CNS stimulants, drugs of abuse, and the addicted patient

Question 1

CNS stimulants

Answer 1

• Are either psychomotor or hallucinogens
• Psychomotor stimulants cause: excitement and euphoria, increased motor activity, decreased appetite, increased nervousness/anxiety
• Hallucinogens cause: profound changes in thought patterns and mood, little effect on brainstem and spinal cord, little effect on motor activity

Question 2

Caffeine 1

Answer 2

• Psychomotor stimulant that binds to adenosine receptors
• Adenosine accumulates during fatigue and binds to receptors which then inhibit the release of NTs to prepare brain for rest
• Caffeine is an adenosine receptor antagonist: blocks all adenosine receptors and increases firing of neurons and brain activity
• This causes the pituitary to release ACTH and other hormones
• Excites the sympathetic NS

Question 3

Caffeine 2

Answer 3

• Actions: decreases fatigue and increases alertness, high doses can produce anxiety and tremors
• Is an inotrope and chronotrope to heart, can cause cardiac ischemia and arrhythmias @ high doses
• Is a mild dieuretic and simtulates secretion of HCl from gastric mucosa
• Moderate doses can cause insomnia, anxiety, and agitation, high doses can cause emesis, convulsion, and arrhythmias

Question 4

Nicotine

Answer 4

• Rapidly crosses BBB and binds to nAchR of autonomic ganglia, adrenal medulla, and CNS (binding to receptor depolarizes all of these cell)
• Effect on CNS: nAchR found in regions involved in learning/memory, motivation and reward (hippocampus, striatum, amygdala, prefrontal cortex)
• Produces paradoxical state of arousal and relaxation via DA neurons in VTA, along w/ improving attention, learning, and problem solving

Question 5

Nicotine on the PNS and withdrawal Sx

Answer 5

• Effects on PNS: sympathetic system activated to increase BP (vasoconstriction) and HR, para activated in GI to increase intestinal motility
• Causes release of epinephrine from the adrenal medulla
• Withdrawal Sx (physical dependance develops rapidly): irritability, anxiety, restlessness, difficulty concentrating, headaches, insomnia

Question 6

Cocaine and ampethamines

Answer 6

• Cocaine locks the reuptake of monoamines (5HT, NE, DA) back into presynaptic terminal, thus potentiating the actions of these NTs in synapse
• Amphetamines increase the release of catecholamines into the synapse and also block the DA transporter

Question 7

Actions of cocaine

Answer 7

• In CNS produce increased awareness and euphoria, tremors and convulsions, respiratory and vasomotor depression, increase in respiration
• In ANS: potentiates action of NE and produces sympathetic hyperstimulation
• Produces hyperthermia by affecting the hypothalamus

Question 8

Therapeutic uses and adverse effects of cocaine

Answer 8

• Cocaine is used as a local anesthetic when applied topically and can be used as a local vasoconstrictor
• Adverse effects: most important are respiratory failure, CV (fatal arrhythmias and MI), and stoke/intracranial hemorrhage

Question 9

Actions of amphetamines

Answer 9

• Stimulates entire neuraxis resulting in increased: alertness, insomnia, decreased appetite, decreased fatigue, activation of SNS
• Adverse effects: highly addictive, can precipitate schizophrenic episodes, can cause heart palpitations, tachyarrhythmias, HTN, MI, CV collapse, nausea, vomiting, cramps, and diarrhea

Question 10

Bath salts

Answer 10

• Designer drugs that have similar actions as cocaine and amphetamines
• Have powerful addictive potential and increase the concentration of monoamines in the synapse

Question 11

Hallucinogens

Answer 11

• Induce altered states of perception, like dreaming but when awake
• Changes shapes and colors
• Being under the influence means you are incapable of normal decision making
• Little effect on motor function

Question 12

LSD

Answer 12

• Binds as an agonist to 5HT receptors on presynaptic cells in the midbrain
• Causes activation of the SNS: pupillary dilation, HTN, piloerection, hyperthermia
• Alter mood, physical dependence and tolerance can occur
• High disease can produce long-lasting psychotic changes in some individuals
• Can rapidly be aborted by use of haloperidol

Question 13

Marijuana

Answer 13

• Produces euphoria, relaxation, impaired short term memory, slow mental status
• Decreases muscle strength and impaired motor activity
• Produces delusions, enhanced sensory activity and is an appetite stimulant
• THC is highly lipid soluble
• @ high doses toxic psychosis can develop, and chronic use in adolescence may promote development of schizophrenia
• Tolerance and dependence can develop w/ chronic use

Question 14

Mechanism of action for marijuana

Answer 14

• Psychoactive ingredient (THC) binds to CB receptors in the presynaptic cells (found on both glutamate and GABA receptors)
• Upon binding to the CB receptors, there is an inhibition of presynaptic Ca channels and thus inhibition of NT release from the presynaptic terminal
• Clinical uses: anorexia from HIV/AIDS, anti-emetic for Cx pts, spasticity due to MS, glaucoma

Question 15

Pharmacology of drugs of abuse

Answer 15

• All addictive drugs increase DA release onto target structures from the VTA in the midbrain
• These targets include: nuc accumbens, prefrontal cortex, amygdala, and hypothalamus
• VTA to nuc accumbens and orbitolfrontal/prefrontal for 2 of the non-motor pathways related to forming goal-oriented behavior

Question 16

DA pathways in addiction

Answer 16

• Drugs will amplify DA release, which signals a positive prediction error and reinforces the behavior
• Chronic drug use leads to insertion of AMPA receptors into the postsynaptic membrane of the VTA leading to development of LTP btwn glutamatergic input on VTA from prefrontal, hippocampus, and amygdala
• Chronic use also stimulates an increase in FosB which leads to increased expression in Cdk5 in striatal neurons to promote axon growth and spine formation

Question 17

DA pathways in drug withdrawal 1

Answer 17

• LTP in VTA remains potentiated even after drug-seeking behavior is extinguished, thus long-term changes in synaptic function are not transient
• This facilitates the reinstatement of the drug-seeking even after years of abstinence
• These changes introduce another layer of neuroplastic changes that may lead to drug cravings and relapse

Question 18

DA pathways in drug withdrawal 2

Answer 18

• Over time initial depression in synaptic transmission reverses, and synaptic potentiation results. This causes behavior to seek the drug upon cues from the environment
• Addicts become progressively sensitized to drug-associated sensory cues that lead to cravings

Question 19

Criteria for etoh use d/o

Answer 19

• Problematic pattern of etoh use leading to clinically significant impairment or distress as manifested by 2 of the following w/in 12 mo period
• Etoh taken in larger amounts or over a longer period of time than was intended
• Persistent desire or unsuccessful efforts to control use
• Great deal of time/effort spent to obtain/use/recover from etoh
• Craving to use etoh
• Using etoh resulting in inability to work/school/home
• Recurrent use despite social or interpersonal problems exacerbated by etoh
• Recurrent etoh use resulting in situations that are physically hazardous
• Severity: 2-3 Sx= mild, 4-5 Sx= moderate, ≥6 Sx= severe

Question 20

Polyvagal theory

Answer 20

• 2 defensive systems, one by sympathetics (fight or flight) and one by parasympathetics (by vagus)
• The vagal defensive system induces immobilization, death feigning, fainting, and dissociation
• But the vagus nerve is 80% sensory (afferent), and visceral feelings are diffuse gets they color our perceptions and reactions to social situations
• This is important b/c the vagal sensory info influences the interaction that addicted pts have w/ their doctor and the best prognostic factor of recovery is the relationship (therapeutic alliance)
• The origin of the more complex (recently evolved) part of the vagus is in the nucleus ambiguous (is myelinated)
• The more complex pathways are used first, and more primitive pathways are used as the recent ones fail