TACRINE

Brand Name: CognexCHEMICAL STRUCTURE:

MECHANISM OF ACTION: a weak base . (Pka, 10). 1st generation of cholinesterase inhibitors. It Blocks both acetyl+butyryl cholinesterase . At !nerve ending: (-)MAO,d.GABA,I ! release of: nor

epinephrine,dopamine,serotonin.It became the 1st compound approved for treatment of AD in

1993.

INDICATION:

M. to Mod.

DOSING INFORMATION:

1. ADULT DOSAGE ORALLY 10\4 mg times\day * IMPORTANT NOTE Pt.>>> liver function tests; esp.

(ALT). empty stomach>>>if stomach

upset occurs, within meals .

C. MAXIMUM DOSE

DRUG INTERACTIONS:

A.Interactions with Foods: abp. reduced. B.Smoking increases the elimination. C.Interaction with other Medicines Theophylline (Theo-Dur, Uniphyl) Cimetidine (Tagamet)

PHARMACOKINETICS: ADME

1.Absorption: . ORAL,capsules/solution Bioavailability 20%

2. DISTRIBUTION : TOTAL PTN. BINDING: 55% 3.METABOLISM: LIVER, extensive within minuets METABOLITES:1-hydroxy-tacrine(Velnacrine),

active.

4. EXCRETION:      1. BREAST MILK: variable 2. RENAL EXCRETION: Less than

3%

5. HALF-LIFE: 2 to 4 hours .

PRECAUTIONS

Concurrent use of NSAIDs.

History of asthma, current liver disease, gastric ulcer disease.

Pre-existing conduction defects, [bradyarrythymias] .

CONTRAINDICATIONS

A. hypersensitivity to anti cholinesterase

agent .

B. tacrine-induced hepatotoixty

ADVERSE REACTIONS

a. HEMATOLOGIC EFFECTS anemia,leukopenia,thrombocytopenia,pan

cytopenia.

b. CARDIOVASCULAR EFFECTS Arrhythmias: arterial fibrillation\flutter,

palpitations, tachycardia\BRADYCARDIA. MI and severe conduction defects, HYPOTENSION .

c.CNS: 1.DIZZINESS:most common CNS side

effect+ATAXIA+INSOMNIA+TREMOR. confusion freq. lead to drug withdrawal. 3.DELIRIUM: characteristic of Cholinergic

excess ( muscle stiffness, weakness, hyperreflexia, extra pyramidal signs, stupor, severe slowing on EEG ).

d. GASTROINTESTINAL EFFECTS N, V, ABD.DISCOMFORT, BELCHING,

DIARRHEA , ANOREXIA [with oral tacrine and are dose-dependent].

...HEPATOTOXICITY : significant dose-related elevations

in liver function tests and Jaundice .

خير الله وجزاكم OHO