Drugs of abuse

Question 1

Major target of addictive drugs is what system. And what 3 mechanisms alter it?

Answer 1

Mesolimbic dopamine system. AKA reward system.

1. Disinhibit DA neurons. Opiods, benzo, alcohol
2. Cause excitation of DA. Nicotine, alcohol
3. Block DA uptake. Leave in synapse. Cocaine, amphetamine, ecstasy.

Question 2

Dependence vs addiction

Answer 2

Dependence- happens at level of MOA (receptor) Withdrawl symptoms when drug is no longer available.

Addiction- Biochemical changes. Compulsive drug use despite negative consequences.

Happen in different areas of the brain, but now being looked at as a continuum.

Question 3

Psychomotor stimulant effects

Answer 3

Decrease feelings of fatigue
Increase motor activity
Cause excitement and euphoria

May also cause changes in thought patterns/mood. Hallucinogens. Little effect on brainstem/spinal cord. Directly affect brain.

Question 4

Most widely consumed stimulant in the world.

Answer 4

Caffeine. Metabolites are theophylline and theobromine.

^^ all methylxanthines

Question 5

methylxanthine proposed mechanism

Answer 5

Blocks adenosine receptors in CNS. Adenosine inhibits dopamine release.
So caffeine indirectly enhances dopamine transmission!

Question 6

methylxanthines actions

Answer 6

CNS: decrease fatigue, increases mental awareness, anxiety, tremors, stimulation of spinal cord at very high doses.

Increase HR and contractility
Increase urinary output
Stimulate secretion of hyrochoric acid in stomach= acid reflux.

Question 7

methylxanthines therapeutic use

Answer 7

Relax smooth muscles of bronchioles. Mainly theophylline for asthma therapy.

Question 8

methylxanthines adverse effects and lethal dose.

Answer 8

Insomnia, anxiety, agitation
Vomiting and convulsions at high dose
Lethal dose is 10 g
Tolerance/withdrawal if 600mg per day then stop.

Question 9

Nicotine mechanism at low and high doses

Answer 9

Low: ganglionic stimulation. Arousal/relaxation.
High: Ganglionic block. Receptors will turn off. Respiratory paralysis.

Question 10

How does nicotine affect the PNS and CNS?

Answer 10

PNS: increases Ach and NE transmission
CNS: Increases dopamine transmission

basically enhances DA transmission and impairs regulatory system.

Question 11

Nicotine CNS low and high dose effects

Answer 11

Low: Euphoria, arousal, relaxation. Attention, learning.
High: Central respiratory paralysis and hypotension.

Question 12

Nicotine PNS low and high dose effects

Answer 12

Low: Increase blood pressure and HR, decreased coronary blood flow, increase bowel activity.

High: Decrease BP, activity of bladder and GI cease.

Question 13

Varenicline MOA and use

Answer 13

Partial agonist at nicotine receptors in CNS
Produces less of an effect than nicotine

Useful as adjunct in management of smoking cessation.
Lessens rewarding effects of nicotine if a person relapses.

Question 14

Cocaine MOA

Answer 14

Blocks reuptake of monoamines - NE, 5HT, and especially DA. This prolongs the effects of the NT.

Chronic use depletes DA= cravings.

Question 15

Cocaine is the only drug that can cause death by

Answer 15

high dose and hyperthermia. Impairs sweating and cutaneous vasodilation, which is in place to help decrease body temp

Question 16

Therapeutic use of cocaine

Answer 16

Can be used as a local anesthetic.
Diagnosis of horner’s. Blocks reuptake of NE= dilation of normal pupil. bc NE stays in gap longer= triggers sympathetic response = dilation of normal pupil.

Question 17

Amphetamine MOA

Answer 17

Basically increases transmission of NE and dopamine.

Substrate for the enzyme responsible for reuptake of NE and DA. AKA prevents reuptake of NE and DA.

Not metabolized by MAO and is stored in NT vesicles.

causes a release of intracellular stores of NT via a reversal of the reuptake enzyme.

Question 18

Amphetamine therapeutic uses

Answer 18

ADHD- improves attention

Narcolepsy

Question 19

Methylphenidate

Answer 19

Very similar to amphetamine, but enters brain more slowly, not allowing dopamine levels to be increased as rapidly. This weakens the reward response - less potential for abuse.

Question 20

Methylphenidate therapeutic use- one of the most rx’d meds for children

Answer 20

Tx of ADHD. Works by self stimulation. unknown.

Question 21

Armodafinil and modafinil MOA and therapeutic use

Answer 21

Similar to amphetamine. Specific for dopamine transporter. Prevents reuptake of dopamine.
Use: Tx narcolepsy and other sleep disorders

Question 22

LSD MOA, dependence and adverse effects.

Answer 22

5HT agonist activity and activation of sympathetic NS
True dependence is rare
Hyperreflexia, nausea, and muscular weakness.

Question 23

How do endogenous cannabinoids work?

Answer 23

They are released from post synaptic neuron after it hyper polarizes. The endocannabinoids bind to the cannabinoid receptors on the presynaptic neuron and stop the release of inhibitory neurons such as GABA

Question 24

PCP MOA
Results
High doses cause what

Answer 24

Inhibits reuptake of DA, 5HT, and NE
Main action is to block NMDA glutamate receptor. This prevents the passage of Ca.

Causes insensitivity to pain without loss of consciousness. Separates mind and body. Numb extremities, staggered gait, slurred speech.

High doses cause anesthesia, stupor, coma.
Eyes stay open in PCP coma!

Question 25

2 nonaddictive drugs of abuse

Answer 25

LSD and PCP
They alter perception without causing sensations of reward/euphoria. May still cause long term side effects- permanently altering perception. Flashbacks/psychosis.