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Morphine Indications, Contraindications, Warning

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.

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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

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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

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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.