Drugs Affecting Adrenergic Function

Question 1

Functions of the Autonomic Nervous System

Answer 1

• Involuntary system
• Responsible for:
  
  • Control of smooth muscle (e.g. bronchi, blood vessels, GI tract)
  • Cardiac muscle
  • Exocrine glands (e.g. gastric, sweat, salivary)
• Monitored by both the sympathetic and parasympathetic nervous systems

Question 2

Balanced Antagonism

Answer 2

• The ANS works by antagonism between the sympathetic and parasympathetic nervous systems
• To effect an action, a neurotransmitter needs to bind with an appropriate receptor site on the effector organ or tissue
• This is accomplished by synaptic transmission

Question 3

Synaptic Transmission

Answer 3

• Involves the synthesis of neurotransmitters in the nerve terminal
• Includes storage of the neurotransmitter awaiting an action potential
• Involves release of the specific neurotransmitter
• After release, the neurotransmitter diffuses across the synaptic gap and reversibly binds to a receptor on the postsynaptic cell
• After binding and exerting an effect, the neurotransmitter is dissociated from its binding site by a variety of mechanisms
• The neurotransmitter is now degraded or “re-uptaked” for reuse

Question 4

Neurotransmitters Involved

Answer 4

• Acetylcholine
• Norepinephrine (NE)
• Epinephrine

Question 5

Preganglionic transmission is mediated by what neurotransmitter?

Answer 5

Acetylcholine

Question 6

Postganglionic transmission is mediated by what neurotransmitter?

Answer 6

Norepinephrine

Question 7

Adrenal medulla stimulation to release epinephrine is mediated by what neurotransmitter?

Answer 7

Acetylcholine

Question 8

Four subtypes of adrenergic receptors

Answer 8

Alpha-1, Alpha-2, Beta-1, and Beta-2

Question 9

Stimulation of Alpha-1 receptors

Answer 9

• Stimulation causes:
• Vasoconstriction/Hemostasis
• Increased peripheral resistance
• Increased blood pressure (BP) – hypertensive patent would benefit from an Alpha-1 antagonist
• Pupil dilation (mydriasis)
• Closure of the internal sphincter of the bladder – a patient with urinary incontinence would benefit from an Alpha-1 agonist
• Blocking causes the opposite effects

Question 10

Adverse effects of Alpha-1 activation

Answer 10

• Hypertension – secondary to widespread vasoconstriction
• Necrosis – IV infiltration can result in extravasation (tissue damage)
• Bradycardia – secondary to reflex slowing of the heart (vasoconstriction triggers baroreceptor reflex which decreases HR)

Question 11

Stimulation of Alpha-2 receptors

Answer 11

• Activation inhibits norepinephrine release
• There are no therapeutic applications related to activation of peripheral Alpha-2 receptors. There is significance to activation of Alpha-2 receptors in the CNS

Question 12

Activation of Alpha-2 receptors

Answer 12

• Activation of Central Alpha-2 receptors
• Reduction of sympathetic outflow from brain to heart and blood vessels
• Relief of severe pain
• Blocking causes the opposite effects

Question 13

Stimulation of Beta-1 receptors

Answer 13

• Clinical Uses – cardiac arrest, heart failure, shock, heart block
• Causes:
  - Tachycardia
  - Increased myocardial contractility
  - Increased lipolysis
• Blocking causes the opposite effects

Question 14

Stimulation of Beta-2 receptors

Answer 14

• Therapeutic applications limited to the lungs and uterus
• Used to treat: asthma, delay preterm labor
• Causes:
  - Bronchodilation
  - Vasodilation
  - Slightly decreased peripheral resistance
  - Increased muscle and liver glycolysis
  - Increased release of glucagon
  - Relaxation of uterine smooth muscle
• Blocking causes the opposite effects

Question 15

Adverse effects of Beta-2 stimulation

Answer 15

• Hyperglycemia

- Tremor

Question 16

Epinephrine

Answer 16

• Nonselective adrenergic agonist
• Stimulates all alpha and beta receptors
• Many therapeutic uses, such as:
  - Cardiopulmonary arrest
  - Ventricular fibrillation
  - Anaphylactic shock – shock decreases blood pressure; epinephrine will increase blood pressure
  - Asthma
• Adverse effects related to stimulation of all receptors are common
• CNS and cardiac adverse effects are the most common and may be the most serious

Question 17

Phenylephrine

Answer 17

• Alpha-1 stimulant (selective!)
• Potent vasoconstrictor
• Avoid IV extravasation
• Pharmacotherapeutics include:
  - Vascular failure
  - Hypotension
  - Shock states
• Topical pharmacotherapeutics:
  - Nasal decongestant – vasoconstricts
  - Patients with hypertension are at risk when taking these medications because their blood pressure will rise even more
  - Pupil dilation (mydriasis)

Question 18

Prazosin

Answer 18

• Alpha-1 blocker
• Used to treat hypertension
• The first dose may cause syncope (fainting)

Question 19

Isoproterenol

Answer 19

• Nonselective Beta-2 stimulant (may stimulate Beta-1 if Beta-2 is not available)
• Pharmacotherapeutics include:
  - Congestive heart failure
  - Various types of shock
  - Hypoperfusion
• Inhaled pharmacotherapeutics include:
  - Asthma
  - Bronchitis
  - Emphysema
  - COPD
• Adverse effects are primarily related to cardiac stimulation

Question 20

Propranolol

Answer 20

• Nonspecific beta-blocker (Beta-1 or Beta-2)
• Used primarily for cardiovascular disorders
• Adverse effects are due to cardiac and respiratory effects
• Discontinue slowly to prevent rebound tachycardia leading to angina and possibly myocardial infarction
• Cannot be abruptly discontinued