Morphine Indications/Morphine is an opiate alkaloid isolated from the plant Papaver somniferum and produced synthetically. Morphine binds to and activates specific opiate receptors (delta, mu, and kappa), each of which are involved in controlling different brain functions. In the central nervous and gastrointestinal systems, this agent exhibits widespread effects including analgesia, anxiolysis, euphoria, sedation, respiratory depression, and gastrointestinal system smooth muscle contraction. (NCI04).
Morphine is one of the natural plant alkaloids found in opium and is the prototype opiate, against which other derivatives are measured in terms of analgesic effects and side effects. Morphine has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.
Mechanism of Action of Morphine
It is important to consider that about 85% of the effect observed by morphine administration is due to the activity of morphine-6-glucuronide. Morphine and its metabolites act as agonists of the mu and the kappa opioid receptors which derive later into analgesia. The mu-opioid receptor is a key part of the effect of morphine in the ventral tegmental area which reinforces the effects of morphine. However, in studies with delta-opioid receptor knock-out mice, it was reported a reduction in the rewarding effect of morphine suggesting that the rewarding effect of morphine is related to activity towards the delta-opioid receptor in the nucleus accumbens. From the three target receptors of morphine, the mu receptor is associated with the side effects of the morphine such as modifications in the respiratory system and addiction.
Drug Indications of Morphine
- Chronic Pain
- Neonatal Abstinence Syndrome
- Opioids, including morphine, can manage pain effectively when used for a short amount of time. The use of opioids for longer periods needs to be monitored as they can develop a physical dependence, addiction disorder, and drug abuse.
- Morphine is used for the management of chronic moderate-to-severe pain. Opioids, including morphine, can manage pain effectively when used for a short amount of time. The use of opioids for longer periods needs to be monitored as they can develop a physical dependence, addiction disorder, and drug abuse.
- Morphine sulfate is strong analgesia used to relieve severe, acute pain or moderate to severe, chronic pain (e.g, in terminally ill patients). The drug is also used parenterally as a supplement for analgesia during labor.
- Chronic epidural or intrathecal administration of highly concentrated injections (i.e., Infumorph) via continuous, controlled microinfusion for the management of chronic intractable pain has been designated an orphan use by the US FDA.
- Morphine is the drug of choice in relieving the pain of myocardial infarction.
- Morphine is used in patients with acute pulmonary edema for its cardiovascular effects and to allay anxiety. Morphine should not be used in the treatment of pulmonary edema resulting from a chemical respiratory irritant.
- Analgesic (narcotic), anesthetic, antitussive, antiperistaltic.
- Morphine sulfate in controlled-release tablet form is an oral preparation being used for the relief of chronic severe pain, such as that related to cancer. A patient with adenocarcinoma of the prostate with bone metastases experienced dyspnea possibly related to the ingestion of these tablets. Discontinuing the drug quickly resulted in the disappearance of the dyspnea. The respiratory effects of morphine and the particular risks posed to the elderly patient are discussed.
Contra Indication of Morphine
- Respiratory depression when appropriate equipment is not available
- Although it has previously been thought that morphine was contraindicated in acute pancreatitis, a review of the literature shows no evidence for this
- Systemic mastocytosis
- Untreated decreased level of thyroid hormones
- Decreased function of the adrenal gland
- Alcohol intoxication
- Drug abuse
- Abnormally low blood pressure
- Asthma Attack
- Decreased lung function
- Stomach or intestine blockage
- Constipation
- Severe liver disease
- Biliary and gallbladder problem
- Acute inflammation of the pancreas
- Severe renal impairment
- Seizures
- Shock
- Weakened Patient
- High pressure within the skull
- Chronic obstructive lung disease
- History of opioid overdose
- Paralysis of the intestines
- General Ill Health and Malnutrition
- Allergies to Opioids – Morphine Analogues and Tramadol
Dosage of Morphine
Strengths – 15 mg/mL; 10 mg; 15 mg; 30 mg; 2 mg/mL; 4 mg/mL; 8 mg/mL; 10 mg/mL; 20 mg/12 to 24 hr
Pain
Immediate-release (IR)
- IR tablets: Initial dose: 15 to 30 mg orally every 4 hours as needed to manage pain
- IR oral solution: Initial dose: 10 to 20 mg orally every 4 hours as needed to manage pain
Chronic Pain
Immediate-release (IR)
- IR tablets: Initial dose – 15 to 30 mg orally every 4 hours
- IR oral solutions: Initial dose – 10 to 20 mg orally every 4 hours.
Extended-release (ER)
- ER Tablets (OPIOID-NAIVE and OPIOID NON-TOLERANT): Initial dose: 15 mg orally every 8 or 12 hours
- ER Capsules (OPIOID NAIVE): Begin treatment with an immediate-release morphine
- ER Capsules (OPIOID NON-TOLERANT): Initial dose: 30 mg orally every 24 hours.
Pediatric Dose for Pain
Less than 6 months (not mechanically ventilated)
- Initial dose: 0.025 to 0.03 mg/kg IV or 0.075 to 0.09 mg/kg orally every 4 to 6 hours as needed to manage pain
6 months or older; weight less than 45 kg: 0.1 mg/kg IV or 0.3 mg/kg orally every 4 to 6 hours as needed to manage pain
6 months or older; weight 45 kg or more: - Immediate-release tablets: Initial dose: 15 to 30 mg orally every 4 hours as needed to manage pain
- Immediate-release oral solution: Initial dose: 10 to 20 mg orally every 4 hours as needed to manage pain
Side Effects of Morphine
More Common
- dizziness, lightheadedness, or feeling faint
- drowsiness
- dry mouth
- headache
- Cramps
- difficulty having a bowel movement
- drowsiness
- false or unusual sense of well-being
- the relaxed and calm feeling
- sleepiness or unusual drowsiness
- weight loss
- heartburn or indigestion
- loss in sexual ability, desire, drive, or performance
- muscle stiffness or tightness
- night blindness
Common
- Blurred vision
- bulging soft spot on the head of an infant
- burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
- change in the ability to see colors, especially blue or yellow
- chest pain or discomfort
- confusion
- cough
- decreased urination
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- fainting
- fast, pounding, or irregular heartbeat or pulse
- headache
- hives, itching, or skin rash
- increased sweating
- loss of appetite
- nausea
Rare Common
- Constricted, pinpoint, or small pupils (black part of the eye)
- decreased awareness or responsiveness
- extreme drowsiness
- fever
- increased blood pressure
- increased thirst
- lower back or side pain
- muscle cramps, spasms, pain, or stiffness
- no muscle tone or movement
- severe sleepiness
- swelling of the face, fingers, or lower legs
- weight gain
Drug Interactions
Morphine may interact with following drugs, supplements, & may change the efficacy of the drug
- abiraterone acetate
- alcohol
- amphetamines (e.g., dextroamphetamine, lisdexamfetamine)
- antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- atorvastatin
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- belladonna
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-blockers (e.g., atenolol, metoprolol, propranolol)
- buprenorphine
- cimetidine
- clopidogrel
- crizotinib
- cyclosporine (systemic)
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- droperidol
- general anesthetics (medications used to put people to sleep before surgery)
- glycopyrrolate
- grapefruit juice
- ipratropium
- ketotifen
- mirtazapine
- monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, procarbazine, tranylcypromine) taken within the past 14 days
- muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine)
- naltrexone
- nilotinib
- other narcotic analgesics (e.g., codeine, fentanyl, meperidine, oxymorphone)
- prazosin
- progesterone
- St. John’s wort
- seizure medications (e.g., clobazam, ethosuximide, felbamate, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- sunitinib
- tacrolimus
- tamoxifen
- tapentadol
- tolterodine
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- warfarin
- verapamil
Pregnancy Category
FDA Pregnancy Category – C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Breast-feeding
This medication passes into breast milk. If you are a breast-feeding mother and are taking morphine sustained release, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. Accidental ingestion of this medication by children may lead to severe and even fatal consequences. Keep this medication out of the reach of children.
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