By:Dr. Dhruva Kumar SharmaDepartment of PharmacologySMU/SMIMS

OPIOID ANALGESICS

Opium Poppy-Papaver somniferum

CLASSIFICATION

Natural opiatesAlkaloids like morphine, codeine and thebaine

Semi-synthetic OpiatesDiacetylmorphine (heroin), pholcodeine, Ethylmorphine

Fully synthetic opioidsPethidine, Fentanyl (Fortwin), methadone and tramadol

History of Opium

Opioids have been the mainstay of pain treatment for thousand of years, and they remain so today

Its use in medicine is quoted in a twelfth-century prescription:

Take opium ,mandragora, and henbane in equal parts and mix with water. When you want to saw or cut a man, dip a rag in this and put it to his nostrils. He will sleep so deep that you may do what you wish.

Terminology

• “opium” is a Greek word meaning “juice,” or the exudate from the poppy

• “opiate” is a drug extracted from the exudate of the poppy

• “opioid” is a natural or synthetic drug that binds to opioid receptors producing agonist effects

Morphine

Opium contains a complex mixture of 20 alkaloids, principle one being morphine› Responsible for analgesic activity

Because of morphine’s poor oral bioavailability, it was little used in medicine until the hypodermic syringe was invented in 1853

Mechanism of Action

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•In general, opioids act upon mu-, delta-, and kappa-receptors on CNS neurons producing: Analgesia via decreased neuronal transmitter release and decreased nociceptive impulse propagation Appears to work by elevating the pain threshold, thus decreasing the brain’s awareness of pain

Receptor type

Location Effects

μ Brain, spinal cord

Analgesia, respiratory depression, euphoria, addiction, ALL pain messages blocked

κ Brain, spinal cord

Analgesia, sedation, all non-thermal pain messages blocked

δ Brain Analgesia, antidepression, dependence

• Morphine is a principal active agent in opium and the prototypical opiate.

Pharmacological Actions:A.CNS1. Analgesia:• Like other opioids, e.g. Diamorphine (heroin),

morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the nucleus accumbens in particular.

• Morphine is highly addictive when compared to other substances, and tolerance and physical and psychological dependences develop very rapidly.

2. Sedation3. Mood and subjective effects- calming

effect, allaying anxiety, Kick, high, Rush4. Respiratory centre depression in a dose

dependent mannerdeath in morphine poisoning is due to resp failure

5. Cough centre6. B.P and Temp also falls

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B. CVS Vasodilatation by-• Histamine release• Depress vasomotor tone• Direct action decreasing tone of b/vC. GITEnteric plexus neurons and g.i mucosa are rich in opioid receptors—constipationD. Other effects- due to Hitamine release

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Administration of Morphine

• Parenterally as subcutaneous, intravenous, or epidural injections. When injected, particularly intravenously, morphine produces an intense contraction sensation in the muscles due to histamine release and also produces a very intense 'rush' which is mediated by several different receptors in the CNS.

• The military sometimes issues morphine loaded in an autoinjector.

Administration

• Orally, it comes as an elixir, concentrated solution, powder (for compounding) or in tablet form.

• Available in extended release capsules for chronic administration, as well as immediate-release formulations

• Poor oral bioavailability• Oral morphine only 1/6th to 1/3rd of the potency

of parenteral morphine.

Dose

10-50 mg oral10-15 mg i.m./s.c.2-6 mg i.v.2-3 mg epidural/intrathecalChildren: 0.1-0.2 mg/kg i.m. or s.c.

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Side Effects

• Most dangerous is respiratory depression. With higher doses respiratory rate decreases, the patient becomes increasingly sedated, and the pupils become very small.

• Common side effects are nausea and vomiting due to a central action on CTZ

Side Effects

• CNS side effects of morphine are cough suppression, sedation, and dependence leading to addiction.

• Muscle of the bowel and urinary tract- contraction of sphincter; reduce the peristalsis delayed emptying of the stomach, constipation

• May also lead to urinary retention.

Side Effects

• Histamine release causes itching of the skin and nose and a mild flushing of the skin.

Unwanted side effects

Dangerous side effects are those of tolerance and dependence, allied with the effects morphine can have on breathing› Most common cause of death from morphine

overdose is suffocation› Severe withdrawal symptoms when the drug is no

longer taken

Tolerance and DependenceWithdrawal symptoms associated with morphine

AnorexiaWeight lossPupil dilationChillsExcessive sweatingAbdominal crampsMuscle spasms

HyperirritabilityLacrimationTremorIncreased heart rateIncreased blood pressure

Treatment of Acute morphine poisoning

• Resp support• Maintennce of B.P, gastric lavage with

potassium permanganate• Antidote : Naloxone 0.4-0.8 mg I.V

repeated every 2-3 min till resp picks up

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• Infants / Elderly: more susceptible to respiratory depression

• Dangerous in resp insufficiency- cor pulmonale, emphysema,pulm fibrosis

• Bronchial asthma: precipitate asthma by histamine release

• Head Injury: C/I retension of CO2 increases intracranial pressure

Vomiting , miosis and altered mentation interfere in the

assessment

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Precautions and C/Is

• Hypotensive states and hypovolemia exagerate fall in B.P. due to morphine

• Elderly male: urinary retention• Unstable personalities : Liable to become

addicted

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Interactions:

• TCAs, MAO inhibitors, Amphetamine and neostigmine potentiate Morphine and other opioids

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Thank You..