Autonomic Nervous System Drugs

Question 1

Sympathetic Nervous System

Answer 1

• “Fight or flight”
• Pupils dilate
- Increased heart rate
• Renin released by kidneys
• Bronchodilation
• Peripheral (skin) & GI tract arterioles constrict.
- Glycogenolysis increases
• Heart, lung, skeletal muscle arterioles dilate
• Uterine relaxation
• Ejaculation in males

Question 2

Parasympathetic nervous system

Answer 2

• “rest and digest”
• Pupils constrict
• Decreased heart rate
• Bronchoconstriction
• GI tract: increased salivation, intestinal motility
• Bladder: voiding
- Constriction of detrusor m.
- Relaxation of sphincter
• Genitals: erection

Question 3

Sympathetic vs. parasympathetic: Different neurotransmitters: Nicotinic receptors

Answer 3

Both use acetylcholine at pre-ganglionic synapses.
- Nicotinic receptors

Question 4

Sympathetic vs. parasympathetic: Different neurotransmitters: Adrenergic receptor (a1, a2, B1, B2)

Answer 4

Sympathetic uses norepinephrine (NE) at post-ganglionic synapses.
- a1, a2, B1, B2 subtypes
- Releases epinephrine & NE via adrenal glands.

Question 5

Sympathetic vs. parasympathetic: Different neurotransmitters: Muscarinic receptors

Answer 5

Parasympathetic uses acetylcholine at post-ganglionic synapses also.
- Muscarinic receptors

Question 6

Adrenergic receptor subtypes allow more specific targeting of drugs: B1

Answer 6

Increased heart rate & force.
- Renin release from kidneys.

Question 7

Adrenergic receptor subtypes allow more specific targeting of drugs: B2

Answer 7

Vasodilation of arterioles in heart, lung, skeletal muscle.
- Bronchodilation, uterine relaxation too.
- Glycogenolysis.
- Norepinephrine will not trigger B2 receptors.

Question 8

Adrenergic receptor subtypes allow more specific targeting of drugs: A1

Answer 8

Vasoconstriction of arterioles in skin, GI tract, & of veins.
- Pupil dilation.
- Ejaculation in males.

Question 9

Adrenergic receptor subtypes allow more specific targeting of drugs: A2

Answer 9

Less significant for pharmacology.

Question 10

Cholinergic (muscarinic) agonists

Answer 10

• Muscarinic acetylcholine receptors are specific to the parasympathetic system.
• bethanechol (Urecholine)
- stimulates contraction of the detrusor muscle of the bladder and relaxation of the bladder sphincter.
- used to stimulate urination post-partum and post-op (abdominal surgery) if urination does not occur naturally.

Question 11

Muscarinic antagonists

Answer 11

• atropine
- Increases heart rate.
- Used to treat bradycardia in emergency medicine.
- “bella donna” formerly used to dilate women’s pupils.
- Treatment for organophosphate poisoning.
• Terrorism, agricultural insecticides.
- Decreases Gl secretions, motility.
• Formerly used pre-op.
- Many side-effects, narrow therapeutic range.
• tropicamide (Mydriacyl) eye drops are also anticholinergic, but shorter (3-4 hour) activity.
- For opthalmologic exams etc.

Question 12

Muscarinic antagonist

Answer 12

Anticholinergic

Question 13

Some muscarinic antagonists treat COPD: Ipratropium bromide (Atrovent)

Answer 13

• inhaler for treatment of emphysema and COPD (chronic obstructive pulmonary disease).
• onset of action occurs in about 15 minutes and lasts 3-4 hours.
• most commonly used in combination with albuterol (a sympathetic system stimulator) as the product Combivent.
• reduces symptoms, but does not slow disease progression.

Question 14

Some muscarinic antagonists treat COPD: tiotropium bromide (Spiriva)

Answer 14

• Newer, under patent, expensive.
• Administered as a dry powder inhaler.
• Onset of about 15 minutes but a half life of 5-6 days!

Question 15

Muscarinic antagonists and urination: oxybutynin (Ditropan and Ditropan XL)

Answer 15

Also tolterodine (Detrol and Detrol LA).

LA, XL pills and transdermal patches for less frequent dosing.

Question 16

Non-specific Adrenergic Agonists: Epinephrine (EpiPen)

Answer 16

• Treats anaphylactic shock, bronchodilator.
• Oral admin not possible.
  
  • metabolized immediately by liver.
  • First pass effect.

Question 17

Non-specific Adrenergic Agonists: Pseudoephedrine

Answer 17

• Stimulates a, B2 receptors.
• decongestant action by nasal vasoconstriction.
• Can be used as a precursor to make methamphetamine.
  
  • Oregon: by prescription only.

Question 18

Non-specific Adrenergic Agonists: Phenylephrine (Sudafed PE)

Answer 18

Like pseudoephedrine, but arguably ineffective.

Question 19

Illegal Adrenergic agonists: amphetamine (schedule II)

Answer 19

• Benzedrine (“bennies”) as an illegal street drug.
  • Formerly used as a decongestant.
• Adderall XR-extended release form, lower dosage.
  • Legal ADHD medication.

Question 20

Illegal Adrenergic agonists: methamphetamine

Answer 20

Schedule II!

Question 21

Illegal Adrenergic agonists: ecstasy (MDMA)

Answer 21

Schedule I

Question 22

Other ADHD drugs: methylphenidate (Ritalin, Concerta)

Answer 22

• dopamine-norepinephrine reuptake inhibitor (DNRI).
  • Works mainly at the prefrontal cortex, which is the part of the brain responsible for maintaining focus, attention, and impulse control.
• Side-effects including insomnia, lower appetite can be concerning in children.
• Usually have extended release pills for qdaily dosing.
• Schedule II-cognitive performance-enhancing uses?

Question 23

B2 agonists

Answer 23

• For bronchodilation (more in asthma section).
- albuterol
• onset 5-15 min, duration 3-6 hours.
• Combivent: combined with ipratropium bromide, for
COPD.
- Salmeterol
• Onset 45 min, 12 hour duration.
• May increase (small) long-term risk of death.
• For preventing premature parturition/labor.
- terbutaline

Question 24

Adrenergic antagonists: a1 blockers: doxazosin (Cardura) and tamsulosin (Flomax)

Answer 24

• treatment of benign prostate hypertrophy (BPH).
• relax the prostate muscles surrounding the urethra, allowing easier urine flow in males.
  • These drugs are a welcome alternative to a TURP (trans-urethral resection of the prostate), a roto-rooter job on the male urethra!
  • Adverse effects:
• orthostatic (postural) hypotension.
  • taking the drug at bedtime (hs) reduces the problem.
• nasal congestion
• Retrograde ejaculation

Question 25

B1-blockers: Metoprolol, atenolol

Answer 25

• All names end in “-olol.”
  • Clinical uses: treating hypertension, some tachycardias, migraine prevention, reduction of tissue damage after MI.
• Off-label for stage fright.
  • Side effects include orthostatic hypotension, lethargy/fatigue.

Question 26

Carvedilol

Answer 26

An A1 and B blocker.

(Synergistic effects on hypertension).

Question 27

Clonidine (Catapres)

Answer 27

• Works indirectly with effects like a B-blocker.
- blocks receptors in CNS, inhibiting sympathetic nervous system.
• Uses:
- Treatment of hypertension.
• Available as a 7 day transdermal patch.
- Withdrawal from alcohol, opiates, other drugs.

Question 28

Neuromuscular blockers (somatic nervous system)

Answer 28

• Muscle relaxation for surgery.
- Adjunct with general anesthesia.
- emergency endotracheal intubation too.
• Succinylcholine
- Quick onset (15 sec), short duration.
- Common side-effect: sore muscles afterward.
- Rare side-effects: malignant hyperthermia, cardiac arrest, prolonged apnea.
• rocuroniumtoo
- Also used in lethal injections.

Question 29

Nicotine

Answer 29

• Stimulates both sympathetic and parasympathetic nerves (pre-ganglionic).
- Highly addictive.
- Used in smoking cessation.
- Chewing gum, transdermal patch.
• varenicline(Chantix) is a partial nicotine agonist.
- Less positive feedback, helps smoking cessation.
- Rare side-effect: suicidal ideation.
• Betel -contains a nicotine analogue.
- Traditional chew in SE Asia.
• stains teeth/gums red, copious salivation.