APOSAN

Indications

• Refractory motor fluctuations in Parkinson's disease ('off' episodes) inadequately controlled by co-beneldopa or co-careldopa or other dopaminergics

Dosage

Adults: For subcutaneous injection, the usual starting dose is 3–30 mg daily in divided doses, with a maximum per dose of 10 mg. For continuous subcutaneous infusion, the initial dose is 1 mg/hour, which can be adjusted according to response, usually ranging from 1–4 mg/hour, with a maximum of 100 mg per day.

Mechanism of action

Apomorphine acts as a non-selective agonist of dopamine receptors, particularly D2 receptors in the central nervous system. This receptor activation helps to restore the impaired dopaminergic transmission in the striatum of the brain, which is associated with the symptoms of Parkinson's disease. By stimulating these receptors, apomorphine mitigates motor symptoms such as bradykinesia and rigidity during 'off' periods.

Pharmacodynamics

The pharmacodynamic profile of apomorphine involves its ability to enhance dopaminergic neurotransmission, leading to improved motor function in patients with Parkinson's disease. Its rapid onset of action makes it particularly effective for acute management of 'off' episodes. However, patients may experience side effects such as nausea, vomiting, and dyskinesia due to the stimulation of dopamine receptors outside the striatum.

Pharmacokinetics

Apomorphine is administered subcutaneously, with peak plasma concentrations typically reached within 20 minutes. It has a half-life of approximately 30-60 minutes, allowing for frequent dosing to manage symptoms effectively. The drug is extensively metabolized in the liver, primarily via the CYP450 enzyme system, and its metabolites are excreted in urine. Caution is advised in patients with hepatic impairment, as the metabolism may be affected.

Contra-indications

• History of hypersensitivity to opioids
• Hepatic insufficiency

Adverse effects

• Bronchospasm
• Eosinophilia
• Peripheral oedema
• Sexual dysfunction
• Syncope
• Impulse control disorders
• Dopamine dysregulation syndrome

Interactions

• Alcohol may increase the risk of sedative effects
• Other dopamine-receptor agonists may enhance the risk of impulse control disorders

Precautions

• Use with caution in patients with renal impairment
• Monitor hepatic, haemopoietic, renal, and cardiovascular function
• Patients should be warned of the risk of sudden onset of sleep and excessive daytime sleepiness

Pregnancy

Avoid unless clearly necessary.

Breast-feeding

No information available; may suppress lactation.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Subcutaneous injection
• Continuous subcutaneous infusion

Indications

• Parkinson's disease
• Management of 'off' episodes in Parkinson's disease
• Motor fluctuations associated with Parkinson's disease

Dosage

Children: Refer to BNF for Children for specific dosage guidance.

Adults: Refer to BNF for specific dosage guidance.

Mechanism of action

Apomorphine has a high binding affinity for dopamine D2, D3, and D5 receptors. Its stimulation of D2 receptors in the caudate-putamen, a brain region critical for motor control, is believed to contribute to its therapeutic effects. While the precise mechanism by which apomorphine alleviates hypomobility in Parkinson's disease is not fully understood, it has shown efficacy in improving motor function in preclinical models of the disease.

Pharmacodynamics

As a dopaminergic agonist, apomorphine stimulates brain regions associated with motor control. Its action is characterized by a short duration and a wide therapeutic index, as significant toxicity typically requires large overdoses. Common side effects include nausea, vomiting, daytime somnolence, hypotension, and potential psychiatric symptoms such as hallucinations and impulsive behavior. Due to the high incidence of nausea and vomiting, pre-treatment with an antiemetic like trimethobenzamide is often recommended.

Pharmacokinetics

Apomorphine is rapidly absorbed following subcutaneous administration, with peak plasma concentrations usually achieved within 20 to 40 minutes. It undergoes extensive metabolism, primarily by O-demethylation and oxidation, leading to various metabolites. The elimination half-life is relatively short, necessitating multiple doses for sustained effect. It is eliminated mainly via the kidneys, and its pharmacokinetic profile may be influenced by factors such as renal function.

Adverse effects

• nausea
• vomiting
• daytime somnolence
• hypotension
• oral mucosal irritation
• falls
• hallucinations
• psychotic-like behaviour
• impulsive behaviour
• withdrawal hyperpyrexia
• prolongation of the QT interval

Interactions

• memantine+apomorphine: Unknown (increases effects)
• metoclopramide+apomorphine: Unknown (decreases effects)

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Apomorphine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether apomorphine is excreted in human milk. Caution should be exercised when apomorphine is administered to a nursing woman.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

The exact mechanism of action for Hemi is not explicitly detailed in the available resources, but compounds with similar structure may act by modulating neurotransmitter levels, inhibiting enzymes, or affecting cellular signaling pathways.

Pharmacodynamics

Hemi may exhibit pharmacodynamic properties that include modulation of neural activity or inhibition of specific biochemical pathways. Its effects could be dose-dependent and vary based on the therapeutic context.

Pharmacokinetics

The pharmacokinetic profile of Hemi, including absorption, distribution, metabolism, and excretion, is not well-documented in the provided resources. Generally, compounds in this class may undergo first-pass metabolism and have a variable half-life.

Dosage

Children: Refer to the specific formulation or active ingredient for dosing information.

Adults: Refer to the specific formulation or active ingredient for dosing information.

Mechanism of action

The mechanism of action of hemihydrate forms of drugs can vary widely depending on the specific compound. In many cases, the hemihydrate form enhances the solubility of the active ingredient, which facilitates its dissolution and absorption in the gastrointestinal tract.

Pharmacodynamics

Pharmacodynamics of hemihydrate compounds generally relates to the pharmacological effects that arise from the active drug once it is absorbed. The effects may vary based on the specific drug and its therapeutic target, but overall, the hemihydrate form aims to improve efficacy by ensuring adequate plasma concentrations are achieved more effectively than non-hydrated forms.

Pharmacokinetics

The pharmacokinetics of hemihydrate drugs typically demonstrate improved dissolution rates due to the presence of water, which can lead to increased absorption. This may result in quicker onset of action and modified half-lives. The specifics of absorption, distribution, metabolism, and excretion will depend on the active ingredient and its properties.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep container tightly closed.

Mechanism of action

Apomorphine is a non-ergoline dopamine agonist with high binding affinity to dopamine D2, D3, and D5 receptors. Stimulation of D2 receptors in the caudate-putamen, a region of the brain responsible for locomotor control, may be responsible for apomorphine's action. However, the means by which the cellular effects of apomorphine treat hypomobility of Parkinson's remain unknown. The exact mechanism of action of apomorphine hydrochloride in the treatment of Parkinson's disease has not been fully elucidated but may involve stimulation of postsynaptic dopamine D2 receptors within the caudate-putamen in the brain. Apomorphine has been shown to improve motor function in an animal model of Parkinson's disease. In particular, apomorphine attenuates the motor deficits associated with neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ([MPTP])-induced lesions in the ascending nigrostriatal dopaminergic pathway in primates. Apomorphine hydrochloride is a nonergot-derivative dopamine receptor agonist that is structurally and pharmacologically related to dopamine. In in vitro studies, apomorphine hydrochloride demonstrated a higher affinity for the dopamine D4 receptor than for dopamine D2, D3, or D5 receptors. Apomorphine hydrochloride binds with moderate affinity to alpha-adrenergic (alpha1D, alpha2B, alpha2C) receptors but has little or no affinity for dopamine D1 receptors, serotonergic (5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C) receptors, beta1- or beta2-adrenergic receptors, or histamine H1 receptors. /Apomorphine hydrochloride/

Pharmacodynamics

Apomorphine is a dopaminergic agonist that may stimulate regions of the brain involved in motor control. It has a short duration of action and a wide therapeutic index as large overdoses are necessary for significant toxicity. Patients should be counselled regarding the risk of nausea, vomiting, daytime somnolence, hypotension, oral mucosal irritation, falls, hallucinations, psychotic-like behaviour, impulsive behaviour, withdrawal hyperpyrexia, and prolongation of the QT interval. Given the incidence of nausea and vomiting in patients taking apomorphine, treatment with [trimethobenzamide] may be recommended prior to or during therapy. Antiemetic pretreatment may be started three days prior to beginning therapy with apomorphine - it should only be continued as long as is necessary and generally for no longer than two months.