Depression and Dementia

What are Ach and glutamates roles in Alzheimer's disease?

low Ach

excessive glutamate (sometimes low glutamate)

What are the goals of treating dementia/alzheimers?

increase Ach

decrease glutamate

MOA of Aricept (Donepezil)?

inhibit AchE to increase Ach

How does Namenda (Memantine) work?

NMDA receptor antagonist, blocks glutamate binding

What are two main drugs used to treat Dementia?

Aricept

Namenda

What are Aricept (donepezil) and Namenda (memantine) used to treat?

Dementia

How do monoamines play a role in depression?

In someone with depression there are more MAO present, resulting in increased metabolism of monoamines --> less monoamines

What are monoamines?

dopamine, norepinephrine, serotonin

How does someones neuroanatomy dictate that they will have mild/moderate depression symptoms?

If they have low monoamine reuptake transporters, more monoamines will stay in the cleft (less degraded) --> less depression symptoms

How does someones neuroanatomy dictate that they will have severe depression symptoms?

If they have normal number of monoamine reuptake transporters, they will be took inside the cell and degraded easier resulting in less monoamines in the cleft --> more depression symptoms

What kind of drug is Amtriptyline (Elavil) and Nortriptyline (Pamelor)?

Tricyclic Antidepressants

Examples of Tricyclic Antidepressants?

Amitriptyline (Elavil)

Nortriptyline (Pamelor)

How do tricyclic antidepressants work?

blocks serotonin and NE reuptake

blocks many NT receptors throughout body

What are the side effects of TCAs?

blurred vision

orthostatic/postural hypotension

sedation

weight gain

seizures

What are the downsides to using TCAs?

lots of side effects

has a delayed effect (takes weeks to work)

What is an example a tetracycline?

mirtazapine (Remeron)

What kind of drug is Mirtazapine (remeron)

tetracycline

MOA of Mirtazapine (Remeron)

blocks presynaptic alpha-2 receptors --> increases NE

What are the side effects of Mirtazapine?

sedation

cardiovascular side effects

Examples of SSRIs?

Fluoxetine (Prozac)

Sertraline (Zoloft)

Citalopram (Celexa)

Paroxetine (Paxil)

Escitalopram (Lexapro)

Drugs that end in -oxetine, are what?

SSRIs

Drugs that end in -opram are what?

SSRIs

MOA of SSRIs

block reuptake of serotonin --> increased serotonin in the cleft

What is the most commonly used antidepressant??

SSRIs

What are the early onset side effects of SSRIs?

nausea

anxiety, agitation

insomnia

What are the late onset side effects of SSRIs?

weight Gain

weakeness

sexual dysfunction

withdrawal syndrome

What are the potential drug interactions with SSRIs?

serotonin syndrome with other drugs that increase serotonin

drugs that are also metabolized by CYPs

What are examples of SNRIs?

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

Desvenlafaxine (Pristiq)

What kind of drug are Venlafaxine (Effexor), Duloxetine (Cymbalta), and Desvenlafaxine (Pristiq)?

SNRIs

What kind of drugs are Prozac, Zoloft, Celexa, Paxil, and Lexapro?

SSRIs

What is the MOA of SNRIs?

block reuptake of serotonin and norepinephrine --> increasing serotonin and NE in the cleft

What other uses besides depression are SNRIs used for?

anxiety disorders

chronic nerve pain

What are the side effects of SNRIs?

blurred vision

dry mouth

insomnia

What a specific side effect of duloxetine (Cymbalta)?

seizures

What kinds of drugs can be used to treat depression?

TCAs

tetracyclines

SSRIs

SNRIs

NDRIs

5HT2 modulators

MOAIs

What kind of drugs is Bupropion (Wellbutrin)?

NDRI

What is an example of an NDRI?

Bupropion (Wellbutrin)

What is the MOA of NDRIs (Wellbutrin)?

blocks reuptake of NE and dopamine --> increased NE and dopamine in the cleft

What monoamine does NDRIs have a higher effect on?

dopamine > NE

What are the side effects of NDRIs?

dry mouth

insomnia

nausea

seizures

What is the benefit to NDRIs?

they dont cause weight gain or sexual dysfunction

What is an example of at 5HT2 modulators

Trazodone (Desyrel)

What kind is the MOA of Trazodone (Desyrel)?

5HT2a receptor antagonist and a 5HT1A receptor agonist --> decreasing serotonin stimulation

and

serotonin and NE reuptake blocker --> increasing serotonin and NE in the cleft

Overall: balances serotonin stimulation

Whats the advantage of using Trazodone?

it balances serotonin stimulation resulting in less side effects

What are the side effects of Trazosone (Desyrel)?

dry mouth

fatigue, sedation

N/V

What are examples of nonselective MAOIs?

Phenelzine (Nardil)

What is the MOA of nonselective MAOIs (Phenelzine/Nardil)?

irreversibly bind and inhibit MAOAs and MOABs, causing and increase in NT

What is the downside to nonselective MAOIs?

lots of side effects

What is an example of a selective MAOI?

Selegline (Emsam)

What kind of drug is Selegline (Emsam)?

selective MAO-B inhibitor

MOA of selegiline (Emsam)?

MOA-B inhibitor --> increases dopamine

What is selegiline (emsam) used for?

Parkinson's disease

What are the side effects of MAOIs?

Drowsiness/fatigue

decreased BP

decreased sexual function

weight gain

blurred vision

What are the drug interactions wit MAOIs?

Can cause serotonin syndrome if taken with another drug that increases serotonin

can cause over effect if taken with high dose of St. Johns Wort

What does St. John's Wort do at high doses?

blocks MAOs