Brands, Medical Use, Clinical Data
- Opiate Agonists
Brands / Synonyms
Centralgin; Demarol; Demerol; Demerol Injection; Dispadol; Dolantin; Dolcontral; Dolosal; Dolsin; Isonipecaine; Lidol; Lydol; Meperidine; Meperidine Hcl; Meperidol; Methyl phenylpiperidine carbonic acid ethyl ester; Nemerol; Operidine; Petantin; Pethanol; Pethidin; Pethidine; Pethidineter; Petydyna; Phetidine; Piperosal; Pipersal; Piridosal
Used to control moderate to severe pain.
Meperidine is a synthetic opiate agonist belonging to the phenylpiperidine class. Meperidine may produce less smooth muscle spasm, constipation, and depression of the cough reflex than equivalent doses of morphine. The onset of action is lightly more rapid than with morphine, and the duration of action is slightly shorter. The chemical structure of meperidine is similar to local anesthetics. Meperidine is recommended for relief of moderate to severe acute pain and has the unique ability to interrupt postoperative shivering and shaking chills induced by amphotericin B. Meperidine has also been used for intravenous regional anesthesia, peripheral nerve blocks and intraarticular, epidural and spinal analgesia. Meperidine is considered a second-line agent for the treatment of acute pain.
Mechanism of Action
Meperidine is primarily a kappa-opiate receptor agonist and also has local anesthetic effects. Meperidine has more affinity for the kappa-receptor than morphine. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Meperidine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
Oral bioavailability is 50-60% in patients with normal hepatic function.
Biotrnasformation / Drug Metabolism
Meperidine is metabolized in the liver by hydrolysis to meperidinic acid followed by partial conjugation with glucuronic acid. Meperidine also undergoes N-demethylation to normeperidine, which then undergoes hydrolysis and partial conjugation. Normeperidine is about half as potent as meperidine, but it has twice the CNS stimulation effects.
Hypersensitivity of meperidine.
Meperidine is contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitors or those who have
recently received such agents. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe,
and occasionally fatal reactions in patients who have received such agents within 14 days. The mechanism of these
reactions is unclear, but may be related to a preexisting hyperphenylalaninemia. Some have been characterized by
coma, severe respiratory depression, cyanosis, and hypotension, and have resembled the syndrome of acute narcotic
overdose. In other reactions the predominant manifestations have been hyperexcitability, convulsions, tachycardia,
hyperpyrexia, and hypertension. Although it is not known that other narcotics are free of the risk of such reactions,
virtually all of the reported reactions have occurred with meperidine. If a narcotic is needed in such patients, a
sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over
the course of several hours while the patient's condition and vital signs are under careful observation. (Intravenous
hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous
chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of narcotic
antagonists in the treatment of these reactions is unknown.)
Solutions of meperidine and barbiturates are chemically incompatible.
Interaction with Other Central Nervous System Depressants: MEPERIDINE SHOULD BE USED WITH GREAT CAUTION AND
IN REDUCED DOSAGE IN PATIENTS WHO ARE CONCURRENTLY RECEIVING OTHER NARCOTIC ANALGESICS, GENERAL ANESTHETICS,
PHENOTHIAZINES, OTHER TRANQUILIZERS, SEDATIVE-HYPNOTICS (INCLUDING BARBITURATES), TRICYCLIC ANTIDEPRESSANTS AND OTHER
CNS DEPRESSANTS (INCLUDING ALCOHOL). RESPIRATORY DEPRESSION, HYPOTENSION, AND PROFOUND SEDATION OR COMA MAY