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3153 > ASM > Flashcards

ASM Flashcards

1
Q

agonistic drug effects

A
  • incr synthesis of neurotransmitters
  • inhibit degrading enzymes
  • incr release of neurotransmitters
  • bind to postsynaptic receptors (incr neurotransmitter effect/ block inhibitory effect)
  • block deactivation (reuptake. degradation)
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2
Q

antagonistic drug effects

A
  • drug block synthesis of neurotransmitter
  • cause neurotransmitter to leak from vesicle/ destroyed by enzyme (less released)
  • drug block release of neurotransmitters
  • activate autoreceptors (inhibit release)
  • receptor blocker, no neurotransmitter effect
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3
Q

BBB functions
ECF 15% of total brain vol

A

□ Modulate entry of metabolic substrates (glucose), level more stable in CSF > blood

□ Ion movement.
* Na-K-ATPase in barrier cells pump Na+ into CSF
* pump K+ out of CSF into blood

□ Prevent access to CNS by toxins, peripheral neurotransmitters (autonomic nerve endings –> blood stream)

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4
Q

drug property — BBB

A

1) non-saturable: transmem diffusion
2) saturable: transporter system (influx & efflux)

drug uptake incr with neuroinflamm (porous cap walls, passage of non-lipid soluble Abx)

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5
Q

1) non-saturable: transmem diffusion

A
  • drugs with low MW, high lipid solubility
    • not too high lipid solubility
  • sequestrated in cap bed
  • uptake by peripheral tissues
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6
Q

Lipinski rule of 5 for BBB penetration

A
  1. <500 Da
  2. uncharged
  3. tertiary struc
  4. degree of protein binding
  5. lipid solubility
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7
Q

2) saturable: transporter system (influx & efflux)

A

10x faster > transmem diffusion

regulated by:
- cerebral blood flow, co factors, hormones/ peptide modulator

  • specific region of brain express transproters for reg. mole (L-dopa, vit B12)
  • EFFLUX TRANSPORTERS (PGP, decr uptake of drug)
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8
Q

strategies to cross BBB

A
  • target transporters (improve PK to corss BBB)
  • analogs of transported ligands (affinity to BBB transporters and CNS target receptor)
  • BBB as the therapeutic target (porous cap walls in disease state)
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9
Q

ASM rationales

A

1) decr mem excitability, alter Na, Ca2+ conductance during AP

2) enhance effect of inhibitory GABA neurotransmitters

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10
Q

1st gen ASM – still effective

A

carbamazepine
Phenobarbital
phenytoin
sodium valproate

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11
Q

2nd gen - better SE

A

gabapentin
lamotrigine
levetiracetam
pregabalin
topiramate

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12
Q

lvl A for new onset focal onset epilepsy

A

CBMZP
LVT
PT

elderly:
lamo
gabapentin

others:
SV (b), TPM (c)

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13
Q

lvl C for new onset GTC epilepsy

A

lamo
SV
cbmp
tpm

oxcarbazepine

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14
Q

refractory = not respond to tx

A

1) used lvl A
2) tried another lvl A
3) tried agent B, C

4) refractory lvl

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15
Q

refractory for focal onset epi

A

clobazam
lacosamide
pregabalin
perampanel

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16
Q

refractory for GTC
adjunctive AEDs

A

clobazam
LVT
lamo
TPM

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17
Q

tonic or atonic

A

SV
TPM

adjunct: lamo

X: CBMP, GP, Pregabalin, oxcarbazepine

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18
Q

absence

A

ethosuximide
lamo
SV

clobazam
leve
TPM

X: CBMP, GP,PT, pregabalin

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19
Q

focal tx

A

CBMP
Lamo
Leve
SV
oxcarbazepine

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20
Q

CBMP MOA

A

Block voltage dependent Na+ channels, less Na+ influx

stabilise hyperexcited nerve mems, inhibit repetitive neuronal discharges & reduce synaptic propagation of excitatory impulses

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21
Q

PK of 1st gen ASM Carbamazepine

A

F: 80%
Protein binding: 75-85%
E: 100% Hepatic
T1/2: 6 - 15hr

DDI: yes

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22
Q

indication and dose of CBM

A

indicated for complex/ simple PARTIAL & GTC
except absence:

initiate 100-200mg OD, BD

  • incr in 200mg/day increments until 400mg BD/TDS or optimum response. (max 2000mg/day)
  • or maintain: 10mg/kg/day in 2-4 divided doses
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23
Q

why titrate and monitor CBMP

A

1) autoinduction, accelerated elimination (t1/2 shortens w/ repeated doses)

2) PGx (HLA)-B*1502 allele – SJS, TEN

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24
Q

CBMP ADR

A

NV, Hepatotoxicity
Peripheral neuropathy
Osteomalacia
Megaloblastic anaemia, leuko, aplastic, SJS
GIT
suicidal ideation
hyponatremia

Moderate: malformation neonatal

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25
Q

common CBMP ADR

A

nystagmus
NV
lethargy
dizz, drowsy
headache
blurred vision, diplopia (double vision)
unsteadiness
ataxia, incoordination

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26
Q

DDI of CBMP

A

Potent enzyme inducer CYP (1A2, 2C, 3A4)

CYP3A4 substrates: affects apixaban, contracep, azoles

CYP3A4i: grapefruit, clarithromycin (macrolides)

UGT, PGP: apixaban, dabigatran, digoxin, edoxaban, rivaroxaban

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27
Q

caution in what pop for CBP

A

renal: no dose adj
hepatic: no dose adj (but risk of hepatotoxicity)

elderly: lower doses
pediatrics: higher doses

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28
Q

preg and lact pop

A

preg: teratogenic risk (only is benefit > risk)
- folic acid suppl
- vit K in last period of preg
- TDM
- do not discontinue abruptly (Status epi), try switch to LEVE, LAMO

lact: can use (monitor infant for ADR - jaundice, V, poor suckling, skin rxn)

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29
Q

distribution of CBMP

A
  • Highly protein bound 75-80%
  • Albumin, a1-acid Glycoprotein
  • Vd (immediate release) =1.4L/kg
    1~2 L/kg
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30
Q

CBMP metabolism

A
  • CYP3A4 (>99%)
  • Form active metabolites, carbamazepine-10,11 epoxide
    ○ 30+ metabolites
  • Undergoes autoinduction (stabilise in 2-3wks)
    ○ Induce own Metabolism
    ○ CL incr, t1/2 decr
    ○ Conc decline and stabilise with new Cl, t1/2
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31
Q

due to autoinduction how to dose CBMP

A

start at lower dose, incr gradually over initial few weeks to desired maintenance dose

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32
Q

monitor CBP

A

baseline & periodic: CBC, LFT, reticulocyte, Fe, renal, Na lvl (hyponatremia <136mmol/L– switch to LEVE)

baseline: HLA-B*1502 pgx

monitor: osteoporosis, LDL

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33
Q

Phenobarbital MOA

A

Acting on GABA-A receptor subunits.
Increases duration chloride channels are open.

at site diff from benzodiazepines

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34
Q

PB indication

A
  • AED (pediatric, neonatal IV LD –> IV/PO maintenance) long-acting 1-2d & child less likely to abuse

sedative-hypnotic <— benzodiazepine
(PB: tolerance & dependence, withdrawal sx)

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35
Q

PB duration of action and indication

A

LA (1-2d): anticonvulsant

SA (3-8hr): sedative, hypnotic

ultrashort (20min): IV induction of anesthesia (thiopental)

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36
Q

PB PK

A

F: 100%
Protein binding: 50%
E: 75% H
T1/2: 72-124 hr

DDI: yes

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37
Q

PB ADR

A

Hepatotoxicity
Peripheral neuropathy
Osteomalacia
dysarthria, ataxia, incoordination
Megaloblastic anaemia

major: malformation neonatal

sedation and drowsiness

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38
Q

common PB ADR

A

sedation, drowsy
nystagmus

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39
Q

PB DDI

A

Potent enzyme inducer
CYP (1A, 2A6, 2B, 3A)

UGT

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40
Q

dose-dependent depression of CNS with benzo vs PB

A

as dose incr
hypnosis –> anesthesia –> medullary depression –> coma

benzo (will plateau, safety) > PB (continues to incr, no plateus)

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41
Q

phenytoin MOA

A

Block voltage dependent Na+ channels

increasing efflux or decreasing influx of sodium ions across cell membranes

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42
Q

PT indication & dose

A

1) partial/ focal GTC
LD: 15mg/kg/d (1-3 divided doses)
F/B: 5mg/kg/d (1-3 divided doses)

2) status epilepticus
LD: 20mg/kd + IV benzodiazepine
F/B: 5mg/kg/d in 2 divided doses

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43
Q

PT PK

A

F: 95%
Protein binding: 90%
E: 100% hepatic
T1/2: 12-60hrs

DDI: yes

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44
Q

PT DDI

A

Potent enzyme inducer
CYP (2C9, C19, 3A)

UGT, PGP

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45
Q

PT ADR

A

Hepatotoxicity
Gingival hyperplasia (gum growth)
Hirsutism (F facial hair)
Peripheral neuropathy, sensory loss
Osteomalacia
Megaloblastic anaemia
rash, SJS

Moderate: malformation neonatal
Affect neonatal cognition

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46
Q

common PT SE

A

nystagmus
NV
lethargy
dizz, drowsy
headache
blurred vision, diplopia (double vision)
unsteadiness
ataxia, incoordination

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47
Q

PT formulation

A
  • Oral susp 125mg/5ml (Phenytoin acid 100%)
  • Capsule, IV (salt form, phenytoin sodium 92%)
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48
Q

PT absorption

A
  • But slow absorption
  • Reduced at higher dose >400mg/dose (break up)
  • Reduced with enteral feed interaction (space 2hrs)
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49
Q

PT distribution

A
  • Vd 0.7L/Kg (0.5 - 0.8L/kg)
  • Highly albumin bound 90%
    ○ Altered by displacement, incr Fu
    ○ Total lvls (bound + unbound)
    § Estimate Fu by eqn
    ○If low albumin –> incr free PT
50
Q

PT correction for albumin <40g/L

A

C corrected = C observed/ [x . (alb/10) +0.1]

Guide estimation of PT in presence of hypoalbuminemia, renal impairment

albumin in g/L
Conc in mg/L

x is albumin coeff, varies

51
Q

free PT conc = Total phenytoin lvl x correction factor

A

new Winter-tozer
X = 0.275 (crcl > 10ml/min)
x = 0.2 (crcl <10 ml/min, HD)

52
Q

PT metabolism/ why need titrate and monitor

A
  • narrow therapeutic range (40-100um)
  • Zero order kinetics, non-linear b. dose & plasma conc
    ○ Capacity limited clearance
    ○ (conc incr, CL decr) non-proportional incr in conc, AUC
  • Saturable protein binding
53
Q

PT CI

A

absence seizure
teratogenic (congenital malformation, neurodev risk)

54
Q

PT monitor

A

CBC, LFT, vit D, suicidal

plasma PT conc (free conc: if renal impair/ hypoalbumin)

monitor for osteoporosis, lipid (cholesterol, LDL)

55
Q

valproic acid MOA

A

Block voltage dependent Na+ and Ca2+ channels

Inhibit GABA transaminases (incr GABA+ mimic its action)

strongly bound to plasma prot, displace other ASM (except PT)

56
Q

VA indication

A

bipolar (fixed 500-700mg/day, 1-4 divided doses)

epilepsy – absence, complex partial (10-15mg/kg/day. 1-4 divided dose), GTC (250mg/day)

migraine (off label)

57
Q

VA PK

A

F: 100%
Protein binding: 75-95%
E: 100% hepatic
T1/2: 6-18hr, shorter in children

DDI: yes

58
Q

VA ADR

A

Hepatotoxicity, Pancreatitis
alopecia
thrombocytopenia
hyperammonemia
haemorrhage
hypersensitivity (SJS, TEN)

(CI) major: malformation neonatal
Affect neonatal cognition

59
Q

common VA ADR

A

NVD (take w/ after food)
weight gain
ataxia (poor muscle control), slurred speech
tremor
dizzy, drowsy , confusion
nystagmus (eyes not aligned)

F: painful/ irregular periods

60
Q

special pop for SV

A

renal: NIL but monitor for clinical resp, free VA

hep: not recc, CI in severe

elderly: lower initial & maintenance doses (monitor ADR)
paediatric: weight based dosing

61
Q

VA DDI

A

Potent enzyme inhibitor
CYP2C9
UGT

1) enhance CNS depressant effect: (nasal: azalastine, olopatadine)
- neuroleptics, MAOi, antidepressants, benzodiazepines

2) decr conc of VA: carbapenems, estrogen, barbiturates,

3) lamotrigine: enhance ADR and incr serum conc (lamo dose adj, decr)

4) incr conc of VA: CBP (plasma displace)

5) affect conc of other drugs (warfarin, NSAID, PHT)

62
Q

VA absorption

A

F~1, (PO)

Inj, enteric coat, sustained release tablets, syrup

63
Q

VA distribution

A
  • Vd = 0.15L/kg
  • Highly albumin bound ~90-95%
    ○ Displaced by endogenous (uraemia, hyperbilirubinaemia)
    ○ Compete for binding (PHT, NSAID, warfarin) displaces other ASM
  • Saturable protein-binding within therapeutic range
    ○ Decr protein binding at higher conc
    ○ More Free at low albumin
64
Q

VA monitor

A

base & periodic: LFT, CBC w/ PLT

as needed: PTT, NH3, pancreatic, hepatotoxic, suicidal sx, osteoporosis

preg

efficacy: n.o. of seizure ep, TDM (ref 50-100mg/L)

65
Q

dose/ plasma conc related ADR

A

CNS - somnolence, fatigue, dizzy, visual disturbances, nystagmus, ataxia

GI - NV (CBMP, SV)
psychiatric - behavioral LEVE
cognition - speech TPM

66
Q

ADR occurs more freq in

A

ASM combination therapy
- additive neurologic effect of ASM
- initiation of therapy (disappear when tolerance develops)

67
Q

mitigate ADR

A
  • initiate at low dose, slow titrate
  • avoid large dose changes
  • restrict to 1 drug only (if feasible)
  • adjust admin schedule
    * largest dose ON
    *divide daily dose across day
    * Sustained release formulation
    * reduce TOTAL DAILY DOSE
68
Q

idiopathic/ hypersensitivity related ADR

A

all ASM except some 2nd gen

  • blood dyscrasia (aplastic, agranulo)
  • hepatotox (1st gen)
  • pancreatitis (SV)
  • lupus like (1st gen)
  • exfoliate dermatitis, severe skin inflamm
  • TEN/ SJSJ

-megaloblastic anaemia (PT, assoc CBMP, PB)

occur in first few mnths of therapy

69
Q

leve ADR

A

somonolence, dizzy
asthenia (weak), coordination difficulties (first 4 wks)
headache
Behavioural disturbances: irritable, aggression, decr renal function

rare: agranulocytosis, suicide, delirium, dyskinesia

70
Q

leve uses

A
  • 1st line for FOCAL SEIZURE
  • adj: partial onset seizures, myoclonic, 1*GTC seizure
  • safe: low intra & inter- variability.
    (highly soluble and perm)
  • safe for preg
71
Q

LAMOtrigine ADR

A

NV
dizzy, somnolence
tremor, coordination difficulties, asthenia
headache

rash, SJS/TEN, DRESS

72
Q

LAMO DDI

A

PK linear

1/2 reduced: CBP, PT (inducer)
1/2 incr: SV (inhibitor)

73
Q

lamo uses

A
  • adj/ mono: partial seizures, generalised (GTC)
  • absence
  • lennox-gastaut (severe childhood eoilepsy)
  • safe for preg
  • PK linear but t1/2 (reduced: CBP, PT) (incr: VA)
74
Q

topiramate ADR

A

somonolence, headache
ataxia, coordination, fatigue

(psychomotor – slow, speech, memory)
weight loss

glaucoma, hyperammonemia, metabolic acidosis
hyperthermia, paresthesia, kidney stones

neutropenia, mania, depression

75
Q

TPM uses

A
  • mono: partial seizure, GTC
  • adjunct: lennox-gastaut
  • prophy for migraine (not ACUTE)
  • sulfamate-substituted monosaccharide
  • safe: not a potent inducer of drug-metabolising enzymes
76
Q

TPM monitor

A

before initiate: eating disorder sx (can cause weight loss)

baseline: electrolytes, SCr

periodic: metabolic acidosis, suicidal, osteoporosis

77
Q

pregabalin, gabapentin adr

A

drowsy, ataxia, weight gain, dizzy

peripheral oedema

78
Q

risk management

A

1) PGx testing (CBMZP)

2) dosing guidelines (lamo)

3) potential cross sensitivity rxn (ASMs w/ aromatic rings: CBMZP, PT, PB, LAMO

79
Q

CBZ pgx testing

A

HLA-B*1502: risk of CBZ-induced SJS/ TEN

  • Han chinese, other Asian ethnic grps (Malay, Indan, Thais)
  • tested +ve: avoid CBP, PT
80
Q

chronic (systemic) ADR

A

LT ASM therapy

drug-specific, not directly linked to plasma conc

may not be life-threatening but affects QOL

  • gingival hyperplasia (PT)
  • hirsutism (PT)
  • alopecia (SV)
81
Q

neurological ADR

A

CNS and resp depression for majority

peripheral neuropathy (long term PT, assoc CBMP, PB)
* may respond to folate suppl

82
Q

metabolic ADR

A
  • incr weight gain (SV) *reversible
  • anorexia (TPM, felbamate) *reversible with discontinuation
83
Q

endocrine ADR

A
  • osteomalacia (PT, PB, CBMP)

incr CL fo vit D –> 2nd Hyperparathyroidism – > incr bone turnover –> reduced bone density

84
Q

neonatal congenital defects

CI; VA

A

1) major malformation risk

HIGH RISK: VA, PB, TPM
MOD RISK: SV, PT

2) neonatal cognition
VA, PT

85
Q

suicidal ideation ADR

A

CBMZP, GP, LAMO, LEVE, PREGABALIN, TPM, SV

oxcarbazepine, tiagabine, zonisamide

*no changes to ongoing therapy unless discussed with physician
- closer monitoring of sx

86
Q

lamotrigine initial dosing risk when __

A

risk of cutaneous reaction at
- higher starting doses
- rapid dose escalation
- concomitant SV

** slow titration

87
Q

lamotrigine doses with SV

A

25mg EOD –> 25mg OD –> incr by 50mg OD (every 1-2 wks)

100-200mg/day with SV only
100-400 mg/day with other drugs that induce glucuronidation

88
Q

lamo dose w/o CBP, SV

A

25mg OD –> 50mg OD –> incr by 50mg/day every 1-2 weeks

maintenance 225-375mg/d (2 divided dose)

89
Q

lamo w/ CBP, PT, PB

A

50mg OD –> 100mg/d –> incr by 100mg/d every 1-2 weeks

maintenance: 300-500mg/d (2 divided doses)

90
Q

potential cross sensitivity rxn (ASMs w/ aromatic rings)

A

CBMZP, PT, PB, LAMO

can form arene-oxide intermediate

immunogenic through int with proteins/ cellular maromolecules

91
Q

which medication to choose

A
  • efficacy and effectiveness (type of seizure/ epilepsy)
  • tolerability (special grps, comorbidity)
  • PK (DDI, hormonal, renal, liver failure)
  • personal pref (formulation, freq)
  • country (cost, availability)
92
Q

adjust tx based on

A

1) seizure free? efficacy
- incr dose / add another ASM

2) SE tolerable?
- No = decr dose

93
Q

when to discontinue ASM?

A

considered: after min of 2 yr w/o seizure

unless: pt with incr risk of seizure recurrence.

94
Q

discussion for discontinuation

A

○ Reason
○ Taper schedule
- Personalise: seizure recurrence, seizure freq, n.o. of meds

○ Monitor before/ after ASM taper
○ Motivation, attitude, potential risks-benefit

95
Q

risk of continuation vs relapse

A

continuation: chronic toxicity, teratogenicity

relapse: injury, SUDEP, employment

96
Q

tapering schedule is individualised based on:

A
  • risk factor for seizure recurrence
  • seizure freq
  • n.o. of medications
97
Q

epilepsy resolved

A

past applicable age of age-dependent epilepsy syndrome (childhood, infancy)

seizure free for last 10 yrs
no seizure meds for last 5 yrs

98
Q

why is it difficult to identify optimal dose on clinical grounds

A
  1. plasma ASM conc correlates better with clinical effects (than dose)
  2. assessment of therapeutic response is difficult
    - ASM tx is prophylactic, seizure occur at irregular intervals
    - difficult to ascertain whether prescribed dose suff to prod. LT seizure control
  3. not always easy to recognise signs of toxicity
  4. ASM subjected to PK variability (large diff in dosage in diff pts)
  5. no lab markers for clinical efficacy or toxicity of ASM
99
Q

indications for ASM TDM

A

Establish indiv therapeutic range

To assess lack of efficacy

To assess potential toxicity

To assess loss of efficacy (breakthrough)

100
Q

Establish indiv therapeutic range

A

Reference range not effective for all

  • Once stable: Document effective lvl which controls seizures whilst minimise SE
  • Help in subsequent changes
    • Anticipated PK changes
    • DDI
    • Medical conditions
101
Q

reference ranges (PT, VA, CBP, PB)

A

CBP 4-12 mg/L

PT 10-20mg/L

PB 15-40 mg/L

VA 50-100 mg/L

102
Q

To assess lack of efficacy

A
  • Fast metaboliser
  • Adherence issues
  • Other problems
  • Decide whether to change drugs vs rework diagnosis
103
Q

To assess potential toxicity

A
  • Changing physiology (preg)
  • Slow metabolisers
  • Change in disease/ drugs
    • Renal – uremia, hypoalbuminemia
    • Liver – CYP enzymes
    • New drugs/ int
  • Danger lvls (conc-dependent ADR)
104
Q

To assess loss of efficacy (breakthrough)

A
  • Change in physiology (Age, preg)
  • Change in pathology
  • Change in formulation
    • Brand vs generic
    • DF
  • DDI
105
Q

infor needed for TDM

A

○ Indication for ASM
○ Dose (when, how long, how much)
○ Sample from pt
- When taken, type
- Eg: short t1/2 take at trough to see maintenance efficacy

○ Clinical condition
- Seizure control (baseline vs current)
- Comorbidities

○ Other lab values
○ Other drugs (when, how long, how much)

106
Q

special pop – women of childbearing potential

A
  • Receive counselling on family planning
  • Potential risk to fetus
    • Uncontrolled seizures
    • Teratogenic potential of ASM
  • Use OC
    • Potent enzyme inducers make OC ineffective
      • Alternative contraceptives needed (backup)
  • lamo dose will decr due to OC = breakthrough seizures
107
Q

contraception

A

potent enzyme inducers make OC inffective

consider other contaception options:
1. prog/ copper IUD
2. prog depot inj (10-12wka)
3. COC (>50ug of E) + barrier

108
Q

special pop – preg

A

VA is CI – unless no suitable alt (epilepsy)
– not for bipolar disorder (look for alt)

congenital malformation: CBP, PB, PT, TPM

dose-dep risk: CBP, PB, TPM

neurodev risk: PB, PT, TPM

109
Q

special pop – lactation

A

ASM not absolute CI for breastfeeding – still encouraged to BF

PB, zonisamide, ethosuximide – higher lvls in breastmilk

110
Q

status epilepticus

A

○ considered an abnormally prolonged seizures (after t1)

○ Long term conseq (after t2)
- Neuronal death, injury, alteration of neuronal networks, depend on type and duration of seizures

t1, t2 depends on type of SE
TC: 5, 30mins

111
Q

0-5min stabilisation phase

(ED, inpt, paramedincs)

A
  1. stabilise: airway, brathing, circ, disability
  2. time seizure from its onset, monitor vital signs
  3. assess O2: intubate/ nasal mask
  4. initiate ECG monitor
  5. glucose (D50W IV)
  6. IV access: electrolytes, hematology, toxicology, anticonvulsant drug lvls
112
Q

5-20min initial therapy phase

A

benzodiazepine

1) IM midazolam (10mg/kg/dose, >40kg)

1) IV lorazepam (0.1mg/kg/dose, max 4mg/dose) can repeat

1) IV diazepam (0.15-.0.2 mg/kg/dose, max 10mg/dose, can repeat dose)

IV PB, rectal diazepam, IM midazolam

113
Q

2nd therapy phase (if seizure continue)
20-40min

non-benzodiazepine ASM, single dose

A

IV fosphenytoin (20mg/kg, max 1500mg)
IV VA (40mg/kg, max 3000mg/dose)
IV levetiracetam (60mg/kg, max 4500mg/dose)

if all not avail: IV PB (15mg/kg)

114
Q

3rd therapy phase (if seizure continues)
40-60mins

continuous admin, anesthetic doses

A

repeat 2nd line therapy

or anesthetic doses (thiopental, midazolam, pentobarbital, propofol)

  • with continuous EEG monitoring
115
Q

at any point if pt at baseline

A

symptomatic medical care

further diagnosis to identify causes (EEG, CT, LP)

116
Q

benzodiazepines MOA

A

potentiates GABA effects – inhibitory transmitter in brain regions
* acts via GABA receptors
* influx of CL- ions

= hyperpolarisation –> neurons not fired

117
Q

benzodiazepine and AED

A

diazepam (43hr half life, long acting for seizure, epilepticus, sedation) – but fast onset 30mins

lorazepam (12hr , intermediate-acting for anxiety, status epilepticus)

Clonazapam (30hr, LA, for panic disorders)

118
Q

benzodiazepines ADR

  • clonazepam, lorazepam, DIAZEPAM
A
  • acute toxicity/ overdose
  • severe resp depression esp W/ ALCOHOL
    - tx with flumazenil - benzo antagonist
  • droswy, confuse, amnesia, coordination
  • tolerance and dependence
    - must withdraw gradually
    - abuse potential
119
Q

tolerance vs dependence

depends on freq of use. tolerance develops faster for epilepsy > sedation use

A

Tolerance: Same dose wont give you same efficacy

dependence: will have withdrawal effects, addictives
- disturbed sleep, rebound ANX, tremor, convulsions

120
Q

counselling points

A

1) adherence
2) missed dose (do not double)
3) if SR, EC do not crushed
4) avoid alcohol (CNS depressive effects)
5) take after food to reduce GIT upset

121
Q

fluctuation index

A

CR is better to decr fluctuation, less peak-to-trough conc variation

less dose-dependent SE and less incidence of subtherapeutic drug conc

3153 (8 decks)

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