Drugs final

Describe the mechanisms of action through which TCAs, MAOis and SSRis produce antidepressant effects

After first treatment, TCA's produce antidepressant effects by inhibiting the norepinephrine transporter, flooding the extrasynaptic space and overstimulating the body's autoreceptors (postsynaptic beta receptors and presynaptic alpha 2 receptors). After 3 weeks, TCA's cause a downregulation of the alpha 2 autoreceptor and beta-receptors which increases the release of norepinephrine and causes antidepressant effects. MAOis produce antidepressant effects by overstimulating presynaptic alpha 2 receptors and postsynaptic beta receptors, which causes downregulation and causes antidepressant effects after several weeks- similar to TCA's. SSRi's produce antidepressant effects by blocking 5-HT transporters and increasing levels of 5-HT. The exact mechanism is unknown, but similar to the other two antidepressants discussed, the antidepressant effects of SSRi's take several weeks to be noticeable.

List an example of an 'agent,' 'host' and 'environmental' factor that might contribute to the addiction process. Briefly describe how these factors might interact to 'fast-forward' the addiction process.

An agent is a drug like heroin which can be consumed into the body and make someone addicted. The route the drug is taken, like IV drugs, can make someone get addicted faster. A host is the user and a factor that affects the addiction process is heredity. If a family member had addiction, someone is more likely to also be an addict. Lastly, the environment, like social settings where others are using drugs, can make someone develop an addiction more easily.

Xanax is a schedule _______ drug.

4

What is a drug?

A chemical that alters the physiology of the body other than food or nutrients

You think a newly discovered drug, EBO71, might be an effective anxiolytic. 1. How would you determine if this drug produces anxiolytic effects? 2. After determining that EBO71 is a benzodiazepine, what differences exist between EBO71 and a barbiturate. 3. If EBO71 is a benzodiazepine, what is its mechanism of action?

(1.9/2) Anxiolytics are drugs are therapies to control anxiety. An elevated plus maze could test this drug in animals in a 4 armed apparatus and judging whether they went to the opened arms. Barbiturates depress ANS transmission and are very potent compared to benzodiazepines, also barbiturates are more addictive. If EBO71 was a benzodiazepine, it would be metabolized in the hepatic system and produce a longer half-life. It helps with sedation in sleep disorders and relaxing muscles for people with muscle spasms. They are potentiators with GABAergic inhibitory transmission but are not uptake inhibitors. This results in decreased neuronal activity.

1) Compare and contrast how amphetamine, MDPV, mephedrone and cocaine are thought to increase dopamine concentration in the brain. 2) Describe the neurotoxic effects of MDMA and how ambient temperature might contribute.

(got 1.9/2) Amphetamines are taken into the terminal and then bind to a carrier and increase inward-facing transportation sites in order to reverse transport dopamine to the outside of the cell. Cocaine is an update inhibitor but amphetamines contrast by being releasers. Mephedrone is very effective in blocking dopamine reuptake and and stimulating its release. It also releases a large amount of serotonin. MDMA has many neurotoxic effects and can cause hyperthermia in high temperate and hypothermia in low temperatures. MDMA decreases serotonin, it's synthesis, metabolites, and transporters.

Match the agonist with the endogenous transmitter it mimics

- Heroin = endorphin - Nicotine = acetylcholine - delta-9-THC = anandamide - Benzodiazepines = GABA

Match the root term to its meaning:

- Psycho = Relating to behavior and mental processes - Neuro = Relating to the nervous system - Pharmaco = Relations to principles of drug action - ? = often (but not always) referring to conditioning models

Many psychoactive drugs (and all drugs of abuse) are scheduled according to the ____________

1970 controlled substances act

Cannabis is a schedule ____ drug; cocaine is a schedule _______ drug.

1; 2

Which of the following is a tryptamine hallucinogen: A. DMT B. Mescaline C. MDA D. Both mescaline and MDA

DMT

Sativex is a medicine currently approved for the treatment of spasticity in Great Britain that is composed of equal parts:

Delta-9-THC and cannabiDiol

List, and briefly describe, three theories that might explain the high co-morbidity between addiction and psychiatric disease.

Disorder Fostering Disorder (continuing to take drugs to not withdraw), overlapping Neurobiological pathways (repeated neural disruptions from drugs causing health problems), Underlying Genetic Factors (more likely to be an addict if a family member was).

Note: hypothetical situation with made up values to simplify your math. We are designing a new analgesic drug. We determined that drug EBO1 has an ED50 of 50 and LD50 of 100; whereas, drug EBO2 has an ED50 of 90 and an LD50 of 100. Which drugs therapeutic index is safer for clinical practice?

EBO1

List 5 potential medicinal uses for cannabis.

Epilepsy, Glaucoma, anti-inflammatory, nausea, anorexia

List three mechanisms a chemist might exploit to enhance neural processing in pathway x.

Examples of correct answers: - A chemist may exploit the precursor and synthesizing process of a target neurotransmitter in the pre-synaptic neuron, reducing the amount of the NT being produced; Target a specific receptor on the post-synaptic neuron, increasing the affinity of a NT to the targeted receptor; or they may target the re-uptake transporter, inhibiting or blocking it's function, allowing for more of the desire NT to remain within the synaptic cleft. Lastly, they may target the enzymes that metabolize NTs in the synapse. 1.) Manipulate vesicular packaging of neurotransmitters that are part of pathway x to enhance neural processing. 2.) Target postsynaptic receptors in pathway x to enhance neural processing. 3.) Target degradative enzymes for neurotransmitters that are in pathway x to enhance neural processing. 1. Target Receptor 2. Synthetic Enzymes 3. Degradation Systems

The below questions refers to the following title of a research article published in the journal Psychopharmacology: The effects of heroin on simulated driving performance. It is likely that the independent variable in this study is ____________.

Heroin dose

Your psychopharmacologist friend quickly intervene, stating that the use of psilocybin or MDMA in your practice would result in you being arrested and might produce serious side effects for the patient if administration is not optimized. Your psychopharmacologist friend shares several behavioral/physiological effects of increasing serotonin neurotransmission in the brain. You disagree, stating that you would NOT observe the following in response to increased serotonin.

Increased aggression

Briefly describe how tardive dyskensia develops (neuroscientific answer)

It is a side-effect of long term treatment with antipsychotics from their dopamine receptor blocking properties. This results in involuntary movements of the body. In the A9 dopamine pathway, it causes a super-sensitivity of D2.

Briefly describe agranulocytosis.

It is the lack of granulocytes and decreased white blood cells. It is often a side-effect of clozapine.

Match the following ligands with their primary receptor target

Kappa = dynorphin Delta = enkephalin Mu= beta-endorphin

Briefly describe how morphine is thought to increase dopamine concentrations within the mesolimbic pathway.

Morphine increases dopamine concentrations in the mesolimbic pathway through binding to mu opioid receptors in the GABA terminal which inhibits GAPA release on the top of the dopamine cell and disinhibits the dopamine neuron. This process then increases dopamine concentrations in the mesolimbic pathway.

How does surround inhibition prevent the spread of a seizure focus? What are three GABA-based mechanisms of drug action that can be used to create surround inhibition? Name one drug corresponding to each of the three mechanisms of action.

NOT GRADED Surround inhibition controls the magnitude of a seizure through GABAergic neurons which help the surround inhibition to be overcome and the afterhyperpolarization helps prevent the spread. AED drugs (barbiturates) are GABA-based mechanisms which creates surround inhibition by binding to GABA receptors and causes potentiation in the receptors. Pintobarbital or benzodiazepines bind to an allosteric modulator of the GABA-a receptor which increases hyper-polarization of the cell. Phenolbarbital, Canabadiol, benzodiazepines.

The psychopharmacologist David Nutt is enjoying an alcohol substitute as Roland Griffiths is enjoying his left hand milk stout, and chimes it that he even considers the use of MDMA is psychotherapy, which is a ______________ hallucinogen that resembles _____ in the brain and is thought to produce visual hallucinations by binding to the ______ receptor, amongst others.

Phenethylamine; catecholamines; 5-HT2A

Morphine is used to synthesize heroin. Heroin is classified by the United States as a ________ drug, meaning that heroin is considered to be devoid of medicinal uses while exhibiting a high abuse liability.

Schedule 1

List two neuroanatomical changes covered in class that occur in schizophrenic patents.

Schizophrenic patients can have 40% enlargement of ventricles and the prefrontal cortex had issues like decreased volume and abnormal white matter.

because vicodin contains both hydrocodone and acetaminophen (trade name tylenol), vicodin is a drug preparation.

True

Frank Grimes walks into the pub, and his feelings are hurt that you failed to invite him to dinner. You see his depressive state of mind emerging and go to speak to him. On your way back to your table a researcher named Roland Griffiths stop you and asks you about your patient. He want to know if you have every considered the use of psilocybin in any of your sessions. You recognize the psilocybin is a ____________ hallucinogen that resembles _____ in the brain and is thought to produce visual hallucinations by binding to the ______ receptor, amongst others.

Trypamine; serotonin; 5-HT2A

This physician introduced Cannabis Indica to Western Europe as a medical treatment to treat spasticity?

William Brook O'Shaughenssy

Chemical warfare agents and insecticides prevent the enzymatic degradation of ____________.

acetylcholine

By administering methadone as an _______ therapy for heroin addiction, medical doctors are most interested in maintaining __________

agonist therapy; steady-state plasma level

Opiates are used medicinally to produce all of the following EXCEPT:

anti-tremor effects

Mu-opioid receptor desensitization is mediated by:

beta-arrestin

Which of the following is a phenethylamine hallucinogen? A. both mescaline and MDA B. MDA C. mescaline D. DMT

both mescaline and MDA

Which is an origin of a dopamine pathway:

both substantia nigra and ventral tegmental area

The following non-psychoactive cannabinoid is well documented to decrease inflammation yet is being bred out of many strains of cannabis in the United States

cannabiDiol

How does a systemic increase in serotonin effect cocaine self-administration in preclinical studies.

decreases motivation for cocaine

Which technique would be best to assess the abuse liability of a drug?

drug self-administration

Many synthetic cannabinoids are _________ agonists for the cannabinoid CB1 receptor, whereas delta-9-THC is a _________ agonists for the cannabinoid CB1 receptor.

full; partial

Which technique would be best to assess whether a syringe increases blood flow in a particular brain region of human heroin addicts?

functional magnetic resonance imaging

The name "morphine" is the ______________ for the predominant psychoactive drug found in the opium poppy.

generic name

AMPA is a(n) ________ receptor; muscarinic is a(n) _________ receptor.

glutamate; acetylcholine

Using the dose response curve below, __________ is the most potent drug; ____________ is the least effective drug.

hydromorphine; aspirin (highest and furthest left; lowest and furthest right)

Freeman & Watts introduced a surgical technique for frontal lobotomy to calm schizophrenic patients. While the early 'technique' involved drilling holes; later Freeman developed his famous transorbital approach by literally pushing a(n) _______ into the brain via the eye sockets.

icepick

Your best childhood friend Samuel Adams was always able to drink four times as much alcohol as you, even the first time you experimented with drinking. As an experienced psychopharmacologist, you are now concerned about Sammy developing alcoholism, as you recognize he displays ____________ tolerance—which likely predisposes him for alcoholism.

innate

Activation of this form of the brains two main receptor classes will elicit the fastest change in neural activity.

ionotropic

A primary origin of brain noradrenergic pathways is _________; a primary origin of brain serotonergic pathways is __________.

locus coeruleus; raphae nuclei

The ____________ neurotransmitter system is thought to be hyperactive in the brains of schizophrenics, while the ______________ neurotransmitter system is thought to be hypoactive in the brains of schizophrenics.

mesolimbic dopamine; frontal glutamate

Naloxone is an prototypical antagonist at the _________ receptor,

mu

This theory posits that 'chasing the dragon' (i.e., trying to achieve a similar heroin high) is impossible due to diminished rewarding effects of heroin resulting from continued abuse; rather, the escape from withdrawal (which becomes more pronounced with repeated abuse) is the primary driving force of addiction.

opponent process

_______ tolerance occurs as a result of cellular adaptation to the presence of a specific drug.

pharmacodymaic

Chlorpromazine (typical) would likely be better at treating __________ symptoms, while clozaril (atypical) would likely be better at treating __________ symptoms.

positive; negative

The Swedish Conscript Study and the Dunedin Study both suggest that, in susceptible individuals, adolescent cannabis use might increase the risk for developing

schizophrenia

The Leyton lab showed that amphetamine can produce enhanced rewarding and dopamine releasing effects following intermittent administration to college students, a phenomenon known as ____________

sensitization

Which of the following neurotransmitter systems is thought to be altered in schizophrenia and is especially being targeted by the development of second-generation atypical antipsychotics:

serotonin

The below questions refers to the following title of a research article published in the journal Psychopharmacology: The effects of heroin on simulated driving performance. It is likely that the dependent variable in this study is ____________.

simulated driving performance

Tasks learned in the presence of a psychoactive drug may subsequently be performed better in the drugged than nondrugged state because of the phenomenon known as.

state-dependent learning

The specific effect of a particular drug at a particular synapse is largely determined by.

the receptor subtype(s) it binds to

In the dose-response curve, a decrease in potency is indicated by a shift

to the right

Which technique would be best to assess whether a drug-paired cue transiently (i.e., in a short lived fashion) increases dopamine release in a behaving rat?

voltammetry