Chemical formula: C₁₇H₁₉NO₃ Molecular mass: 285.338 g/mol PubChem compound: 5288826
Morphine interacts in the following cases:
The sedative effects of morphine (opioid analgesics) are enhanced when used with depressants of the central nervous system such as hypnotics, anxiolytics, tricyclic antidepressants and sedating antihistamines.
A reduction in dosage of morphine should be considered in hepatic impairment.
Enhanced sedative and hypertensive effects of alcohol in coadministration with morphine.
The dosage of morphine should be reduced in moderate to severe renal impairment.
Morphine may reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
There is possible enhanced sedative and hypotensive effect in coadministration of morphine with antipsychotics.
The analgesic effect of opioids tends to be enhanced by co-administration of dexamfetamine, and hydroxyzine.
Medicinal products that block the action of acetylcholine, for example anti-histamines, anti-parkinsonian agents and anti-emetics, may interact with morphine sulphate to potentiate anti-cholinergic adverse events.
Effects of morphine exposure on sexual maturation of male rats, their reproductive capacity and the development of their progeny have been examined. Results indicated that exposure during adolescence led to pronounced inhibition of several indices of sexual maturation (e.g. hormone levels, reduced gonad weights), smaller litters and selective gender specific effects on endocrine function in the offspring.
Animal studies have shown that morphine may reduce fertility.
A disruption in ovulation and amenorrhoea can occur in women given morphine.
Agents such as atropine antagonise morphine-induced respiratory depression and can partially reverse biliary spasm but are additive to the gastrointestinal and urinary tract effects. Consequently, severe constipation and urinary retention may occur during intensive antimuscarinic analgesic therapy.
Cimetidine inhibits the metabolism of morphine.
The opioid analgesic papaveretum has been shown to reduce plasma ciprofloxacin concentration. The manufacturer of ciprofloxacin advises that premedication with opioid analgesics be avoided.
Concurrent use of morphine and loperamide or kaolin may increase the risk of severe constipation.
There may be antagonism of the gastrointestinal effects of metoclopramide and domperidone in coadministration with morphine.
There may be delayed absorption of mexiletine in coadministration with morphine.
Propranolol has been reported to enhance the lethality of toxic doses of opioids in animals, although the significance of this finding is not known for man. Caution should be exercised when these drugs are administered concurrently.
Plasma concentrations of morphine sulphate may be reduced by rifampicin.
Although there are no pharmacokinetic data available for concomitant use of ritonavir with morphine sulphate, ritonavir induces the hepatic enzymes responsible for the glucuronidation of morphine sulphate, and may possibly decrease plasma concentrations of morphine sulphate.
Opioids such as morphine should either be avoided in patients with biliary disorders or they should be given with an antispasmodic.
Morphine can cause an increase in intrabiliary pressure as a result of effects on the sphincter of Oddi. Therefore, in patients with biliary tract disorders morphine may exacerbate pain (use in biliary colic is a contraindication). In patients given morphine after cholecystectomy, biliary pain has been induced.
Repeated use can cause tolerance and dependence. Caution in use of morphine should be exercised and a reduction in dose may be advisable in the elderly and in the following cases:
Repeated use can cause tolerance and dependence. Caution in use of morphine should be exercised and a reduction in dose may be advisable in the elderly and in the following cases:
Morphine should only be used when benefit is known to outweigh risk.
As with all drugs it is not advisable to administer morphine during pregnancy.
Morphine crosses the placental barrier. Administration during labour may cause respiratory depression in the new born infant and gastric stasis during labour, increasing the risk of inhalation pneumonia. Therefore, it is not advisable to administer morphine during labour.
Babies born to opioid-dependent mothers may suffer withdrawal symptoms including CNS hyperirritability, gastrointestinal dysfunction, respiratory distress and vague autonomic symptoms including yawning, sneezing, mottling and fever.
Newborns whose mothers received opioid analgesics during pregnancy should be monitored for signs of neonatal withdrawal (abstinence) syndrome. Treatment may include an opioid and supportive care.
Administration to nursing mothers is not recommended as morphine is excreted in breast milk. Withdrawal symptoms may be observed in the new born of mothers undergoing chronic treatment.
While morphine can suppress lactation, the quantity from therapeutic doses that may reach the neonate via breast milk is probably insufficient to cause major problems of dependence or adverse effects.
Effects of morphine exposure on sexual maturation of male rats, their reproductive capacity and the development of their progeny have been examined. Results indicated that exposure during adolescence led to pronounced inhibition of several indices of sexual maturation (e.g. hormone levels, reduced gonad weights), smaller litters and selective gender specific effects on endocrine function in the offspring.
Animal studies have shown that morphine may reduce fertility.
A disruption in ovulation and amenorrhoea can occur in women given morphine.
Morphine causes drowsiness so patients should avoid driving or operating machinery. Morphine may modify the patient’s reactions to a varying extent depending on the dosage and susceptibility. If affected, patients should not drive or operate machinery.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
In normal doses, the most common side effects of morphine are nausea, vomiting, constipation, difficulty in micturition and drowsiness. With chronic therapy, nausea and vomiting are unusual with morphine tablets but should they occur the tablets can be readily combined with an anti-emetic if required. Constipation may be treated with appropriate laxatives.
A case of morphine induced thrombocytopenia has been reported.
Morphine has a depressant effect on gonadal hormone secretion which can result in a reduction of testosterone leading to regression of secondary sexual characteristics in men on long-term therapy.
Very Common (incidence ≥1/10), Common (incidence of ≥1%) and Uncommon (incidence of <1%) adverse drug reactions are listed below:
Uncommon: Allergic reaction
Frequency Unknown: Anaphylactic reaction, Anaphylactoid reaction
Common: Confusion, Insomnia
Uncommon: Agitation, Euphoria, Hallucinations, Mood altered
Frequency Unknown: Drug dependence, Dysphoria, Thinking disturbances restlessness
Common: Headache, Involuntary muscle contractions, Somnolence, Dizziness
Uncommon: Convulsions, Hypertonia, Myoclonus, Paraesthesia, Syncope
Frequency Unknown: Raised intracranial pressure, Coma, Hyperalgesia, hyperaesthesia/allodynia, Hyperhidrosis
Uncommon: Visual disturbance
Frequency Unknown: Miosis
Uncommon: Vertigo
Uncommon: Palpitations
Frequency Unknown: Bradycardia, Tachycardia
Uncommon: Facial flushing, Hypotension
Frequency Unknown: Circulatory failure, Hypertension
Uncommon: Bronchospasm, Pulmonary oedema, Respiratory depression
Frequency Unknown: Cough decreased
Very Common: Constipation, Nausea
Common: Abdominal pain, Anorexia, Vomiting
Uncommon: Dyspepsia, Ileus, Taste perversion
Frequency Unknown: Narcotic bowel syndrome, Dry mouth
Uncommon: Increased hepatic enzymes
Frequency Unknown: Exacerbation of pancreatitis, Biliary pain
Common: Hyperhidrosis, Rash
Uncommon: Urticaria
Uncommon: Urinary retention
Frequency Unknown: Ureteric spasm, Dysuria
Frequency Unknown: Amenorrhea, Decreased libido, Erectile dysfunction
Common: Asthenic conditions, Pruritus
Uncommon: Peripheral oedema
Frequency Unknown: Drug tolerance, Drug withdrawal (abstinence) syndrome, Hypothermia, Anxiety, Dysphoric mood
* Physical and psychological dependence may appear after administration of therapeutic doses for periods of 1 to 2 weeks. Some cases of dependence have been observed after only 2 to 3 days.
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.
Physiological withdrawal symptoms include: Body aches, tremors, restless legs syndrome, diarrhoea, abdominal colic, nausea, flu-like symptoms, tachycardia and mydriasis. Psychological symptoms include dysphoric mood, anxiety and irritability. In drug dependence, “drug craving” is often involved.
The most serious hazard of therapy is respiratory depression.
The commonest side-effects of morphine are:
Tolerance generally develops with long term use, but not to constipation.
Other side effects include the following:
Immune system disorders: Anaphylactic reactions following intravenous injection have been reported rarely.
Cardiac disorders: Bradycardia, Palpitations, Tachycardia, Orthostatic hypotension
Nervous system disorders: Myoclonus, Mental clouding, Confusion (with large doses), Hallucinations, Headache, Vertigo, Mood changes including dysphoria, Euphoria
Gastrointestinal disorders: Dry mouth, Biliary spasm
Eye disorders: Blurred or double vision or other changes in vision, Miosis
Reproductive system and breast disorders: Long term use may lead to a reversible decrease in libido or potency.
Skin and subcutaneous tissue disorders: Pruritus, Urticaria, Rash, Sweating, Contact dermatitis has been reported and pain and irritation may occur on injection, Facial flushing
Musculoskeletal and connective tissue disorders: Muscle rigidity
Renal and urinary disorders: Difficulty with micturition, Ureteric spasm, Urinary retention, Antidiuretic effect
Tolerance develops to the effects of opioids on the bladder.
The euphoric activity of morphine has led to its abuse and physical and psychological dependence may occur.
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