MORPHINE

Opioids are a group of analgesic agents commonly used in clinical practice.

Morphine is commonly considered to be the prototype opioid analgesic and the agent to
which all other analgesics are compared.

Milky exudate obtained from the unripe seed capsules of the poppy plant Papaver
somniferum, dried and powdered – opium powder.

Opioids are classified into naturally occurring alkaloids, semi-synthetic and synthetic
compounds.

Four naturally occurring alkaloids isolated from Papaver somniferum are morphine, codeine,
papaverine and thebaine.

Semi-synthetic opioids - diamorphine, dihydrocodeine, buprenorphine, nalbuphine, naloxone

and oxycodone.

Synthetic opioids the morphinan derivatives (levorphanol, butorphanol), the diphenylheptane

derivatives (methadone, propoxyphene), the benzomorphan derivatives (pentazocine,
phenazocine) and the phenylpiperidine derivatives (pethidine, alfentanil, fentanyl, sufentanil
and remifentanil)

Classification of opioids

Naturally occurring compounds Semi-synthetic compounds Synthetic compounds

Morphine Diamorphine (heroin) Pethidine

Codeine Dihydromorphone Fentanyl

Thebaine Buprenorphine Methadone

Papaverine Oxycodone Alfentanil

Remifentanil

Tapentadol

Opioid receptors

As morphine binds to opioid receptors, molecular signalling activates the receptors to

mediate certain actions.

There are three important classes of opioid receptors and these are:
μ receptor or Mu receptors - There are three subtypes of this receptor, the μ1, μ2 and μ3
receptors. Present in the brainstem and the thalamus, activation of these receptors can result
in pain relief, sedation and euphoria as well as respiratory depression, constipation and
physical dependence. (affinity +++)

κ receptor or kappa receptor - This receptor is present in the limbic system, part of the
forebrain called the diencephalon, the brain stem and spinal cord. Activation of this receptor
causes pain relief, sedation, loss of breath and dependence. (affinity +)

δ receptor or delta - This receptor is widely distributed in the brain and also present in the
spinal cord and digestive tract. Stimulation of this receptor leads to analgesic as well as
antidepressant effects but may also cause respiratory depression. (affinity +)

Pharmacokinetics

Morphine can be administered orally, intravenously, intramuscular, rectally, subcutaneously,

through spinal injection (e.g. epidural) as well as through inhalation. (parenteral – 10 mg)

Absorption-It is slowly absorbed through orally. During sub cutaneous and intravenous
administration it is absorbed very rapidly.
Distribution-It is widely distributed throughout body. 50% of it`s seen as bound and rest is
seen unbound with plasma protein. It crosses the placental barrier.
Metabolism-It is metabolized in liver by glucoronide conjugation. Morphine 6- glucoronide is
one of the active metabolite. During oral administration there is first metabolism.
Excretion- Excreted via urine and through bile.

Adverse effects

Morphine has many side effects. Some of the more common and more serious are:

 Nausea, vomiting and abdominal cramps

 Constipation

 Sedation and drowsiness

 Itching and allergic skin reactions causing warmth and flushing

 Shrinking of the pupils to pin points

 Respiratory depression or suppressed breathing

 Initial doses lead to euphoria but higher doses cause unpleasant symptoms such as
hallucinations, delirium, dizziness and confusion
  Formation of physical or psychological dependence and development of withdrawal
symptoms when use of the drug is stopped

 Development of tolerance and the need to increase dose to achieve the same degree of
effects as before

 Risk of overdose and poisoning

 Transmission of HIV/AIDS and hepatitis B and C among needle users.

Therapeutic uses

1. Pain due to -cancer, Acute myocardial infarction, Angina, labour etc

2. Preoperative sedation
3. Post operative analgesia
4. Adjunctive treatment of acute pulmonary Oedema.
5. Adjuncts to anesthesia

FENTANYL

Synthetic opioid analgesic

μ receptor (affinity +++)

κ receptor (affinity -)

δ receptor (affinity +)

Dose – 0.05 – 0.1 mg iv, im

Uses – Acute pain, Neurolept analgesia with droperidol

Dependence liability – High, but shorter duration of action (1-1.5 hrs) discourages its use

High potency allows even transdermal administration.

Other substitutes like Alfentanil (0.5 hr) and Sufentanil (0.5 - 1 hr) have shorter duration of
action and are more potent.

PETHIDINE (MEPERIDINE)

Synthetic opioid analgesic

μ receptor (affinity ++)

κ receptor (affinity+)

δ receptor (affinity +)

Dose – 50 – 100 mg im, sc

Uses – Acute pain (less in use), preanaesthetic medication, post anaesthetic shivering

Dependence liability – High, no miosis

The metabolite Norpethidine is toxic – risk of convulsions, no antitussive action, less

histamine release, less constipation.