Drugs of abuse I Flashcards by tcarlso 3

What are the two qualities of dependence?

Development of tolerance

2. Withdrawal symptoms

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How does tolerance come about?

Decrease in amount of available drug

2. Changes of drug receptor action

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What is addiction?

Relapsing drug use despite negative consequences

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What is the dopamine hypothesis of addiction?

All addictive drugs target the mesolimbic dopamine system in the VTA

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What is the role of the ventral tegmental area in addiction?

Dopamine neurons in this area project to several brain receptors involved in reward processing

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What are the two parts to drug abuse?

get euphoria/reward

2. Detrimental to health

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What is the hallmark of drug addiction?

Compulsive drug use

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What is pharmacokinetic tolerance?

Increased drug metabolism or amount of drug availability

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What is pharmacodynamic tolerance?

Desensitization and/or downregulation of receptors

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What are the areas in the brain that the VTA projects neurons to in the reward pathway? (4)

Nucleus accumbens
Amygdala
Hippocampus
Prefrontal cortex

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What is the general principle with withdrawal ssx?

Opposite of the drugs taken

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What is “psychological dependence”? “Physiological dependence”?

Psychological = Addiction
Physiological = dependence

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What is the scale used for the relative risk of addiction?

1 through 5, with 1 being non-addictive and 5 being highly addictive

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What are the three MOAs of increased dopamine release in the reward pathway via addictive drugs?

Activation of Gi
Activation of ionotropic receptors
Targeting dopamine transporter

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What does activation of Gi do in the dopaminergic neurons of the reward pathway do, and how does this lead to increased reward?

Inhibits the firing of the inhibitory interneurons on Dopaminergic neurons

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What does activation of ionotropic receptors do in the dopaminergic neurons of the reward pathway do, and how does this lead to increased reward?

Enhances release of dopamine in activation of GABAergic neurons

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What does targeting of dopamine transporter do in the dopaminergic neurons of the reward pathway do, and how does this lead to increased reward?

Blocks dopamine reuptake, leading to increased dopamine in the synapse

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What is the MOA of opioids in generating reward pathway stimulation?

Activate Gi/GABA on inhibitory interneurons

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What is the MOA of THC in generating reward pathway stimulation?

Activate Gi/GABA on inhibitory interneurons

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What is the MOA of cocaine in generating reward pathway stimulation?

Block dopamine reuptake

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What is the MOA of amphetamine in generating reward pathway stimulation?

Block dopamine reuptake and cause release of dopamine from vesicles

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What is the MOA of nicotine in generating reward pathway stimulation?

Activates ion receptors to increase release of dopamine

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What is the MOA of benzodiazepines in generating reward pathway stimulation?

Activates ion receptors to increase release of dopamine

What is the MOA of EtOH in generating reward pathway stimulation?

Activates ion receptors to increase release of dopamine

True or false: the area of the brain that is involved in addiction is usually different from its site of action

True

What is the relative risk of addiction for CNS depressants?

What are the three CNS depressants?

EtOH Benzos Barbiturates Gamma-hydroxybutyric acid

When does EtOH reach its peak concentration in the blood?

30 minutes

True or false: EtOH is soluble in fat and water, and thus diffuses easily across all biological membranes

True

How does the EtOH concentration of a mother's blood compare to that of the fetus?

Same

What percent of EtOH is metabolized by the liver? What is the metabolic process occurring here?

90% oxidation

Why do women have a higher EtOH levels than men for the same dose?

Decreased first pass effect | Lower total body water

What are the three MOA of EtOH metabolism?

1. Alcohol dehydrogenase 2. MEOS 3. Aldehyde dehydrogenase

Is EtOH zero or first order elimination? What does this mean?

Zero order--constant amount eliminated regardless of serum concentration

What other organs metabolize EtOH besides the liver? What percent?

Kidney and lungs--10%

Alcohol dehydrogenase catalyzes alcohol into what chemical?

acetaldehyde

What is the cause of fatty liver of alcoholism?

Overproduction of NADPH and lower amount of NAD+ shunts energy down the FA synthesis pathway

What is the drug that treats methanol and ethylene glycol poisoning? MOA?

Fomepizole Inhibits ADH, which is involved in the conversion of these two substances into toxic metabolites

What is the MEOS system?

Microsomal ethanol oxidizing system--complex of p450s

After alcohol dehydrogenase turns alcohol into acetaldehyde, what is the next enzyme in the pathway? What does this produce?

Aldehyde dehydrogenase Acetate

What happens if Aldehyde dehydrogenase is not functioning properly? Symtoms?

Build up of acetaldehyde, causing hangover feeling + flushing

What is the cofactor needed for Aldehyde dehydrogenase?

NAD+

What is the drug that is used to treat alcoholism? MOA?

Disulfiram Inhibits ALDH, causing a buildup of acetaldehyde, and sickness

How many drinks does it take most adults to reach the legal limit of 0.08% BAC?

2-4

What is the ABV of beer? Wine? Liquor?

``` Beer = 3.5-10% Wine = 12% Liquor = 40-50% ```

What is one drink (in oz) for beer, wine, and liquor?

``` Beer = 12 oz Wine = 5 oz Liquor = 1.5 oz ```

What is the MOA of EtOH?

Potentiates GABA-(A- receptors, causing a Cl influx and inhibition of neurons. Also inhibits glutamate excitatory neurons (NMDA receptors)

What are the effects of CNS depressants with EtOH?

Additive effects

What is Wernicke-Korsakoff syndrome?

Thiamine (vit B1) deficiency characterized by paralysis of the external eye muscles, ataxia and a confused state that can progress to coma and death. Also, confabulations.

What are the three classic characteristics of fetal alcohol syndrome?

MR Hyperactivity Antisocial behavior

What are the cells that are primarily affected in the pancreas with EtOH?

Acinar cells

What are the 4 stages of liver changes with EtOH use?

Alcoholic fatty liver Alcoholic hepatitis Liver cirrhosis Liver failure

What is the effect of EtOH use and cocaine?

Liver combines the two to form cocaethylene, that potentiates the effects of cocaine

Why is thiamine given to drunks in the ER?

Prevent Wernicke-Korsakoff syndrome

What is the drug type of choice for treating acute EtOH withdrawal?

Benzodiazepines

What is the MOA of naltrexone in treating chronic alcoholism?

Opioid antagonist that blocks the reinforcing properties of EtOH

What is the MOA of disulfiram in treating chronic alcoholism?

Inhibits ALDH and produce acute sensitivity to EtOH ("hangover" ssx).