OPTION D – Medicinal Chemistry D.3 - Opiates Jan 3, 2010

Strong Analgesics Opiates are strong analgesics that temporarily bind to the opioid receptors in the brain preventing the transition of pain impulses. The physiological effect of the opiates strongly depends on their ability to cross the so-called blood-brain barrier: a series of lipophilic cell membranes that coat the blood vessels in the brain and prevent polar molecules from entering the central nervous system (CNS).

Opiates The primary active ingredient in opium, morphine, belongs to the group of alkaloids: - naturally occurring compounds containing basic nitrogen atoms. Opiate - a natural or synthetic drug that exerts actions on the body similar to those induced by morphine. Narcotic – in addition to their analgesic effects, larger doses of opiates can cause a strong feeling of euphoria, provide relief from all kinds of distress, and stimulate sociability. As a result, they have a very high potential for misuse, which often leads to drug addiction.

Morphine, Heroin and Codeine Morphine - the principal alkaloid and makes up about 10% by mass of raw opium, obtained by extraction and crystallization. It is a white, bitter, crystalline alkaloid (C17H19NO3•H2O) narcotic and addictive. It is used chiefly as a pain reliever and sedative.

Morphine, Heroin and Codeine Codeine - makes up about 0.5% by mass of raw opium. It is a white, crystalline, slightly bitter alkaloid (C18H21NO3). It readily crosses the blood-brain barrier, but does not bind to the opioid receptor because of the steric effect fo the ester group. Used chiefly as an analgesic or sedative, and as a cough suppressant.

Morphine, Heroin and Codeine Heroin (diamorphine) is usually synthesized from morphine and thus is a semi-synthetic drug and it is obtained by relatively simple structural modification of morphine or codeine. It is a white, crystalline, narcotic powder (C21H23NO5) derived from morphine, formerly used as an analgesic and sedative: manufacture and importation of heroin are now controlled by federal law in the U.S. because of the danger of addiction. Similar to codeine, diamorphine is soluble in lipids and can easily cross the blood-brain barrier. In the brain diamorphine is quickly metabolized into morphine, which binds to the opioid receptor. This mechanism makes it five times more potent as an analgesic than morphine.

Opium plant Morphine

Opiate Advantages/Disadvantages Pharmacological effects: Opiates exert major effects on: The central nervous system. The eye The gastrointestinal tract (the digestive system) The prime medical uses of opiates are: As strong analgesic in the relief of severe pain caused by injury and chronic disease. In the treatment of diarrhea by producing a constipating effect. To relieve coughing by suppressing the “cough centre” situated in the brain system.

Opiate Advantages/Disadvantages Physiological effects of opiates: Opiates produce: Analgesia Drowsiness Mood changes Some individuals experience: Anxiety Fear Lethargy Sedation Lack of concern Inability to concentrate

Tolerance Over time and with regular use, the user requires larger dose of the drug to achieve the effect originally obtained by smaller dose Increase of hazards (larger amounts) No tolerance to side effects If drug not taken for long time > decrease of tolerance > overdose Jan 3, 2010

Tolerance Tolerance appears due to the induction of drug metabolizing enzymes in the liver and also to the adaptation of neurons in the brain to the presence of the drug. Users that become tolerant to one opiate will also exhibit a tolerance to all other opiates.

Dependence Physical dependence is the state in which people do not function properly without a drug. Symptoms: Restlessness Sweating Fever Chills Vomiting Increase rate of respiration Cramping Diarrhea Unbearable aches

Dependence Depends on: The dose Frequency of drug administration The duration of the drug dependence The opiate used

Opiates (in general) Extremely potent and valuable drugs for the treatment of pain Have the capacity of inducing a state of euphoria and relief from physiological pain Induce profound tolerance and physiological dependence Important both medically and sociologically as the user is difficult to treat and must frequently resort to crime to support the habit and reach a source of supply.

Summary of the Effects of Opiates Short-term Effects Sedation and stupor Euphoria Reduced tension, worry and fear Reduced coughing reflex Occasional death from overdose Long-term Effects Loss of appetite Sterility Withdrawal illness, loss of job, crime Diversion of energy and money Risk of dangerous infections due to shared needles.

Homework Answer the questions at the end of the section, page 736. Read Section D.4 – pH Regulation of the Stomach Jan 3, 2010