METHYLDOPA TABLETS BP 250mg

Indications

• Parkinson's disease
• Dopamine-responsive dystonia

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines for adults.

Mechanism of action

Levodopa crosses the blood-brain barrier and is decarboxylated to form dopamine. This supplemental dopamine compensates for the decreased natural concentrations and stimulates dopaminergic receptors, particularly in the caudate nucleus and substantia nigra of the brain. While levodopa is not directly acting on dopamine receptors, its conversion to dopamine by serotonergic terminals facilitates its therapeutic effects.

Pharmacodynamics

Levodopa is able to penetrate the blood-brain barrier, unlike dopamine. The administration of a peripheral dopa decarboxylase inhibitor alongside levodopa ensures that more levodopa reaches the central nervous system by preventing its conversion to dopamine in the periphery. Once in the brain, levodopa is converted to dopamine by aromatic L-amino-acid decarboxylase, enhancing dopaminergic activity and improving motor function.

Pharmacokinetics

Levodopa is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. Its bioavailability can vary based on the presence of food, with high-protein meals potentially reducing absorption. The elimination half-life of levodopa is approximately 1 to 3 hours, and it is primarily metabolized in the liver and other tissues. Renal excretion accounts for the majority of the drug's elimination, with both unchanged drug and metabolites being excreted.

Interactions

• antipsychotics, second generation (amisulpride, olanzapine, paliperidone, quetiapine, risperidone) + dopaminergic receptor agonists: Severe (decreases effects)
• benperidol + dopaminergic receptor agonists: Severe (decreases effects)
• droperidol + dopaminergic receptor agonists: Severe (decreases effects)
• flupentixol + dopaminergic receptor agonists: Severe (decreases effects)
• haloperidol + dopaminergic receptor agonists: Severe (decreases effects)
• phenothiazines + dopaminergic receptor agonists: Severe (decreases effects)
• pimozide + dopaminergic receptor agonists: Severe (decreases effects)
• sulpiride + dopaminergic receptor agonists: Severe (decreases effects)
• zuclopenthixol + dopaminergic receptor agonists: Severe (decreases effects)
• ergometrine + dopamine: Severe (increases risk of peripheral vasoconstriction)

Pregnancy

Levodopa should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Levodopa is excreted in breast milk, and caution is advised when administering to nursing mothers.

Storage

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

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Mechanism of action

Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors. MOST WIDELY ACCEPTED THEORY IS THAT LEVODOPA INCR LEVEL OF DOPAMINE & THUS ACTIVATION OF DOPAMINE RECEPTORS IN EXTRA-PYRAMIDAL CENTERS IN THE BRAIN (PRIMARILY IN CAUDATE NUCLEUS & SUBSTANTIA NIGRA). The present data indicate that the major effects observed after administration of exogenous levodopa are not due to a direct action of levodopa on dopamine receptors, or to extrastriatal release of dopamine, but to conversion of levodopa to dopamine by serotonergic terminals and probably some intrastriatal cells. EFFECTS OF LEVODOPA ON HUMAN & MURINE MELANOMA CELLS EXAMINED. WHEN EXPONENTIALLY GROWING CELLS WERE EXPOSED TO L-DOPA, CHARACTERISTIC INHIBITION OF THYMIDINE INCORPORATION OBSERVED. IN RATS, DOPAMINERGIC AGONISTS ALL CAUSED DECR IN SERUM PROLACTIN LEVELS.

Pharmacodynamics

Levodopa is able to cross the blood-brain barrier while dopamine is not. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase.