Opioid Analgesics

Opioid medications are generally reserved for moderate-to-severe pain. Codeine, dihyrocodeine, hydrcodone and oxycodone are commonly prescribed with combination of aspirin, acetaminophen or ibuprofen to manage acute, dental and post-operative pain in dental practice.

Natural and Semi-Synthetic Opioids

Generic Name: Morphine

Brand Name: Morphine Sulphate 10mg/ml inj ;Morcontin 10, 30, 60, 100 mg CR tabs;30 -100mg BD.

Mechanism of Action

Morphine acts as an anesthetic without decreasing consciousness and it is one of the most powerful analgesics. However it also suppresses the respiratory system and high doses can cause death by respiratory failure.

Its analgesic properties are related to the ability of the molecule to fit into and block a specific receptor site on a nerve cell. This eliminates the action of the pain receptor, preventing the pain signals from reaching the brain. This is similar to the way in which the body's natural painkillers (endorphins and enkaphalins) work.

Indications

Morphine can be used:

• As an analgesic in hospital to relieve pain in-
  • Myocardial infarction.
  • Sickle cell crisis.
  • Surgical conditions, pre- and postoperatively.
  • Trauma.
• In the relief of severe chronic pain in-
  • Cancer.
  • Pain from kidney stones (renal colic, ureterolithiasis).
  • Severe back pain.
• As an adjunct to general anaesthsia
  • In epidural anaesthsia or intrathecal analgesia.
  • For palliative care (i.e. to alleviate pain without curing the underlying reason for it).
  • As an anti-tussive for severe cough.
  • In nebulized form, for treatment of dyspnoea.
  • As an antidiarrhoeal in chronic conditions (e.g. for diarrhea associated with AIDS, although loperamide (a non-absorbed opioid acting only on the gut).

Precautions and contraindications

Avoid using for-

• Infants and elderly, as they are more susceptible to the respiratory depressant activity of morphine.
• Acute respiratory depression.
• Bronchial asthma.
• Morphine is contraindicated in patients with head injury, as
  • It can increase intracranial pressure by retaining CO2.
  • Respiratory depression.
  • Vomiting, miosis and altered mentation by morphine may interfere with assessment of progress in injury.
• Hypotensive patients.
• Hypothyroidism, liver and kidney disease.

Adverse effects

• Less serious side effects are:
  • Constipation.
  • Warmth, tingling or redness under the skin.
  • Nausea, vomiting, stomach pain, diarrhea, loss of appetite.
  • Dizziness, headache, anxiety.
  • Memory problems.
  • Sleep problems (insomnia).
• Get emergency medical help in case of an allergic reaction(e.g. hives; difficulty in breathing; swelling of the face, lips, tongue or throat) shallow breathing, slow heartbeat, seizure (convulsions) and severe weakness or dizziness.

Acute Morphine Poisoning

It is accidental or seen in drug abusers. 50mg of morphine produces serious toxicity.Human lethal dose is 250 mg.

Stupor or coma, flaccidity, shallow and occasional breathing, cyanosis, pinpoint pupils, fall in BP and shock, convulsions may be seen in few, pulmonary edema occurs at terminal stage, death is due to respiratory failure.

Treatment:

• Respiratory support.
• Gastric lavage.
• Specific antidote: Naloxone 0.4-0.8mg IV, repeated every 2-3mins till respiration picks up. Injection may be prepared every 1-4hrs according to response.

Tolerance and Dependance

Tolerance to the analgesic effects of morphine is fairly rapid. Morphine is a highly addictive substance, as it can cause psychological and physical dependence as well as tolerance, with an addiction potential identical to heroin.

Withdrawal

The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next scheduled dose (usually between 6–12 hours).

Early symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria and sweating and in some cases a strong drug craving. Severe headache, restlessness, irritability, loss of appetite, body aches, severe abdominal pain, nausea and vomiting, tremors and even stronger and more intense drug craving appear as the syndrome progresses. Severe depression and vomiting are very common.

During the acute withdrawal period systolic and diastolic blood pressure increase, usually beyond pre-morphine levels and heart rate increases, which could cause a heart attack, blood clot or stroke.

Chills or cold flashes with goose bumps ("cold turkey") alternating with flushing (hot flashes), kicking movements of the legs and excessive sweating are also characteristic symptoms. Severe pains in the bones and muscles of the back and extremities occur, as well as muscle spasms.

Major withdrawal symptoms peak between 48 and 96 hours after the last dose and subside after approximately 8 to 12 days.

Treatment:

Consist of withdrawal of morphine and substitution with oral methadone followed by its gradual withdrawal.

Generic Name:Codeine

Indication

• Codeine is suitable for the treatment of mild and moderate pain. The analgesic action of 30 mg of codeine corresponds approximately to 325-600 mg of paracetamol or aspirin.
• Codeine is the cough medicine to which all other antitussive drugs are compared.
• It can also be used in irritable bowel syndrome.

Contraindications

Advanced respiratory insufficiency, bronchial asthma, raised intracranial pressure.

Adverse effects

Common effects include euphoria, itching, nausea, vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention, depression and constipation.

Synthetic Opioids

Generic Name: Pethidine

Brand Name: Pethicine HCl 100mg/2ml inj; 50,100 mg tab.

Mechanism of Action

• Pethidine is an opioid analgesic with some antimuscarinic effects.
• Pethidine acts on the opioid receptors to cause analgesia and sedation, by acting as an agonist at the μ- opioid receptor.
• Besides, it also acts as an antagonist at the cholinergic receptors to produce atropine like effects.
• It has local anaesthetic activity related to its interactions with sodium channel receptors.

Indication

• Used in pre operative medication as an adjuvant to anaesthesia – for sedative and anxiolytic effects.
• Relief of moderate to severe pain of any cause.
• Obstetrical analgesia.
• Dosage: 50 - 100mg I.M., S.C., occasionally given orally or I.V.

Contraindication

• Patients receiving MAO inhibitors may suffer agitation, delirium, headache, convulsions and/or hyperthermia. Fatal interactions have been reported including death.
• In acute alcoholism, head injuries, states of pre-existing CNS, depression and conditions in which increased intracranial tension occurs.
• Hypersensitivity.
• Severe renal /hepatic failure.

Precautions

• Should be given cautiously to patients with supraventricular tachycardia or with history of convulsive disorders.
• Being an opioid, the drug has an abuse potential and can be addictive.
• Use with caution in conditions like bronchial asthma, COPD, states with reduced respiratory reserve, because it is a respiratory depressant.
• Instruct patients not to drive or operate machinery as it causes sedation and drowsiness.
• Can cause respiratory depression in newborn. Judicious use is necessary in obstetrical analgesia.
• Not suitable for chronic use as, cumulative toxicity with its active metabolite (non pethidine) can occur.

Administration instruction

• Incompatible with aminophylline, barbiturates, heparin, phenytoin and sodium bicarbonate and should not be mixed or given in the same syringes.
• I.M. administration is preferred. If given intravenously, a solution of concentration 10 mg/ml should be used and given very slowly. Rapid I.V. administration may result in hypotension, apnoea and collapse.

Adverse effects

• Common effects
  • Local pain at injection site.
  • Sedation, nausea, light headedness, vomiting, dry mouth, muscular twitches.
• Rare effects
  • CNS effects - euphoria, mood changes, agitation, tremor, disorientation and hallucinations.
  • Dependency and drug abuse.
  • CVS – tachycardia, hypertension.
  • Constipation.

Other Similar Drugs

Generic Name: Fentanyl

Brand Name: Durogesic transdermal patch

A pethidine congener is more potent than morphine both as analgesia as well as respiratory depressent.

Transdermal fentanyl has become available for use in cancer or other chronic pain for patients requiring opioid analgeisa.

Generic Name: Methadone

Mechanism of Action

Methadone is a full µ-opioid agonist.

Methadone also binds to the glutamatergic NMDA (N-methyl-D- aspartate) receptor, and thus acts as a receptor antagonist against glutamate. Glutamate is the primary excitatory neurotransmitter in the CNS.

Acting as an NMDA antagonist may be one mechanism by which methadone decreases craving for opioids and tolerance. It has been proposed as a possible mechanism for the treatment of neuropathic pain.

Indication

MMT (Methadone Maintenance Treatment)

It reduces and/or eliminates the use of heroin and criminality associated with heroin use. It allows patients to improve their health and social productivity.

In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV.

The principal effects are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. Methadone maintenance has been found to be medically safe and non-sedating. It is also indicated for pregnant women addicted to heroin.

Methadone linctus, which is about one-third the concentration of the liquid methadone used for opioid maintenance, is used where available and approved as a cough syrup for violent coughing. Narcotic cough suppressants are very useful against dry, unproductive coughing, especially that which persists after an illness and/or is a manifestation of recurring bronchitis, causes pain in the chest and/or prevents the patient from sleeping.

Generic Name: Tramadol

Brand Name: Tramazac, Domadol 50 mg cap, 100mg SRtab; 50mg/ml inj in 1 and 2 ml amps.

Mechanism of Action

It is believed to work through modulation of the noradrenergic and serotonergic systems in addition to its mild agonism of the μ- opioid receptor. The contribution of non-opioid activity is demonstrated by the analgesic effects of tramadol not being fully antagonised by the μ- opioid receptor antagonist naloxone.

It is well tolerated and side effects are dizziness, nausea, sleepiness, dry mouth and sweating. Safer in patients with compromised cardiovascular function as heamodynamic results are minimal.