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Flashcards in psychomotor stimulants Deck (46):
1

psychomotor stimulants

Amphetamines, Cocaine, Methylxanthines & Convulsive Stimulants

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amphetamine (BENZEDRINE, BIPHETAMINE, ADDERAL)

stimulant

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d-amphetamine (DEXEDRINE, BIPHETAMINE, ADDERAL)

-greater effect in CNS than amphetamine

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Lisdexamfetamine (Vyvanse)

prodrug, amphetamine is linked to lysine
-Moderate rate of conversion to amphetamine limits abuse
-Used for ADHD but might not work as well as traditional amphetamines in some patients

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methamphetamine (DESOXYN) - "speed" “crank” - "ice"

-methyl group: resistant to metabolism by MAO and increases its lipid solubility
-intense effects in the CNS, widely abused
-"ice": crystalline smokable form, like crack
-*meth is much longer acting than crack cocaine: 12 hours or more vs 15-30 min. for crack!*

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methylphenidate (RITALIN)
and (permoline (Cylert) FYI)

similar to amphetamines - used to tx ADD in kids - paradoxical effect of amphetamine and related agents is to stimulate areas of the brain such as the locus ceruleus that enable the child to focus attention

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Cathinone (Khat, "Kat", or "Cat")

-plant from Eastern Africa and Mid East
-analogs easy to synthesize chemically (DOAs in US, Europe)
-*“bath salts”* from the internet and in “head shops”.
-usually taken by “snorting”
-Some products include: “Ivory Wave”, “Vanilla Sky”, “Raving Dragon” and “Purple Wave”.
-recently banned by the DEA

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Ephedrine

-sympathomimetic agent
-used in various OTC pep pills
-banned by FDA but can get over internet

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Modafanil (Provigil) and Armodafanil (Nuvigil)

newer drugs, used to tx narcolepsy and shift work disorders
-unclear MOA, have many amphetamine-like effects

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Pharmacological Effects (amphetamine, methamphetamine): CNS

-stimulation: ^arousal and wakefulness via stimulating the reticular activating system
-euphoria: most pleasant, some dysphoric and anxious
-delay of "fatigue induced" decline in intellectual/motor performance
-rebound effects (crash) may lead to cycle of drug use
-tolerance and dependence: both psychological and physical (w/drawal: fatigue, lethargy, depression)
-amphet. psychosis: like paranoid shizo, but reversible
-appetite suppression: action on hypothalamus, tolerance develops

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Pharmacological Effects (amphetamine, methamphetamine): Peripheral effects

primarily sympathomimetic
-autonomic - HTN, tachy, arrhythmias, mydriasis (dilated)
-metabolic - decreased food intake; malnutrition

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Pharmacological Effects (amphetamine, methamphetamine): toxicity

sympathomimetic effects -
-CV: HTN, tachy, arrhythmias, and sudden death
-CNS: excessive stimulation, hostility, aggression, psychotic reactions (amphetamine psychosis), tactile hallucinations (formication)
-dental problems (meth mouth) and lung damage from smokable forms

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MOA

-acute effect: enhanced release and inhibition of the uptake of NE and DA (acute effect)
-possible direct stimulation of alpha receptors in reward centers of brain
-chronic effect: decreased levels of DA in reward centers of brain

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pharmacokinetics

-absorption from GI tract
-IV use by abusers
-metabolism by liver but large amounts are excreted unchanged
-enhanced excretion in acidic urine

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use of amphetamines

-ADD: "hyperkinetic syndrome" in children - paradoxical effect in that it may stimulate catecholamine pathways in the brain that enable the child to focus attention properly
-narcolepsy
-obesity and weight reduction (but tolerance develops and drugs aren't effective long term)
-stimulants
-abuse

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Cocaine

from Erythroxylon coca plant of Peru and Columbia
hydrochloride vs. free base vs. "crack":

cocaine "base/paste" (crude coca extract)-->COCAINE-HCL (50-75mg/line)-->cocaine-free base
either heat to remove water-->CRACK (15-25 mg/dose)
or ether extraction/evaporation-->FREE BASE (15-25 mg/dose)

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cocaine entry pharmacokinetics

-HCl salt - water soluble; absorption through mucous membranes - commonly "snorted"
-HCl salt - IV use by abusers
-inhalation of the lipid soluble free base forms provides very rapid delivery of a concentrated bolus to the brain

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cocaine metabolism

metabolism by plasma esterase and by liver
-half-life of HCl form is about 1 hour
-major metabolite is benzoylecognine

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when cocaine used in combo with etOH..??

an active metabolite
(cocaethylene) is formed. Since it has a much longer half-life than cocaine, the drug effects may be prolonged

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cocaine pharmo effects

local anesthetic with vasoconstriction
CNS effects (like amphetamines):
-stimulation, ^ arousal
-euphoria, dysphoria
-increased confidence and social activity
-*powerful reinforcer* on reward center
-tolerance and dependence: psychological and physical (w. drawl: lethargy, fatigue, depression)
-psychotic symptoms like amphetamines at high doses

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cocaine peripheral effects

autonomic - HTN; tachy; arrhythmias; sudden death, mydriasis
-teratogenic effects - low birth weight, mental retardation, neuro/dev deficit
-deterioration and perforation of nasal septum with chronic snorting
-lung damage and pulmonary edema from smoking crack
-AIDS, hepatitis and other infections from IV use

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state of cocaine dependence results from ??

drug induced adaptive changes in specific dopaminergic pathways in limbic areas of the brain

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a primary effect of acutely admin. cocaine is to ??

block the synaptic reuptake dopamine that is available to act on the target cell
-the extra dopamine that is present in the synapse is thought to act on the target cells to produce the euphoria and reinforcing effects of acutely administered cocaine

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what is thought to be responsible for the craving for cocaine and the development of tolerance and dependence?

With repetitive usage, the presynaptic neuron is unable to replenish lost dopamine

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how do antipsychotics affect acutely admin. cocaine??

amphetamines produce what sort of effects??

inhibit many of the behavioral effects (via blocking dopamine receptors)

produce effects that closely resemble those of cocaine (stimulate the synaptic release of dopamine)

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novel tx for cocaine dependence/addiction

-nutritional supplements to replenish dopamine stores
-l-DOPA to increase brain levels of dopamine
-certain opioids (buprenorphine): used to decrease cravings, tx for addiction

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novel cocaine dependence tx: ?? block the reuptake of dopamine but do not deplete levels of dopamine (may suppress cravings)

Antidepressant drugs: i.e. bupropion (Wellbutrin)

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novel cocaine dependence tx: ?? is being tried in hopes that it may provide some stimulation of the post synaptic receptors until dopamine stores can be replenished (substitute)

Bromocriptine (Parlodel): dopamine agonist

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caffeine

methylated xanthine

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Theophylline

methylated xanthine, used in the treatment of asthma

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Aminophylline

methylated xanthine,
Ethylenediamine salt of theophylline - used in the treatment of sever asthma

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caffeine and related methylxanthine CNS effects

-cortical stimulation
-increased mental alertness and improvement in some types of mental
function
-respiratory stimulation – *caffeine and theophylline* are sometimes used to
treat apnea in preterm infants

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caffeine tolerance and dependence -

caffeine is both psychologically and physically addicting. The withdrawal syndrome consists of headache, fatigue, and depression, but is usually relatively mild. Some degree of dependence can result from drinking 3-4 cups of coffee/day for 2-4 weeks.

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caffeine cardiac effects

-cardiac stimulation: increased rate and contractility; usually not severe but may cause problems in OD or in pts with cardiac conditions
Some people are far more sensitive to caffeine than others


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caffeine vascular effects

-peripheral (dilation of most vascular beds)
-renal: dilation; diuretic effect
-cerebral: constriction; caffeine is sometimes included in headache
preparations

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other caffeine peripheral effects

-relaxation of bronchioles - use of *theophylline and aminophylline* in asthma
-stimulation of gastric secretion - avoid use in patients with peptic ulcer disease
-controversies regarding carcinogenesis and teratogenesis

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Methylxanthine Overdose is characterized by ??

excessive CNS stimulation which can result in life threatening seizures. In addition, there may be excessive cardiac stimulation and eventual cardiovascular collapse.
Tx is mainly symptomatic (anticonvulsants and antiarrhythmics)

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MOA of caffeine, etc.

-inhibition of phosphodiesterase
-blockade of adenosine receptors
-release of Ca2+

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caffeine uses

-CNS stimulants (Vivarin, No Doz, etc..)
-asthma - theophylline and aminophylline
-in combination with other drugs (e.g. headache remedies)
-as diuretics (e.g. caffeine in OTC preps)
-as respiratory stimulants in preterm infants
-in beverages

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Health Effects Associated with Chronic Uses of Caffeine??

up for debate
-possibly associated with a variety of disorders (e.g. HTN, arrhythmias, cancer, PUD, etc..)
-should be avoided by individuals with various health problems (e.g. CV disease, peptic ulcers, seizure disorders, etc..)

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Strychnine

Spinal cord stimulant (mostly toxicologic); potent convulsant used as a rat poison

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Strychine MOA


tx??

-antagonist at glycine receptors in the spinal cord and other areas of the CNS. This removes post synaptic inhibitory influences and leads to the development of severe toxic seizures

tx: symptomatic support plus the use of diazepam to control seizures.

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Tetanus Toxin

spinal cord stimulant; released by C. tetani
Produces generalized tetanus and tonic convulsions similar to those produced by strychnine.
-inhibits release of glycine from Renshaw cells in the spinal cord and other areas.
Tx: symptomatic support, diazepam for the control of seizures, and appropriate antimicrobial therapy.

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Doxapram (DOPRAM) FYI
questionable efficacy

Respiratory Stimulant (Analeptic)
-Acts on carotid chemoreceptors and medullary respiratory centers to stimulate respiration.
-tx of drug induced respiratory depression particularly after surgery.

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Doxapram (DOPRAM) SEs FYI

excessive CNS stimulation: headache, hyperreflexia, spasticity, and convulsions
CV effects: flushing, HTN, tachycardia, and arrhythmias

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Nikethamide (CORAMINE) FYI

Respiratory Stimulant (Analeptic)
Old drug that used to be used to stimulate respiration in barbiturate poisoning - not very effective - now obsolet