exam 2

Question 1

What does “vesiculation” mean? Do you think that drugs could affect it?

Answer 1

vesiculation = packaging neurotransmitter into vesicles in the presynaptic neuron
drugs absolutely can affect this process

Question 2

How are NMDA receptors and AMPA receptors similar? How are they different?

Answer 2

similar: they both bind glutamate
different: NMDA is ionotropic, admits Na+ and Ca2+ ; AMPA is ionotropic, admits Na+

Question 3

What role do astrocytes play in the breakdown and recycling of glutamate?

Answer 3

astrocytes mop glutamate out of the synapse, break it down into glutamine and then feed the glutamine back to neurons so they can make it into glutamate

Question 4

Explain what “excitotoxic” means.

Answer 4

basically, it means to excite a neuron so much, you kill it with excessive Ca2+ influx – a little Ca2+ causes plasticity, too much causes overexcitation and death

Question 5

Name one natural source of toxic levels of glutamate.

Answer 5

Red tide, grass pea, possibly cycads

Question 6

How are GABAA receptors and GABAB receptors similar? How are they different?

Answer 6

similar: they both bind GABA
different: GABAA is ionotropic, admits Cl- ; GABAB is metabotropic, lets K+ out

Question 7

What is the difference between GAD, GAT and GABA-T?

Answer 7

GAD (glutamic acid decarboxylase) makes GABA from glutamate
GAT (GABA transporter) = GABA reuptake transporter
GABA-T (GABA transaminase) breaks down GABA

Question 8

Name 3 conditions that anticonvulsants have been used to treat.

Answer 8

epilepsy, bipolar disorder, chronic pain, alcohol withdrawal, anxiety

Question 9

Describe 2 different ways a drug can act as a GABA agonist.

Answer 9

analogue (looks like GABA), can disable the GABA transporter (GAT), can disable GABA-T (enzyme that breaks down GABA)

Question 10

Name 2 ways that barbiturates differ from benzodiazepines.

Answer 10

barbiturates open the Cl- channel, benzodiazepines don’t
[barbiturates are more deadly than benzodiazepines for the above reason]
they bind different sites on the GABAA receptor
barbiturates disrupt sleep pattern
benzodiazepines have short, mid and long-acting forms
there is an antagonist for benzodiazepines (flumazenil)

Question 11

Take a look at the slide that lists the properties of barbiturates (slide # 11). What conditions do you think barbiturates were used to treat? Name at least 2.

Answer 11

insomnia, anxiety, epilepsy

Question 12

Name 2 ways that barbiturates differ from benzodiazepines.

Answer 12

barbiturates open the Cl- channel, benzodiazepines don’t
[barbiturates are more deadly than benzodiazepines for the above reason]
they bind different sites on the GABAA receptor
barbiturates disrupt sleep pattern
benzodiazepines have short, mid and long-acting forms
there is an antagonist for benzodiazepines (flumazenil)

Question 13

GHB, the “date rape drug” has a medical use. What is it?

Answer 13

it is prescribed to people with narcolepsy, to help alleviate daytime sleepiness and cataplexy

Question 14

Why is it problematic to prescribe benzodiazepines to the elderly?

Answer 14

• many benzodiazepines have long half lives and active metabolites and this is augmented in the elderly, such that some benzos can have a half life of days in the elderly
• their long action in the elderly can artificially induce dementia

Question 15

What is flumazenil and what is it used for?

Answer 15

• a benzodiazepine receptor antagonist
• it reverses benzodiazepine overdose

Question 16

What are DAT, NET and VMAT and what do they do?

Answer 16

DAT = dopamine transporter –> brings dopamine back into presynaptic cell

NET = norepinephrine transporter –> brings norephinephrine back into presynaptic cell

VMAT = vesicular monoamine transporter –> puts dopamine and norepinephrine into vesicles

Question 17

How does cocaine affect DAT, NET and VMAT? How does amphetamine affect them?

Answer 17

cocaine blocks DAT and NET
amphetamine reverses the action of DAT, NET and VMAT

Question 18

In your own words, explain what receptor downregulation means.

Answer 18

increased neurotransmitter release (perhaps due to drug influence) leads to a decrease in receptors on the post-synaptic cell

Question 19

Why do you think that anhedonia happens with long-term cocaine exposure?

Answer 19

cocaine is a dopamine agonist, but the long term effect of increasing it is to decrease the brain’s ability to react to it, leading to decreased overall dopamine activity and thus anhedonia

Question 20

Which has a longer duration of effect, cocaine or amphetamine?

Answer 20

amphetamine

Question 21

What are the symptoms of Parkinson’s disease? What is going wrong in the brain that causes those symptoms?

Answer 21

• there are a laundry list of symptoms, which include slowed movements (bradykinesia), muscle rigidity, resting tremor, postural insecurity
• the core problem is a lack of dopamine input to the basal ganglia, due to cell loss in the substantia nigra

Question 22

L-DOPA is a precursor of dopamine, used to treat Parkinson’s disease. Why can’t dopamine be administered, instead of its precursor?

Answer 22

• because dopamine does not cross the blood brain barrier
• the body also uses dopamine

Question 23

What is COMT? Why is it helpful to administer a COMT inhibitor in conjunction with L-DOPA?

Answer 23

• COMT is an enzyme that breaks down dopamine
• giving a COMT inhibitor along with L-DOPA prevents the L-DOPA from being broken down by COMT in the periphery

Question 24

Why can’t the cognitive side effects of Parkinson’s be treated with antipsychotics?

Answer 24

because those side effects are due to increased dopamine availability and if that was treated with antipsychotics those would decrease dopamine and bring on the movement symptoms again

Question 25

What would be the ideal treatment for Parkinson’s Disease?

Answer 25

the ideal treatment would be one that restores the dopamine producing cells in the substantia nigra, but the reason they are dying is unknown, so we can’t replace them unless we know what is killing them in the first place

Question 26

What are the positive symptoms of schizophrenia? What are the negative symptoms? How are the 2 categories of symptoms different from each other?

Answer 26

positive = hallucinations, delusions, disordered thought
negative = anhedonia, social withdrawal, blunted affect
positive are defined by the presence of something – like delusions, whereas the negative are defined by the absence of something – like affect

Question 27

Compare Parkinson’s Disease with schizophrenia – how is dopamine thought to be involved in each?

Answer 27

schizophrenia positive symptoms are associated with too much mesotelencephalic dopamine
Parkinson’s Disease is associated with too little dopamine in the nigrostriatal dopamine system

Question 28

What is the therapeutic mechanism of action of first generation antipsychotics (FGA)? [how do they suppress psychosis?] Also name one drug that is an FGA.

Answer 28

they block D2 receptors
chlorpromazine (Thorazine), haloperidol (Haldol)

Question 29

FGA are “dirty”, which means that they affect many neurotransmitters. Name one neurotransmitter (besides dopamine) that the FGA affect, and the associated adverse side effect.

Answer 29

possible answers include:
acetylcholine - memory impairment, sedation
histamine - sedation
norepinephrine - sedation

Question 30

How do the second generation antipsychotics differ from the first generation antipsychotics? How are they similar?

Answer 30

different: they block D2 receptors less strongly than the FGA and they also block 5-HT2 receptors, also, different side effects
similar: the SGAs block D2 receptors, mAch and histamine receptors