Drugs affecting neurotransmitters Flashcards Preview

Cardiovascular & Respiratory Pharmacology (Karen) > Drugs affecting neurotransmitters > Flashcards

Flashcards in Drugs affecting neurotransmitters Deck (26)
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1
Q

What is the action of BoTox (Botulinum toxin A)?

A
  • modulates release of ACh by blocking vesicular exocytosis
  • Tx: wrinkles, dystonia (e.g. blepharospasm/abnormal eye contraction), hyperhydrosis
2
Q

How does BoTox function?

A
  • taken up selectively into cholinergic fibres
  • light chain acts as a protease to cleave SNARE proteins
    • SNARE proteins on the outer synaptic vesicle interact with the neuronal membrane to trigger exocytosis
  • tf blocks exocytosis of NT into the synaptic cleft
3
Q

How is AChE modulated?

A
  • AChE inhibitors
  • false substrates that mimick ACh
  • bind to AChE active site, blocking degradation of ACh
  • tf ACh acts in synaptic cleft for longer
4
Q

What are the differentiating properties of anticholinesterases?

A
  • variable selectivity
    • NMJ (somatic) versus parasympathetic junctions
  • variable CNS access (many cannot permeate BBB)
  • variable duration of action
    • short, medium, irreversible
5
Q

Edrophonium

A
  • short acting AChE
  • used in Dx of myasthenia gravis
6
Q

Neostigmine/Pyridostigmine

A
  • reverse effect of neuromuscular blockers
  • used in Tx of myasthenia gravis
7
Q

Donepezil

A
  • enters CNS
  • used in Tx of Alzheimer’s (one of the few)
8
Q

What is myasthenia gravis?

A
  • autoimmune disorder
  • formation of Abs to own nicotinic receptors
  • causes immune response and complement activation at NicRs and their site
    • flattens architecture of the NMJ (normally cilia-like)
    • cross-linking of 2 AChRs causing them to internalize on the postsynaptic membrane
    • [rare] autoAbs prevent ACh binding to NicRs
9
Q

How do anticholinesterases help in myasthenia gravis?

A
  • blocks degradation of ACh so there is more in the synaptic cleft to activate the remaining ACh NicRs
    • early stage compensation
    • long-term lose more receptors and this method is ineffective
      • plasmaphoresis to try to remove Ab or immunosuppressive drugs to target underlying cause
10
Q

What is the Tensilon test?

A
  • administration of edrophonium, short-acting AChE inhibitor to test myasthenia gravis as a cause of muscle weakness
    • if edrophonium relieves weakness, MG is likely cause
11
Q

What are Nm receptors?

A
  • peripheral somatic nicotinic receptors
  • cause contraction of skeletal muscle
12
Q

What are Nn receptors?

A
  • peripheral neuronal nicotinic receptors of the ANS ganglia
  • stimulate both ANS branches
13
Q

Nicotinic agonists are not typically used for

A
  • peripheral disorders
  • can be used for smoking cessation (e.g. patches)
14
Q

What are the clinical uses of nicotinic receptor antagonists?

A
  • presurgical skeletal muscle relaxants (Nm selective)
    • e.g. non-depolarising forms tubocurarine/vecuronium
  • ANS ganglion blockers (Nn selective) - rare and limited use
    • e.g. hexamethonium
15
Q

Agonist stimulation of ANS muscarinic receptors yields

A
  • SLUD:
    • Salivation, Lacrimation, Urination, Defecation
  • sweating
  • bradycardia
  • bronchoconstriction
  • vasodilation (non-neural)
16
Q

What is an example of the clinical use of ANS muscarinic receptor agonists?

A

Pilocarpine for glaucoma Tx; reduces intra-occular pressure

17
Q

Antagonistic stimulation of ANS muscarinic receptors yields

A

dependent on level of PS tone

  • reduced SLUD (Salivation, Lacrimation, Urination, Defecation)
  • reduced sweating
  • tachycardia - if fit, high PS dependence; if unfit, high SNS dependance tf no change
  • bronchodilation
18
Q

What are some clinical uses of muscarinic antagonists?

A
  • Atropine
    • reduce secretions triggered by anaesthesia (irritant) and produce bronchodilation pre-anaesthesia
    • bradycardia if driven by increased PS tone (unfit)
    • pupil dilation for retinal examination
    • AChE-inhibitor poisoning
  • Hyoscine
    • motion sickness (CNS action)
  • Ipratropium
    • COPD (inhaled)
19
Q

How can NA reuptake at the neuronal membrane be impeded?

A
  • Cocaine and tricyclic antidepressents block mechanism (high-affinity uptake 1)
    • can increase HR and BP
  • this increases NA in the synaptic cleft and stimulation of receptors downstream
  • effect is mediated by CNS
    • similar mechanisms for uptake of dopamine and serotonin
20
Q

How can metabolism of NA inside the neuron be impeded?

A
  • in sympathetic neurons monoamine oxidase (MAO) normally degrades NA released and re-uptaken by neuron
  • MAO inhibitors lead to increased NA leak and +NA in the synaptic cleft
  • commonly used as anti-depressents in the past
21
Q

What is the mechanism of indirectly actin sympathomimetics?

A
  • taken up by the high-affinity Uptake 1 transporter on the sympathetic neuronal membrane similar to NA
  • displace NA from synaptic vesicle storage
    • NA degraded by MAO or
    • released into cleft via transporter in reverse
  • acting** **indirectly by displacing endogenous agonists, driving NA into the cleft
22
Q

What are examples of indirectly acting sympathomimetics?

A
  • amphetamine
  • ephedrine (pseudoephedrine)
  • tyramine
23
Q

Ephedrine (pseudoephedrine)

A
  • indirectly acting sympathomimetic
  • used as nasal decongestant
  • displaces NA in leaky, swollen nasal blood vessels
    • NA stimulates alpha-adrenoceptors on BV to constrict, reducing leakiness and swelling
24
Q

Tyramine

A
  • indirectly acting sympathomimetic
  • used as a dietary product (cheese, salami, vegemite)
  • substrates for MAO
    • abundant in GIT, tf little reaches systemic circulation
    • if on MAO-inhibitors (depression), can cause unwanted cardio effects like tachycardia, hypertension
25
Q

Why is use of isoprenaline limited in asthma?

A
  • Isoprenaline causes bronchodilation via beta-2 aRs, but also tachycardia via beta-1 aRs
  • tf selective beta-2 aR agonist salbutamol is better, causes only the bronchodilation
26
Q
A