Rivastigmine Tartrate Presented by: Mona Abdulrahman Alkallabi Mona Abdulrahman Alkallabi

Chemistry Rivastigmine tartrate is known chemically as (S) – N- Ethyl-N – Methyl -3 [1 – (dimethylamino) ethyl ] – phenyl carbamate hydrogen – (2R, 3R) – tartrate. Rivastigmine tartrate is commonly referred to in the pharmacological literature as SDZ ENA 713 or ENA 713. Its trade name is Exelon. Rivastigmine tartrate is known chemically as (S) – N- Ethyl-N – Methyl -3 [1 – (dimethylamino) ethyl ] – phenyl carbamate hydrogen – (2R, 3R) – tartrate. Rivastigmine tartrate is commonly referred to in the pharmacological literature as SDZ ENA 713 or ENA 713. Its trade name is Exelon.

Pharmacokinetics Absorption : Absorption : Rivastigmine is rapidly and completely absorbed. Absolute bioavailability after a 3 – mg dose is about 36%. Rivastigmine is rapidly and completely absorbed. Absolute bioavailability after a 3 – mg dose is about 36%. Distribution : Distribution : Rivastigmine is widely distributed throughout the body,and penetrates the blood brain barrier. Rivastigmine is about 40% bound to plasma proteins. Rivastigmine is widely distributed throughout the body,and penetrates the blood brain barrier. Rivastigmine is about 40% bound to plasma proteins.

Metabolism Rivastigmine is largely metabolised by its target enzymes AChE and BuChE in brain, liver, and intestine. Rivastigmine is largely metabolised by its target enzymes AChE and BuChE in brain, liver, and intestine. Excretion: The major pathway of elimination is via the kidney. Nicotine use increases the oral clearance of rivastigmine by 23%.

Dose and Administration The dosage of rivastigmine tartrate shown to be effective in controlled clinical trials is 6 – 12 mg/day, given as twice a day dosing (daily dose of 3 to 6 B.I.D). Rivastigmine tartrate should be taken with meals in divided doses in the morning and evening. The dosage of rivastigmine tartrate shown to be effective in controlled clinical trials is 6 – 12 mg/day, given as twice a day dosing (daily dose of 3 to 6 B.I.D). Rivastigmine tartrate should be taken with meals in divided doses in the morning and evening.

Pharmacodynamics 1- Mechanism of action : 1- Mechanism of action : Rivastigmine increases the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. Rivastigmine is a slowly non competitive pseudo irreversible dual cholinesterase (ChE) inhibitor, with brain regional specifity for the cerebral cortex and hippocampus. Its target is both acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE). Rivastigmine increases the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. Rivastigmine is a slowly non competitive pseudo irreversible dual cholinesterase (ChE) inhibitor, with brain regional specifity for the cerebral cortex and hippocampus. Its target is both acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE).

2- Pharmacological Actions : - Neurogenic Effects : - Neurogenic Effects : BuChE inhibition may maintain cholinergic function more effectively along the continue of Alzheimer disease than inhibition of AChE alone. In addition, rivastigmine is the only ChE inhibitor with preferential selectivity for the G1, molecular form of AChE, compared with the G4 form. BuChE inhibition may maintain cholinergic function more effectively along the continue of Alzheimer disease than inhibition of AChE alone. In addition, rivastigmine is the only ChE inhibitor with preferential selectivity for the G1, molecular form of AChE, compared with the G4 form.

Cardiovascular Effects Rivastigmine has not demonstrated significant effects on heart rate and blood pressure and other cardiovascular parameters at doses that produced clear central effects. Rivastigmine can be safely administered to Alzheimer disease patients without the need for cardiac monitoring. There is a possibility of a causal relationship between rivastigmine and prolonged QTC interval. Rivastigmine has not demonstrated significant effects on heart rate and blood pressure and other cardiovascular parameters at doses that produced clear central effects. Rivastigmine can be safely administered to Alzheimer disease patients without the need for cardiac monitoring. There is a possibility of a causal relationship between rivastigmine and prolonged QTC interval.

Haemodynamic Effects It inhibit ChE activities in the plasma and CSF. Plasma ChE inhibition levels were significantly lower than, but highly correlated with levels of inhibition in the CSF, indicating that rivastigmine passes through the blood brain barrier and causes a higher inhibition of ChE in the central compartment. It inhibit ChE activities in the plasma and CSF. Plasma ChE inhibition levels were significantly lower than, but highly correlated with levels of inhibition in the CSF, indicating that rivastigmine passes through the blood brain barrier and causes a higher inhibition of ChE in the central compartment.

Clinical Uses 1-Rivastigmine is indicated for the treatment of mild to moderate dementia of the Alzheimer type. 1-Rivastigmine is indicated for the treatment of mild to moderate dementia of the Alzheimer type. 2- The apparent selectivity of rivastigmine for the frontal lobe may be important in patients with parkinson's disease dementia, in whom this region of the brain is particularly affected. 2- The apparent selectivity of rivastigmine for the frontal lobe may be important in patients with parkinson's disease dementia, in whom this region of the brain is particularly affected.

3- Rivastigmine is also used in Lowy body variant of Alzheimer disease. 3- Rivastigmine is also used in Lowy body variant of Alzheimer disease. 4- Rivastigmine is used in the treatment of Huntington's disease by improving motor, cognitive and behavioral functions in Huntington's disease. 4- Rivastigmine is used in the treatment of Huntington's disease by improving motor, cognitive and behavioral functions in Huntington's disease. 5- Rivastigmine used also in patients with Alzheimer disease who failed to benefit from treatment with donepezil. 5- Rivastigmine used also in patients with Alzheimer disease who failed to benefit from treatment with donepezil.

Adverse Effects In general, adverse reactions were less frequent later in the course of treatment. No systematic effect of race or age could be determined. In general, adverse reactions were less frequent later in the course of treatment. No systematic effect of race or age could be determined. -On the body as a whole : -On the body as a whole : Fatigue. Fatigue. Asthenia. Asthenia. Weight loss. Weight loss.

 -Cardiovascular disorders:- General hypertension. General hypertension. Cardiac failure. Cardiac failure.  - Central and peripheral nervous system disorders : Dizziness Dizziness Headache Headache Somnolence Somnolence

-Respiratory system disorder : Rhinitis Rhinitis Endocrine disorders Endocrine disorders Goiter Goiter Hypothyroidism (In frequent) Hypothyroidism (In frequent)

- Gastrointestinal system disorders (frequent) Nausea Nausea Vomiting Vomiting Abdominal pain Abdominal pain Constipation Constipation Resistance mechanism disorders: Resistance mechanism disorders: Urinary Tract infection. Urinary Tract infection.

- Psychiatric disorders : Insomnia. Insomnia. Confusion Confusion Depression. Depression. Anxiety. Anxiety. -Rivastigmine can be a risk for aspiration from frequent nausea and vomiting especially in the elderly population with known dementia. -Rivastigmine can be a risk for aspiration from frequent nausea and vomiting especially in the elderly population with known dementia.

Precautions For gastrointestinal adverse effects, patients should always be starting rivastigmine at a dose of 1.5 mg B.I.D and titrated to their maintenance dose. Rivastigmine has no effect on fertility or reproductive performance and nursing mothers. For gastrointestinal adverse effects, patients should always be starting rivastigmine at a dose of 1.5 mg B.I.D and titrated to their maintenance dose. Rivastigmine has no effect on fertility or reproductive performance and nursing mothers. Contraindications Contraindications Rivastigmine is contraindicated in patients with known hypersensitivity to rivastigmine, other carbamate derivatives or other components of the formulations. Rivastigmine is contraindicated in patients with known hypersensitivity to rivastigmine, other carbamate derivatives or other components of the formulations.

Drug – Drug interactions No effect of rivastigmine on the metabolism of other drugs. No effect of rivastigmine on the metabolism of other drugs.  No effect of other drugs on rivastigmine metabolism.

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