Wk9 Hexamethonium Man

Question 1

What is the mechanism of action of hexamethonium?

Answer 1

Nicotinic cholinergic receptor antagonist in the ANS – non depolarising ganglionic blocker in the
ganglions of both the parasympathetic and sympathetic system
- These receptors are ligand gated ionotropic receptors (ligand gated ion channels)
- It is neuronal nicotinic- does not affect skeletal muscle – neuronal nicotinic receptors
- Note – Neuronal and muscle nicotinic receptors are different; they bind different substances, one of these substances being hexamethonium

Question 2

Which divisions of the autonomic nervous system will it affect

Answer 2

• Hexamethonium causes overall paralysis of the autonomic nervous system because it does not distinguish between sympathetic and parasympathetic ganglia and therefore is not specific in its action
  (widespread effect).
• Has effects on adrenal medulla cells as it has nicotinic receptors

Question 3

Can you explain how each of the symptoms described above is produced ?

Answer 3

• Pink complexion → blockage of the SNS means less sympathetic innervation of the smooth muscle of
  the blood vessels in the skin, which leads to vasodilation; change in vascular tone in his skin
  (innervated by SNS)
• Vasomotor tone is important when thinking about the impact of drugs
• Smooth muscle of blood vessels in the skin have sympathetic innervation only
• Pale and faint upon standing for a long time → body wide vasodilation due to reduced sympathetic
  innervation results in blood accumulating in the feet/legs, and reduced blood flow to the brain as
  constriction of blood vessels doesn’t occur to push blood upwards towards the brain
• Benefits of a corset - applying pressure to the abdomen keeps the fluid inside the blood vessels
  rather than in the periphery
• Hands are warm and dry → warm due to vasodilation in the skin (SNS block), dry due to reduced sweat
  gland activity (SNS block)
• No chilblains → change in vascular function as vasoconstriction cannot occur due to reduced
  sympathetic innervation so less likely to get chilblains
• Clean and sweet feet, clean collars → reduced sweat gland activity (SNS block)
• Cannot cry → no activity of lacrimal glands (PNS block)
• Can’t blush nor become pale → neither vasodilation (PNS block) nor vasoconstriction (SNS block) of
  blood vessels in the face- Already pink due to vasodilation.
• Dry mouth and throat → reduced activity of sublingual, submandibular and parotid glands (SNS block)
• Long sightedness → reduced parasympathetic innervation to/control of ciliary muscles that control
  accommodation in the lens of the eye (PNS block in ciliary ganglia);
• Ciliary muscles (control lens shape) have single innervation - only parasympathetic
• Easily blinded by bright light → reduced parasympathetic innervation to/control of the circular
  muscles of the iris that control pupil constriction (PNS block in ciliary ganglia); loss of parasympathetic
  mediated constriction
• Iris has dual innervation but the parasympathetic innervation is dominant, so the loss of dominant input is what would be seen if both are blocked
• Pupil- Para. dominates
• Increased heart rate at rest → parasympathetic (dominant during rest) block causes increase in heart
  rate
• Red eyes- no tears due to lack of innervation to lacrimal glands
• Belching and hiccups → ….
• Feels cold → vasodilation (SNS block) so cannot conserve heat
• Modest appetite → reduced parasympathetic innervation of the stomach and small intestine (PNS
  block)
• GIT is controlled by the SNS, PNS and ENS
• No peptic ulcers → reduced enteric innervation to the acid secreting glands of the stomach
• Constipation → reduced innervation to the colon (PNS block) + less secretions to lubricate the
  movement of the faeces through the tract
• Retention of urine → reduced innervation to the smooth muscle of bladder
• (SNS and PNS block)
• Impotence?