Meperidine
Introduction
Meperidine is a synthetic opiate like drug with high addiction potency. It was synthesized in 1932 as an antimuscarinic agent. Pethidine also has structural similarities to atropine and other tropane alkaloids and may have some of their effects and side effects It is used for acute pain. Meperidine, commonly known by its trade name Demerol.
Mechanism of Action
Meperidine binds to opioid receptors particularly receptors. It also bind well to kappa receptor. Opioid receptors are G-protein couple receptors. The inhibit adenylyl cyclase so decrease the cAMP level and decrease the protein phosphorylation. They also effect on potassium and calcium channels. Potassium channels are open while calcium channels are block. As the end result is neuralexcitibility is decease. Because postassium conductance cause the hyperpolarisation of membraine.
Pharmacological Effects
Analgesia
Meperidine relieve pain both by raising the pain threshold at the spinal cord level and more importantly perception of brain.
Respiratory Depression
Partial pressure of Co2 increase in the arteries because of the decrease sensitivity of respiratory center.
Sedation
It consist of drowsiness clouding of mentation and some impairment of reasoning ability. Pupillary Dilation Meperidine does not cause pinpoint pupils but rather cause the pupils to dilate because of an atropine like action. Meperidine dilate the cerebral vessels and increase the CSF pressure and contract the smooth muscles. Euphoria It produce a powerful sense of well-being. This effect is due to receptor. Nausea and vomiting Nausea and vomiting occur because Meperidine interact with chemoreceptor's trigger zone. Constipation Meperidine decrease motility of GIT so it cause constipation.
Skin
Opioids produce flushing & warming of skin, sometime accompanied by sweating & itching. These effects result from opioids central effects as well as histamine release causing cutaneous vasodilation.
Immunosuppressants
Opioids are Immunosuppressant on long term used.
Pharmacokinetics
Route of administration orally or parentally : Bioavailability: Metabolism: Half-life: Excretion: 5060% Liver 35 hours Renal
Protein binding:
60-80% bound to plasma proteins, primarily albumin and 1-acid glyco protein.
Volume of distribution: Meperidine crosses the placenta and is distributed into breast milk.
Clinical Uses
Analgesia
Use for relief of pain resulting from myocardial infarction, terminal illness, surgery, cancer & biliary & renal colics.
Diarrhea
Meperidine is used to treat diarrhea because it decrease the motility of GIT.
Urinary Retention
Meperidine produce less of an increase in Urinary Retention then does morphine.
Mydriasis
By Dilating the pupil. As premedicant drugs before anesthesia & surgery
Adverse Effects
Large or repetitive dose of Meperidine can cause anxiety tremors muscle twitches and rarely, convulsions due to the accumulation of toxic metabolite normeperidine. Due to its antimuscrinic action patient may experience dry mouth and blurred vision. Urticaria and itching. Drug Interaction
With Phenytoin The therapeutic actions of MEPERIDINE may be reduced, while adverse reactions might be enhanced.
Mechanism:
Phenytoin appears to increase the metabolism of meperidine to normeperidine.
With Duloxetine:
The concurrent use of duloxetine with tramadol or pethidine (Meperidine)may lead to serotonin syndrome,
Ritonavir:
Reduced MEPERIDINE and increased normeperidine serum levels may occur, possibly decreasing efficacy but increasing neurologic toxicity.
Mechanism:
RITONAVIR may enhance the metabolism of MEPERIDINE.
Contraindication:
Pregnancy
Pts with impaired pulmonary function
Liver disease
Pts with endocrine disease for example Addison's disease. Dosage:
60-100 mg, oral, sc, im, iv
