Morphine

Morphine is a powerful analgesic drug that is considered the standard for narcotic painkillers. Morphine, derived from opium, is typically used to treat severe or chronic pain and is often abused because of the strong feelings of euphoria it produces.

Description and Uses
Morphine, a narcotic analgesic, is used to treat moderate to severe pain, particularly chronic pain. Morphine also causes drowsiness and feelings of euphoria. Due to its addictive nature, morphine should only be taken as directed by a medical doctor. Commonly administered as morphine sulfate or morphine hydrochloride, morphine is available in a wide variety of forms. It can be taken in pill or tablet form, in liquid form, as a rectal suppository, or with an IV or hypodermic needles.

First used in the early 1800s, morphine remains a widely used painkiller. The U.S. Drug Enforcement Agency recognizes morphine as the standard for measuring the potency of other analgesic drugs. For example, morphine is half as strong as heroin but has twelve times the potency of codeine. Morphine is most commonly used to treat severe pain and may be administered before and after surgeries. It is also used to treat long-term or chronic pain, such as in cancer patients. It may also be used as a cough suppressant.

Brand names of morphine include Avinza, Kadian, MS Contin, MSIR, Oramorph SR, Roxanol, Roxanol-T, Astramorph, DepoDur, Duramorph.

How Morphine Works
Morphine acts on the central nervous system by binding to opioid receptors. It binds primarily to the mu-receptors in the thalamic, hypothalamic, and amygdalar regions of the brain, the nucleus caudatus, the putamen, and certain cortical areas, as well as the periaqueductal grey area of the brain, the substantia gelatinosa region of the spinal cord, and the spinal nucleus of the trigeminal nerve. It can also bind to kappa and delta-type opioid receptors.

In the brain, morphine works by altering the body's perception of pain. It binds to mu-receptors in the brain and keeps them from receiving pain signals. When morphine binds to and activates the mu-receptors, it also causes sedation, euphoria, physical dependence, and respiratory depression. Morphine binds to the mu-receptors at the same sites that endorphins and dynorphins usually do. Endorphins and dynorphins are responsible for relieving pain or anxiety when a person is injures, and since morphine can bind to the mu-receptors in much greater quantities than endorphins normally do, it creates feelings of euphoria. Morphine also attaches to GABA inhibitory interneurons that control the inhibition of pain. The morphine also binds to the descending pain inhibitory pathway in the spinal cord, where it inhibits the release of neurotransmitters in the opioid receptors. This decreases the amount of pain stimuli that reach the brain from the body. Morphine can bind to the opioid receptors because it has the same B-phenylthylamine unit that endorphins have. LSD and many other hallucinogens also possess this unit and can bind to the same sites.

Morphine affects the respiratory center of the brain as well. It makes the brain less responsive to changes in carbon dioxide levels in the bloodstream, causing respiratory depression. Morphine also often causes vomiting because it stimulates the vomiting center, causing 40 percent of patients to feel nauseous. Morphine also affects the intestinal tract by making the smooth muscles perform peristalsis more slowly, meaning that the food moves more slowly through the digestive tract. More water is removed from the feces the longer they remain in the intestines, resulting in very solid feces and constipation.

Chemical Structure
The morphine molecule has five rings, with two of them at right angles to the other three, and a methyl group bonded to a nitrogen atom. In its chemical structure, morphine shares several common characteristics with other opioids. According to the "morphine rule", most opioid painkillers have an aromatic ring attached to a quaternary carbon atom which is attached to a tertiary amine by two carbon atoms. Morphine, codeine, and heroin all follow this morphine rule and have very similar structures. The morphine rule is necessary for the molecules to be effective analgesics, but many researchers have attempted to develop similar drugs based on this rule that do not have the addictive properties of morphine and the other opiates.

The morphine rule becomes important when morphine binds to the opioid receptors in the central nervous system. The flat aromatic ring, the two carbon atoms, and the tertiary nitrogen atom fit perfectly into the mu-receptors. When they attach to the receptors, the morphine molecules decrease the cells' affinity to attract Na+ ions. This subsequently decreases the amount of neurotransmitters that these cells release.

Morphine in its pure form is barely soluble in water; only one gram of morphine will dissolve in five liters of water. To make morphine easier to administer intravenously, morphine is combined with sulfate or hydrochloride salts, which makes it around 300 times more soluble. This also changes the pH. Morphine on its own has a pH of 8.5, but when it reacts with the sulfate or hydrochloride salts, the resulting compounds are weak acids around pH 5. Pharmaceutical companies then mix the morphine with NaOH so that it can be injected safely.

History of Morphine
Freidrich Wilhelm Adam Serturner (1783-1841), a German pharmacist's assistant, first derived morphine from opium in 1803. Morphine, like opium, comes from the opium poppy (Papaver somniferum). Specifically, it comes from the milky sap produced by the mature buds of these poppies. After several experiments, Serturner isolated an organic alkaloid from this sap and found that this alkaloid was ten times more powerful than opium itself. He named this new substance morphine after Morpheus, the Greek god of dreams, due to morphine's ability to induce sleep. Sertürner and Company first marketed morphine to the public in 1817.

Morphine became more commonly used in the medical community after French physician Francois Magendie published a paper in 1818 describing the use of morphine to treat pain in a young girl and help her sleep. Interestingly, morphine was often used at first to cure opium addictions as well as alcohol addictions, because doctors at the time considered morphine less harmful than alcohol. The drug gained increasing popularity in the 1920s, and it became even more widely used after the invention of the hypodermic needle in 1853. During the Civil War, morphine was widely used to relieve pain in soldiers who were injured or had to undergo surgery. This led to roughly 400,000 soldiers who came home with "soldier's disease" (morphine addiction). Morphine was also used to treat soldiers in the European Franco-Prussian War and many other wars. Today, soldiers still carry morphine with them in case of being severely injured.

During the 1800s, morphine was frequently mixed with ethyl alcohol to produce laudanum, an inexpensive drug that was considered a cure for nearly all ailments. It was not until the 1870s that many physicians began to realize the addictive qualities of morphine and the extent of its damaging effects on the body.

In 1874, heroin was synthesized from morphine. The Bayer company, a pharmaceutical company, attempted to develop a non-addictive painkiller based on the structure of morphine. Instead, however, their experiments led to the creation of heroin. Heroin became an extremely popular drug and was initially used to cure morphine addictions, just as morphine had been used to cure opium addictions. Until the invention of heroin, morphine was more abused than any other narcotic painkiller.

Morphine retained its popularity even after many countries passed laws requiring strict regulation and labeling of medicines. In the United States, Congress passed the Harrison Narcotics Act (1914), which forbid the possession of narcotics such as morphine without a valid doctor's prescription.

In 1924, Robert Robinson uncovered the chemical structure of morphine. This led to research in developing compounds similar to morphine that were not as addictive, and since the 19th century over 200 new analgesics of varying potency and addictiveness have been synthesized. Several antagonists have also been developed that can be used to treat people with morphine addiction, including naloxone (Narcan), naltrexone (Trexan), and nalorphine (Nalline). Methods of creating morphine synthetically were also developed, although it is still primarily obtained through processing the opium poppy. In 1952, Dr. Marshall D. Gates, Jr., patented a method for creating morphine from coal tar and petroleum distillates.

Today, morphine is listed as a Schedule II drug in the United States according to the Controlled Substances Act. The United Kingdom passed the Misuse of Drugs Act in 1971, which lists morphine as a Class A drug, and in 1989 Australia designated morphine as a Schedule 8 drug under the Therapeutic Goods Act. The International Single Convention on Narcotic Drugs named morphine a Schedule 1 drug.

Morphine Addiction
Although morphine can be used for medical purposes, many people abuse morphine as well. Abuse includes using morphine more often or in larger amounts than prescribed by a doctor, or using morphine solely for the euphoric effects. This can be very harmful to the body and often leads to addiction. Morphine causes physical and psychological dependence by stimulating the reward center in the brain. It produces high levels of euphoria, and the brain begins to crave the pleasurable sensations, causing people to crave the drug. Signs of morphine addiction may include abnormal sweating, an unusual sense of happiness or well-being, involuntary eye movement or twitching, hallucinations, and needle marks.

Morphine is extremely addictive and creates high levels of tolerance in patients, meaning that after a while it takes much more morphine to achieve the same effects. People who abuse morphine to get high must continually increase their dosage as they build up tolerance to the drug. Addicts might end up taking 5 grams of morphine a day or more because they have built up such a high tolerance--this dose would kill a normal person. Normal doses of morphine range from 50 to 80 milligrams per day. Morphine can cause mild addiction in as little as one to two weeks, and will result in stronger addiction if taken for a longer period of time.

People often try to illegally obtain morphine by increasing their prescription, doctor or pharmacy shopping (obtaining prescriptions from more than one place to obtain extra morphine), or getting illegal prescriptions. Street names for morphine include M, Number 13, white nurse, cube juice, monkey dust, white lady, Miss Emma or Aunt Emma, salt, sugar, Mister Blue, morpho, dreamer, and God's drug. Typically, illicit morphine is taken as an oral liquid, injected using needles, smoked or snorted as a powder, or mixed with alcohol, cocaine, or some other substance to make it more powerful. Morphine powder is sometimes obtained by breaking open extended-release tablets or grinding up morphine pills. Although morphine is popular where readily available, it is not commonly found on the street. Heroin is usually preferred to morphine, and produces nearly identical effects unless injected, in which case it acts much more quickly than morphine. Heroin, being more fat-soluble than morphine, can be absorbed more quickly by the body to produce more immediate feelings of euphoria. Heroin is also twice as potent as morphine and is preferred in the illegal drug trade because it is easier to produce.

The best way to overcome a morphine addiction is by going to a drug rehabilitation center, where both the physical and psychological addictions can be treated. Morphine withdrawal can have serious and potentially life-threatening side effects. Going to a rehab center can help avoid any complications and protect the patient against overdose, health problems, and relapses. Drug rehab centers typically offer both short-term and long-term treatment options, and may provide either psychological treatment or physical treatment through morphine detox, although most places offer comprehensive treatment. Medications may be used to help with the pain of morphine withdrawal, such as methadone, buprenorphine, and naltrexone

Side Effects and Withdrawal
Common side effects of morphine include:
 * constipation
 * nausea or vomiting
 * dizziness or lightheadedness
 * drowsiness
 * headache
 * sweating
 * anxiety/restlessness
 * dependence/addiction
 * falling/unsteadiness
 * mood or behavior changes
 * confusion
 * hypotension (low blood pressure)
 * abnormal dreams
 * anemia
 * back pain
 * changes in taste or loss of appetite
 * chills
 * diarrhea and cramps
 * dry mouth
 * dry skin
 * flushed face
 * fever
 * fluid retention
 * hiccups
 * hypertension (high blood pressure)
 * indigestion or heartburn
 * insomnia
 * skipped menstrual periods
 * erectile dysfunction, decreased sex drive, or abnormal ejaculation
 * stiff or shaky muscles
 * thirst
 * voice changes
 * weakness
 * weight loss
 * difficulty passing urine
 * memory loss
 * pinpoint pupils
 * depression
 * irritability

Contact your doctor if the above side effects become severe, or if you have any of the more serious side effects below, including:
 * respiratory depression or irregular breathing
 * blue or purple tint to the skin
 * heart palpitations
 * seizures
 * hallucinations
 * blurred or double vision
 * slow heart rate (bradycardia)
 * fainting
 * signs of an allergic reaction, including rashes, hives, itching, swelling of the mouth or throat, and wheezing or difficulty breathing
 * tightness in throat or difficulty swallowing
 * swelling of the arms, hands, feet, ankles, or lower legs

Contact a doctor immediately if you think you may have overdosed on morphine. Symptoms of overdose may include:
 * drowsiness
 * pinpoint pupils
 * confusion
 * cold or clammy skin
 * weak pulse
 * shallow breathing
 * fainting
 * nausea
 * blurred vision
 * limp muscles
 * loss of consciousness
 * breathing that stops

Morphine creates dependence when taken over long periods of time, and patients can go into withdrawal if they suddenly stop taking it. According the U.S. National Institute of Health, morphine changes the size and shape of the receptors in the brain, which increases dependence. Symptoms of withdrawal can be mild or severe, and may even cause death in extreme cases. Usually, withdrawal causes flu-like symptoms and a craving for more morphine and the euphoria it causes.

Warning
Morphine can be extremely addictive and may have serious short and long-term side effects. It should never be taken except as prescribed by a medical doctor. Morphine should not be taken during pregnancy because it can cross the placental barrier and may cause respiratory depression, addiction in the baby, and higher risk of complications during birth. Morphine should never be given to children as it may have serious mental and physical effects, and it may also have negative effects on the elderly. Morphine should not be taken with alcohol, as this may cause serious and potentially life-threatening side effects. People who experience allergic reactions to other narcotic medications should not take morphine. Ask a doctor before taking morphine if you have:
 * drug allergies
 * asthma, COPD, sleep apnea, or other breathing disorders
 * liver or kidney disease
 * underactive thyroid
 * curvature of the spine
 * head injury or brain tumor
 * epilepsy or other seizure disorder
 * low blood pressure
 * gallbladder disease
 * Addison's disease or other adrenal gland disorder
 * enlarged prostrate or urination problems
 * mental illness
 * history of drug or alcohol addiction
 * central nervous system depression
 * fever
 * recent gastrointestinal surgery
 * pulmonary disease

Morphine may cause unsteadiness, weakness, and dizziness and impairs balance and coordination. People taking morphine should not operate heavy machinery or any other type of equipment.

Ask a doctor before taking morphine in combination with other medications. Medications such as pentazocine (Talwin), nalbuphine (Nubain), butorphanol (Stadol), or buprenorphine (Buprenex, Subutex), or MAO inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) may interact with morphine. Consult a doctor before taking morphine while on these medications.

This is not a complete list, and other drugs and conditions may interact with morphine as well.