Relipen

Uses

Chlordiazepoxide is a benzodiazepine used to treat the withdrawal symptoms of acute alcoholism, to treat preoperative anxiety, and to treat anxiety over a short term period.

For the management of anxiety disorders or for the short-term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety.

Dextropropoxyphene is an opioid analgesic used to treat mild to moderate pain.

For the relief of mild to moderate pain.

Dicycloverine is used for:

• Functional bowel/ irritable bowel syndrome
• Urinary incontinence secondary to unstable detrusor muscle
• Infantile colic
• GIT spasm
• Colicky abdominal pain
• Diverticulitis
• Abdominal colic

Relipen is also used to associated treatment for these conditions: Alcohol Withdrawal Syndrome, Anxiety, Anxiety Disorders, Depression, Peptic Ulcer Disease, Acute Anxiety, Pyschosomatic diseasePainFunctional bowel syndrome, Irritable Bowel Syndrome (IBS), Gastrointestinal cramps caused by Gas

How Relipen works

Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor. BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro-inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties.

Propoxyphene acts as a weak agonist at OP1, OP2, and OP3 opiate receptors within the central nervous system (CNS). Propoxyphene primarily affects OP3 receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as propoxyphene also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

Dicyclomine achieves its action partially through direct antimuscarinic activity of the M1, M3, and M2 receptors; and partially through antagonism of bradykinin and histamine. Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum.

Dosage

Relipen dosage

Oral dosage forms-

• Adults:10 to 20 mg three times a day.
• Children >6 months of age: 5 to 10 mg three times a day.
• Children <6 months of age: Dose must be determined by the doctor.

Oral dicycloverine Hydrochloride should be started as soon as possible

Intramuscular dosage form

• Adults:Intramuscular injection. Not for intravenous use. The recommended intramuscular dose is 80 mg daily (in 4 equally divided doses).

Intramuscular dosage form should not be used for periods longer than 1 or 2 days.

Side Effects

Insomnia, mydriasis, cycloplegia, increased ocular tension, urinary hesitancy, palpitations, dyspnea.

Toxicity

LD₅₀=537 mg/kg (Orally in rats). Signs of overdose include respiratory depression, muscle weakness, somnolence (general depressed activity).

Coma, respiratory depression, circulatory collapse, and pulmonary edema. Seizures occur more frequently in patients with propoxyphene intoxication than in those with opiate intoxication. LD₅₀=230mg/kg (orally in rat, Emerson)

Patients experiencing an overdose may present with headache, nausea, vomiting, blurred vision, dilated pupils, dizziness, dry mouth, difficulty swallowing, CNS stimulation, as well as hot, dry skin. Treat patients with gastric lavage, emetics, activated charcoal, sedatives for excitement, and a cholinergic agent if indicated.

The oral LD₅₀ in mice is 625mg/kg.

Precaution

Use with caution in patients with autonomic neuropathy, hepatic or renal disease, ulcerative colitis, coronary heart disease, congestive heart failure, cardiac tachyarrhythmia, known or suspected prostatic hypertrophy.

Interaction

The following agents may increase certain actions or side-effects of Dicycloverine-antiarrhythmic agents, antihistamines, antipsychotic agents, benzodiazepines, MAO inhibitors, narcotic analgesics, nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants and other drugs having anticholinergic activity.

Volume of Distribution

• 16 L/kg

The volume of distribution for a 20mg oral dose is 3.65L/kg.

Elimination Route

The bioavailability of dicyclomine has not been determined, though it is likely well absorbed as the primary route of elimination is in the urine. Dicyclomine has a T_max of 1-1.5h.

Half Life

24-48 hours

6-12 hours

The mean plasma elimination half life is approximately 1.8 hours.

Clearance

• 2.6 L/min

Data regarding the clearance of dicyclomine is not readily available.

Elimination Route

Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.

The major route of metabolism is cytochrome CYP3A4 mediated N-demethylation to norpropoxyphene, which is excreted by the kidneys. In 48 hours, approximately 20% to 25% of the administered dose of propoxyphene is excreted via the urine, most of which is free or conjugated norpropoxyphene.

Dicyclomine is 79.5% eliminated in the urine and 8.4% in the feces.

Pregnancy & Breastfeeding use

Pregnancy: Category B. Dicycloverine was neither teratogenic nor embryocidal in animal trial. It, like other drugs should be used during pregnancy only if clearly needed. There are no data on the secretion of this drug into breast milk. Dicycloverine should be used cautiously in case of lactating mother.

Contraindication

Dicycloverine is contraindicated in:

• Obstructive uropathy
• Obstructive disease of the gastrointestinal tract
• Severe ulcerative colitis
• Reflux esophagitis
• Unstable cardiovascular status in acute hemorrhage
• Glaucoma
• Myasthenia gravis
• Evidence of prior hypersensitivity to dicycloverine hydrochloride or other ingredients of this formulation
• Infants less than 6 months of age

Acute Overdose

Toxic reaction seldom occurs with dicycloverine. The signs and symptoms of overdosage are headache; nausea; vomiting; blurred vision; dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation.

Storage Condition

Store below 30°C.

Innovators Monograph

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