GABAMED-M

Indications

• Epilepsy
• Neuropathic pain
• Generalized anxiety disorder

Dosage

Adults: The usual starting dose is 150 mg daily, divided into two or three doses. The dose may be increased to a maximum of 600 mg daily based on clinical response and tolerability. Refer to the BNF for specific dosing adjustments in

Mechanism of action

Pregabalin binds presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding modulates the release of several excitatory neurotransmitters, including glutamate, substance P, norepinephrine, and calcitonin gene-related peptide. By preventing the trafficking of the alpha2-delta subunit from the dorsal root ganglia to the spinal dorsal horn, pregabalin contributes to its anticonvulsant and analgesic effects.

Pharmacodynamics

Pregabalin increases the density of GABA transporters in cultured neurons but does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors. It does not affect dopamine, serotonin, or opiate receptors, nor does it modulate sodium channels or cyclooxygenase activity. Its primary action is through the inhibition of excitatory neurotransmitter release, which helps in controlling seizures and alleviating neuropathic pain.

Pharmacokinetics

Pregabalin is rapidly absorbed after oral administration, with peak plasma concentrations usually reached within 1 hour. It has a bioavailability of approximately 90%, and its plasma concentration does not significantly change with increasing doses. Pregabalin is not extensively metabolized; it is primarily excreted unchanged in the urine. The elimination half-life is about 6 hours, and dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Dizziness
• Somnolence
• Dry mouth
• Edema
• Weight gain
• Blurred vision
• Difficulty concentrating
• Euphoria
• Depression
• Angioedema

Interactions

• CNS depressants may enhance the sedative effects of pregabalin
• Concurrent use with opioids may increase the risk of respiratory depression
• Antiepileptic drugs may have additive effects

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of angioedema, especially in patients with a history of angioedema
• Caution in patients with renal impairment, as dosage adjustments may be necessary

Pregnancy

Pregabalin is classified as category C. Animal studies have shown adverse effects, and there are no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pregabalin is excreted in breast milk. The effects on a nursing infant are unknown, and caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg
• Oral solution: 20 mg/mL
• Chewable tablets: 50 mg

Indications

• Vitamin B12 deficiency
• Megaloblastic anemia
• Pernicious anemia
• Neurological disorders related to cobalamin deficiency
• Dietary deficiency in vegetarians and vegans

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Cobalamin functions as a cofactor for two essential enzymes in the body: methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase is involved in the conversion of homocysteine to methionine, while L-methylmalonyl-CoA mutase is crucial in the metabolism of certain fatty acids and amino acids. Through these pathways, cobalamin is integral in cellular metabolism and the production of red blood cells.

Pharmacodynamics

Cobalamin is involved in the cellular metabolism of folate, which is necessary for the synthesis of nucleic acids and amino acids. It helps in the conversion of homocysteine to methionine, reducing the risk of cardiovascular diseases associated with elevated homocysteine levels. Additionally, cobalamin contributes to the production of myelin, the protective sheath surrounding nerve fibers, thus supporting neurological health.

Pharmacokinetics

Cobalamin is absorbed in the ileum through a specific transport mechanism involving intrinsic factor, a glycoprotein secreted by the stomach. Once absorbed, it is transported in the bloodstream bound to transcobalamin II. The liver stores a significant amount of cobalamin, which can be released as needed. The elimination half-life of cobalamin can vary, but it is generally long due to its storage in the liver. Excretion occurs primarily through urine as metabolites.

Adverse effects

• Itching
• Rash
• Diarrhoea
• Nausea
• Headache

Interactions

• Chloramphenicol may reduce the efficacy of cobalamin
• Some anticonvulsants may interfere with cobalamin metabolism

Precautions

• Monitor patients with renal impairment
• Caution in patients with Leber's disease

Pregnancy

Cobalamin is generally considered safe during pregnancy, and deficiency should be corrected to avoid risks to the fetus.

Breast-feeding

Cobalamin is excreted in breast milk, but supplementation is usually safe and recommended for breastfeeding mothers with deficiency.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Injection
• Oral tablets
• Sublingual tablets
• Nasal spray

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

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models. By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. Pregabalin is an anticonvulsant that is structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Pregabalin also has demonstrated analgesic activity. Although pregabalin was developed as a structural analog of GABA, the drug does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors; does not augment GABA-A responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation. However, in cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues. ... In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, and substance P, possibly by modulation of calcium channel function. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. ... Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. ... For more Mechanism of Action (Complete) data for PREGABALIN (6 total), please visit the HSDB record page.

Pharmacodynamics

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.