Ketotifen

Mechanism of action (Pharmacodynamics)

Ketotifen has a unique dual mechanism that distinguishes it from classical antihistamines and pure chromones (such as cromoglicic acid or nedocromil sodium).

• Mast cell membrane stabilization: the drug reliably blocks the degranulation process. This prevents the release of allergy and inflammation mediators into the tissues.
• Blockade of $H_1$-histamine receptors: acts as a competitive antagonist of histamine. The blockade of these receptors prevents the triggering of the intracellular calcium cascade and subsequent smooth muscle contraction.

Additionally, the drug inhibits the release of inflammatory mediators and suppresses the chemotaxis of immune cells to the focus of the allergic reaction. By chemical structure, it is a tricyclic structure (containing sulfur and nitrogen atoms in the central ring), which is very close to traditional antihistamines.

Pharmacokinetics

After oral administration, the drug is almost completely absorbed from the gastrointestinal tract. However, its final bioavailability is only about 50%. This pharmacokinetic phenomenon is associated with a pronounced first-pass effect through the liver, where a significant portion of the active substance is metabolized before reaching the systemic circulation. The half-life ($t_{1/2}$) is relatively short, at 3–5 hours.

Indications for use

The drug is prescribed exclusively for baseline therapy and the prevention of allergic conditions. The main indications include:

• Prevention of bronchial asthma attacks.
• Atopic dermatitis.
• Hay fever (allergic rhinoconjunctivitis).
• Food allergy.

Critically important for clinical practice: Ketotifen does not cause bronchodilation. It is completely unsuitable for relieving acute asthma attacks. Emergency care requires drugs with a different mechanism of action (e.g., beta-adrenoreceptor agonists).

Side effects

Due to its systemic action and ability to cross the blood-brain barrier, the drug causes a number of characteristic adverse reactions:

• Central nervous system: pronounced sedative effect, drowsiness, slowing of psychomotor reactions (patients must be warned about the danger of driving).
• Digestion and metabolism: dry mouth, nausea, clinically significant weight gain.
• Other reactions: dizziness, thrombocytopenia (decrease in platelet count in peripheral blood).

Dosage form and prescription rules

The drug is available in solid dosage forms: tablets and capsules of 0.001 g (1 mg). It is administered orally during meals. The standard dosage regimen to maintain therapeutic concentration is 2 times a day.

Prescription example: Rp.: Tab. Ketotifeni 0.001 D.t.d. N. 30 S. Take 1 tablet orally 2 times a day during meals.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Differences between ketotifen and pure membrane stabilizers (cromoglicic acid, nedocromil sodium).
• The mechanism of mast cell degranulation and the role of the intracellular calcium cascade.
• Classification and pharmacodynamics of 1st and 2nd generation $H_1$-histamine receptor blockers.
• The leukotriene pathway of inflammation and sites of action of inhibitors (montelukast, zileuton).
• Anti-IgE therapy (omalizumab) in the treatment of severe allergic diseases.

Other topics in the «Drugs and Prescriptions» section

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