Anafranil

Anafranil is the trade name of a drug whose active substance is clomipramine. Clomipramine belongs to the class of tricyclic antidepressants (TCAs) and is used to treat a variety of psychiatric and neurological conditions.

Clomipramine inhibits the reuptake of serotonin and norepinephrine in neurons of the central nervous system, which increases the concentration of these neurotransmitters in the synaptic cleft and enhances their effect. It also has anticholinergic, antihistamine and sedative effects.

Indications Anafranilla

1. Depression: Anafranil can be used to treat various forms of depression, including major depressive disorder (major depressive disorder).
2. Obsessive-compulsive disorder (OCD): This drug is widely used to treat OCD, a serious mental condition characterized by intrusive thoughts (obsessions) and compulsive actions (compulsions).
3. Panic attacks: Anafranil can be used to treat panic disorder with or without agoraphobia.
4. Anxiety Disorders: It can also be used to treat various anxiety disorders.
5. Natural enuresis (sleep incontinence): In children and adolescents, Anafranil can be used to treat bedwetting.

Release form

Tablets: This is the most common form of release and is taken orally (by mouth). Tablets may be available in different dosages.

Pharmacodynamics

1. Blocking neurotransmitter reuptake: Clomipramine inhibits the reuptake of the neurotransmitters serotonin and norepinephrine at synaptic clefts. This leads to an increase in the concentration of these neurotransmitters in the brain, which can improve mood and reduce symptoms of depression.
2. Blocking adrenergic receptors: Clomipramine also has an antagonistic effect at adrenergic receptors, which may have additional antidepressant effects.
3. Serotonin receptor blocking: Some studies suggest that clomipramine may also act on serotonin receptors, although the mechanism of this action is not fully understood.

Pharmacokinetics

1. Absorption: After oral administration, clomipramine is rapidly and completely absorbed from the gastrointestinal tract. However, absorption may vary depending on individual factors such as the presence of food in the stomach.
2. Metabolism: Clomipramine is metabolized in the liver with the participation of cytochrome P450, mainly undergoing demethylation and hydroxylation. The resulting metabolites have lower activity than clomipramine itself.
3. Bioavailability: The oral bioavailability of clomipramine is approximately 50-60% due to strong first-pass metabolism through the liver.
4. Distribution: Clomipramine is highly bound to plasma proteins (about 97-98%). It has a large volume of distribution, which means it can be distributed widely throughout the body's tissues.
5. Excretion: Clomipramine and its metabolites are excreted primarily via the kidneys as conjugates and unmetabolized forms. Its half-life is approximately 19-37 hours.
6. Metabolites: The main metabolites of clomipramine are desmethylclomipramine (norclomipramine) and hydroxyclomipramine. They also have antidepressant activity, although to a lesser extent than clomipramine itself.

Dosing and administration

1. Initial dosage: The usual starting dose for adults is 25 mg 1-3 times daily. This dose may be gradually increased under medical supervision.
2. Maintenance dose: The usual maintenance dose for adults is 50-100 mg per day, divided into several doses.
3. Maximum Dose: The maximum recommended daily dose for adults usually does not exceed 250 mg, but in some cases may reach 300 mg per day.
4. Dosage for children: Dosage for children is usually lower and should be prescribed individually depending on the age and weight of the child.
5. Duration of the course: The duration of the course of treatment is determined by the doctor and can be as long as several months or even years, depending on how well the patient responds to the treatment.

The drug should be taken orally, preferably with or immediately after meals, to reduce possible irritation of the gastric mucosa. To avoid missing doses, take the drug at the same time every day.

Use Anafranilla during pregnancy

1. Neonatal effects:

   • Treatment of pregnant women with clomipramine may cause neonatal problems. There have been several case reports of newborns whose mothers took clomipramine during pregnancy having symptoms such as respiratory distress, irritability, and tremors (Ostergaard & Pedersen, 1982).

2. Toxic effects:

   • Studies suggest that clomipramine may cause toxic effects in newborns, including decreased muscle tone, difficulty breathing, and drowsiness. These effects may be related to the drug concentration in neonatal plasma (Schimmell et al., 1991).

3. Risks of congenital anomalies:

   • There is an increased risk of congenital anomalies when clomipramine is taken during the period of organogenesis (first trimester of pregnancy). This risk is similar to that associated with other tricyclic antidepressants and serotonin reuptake inhibitors (SSRIs) (Tango et al., 2006).

Contraindications

1. Individual intolerance: Patients with a known allergy to clomipramine or other components of the drug should not use it.
2. Use of monoamine oxidase inhibitors (MAOIs): Anafranil is contraindicated in combination with monoamine oxidase inhibitors and within 14 days after stopping their use, as this may lead to serious side effects such as serotonin syndrome.
3. Acute stage of myocardial infarction: The drug should be used with caution or completely avoided in the acute stage of myocardial infarction.
4. Acute alcohol intoxication: Use may be undesirable in case of acute alcohol intoxication due to the possibility of enhancing the sedative effect.
5. High blood pressure: Clomipramine may increase blood pressure and should be used with caution in patients with hypertension.
6. Angle-closure glaucoma: The drug is contraindicated in angle-closure glaucoma due to the risk of increasing intraocular pressure.
7. Other conditions: Avoid use in patients with active epilepsy or severe agitation or aggressiveness.

Side effects Anafranilla

1. Drowsiness and fatigue: These are some of the most common side effects of tricyclic antidepressants, including Anafranil.
2. Dry mouth: Increased secretion of anti-mucus fluid can cause dry mouth.
3. Constipation or problems with urination: Clomipramine may reduce intestinal motility and increase bladder tone.
4. Increased or decreased blood pressure: Some patients may experience hypertension, while others may experience hypotension.
5. Loss of appetite or weight gain: Anafranil can cause both loss of appetite and weight gain in different patients.
6. Decreased libido and sexual dysfunction: This may include both decreased sexual desire and problems with erection or orgasm.
7. Tremor, dizziness and headache: These symptoms may occur at the beginning of treatment and usually decrease with increasing dose.
8. Dry Eyes: Some patients may experience increased eye dryness.
9. Psychomotor retardation: This condition is characterized by slow thinking and movement.
10. Mental reactions: Include anxiety, restlessness, insomnia, agitation, aggression, or the possibility of worsening symptoms of depression.

Overdose

1. Cardiac arrhythmias, including tachycardia (rapid heartbeat) or arrhythmias such as atrial fibrillation or ventricular fibrillation.
2. Significant decrease in blood pressure.
3. Pulmonary edema.
4. Dizziness and drowsiness.
5. Loss of consciousness.
6. Convulsions.
7. Increased intraocular pressure.
8. Acute mental activity, including aggression or agitation.
9. Difficulty breathing.

Interactions with other drugs

1. Monoamine oxidase inhibitors (MAOIs): Concomitant use of clomipramine with MAOIs may result in serious side effects such as hypertension (high blood pressure) and serotonin syndrome. Before starting treatment with clomipramine, you must stop taking MAOIs and wait for the period of time specified in the instructions for the drug before starting treatment with clomipramine.
2. Alcohol and sleeping pills: Clomipramine enhances the depressant effects of alcohol and other drugs that depress the central nervous system (such as sleeping pills), which can lead to drowsiness and increased other side effects.
3. Anticholinergic drugs: Clomipramine enhances the anticholinergic effects of other drugs such as anti-seizure drugs, antihistamines and antidepressants, which may lead to increased dry mouth, constipation, urinary retention and other undesirable effects.
4. Sympathomimetics: Clomipramine may enhance the effects of sympathomimetics such as epinephrine and norepinephrine, which may lead to an increase in blood pressure.
5. Antiarrhythmic drugs: Clomipramine may alter electrocardiographic parameters, which may lead to serious arrhythmias when taken concomitantly with antiarrhythmic drugs.