meperidine

MEPERIDINE

WHAT IS MEPERIDINE?
Meperidine is in a group of drugs called narcotic pain relievers. It is similar to morphine.
Meperidine is used to treat moderate-to-severe pain. It is a synthetic morphine derivative.

DESCRIPTION
Meperidine hydrochloride is ethyl 1-methyl-4-phenylisonipecotate hydrochloride, a white crystalline substance with a melting point of 186°C to 189°C. It is readily soluble in water and has a neutral reaction and a slightly bitter taste. The solution is not decomposed by a short period of boiling


PHARMACOLOGICAL ACTION

Analgesics, Opioid - Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
Adjuvants, Anesthesia - Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage.
Narcotics - Agents that induce NARCOSIS. This term is considered outdated due to imprecision but continues to be widely used. Originally, agents that caused somnolence or induced sleep (STUPOR); now, any derivative, natural or synthetic, of OPIUM or MORPHINE or any substance that has their effects. Narcotics are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.
Ii also has atropine like action which is parasympatholytic and also has papaverine like action which can give smooth muscle relaxant effect.

PHARMACOLOGY AND USE:
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. Used to control moderate to severe 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.


DOSAGE OF ADMINISTRATION

For Relief of Pain
Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than on parenteral administration. The dose of meperidine should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine.
Adults: The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary.
Pediatric Patients: The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary.
Each dose of the oral solution should be taken in one-half glass of water, since if taken undiluted, it may exert a slight topical anesthetic effect on mucous membranes.



PHARMACOKINETICS
Pethidine is quickly hydrolysed in the liver to pethidinic acid and is also demethylated to norpethidine, which has half the analgesic activity of pethidine but a longer elimination half-life (8-12 hours[13]); accumulating with regular administration, or in renal failure. Norpethidine is toxic and has convulsant and hallucinogenic effects. The toxic effects mediated by the metabolites cannot be countered with opioid receptor antagonists such as naloxone or naltrexone and are probably primarily due to norpethidine's anticholinergic activity probably due to its structural similarity to atropine though its pharmacology has not been thoroughly explored. The neurotoxicity of pethidine's metabolites is a unique feature of pethidine compared to other opioids. Pethidine's metabolites are further conjugated with glucuronic acid and excreted into the urine.
Difference of meperidine to morphine.
• Its analgesics action is only 10% of morphine with the same dose.
• Its does not depress cough center so have no use to suppress cough.
• In therapeutics dose its does not cause respiratory distress.
• Its does not cause constipation.
• It has atropine like action.
• It does not cause PPP so pupil is dilated.
• Its tolerance and addiction is less than with morphine.

Similarities of morphine to meperidine.
• Stimulation of CTZ which lead to vomiting.
• Also release of ADH.
Therapeutic uses of meperidine.
• As analgesics instead of morphine.
• In obstetrics to reduce labour pain.
• As preanesthetic medication instead of morphine.
• Better than morphine in renal and biliary colics .



WARNING
Misuse, Abuse, and Diversion of Opioids
Meperidine is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Meperidine can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Meperidine in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.
Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Interactions with Alcohol and Drugs of Abuse
Meperidine may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of meperidine and its capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries. In such patients, meperidine must be used with extreme caution and only if its use is deemed essential.
Asthma and Other Respiratory Conditions: Meperidine should be used with extreme caution in patients having an acute asthmatic attack, patients with chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve, and patients with preexisting respiratory depression, hypoxia, or hypercapnia. In such patients, even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.
Hypotensive Effect: The administration of meperidine may result in severe hypotension in the postoperative patient or any individual whose ability to maintain blood pressure has been compromised by a depleted blood volume or the administration of drugs such as the phenothiazines or certain anesthetics.
Usage in Ambulatory Patients: Meperidine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient should be cautioned accordingly.
Meperidine, like other narcotics, may produce orthostatic hypotension in ambulatory patients.
Usage in Pregnancy: Meperidine should not be used in pregnant women prior to the labor period, unless in the judgment of the physician the potential benefits outweigh the possible risks, because safe use in pregnancy prior to labor has not been established relative to possible adverse effects on fetal development.
Labor and Delivery: Meperidine crosses the placental barrier and can produce depression of respiration and psychophysiologic functions in the newborn. Resuscitation may be required
Nursing Mothers: Meperidine appears in the milk of nursing mothers receiving the drug. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential benefits of the drug to the nursing woman.
OVERDOSE
Symptoms: Serious overdosage with meperidine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.


Treatment: Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including meperidine. Therefore, an appropriate dose of this antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation.
An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
SIDE EFFECTS
• lightheadedness
• dizziness
• weakness
• headache
• extreme calm
• mood changes
• confusion
• agitation
• upset stomach
• vomiting
• stomach pain or cramps
• constipation
• dry mouth
• flushing
• sweating
• changes in vision
Some side effects can be serious. The following symptoms are uncommon.
• slow or difficult breathing
• shaking hands that you cannot control
• muscle twitches or stiffening
• seizures
• hallucination (seeing things or hearing voices that do not exist)
• slow, fast, or pounding heartbeat
• difficulty urinating
• fainting
• rash
• hives



CONTRAINDICATIONS OF MEPERIDINE
1. Presence of hypersensitivity to narcotics,
2. Diarrhea caused by poisoning (before toxins are eliminated)
3. Bronchial asthma, COPD, cor pulmonale, respiratory depression, anoxia
4. Kyphoscoliosis
5. Acute alcoholism
6. Increased intracranial pressure
7. Pregnancy
http://www.rxlist.com/demerol-drug.htm
www.NovoNordisk.com
Basics and clinical concepts in pharmacology( alexandria university)

tetanus treatment

When a tetanus infection becomes established, treatment usually focuses on :



a) controlling muscle spasms.
b) stopping toxin production
c) neutralizing the effects of the toxin



a) . controlling muscle spasms and supportive treatment.
• Sedatives such as diazepam (Valium) to control muscle spasms , also supportive treatment are given to patient such as Ventilator support to help with breathing in the event of spasms of the vocal cords or the respiratory muscles . other than that IV rehydration also can be given because, as your muscles spasm constantly, increased metabolic demands are placed on your body.
• Analgesics also can be given as needed.
• Patients should be put in quite dark environment to prevent more stimulus that can cause muscle spasm.





b) stopping toxin production
stopping toxin production can be done by administering antibiotics . it is done to kill the causative agent for tetanus which is clostridium tetani. Large doses of antibiotic drugs (such as metronidazole or intramuscular penicillin G) are also given once tetanus infection is suspected, to halt toxin production. Surgical debridement is important to remove the necrotic tissue that is essential for proliferation of the organisms.

c) neutralizing the effects of the toxin
Treatment includes administration of tetanus immune globulin (TIG), which comprises antibodies that inhibit tetanus toxin (also known as tetanus antitoxins), by binding to and removing unbound tetanus toxin from the body. Binding of the toxin to the nerve endings appears to be an irreversible event, and TIG is ineffective at removing bound toxin. Recovery of affected nerves requires the sprouting of a new axon terminal. There are two type of antitoxin, either antitetanic serum (ATS) obtain by immunizing horses with toxoid or hbuman tetanus immunoglobulin (HGIG) which does not have hypersensitivity reaction as a side effect . Antitetanic serum can cause hypersensitivity reaction so a skin sensitivity test should be done.