nha 0813

Mood Stabilizer Stabilizes mood: Abolish :

Excitement

Euphoria (state o optimism, cheerfullns & well being)

Insomnia Prevent relapse

Lithium Sodium valproate (epilim) Carbamazepine

PK Well absorbed orally

X metabolized , x protein bound

Cross BBB

T ½ = 20-24hr

↓ therapeutic index : monitor [Li+]

Effect : several d & 2-4 wks to fully dvlp

Oral/IV

Broad therapeutic index

Rapidly & completely absorbed following oral admin

T ½ = 8-17hr

Mets : liver

Oral →complete absorp

Induce hepatic microsomal enzyme→ inhibit owns mets

Monotherapy or combine wif Li+

T ½ = 18-55hrs

Mets : liver

Safe in pregnancy

Indication Prevent relapse of affective disorder (prophylaxis)

Mania , bipolar

Stabilze mood – control mania symtoms

Acute manic

Resistan depression – augment effect o anT depressant

Schizoaffective or cyclothymia

Absence seizure w concomitant generalized tonic clonic seizure

Myoclonic seizure

Atonic seizure

Partial seizure

Bipolar disorder

Migraine

Acute mania in child & elderly

Schizoaffective d/o

Generalized tonic clonic

Complex partial seizure

Trigeminal neuralgia

Bipolar dz

Acute mania

Prophylactic therapy

MOA Specific mechanism : unknown

Li+ replaces Na+ → equally distributed → affect ion flux across brain cell & modify cellular m’brane property

Li+ x NA & DA in CNS

Li+ x enzyme involve in recycling o m’brane phosphoinositide →↓ 2nd messenger →↓α adrenergic & muscarinic transmission

Block high frequency repetitive firing o neurons

Block Na+ currents

BlocK NMDA R – mediated excitation

Bind + prolong inact state o Na+ channel →block o sustained ↑ frequency repetitive firing o AP

Alter Na+ K+ Ca2+ conductance membrane potential [amino acid] [NA] [A] [Ach] [GABA]

↑[ ]→ - release o serotonin/NA promotes uptake o dopamine inhibit MAO actvt

Interact w membrane lipid → stabilize mmbrane

Block Na+ channel

Inhibit repetitive firing in neurons

Acts presynapticly →↓ synaptic transmission

Drp lbnu 'Umar r.a. bahawa Rasulullah SAW telah bersabda: "Aku telah

diperintahkan supaya memerangi manusia sehingga mereka naik saksi bahawa

sesungguhnya tiada Tuhan melainkan Allah dan bahawa sesungguhnya

Muhammad utusan Allah, sehingga mereka mendirikan sembahyang dan membayar

zakat. Apabila mereka telah berbuat demikian, maka mereka telah memelihara darah

mereka dan harta mereka daripada aku, melainkan dengan hak lslam, dan hisab

perhitungan amal mereka terserah kepada Allah Ta'ala.

nha 0813

Drug intrxn Li+ clearance ↓ → ↑ Li+ toxicity

Thiazide diuretics

ACEi

Tetracyclines

NSAID (xcept aspirin + acetaminophen)

All anTpsychotic drug (xcept clozapine & newer drug) → ↑ xtrapyramidal sx

Inhibit own mets

Inhibit mets o :

Phenobarbital, phenytoin, carbamazipine, ethosuximide

Displace phenytoin from plasma prot

↑ hep mets o other drug→ primidone, phenytoin, ethosuximide, valproate, clonazepam

Phenytoin, Phenobarbital →induce hep enzyme →↑ carbamazepine mets

Propoxyphene, valproate → inhibit carbamazipine clearance

s/e CNS

Tremor, ataxia, choreoathetosis

Slurred speech/aphasia

Mental confusion, forgetfullns, drowsins

Motor hyperactvt

Thyroid dysfx

Goiter (interfere tyrosine iodination but norm px euthyroid)

Hypothyroidism

Kidney

Nephrogenic diabetes insipidus

Minimal ∆ glomerulopathy

Chronic interstitial nephritis

Electrolyte

Initial Na+ & H2O loss → Na+ & H2O retention → edema (d/t ↑ aldosterone secretion)

CVS

Benign & reversible inversion T wave

Others

GIT : N+V+D / Wt gain / Rash

N,V, abd pain, heartburn

Sedation ++ (used w phenytoin)

Thrombocytopenia

Hepatotoxicity

Idiosyncratic rxn

Severe fatal

Px < 2y/o

Congenital abnor – caution in preg

Diplopia

Ataxia

GIT upset

Unsteadiness

↑ dose →drowsiness

hypoNatrinaemia

water intoxication

blood dyscrasias : aplastic anaemia, agranulocytosis

erythematous skin rash ; SJS (rare)

C/I Sick sinus syndrome px

Pregnancy

Fetal congenital abnorm: cardiac Ebstein’s anomaly

Fetal goiter, hypotonia

B-feed

Secreted in milk → Baby lethargic, cyanose, abnorm Moro reflex

Renal failure/ cardiac failure or recent MI

Pregnancy