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Waqas TahirWaqas TahirGPST2GPST2
OverviewOverview
IntroductionIntroduction Mechanism of actionMechanism of action Therapeutic usesTherapeutic uses PharmacokineticsPharmacokinetics Adverse effects Adverse effects Discontinuation SyndromeDiscontinuation Syndrome PrecautionsPrecautions InteractionsInteractions
IntroductionIntroduction
TCAs discovered in 1950sTCAs discovered in 1950s
22ndnd member of TCA , amitriptyline introduced in member of TCA , amitriptyline introduced in 19611961
- Classification -- Classification - Tertiary aminesTertiary amines : : imipramine , amitriptyline , imipramine , amitriptyline ,
clomipramine , doxepin and trimipramineclomipramine , doxepin and trimipramine
Secondary aminesSecondary amines : : desipramine , nortriptyline , desipramine , nortriptyline , protriptylineprotriptyline
Mechanism of actionMechanism of action
1.1. Inhibition of neurotransmitter reuptakeInhibition of neurotransmitter reuptake
2.2. Blocking of receptorsBlocking of receptors Serotonergic receptorSerotonergic receptor Alpha-adrenergic receptorAlpha-adrenergic receptor Histamine (HHistamine (H11 receptor) receptor) Muscarinic receptorMuscarinic receptor
Therapeutic usesTherapeutic uses
DepressionDepression : initially 75mg , increased gradually : initially 75mg , increased gradually to 150-200mgto 150-200mg
Nocturnal EnuresisNocturnal Enuresis : child (7-10 yrs) 10-20 mg , : child (7-10 yrs) 10-20 mg , (11-16 yrs) 25-50mg at night(11-16 yrs) 25-50mg at night
Neuropathic painNeuropathic pain : initially 10-25mg at night , : initially 10-25mg at night , increased if necessary to 75mgincreased if necessary to 75mg
Migraine prophylaxisMigraine prophylaxis : initially 10mg at night , : initially 10mg at night , increased if necessary to maintenance of 50-increased if necessary to maintenance of 50-75mg75mg
PharmacokineticsPharmacokinetics Lipophilic nature & readily penetrate CNSLipophilic nature & readily penetrate CNS
Therapeutic lagTherapeutic lag
BioavailabilityBioavailability Peak plasma Peak plasma levellevel
Plasma half -Plasma half -lifelife
Active Active metabolitesmetabolites
EliminationElimination
Very variableVery variable
30 – 60%30 – 60%
4 to 8 hours4 to 8 hours 15 hours 15 hours
(10 – 28 hrs)(10 – 28 hrs)
importantimportant ExtrarenalExtrarenal
RenalRenal
Adverse effectsAdverse effects
Blockade of Blockade of MuscarinicMuscarinic receptors receptors blurred vision , xerostomia , urinary retention , constipation & blurred vision , xerostomia , urinary retention , constipation &
aggravation of narrow angle glaucomaaggravation of narrow angle glaucoma
Blockade of Blockade of Alpha-adrenergicAlpha-adrenergic receptors receptorsorthostatic hypotension , dizziness & reflex tachycardiaorthostatic hypotension , dizziness & reflex tachycardia
Blockade of Blockade of Histamine (HHistamine (H11)) receptors receptorsSedationSedation
Blockade of Blockade of Sodium channelsSodium channelsslow cardiac conduction slow cardiac conduction precipitate life threatening precipitate life threatening
arrhythmias as seen in ODarrhythmias as seen in OD
Adverse EffectsAdverse Effects
Discontinuation syndromeDiscontinuation syndrome
Group of symptoms that occurs upon the abrupt Group of symptoms that occurs upon the abrupt discontinuation/withdrawal of anti-depressantsdiscontinuation/withdrawal of anti-depressants
Higher risk for agents with the shorter half-lives Higher risk for agents with the shorter half-lives and inactive metabolitesand inactive metabolites
In tricyclics, discontinuation syndrome symptoms In tricyclics, discontinuation syndrome symptoms include include anxietyanxiety, , insomniainsomnia, , headacheheadache, , nauseanausea, , malaisemalaise, or , or motor disturbancemotor disturbance
PrecautionsPrecautions an alcohol probleman alcohol problem bipolar disorderbipolar disorder or or schizophreniaschizophrenia difficulty passing urine, prostate troubledifficulty passing urine, prostate trouble glaucomaglaucoma heart disease or previous heart attackheart disease or previous heart attack liver diseaseliver disease over active thyroidover active thyroid seizuresseizures thoughts or plans of suicide, a previous suicide attempt, thoughts or plans of suicide, a previous suicide attempt,
or family history of suicide attemptor family history of suicide attempt an unusual or allergic reaction to amitriptyline, other an unusual or allergic reaction to amitriptyline, other
medicines, foods, dyes, or preservativesmedicines, foods, dyes, or preservatives pregnant or trying to get pregnantpregnant or trying to get pregnant breast-feedingbreast-feeding
InteractionsInteractions
MAO inhibitors MAO inhibitors mutual enhancement ; HTN , mutual enhancement ; HTN , hyperpyrexia , convulsions , and comahyperpyrexia , convulsions , and coma
Direct-acting adrenergic drugs Direct-acting adrenergic drugs potentiate potentiate effectseffects
Ethanol ,other CNS depressants Ethanol ,other CNS depressants toxic toxic sedationsedation
Indirect –acting adrenergic drugs Indirect –acting adrenergic drugs blocks the blocks the effect effect
All TCAs lower seizure thresholdAll TCAs lower seizure threshold
Grapefruit juice may interact with amitriptylineGrapefruit juice may interact with amitriptyline
Thank YouThank You