NORFLEX TABLETS

Indications

• Acute painful musculoskeletal conditions
• Parkinson's disease
• Parkinsonian syndromes

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to the BNF for specific dosing recommendations, typically starting at 100 mg orally twice daily, adjusted based on response and tolerance.

Mechanism of action

Orphenadrine binds to and inhibits histamine H1 receptors and NMDA receptors. It counteracts the stimulation of the cholinergic system due to dopamine deficiency in the striatum, exerting an anticholinergic effect that helps relieve motor disturbances. This action reduces voluntary muscle spasms by central antimuscarinic action, selectively depressing spinal polysynaptic reflexes over monosynaptic reflexes.

Pharmacodynamics

Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. It mainly acts centrally as an anticholinergic, with a weak peripheral effect. It also helps restore the balance between cholinergic and dopaminergic neurotransmission in conditions like Parkinson's disease, improving rigidity and tremor, though its effect on bradykinesia is less pronounced.

Pharmacokinetics

Orphenadrine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It has a half-life of approximately 14 hours, allowing for once or twice daily dosing. The drug is metabolized in the liver and excreted primarily in urine, with a small percentage eliminated unchanged. Its pharmacokinetic profile may be influenced by factors such as liver function and patient age.

Adverse effects

• Dizziness
• Drowsiness
• Dry mouth
• Nausea
• Confusion
• Blurred vision
• Constipation

Interactions

• clozapine+orphenadrine: Unknown (additive effect)
• antipsychotics, second generation+orphenadrine: Unknown (additive effect)

Precautions

• Use with caution in patients with glaucoma
• Use with caution in patients with urinary retention
• Use with caution in elderly patients due to increased sensitivity to anticholinergic effects

Pregnancy

Orphenadrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as a pregnancy category C drug.

Breast-feeding

Orphenadrine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Syrup

Indications

• Parkinson's disease
• Nocturnal akinesia
• Drooling of saliva in Parkinson's disease

Dosage

Children: Refer to the BNF for Children for specific dosing information, as pediatric dosing is based on individual patient assessment.

Adults: Refer to the BNF for specific dosing information, as doses may vary based on the condition being treated.

Mechanism of action

Orphenadrine acts as an anticholinergic agent, antagonizing muscarinic receptors in the central nervous system. This reduces the activity of acetylcholine, thereby balancing the neurotransmitter levels disrupted by dopamine deficiency. The reduction in cholinergic activity helps alleviate symptoms of Parkinson's disease and other movement disorders.

Pharmacodynamics

The drug has a significant effect in reducing tremors and rigidity associated with Parkinson's disease. By blocking cholinergic receptors, orphenadrine helps to restore the balance between dopaminergic and cholinergic systems, thus improving motor function. Its sedative properties may also contribute to its therapeutic effects.

Pharmacokinetics

Orphenadrine is well-absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours. It has a large volume of distribution, indicating extensive tissue binding. The drug is metabolized in the liver and has a half-life of approximately 14 hours. Renal excretion plays a minor role in its elimination, as the metabolites are primarily excreted in urine.

Contra-indications

• Hypersensitivity to orphenadrine or any component of the formulation
• Glaucoma
• Prostatic hypertrophy
• Urinary retention
• Myasthenia gravis

Adverse effects

• Dry mouth
• Dizziness
• Constipation
• Blurred vision
• Sedation
• Nausea
• Confusion
• Hallucinations

Interactions

• Increased sedative effects with alcohol, antihistamines, and other CNS depressants
• Anticholinergic effects may be enhanced with other anticholinergics
• May reduce the effectiveness of certain medications for Parkinson's disease

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor for signs of urinary retention
• Avoid abrupt withdrawal to prevent potential withdrawal symptoms
• Caution in the elderly or those with cognitive impairment

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on safety.

Breast-feeding

Orphenadrine is excreted in breast milk; use with caution in nursing mothers.

Storage

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

Formulations

• Orphenadrine hydrochloride 100 mg tablets
• Orphenadrine hydrochloride 35 mg/5 mL oral solution

Mechanism of action

Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. ANTIPARKINSONISM DRUGS ALSO BLOCK CHOLINERGIC RECEPTORS. THEY ARE... ORPHENADRINE (DISIPAL)... BLOCKADE PREVENTS ACTIONS OF ACETYLCHOLINE RELEASED FROM PARASYMPATHETIC NERVE ENDINGS. ...REDUCES VOLUNTARY MUSCLE SPASM BY CENTRAL ANTIMUSCARINIC ACTION & RESEMBLES ATROPINE IN THIS RESPECT. /CITRATE/ NEURONAL CONDUCTION, NEUROMUSCULAR TRANSMISSION, & MUSCLE EXCITABILITY ARE NOT DEPRESSED EXCEPT AFTER NEARLY LETHAL DOSES. PROMINENT EFFECT...IS TO DEPRESS SPINAL POLYSYNAPTIC REFLEXES PREFERENTIALLY OVER MONOSYNAPTIC REFLEXES. /CENTRALLY ACTING MUSCLE RELAXANTS/

Pharmacodynamics

Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anaesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favourable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. The effect is somewhat less on bradykinesia.