Pharmacology of the Autonomic Nervouse System II Flashcards

1
Q

What is the problem with M3 cholinoceptor targetting drugs?

A

Drugs that act on the parasympathetic nervous system lack specificity. meaning they produce many side effects.

Limited number of drugs used clinically as a result.

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2
Q

Which drug activates muscarinic cholinoceptors?

A

Pilocarpine

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3
Q

Which drugs block muscarinic cholinoceptors?

A

Atropine

Tiotropium

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4
Q

What other receptors are activated by M3 agonists?

A

M1, M2, and nicotinic receptors

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5
Q

How are side-effects of muscarinic cholinoceptor agonists reduced? How is pilocarpine a good example of this?

A

Through topical administration.

Pilocarpine, for example is administered topically (via eye-drops) to the eyes to constrict pupil and promote drainage of aqueous humour thus reducing intraocular pressure.

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6
Q

What condition can pilocarpine be used for?

A

Glaucoma, however it is not a first or second line treatment (beta blockers are a better idea).

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7
Q

What is the most commonly used muscarinic receptor antagonist?

A

Atropine

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8
Q

What receptors does atropine block?

A

Blocks all muscarinic cholinoceptor subtypes (muscarinic receptor antagonist

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9
Q

What is the resulting physiological effect of atropine administration?

A

Dries up secretions (saliva, sweat, tears, gut, and lung)

Inhibits smooth muscle contraction (gut, lungs, eyes)

Increases heart rate (blocks M2)

Crosses into CNS to block muscarinic receptors creating excitatory effects (including restlessness, hyperactivity, and increased body temperature)

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10
Q

What limits atropine use?

A

It is difficult to obtain organ selectivity without side effects.

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11
Q

What problem is atropine commonly used for?

A

It is frontline therapy for poisoning with anticholinesterase agents (pesticides and war gases). This is because it blocks the muscarinic side effects.

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12
Q

What is tiotropium used for?

A

COPD. It dilates the airways and reduces mucous secretion.

It is a long-acting drug (due to getting trapped within binding site without getting covalently attached) that is used for maintenance therapy rather than as a reliever.

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13
Q

What does tiotropium do?

A

It is a muscarinic cholinoceptor antagonist. It is more selective than atropine for M3 receptor.

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14
Q

How is tiotropium administered to COPD patients?

A

As an aerosol to avoid CNS effects

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15
Q

What is tropicamide used for?

A

Short-term dilatation of eyes for clinical examination. (this drug is quite similar to tiotropium)

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16
Q

What is solifenacin used for?

A

For urinary incontinence. (selective for the M3 receptor with less CVS side-effects)

17
Q

What do amphetamines do?

A

They block removal of noradrenaline from synaptic region.

18
Q

What does neostigmine do?

A

Blocks acetylcholine metabolism

19
Q

What happens when drugs alter neurotransmitter removal?

A

Increases synaptic levels of NT which results in increased activation of NT receptors and increased responses in effector cells.

20
Q

Describe the process of noradrenaline production and release from pre-synaptic neuron to post-synaptic neuron and what happens after nerve transmission at the synapse:

A

Tyrosine is hydroxylated to form DOPA and decarboxylated to form dopamine which sit in vesciles and is hydroxylated into noradrenaline.

NA then is released and acts on postsynaptic cell.

Noradrenaline transporter transports noradrenaline back into the neuron of the presynaptic neuron. (Neuronal reuptake) which halts signalling.

After beign taken up by presynaptic neuron the noradrenaline can be broken down via a monoamine oxidase which deactivates the noradrenaline.

Non-broken down noradrenaline is added to vesicles that are about to be released again.

21
Q

How does amphetamine interfere with noradrenaline signal transduction pathway?

A

Amphetamine is taken up from synapse via the same transporter as noradrenaline.

Amphetamine then blocks the monoamine oxydase which is responsible for breaking down noradrenaline

Amphetamine also induces reverse operation of noradrenaline transporter resulting in increased release of noradrenaline from the cell.

Increased noradrenaline in the junction stimulates adrenoceptors on effector cell resulting in increased sympathetic nerve activity

22
Q

Why is pseudoephedrine no longer used as a nasal decongestant?

A

It can be converted into methamphetamine.

23
Q

What is the use of amphetamine clinically?

A

CNS effects in children with ADHD

24
Q

What does pseudoephedrine do?

A

Increases amount of noradrenaline released from adrenergic nerves

25
Q

How does neurotransmission take place for cholinoceptors?

A

Cholinergic nerves synthesize and store acetylcholine

Upon stimulation nerves release acetylcholine which activates cholinoceptors on postsynaptic cells

Acetylcholine is then metabolised by enzyme AChE which terminates signalling by reducing [Ach] in region of cholinoceptor and instead converts acetylcholine into acetate and choline.

26
Q

What drugs take advantage of acetylcholine signal transmission pathway?

A

Acetylcholinesterase inhibitors such as neostigmine

27
Q

What are the major types of anticholinesterases?

A

Long-acting (act for days) due to irreversible covalent bond with active site. (eg. organophosphate pesticides and war gases) diagnosed via dumbbelss pneumonic.

Medium-acting (hours) such as neostigmine

Short-acting (minutes) such as edrophonium

Medium and short term are more clinically useful

28
Q

How can cholinergic overdose be diagnosed?

A

Dumbbelss

Diarrhoea
Urination
Miosis/muscle weakness
Bronchorrhea/Bronchoconstriction
Bradycardia
Emesis
Lacrimation
Salivation/Sweating
Seizures
29
Q

What kinds of conditions can be diagnosed and managed using acetylcholinesterase inhibitors?

A

Myasthenia gravis

Reversing neuromuscular blockade induced by non-depolarising neuromuscular blockers

30
Q

What is myasthenia gravis?

A

Condition that causes muscle weakness due to autoantibody activity against Nm receptors. This lost sensitivity can be overcome by increased acetylcholine in NMJ.

31
Q

What drug is commonly used to treat myasthenia gravis?

A

Neostigmine

32
Q

Where are neuromuscular blockers commonly used?

A

In general anaesthesia

33
Q

What are potential side effects in using neostigmine and other inhibitors of acetylcholinesterase?

A

Actions on the autonomic and central nervous systems