PETHIDINE (Introduction, Mode of action, Pharmacokinetics, Dosage and Adverse effects)

 INTRODUCTION:-

Pethidine is the street name of meperidine. It was firstly synthesized as atropine substitute in 1939. It is relatively weak mu opioid agonist with only around 10% effectiveness of morphine with notable anti-cholinergic and local anesthetic effects and acts primarily as kappa agonist. Pethidine is very lipophilic in nature and its active metabolite is normeperidine which is potentially neurotoxic.

MODE OF ACTION:-

When pethidine binds to its respective receptor which is the G protein coupled receptor, it activates the receptor and converts the GDP into GTP, this GTP activates the G alpha subunit of G protein which is the inhibitory subunit, this G alpha subunit goes and inhibit the adenylate cyclase enzyme which is the effector system and present at the inner surface of the plasma membrane so due to inhibition of adenylate cyclase enzyme, it becomes unable to convert the ATP into CAMP. So because of decreased level of CAMP intracellularly, the release of nociceptive neurotransmitters like acetylcholine, substance P, noradrenaline, GABA and dopamine is inhibited by closing calcium channel so it reduces the propagation of effect and open the potassium channels for hyperpolarization due to which it reduces the neuronal excitability.

PHARMACOKINETICS:-

ü  The oral bioavailability of pethidine in those patients which have normal hepatic function is 50 to 60% due to large first pass metabolism but bioavailability increases up to 80 to 90% in liver impairment patients like in liver cirrhosis.

ü  It can easily cross the placenta and distributed in breast milk.

ü  It is bounded 60 to 80% with the plasma proteins primarily albumin then alpha-1 acid glycoprotein.

ü  Pethidine is metabolized in the liver by hydrolysis to meperidinic acid followed by partial conjugation with glucuronic acid. Pethidine also converts into normeperidine by N-demethylation which then undergoes hydrolysis and partial conjugation.

ü  It is excreted out in urine. Amount of drug that is excreted out as unchanged or as metabolites is dependent on PH. Pethidine and normeperidine are found in the acidic urine, whereas free and conjugated forms of meperidinic acid and normerperidinic acid are found in alkaline urine.

DOSAGE:-

      In ADULTS:-       

ü  Pain:-50 to 150mg PO/IM/SC Q3-4H

ü  Preoperatively:-50 to 100mg IM/SC 30 to 90 minutes before beginning of anesthesia.

ü  Continuous infusion:-15 to 35 mg/hr

ü  Obstetrical analgesia:-50 to 100mg IM/SC repeated Q1-3H (if necessary).

ADVERSE EFFECTS:-

ü  Tolerance and physical dependence

ü  Dry mouth

ü  Tachycardia

ü  Tremors

ü  Mydriasis

ü  Hyperreflexia

ü  Delirium

ü  Myoclonus and convulsions.