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Mechanism of Action

Receptor antagonist. Memantine is believed to function as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds to the NMDA receptor-operated cation channels.

Therapeutic Use

Absorption

Memantine is highly absorbed with peak concentrations reached in about 3-7 hours. Food has no effect on the absorption of memantine.

Metabolism

Memantine undergoes little metabolism, with the majority (57-82%) of an administered dose excreted unchanged in urine; the remainder is converted primarily to three polar metabolites . Renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption.

Half-life

Average Daily Dose (adult)

Twice per day for doses above 5 mg, with dose escalation at a minimum interval of one week between increases.

Adverse Effects

Agitation, fall, inflicted injury, urinary incontinence, diarrhea, bronchitis, insomnia, urinary tract infection, influenza-like symptoms, gait abnormal, depression, upper respiratory tract infection, anxiety, peripheral edema, nausea, anorexia, and arthralgia were experienced at a greater or equal rate inNamenda-treated patients as in placebo-treated patients.

Drug Interaction

The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline state may lead to an accumulation of the drug with a possible increase in adverse effects. Drugs that alkalinize the urine (e.g. carbonic anhydrase inhibitors, sodium bicarbonate) would be expected to reduce renal elimination of memantine.

The combined use of Namenda with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and should be approached with caution.

Contraindication

Memantine is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.

Mechanism of Action

Therapeutic Use

Absorption

Galantamine is well absorbed with absolute oral bioavailability of about 90%.

Metabolism

20% dose was excreted as unchanged galantamine in the urine in 24 hours, representing a renal clearance of about 65 mL/min, about 20-25% of the total plasma clearance of about 300mL/min.

Half-life

Average Daily Dose (adult)

• 4mg, twice a day (8mg/day)

• Increase by 8mg/day after 4 weeks to 8mg, twice a day (16mg/day).

• After another 4 weeks, increase to 12mg, twice a day (24mg/day), if well tolerated.

Adverse Effects

Drug Interaction

Clearance of galantamine was decreased about 25-33% by concurrent administration of amitriptyline, fluoxetine, fluvoxamine, and quinidine, known inhibitors of CYP2D6, an isozyme involved in galantamine's metabolism.

Contraindication

Some antidepressants such as paroxetine, amitriptyline, fluoxetine, fluvoxamine, and other drugs with anticholinergic action may cause retention of excess Reminyl in the body, leading to complications.

Use of cholinesterase inhibitors can increase risk of stomach ulcers, and because prolonged use of non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin or ibuprofen can also cause stomach ulcers, NSAIDS should be used with caution in combination with these medications.

Mechanism of Action

Prevents the breakdown of acetylcholine and butyrylcholine (a brain chemical similar to acetylcholine) in the brain.

Therapeutic Use

Absorption

Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in approximately 1 hour. Absolute bioavailability after a 3 mg dose is about 36%. Administration of Exelon wiith food delays absorption by 90 minutes and reduces effect by 30%.

Metabolism

Rivastigmine is rapidly and extensively metabolized, primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. The major pathway of elimination is via the kidneys. No parent drug was detected in urine. The decarbamylated metabolite is the major component excreted in urine and represents 40% of the dose.

Half-life

Average Daily Dose (adult)

• 1.5mg, twice a day (3mg/day)

• Increase by 3mg/day every 2 weeks to 6mg, twice a day (12mg/day).

• Continue up to 6mg, twice a day (12mg/day), if well tolerated.

Adverse Effects

Drug Interaction

Use of cholinesterase inhibitors can increase risk of stomach ulcers, and because prolonged use of non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin or ibuprofen can also cause stomach ulcers, NSAIDS should be used with caution in combination with these medications.

Contraindication

Following a single 3 mg dose, mean oral clearance of rivastigmine was 60% lower in hepatically and renally impaired patients than in healthy subjects. For unexplained reasons, the severely impaired renal patients had a higher clearance of rivastigmine than moderately impaired patients. However, dosage adjustment may not be necessary in renally impaired patients as the dose of the drug is individually titrated to tolerability.

Mechanism of Action

Donepezil inhibits the action of cholinesterase, one of the enzymes that breaks down acetylcholine. This inhibition increases the amount of acetylcholine available for cell-to-cell communication, which may relieve some memory impairment.

Therapeutic Use

Absorption

Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours. Neither food nor time of administration (morning vs. evening dose) influences absorption.

Metabolism

Following multiple dose administration, donepezil accumulates in plasma by 4-7 fold and steady state is reached within 15 days. The steady state volume of distribution is 12 L/kg. Donepezil is approximately 96% bound to human plasma proteins, mainly to albumins (about 75%) and alpha 1 - acid glycoprotein (about 21%). It is excreted in the urine intact and metabolized to four major metabolites, two of which are known to be active.

Half-life

Average Daily Dose (adult)

5 or 10 mg daily.

Adverse Effects

Drug Interaction

The most frequent side effects of donepezil include diarrhea, nausea and vomiting, insomnia, fatigue, and loss of appetite. In most cases, these side effects were observed to be mild, usually lasting from one to three weeks and declining with continued use of the drug.

Use of cholinesterase inhibitors can increase risk of stomach ulcers, and because prolonged use of non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin or ibuprofen can also cause stomach ulcers, NSAIDS should be used with caution in combination with these medications.

Contraindication

Aricept is contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.

Mechanism of Action

Presumably acts by elevating acetylcholine concentrations in the cerebral cortex by slowing the degradation of acetylcholine.

Therapeutic Use

Absorption

Metabolism

Half-life

Average Daily Dose (adult)

Adverse Effects

Drug Interaction

Contraindication

Cognex is still available but no longer actively marketed by the manufacturer.