MEPERIDINE (PETHIDINE)

• Is Synthetic opioid, it also possesses antimuscuranic effect.

• It is structurally unrelated to morPhine
• It is used for the treatment of acute pain.

HISTORY OF MEPERIDINE:
➢ Meperidine, also known as pethidine, was first synthesized in 1938 by
Otto Eisleb, a German chemist, as a potential anticholinergic agent.
➢ Its analgesic properties were later recognized by Otto Schaumann
while working for IG Farben in Germany
➢ Meperidine was patented in 1937 and approved for medical use in
1943.
➢ It was widely used as a painkiller, especially during childbirth, and was
considered safer and less addictive than morphine.
➢ However, it was later discovered that meperidine carries similar risks of
addiction and has toxic metabolites that can cause serotonin
syndrome.

CHEMISTRY AND STRUCTURE:

• Molecular formula is C15H21NO2·HCl

• Chemical class: Piperidine derivative
• Synthesis: Meperidine is synthesized from phenylpiperidine and
acetophenone, followed by reduction and methylation.
 • 4,4-Diphenyl-3-methyl-1-methylpiperidine

• Meperidine is a piperidine derivative, which is a class of compounds that

contain a piperidine ring. The chemical structure of meperidine includes:
•
• - A piperidine ring with a methyl group attached to the nitrogen atom
• - Two phenyl groups (benzene rings) attached to the 4-position of the
piperidine ring
• - A methyl group attached to the 3-position of the piperidine ring

MECHANISM OF ACTION:
It primarily bind to mu receptor
Also bind to kappa receptor
(Mechanism of action as same as Morphine)

PHARMACOKINETICS:
Absorption:

• Meperidine can be administered orally, intramuscularly, or

intravenously.
• Orally administered meperidine is partially metabolized in the liver
before reaching systemic circulation due to first-pass metabolism.
• Peak plasma concentration: 1-2 hours
• Bioavailability: 60% (oral)
Distribution:

• Meperidine has a moderate distribution into tissues.

• It crosses the blood-brain barrier, leading to its analgesic effects.
• It also crosses the placenta and is found in breast milk.
• Volume of distribution: 4.5 L/kg
• Protein binding: 60-80% (alpha-1-acid glycoprotein)

Metabolism:

• Meperidine is primarily metabolized in the liver by the enzyme CYP3A4

to normeperidine, which has neuroexcitatory effects.
• Normeperidine is further metabolized and eventually eliminated from
the body.
Elimination:

• Both meperidine and normeperidine are eliminated primarily via the

kidneys.
• The elimination half-life of meperidine is about 3 to 5 hours,
• while normeperidine has a longer half-life of about 15 to 20 hours.
• Clearance: 1.5 L/min
• Excretion: Urine (metabolites), feces (unchanged)
• Accumulation of normeperidine can occur in patients with renal
impairment, leading to central nervous system excitability and potential
seizures.
Excretion:

• The main route of excretion for meperidine and normeperidine is via the
kidneys, primarily as metabolites.
• Adjustments in dosing are often necessary in patients with renal
impairment to avoid accumulation and potential toxicity.
 ❖ Meperidine, also known as Demerol, is a synthetic opioid analgesic used for
various medical purposes.

Actions:
- Analgesia (pain relief)

- Sedation

- Anticholinergic effects (drying of secretions, relaxation of smooth muscle)

Uses:
- Moderate to severe pain relief (e.g., postoperative, cancer, trauma)

- Obstetric pain relief (during labor and delivery)

- Preoperative sedation and anesthesia

- Surgical procedures (e.g., general surgery, orthopedic, neurosurgery)

- Cancer pain management

- Trauma pain management

- Burn pain management

ADVERSE EFFECT OF MEPERIDINE:

Common adverse effects:

1. *Drowsiness*

2. *Dizziness*

3. *Lightheadedness*

4. *Nausea*

5. *Vomiting*

6. *Constipation*

7. *Headache*

8. *Dizziness*

9. *Sweating*
10. *Flushing*

Less common adverse effects:

1. *Respiratory depression* (slowed breathing)

2. *Hypotension* (low blood pressure)

3. *Tachycardia* (rapid heartbeat)

4. *Palpitations*

5. *Urinary retention*

6. *Dry mouth*

7. *Blurred vision*

8. *Confusion*

9. *Hallucinations*

10. *Seizures* (rare)

Rare but serious adverse effects:

1. *Anaphylaxis* (severe allergic reaction)

2. *Serotonin syndrome* (a potentially life-threatening condition)

3. *Respiratory arrest*

4. *Cardiac arrest*

5. *Coma*

Large doses causes: Convulsions due to accumulation of Normepridine.

TOXICITY OF MEPERIDINE:

OVERDOSE OF MEPERIDINE:

Meperidine overdose can lead to severe symptoms, including:

1. Respiratory depression (slowed breathing)

2. Hypotension (low blood pressure)

3. Coma

4. Seizures

5. Cardiac arrest

6. Death

Other symptoms of meperidine overdose may include:

1. Drowsiness

2. Confusion

3. Dizziness

4. Nausea and vomiting

5. Slurred speech

6. Slow or shallow breathing

7. Pinpoint pupils

8. Decreased reflexes

Overdose treatment:

1. Activated charcoal to absorb the drug

2. Naloxone to reverse respiratory depression

3. Supportive care, such as oxygen and fluids

4. Monitoring of vital signs and cardiac function

5. Gastric lavage (stomach pumping)

In severe cases, hospitalization may be necessary to manage complications and prevent

long-term damage.

INTERACTIONS:
 • Serotonin syndrome has also been Reported in patients receiving both meperidine
and selective serotonin Reuptake inhibitors (SSRIs).
• Meperidine interact with Benzodiazepine increases the risks of respiratory
depression sedition dizziness and coma.
• Meperidine interact with dexomethorphen increase the risk of respiratory
depression, sedation, confusion and coma.

TOLERANCE AND DEPENDENCE:

Meperidine can lead to:

Tolerance:
- Need for increasing doses to achieve pain relief

- Reduced effectiveness with repeated use

Dependence:

- Physical dependence: withdrawal symptoms when stopping or reducing dose

- Psychological dependence: craving and compulsive drug-seeking behavior

Withdrawal symptoms may include:

- Anxiety

- Insomnia

- Muscle and bone pain

- Restlessness

- Nausea and vomiting

- Diarrhea

- Abdominal cramps