psychomotor stimulants

Question 1

psychomotor stimulants

Answer 1

Amphetamines, Cocaine, Methylxanthines & Convulsive Stimulants

Question 2

amphetamine (BENZEDRINE, BIPHETAMINE, ADDERAL)

Answer 2

stimulant

Question 3

d-amphetamine (DEXEDRINE, BIPHETAMINE, ADDERAL)

Answer 3

-greater effect in CNS than amphetamine

Question 4

Lisdexamfetamine (Vyvanse)

Answer 4

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

Question 5

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

Answer 5

• 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!

Question 6

methylphenidate (RITALIN)

and (permoline (Cylert) FYI)

Answer 6

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

Question 7

Cathinone (Khat, “Kat”, or “Cat”)

Answer 7

• 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

Question 8

Ephedrine

Answer 8

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

Question 9

Modafanil (Provigil) and Armodafanil (Nuvigil)

Answer 9

newer drugs, used to tx narcolepsy and shift work disorders

-unclear MOA, have many amphetamine-like effects

Question 10

Pharmacological Effects (amphetamine, methamphetamine): CNS

Answer 10

• 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

Question 11

Pharmacological Effects (amphetamine, methamphetamine): Peripheral effects

Answer 11

primarily sympathomimetic

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

Question 12

Pharmacological Effects (amphetamine, methamphetamine): toxicity

Answer 12

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

Question 13

MOA

Answer 13

• 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

Question 14

pharmacokinetics

Answer 14

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

Question 15

use of amphetamines

Answer 15

• 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

Question 16

Cocaine

Answer 16

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)

Question 17

cocaine entry pharmacokinetics

Answer 17

• 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

Question 18

cocaine metabolism

Answer 18

metabolism by plasma esterase and by liver

• half-life of HCl form is about 1 hour
• major metabolite is benzoylecognine

Question 19

when cocaine used in combo with etOH..??

Answer 19

an active metabolite

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

Question 20

cocaine pharmo effects

Answer 20

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

Question 21

cocaine peripheral effects

Answer 21

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

Question 22

state of cocaine dependence results from ??

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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

Answer 24

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

Question 25

how do antipsychotics affect acutely admin. cocaine?? amphetamines produce what sort of effects??

Answer 25

inhibit many of the behavioral effects (via blocking dopamine receptors) produce effects that closely resemble those of cocaine (stimulate the synaptic release of dopamine)

Question 26

novel tx for cocaine dependence/addiction

Answer 26

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

Question 27

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

Answer 27

Antidepressant drugs: i.e. bupropion (Wellbutrin)

Question 28

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)

Answer 28

Bromocriptine (Parlodel): dopamine agonist

Question 29

caffeine

Answer 29

methylated xanthine

Question 30

Theophylline

Answer 30

methylated xanthine, used in the treatment of asthma

Question 31

Aminophylline

Answer 31

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

Question 32

caffeine and related methylxanthine CNS effects

Answer 32

-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

Question 33

caffeine tolerance and dependence -

Answer 33

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.

Question 34

caffeine cardiac effects

Answer 34

-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

Question 35

caffeine vascular effects

Answer 35

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

Question 36

other caffeine peripheral effects

Answer 36

- 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

Question 37

Methylxanthine Overdose is characterized by ??

Answer 37

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)

Question 38

MOA of caffeine, etc.

Answer 38

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

Question 39

caffeine uses

Answer 39

- 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

Question 40

Health Effects Associated with Chronic Uses of Caffeine??

Answer 40

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..)

Question 41

Strychnine

Answer 41

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

Question 42

Strychine MOA tx??

Answer 42

- 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.

Question 43

Tetanus Toxin

Answer 43

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.

Question 44

Doxapram (DOPRAM) FYI | questionable efficacy

Answer 44

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

Question 45

Doxapram (DOPRAM) SEs FYI

Answer 45

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

Question 46

Nikethamide (CORAMINE) FYI

Answer 46

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