Psychopharmacology Exam Two

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What are the basic pharmacodynamics and synaptic effects of amphetamines?

PNS: Powerful sympathomimetic CNS: blocks DAT and enters them to interfere with VMAT function[DAT run in reverse to release excess DA] similar effects at NETs, the norepinephrine transporters

The brain "reward circuit" involves neurons projecting from the ____ to the ___

Ventral Tegmental are (VTA); Nucleus Accumbens (NAc)

What are the distinctions between the addiction processes called "wanting" versus "liking"?

Wanting: dopamine released in pathways (VTC, PFC, NAc) Liking: Opioid peptides (endorphin, enkephalin) & endocannabinoid released in pathways

An important change that appears to commonly develop in the brain of chronic drug users:

a lower metabolic rate in the frontal lobe

Caffeine, nicotine, and ___ are the most widely used psychoactive drugs in our society

alcohol

Caffeine promotes wakefulness by acting as a(n):

antagonist as adenosine receptors

Regarding the neurotransmitter from the last question, what medical condition was it typically used to treat in the early 20th century?

asthma

The main current therapeutic use(s) of amphetamine is(are):

both narcolepsy & ADHD

From your reading: Which of the following would Lewis (2017) most agree with?

brain changes in addiction are similar to those in the development of other deeply learned habits

What are the pharmacokinetics of cocaine, including half-life?

cocaine half -life is 45 mins, coke and ethyn: 3 hours

When were the amphetamines discovered, and what are the historical trends in both its medical use abuse?

1920, medically used for asthma/inhalant ephedra in south america. in 70s abused and gov. pressured companies to decrease.

Nicotine withdrawal symptoms occur within about:

2 hours

Amphetamine abuse declined in the 1960s and 1970s due to all of the following reasons EXCEPT

A new fom of the dug appeared on the street that could be smoked known as "ice."

Combining the two isomers of amphetamine is used to create the drug ______________.

Adderall, for ADHD

At low doses, all amphetamines have the following effects, EXCEPT

decreasing blood pressure

Which of the following is MOST associated with developing stereotyped behaviors, paranoid delusions, and severe anorexia?

high dose (>50 mg), chronic amphetamine use

What brain damage has been associated with the abuse of methamphetamine?

maller hippocampus volume, linked with dementia-like symptoms at an earlier age decreased gray matter density in frontal lobe , cingulate gyrus Increased ventricular volume, reflects loss of tissue Increased white matter volume, due to glial scarring.

How does cocaine metabolism typically occur? Are there any substances that, if present in the bloodstream, substantially change this process?

metabolied by benzoylecgonine (6hr half-time). If mixed w alcohol half time is 3hrs and cocaine effects are longer.

Which of the following routes of administration would give the longest, most-sustained plasma levels of nicotine

patch

Higher doses of amphetamine (compared to low doses) are thought to stimulate:

release of norepinephrine

What are the general pharmacokinetics of ethyl alcohol?

- 20% occurs in stomach as first-pass metabolism - 80% in liver 1. ETHO. gets turned into acetaldehyde by alc. dehydrogenase (adh, makes it more toxic) 2. Acetal. into acetic acid by aldehyde dehydrogenase {ALDH} 3. Acetic Acids -> Co2 & h2o by ATOP [source of calories]

What are the general pharmacokinetics of caffeine?

- Absorption & Distribution: 99% absorbed in GI tract, water & lipid soluble reached blood in 45 min, peak ~2 hours - Metabolism: liver metabolizes 90% by CYP-1A enzymes

What are synthetic cathinones?

- Bath salts, designer stimulants; popularized as a "legal high" sold in gas stations, smoke shops, etc. - Effects similar to high dose methamphetamine, very bad side effects: psychosis, tachycardia, heart population, hyperthermia, tissue necrosis, rhabdomyolysis: body consumes its own protein. similar structure to amphetamines.

What brain areas are first affected by low doses of alcohol?

- Brain shrinkage - Left Putamen - right hippocampus

What are the pharmacologic approaches available for alcohol addiction?

- Diazepam - Disulfiram - Naltrexone - Acamprosate - Fluoxetine

What are the symptoms of caffeine withdrawal? How long do they last?

- Headache, tiredness, inability to concentrate, anxiety, irritability, low mood, muscle tension - Symptoms last 2-3 days; occur 12-24 hours after stopping

What are the general pharmacokinetics of nicotine?

- Inhalation, peal plasma level in about 10 mins, 1 cigg per hour will achieve steady-state plasma levels of nic to avoid withdrawal. - Nic quickly distributed throughout body, to brain, placenta and all body fluids. -Liver CYP-2A enzyme metabolizes 80-90% before kidney excretion.

What are the distinctions between treating alcoholism on the "reward" side vs. the "craving" side?

- Reward: naltrexone (revia, opioid antagonist) can reduce alcohol cravings & SSRI antidepressants - Craving: acamprosate (campral) acts as a NMDA Glu Antagonist (desensitizes receptors) & GABA agonist - 1st drug to detox & maintain alcohol abstinence

What do we mean when we say a drug is a sympathomimetic? How about parasympathomimetic?

- Sympathetic: release of adrenal gland epinephrine - Parasympathetic: NMJs of skeletal muscles

How do the pharmacokinetics of amphetamine differ from cocaine?

- amphetamine has a longer duration time

What brain areas make up what is often called the "reward pathway" in the brain?

- brain systems underlying pleasurable sensations from activities/substances - mesolimbic system: amygdala & nucleus accumbens - Mesocortical system: prefrontal cortex

What physiological effects does cocaine have on the cardiovascular and nervous systems, both short - and long-term?

- degrease gray matter with length of use - orbitofrontal cortex, anterior cingulate, parietal & temporal lobes, cerebellum

How do brain regions, neurotransmitters, and peptides play different roles in various addiction process?

- glutamate systems in the cerebral cortex - OFC, ACC, hippocampus (orbitofrontal cortex, anterior cingulate) - attention, learning, & memory systems in the brain

What is the nature of the evidence for cocaine's detrimental effects on the brain of users?

- gray matter reduction and more white matter - brain is overcompensating for damage by using glial cells as "scarring" causing permanent damage

What are the basic pharmacodynamics and synaptic effects of cocaine?

- interferes with presynap of dopamine transporters - reuptake inhibitor - direct influence on mesolimbic "reward" pathway and caudate-putamen, part of mesotriatal movement pathway

What do we mean when we consider drug "craving" as a learning phenomenon, related to classical conditioning?

- learning/memory of drug experience leads to intense wanting of drug

What are the criteria used to determine what "schedule" a controlled

- medical use - abuse potential - risk of dependency

The reinforcing effects of nicotine are due to nicotine's ability to

- stimulate VTA neurons to increase dopamine release into the nucleus accumbens. - increase glutamate release, which stimulates the VTA to release more dopamine. - lowering GABA release into the VTA, resulting in more dopamine release from VTA

How does genetics play a role in the effect of alcohol on different individuals?

- women take less to have higher BAC - high % of East Asians (Japan, Korea, some china) have a mutation in gene that produces aldehyde dehydrogenase (ADH)

What are some pharmacological or other approaches to treating nicotine addiction?

-Nonpharmacological approaches: likeliness of successful cessation increases w encouragement from health professional, rather than alone. -Nicotine replacement therapies (NRT): Objective isn't replace cigg with healthier alternatives. [gums, transdermal patches,inhaer] -e ciggs: controver. - Antidepressants: bupropion, wellbutrin, zyban. - varenicline, chanted.

How does the route of administration for various forms of cocaine affect the "high" experienced?

-chewing leaves is small high, cocaine HCL is powder, no effect if ate, intranasal is slightly more, IV faster peak. Smoking 8-10 seconds, highest peak

Can you describe the pharmacodynamics of alcohol?

-disrupts intracellular processes -positive allosteric modulator at GABA receptors -negative allosteric modulator at Glu NMDA receptors

What are the 2 main ways that the body and brain can develop tolerance to drugs?

1. Metabolic tolerance (metabolizing dose more quickly) 2. Cellular Adaptive Tolerance (receptor changes compensating for presence of drugs & its effects) 3. conditioned tolerance (behavior conditioning; drugs taking occurs in contexts)

What are the symptoms and criteria that the DSM-5 specifies for a diagnosis of Substance Use Disorder?

2-3 mild, 4-5 moderate, 6+ severe - impaired control, social impairment, risky use, pharmacologic dependence 1. Taking substance in larger amounts or longer than meant to 2. Wanting to cut back/stop but not being able to manage to do so 3. Spending a lot of time getting, using, or recovering 4. Cravings and urges to use 5. Not managing to do what you should at work, home and school 6. Continuing to use, even when it causes problems in relationships 7. Giving up important social, occupation or recreational activities 8. Repeatedly using over and over again even when it's caused damage 9. Continuing to use even when you know you have a physical/psychological issue that could worsen 10. Needing more of the substance to get the desired effect (tolerance) 11. Development of withdrawal symptoms, which is relived by more substance use

Can you describe the pharmacodynamics of caffeine?

3 Metabolites. Theophylline & Paraxanthine effects similar to caffeine (active), Thebromine [inactive, no brain effect] - caffeine can be converted into any of these. > ATP-> ADP-> AMP-> Adenosine.

The half-life of caffeine is

3 to 10 hours

What are the different forms and routes of administration for amphetamines and methamphetamine?

AM: oral, pill, nasal inhalation Meth: smoking "ice" iv

What kind of approaches are being tried to treat cocaine addiction? How are they proposed to work (if shown to be successful)?

Anti-depressants, mood stabilizers (bipolar): most show mixed record of success Dopaminergic agonists: can ease withdrawal symptoms, reduce relapse [ex: Wellbutrin] Antidepressants, re-uptake inhibitor for DA [amantadine: PD drug, Flu NMDA antagonists, increase DA release] actually a glutamate antagonist but by stand effect is elevated DA Glutamate/GABA regulations: Endabuse [Glu NMDAR antagonist, may also affect 5-HT] some trails indicate it helps ppl with addiction Topamax: an anticonvulsant: GABA agonist, also prescribed for migraine

What are the symptoms of nicotine withdrawal? How long do they last?

Anxiety, irritability, difficult concentrating, restlessness, weight gain, insomnia 2 hrs

What different kinds of pharmacological approaches exist for treating addiction?

Detoxification: Agonist substitution: Partial agonist substitution: Antagonists: Non-dopaminergic approaches: "New directions in treatment": vaccines, deep brain stimulus (DBS)

Research indicates that nerve fibers connecting the frontal lobe with the reward circuit involve:

Glutamate

Can you describe the pharmacodynamics of nicotine?

Nic fill agonists at nicotinic cholinergic receptors [nAChr], which are ionotropic [control NA+ & cA2+] - PNS (Sympathetic & Parasympathetic) - 2 hr half time - stimulates ACh release (from basal forebrain) also activates Dopamine & Opioid pathways

A drug company is developing a new drug, Ligabamax, they plan to market for chronic pain. Initial tests suggest that the drug has a high potential for abuse. This drug would most likely be placed on Schedule ___ if it eventually gets FDA approval

Schedule 2

Drugs are controlled substances which the DEA places on 5 schedules established by the controlled substances act (CSA). Placement on a schedule is based on all of the following except

The short-versus long-term toxicities of the drug

Currently, the most well-established pharmacological intervention for heroin addiction

agonist substitution treatments

From your reading: Lewis (2017) would agree with this statement: "if addiction is a disease, then so apparently is love". True or False?

True

Caffeine __ coronary arteries and ___ cerebral blood vessels

dilates; constricts

The pleasurable effects associated with drugs of abuse and "natural addictions" (e.g., overeating) are thought to involve effects on the

dopamine system

Amphetamine was originally synthesized from

ephedrine

In 1924, the raw material that amphetamine was originally synthesized from was found to have an effect similar to what neurotransmitter?

epinephrine

Amphetamine, in comparison to cocaine,

has a longer half-life

Adenosine levels ___ during the day promoting ___

increase; sleep

Evidence suggests that chronic drug use causes the brain of abusers to be _____ responsive to natural reinforcers, and _____ responsive to the presence of drugs with respect to dopamine transmission.

less;more

What effects of amphetamines are typical at low doses versus high doses?

low: 1 binds to presynap of dopaminergetic neuron, induces dopamine release in nerve terminal, binds to re-uptake receptors and blocks re-uptake, reverse and transports free range dopamine high: interacts w dopamine containing synaptic storage vesicles release dopamine [nerve terminal?] binds MAO in dopamine. and presents degradation of dopamine leaving free dopamine in nerve terminal.

Which route of administration for nicotine produces the highest peak plasma level of nicotine.

smoking a cigarette

How does route of administration affect the likelihood of cocaine addiction?

smoking it creates a high peak, and people want to keep feeling keep consuming the drug

The direct mechanism of action of nicotine on arousal levels is

stimulation of acetylcholine receptors

How easily is cocaine distributed throughout the brain and body?

very easily since its lipid and water solube

Do amphetamines still have legitimate medical use? If so, for what condition(s)?

yes, narcolepsy, asthma, limited military use and ADHD


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