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Phase 2a - ICS > Autonomic pharmacology > Flashcards

Autonomic pharmacology Flashcards

1
Q

What are the responses to acute stress? (Sympathetic drive).

A
  • Increased heart rate and contractility
  • Bronchodilation, increased respiratory rate and depth
  • Vasoconstriction of skin but vasodilation of muscle
  • Mobilisation of energy sources
  • Dilation of pupils, better distant vision and night vision
  • Reduction in secretion production
  • Increase in muscle tone
  • Reduction in pain
    Inhibition of digestion, urination, erection
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2
Q

What are the responses of the parasympathetic nervous system?

A

Essentially directly opposes the effect of the sympathetic N.S.

  • Decreased heart rate
  • Decrease in respiratory rate
  • Increased blood supply to the gut
  • Building energy stores
  • Constriction of pupils, better close up vision
  • Increase in secretion production
  • Increase in GI motility
  • Defecation, urination, sexual arousal
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3
Q

Location of parasympathetic nerves.

A

Cranio-caudal

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4
Q

Location of sympathetic nerves.

A

Thoraco-lumbar.

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5
Q

Why does a high thoracic or cervical injury cause loss of sympathetic drive?

A
  • The sympathetic nerves in the spine are damaged.
  • The vagus nerve is not damaged.
  • Unopposed parasympathetic innervation causes a bradycardia.
  • Loss of sympathetic tone causes vasodilation and hypotension.
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6
Q

How is hypotension managed in a hospital setting?

A

Administration of vasopressors (epinephrine, norepinephrine).

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7
Q

How is bradycardia managed in a hospital setting?

A

Administration of anticholinergics (atropine).

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8
Q

What is a red flag in back injuries?

A

Loss of pain sensation from the injuries can mask hidden (internal) bleeding.

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9
Q

How do synapses work?

A
  1. AP arrives at axon terminal
  2. VGCC open
  3. Ca2+ enters the presynaptic neuron
  4. Ca2+ signals to NT vesicles
  5. Vesicles move to the membrane and dock
  6. NT release via exocytosis
  7. NT binds to receptor
  8. Signal is initiated in postsynaptic cell.
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10
Q

What are the different types of receptors of the sympathetic nervous system?

A

Alpha1 (postsynaptic) - vasoconstriction.

Alpha2 (presynaptic) - negative FB suppresses noradrenalin realease.

Beta1 - Increased HR and contractility.

Beta2 - Bronchodilation.

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11
Q

Treatment of meningitis with septic shock and MOF.

A

IV metaraminol - acts through peripheral vasoconstriction by acting as a pure alpha-1 adrenergic receptor agonist thus increases BP.

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12
Q

Blood pressure is determined by (3)

A

HR
SV
SVR - can be increased by using vasopressors such as metaraminol.

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13
Q

Chronic hypertension - why is prevention important?

A

Alpha blockers are useful treatment for hypertension -> causes vasodilation (Alfuzosin -suffix=zosin).

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14
Q

Step up treatment for hypertension post MI and prevention.

A

ACEi
Antiplatelets (aspirin, clopidogrel)
Statins (simvastatin)
Beta blocker (-olol)

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15
Q

Severe asthma attack

A

Oxygen
Salbutamol (Inhalers with spacer; nebulisers, IV)
IV Hydrocortizone
Oral Prednisolone

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16
Q

Alpha 2 agonists

A

Act presynaptically - reduce the amount of noradrenaline released.

Receptors found in the brain and spine.

They form a negative FB loop.

They work in a counter-intuitive manner:
- antihypertensives
- sedatives
- analgesics

Clonidine - sedative on ITU, orally for drug withdrawal, menopausal flushing and certain pain conditions.

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17
Q

Adrenaline

A

Stimulates ALL sympathetic receptors. (*This can cause problems).

Used in very serious situations.
Cardiac arrest - 1mg IV 1:10000
Anaphylaxis - 0.5mg IM 1:1000

Short duration of action and can be repeated every 3-5 mins.

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18
Q

Adrenaline and dilated pupils

A

Dilated pupils after a cardiac arrest aren’t always a sign of neurological injury.

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19
Q

Alpha 1 and Alpha 2 antagonists

A

Phenozybenzamine
Phentolamine

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20
Q

Alpha 1 antagonists

A

Prazosin
Doxazosin

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21
Q

Beta 1 and Beta 2 antagonists

A

Propanolol
Carvediol

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22
Q

Beta 1 antagonists

A

Metoprolol
Atenolol

23
Q

Alpha 1, Alpha 2, Beta 1, Beta 2 agonists

A

Adrenaline (noradrenaline is a precursor)

24
Q

Alpha 1, Alpha 2, Beta 1 Agonists

A

Noradrenaline (Dopamine)

25
Q

Beta 1 and Beta 2 Agonists

A

Isoprenaline
Milrinone

26
Q

Alpha 1 agonists

A

Phenylephrine, Metaraminol

27
Q

Alpha 2 agonists

A

Clonidine, Dexmedetomidine

28
Q

Beta 1 agonist

A

Dobutamine

29
Q

Beta 2 agonist

A

Salbutamol

30
Q

Too much beta 1 blockade can…

A

Effect beta 2 leading to bronchoconstriction - careful in asthma.

31
Q

Too much beta 2 stimulation can

A

Affect beta 1 - tachycardia and tremor.

32
Q

Which of the following are clinical uses for phenylephrine?
A - Decongestant nasal spray
B - Intra-penile injection for priaprism
C - During a C-section birth to manage hypotension
D - As a cream to treat haemorrhoids
E - All of the above

A

E - direct alpha 1 agonist, causes constriction of arteries and veins.

33
Q

Which of the following drug - action pairings are correct?
A - Metaraminol - treats hypertension
B - Tamsulosin - treats Benign Prostatic Hyperplasia
C - Salbutamol - directly acts on beta 1 receptors
D - Carvedilol - safe for use in patients with asthma
E - Isoprenaline - reduces obesity

A

B

A - false, its an alpha 1 agonist so treats hypotension by causing vasoconstriction

B - True, its action as an alpha 1 blocker relaxes the smooth muscle of the bladder wall

C - False, salbutamol is a beta 2 receptor agonist (2 lungs!)

D - False, beta blockers, especially non-selective ones, can exacerbate asthma

E - False, Isoprenaline is a non-selective alpha and beta agonist. Beta 3 receptor is involved in lipolysis but B2AR agonist drugs for obesity are still in research stage

34
Q

Vasovagal syncope

A

Emotional or environmental trigger (prolonged standing, fasting, dehydration, seeing blood or needles).

Activation of PNS.

Vasovagal reaction (bradycardia and vasodilation of peripheral blood vessels.

Drop in BP and reduction in Brain’s O2 supply.

Leads to cerebral hypoperfusion and loss of consciousness.

35
Q

Farmer presenting with dyspnoea, lacrimation, salivation and eye pain.

A

Organophosphate poisoning.

They activate the PNS by inhibiting AChE so preventing the breakdown of ACh -> accumulates and overstimulates the nAChR and mAChr.

36
Q

Atropine

A

Competes with ACh at the muscarinic receptors.

37
Q

Nicotinic cholinergic receptor

A

Pre-ganglionic, SNS and PNS

Ligand gated ion channels

Action increases membrane permeability to Na+ and K+

Subgroups: ganglionic, neuromuscular and CNS

38
Q

Muscarinic Cholinergic Receptors

A

GPCR
M1 - CNS, higher cognitive
M2 - Cardiac
M3 - Exocrine glands and smooth muscle
M4 - CNS only
M5 - CNS only

39
Q

Nicotinic signs of AChEi toxicity

A

Mydriasis - dilation of pupil
Tachycardia
Weakness
Hypertension
Fasciculations - invol, rapid muscle twitches.

40
Q

Muscarinic signs of AChEi (organophosphate poisoning)

A

Defecation/diaphoresis
Urination
Miois - excessive constriction of the pupil.
Bronchospasm/bronchorrhea (watery sputum production)
Emesis
Lacrimation
Salivation

41
Q

Physiological manifestations of atropine overdose

A

Hot as a hare
Blind as a bat
Dry as a bone
Red as a beet
Mad as a hatter

42
Q

What medication is given during colonoscopy for bowel spasms?

A

IV buscopan (hyoscine butylbromide) muscarinic receptor antagonist.

Similar to atropine - does not cross BBB.

Also an antiemetic (acts on CTZ), used for abdominal cramps in irritable bowel syndrome and reduce excess respiratory secretions in CP or end of life care.

43
Q

Urinary incontinence management

A

Oxybutinin - direct antispasmodic effect on smooth muscle and inhibits muscarinic action of ACh.

(No anti-nicotinic effect at NMJ and skeletal muscle or autonomic ganglia).

44
Q

If oxybutinin treatment failed- next line treatment:

A

Botox - multiple uses acts pre-synaptically, prevents the release of ACh = flaccid paralysis.

45
Q

Treatment for acute angle closure glaucoma

A

Untreated this causes blindness.

Pilocarpine is a muscarinic acetylcholine receptor agonist, it constricts the pupil, opens the trabecular meshwork and increases the drainage of aqueous humor.

The increased drainage reduces the intraocular pressure preventing further damage to the optic nerve.

A surgical procedure called a trabeculectomy can be performed later to form a permanent channel for drainage

46
Q

Atropine

A

Atropine blocks parasympathetic action.

It crosses the blood-brain-barrier and can cause confusion. Especially in the elderly.

It is used, but only in the most serious situations.

Life threatening bradycardia - 500mcg iv

It can be repeated up to 3mg if needed

If blocking parasympathetic receptors is ineffective then the next step is stimulating sympathetic ones.

If these drugs fail then electrical pacing is used.

47
Q

Nicotinic antagonists

A

Trimethaphan (rarely used for hypertensive crisis)

48
Q

Muscarinic antagonists

A

M1 - increases motility and secretions in the gut, CNS effects.

M2 - bradycardia, reduced contractility.

M3 - vasodilation, bronchoconstriction, pupil constriction.

49
Q

Muscarinic antagonists

A

Atropine (crosses BBB)

Glycopyrrolate (does not cross BBB)

Hyoscine

Ipratropium (topical effect in lungs)

50
Q

Nicotinic agonists

A

Nicotine, ACh, Neostigmine (reversible inhibitor of AChE), organophosphates (irreversible inhibitor of AChE).

51
Q

Muscarinic agonists

A

Pilocarpine, muscarine.

ACh, Neostigmine organophosphates.

52
Q

Muscle relaxants

A

Most muscle relaxants used in anaesthesia block the neuromuscular junction by competing with acetylcholine for nicotinic receptors.

Neostigmine blocks the breakdown of acetylcholine so its levels increase and the muscle can work again.

Acetylcholine is found in both parasympathetic nerves and the neuromuscular junction.

Neostigmine alone would have side effects of bronchospasm, bradycardia and diarrhoea.

It comes pre-mixed with glycopyrrolate which blocks all these effects.

53
Q

Which of the following is false of drugs affecting the cholinergic system?
A - Botox acts on the ACh presynaptic vesicles to treat cause intentional paralysis

B - Nicotine and pilocarpine are parasympatheticomimetics

C - Pyridostigmine treats Myasthenia Gravis by inhibiting anticholinesterase

D - Atropine has minimal side effects and is safe in the elderly

E - Research on ACh re-uptake inhibitors for Alzheimer’s is still underway

A

A - True - Botox has an irreversible effect on exocytosis of ACh in the pre-synaptic neurone (treating spasticity, bladder instability, wrinkles!)

B- True - they are nicotinic and muscarinic receptor agonists, respectively

C - True

D - False - Atropine crosses the BBB and can cause delirium, confusion and hallucinations

E - True

54
Q

Which of the following drugs does not cause an increase in heart rate:

a) Atropine
b) Adrenaline
c) Cyclizine
d) Digoxin
e) Caffeine

A

Answer: D digoxin is used in the treatment of tachyarrhythmias

Phase 2a - ICS (43 decks)

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