Chlordiazepoxide

Chlordiazepoxide is a benzodiazepine that is used to treat anxiety disorders as well as to temporarily relieve acute alcohol withdrawal symptoms and anxiety symptoms. Chlordiazepoxide can be administered off-label for the treatment of a number of illnesses, including premenstrual syndrome, social anxiety, insomnia, and PTSD.
Federal and state laws limit chlordiazepoxide as an illicit substance because, like other benzodiazepines, it is susceptible to dependency and misuse.

How does chlordiazepoxide works?

The way that chlordiazepoxide works pharmacologically in the brain at certain receptor locations may help to explain why it is such an excellent anxiety treatment. Receptors are certain areas on the membrane of nerve cells that receive signals from neurotransmitters, which are neurochemicals. A neurotransmitter attaches to the receptor and travels along the neuron to convert the neurochemical signal into an electrical or other chemical signal. these particular receptors are also referred to as benzodiazepine receptors.

The neurotransmitter γ-aminobutyric acid (GABA) in that area of the brain is facilitated in its inhibitory effect by the combined action of benzodiazepines on the receptors.

It appears that benzodiazepines’ anxiolytic, sedative, and anticonvulsant effects are due to their interaction with GABA receptors. For example, chlordiazepoxide is a useful hypnotic and anxiolytic drug.

What is the recommended dose of chlordiazepoxide? 

Smaller doses of 5–10 mg three or four times a day work effectively for mild to moderate anxiety. Higher doses of chlordiazepoxide are needed for the management of alcohol withdrawal symptoms and severe symptoms. A usual initial dosage for severe anxiety is 25 mg two or three times a day; doses are subsequently increased as necessary to control symptoms. However, 300 mg per day is the maximum amount of chlordiazepoxide that should be used.

• Compared to benzodiazepines with shorter half-lives, such as alprazolam, withdrawal symptoms from chlordiazepoxide are often milder due to its prolonged duration of action.

What happens when you take an overdose of chlordiazepoxide?

Oral benzodiazepine as chlordiazepoxide overdoses are rarely lethal. Benzodiazepines sometimes cause mortality when taken with other CNS depressants, particularly alcohol, narcotics, and barbiturates.  

• Drowsiness, confusion, somnolence, weariness, dropped coordination, clumsiness while walking (ataxia), and sluggish reflexes are some of the mild indications of benzodiazepine overdose. 

When taken alone, benzodiazepines hardly cause death. When some drugs participate in benzodiazepine overdose, severe symptoms such as trouble breathing, slowing heart rate, decreased blood pressure, lack of coordination, and loss of consciousness lead to coma and death.

• Every potential overdose should be considered an emergency at the ER. The prescription bottle of  the drug along with any extra drugs linked to the overdose should also be brought, as the data on the prescription label can help the treating physician estimate the quantity of pills consumed.

What are the side effects of chlordiazepoxide?

Sedation and drowsiness are the most often reported, particularly in the early stages of therapy. Other common symptoms include difficulty focusing and remembering things, a dissociative or “spacey” feeling, and trouble with coordination. 

• constipation, change in appetite, decreased interest in sexual intercourse. 

In some individuals, benzodiazepines may possess paradoxical effects. In susceptible individuals, the drug stimulates enthusiasm, aggression, hostility, uncontrolled behavior, and wrath rather than the expected depressive effects. These reactions are especially common in the elderly, people with brain injuries, and people with personality and impulse control difficulties.

• Dizziness, headache, nausea, facial or muscle twitching, muscle weakness, balance disorder, Painful or difficult urination, Chills, slow heart rate, slow breathing, and dark urine.

What are the precautions of chlordiazepoxide usage?

• Chlordiazepoxide, like other benzodiazepines, is categorized as a restricted substance due to its potential for misuse and dependence, according to state and federal laws. 
• The drug impairs awareness and coordination; therefore, patients should use caution when driving or performing other tasks that require alertness while taking this medicine. 

Seniors may be more vulnerable due to impaired coordination and reflexes, perhaps leading to falls and injuries. 

• Co-administration with other central nervous system (CNS) depressants such as alcohol, opioids, and barbiturates may exacerbate these CNS effects. So quit drinking while taking the drug. 
• Prolonged usage of benzodiazepines as chlordiazepoxide could end in dependence. When the medicine is abruptly stopped, withdrawal symptoms may appear. Headaches, vomiting, decreased attention, confusion, tremors, muscle cramps, and seizures are among withdrawal symptoms. 
• Benzodiazepines, such as chlordiazepoxide, are systemically acting depressants that might reduce breathing. This is especially challenging for people with chronic obstructive lung disease and emphysema. The respiratory depressive effect of benzodiazepines may further suppress respiratory drive in these patients, putting them at greater risk for respiratory depression and death. 

If you miss a dose, take it right away. If it is near the next planned dose, cancel the missed dose and resume your normal dosing schedule. Avoid taking double the prescribed dose.

• Chlordiazepoxide can be taken before or after meals. 
• Keep the medication in the original labeled, light-resistant container, away from heat and moisture, to avoid drug degradation by them. 
• Keep chlordiazepoxide away from your children.

How does chlordiazepoxide affect pregnancy and lactation?

• Chlordiazepoxide is classified as pregnancy category D.

Benzodiazepines and their metabolites are known to cross the placenta and accumulate in the fetal circulation. 

• They are associated with a risk of congenital malformations when used during pregnancy, causing cleft lip and heart deformities in the fetus. 
• Benzodiazepines such as Chlordiazepoxide should be avoided during pregnancy, particularly in the first trimester. The use of benzodiazepines during pregnancy should be considered only when the need for the medication outweighs its risk and alternative therapies have failed. 

Nursing mothers should not take chlordiazepoxide  because it will pass into breast milk and be ingested by the baby. If stopping the drug is not an alternative, breastfeeding should not be started or should be discontinued.

What are the drugs contraindicated with chlordiazepoxide?

Chlordiazepoxide is metabolized hepatically by cytochrome P450 by glucuronidation to give an inactive metabolite.

• So coadministration of any Cytochrome P450 inhibitors, inducers, or metabolites could affect its excretion and concentration.
• CNS depressants (alcohol, narcotics, barbiturates, and hypnotics) and antihistamines could affect coordination and breathing while increasing drowsiness.

• Cimetidine, fluoxetine, ketoconazole, propranolol, divalproex sodium, propoxyphene, disulfiram may inhibit the metabolism of chlordiazepoxide, thus increasing the level and pharmacological effects of the drug and producing excessive sedation and other adverse CNS effects.

Chlordiazepoxide may raise digoxin levels in the blood, which may contribute to toxicity.Patients should have their digoxin levels constantly monitored when taken with chlordiazepoxide.  

• Taking chlordiazepoxide with oral contraceptives may raise its clearance rate, potentially reducing its effectiveness.