Drug abuse, drug addiction. OBJECTIVES Describe the major actions of drugs that are commonly abused and the likely mechanisms behind addiction. Understand the central role of dopamine in the central reward circuitry.
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Describe the major actions of drugs that are commonly abused and the likely mechanisms behind addiction.
Understand the central role of dopamine in the central reward circuitry.
Describe the major signs and symptoms of overdose with, and withdrawal from, CNS stimulants, opioid analgesics, and sedative-hypnotics, including ethanol.
Describe the general principles of the management of overdose of commonly abused drugs.
E.J. Nestler, Historical Review: Molecular and Cellular Mechanisms of Opiate and Cocaine Addiction, Trends Pharmacological Sciences 25, 210-218, 2004.
Trainspotting (1996) director Danny Boyle, from the Novel by Irving Welsh (available at Video Difference, Quinpool)
-Activation of reward system
b) Physiological -withdrawal
Dialysis tubing in blue
Steel tubing in black
Drugs exert addictive effects via specific receptors or neurotransmitters
Ecstasy is the name of a class of drugs that includes a large variety of derivatives of the amphetamine-related compound methylenedioxymethamphetamine (MDMA). Today, MDMA and its many derivatives are often produced in small quantities in ad hoc laboratories and distributed at parties or "raves" where it is taken orally.
Preferential affinity for the serotonin transporter (SERT) and therefore most strongly increases the extracellular concentration of serotonin. Serotonin depletion may become permanent, which has triggered a debate on its neurotoxicity.
Although direct proof from animal models for neurotoxicity remains weak, several studies report long-term cognitive impairment in heavy users of MDMA.
In contrast, there is a wide consensus that MDMA has several acute toxic effects, in particular hyperthermia, which along with dehydration may be fatal.
Other complications include serotonin syndrome and seizures. Following warnings about the dangers of MDMA, some users have attempted to compensate for hyperthermia by drinking excessive amounts of water, causing water intoxication involving severe hyponatremia, seizures, and even death. Withdrawal is marked by a mood "offset" characterized by depression lasting up to several weeks. There have also been reports of increased aggression during periods of abstinence in chronic MDMA users.Taken together, the evidence for irreversible damage to the brain, although not completely convincing, implies that even occasional recreational use of MDMA cannot be considered safe.
1) Which one of the following chemicals does not satisfy the criteria for a neurotransmitter role in the CNS?
D) Nitric oxide
E) Substance P
6) Which of the following statements is true?
A) Lamotrigine combined with clozapine is useful in treating depression
B) Lamotrigine combined with carbamazepine is useful in treating schizophrenia
C) Carbamazepine is not useful in trigeminal neuralgia
D) Valproic acid and carbamazepine are effective in bipolar disorder
E) None of the above is true
11) Which of the following is correct?
A) Knockout of 5-HT1A receptors blocks the antidepressant effect of haloperidol
B) Preventing hippocampal neurogenesis blocks the antidepressant effects of fluoxetine
C) Fluoxetine is selective for 5-HT1A receptors
D) X-irradiation kills 5-HT neurons and causes depression
E) None of the above is correect
Barbiturates and other sedative hypnotics
-ether, cloroform, solvents