Drugs of abuse Flashcards
Major target of addictive drugs is what system. And what 3 mechanisms alter it?
Mesolimbic dopamine system. AKA reward system.
- Disinhibit DA neurons. Opiods, benzo, alcohol
- Cause excitation of DA. Nicotine, alcohol
- Block DA uptake. Leave in synapse. Cocaine, amphetamine, ecstasy.
Dependence vs addiction
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.
Psychomotor stimulant effects
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.
Most widely consumed stimulant in the world.
Caffeine. Metabolites are theophylline and theobromine.
^^ all methylxanthines
methylxanthine proposed mechanism
Blocks adenosine receptors in CNS. Adenosine inhibits dopamine release.
So caffeine indirectly enhances dopamine transmission!
methylxanthines actions
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.
methylxanthines therapeutic use
Relax smooth muscles of bronchioles. Mainly theophylline for asthma therapy.
methylxanthines adverse effects and lethal dose.
Insomnia, anxiety, agitation
Vomiting and convulsions at high dose
Lethal dose is 10 g
Tolerance/withdrawal if 600mg per day then stop.
Nicotine mechanism at low and high doses
Low: ganglionic stimulation. Arousal/relaxation.
High: Ganglionic block. Receptors will turn off. Respiratory paralysis.
How does nicotine affect the PNS and CNS?
PNS: increases Ach and NE transmission
CNS: Increases dopamine transmission
basically enhances DA transmission and impairs regulatory system.
Nicotine CNS low and high dose effects
Low: Euphoria, arousal, relaxation. Attention, learning.
High: Central respiratory paralysis and hypotension.
Nicotine PNS low and high dose effects
Low: Increase blood pressure and HR, decreased coronary blood flow, increase bowel activity.
High: Decrease BP, activity of bladder and GI cease.
Varenicline MOA and use
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.
Cocaine MOA
Blocks reuptake of monoamines - NE, 5HT, and especially DA. This prolongs the effects of the NT.
Chronic use depletes DA= cravings.
Cocaine is the only drug that can cause death by
high dose and hyperthermia. Impairs sweating and cutaneous vasodilation, which is in place to help decrease body temp
Therapeutic use of cocaine
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.
Amphetamine MOA
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.
Amphetamine therapeutic uses
ADHD- improves attention
Narcolepsy
Methylphenidate
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.
Methylphenidate therapeutic use- one of the most rx’d meds for children
Tx of ADHD. Works by self stimulation. unknown.
Armodafinil and modafinil MOA and therapeutic use
Similar to amphetamine. Specific for dopamine transporter. Prevents reuptake of dopamine.
Use: Tx narcolepsy and other sleep disorders
LSD MOA, dependence and adverse effects.
5HT agonist activity and activation of sympathetic NS
True dependence is rare
Hyperreflexia, nausea, and muscular weakness.
How do endogenous cannabinoids work?
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
PCP MOA
Results
High doses cause what
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!
2 nonaddictive drugs of abuse
LSD and PCP
They alter perception without causing sensations of reward/euphoria. May still cause long term side effects- permanently altering perception. Flashbacks/psychosis.
