 22

• Reduce cardiac output
• Reduce sympathetic activity
• Modify renin (kidney hormone that is involved in blood pressure) release

Question 23

Why is hypertension bad?

Answer 23

• May lead to heart attacks or strokes

Question 24

What are the uses of beta 1 adrenoreceptor antagonists?

Answer 24

• While receptor agonists are used to stimulate failing heart, antagnists also used to treat angina pectoris
• Work by improving oxygenation of heart muscle
• Also used to regulate dysrhythmias

Question 25

What are the side effects of beta blockers?

Answer 25

• Bradycardia
• Hypoglycaemia- glucose release in response to adrenaline blocked
• Fatigue- reflects reduced cardiac output and exercise tolerance
• Cold extremities- due to loss of beta-adrenoreceptor induced vasodilation
• Bronchoconstriction- asthmatics who use beta agonists

Question 26

What happens when beta blockers are abused?

Answer 26

• E.g. propanolol used as anxiolytics
• Modulate autonomic symptoms such as palpitations and tremore
• Widely used and abused treat stage fright