Morphine

BRANDS / TRADE NAMES OF MORPHINE IN KENYA

Morphine Sulphate Injection, Macarthys Laboratories Ltd T/a Martindale Pharmaceuticals

Morphine Sulphate Fresenius PF , Fresenius Kabi Manufacturing SA (Pty) Limited

MST Continus , Napp Pharmaceuticals Limited

Vermor , Verve Human Care Laboratories

Zomorph ,Ethypharm


Morphine Chemical Structure: Morphine in Kenya
Morphine Chemical Structure

Morphine is a pain medication of the opiate family which is found naturally in a number of plants and animals, including humans.It acts directly on the central nervous system (CNS) to decrease the feeling of pain.It is on the World Health Organization’s List of Essential Medicines and Kenya’s List of Essential Medicines

MODE OF ACTION

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.
  • 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.
  • 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.

INDICATIONS

Morphine sulfate is indicated for the relief of moderate to severe pain. Morphine sulfate  is used especially in pain associated with cancer, myocardial infarction and surgery. Morphine also helps to relieve the anxiety and insomnia which may be associated with severe pain.

DOSAGE AND ADMINISTRATION

Adults and children over 12 years:

There is a considerable variation in analgesic requirements among patients and therefore individualised treatment strategies are required. Dosage should be based on the severity of the pain and the response and opiate tolerance of the patient.

Intravenously
2.5-10mg

Subcutaneously, intramuscularly

5 – 20 mg

Oral

Recommended dose: 10-20 mg (5-10 ml) every 4 hours.

Maximum daily dose: 120 mg per day

Loading dose

Loading doses of typically between 1 mg and 10 mg (maximum 15 mg) of morphine sulfate may be given by intravenous infusion over four or five minutes. The loading dose used will depend upon the patient’s diagnosis and condition.

PCA demand dose

An initial demand dose of 1 mg Morphine sulfate injection with a lockout period of 5 to 10 minutes is recommended. Dosages may vary depending on the loading dose, the tolerance and condition of the patient, and whether a background infusion of morphine is being given.

The patient should be specifically monitored for pain, sedation and respiratory rate during the first few hours of treatment to ensure that the dosage regimen is suitable.

The duration of treatment should be kept to a minimum, although dependence and tolerance are not generally a problem when morphine is used legitimately in patients with opioid-sensitive pain.

Discontinuation of therapy:

An abstinence syndrome may be precipitated if opioid administration is suddenly discontinued. Therefore the dose should be gradually reduced prior to discontinuation.

Use in children:

Not recommended for children under 12 years.

Use in the elderly:

Morphine doses need to be reduced in elderly patients.

Method of administration

For intravenous injection.

The product should not be diluted before use.

The medicinal product is to be visually inspected prior to use. Only clear solutions practically free from particles should be used.

 

CONTRAINDICATIONS

Morphine sulfate injection is contraindicated in:

  • Hypersensitivity to the active substance, to other opioid preparations or to any of the excipients.
  • Respiratory depression; obstructive airways disease; excessive bronchial secretions; during a bronchial asthma attack or in heart failure secondary to chronic lung disease
  • Head injury; raised intra-cranial pressure
  • Coma
  • Convulsion disorders
  • Ulcerative colitis
  • Presence of a risk of paralytic ileus
  • Biliary and renal tract spasm
  • Acute alcoholism
  • Pheochromocytoma
  • Moderate to severe renal impairment (glomerular filtration rate <20ml/min)
  • Severe or acute liver failure
  • Patients receiving monoamine oxidase inhibitors or within two weeks of discontinuing such treatment
  • Use of Morphine sulfate  during pregnancy or lactation is not recommended.

DRUG INTERACTIONS

Monoamine oxidase inhibitors (MAOIs):

Concomitant or recent use of monoamine oxidase inhibitors with morphine is contraindicated since interactions have been reported, resulting in CNS excitation or depression with hyper- or hypotensive crises

Hyperpyrexia and CNS toxicity may result from an opiate selegiline combination. Such combinations should, therefore, be used with extreme caution.

Sedative medicines such as benzodiazepines or related drugs

The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited .

Other CNS depressants

The CNS depressant effects of morphine are increased by the co-administration of CNS depressants including alcohol, anaesthetics, muscle relaxants, hypnotics, sedatives, tricyclics, neuroleptics and phenothiazines as well as other opioid analgesics.

The analgesic effects of opioids tend to be enhanced by the concomitant administration of dexamphetamine, hydroxyzine and some phenothiazines (although the latter may also cause respiratory depression).

Diuretics:

Morphine may reduce the efficacy of diuretics by inducing the release of the antidiuretic hormone.

Anticholinergics:

The combination of morphine with anticholinergics may enhance the constipatory effect and urinary retention.

Antihistamines:

Cimetidine and ranitidine appear to interfere with the metabolism of morphine.

Disulfiram:

The metabolism and excretion of morphine may be inhibited by disulfiram.

Prokinetics:

Increased morphine levels may result from the co-administration of cisapride.

Metoclopramide and domperidone may antagonise morphine’s gastrointestinal effects and metoclopramide enhances it sedative effect.

Antibiotics:

Ciprofloxacin concentration may be reduced.

Anti-arrhythmics:

Mexiletine absorption may be delayed by co-administered opiate. Co-administration of morphine with esmolol results in a slight increase in the esmolol levels, but the clinical implications of this increase are not considered very significant.

Enzyme modulating agents :

Animal data suggest that propranolol may increase the toxicity of opioids. Ritonavir can induce the formation of metabolising enzymes made in the liver and can cause increased metabolism of morphine which can reduce the clinical efficacy of the analgesic.

Rifampicin

Plasma concentrations of morphine may be reduced by rifampicin. The analgesic effect of morphine should be monitored and doses of morphine adjusted during and after treatment with rifampicin

ADVERSE EFFECTS

The side-effects most commonly seen with morphine and other opioids are respiratory depression, nausea, vomiting, constipation, drowsiness and confusion. With long term use these symptoms generally lessen, although constipation frequently persists.

The following adverse events are from published literature and frequencies are not known.

Immune system disorders

Anaphylactic reactions and anaphylactoid reactions to morphine have been reported rarely.

Endocrine disorders

Long term use of opioid analgesics can cause adrenal insufficiency. Exacerbation of pancreatitis.

Psychiatric disorders

Drug dependence , restlessness, mood changes, hallucinations, delirium, disorientation, excitation, agitation, sleep disturbance.

Nervous system disorders

Headache, vertigo, euphoria, dysphoria, dizziness, taste disturbances, seizures, paraesthesia, raised intracranial pressure, hyperhidrosis. Allodynia and hyperalgesia have been reported .

Eye disorders

Visual disturbances, nystagmus, miosis.

Ear and labyrinth disorders

Vertigo.

Cardiac disorders

Bradycardia, tachycardia, palpitations, syncope.

Vascular disorders

Orthostatic hypotension, hypotension, hypertension, facial flushing, oedema.

Respiratory, thoracic and mediastinal disorders

Bronchospasm (in association with anaphylaxis), inhibition of cough reflex.

Gastrointestinal disorders

Dyspepsia, paralytic ileus, abdominal pain, anorexia, dry mouth.

Hepatobiliary disorders

Biliary spasm.

Skin and subcutaneous tissue disorders

Rashes, urticaria, pruritus.

Musculoskeletal and connective tissue disorders

Muscle fasciculation, myoclonus, rhabdomyolysis, muscle rigidity.

Renal and urinary disorders

Difficult micturition, ureteric spasm, urinary retention.

Reproductive system and breast disorders

Long term use of opioid analgesics can cause hypogonadism in both men and women.

This can lead to amenorrhoea, reduced libido, infertility, depression and erectile dysfunction.

General disorders and administration site conditions

Hypothermia, malaise, asthenia, pain and irritation at the injection site.

The side effect uncommonly seen with morphine and other opioids is drug withdrawal syndrome .

Long Term Use

Long term use of opioid analgesics has been associated with a state of abnormal pain sensitivity (hyperalgesia).

Tolerance and psychological and physical dependence may occur (see below). Decreased potency may be experienced.

High doses may produce respiratory depression and hypotension, with deepening coma. Convulsions may occur particularly in infants.

Drug dependence and withdrawal syndrome

Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. An abstinence syndrome may be precipitated when opioid administration is suddenly discontinued or opioid antagonists administered, or can sometimes be experienced between doses. For management.

Physiological withdrawal symptoms include restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Reporting of suspected adverse reactions

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients  are encouraged  to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:

Where to Obtain Morphine in Kenya:

Morphine is a Schedule 1 Drug ,Narcotic Drugs and Psychotropic Substances (Control ) Act and hence a controlled substance only obtained under prescription from a registered doctor / Physician. It can be only be obtained from board registered chemists or from wholesaler dealers.
All registered chemists / Pharmacies must display PPB Authorization code at all times

Clinical | Pharmacokinetic data


Pregnancy Category: C
Routes of Administration: Inhalation (smoking), insufflation (snorting), by mouth (PO), rectal, subcutaneous (SC), intramuscular (IM), intravenous (IV), epidural, and intrathecal (IT)
Bioavailability: 20–40% (by mouth), 36–71% (rectally),100% (IV/IM)
Protein Binding: 30–40%
Metabolosim: Hepatic 90%
Onset of Action: 5 minutes (IV), 15 minutes (IM),20 minutes (PO)
Elimination Half life: 2–3 hours
Excretion: Renal 90%, biliary 10

Legal Status | Dosage forms & Strengths


Prescription Category:
Prescription only Medicine (POM) , ℞-only
Narcotic Drugs and Psychotropic Substances (Control ) Act Schedule:
Schedule 1 ,Narcotic Drugs and Psychotropic Substances (Control ) Act
Dosage Forms | Strengths:
Tablets : 10mg , 30mg | Injectable 10mg/ml, 1ml

Drug Indentifiers:

CAS Number
  • 57-27-2 
    64-31-3 (neutral sulfate),
    52-26-6 (hydrochloride)
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard


Drug Images

References/ Citation:




What was the patient being treated for
%d bloggers like this: