Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

pr3153 COPY (Adeline) > ic4 - neuropharmacology for antimigraine and antiepileptic drugs > Flashcards

ic4 - neuropharmacology for antimigraine and antiepileptic drugs Flashcards

1
Q

what are examples of some other brain cells and its functions

A

astrocytes, oligodendrocytes, schwann cells

astrocytes have protective, tropic support, electrolyte balance and its own membrane potential, it is important for maintaining homeostasis and formation of BBB and supports neurons by ensuring they have sufficient O2, metabolites and are not exposed to external environment and removes waste

oligodendrocytes forms the myelin sheath for brain neurons

schwann cells forms the myelin sheath for PNS neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the process of synaptic transmission

A

[initiation] when action potential reaches the terminal, it causes opening of voltage gated Ca channels in presynaptic membrane which gives rise to influx of Ca2+ -> Ca2+ acts on Ca2+ sensitive vesicle membrane proteins (VAMPs) to release vesicles from its cytoskeleton and facilitated vesicle docking to presynapse, fusion with presynaptic membrane and exocytosis -> result in release of neurotransmitters

to regulate, presynaptic autoreceptors are activated together with postsynaptic receptors to inhibit further release of neurotransmitter via feedback inhibition

[propagation and termination] neurotransmitters in the synpatic cleft activates postsynaptic receptors, signal terminates by action of catalytic enzymes and/or reuptake transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the different neurotransmitters and its respective features (type, location, function etc)

A
  1. glutamate (excitatory, found in pyramidal neurons in neocortex, implicated in learning and memory)
  2. GABA - gamma-aminobutyric acid (inhibitory, receptors are impt for action of sedatives)
  3. ACh (from nucleus basalis of meynert, implicated in learning, arousal and reward)
  4. dopamine (from substantia niagra, involved in motor system and reward)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the potential drug targets of synaptic transmission that can produce agonistic or antagonistic effects

A

a drug that is agonistic in nature will increase neurotransmission while a drug that is antagonistic in nature will decrease neurotransmission

[agonist] increase synthesis of neurotransmitter molecules, increase number of neurotransmitter molecules by destroying degrading enzymes, bind to autoreceptors to block inhibitory effects on neurotransmitter release, increase release of neurotransmitter from terminal buttons, binds to postsynaptic receptors and either activate them or increase effect on them as per a neurotransmitter would, block deactivation of neurotransmitters by blocking degradation or reuptake

[antagonistic] block synthesis of neurotransmitter molecules, cause neurotransmitter molecules to leak from vesicles and get destroyed by degrading enzymes, block release of neurotransmitters from terminal buttons, binds to autoreceptors and activate their inhibitory effects on release of neurotransmitters, binds to postsynaptic receptors to block neurotransmitter binding thus blocking its effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the functions of the BBB

A
  1. modulation of entry of metabolic substrates
  2. control ion movements
  3. prevent access of toxins into CNS and peripheral neurotransmitters from escaping into bloodstream from autonomic nerve endings
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the types of drugs and its movement across the BBB

A

non saturable and saturable

[non saturable] movement by transmembrane diffusion (incr amount of drug incr rate across BBB), suitable for drugs of low MW (<5kDa) and high lipid solubility (but note not too high lipid solubility as it can cause high affinity -> drug either gets sequestered in BBB capillary bed or gets uptaken by peripheral tissues), movement is affected by charge, tertiary structure and degree of protein binding and degree of P-gp expression

[saturable] movement by transporter system and once saturated an incr in amount of drug will not affect rate, has 10x higher uptake rate than transmembrane diffusion, uptake rate is regulated by cerebral bloodflow, co factors, hormones/ peptide modulators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is transmembrane diffusion movement of drugs affected by

A

charge, tertiary structure, degree of protein binding, expression of P-gp (an efflux transporter thus overexpressors of P-gp leads to lower rate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is transport system movement of drugs affected by

A

cerebral bloodflow, co factors, hormones/ peptide modulators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is “epilepsy”

A

epilepsy is a condition of repeated seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the pathophysiology of epilepsy

A

neuronal depolarisation is dependent on membrane potential

a seizure occurs due to excessive synchronous depolarisation usually starting from defined regions (foci) and spreading to other regions

dysregulated discharges due to unbalanced excitatory and inhibitory receptor or ion channel function which favours depolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the classification of seizures

A
  1. generalised seizures (tonic clonic, absence, myoclonic, atonic)
  2. partial seizures (simple, complex)
  3. status epilepticus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

differentiate between the types of generalised seizures

A

generalised seizures includes tonic clonic, absence, myoclonic and atonic

[tonic clonic] aka grand mal, involves tonic and clonic movements at the same time, tonic movement = muscle stiffening and loss of consciousness, clonic movement = muscle spasm and jerk

[absence] aka petite mal, start from staring spells and can be mistaken for simple daydreaming

[myoclonic] think of it as body jolts (like theres electricity), involves sudden incr in muscle tone

[atonic] think of it as drop attacks, involves sudden decr in muscle tone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

differentiate between the types of partial seizures

A

partial seizures are categorised into simple and complex

[simple] consciousness not impaired
[complex] consciousness impaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

differentiate between generalised grand mal seizure, generalised petite mal seizure and partial seizure ECG and which part of the brain is affected

A

generalised seizures affect frontal, temporal and occipital lobes

grand mal ECG is alot more crazy looking than petite mal ECG (still can see waves)

partial seizures affect frontal and temporal lobes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the possible moa of antiepileptics

A
  1. decrease membrane excitability by altering Na and Ca conductance during action potential
  2. enhance effects of inhibitory GABA neurotransmitters
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

list examples of antiepileptics

A

PHT, CBZ, VPA, PB, diazepam, levetiracetam, lamotrigine, topiramate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the first line antiepileptics for newly diagnosed generalised tonic clonic seizures

A

PHT, CBZ, VPA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the moa for PHT

A

blockade of voltage dependent Na channels which prevents further influx of Na thus preventing action potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is PHT indicated for

A

PHT is indicated for all types of seizures except absence seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is the PK characteristics of PHT

A

PHT has narrow therapeutic range, will require titration and monitoring due to saturation kinetics

PHT is also teratogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what are the s/e for PHT

A

dose related s/e of PHT includes drowsiness, confusion, nystagmus (misalignment of eyes), ataxia, unusual behavior, mental changes, coma, N

non related s/e of PHT includes hirsutism, hypersensitivity, gingival hyperplasia, acne, folate deficiency, osteomalacia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the moa of CBZ

A

blockade of voltage dependent Na channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is the indication for CBZ

A

for all types of seizures except absence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are some PK characteristics of CBZ

A

CBZ is a cyp450 inducer which induces its own metabolism (thus half life decr with repeated dosing) and incr elimination of other drugs

CBZ is also affected by PGx, HLAB*1501 allele in Asians can incr risk of SJS/ TEN -> gives rationale for screening prior to initiating CBZ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is the s/e of CBZ

A

dose related s/e of CBZ includes drowsiness, confusion, ataxia, slurred speech, N, mental changes, unusual behavior, coma, nystagmus (eyes becoming unaligned)

non dose related s/e of CBZ includes hypersensitivity, hirsutism, folate deficiency, gingival hyperplasia, osteomalacia, acne

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is the moa of VPA

A

blockade of voltage gated Na and Ca channels and also inhibits GABA transaminase enzyme which results in decr GABA breakdown and thus incr GABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is the indication for VPA

A

for all types of seizures including absence seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what are some PK characteristics of VPA

A

VPA is strongly bound to plasma protein which makes its F lesser than expected and bc of this VPA displaces other antiepileptics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is the s/e of VPA

A

dose related s/e of VPA includes drowsiness, confusion, nystagmus (eyes becoming unaligned), slurred speech, N, ataxia, mental changes, unusual behavior, coma

non dose related s/e of VPA includes hirsutism, acne, gingival hyperplasia, hypersensitivity, folate deficiency, osteomalacia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is the moa of diazepam

A

diazepam is a benzodiazepine that enhances effects of inhibitory GABA neurotransmitters by acting via GABA-A receptor Cl channels (aka a ligand gated binding site for GABA neurotransmitters) to potentiate influx of Cl- ions which leads to hyperpolarisation and causes neurons not to fire

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what are the sites on GABA-A receptor Cl channels

A

it has various ligand binding site where one recognises GABA and another allosteric regulatory site recognises benzodiazepines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what are the indications for diazepam

A

alcohol withdrawal sx, anxiety, seizure, sedation, refractory seizure, status epilepticus, adjunct skeletal muscle spasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what are the PK characteristics of diazepam

A

fast acting (onset 0.5h)
long acting (half life 43h)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what are the s/e of diazepam

A
  1. toxicity and overdose (results in severe respiratory depression esp if used concom alcohol, treat with flumazenil)
  2. s/e during use (includes drowsiness, confusion, amnesia, impaired muscle coordination thus do not operate machinery)
  3. tolerance and dependence (tolerance is dependent on freq of dosing and refers to the same dose no longer producing the same efficacy and dependence suggests that there would be withdrawal effects such as disturbed sleep, rebound anxiety, tremor and convulsions thus impt to withdraw gradually)
35
Q

what is the key characteristic to note for diazepam

A

it has abuse potential

36
Q

what is flumazenil

A

flumazenil is a benzodiazepine antagonist with specificity for benzodiazepine binding site on GABA(A) receptor Cl channel

37
Q

what is the moa of PB

A

potentiates effects of GABA-A receptor Cl channel but at a site distinct from benzodiazepines

38
Q

what is the key characteristic to note for PB

A

it is replaced by benzodiazepines due to its even greater risk of developing tolerance and dependence

39
Q

what are the PK characteristics of PB

A

long acting (1-2days)

40
Q

what are the indications for PB

A

for pediatrics or neonatal patients, mostly in emergency settings (IV LD f/b IV/PO MD)

41
Q

what are the s/e of PB

A

tolerance and dependence and withdrawal sx

42
Q

what is the indication of levetiracetam

A

as adjunctive tx for partial onset seizures, myoclonic and primary generalised tonic clonic seizures

can be monotx for partial onset seizures in newly diagnosed epilepsy

43
Q

what is the chemical structure of levetiracetam

A

a pyrrolidone derivative (chemically unrelated to existing ASM)

44
Q

what are the PK characteristics of levetiracetam

A

highly soluble and permeable

low intra and intersubject variability thus no need for routine monitoring

PO or IV route

45
Q

what are the s/e of levetiracetam

A

common s/e of levetiracetam: headache, vertigo, depression, cough, insomnia

rare s/e of levetiracetam: agranulocytosis, dyskinesia, suicidal, delirium

46
Q

what is “dyskinesia”

A

uncontrolled involuntary movement

47
Q

what is the moa of levotiracetam

A

unclear

48
Q

what is the moa of lamotrigine

A

blocks voltage gated Na channels, inhibit release of glutamate, impedes sustained repetitive neuronal depolarisation

49
Q

what is “lennox-gastaut syndrome”

A

severe childhood epilepsy

50
Q

what are the indications for lamotrigine

A

mono or adjunctive tx for partial, generalised, tonic clonic seizures

monotx for absence

initial or adjunctive for lennox-gastaut syndrome

51
Q

what are the PK characteristics of lamotrigine

A

linear r/s

PO and chewable thus suitable for children

half life generally shorter in children and half life significantly reduced by co administration with CBZ and PHT (bc both CBZ and PHT are inhibitors) vs increased by co administration with VPA (bc VPA is inducer)

52
Q

what are the ASM suitable for absence

A

VPA and lamotrigine

53
Q

what are the s/e of lamotrigine

A

common s/e of lamotrigine includes headache, irritability or aggression, tiredness

rare s/e of lamotrigine includes agranulocytosis, hallucination, movement disorders, SJS/TEN, hepatic failure

54
Q

what is the moa of topiramate

A

unclear but likely incr GABA activation of GABA(A) receptor to enhance GABA induction of Cl- flux but does not incr channel opening time (or may act on benzodiazepine insensitive subtype of GABA-A receptors)

55
Q

what are the indications for topiramate

A

mono for partial, generalised and tonic clonic

adjunctive for lennox-gastaut syndrome

prophylaxis of migraine in adults (BUT NOT ACUTE TX)

56
Q

what are the PK characteristics of topiramate

A

linear r/s

PO

long plasma half life

predominantly renal CL

not a potent inducer of drug metabolising enzymes

57
Q

what are the s/e of topiramate

A

common s/e of lamotrigine includes depression, fatigue, somnolence, N, weight changes

rare s/e of lamotrigine includes neutropenia, SJS/TEN, hepatic failure, mania, tremor, transient blindness

58
Q

what is the chemical structure of topiramate

A

sulfamate substituted monosaccharide

59
Q

what are the main considerations for ASM drug tx (regarding drug choice and regimen and monitoring)

A

individualisation according to seizure type, epilepsy syndrome, co medication, comorbidity, lifestyle and preferences

avoid polytherapy as much as possible

routine checking of drug levels without clear clinical indication not required and not cost effective

60
Q

when should ASM be monitored

A

drug levels are not routinely monitored without clear clinical indication

only check drug levels routinely if (i) assessing compliance to drug tx for refractory epilepsy (ii) assessing sx due to potential drug toxicity (iii) titration of PHT dose

61
Q

what is the pathophysiology of headache and migraines

A

vasodilation of intracranial extracerebral blood vessels result in activation of perivascular trigeminal nerves that releases vasoactive neuropeptides to promote neurogenic inflamm

central pain transmission may activate other brainstem nuclei thus resulting in assoc sx like N/V, photophobia and phonophobia

62
Q

what might hyperresponsiveness of brain be a result of (what affects migraine threshold)

A

hyperresponsiveness of the brain may be a result of inherited abnormality in Ca and/or Na channels and Na/K pumps that regulate cortical excitability through release of serotonin and other neurotransmitters

migraine threshold may also be affected by increased levels of excitatory AA like glutamate and alterations in extracellular K

63
Q

list examples of drugs that can be used for tx of headache and migraine

A

cafergot, sumatriptan, erenumab, paracetamol, NSAIDs

64
Q

what is the role of serotonin

A

serotonin is an important mediator of migraine headaches as it is an agonist of vascular and neuronal 5HT1 receptor subtypes that are known to have vasoconstrictive effects on meningeal blood vessels and inhibition of release of vasoactive neuropeptides and pain signal transmission

65
Q

what is the moa of cafergot

A

tonic action on vascular smooth muscles in the external carotid network which leads to vasoconstriction and thus prevents neuropeptides and inflamm mediators from leaking out, through stimulation of alpha adrenergic 5HT receptors (specifically 5HT1B and 5HT1D which are the two main receptor subtypes found on vascular structures that mediate vasoconstriction)

66
Q

what are the indications for cafergot

A

cafergot is indicated for acute tx of migraine

67
Q

what is the ingredient in “cafergot”

A

it contains caffeine and ergotamine

68
Q

what are the PK characteristics of cafergot

A

PO or rectal

rapidly absorbed

high plasma protein binding thus low absolute F

inhibits cyp3A (do not use with 3A inhibitors like macrolides as incr exposure to ergot toxicity presents as vasospasm and tissue ischemia (as can have vasoconstrictive effects on not just 5HT1D receptor but also on other peripheral small vessels)

69
Q

what are the ddi for cafergot

A

cyp3A inhibitors (eg. macrolides) as it can incr serum conc of cafergot which incr exposure to ergot toxicity

other vasoconstrictive agents (eg. ergot alkaloids, sumatriptan and other 5HT1 agonists)

70
Q

what does ergot toxicity present as (recall what drug can cause this) and why

A

cafergot

presents as vasospasms and tissue ischemia as cafergot may bind to 5HT1D receptors on peripheral small vessels as well

71
Q

what are the s/e for cafergot

A

common s/e of cafergot are N/V

rare s/e of cafergot is hypersensitivity, myocardial infarct and ergotism (vascular ischemia)

72
Q

what is the moa of sumatriptan

A

selective agonist of vascular serotonin (5HT1D) receptor that selectively constricts carotid arterial circulation but does not alter cerebral blood flow, and also inhibits trigeminal nerve activity

73
Q

what are the indications for sumatriptan

A

migraine with or without aura

74
Q

what are the c/i for sumatriptan

A

hypersensitivity to triptans, concurrent MAOi, MI

75
Q

why is sumatriptan c/i with concom MAOi

A

due to inability to clear drug thus toxicity issues arises

76
Q

what are the PK characteristics of sumatriptan

A

PO, nasal, IV

rapidly absorbed

low plasma protein binding

eliminated primarily by oxidative metabolism mediated by monoamine oxidase A (MAO)

77
Q

what are the s/e of sumatriptan

A

common s/e of sumatriptan includes dysgeusia (unpleasant taste), transient BP incr due to vasconstriction, flushing, sensation of cold, pressure, tightness

rare s/e of sumatriptan includes minor disturbances in LFTs but NOT hepatic failure

78
Q

what is one key consideration for sumatriptan (regarding length of tx regimen)

A

do not use sumatriptan for more than 10 days a month

79
Q

what is the moa of erenumab

A

erenumab is a MAb that is a calcitonin gene related peptide (GCRP) inhibitor

GCRP are found to relate to migraines as nociceptive neuropeptides transmits pain sensation and activates trigeminal ganglion that causes vasodilation which makes it leaky and results in vasoactive peptides like GCRP to leak out which potentiates vasogenic inflamm

blocking of GCRP can cause lost of nociceptive perception thus decr pain sensation and no vasodilation occurs

80
Q

what are the indications for erenumab

A

prophylaxis of migraines in adults who have at least 4 migraine days per month

81
Q

what are the PK characteristics of erenumab

A

SQ inj given monthly

82
Q

what are the s/e of erenumab

A

hypersensitivity, inj site reactions, constipation, pruritis

83
Q

what are the s/e of erenumab

A

hypersensitivity, inj site reactions, constipation, pruritis

pr3153 COPY (Adeline) (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions