Pethidine differs from morphine is producing which of the following effect?
Ans. B. Tachycardia.There are some pharmacological differences of pethidine from morphine. Pethidine produces tachycardia, dry mouth and less marked meiosis.Pethidine# It is a synthetic phenylpyperidine derivative and was originally developed as an antimuscarinic agent.# Dose: Pethidine is available as 50 mg tablets and ampoules of different strength (10 mg/ml and 50 mg/ml). For acute pain, it can be administered orally (50-150 mg), SC (50-100 mg), IM (50-100 mg) or IV (25-100 mg). The doses can be repeated every 4 hours.# Pharmacokinetics: Pethidine is 30 times more lipid soluble than morphine. Oral bio-availability is 50%. It is metabolized in the liver by ester hydrolysis to norpethidine and pethidinic acid that are excreted in urine and therefore accumulate in renal failure. At higher concentration, norpethidine can produce hallucination and convulsions. Pethidinic acid is an inactive compound. Pethidine is often used for labour analgesia. It readily crosses placenta, and a significant amount reaches to the foetus over several hours.# Effects: There are some pharmacological differences from morphine. It produces tachycardia, dry mouth and less marked meiosis. However, significant fall in BP may occur when pethidine is administered to elderly or hypovolaemic patients. It may produce less biliary tract spasm than morphine. Pethidine is absolutely contraindicated in patients on monoamine oxidase inhibitors (MAOI), as serious side effects like hypotension or hypertension, hyperpyrexia, convulsion and coma may occur. The underlying mechanism is not clear but may involve reduced metabolism of pethidine by MAOI and pethidine's effect on turnover of 5-hydroxytryptamine in the brain.# Like morphine, pethidine exerts its analgesic effects by acting as an agonist at the mu opioid receptor. It also has a kappa opioid receptor action, which is of unknown clinical significance. It has structural similarities to atropine and other tropane alkaloids and may have some of their effects and side effects. In addition to these opioidergic and anticholinergic effects, it has local anesthetic activity related to its interactions with sodium ion channels.# Pethidine is no more effective than morphine at treating biliary or renal pain, and its low potency, short duration of action, and unique toxicity (i.e., seizures, delirium, other neuropsychological effects)# It is more lipid-soluble than morphine, resulting in a faster onset of action. Its duration of clinical effect is 120-150 minutes although it is typically administered in 4-6 hour intervals.# Pethidine has been shown to be less effective than morphine, diamorphine or hydromorphone at easing severe pain, or pain associated with movement or coughing. It is also used for the treatment of postanesthetic shivering.# Like other opioid drugs, pethidine has the potential to cause physical dependence or addiction. Pethidine may be more likely to be abused than other prescription opioids, perhaps because of its rapid onset of action. When compared with oxycodone, hydromorphone, and placebo, pethidine was consistently associated with more euphoria, difficulty concentrating, confusion, and impaired psychomotor and cognitive performance when administered to healthy volunteers.Morphine# Morphine is a naturally occurring phenanthrene derivative. It is the standard drug against which all other opioids are compared.# Dose: Morphine can be given orally, intramuscularly (IM), intravenously (IV), subcutaneously (SC), rectally, epidurally and intrathecally.# The intramuscular dose is 0.1-0.2 mg/kg, time to peak effect is 30-60 minutes and duration of action is 3-4 hours. Intravenous administration should be titrated to effect (usually l-2mg boluses), but the total dose is similar. The onset of action is slightly more rapid with following IV administration, as the main factor responsible for its latency is low lipid solubility and slow penetration of blood brain barrier. Morphine may be given epidurally at 10% and intrathecally at 1% of the parenteral dose.# Pharmacokinetics: Morphine is extensively metabolised by the gut wall and the liver to morphine-3-glucuronide (M3G) (70%), morphine-6-glucuronide (M6G) (10%) and to sulphate conjugates. M6G is 10-20 times more potent than morphine and is normally excreted in urine. It accumulates in renal failure and accounts for increased sensitivity to morphine. Neonates are more sensitive than adults to morphine due to reduced hepatic conjugating capacity. In the elderly, owing to reduced volume of distribution, peak plasma level of morphine is higher compared to younger patient.# Effects: The main effects are mediated through MOP receptors. It is a potent analgesic with good sedative and anxiolytic properties. It may cause euphoria, dysphoria and hallucination. It produces respiratory depression and cough suppression. It has minimal effect on cardiovascular system and may produce bradycardia and hypotension. Nausea and vomiting are common side effects. Histamine release may lead to rash, itching and bronchospasm (in susceptible patients). Meiosis is common. Tolerance and dependence may develop.Pharmacokinetics of commonly used opioids MorphinePethidineFentanylAlfentanilRemifentanilpKa8.08.58.46.57.1Unionised at pH 7.4 (%)23599068Plasma protein bound (%)3040849070Terminal half life (hrs)343.51.60.06Clearance (ml/min/kg)15-308-180.8-1.04-930-40Volume of distribution (L/kg)3-53-53-50.4-1.00.2-0.3Relative lipid solubility1285809050
Sedation
Tachycardia
Euphoria
All of the above
C.N.S