Medical Pharmacology Topics
| Preliminary Outline |
Opioids |
Addiction is a behavioral pattern of compulsive drug use, characterized by an overwhelming involvement with drug use and a high relapse tendency. Behavioral tolerance to a drug may develop, when there is a learned behavior modifying response that mimics a decreased drug effect (for example, alcoholics learning to walk straight).
Physiological dependence is a state of latent hyperexcitability which develops in cells following frequent exposure to drugs. A physiological abstinence syndrome may persist for months or ears after drug use has stopped. Psychological dependence is the strong desire to achieve pleasure and avoid dysphoria. In some cases withdrawal of drug does not result in physiological symptoms but psychological, mostly drug seeking behavior
There are five major categories of drugs self-administered by people for recreation: opioids, CNS depressants, CNS stimulants, hallucinogens and inhalants. The only commonality between these drugs is the psychological reinforcement resulting from the euphoric experience.
Opioid
Opioids are abuse for their euphoric and sedative effects. Agents of abuse include opium, heroin, morphine, methadone, meperidine, codeine, propoxyphene, pentazocine and hydromorphine. They are usually injected or smoked, and result in a warm, flushing, comforting sensation. Initial administration may result in emesis. Tolerance develops to euphoric feelings and most side effects. There is a high recidivism rate (85%).
Opioid use may be recreational or build into chronic dependence A person can be dependent and still function well. Strong psychological and physiological dependence develops and users may stay dependent because they crave the drug, no just to avoid abstinence symptoms. The abstinence syndrome is not as severe as with other CNS depressants and the severity depends on drug use history. Withdrawal symptoms differ with time:
Medical problems associated with opioid abuse include acute overdose, chronic overdose, abstinence syndrome and pregnancy complications. Acute overdose is characterized by respiratory depression and cardiovascular collapse, and is treated with naloxone. Chronic overdose is treated with supportive therapy since naloxone may precipitate abstinence symptoms. The abstinence syndrome are treated with long term detoxification using methadone to prevent withdrawal symptoms and clonidine to treat autonomic symptoms.
CNS Depressants
The CNS depressants include alcohol, barbiturates, benzodiazepines, non-barbiturate sedatives and methagualone. They are abused for relaxation, anti-anxiety, euphoria, and sometimes the initial rush. Intoxicated individuals are sluggish, have difficulty thinking, have impaired memory, slow speech, etc.
Tolerance develops to the euphoric and sedative actions of CNS depressants. Metabolic tolerance may also develop. Little tolerance develops to the lethal effects. The will be synergistic effects with different agents, and cross tolerance and cross dependence also occurs.
Psychological and physiological dependence develops to CNS depressants. Withdrawal from CNS depressants may be life threatening, usually due to convulsions, exhaustion and cardiovascular collapse. This may be prevented by attaining a maintenance dose and reducing it slowly.
For a short acting drug like pentobarbital, restlessness, tremors, weakness, nausea, cramping and vomiting will be seen in 12-16 hours. At 24 hours, the patient will be too weak to get up, have a coarse tremor, be hyper-reflexic and ha purposely behavior The peak symptoms occur 2-3 days after withdrawal, and convulsions may occur. After 4 days, delirium, hallucinations, exhaustion, cardiovascular collapse and hyperthermia are often seen.
Alcohol withdrawal is similar in sequence but shorter in time course. Tremor will be present during the first few hours. Seizures are likely in the first 24 hours. Symptoms reach a maximum in 24-48 hours.
Benzodiazepine overdose can be treated with flumazenil. Alcoholism may be treated with disulfuram, an aldehyde dehydrogenase blocker, and naltrexone.
CNS Stimulants
The CNS stimulants include amphetamine, methanphetamine, cocaine, methylphenidate (Ritalin™), Phenmetracine, and weaker stimulants like caffeine and nicotine. They are abused for the euphoria, exhilaration, decrease fatigue, confidence and feeling of heightened abilities. The user appear exited, has rapid speech, cannot sit still, may be confused, paranoid, irritable, and have dilated pupils. Wit chronic use there is an increase in paranoia and psychosis. The effects of cocaine and amphetamine are similar except cocaine has a shorter duration of action and is initially more intense.
The CNS stimulants also stimulate the cardiovascular system with potential for severe toxicity, including arrhythmias and hypertension.
Tolerance to the effects of CNS stimulants may develop. There is strong psychological dependence and little physical dependence. Withdrawal produces REM rebound (?), and depressive reaction with possibility of suicide. There is a high recidivism rate. Replacement therapy is available for nicotine.
Other problems associated with CNS stimulants are plastic poisoning, nasal septal ulceration or perforation, and eye damage. A chronic user or someone in an "amphetamine run" will develop temporary psychosis, violent and paranoid behavior, exhaustion and convulsions.
Hallucinogens
The hallucinogens include lysergic acid dethylamine (LSD), mescaline, psylocybin (mushroom), dimthoxymethylamphetamine (DOM, STP), methylenedioxymethamphetamin (MDMA, ecstasy), phencyclidine (angel dust), and tetrahydrocannabinol (marijuana). These drugs alter the senses and produce hallucinations when taken in sufficient doses. They are abused for the feelings of "oness with the universe", unique experiences, altered reality, distortion of space and time, and great sense of purpose.
Tolerance develops to the actions of hallucinogens. They produce strong psychological dependence, but little physiological dependence.
LSD is highly potent, just 25-50 mg causes hallucinations, mood changes, sensory disturbances, distortion of body image, and transcendental feelings. Side effects include mydriasis, tachycardia, increased blood pressure, hypereflexia, weakness, nausea, piloerection, hyperthermia and paresthesias. CNS side effects include depersonalization, panic reactions, acute paranoia, depression, suicide, flashback and "bad trip".
Tetrahydrocannabinol is the active ingredient in marijuana. It can product tachycardia, hypertension followed by hypotension, reddening of the conjunctiva (vasodilation), sedation, impaired memory and motor skills, and decreased task-oriented behavior At high doses it induces visual hallucinations, anxiety reactions and altered memory storage. The cannabinoid receptor has been isolated, as well as an endogenous ligand (anandamide).
Tolerance develops to the euphoria from tetrahydrocannabinol. There is a strong psychological dependence and minor abstinence symptoms like restlessness, weight loss, irritability, tremor, hyperthermia and insomnia. Chronic use leads to apathy, impaired memory and judgment, asthma and bronchitis.
Pheniclidine (PCP, angel dust) was originally produced as a dissociative anesthetic (i.e. a long lasting ketamide). It is abused for euphoria, sense of power, strength, invulnerability, depersonalization, and distortion of distance and body image. At low doses, there is a subjective sense of intoxication, numbness, slurred speech, nystagmus, sweating, gait disturbances and unprovoked aggression. At large doses there is analgesia, stupor, delirium, hallucinations, psychosis and coma. PCP psychosis may occur temporally distant from drug use and may require prolonged hospitalization. It will mimic schizophrenia and may be precipitated by re-exposure to the drug.
At low level overdose, the patient will be conscious and displaying violent or self destructive behavior At a moderate dose, the patient will be conscious but breathing normally. In a severe overdose the patient will have seizures or go into coma, and the airway will be compromised. Overdose symptoms hat may last for 72-96 hours include hypertensive crisis, hyperthermia and psychosis.
Inhalants
The inhalants include toluene (glue), kerosene, gasoline, nitrous oxide and aerosol propellant. They are abused for the euphoria, especially by young people that cannot get other drugs. They are highly toxic to the liver, kidney and brain. Anoxia may occur during administration, and death is usually due to asphyxiation.
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Opium