TRIMETABOL

Indications

• Allergic conditions
• Hay fever
• Urticaria
• Pruritus
• Appetite stimulation

Dosage

Children: For children aged 6 months to 5 years, the dose is 5-15 mg daily in divided doses, adjusted according to weight, with a maximum of 2 mg/kg per day. For children aged 6-17 years weighing up to 40 kg, the initial dose is 15-25 mg daily in divided doses, adjusted as necessary to a maximum of 2 mg/kg per day. For those weighing 40 kg and above, the initial dose is 15-25 mg daily in divided doses, increased if necessary to 50-100 mg daily.

Adults: Initially, 25 mg daily, taken at night; may be increased if necessary to 25 mg 3-4 times a day. Maximum dose is 32 mg per day.

Mechanism of action

Cyproheptadine acts as a competitive antagonist at histamine H1 receptors, thereby inhibiting the action of histamine, which is responsible for allergic symptoms. Additionally, it may also block serotonin receptors, contributing to its appetite-stimulating effects.

Pharmacodynamics

The drug exhibits sedative effects by crossing the blood-brain barrier, leading to central nervous system depression. It can also produce anticholinergic effects, such as dry mouth and urinary retention, due to its action on muscarinic receptors. The sedative properties can impair the performance of skilled tasks and may be potentiated by alcohol consumption.

Pharmacokinetics

Cyproheptadine is well-absorbed from the gastrointestinal tract and undergoes hepatic metabolism. Its elimination half-life is approximately 8-12 hours, and it is excreted primarily in urine. The onset of action is typically within 1-2 hours, with effects lasting for several hours.

Contra-indications

• Acute porphyrias
• Prolonged QT-interval
• Risk factors for QT prolongation

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Nausea
• Constipation
• Headache
• Palpitations
• Tachycardia
• Fatigue
• Irritability
• Paradoxical excitability
• Tremor

Interactions

• Antihistamines
• Sedating agents
• Alcohol

Precautions

• Use with caution in the elderly
• Patients with epilepsy
• Prostatic hypertrophy
• Pyloroduodenal obstruction
• Susceptibility to angle-closure glaucoma
• Urinary retention

Pregnancy

Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity. Use in the latter part of the third trimester may cause adverse effects in neonates.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in mothers who are breastfeeding.

Storage

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

Formulations

• Oral suspension
• Tablets (4 mg)

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm associated with respiratory conditions

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Acefyllinate works by inhibiting phosphodiesterase, leading to an increase in intracellular cyclic AMP (cAMP) levels. This process results in the relaxation of bronchial smooth muscle and bronchodilation. Additionally, it may have anti-inflammatory effects, contributing to its therapeutic benefits in respiratory diseases.

Pharmacodynamics

The pharmacodynamics of acefyllinate involve its ability to enhance bronchial airflow and reduce airway resistance. It exhibits a dose-dependent response, where increased doses can lead to improved bronchodilation. The onset of action typically occurs within 15 to 30 minutes, and the effects can last for several hours, making it suitable for both acute and chronic management of bronchospasm.

Pharmacokinetics

Acefyllinate is absorbed rapidly from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours post-administration. It is metabolized primarily in the liver, and its metabolites are excreted primarily through the kidneys. The elimination half-life ranges from 5 to 6 hours, which may vary based on individual patient factors such as age and renal function.

Contra-indications

• Hypersensitivity to acefyllinate or other xanthines
• Severe cardiac disorders
• Peptic ulcer disease

Adverse effects

• Nausea
• Vomiting
• Insomnia
• Headache
• Tachycardia
• Palpitations
• Gastrointestinal disturbances
• Nervousness

Interactions

• May enhance the effects of other stimulants
• Concurrent use with certain antibiotics may increase plasma levels
• Use with caution in patients taking beta-adrenergic agonists

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor serum levels in patients with liver impairment
• Avoid abrupt withdrawal in patients on long-term therapy

Pregnancy

There are limited studies on the use of acefyllinate in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether acefyllinate is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

Formulations

• Oral tablets
• Syrup

Indications

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria
• Angioedema
• Anaphylaxis (as adjunct therapy)
• Appetite stimulation in certain conditions

Dosage

Children: Refer to BNF for Children for appropriate pediatric dosing, as it varies by age and condition. Generally, doses may start at 0.25 mg/kg for younger children, but specific guidelines should be

Adults: The usual adult dose for allergic conditions is 4 mg three times daily, which may be increased to a maximum of 12 mg per day as needed. For appetite stimulation, the starting dose is often 4 mg taken once or twice daily.

Mechanism of action

Cyproheptadine exerts its effects by competing with free histamine and serotonin for binding at their respective receptors. Its action as an H1 blocker is complemented by its antagonism of serotonin at 5-HT2A receptors, particularly influencing the appetite center in the hypothalamus. This dual action accounts for its appetite-stimulating properties and mitigates several pharmacodynamic effects of serotonin.

Pharmacodynamics

Cyproheptadine antagonizes several effects of serotonin and histamine, including bronchoconstriction and vasodepression. Its efficacy in combatting histamine-mediated effects has been established, although the details regarding its role in preventing anaphylactic shock remain unclear, likely linked to its anti-serotonergic activity. The drug's sedative properties arise from its central nervous system effects.

Pharmacokinetics

Cyproheptadine is well-absorbed after oral administration. It is metabolized in the liver, with a variable half-life and is primarily excreted in urine. The onset of action typically occurs within one to two hours, and the duration of action can last up to 12 hours. The pharmacokinetic profile may be influenced by individual metabolic variations.

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Blurred vision
• Increased appetite

Interactions

• cyproheptadine+metyrapone: Severe (decreases effects)
• cyproheptadine+fenfluramine: Unknown (decreases efficacy)

Precautions

• Caution in patients with glaucoma
• Caution in patients with prostate hypertrophy
• Use with caution in elderly patients due to increased sensitivity

Pregnancy

Cyproheptadine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety.

Breast-feeding

Cyproheptadine is excreted in breast milk. Caution is advised when administered to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Syrup

Mechanism of action

Cyproheptadine appears to exert its antihistamine and antiserotonin effects by competing with free histamine and serotonin for binding at their respective receptors. Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine's ability to stimulate the appetite. CYPROHEPTADINE...IS A SEROTONIN & HISTAMINE ANTAGONIST... ... It is an effective H1 blocker. Cyproheptadine also has prominent 5-H blocking activity on smooth muscle by virtue of its binding to 5-HT2A receptors. ... It has weak anticholinergic activity and possess mild central depressant properties.

Pharmacodynamics

Cyproheptadine has been observed to antagonize several pharmacodynamic effects of serotonin in laboratory animals, including bronchoconstriction and vasodepression, and has demonstrated similar efficacy in antagonizing histamine-mediated effects. The reason for its efficacy in preventing anaphylactic shock has not been elucidated, but appears to be related to its anti-serotonergic effects.