Haf Pharm Drugs Of Abuse 2008

Front 1

What is the mesocorticolimbic projection?

Back 1

"Reward Pathway"
DA from VTA released into the Nuc Accumbens and Prefrontal Cortex.

Drugs of abuse stimulate this pathway.

Front 2

Cellular mechanism of opiods:

Back 2

Opiods bind mu receptor of pre-synaptic nerves. (Gi inhibits adenylate cyclase)

Hyperpolarization results.

Decreased Ca2+ entry results.

Less GABAa released from the inhibitory neurons that feed into VTA.

DISINHIBITION!

Front 3

Metabolic tolerance is:

Back 3

Pharmacokinetic (tissue on drug)

Tolerance induced by enzymes for more effecting metabolism.

Front 4

Functional tolerance is:

Back 4

Pharmacodynamic (drug on tissue)

Alters cell physiology to make cells less responsive to a substance that is there all of the time.

Front 5

CREB is what?

Back 5

cAMP response element binding protein

It is a TF that is upregulated in Functional Tolerance with chronic opioid abuse, causing symptomatic drug withdrawal symptom: EXCITABILITY.

When opioid is not present increased GABA is released and less DA is released.

Front 6

Pinpoint pupils is a sign of which intoxication.

Back 6

Opioid intoxication

Front 7

Cocaine is metabolized where and how?

Back 7

Plasma and Liver pseudocholinesterases

hepatic N-demethylation

Ultimate metabolite is: Norcocaine nitroxide which is toxic to the liver

Front 8

Cocaine cellular mechanism

Back 8

Cocaine inhibits the transporter used for DA uptake.

It doesn't cause disinhibition like opioids (mu receptor, less GABA)

It doesn't bind a specific receptor like opioids

Front 9

What is sensitization?

Back 9

Produced by intermittent drug use and my be responsible for conditioning (exposure to

Front 10

Peripheral actions of amphetamine include:

Back 10

Adrenergic actions: sweating, tachy, nausea, headache, abdominal cramps

Front 11

Amphetamine cellular mechanism:

Back 11

Increases amount of DA and NE released into the synapse because it prevents packing into vesicles. DA and NE are kicked out by the NET into the synapse and MAO can't degrade it fast enough to keep up.

Front 12

Amphetamine overdose:

Back 12

Same as for cocaine, except seizures do not occur and amphetamine lasts longer.

Treat hypertension and arrhythmia with alpha and beta blockers.

Front 13

Caffeine's mechanism of action:

Back 13

Increases cAMP levels through competitive antagonism of phosphodiesterase and adenosine receptors.

Increases NE secretion.

Front 14

Nicotine mechanism:

Back 14

Nicotine receptors on DA neurons are activated and increase in action potential frequency.

Desensitization decreases the stimulatory effects.

Front 15

Metabolism of LSD

Back 15

Plasma half-life = 12 hours

Hydroxylation and conjugation is followed by excretion into the bile.

Front 16

LSD mechanism:

Back 16

Mimics 5-HT at central 5-HT1a autoreceptors.

Acts as agonist at 5-HT2a and 2C receptors.

Different affinities for various subtypes produces altered perception.

Front 17

Mechanism of MDMA and methamphetamine psychedelics:

Back 17

Hallucinogenic effects are mediated through 5-HT2 receptors.

Front 18

Mechanism of PCP and Ketamine:

Back 18

Binds Glutamate NMDA receptors (excitatory), causing hallucinations and delirium.

Front 19

Cannabis mechanism:

Back 19

CB1 is the important receptor. It has same mechanism as opioid receptors (pre-sumably Gi).

The 2 drugs have different distribution of receptors through the brain and therefor have different effect.

Cerebellum
Cerebral cortex
Hippocampus
Striatum

Front 20

GHB mechanism:

Back 20

GABAb receptor.

Mechanism is unclear. It is metabolized to CO2 and H2O.

Front 21

Cross-tolerance example:

Back 21

The tolerance developed to methadone makes the patient insensitive to heroin.

Front 22

LAAM

Back 22

Competes with opioids to aid in withdrawl. Longer acting: 72 hours. Take 2-3 times a week.

Front 23

Buprenorphine

Back 23

A partial mu receptor agonist and kappa antagonist, to aid in opioid withdrawl.

Patients do become dependent, however the withdrawl is mild and overdose is rare.

Front 24

Naltrexone

Back 24

Mu opiod receptor antagonist aids in withdrawl but does not treat addition.

Competitive antagonist may cause addict to overdose upon self-administering more opioid.

It also blocks endogenous opioid system.

Remarkably effective in treating alcohol abuse!