It's black and white - PETHIDINE aka MEPERIDINE is a bad drug

Now a sufficient time has elapsed since the untimely death of the self-abusive and much abused Michael Jackson, we should question the availability of one of the purported agents of death, pethidine (known as meperidine in North America).

Many authorities believe that pethidine (meperidine) is a drug that has had it’s time. It no longer serves any useful purpose, it is no longer the drug or first choice (or indeed even the drug of second choice) when opioid analgesia is required. Sensibly, it is not available as a subsidised drug under the Pharmaceutical Benefits Scheme (PBS) in Australia.

THE CASE

All opioids have equi-analgesic effects when equivalent doses are given. Despite any advertising hype they all the work the same way to the same extent - although some may be shorter or longer acting than others. This enables the clinician to choose the opioid with the lowest side-effect profile. This is NEVER pethidine.

Pethidine is currently approved in Australia for:

Short term relief of moderate to severe pain not responsive to non-opioid analgesics.

Preoperative medication.

Analgesic adjunct in general anaesthesia.

Obstetric analgesia

(most literature stresses that pethidine therapy should be limited to 24-36 hours for all indications)

The following conditions are NOT indications for pethidine:

Migraine:
Pethidine is too short acting, has an addictive potential and is not as effective as specific anti-migraine treatments such as 5HT and ergot alkaloids. Indeed it is no more effective than NSAIDs or prochlorperazine.

Low Back Pain:
Intramuscular morphine, not pethidine, is the drug of choice for a single dose of opioid for treating acute lower pack pain.

Post Caesarian Pain:
Pethidine is less effective than morphine in controlling pain after Caesarian delivery.

Biliary Colic:
Despite a long held belief there is no real evidence that pethidine causes any greater increase in intrabiliary pressure than morphine.

Renal Colic:
Although renal colic is often listed as a contra-indication for morphine, there is little evidence to support this. Nor is there any evidence that pethidine is free of this side-effect.

In summary the only real indication for pethidine is in obstetric analgesia where there is no possibility of the therapy extending for more that 24-36 hours. For this indication the dose is 50–100 mg IM or SC when labour becomes regular, may be repeated 1–3-hourly (to a maximum of 400 mg)

Why is it such a crock?

Drug Interactions:
Pethidine has such a wide spectrum of serious drug interactions, (some not shared with other opioids) including:

monoamine oxidase inhibitors, selegiline, anticoagulants, seizure treatments, urinary alkalizers, barbiturates, amphetamines, phenothaizines, bromocriptine, lithium and SSRIs

It really is not a drug suitable for patients using a lot of different medications (or street drugs).

Contra-indications:
As for the drug interactions, pethidine has such a variety of contra-indications, many not shared with other opioids:

Pethidine allergy, monoamine oxidase inhibitors, selegiline, respiratory depression, emphysema, severe chronic bronchitis, kyphoscoliosis, acute bronchial asthma, chronic airway disease, status epilepticus, tetanus and strychnine poisoning, pre-eclampsia, eclampsia, cardiac arrhythmias, diabetic acidosis, acute alcoholism, delirium tremens, liver disease, hepatic encephalopathy, head injury, raised intracranial pressure, brain tumour, low platelet count, coagulation disorders, anticoagulant treatment.

Histamine Release:
All opioids occasionally cause the release of histamine from tissue mast cells through independent triggering mechanisms. This causes hypotension, tachycardia, erythema and increased adrenaline levels. Patients noted flushing of face, neck chest and extremities and a generalised sensation of warmth.

Seizures:
The active metabolite of pethidine, nor-pethidine is associated with an increased likelihood of seizures, it can also make some anti-seizure treatments less effective.

Short Duration of Action:
The effectiveness of pethidine analgesia is only two to four hours, compared with four to six hours for morphine. In a rare plus for pethidine this may be an advantage in obstetrics.

Abuse Potential:
Because it excites the nervous system as well as being a narcotic, many abusers favour pethidine over other legal opoids.

Pregnancy:
Pethidine is category C for pregnancy. Drugs in this category “have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations.”

Lactation:
Maternal pethidine is secreted in breast milk, therefore pethidine administration to breastfeeding mothers is not recommended. Neonates metabolise pethidine more slowly than older persons.

Sport:
Pethidine is banned in all sports under national and international rules.

Glaucoma:
Pethidine can raise intraocular pressure.

MY VERDICT
Pethidine acts for a shorter time than morphine with no analgesic or other benefits.

Pethidine has similar side effects to morphine, including increased biliary pressure.

Pethidine can cause seizures, because it’s main metabolite, nor-pethidine, has many toxic side-effects (including convulsions).

Pethidine has many significant drug interactions.

Because other analgesics are less toxic when given at an equivalent dose pethidine is never the first line agent for treatment of severe pain. There is absolutely no case to allow a patient to self-inject pethidine.