Drugs of Abuse Flashcards
What is physical dependence?
State of adaption that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction ,decreasing blood level of the drug, and/or administration of an antagonist
What is tolerance?
State of adaption in which exposure to a drug induces changes that result in a diminution of one or more of the drugs effects over time
Physical dependence and tolerance are normal responses that often occur with the persistent use of certain medications. While dependence will invariably occur with chronic exposure, only a fraction of subjects will become addicted. What are the mechanisms for addiction?
Mesolimbic dopamine system is the prime target of addictive drugs
- -this system originates in the ventral tegmental area and projects to the nucleus accumbens, the amygdala and the prefrontal cortex
- -all addictive drugs activate the mesolimbic dopamine system.
Lets go through the drugs of abuse. First up are the CNS depressants. First up in this category is ethanol. What are some features?
MOA:
–influences several cellular functions (GABAa receptors, Kir3/GIRK channels, adenosine reuptake, glycine receptor, NMDA receptors and 5-HT3 receptors)
What is withdrawal syndrome in regards to alcohol?
6-12 hours after cessation of heavy drinking
–tremor, nausea, vomiting ,excessive sweating, agitation and anxiety and sometimes hallucinations
Seizures can occur 24-48 hours later
48-72 hours later an alcohol withdrawal delirium becomes apparent
What is the treatment of alcohol withdrawal?
Meds are cross tolerant with alcohol
–benzos
–diazepam and chloridazepoxide are long acting agents that have been shown to be excellent in treating alcohol withdrawal and because of the long half life of these drugs, withdrawal is smoother, and rebound withdrawal symptoms are less likely to occur
Lorazepam and Oxazepam: are intermediate short acting drugs and are preferable in the elderly and those with liver failure
Tx of alcoholism is Disulfiram, Naltrexone and Acamprosate. What are features of these drugs?
- Disulfiram: inhibitor of aldehyde dehydrogenase
- -aversion to drinking, if drinking does occur, acetaldehyde accumulates and headache and hypotension happens. - Naltrexone: opioid receptor antagonist. reduces craving for alcohol
- Acamprosate: NMDA receptor antagonist, prevents relapse to alcohol drinking
- Topiramate (NOT FDA approved): facilitates GABA function and antagonizes glutamate receptors and may decrease mesocorticolimbic dopamine release after alcohol and reduce cravings
The second CNS depressant drug of abuse are the Benzodiazepines. What are some features?
Used for tx of anxiety disorders and insomnia
–physical dependence and addiction
Withdrawal:
–include tremors, anxiety, perceptual disturbances, dysphoria, psychosis and seizures
Management:
–Diazepam
–dose needs to be gradually reduced
–long acting has less severe withdrawal syndrome
The third CNS depressant drug of abuse are the barbiturates. what are some features?
Use has declined greatly due to increased safety and efficacy of newer medications.
Next category of drugs of abuse are the psychostimulants, first up are the methylxanthines. What are these drugs and what is the MOA?
Caffeine and the related methylxanthines theophylline and theobromine
MOA:
–block adenosine receptors that are expressed presynaptically on many neurons, including adrenergic neurons. Antagonism of the receptors by caffeine disinhibits NE release and thus acts as a stimulant.
–adenosine is a natural promoter of sleep and drowsiness. so caffeine blocks this.
What are the methylxanthines action on CNS, CV and GI?
CNS:
–decrease in fatigue and increased mental alertness as a result of stimulating the cortex
–1.5 grams of caffeine produces anxiety and tremors
CV:
–positive inotropic and chronotropic effects on the heart
–mild diuretic actions
GI:
–stimulate secretion of HCl from the gastric mucosa
–if peptic ulcer avoid
What are the pharmacokinetics, uses, AE, tolerance of methylxanthines?
PK:
–cross the placenta to the fetus and is secreted into the mother’s milk
–metabolized in liver
Use:
–theophylline: chronic asthma
–caffeine + ergotamine is used for migraine (adds to the vasoconstrictive effects)
AE:
–insomnia, anxiety and agitation
–lethal dose is 10g of caffeine, which induces cardiac arrhythmias
Tolerance:
–rapidly develops
–withdrawal: feelings of fatigue and sedation
The next psychostimulant is cocaine, what is the MOA and actions?
MOA:
–inhibits dopamine, NE and 5-HT reuptake therefore prolonging and potentiates CNS and peripheral actions of these monoamines
–prolonged dopamine produces the intense euphoria that cocaine initially causes
–craving comes from the depletion of dopamine
Actions:
–CNS: stimulation of cortex and brainstem (behavioral changes)
–sympathetic nervous system: increased NE adrenergic stimulation, thus producing tachy, and HTN
What are the PK, withdrawal and treatment of cocaine addiction?
PK:
–rapid onset, potential for overdosage and dependence is greatest with IV injection and freebase smoking
Withdrawal:
–dysphoria, depression, sleepiness, fatigue, cocaine, craving and bradycardia
–generally mild so no treatment
Tx of addiction:
–antidepressants and dopamine agonists but there is no clear treatment
The last psychostimulant drug of abuse is Amphetamines. What is the MOA and actions?
Methamphetamne and Methylphenidate
MOA:
–increased release of catecholamine neurotransmitters, including dopamine.
–inhibitors of MAO and direct catecholaminergic agonists in the brain
–behavioral effects similar to cocaine
Actions:
-CNS: stimulates entire cerebrospinal axis, cortex, brainstem and medulla
–Sympathetic Nervous System: acts on adrenergic system, indirectly, stimulating receptors through NE release