Block 2: Drugs Of Abuse: Stimulants

Front 1

1,3,7 trimethylxanthine
1,3 dimethylxanthine
3,7 dimethylxanthine

Back 1

caffeine
theophylline
theobromine

Front 2

At what dose of caffeine are measurable CNS effects seen?

Back 2

oral ingestions of 150 mg caffeine- giving plasma levels of 10 mg/ml (50uM)

Front 3

Of the three caffeine drugs, which is the weakest stimulant?

Back 3

theobomine

Front 4

What is the mechanism of CNS effects?

Back 4

disinhibition of forebrain arousal pathways

Front 5

At high doses of caffeine, what happens to medullary stimulation?

Back 5

respiratory, vasomotor, and vagal centers stimulated
even inc reflex excitability in spinal cord

Front 6

Is there a lot of tolerance/dependence with caffeine?

Back 6

little tolerance but heavy coffee drinkers may get headache and depression in morning upon withdrawal

Front 7

How can a xanthine be used in smooth muscle relaxation?

Back 7

theophylline in asthma

Front 8

What can large amounts of strong coffee do to CV stimulation?

Back 8

produce cardiac irregularities

Front 9

What do xanthines do to GFR?

Back 9

increase rate- caffeine induced diuresis

Front 10

What do xanthines do to the GI tract?

Back 10

inc HCl secretion- heartburn; lower bowel irritability

Front 11

Describe caffeines affect on adenosine receptors

Back 11

non selective A1 and A2 antagonist at fairly low concentrations (50 uM)

Front 12

What does A1 do?

Back 12

inhibits adenylyl cyclase --> dec cAMP
inc adenosine (from ATP brkdwn and cAMP) --> A1 inhibits forebrain cholinergic arousal pathways --> drowsiness and sleep
(caffeine inhibits the adenosine--> delays sleep)

Front 13

What does A2 do?

Back 13

stimulate adenylyl cyclase
inc cAMP

Front 14

What does ethanol do to the adenosine actions at A1 receptors?

Back 14

potentiates them, regulating ACh release in thalamus

Front 15

What does caffeine do at >100 uM concentrations

Back 15

1. inhibits phosphodiesterase --> inc cAMP
2. releases Ca from intracellular stores

Front 16

What are the two phases of tobacco smoke?

Back 16

gas phase
and
particulate phase

Front 17

What does the gas phase of tobacco smoke contain?

Back 17

CO2, CO, acetaldehyde, acetone, hydrogen cyanide, ammonia, etc

Front 18

What does the particulate phase of tobacco smoke contain?

Back 18

nicotine
phenol, cresols, beta-naphthylamine, etc

Front 19

Through what receptors does nicotine activate the sympathetic nervous system?

Back 19

nACHn receptors

Front 20

Through what receptors does nicotine activate the parasympathetic nervous system?

Back 20

nAChn receptors

Front 21

How can nicotine cause ganglionic blockade?

Back 21

through nAChn receptors- only at high doses (not smoking)

Front 22

What are the effects of chemoreceptor stimulation by nicotine at nAChn receptors?

Back 22

aortic arch and carotid body- respiratory stimulation
emetic trigger zone (postrema)- nausea, vomitting
hypothalamus (supraoptic nu)- ADH secretion

Front 23

What is the most obvious effect of motor reflex stimulation/depression in smokers?

Back 23

depression of knee jerk
*only weak activity at nAChm receptors

Front 24

differences in motor stimulation with different nicotine doses?

Back 24

stimulation at low doses
depression at high doses with very rapid tolerance to stimulant

Front 25

How does nicotine create an effect associated with behavioral reinforcement

Back 25

increases DA release in nuc Accumbens

Front 26

How good is nicotine at analgesia?

Back 26

great, but not used because of other effects

Front 27

What is the major metabolite of nicotine?
longer or shorter t1/2?
less or more pharmacologic activity?

Back 27

cotinine
longer (19 hrs)
less

Front 28

What is green tobacco sickness?

Back 28

acute intoxication of nicotine- nausea, vomiting, weakness, headache, sweating, salivation

Front 29

How common are daths due to oral ingestion of nicotine?

Back 29

rare due to vomiting and first-pass metabolism

Front 30

What happens with chronic nicotine toxicity?

Back 30

CV toxicity, hypertension, COPD, low birth weight babies

Front 31

Name some different nicotine replacement therapies?

Back 31

NICOTINE skin patches, nasal spray, inhalers, chewing gum

Front 32

What is the success rate of the patch?

Back 32

10% at 1 yr

Front 33

What antidepressant may be used for nicotine cessation?

Back 33

buproprion- 23% success rate at 1 yr
(tremor 3%, headache 1%, skin rash 1%)

Front 34

What are some possible therapeutic applications of nicotine?

Back 34

1. ulcerative colitis- symptoms develop when smokers quit- use of nicotine patches have reduced sx in ex smokers
2. alzheimer's disease- lower incidence of AD and Parkinson's, some symptomatic relief with patch

Front 35

Is nicotine approved by the FDA for tx of UC or AD?

Back 35

no

Front 36

What are amphetamines?
What type is more effective

Back 36

synthetic benzylethylamine derivates- the D-isomer (dexamphetamine) is ore active than the l-isomer in CNS

Front 37

What is the amphetamine MOA?

Back 37

indirectly acting sympathomimetic amines- release NE, DA (and 5-HT) in periphery and CNS (like tyramine)

Front 38

Down to the details, how does amphetamine do its thing?

Back 38

enters neurons through DA transporter (DAT) and inhibits MAO --> displaces monoamines by getting into vesicles with help of VMAT --> elevated monoamines go into extracellular space via reversal of plasma membrane transporter --> inc local monoamine receptor activation

Front 39

Where are the critical places for the euphoriant and motor effects of amphetamines?

Back 39

effects on DA receptors in nuc Accumbens and caudate-putamen

Front 40

What happens with chronic amphetamine use?

Back 40

tolerance
tendency to inc dose, compulsive use,
severe pranoia
psychotic behavior
skin crawling delusions

Front 41

Even though there are "no good reasons for using amphetamines becuase of there abuse potential" why does the military use them? What about athletes?

Back 41

military- delay onset of fatigue in military personnel (e.g., pilots)
athletes- enhance physical performance

Front 42

How do you tx acute amphetamine intoxication?

Back 42

symptomatically
lorazepam for agitation, irritability
antipsychotic

Front 43

What comes from the leaves of Erythroxylon coca

Back 43

cocaine (the hydrochloride salt)
powder
snow

Front 44

What is the "free base" form of cocaine?

Back 44

crack- more rapidly absorbed across mucous membranes

Front 45

Cocaine MOA?

Back 45

local anesthetic and indirectly acting sympathomimetic amine- blocks re-uptake of NE, DA, 5-HT

Front 46

How much cocaine administered intranasally incresaes heart rate and raises BP?

Back 46

25-100 mg

Front 47

How does smoking crack differ from oral ingestion?

Back 47

smoking can induce very intese effects; oral ingestion gives prolonged intesnse stimulation and high risk of CV and CNS toxicity

Front 48

What happens after the euphoria induced by cocaine?

Back 48

it declines before the drug plasma levels do --> 40-80 minutes of depression, dysphoria, and intense craving for more

Front 49

What antagonizes cocaine euphoria?

Back 49

DA antagonists

Front 50

What may explain the depression and drug-craving of drug-free cocaine addicts?

Back 50

DA neurons of striatum in detoxified human cocaine users release less DA in response to stimulus than drug-naive subjects

Front 51

What can high doses of cocaine do?

Back 51

tremor, tonic-clonic convulsions, vasomotor stimulation, vomiting, cardiac arrhythmias, heart block ,sudden death, or death from respiratory depression

Front 52

what causes nasal septum damage associated iwth cocaine?

Back 52

repeated local vasoconstriction

Front 53

What can chronic use cause?

Back 53

permanent cardiac damage, paranoia, psychotic behavior

Front 54

What are the withdrawal sx associated with cocaine?

Back 54

increased appetite, lethargy, depression

Front 55

What is a speedball?

Back 55

opiate comibined with amphetamine to reduce anxiety provoking effects

Front 56

Is cocaine an aphrodesiac?

Back 56

reportedly, but is definitely associated with sexual dysfunction

Front 57

How would you tx acute cocaine toxicity causing CV complications and anxiety attacks?
psychosis?
seizures?

Back 57

beta blocker
laoperidol (DA antagonist)
diazepam

Front 58

What drugs may be used to treat chronic cocaine use?

Back 58

bromocryptine- DA agonist
or
desipramine- NE uptake inhibitor

Front 59

this drug is chemically similar to amphetamines but has fewer CNS affects; used as appetite supressant; may deplete 5-HT stores and lead to cell death

Back 59

fenfluramine

Front 60

What is fen/phen

Back 60

combo of fenfluramine and amphetamine like drug (phenteramine)- was sold for wt. loss; --> valvular heart disease

Front 61

This drug was approved to tx daytime sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea, shift work sleep disorder; and is used by military to maintain alertness

Back 61

modafinil (provigil)

Front 62

What is the MOA of modafinil?

Back 62

involves inhibition of NE uptake by neurons in sleep promoting areas of ventrolateral pre-optic area

Front 63

What does modafinil do to CYP3A4 and CYP2C19

Back 63

induces
inhibits

Front 64

this drug inhibits NE, DA, and 5HT like cocaine, but is less reinforcing?

Back 64

methylphenidate (ritalin)

Front 65

What is methylphenidate used for?

Back 65

tx of ADD/ADHD

Front 66

What is the MOA of methylphenidate?

Back 66

deficiency of central MOAs leads to reduced ability to forcus attention --> blocking re-uptake reverses this effect

Front 67

What was the first NE-selective re-uptake inhibitor approved for ADHD?

Back 67

atomoxetine

Front 68

Why might atomoxetine be a choice for children who can't take stimulants?

Back 68

it has non-stimulant action