Opioids

Opioids

Opioid

The term opioid refers to a drug that binds to all or part of a subtype of opioid receptors. An opioid may be synthetic, semisythetic or naturally occurring.

Opiates

This term refers to drugs derived from the poppy (opium) plant Papaver somniferum

Opium

Opium is the dried milky exudates produced by incision of the unripe seed capsules of the poppy plant, Papaver somniferum. It contains number of pharmacologically active alkaloids like morphine, codeine, Thebaine etc.,

Norcotics

This term is commonly used to refer to opioid analgesics. In Pharmacology, the term refers to drugs that induce sleep, but in the legal arena, it is used to indicate any drugs that cause dependence.

Endogenous opioids

Endorphine, enkaphaline and dynorphines

Classification

1.       Natural opium alkaloids – Morphine, Codeine

2.       Semisynthetic opiates – Diacetylmorphine(Heroin), Pholcodeine, etorphine, oxymorphone, Hydrocodine, Oxycodone

3.       Sythetic opioids – Pethidine, Fentanyl, Tramadol, Methadone

Based on their action on receptors, the synthetic opioids are classified into,

1.       Agonist – Fentanyl, Tramadol

2.       Agonist – Antagonist – Pentazocine, Butorphenol

3.       Partial/weak agonist – Buprenorphine

4.       Pure antagonist – Naloxone, Naltrexone

Mechanism of action

·         All opioid receptors are G protein coupled receptors.

·         In CNS, opioid analgesics modify pain perception and behavioural reaction to pain.

·         Activation of opioid receptor causes decreased production of intracellular cAMP through inhibition of adenylate cyclase enzyme or a direct G-Protein coupling. Opioids open potassium channels (through µ and δ receptors) and inhibit opening of voltage gated calcium channels (via к). This results in neuronal hyperpolarization and resulting in diminishing neuronal excitability.

Pharmacological effects

·         Morphine has site specific depressant and stimulant action in the CNS.

·         Strong analgesics. Perception of pain and reaction to it are both altered so that pain is no longer as unpleasant or distressing.

·         Drowsiness and indifferent to surroundings without motor incordination.

·         Depress respiratory centre in dose dependant manner.

·         Cough centre – depressed

·         Vasomotor centre – Depressed at higher dose and contributes to fall in B.P.

·         Nausea and vomiting occurs as side effect.

·         Miosis on topical application. But mydriasis in cats.

·         Vagal centre – stimulated and results in Bradicardia.

·         Cortical and hyppocampal areas – stimulated which results in muscular rigidity and convulsions.

·         Release antidiuretic hormone and decrease urine volume.

·         Vasodilation due to decrease in tone of blood vessels, histamine release and depression of vasomotor centre.

·         Constipation is a prominent feature.

Adverse effects

·         Sedation, lethargy

·         Respiratory depression

·          Blurring of vision

·         Urinary retention

·         Constipation

·         Vomiting

·         Fall in blood pressure

·         Allergy and idiosyncrasy

·         Tolerance and dependence

Contradindications

·         Respiratory insufficiency

·         Bronchial asthma (as it release histamine)

·         Head injury

·         Hypotension

Natural opium alkaloids

Morphine

·         Morphine is the principal alkaloid of opium and was the first plant alkaloid to be isolated in 1805.

·         Morphine provides the standard against which the analgesic potency and actions of other opoid analgesics are compared.

Codeine

·         Second most important alkaloid of opium

·         Less potent than morphine.

·         Used primarily as cough suppressant

Semisynthetic opiates

Diacetyl morphine (Heroin)

·         Three times more potent than morphine

·         Highly euphorient and addicting

·         Banned in most countries

Pholocodine

·         Has codeine like properties

·         Mainly used as antitussive

Carfentanil

·         10000 more potent than morphine in analgesic activity

·         Used to immobilize large / wild animals.

Etorphine

·         Used for immobilization of wild animals

Oxymorphone

·         Dihydroxy derivative of morphine

·         Analgesic potency is ten times that of morphine

Hydromorphone

·         Injectable opioid used as sedative, restraining agent, analgesic and Preanaesthetic.

·         Similar to oxymorphone but shorter duration of action.

Sythetic opioids

Pethidine

·         Analgesic efficacy approaches near to morphine and is more than codeine.

Tramadol

·         Synthetic µ - receptor opiate agonist also inhibits reuptake of serotonin and non epinephrine.

·         Useful as an analgesic and antitussive.

·         It can be administered orally.

Fentanyl

·         Potent µ - receptor agonist.

·         50- 100 times more potent than morphine.

·         Used in dogs and cats as preanaesthetic medicament or a potent analgesic to control postoperative and chronic pain.

Pentazocin

·         First agonist – antagonist used

·         Has weak antagonistic and more marked agonistic action

·         Indicated for post operative and moderately severe pain

·         Though abuse liability is low, potential for dysphoric/ psychotomimetic effect limits its utility in chronic (cancer) pain.

·         Used as a part of premedication protocol.

Butorphanol

·         4-7 times more potent analgesic than morphine

·         µ antagonist and к agonist

Buprenorphine

·         25 – 30 times more potent than morphine

·         Useful in long-lasting painful conditions like cancer pain

Naloxone

·         High affinity for µ receptors and low affinity for к and δ receptors.

·         Used for reversal of respiratory depression

Naltrexone

·         Long lasting opioid receptor antagonist which can be used to reverse opioid induced respiratory depression

·         Used to antagonize the immobilizing effect of a potent opioid (Carfentanil)

·         µ partial agonist and к agonist