Antidepressants

Question 1

What theory describes depression?

Answer 1

Biogenic amine theory.

Deficiency in NE and 5-HT

Question 2

What supports the biogenic theory?

Answer 2

Drugs that inhibit the reuptake and inhibit metabolism of neurotransmitters

Question 3

TCAs block the reuptake of what neurotransmitters?

Answer 3

NE,DA,5-HT

Question 4

TCAs can also block what receptors?

Answer 4

H1, muscarinic, alpha1 alpha2, D2, 5-HT1, 5-HT2

Question 5

Which class has a twisted structure?

Answer 5

TCAs

Question 6

TCAs with basic 3’ amine are selective for? 2’ amine?

Answer 6

3’ amine = 5-HT
2’ amine = NE
Reuptake transporter

Question 7

What are the three subclasses of TCAs?

Answer 7

Dibenzoazepines
Dibenzocycloheptanes
Dibenzoxepines

Question 8

How do TCAs differ from typical antipsychotics?

Answer 8

Antipsychotics are symmetrical, central ring contains 2 heteroatoms

Question 9

On a TCA the N-substituent should be what? Why?

Answer 9

No longer than a methyl.
Will cause decrease in activity.
Will cause increase in toxicity.

Question 10

What is bioisosteric?

Answer 10

Exchange atom or group to another to create a new compound similar to the parent compound.

Question 11

The aminoketone drug is used to treat what? Which uptake is blocked?

Answer 11

Treats smoking cessation, depression, withdrawal
Blocks DA in ketone form.
Blocks NE when reduce to an alcohol.

Question 12

What do triazolopyridines do?

Answer 12

5-HT2 antagonist
5-HT1 agonist
5-HT reuptake blocker

Question 13

What are some characteristics of triazolopyridine?

Answer 13

Aryl piperazine long chain
Cause hepatotoxicity
Increase sucidial ideation

Question 14

What is the difference between TCAs and SNRIs?

Answer 14

Missing central ring
Cyclohexane in place of aromatic ring
Fewer side effects

Question 15

What is important about the SNRI that contains an ether off aromatic ring?

Answer 15

It is weak DA reuptake inhibitor.

Question 16

What is important with the SNRI that contains a 3 atom ring?

Answer 16

It is used to treat fibromyalgia as well as depression.

Question 17

What is important about the aryl piperazine long chain that contains an alkyne(triple bond)?

Answer 17

It is not a triazolopyridine.

It has a lower risk of hepatotoxicity.

Question 18

How does the selective a2- antagonist help treat depression?

Answer 18

Blocks NE and 5-HT receptors presynaptic

Question 19

The long chain aryl piperazine that contains a 5 member ring, di-amide functions as?

Answer 19

5-HT1a agonist
Postsynaptic in limbic cortex
Treats depression

Question 20

The subtype MAO-A metabolizes what?

Answer 20

NE & 5-HT

Question 21

The subtype MAO-B metabolizes?

Answer 21

DA, phenylethylamines.

Question 22

MAO catalyzes what type of reaction?

Answer 22

Oxidative deamination.

Primary amine becomes an aldehyde.

Question 23

What cofactor is needed for MAO to function?

Answer 23

FAD becomes FADH.
Radical combination then protonation
Electron transfer then protonation

Question 24

Describe the non selective MAO inhibitors.

Answer 24

They contain a hydrazine or hydrazide.

They produce free radicals such as phenethyl, isopropyl, benzyl

Question 25

The non selective MAO that contains a propargylamine, describe its differences.

Answer 25

Michael acceptor that alkylates the flavin cofactor. Conjugated with double and triple bonds. Its a very reactive electrophile. Forms an iminium.

Question 26

Describe the selective MAO-A inhibitor.

Answer 26

Aryloxypropylamine. Propargylamine Blocks metabolism of NE and 5-HT

Question 27

Describe the selective MAO-B inhibitors.

Answer 27

Propargylamine Phenethylamine Benzylamine- fusion. Blocks metabolism of DA.

Question 28

Why should patients avoid tyramine when taking an MAOI?

Answer 28

Tyramine is converted to a false neurotransmitter | May precipitate hypertensive crisis.

Question 29

Bipolar disorders may result from abnormalities in what?

Answer 29

Abnormal G proteins. | Abnormal signaling: adenylase cyclase, phosphoinositide, Na/K/Ca exchange, phospholipase, cAMP

Question 30

What are the causes of bipolar disorder?

Answer 30

1. Genetics 2. Environment 3. Stress 4. Nutrition 5. Neurotransmitters

Question 31

What are the excitatory neurotransmitters? Inhibitory?

Answer 31

``` Excitatory= Ne, Da, glu, asp Inhibitory= gaba, serotonin ```

Question 32

What causes mania? | What drugs treat?

Answer 32

Excess Da and Ne | Da antagonists, a2 agonist

Question 33

What causes depression? | What treats it?

Answer 33

Deficiency in Da, Ne, 5-HT | Uptake blockers for da,ne,5-ht and maoi

Question 34

What can cause an increase in Da or NE?

Answer 34

Deficiency in GABA treat with benzodiazepine or valproate | Excess glu treat with lamotrigine, lithium

Question 35

What can cause manic episode by disrupting cholinergic-adrenergic balance? What treatments?

Answer 35

Deficiency in Ach. | Treat with cholinesterase inhibitor, central muscarinic agonist

Question 36

What can increase the risk of depressive episodes? | What treatment?

Answer 36

Increased Ach levels in CNS | Anticholinergics

Question 37

How do hormones affect bipolar disorder?

Answer 37

``` Hyperthyroidism = mania Hypothyroidism = depression ```

Question 38

What type of pumps can lithium occupy, what effect does it have?

Answer 38

Sodium pumps, failure of action potential thus decrease in neurotransmitter release.

Question 39

What are all of the actions of lithium?

Answer 39

1. Suppression IP3 by inhibition of inositol 2. Normalize G protein, adenylate cyclase 3. Decrease uptake of 5-HT 4. Increase sensitivity of 5-HT receptors 5. Decrease DA synthesis 6. Increase Gaba activity 7. Decrease glu activity 8. Decrease calcium transport into cells

Question 40

What drug can cause nephrogenic diabetes insipidus?

Answer 40

Lithium

Question 41

What drug is a succinic semialdehyde dehydrogenase SSD inhibitor? What effect does it have?

Answer 41

``` Valproic acid Decrease metabolism of GABA Blocks GABA uptake Normalize Na/Ca channel Decrease inositol and protein kinase C ```

Question 42

What does the drug containing a diaminotriazine do?

Answer 42

Lamotrigine Blocks voltage sensitive Na and Ca channels Decrease asp/glu release

Question 43

What receptors do the atypical antipsychotics function at?

Answer 43

Weak D2 antagonists | 5-HT2a/2c antagonists

Question 44

What drugs block Na and Ca channels?

Answer 44

Anticonvulsants | Off label for bipolar disorder