December 2005

Drugs – baby!

At the Neuromuscular Junction: (the junction between a motor neurone and a muscle cell.)
1. An Action potential flows along the motor neurone to the presynaptic end.
2. Ca2+ flows into presynaptic terminal, causes vesicles of ACh to be released
3. ACh crosses synaptic cleft, bind to nicotinic receptors on muscle end-plate.
4. Voltage-gated Na+ channels open, and Na+ enters muscle cell, causing a depolarisation.
5. Depolarisation flows along muscle cell and causes contraction.
6. ACh is broken down to choline and acetate, which can be reused.

Drug What it does What it is used for Notes

Prevents choline from entering

Hemacholinium presynaptic terminal, so ACh cannot No therapeutic use
be synthesised

Vesamicol Prevents ACh from entering vesicles No therapeutic use

Blocks Na+ channels in motor

Tetrotoxin No therapeutic use Puffer-fish Poison!
neurone, so stops AP

Prevents fusion of vesicle to

Botulinum No therapeutic use Poison!
membrane, so ACh is not released

Non-depolarising blocker. Blocks

Used along with Relieved by anti-
Atracurium Nicotinic receptor, no depolarisation
general anaesthesia cholinesterase.
of muscle so no contraction

Depolarising blocker. Blocks nicotinic Short duration of

receptor and causes a short action, so used for Not relieved by
Suxamethonium
depolarisation, followed by quick procedures such anti-cholinesterase.
inactivation of receptor as intubation.

Diagnosis of
Edrophonium Short-acting Anti-cholinesterase.
Myasthenia gravis.

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 December 2005

Treatment of
Neostigmine Medium-acting Anti-cholinesterase
Myasthenia gravis.

Ecothiopate Long-lasting Anti-cholinesterase Treatment of glaucoma

Sarin Long-lasting Anti-cholinesterase No therapeutic use Nerve Gas!

Used to save the life of

people with Malignant
Dantrolene Direct-acting muscle relaxant Hyperthermia (who can
die if they are given
suxamethonium)

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 December 2005
In the Parasympathetic NS:

Muscarinic Receptors, five types:

M1 – Stomach
M2 – Heart
M3 – Smooth muscle / exocrine glands
M4/M5 – Brain

Effects: (think R ‘n R)
• Contracts gut
• Contracts Bladder
• Contracts Bronchioles
• Decreases HR, BP and force of heart
• Increases secretions
• Contracts pupils

Agonists – mimic these effects (parasympathomimetics)

Antagonists – block Parasympathetic NS, so sympathetic NS predominates.

Parasympathetic Agonists
Kick starts GI tract and bladder after a long Op, used to prevent
Bethanechol
constipation.
Pilocarpine Treatment of Glaucoma (contraction of pupil releases pressure)

Parasympathetic Antagonists

Atropine Cardiac arrest – kick starts heart.

Hyoscine Motion sickness, “pre-op” to dry up secretions..

Dilates pupil for eye examination (raises intraocular pressure so don’t give
Tropicamide
if patient has glaucoma!)

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 December 2005
In Sympathetic NS:

NA / adreno
(ACh / Mus in sweat glands)
Long post-ganglion
CNS Effector organ
ACh / Nic

4 main types of Adrenergic Receptor:

α 1: Activates PLC, forms IP3 and DAG.

α 2: Inactivates adenylyl cyclase, decreases cAMP.
β 1: Activates adenylyl cyclase, increases cAMP.
β 2: Activates adenylyl cyclase, increases cAMP.

(β3: in adipose tissue, involved in lipid metabolism)

Effects of Sympathetic NS (think Fight or Flight):

• Relaxes GI tract
• Relaxes Bladder
• Dilates bronchioles
• Increases HR, BP, force of contraction
• Less secretion
• Dilates pupils
• Piloerection

NA / A
α1 Agonist
Phenylephrine Nasal Decongestion
NA / A
α2 Agonist
Clonidine

α1 Antagonist
Phenyoxybenzamine
Decrease BP in people with hypertension.
Doxazosin
α2 Antagonist

β1 Agonist NA / A

A
β2 Agonist Treatment of Asthma (it dilates the bronchioles)
Salbutamol
“Beta-blockers”
Atenolol
β1 Antagonist after an MI, for Angina, cardiac arrhythmias,
Propanolol
hypertension.
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 December 2005
(don’t need to know β2 antagonist)