Piromide (tiropramide)

Oscar Ty Cabahug, M.D., FPCP, FPSG, FPSDE

UERM Medical Center
MCU Medical Center

Piromide
100 mg tablets Manufactured by Kyung Dong Pharm., Co., Ltd. Imported by 1 GN Trade Corporation Repackaged by Ashford Pharmaceutical Laboratories

Piromide Pharmacodynamics
Is pharmacologically characterized as a calmodulinindependent broad-spectrum antispasmodic Is regarded as a eukinetic agent as it has greater potency in the inhibition of pathological smooth muscle contractions than of physiological contractions

Piromide Pharmacodynamics
Its smooth muscle relaxant activity as observed in isolated detrusor muscle of rats is predominantly due to inhibition of Ca++ influx into the smooth muscle cells via voltage dependent Ca++ channels and to a lesser extent related to an increase in intracellular cyclic AMP due to inhibition of phosphodiesterase activity.

Piromide Pharmacodynamics
Shows very little calcium channel blocking activity in the vascular smooth muscle indicating its selectivity of its calcium channel blockade in the smooth muscles of non-vascular hollow organs Does not compete with acetylcholine in muscarinic receptors and would therefore be expected to be devoid of anticholinergic effects as observed with muscarinic receptor antagonists including tachycardia, dry mouth, blurring of vision and inhibition of micturition.

Piromide Pharmacodynamics
Has been shown to be efficacious in controlling spastic conditions involving the small and large intestines, in normalizing the intestinal transit times in diarrhea-dominant irritable bowel syndrome, in normalizing the motor activity of the gallbladder in biliary dyskinesia and in alleviating spasms of the urinary bladder.

Piromide Pharmacodynamics
Since the urinary bladder is mainly innervated by non-cholinergic excitatory neurons, antispasmodics of the muscarinic receptor antagonist class of drugs are ineffective whereas tiropramide, because of its pure musculotropic smooth muscle relaxant activity has been found useful in controlling spasms of the urinary bladder.

Piromide Pharmacodynamics
Because of its lack of anticholinergic effects, tiropramide has been shown to be an excellent premedication drug in patients undergoing diagnostic or therapeutic endoscopic procedures including ERCP, colonoscopy and flexible procto providing control of intestinal peristalsis without the frequently observed adverse effect of tachycardia. Because of the higher threshold for the inhibition of gastric peristalsis, tiropramide inhibits intestinal, biliary and urinary spasms without affecting gastric emptying time.

Piromide Pharmacokinetics
Peak plasma concentrations (Tmax) are reached 1 to 1.7 hours after the oral administration of tiropramide tablets. Orally administered tiropramide undergoes first pass metabolism in the liver resulting in an AUC ratio between orally and intravenously administered tiropramide of 0.67.

Piromide Pharmacokinetics
About 35% of orally or intravenously administered tiropramide is excreted in the urine either as unchanged drug or as metabolites while the rest are recovered in the feces. Of the total amount of drug excreted in the urine, about 16% of intravenously administered and 20% of orally administered tiropramide are in the form of unchanged drug while the rest are in the form of metabolites.

Piromide Pharmacokinetics
Its metabolites retain biologic activity but have significantly less potency than the parent drug. Its elimination half-life (T1/2) is about 2.5 hours after a single oral dose.

Piromide Indications
Symptomatic relief of painful spastic conditions involving the hepatobiliary, gastrointestinal and urinary tracts.

Piromide Dosage
Usual adult dose is 100 mg tablets given one tablet three times daily. Dosage may be adjusted according to the patient's age or symptoms or as prescribed by a physician.

Piromide Adverse Events

The most commonly encountered adverse events include xerostomia, dyspepsia, nausea and vomiting. Hypersensitivity reactions characterized by pruritus and erythema have also occasionally been observed.

Piromide Special Warnings and Precautions

Although tiropramide is expected to be devoid of anticholinergic side effects at the usual therapeutic doses, caution should still be exercised when administering the drug to patients with glaucoma or benign prostatic hyperplasia. Tiropramide administered at supra-therapeutic doses may have additive hypotensive effects when given concomitantly with other antihypertensive medications.

Piromide Special Warnings and Precautions

Large intravenous doses of tiropramide may likewise have depressive effects on the cardiovascular system but are less pronounced after oral administration. Though specific safety parameters have not been established among patients with mild to moderate renal insufficiency, it would be prudent to undertake dosage reduction in such a situation.

Piromide Special Warnings and Precautions

Although animal studies have not demonstrated any teratogenic effect, it should not be prescribed during pregnancy, unless there are compelling reasons for doing so. Its safety in lactating women and in pediatric patients has not been established and therefore should not be used in these patients.

Piromide Contraindications
Patients who have exhibited a history of hypersensitivity reaction to tiropramide Severe renal insufficiency Gastrointestinal obstruction or megacolon

Thank You