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Flashcards in Stimulants & Alcohol Deck (28)
1

PSYCHOMOTOR STIMULANTS

(1)  METHYLXANTHINES
(2)   NICOTINE
(3)   AMPHETAMINE
(4)   EPHEDRINE
(5)   COCAINE

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METHYLXANTHINES moa

caffeine & theophylline
-inhibition of phosphodiesterases, thereby increasing cyclic AMP
-antagonist at both adenosine A1 and A2 receptors
Both of these actions result in enhanced neurotransmission by amplifying the cyclic nucleotide second-messenger cascade. 

3

METHYLXANTHINES kinetics

-absorbed readily after oral, rectal, or parenteral administration
-metabolized in the liver by demethylation and oxidation.

4

NICOTINE moa

-low doses stimulate nicotinic receptors in the CNS resulting in depolarization
producing some degree of euphoria and arousal
-improves attention, learning, problem solving, and reaction time
-no therapeutic use: except for smoking cessation

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NICOTINE kinetics

-highly lipid soluble
-absorption readily occurs by oral mucosa, lungs, gastrointestinal mucosa, and skin
-metabolized in the lung and liver

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AMPHETAMINES

At present amphetamines are indicated for treatment of two disorders
(1)   treatment of NARCOLEPSY-a disorder characterized by uncontrollable desire for sleep. –about 200,000 patients
(2)   Attention-deficit hyperactivity disorder (ADHD)-hyperactivity syndrome in children

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AMPHETAMINES moa

-amphetamine appears to exert most of it’s effects by causing the release of biogenic amines(norepinephrine, dopamine, and serotonin) from their storage sites in nerve terminals. There is also some evidence that suggest that amphetamine may interfere with the re-uptake of these neurotransmitters into neurons.
-the major behavior effects are probably due to the release of dopamine which leads to increased alertness, decreased fatigue, depressed appetite, and insomnia.

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AMPHETAMINES kinetics

-well absorbed after oral administration
-metabolized by several catabolic pathways, however considerable amount of untransformed drug is excreted in the urine. Therefore it is possible to “ion-trap” this weak organic base.

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AMPHETAMINES adverse

The acute toxic effects of amphetamine usually are extensions of its therapeutic actions.
CNS- restlessness, tenseness, irritability, weakness, insomnia, confusion, delirium, paranoid hallucinations, suicidal or homicidal tendencies.
CARDIOVASCULAR-headache, palpitation, cardiac arrhythmias, hypertension, circulatory collapse
-excessive sweating.

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AMPHETAMINES agents

DEXTROAMPHETAMINE
METHAMPHETAMINE
METHYLPHENIDATE
PHENTERMINE

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DEXTROAMPHETAMINE
METHAMPHETAMINE

(1)   DEXTROAMPHETAMINE (DEXEDRINE) CII
(2)   METHAMPHETAMINE (DESOXYN) CII-more central effects and less peripheral effects (CV) than dextroamphetamine
Amphetamines have a very high abuse potential, tolerance develops to the anorexic and euphoric effects. Psychological dependence occurs with chronic use

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METHYLPHENIDATE

-used for (1) treatment of NARCOLEPSY-a disorder characterized by uncontrollable desire for sleep. (2)Attention-deficit hyperactivity disorder (ADHD)-hyperactivity syndrome in children
-has less euphoric effect and central stimulant effect
-same mechanism and profile as amphetamines

13

PHENTERMINE

MOA-acts on adrenergic and dopaminergic pathways, possibly like amphetamine
-short term therapy as adjunct to behavioral modification, diet, and exercise in the management of exogenous obesity ( use only for 3 weeks)
-contraindicated in patients with history of CV problems
-hypertensive crisis with monoamine oxidase inhibitors (MAOI’s)

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EPHEDRINE

MOA -alpha and beta –adrenergic agonist, in addition it enhances the release of norepinephrine from sympathetic neurons.
-orally active
-not really used therapeutically, but is found in OTC asthma preps.
-biggest use for OTC “stay awake preps”

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COCAINE (CII)

MOA- blocks the reuptake of dopamine by inhibiting the re-uptake transporter of neurotransmitter in the pre-synaptic neuron

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Non-amphetamine for ADHD & Narcolepsy

Modafinil (SPARLON) for the treatment of ADHD
Modafinil (PROVIGIL) is used in the treatment of Narcolepsy
Higher doses will be used in the treatment of ADHD than used for narcolepsy

The mechanism of action of modafinil is unknown, but the drug has some properties of the amphetamine (stimulation) also it weakly blocks dopamine up-take transporter.

FDA has asked for additional studies concerning the safety in children

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Modafinil adverse

It can cause psychoactive & euphoric effects as seen with CNS stimulants such as amphetamine & methylphenidate
Stevens Johnson syndrome*****************************

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Sodium Oxybate (A.k.A Gamma hydroxybutyrate) moa & use

In some cases of narcolepsy, the condition can cause a sudden loss of muscle control and weakness (cataplexy). Gamma hydroxybutyrate reduces the number of attacks when taken at bedtime and again 2 ½ to 4 hours after falling asleep
MOA- not understood, generally gamma hydroxybutyrate is a unspecified CNS depressant

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Sodium Oxybate (A.k.A Gamma hydroxybutyrate) adverse

depression, bedwetting, sleepwalking, and abuse potential
----- access will be controlled through a single, centralized pharmacy.

20

ATOMOXETINE

for ADHD
MOA- re-uptake inhibitor of norepinephrine and serotonin.

SIDE-EFFECTS- suicidal thoughts and liver disease

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GUANFACINE

for ADHD
MOA-Agonist at postsynaptic alpha-2A adrenergic receptors
 
SIDE-EFFECTS- caution with cardiac problems

22

alcohol metabolism

Most of the ethanol is metabolized in the liver parenchyma, catalyzed by Alcohol dehydrogenase (ADH) to acetaldehyde (toxic) which in turn is oxidized to acetate by Aldehyde dehydrogenase (ALDH). The acetate is then oxidized to CO2 and water primarily in peripheral tissues.

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alcohol kinetics

Depending on the mix of isoenzymes (genetic)** alcohol disappearance will vary with the blood alcohol concentration, this leads to limited metabolism and zero-order kinetics.

24

alcohol in asians

** 50% of Asians have an inactive ALDH that renders them incapable of oxidizing aldehyde efficiently ( all races have different percentages of ADH & ALDH). When they consume ethanol, high concentrations of acetaldehyde occur bringing about a flushing reaction and unpleasant effects.

25

Treatment of alcohol abuse

Disulfiram (Antabuse) inhibits ADH so acetaldehyde accumulates---Vasodilatation -face is hot and flushed, throbbing headache, hypotension-other effects--Thirst, sweating, chest pain, and copious vomiting
Naltrexone (opiate antagonist) also has been use to treat alcohol abuse.

26

new tx of alcohol

Acamprosate calcium (Campral)-MOA- not sure but:
(1)it has in vitro affinity for GABA type A and GABA type B receptors, so it's been assumed that the therapeutic effects of acamprosate are due to actions on GABA receptors. However, acamprosate does not share most of the other effects of GABA receptor modifying drugs, such as antianxiety, hypnotic, or muscle relaxant activity. It is therefore possible, perhaps likely, that the effects are mediated some other way.

(2) Acamprosate is structurally related to l-glutamic acid (l-glutamate), which is an excitatory neurotransmitter. It's been proposed that acamprosate decreases the effects of the naturally-occurring excitatory neurotransmitter glutamate in the body. Since chronic alcohol consumption disrupts this system, and the changes last many months after alcohol ingestion is stopped, it's possible that acamprosate somehow restores the glutamate system towards normal. It's thought, no matter how it acts, that Campral decreases the pleasant "high" associated with alcohol consumption, and thus decrease the frequency of relapse during abstinence.

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Therapeutic use of ethanol

Treatment of methanol poisoning- ADH metabolizes methanol to formaldehyde and formic acid, which cause blindness and severe acidosis
Treatment of ethylene glycol – ADH metabolizes ethylene glycol to glycolic and oxalic acids, which can cause renal toxicity and severe acidosis
Treatment of isopropyl alcohol- ADH metabolizes isopropyl alcohol to acetone, which is CNS toxic.
In methanol, ethylene glycol or isopropyl alcohol ingestion, ethanol successfully competes for ADH and prevents the conversion to toxic substances. Usually hemodialysis is require to remove the poison.

28

fomepizole

long acting inhibitor of alcohol dehydrogenase used in alcohol poisoning