IC4: Pharmacology Flashcards
What molecule synthesises neurotransmitters?
ChAT (choline acetyltransferase)
What are the 2 receptors that neurotransmitters bind to?
GPCR (mAChR = muscarinic)
Ion channels (nAChR = nicotinic)
What are the 2 receptors that neurotransmitters bind to?
GPCR (mAChR = muscarinic)
Ion channels (nAChR = nicotinic)
What are the 4 main neurotransmitters found in the body and what kind of synapses are they usually involved in?
Glutamate - excitatory
GABA - inhibitory
Acetylcholine - learning, arousal and reward
Dopamine - motor systems and reward
what are the 3 functions of the blood brain barrier?
- Modulation of the entry of metabolic substrates (especially glucose)
- Control of ion movement → Na-K-ATPase in barrier cells pump Na into the CSF and pumps K out into blood
- Prevention of access to CNS by toxins and peripheral neurotransmitters
What is the non-saturable method of crossing the BBB and what characteristics make a drug a good candidate for this method?
Transmembrane passive diffusion
Drugs w LMW, high lipid solubility (not too high)
What is the saturable method of crossing the BBB and what are the 4 things that regulate it
Transporter systems
Regulated by cerebral blood flow, co-factors, hormones and efflux transporters (eg. P-glycoprotein)
Describe generalised seizures
involve the entire brain, will cause loss of consciousness
What are the 4 main types of generalised seizures?
Tonic clonic (Grand mal)
Absence (Petit mal)
Myoclonic
Atonic
What are the 2 types of partial seizures
Simple (consciousness not impaired)
Complex (impaired consciousness)
What is phenytoin’s MOA
Blocks VG-Na+ channels, decreasing Na+ influx hence preventing the formation of an AP
Where can phenytoin be used
All but absence seizures
What must be taken note of for PHT monitoring
Narrow tp range, w saturation kinetics, non-linear relationship between dose and plasma concentration necessitating titration and monitoring
PHT is also teratogenic
What is CBZ’s MOA
Blocks VG-Na+ channels, decreasing Na+ influx hence preventing the formation of an AP
Where can CBZ be used?
All but absence seizures
What enzymes are implicated with CBZ?
CYP450 inducer
Its own t-half decreases with repeated doses and increases elimination of other drugs
What must be screened for prior to CBZ use?
HLA-B*1502 (SJS/TEN risk)
What is valproate’s MOA? (3)
Blocks VG-Na+ AND Ca2+ channels, decreasing Na+ influx hence preventing the formation of an AP
Also inhibits GABA transaminase (hence increasing GABA levels)
Where can valproate be used?
Suitable for ALL seizure types
What should be taken note of for valproate?
Highly protein bound and will displace other ASMs
What are the general dose-related SEs for ASMs? (6)
drowsiness, confusion, ataxia, slurred speech, mental changes, coma
What are the general non-dose-related SEs for ASMs? (6)
hirsutism, acne, gingival hyperplasia, folate deficiency, osteomalacia, HS rxns
How can ODs occur with benzodiazepines and what should be used to treat it?
Overdose and/or concurrent use with alcohol
Treat with flumazenil
Why arent benzodiazepines and barbituates used as often?
High instances of tolerance and dependence
Barbituates have a worse profile than benzodiazepines
How do barbituates differ from benzodiazepines in terms of MOA?
Barbituates also potentiate GABA(A) mediated Cl- currents but at a site distinct from benzodiazepines
(hence flumazenil does not work in cases of overdose)
What are the 3 other non-first line ASMs?
Levetiracetam
Lamotrigene
Topiramate
What is levetiracetam used for? (3)
Adjunctive therapy for:
partial onset seizures
myoclonic seizures
primary generalised tonic-clonic seizures
What are some common and rare SE for levetiracetam? (3+3)
Common: HA, vertigo, insomnia
Rare: agranulocytosis, suicide, delirium
What is lamotrigene’s MOA?
Blocks VG-Na+ channels and inhibits glutamate release
What is lamotrigene indicated for? (3)
adjunctive or monotherapy treatment of:
partial seizures
generalised seizures (including absence)
lennox-gastaut syndrome
What are some rare SEs of lamotrigene? (4)
agranulocytosis
movement disorders (worsens Parkinson’s)
SJS/TEN
hepatic failure
What is topiramate indicated for? (2 monotx, 1 adj)
monotherapy for:
partial
generalised seizures
adjunctive therapy for:
Lennox-Gastaut syndrome
Under which 3 circumstances should monitoring for ASMs be done?
- assess compliance in pts w refractory epilepsy (but claim to be compliant)
- assess sx due to ASM toxicity (especially w PHT)
- to titrate PHT dose
Describe the general pathophysiology of a headache (4) VTNI
Vasodilation of intracranial extracerebral blood vessels →
activation of the perivascular trigeminal nerves →
release vasoactive neuropeptides →
promote neurogenic inflammation
Which biological molecule has been implicated as an important mediator of migraines?
Serotonin (5-HT)
What is the general flow in migraine pharmacological management?
NSAIDs or paracetamol first
If fail or in cases of moderate to severe migraines, try cafergot, sumatriptan or erenumab
What is cafergot and what is its MOA? (3)
caffeine + ergotamine
tonic action on vascular smooth muscles in the external carotid network →
stimulates α-adrenergic and 5-HT receptors →
leading to vasoconstriction
When is cafergot indicated?
Acute tx of migraine, given at first sx of attack
What other drugs should cafergot not be given with? (2)
- other CYP3A4 inhibitors (eg. macrolides)
- other vasoconstrictors (ergot alkaloids, sumatriptan, other 5HT-1 agonists)
What are the two main severe SE to look out for with cafergot
MI and ergotism (vascular ischemia)
What is sumatriptan’s MOA (2)
selective vascular serotonin (5-HT1d) receptor agonist →
selectively constricts the carotid arterial circulation but does not alter cerebral blood flow →
inhibits trigeminal blood flow
What is sumatriptan indicated for?
acute treatment of migraine with or without aura
What are the contraindications for taking sumatriptan? (3)
HS to triptans
MI
concurrent administration with MAOis
What is the main rare SE of sumatriptan?
minor disturbances in LFTs
What is CGRP?
Nociceptive neuropeptide at the trigeminal ganglion that acts as a vasodilator (more neuropeptide comes out, causes more pain)
What is erenumab’s MOA (2)
Monoclonal antibody CGRP inhibitor
blocks nociceptive perception (pain is decreased)
alleviates vasodilation (less neuropeptide is released)
What is erenumab indicated for?
prophylaxis for migraine in adults who have at least 4 migraine days a month
How should erenumab be taken
SQ injection monthly, clinical benefit typically seen within 3 months
