Drug Mechanisms Flashcards by Caroline Motschwiller

Mechanism of action of typical antipsychotics

(a) pathway of therapeutic efficacy

Antagonism of dopamine D2 receptors

(a) Therapeutic efficacy against positive symptoms due to D2 blockade in mesolimbic dopamine pathway

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What side effects does D2 blockade cause by blocking the following pathways

(a) nigrostriatal
(b) tuberoinfundibular
(c) mesocortical

Dopmaine pathways

(a) Nigrostriatal blockade => EPS
(b) Tuberoinfundibular blockade => hyperprolactinemia
(c) Mesocortical blockade worsens negative symptoms (alogia, avolition) and cognitive symptoms (poor attention and vigilance)

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3 receptors (besides DA) antagonized by typical antipsychotics

Anti:

histamine-1
alpha-adrenergic
muscarinic (type of cholinergic)

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General mechanism of atypical antipsychotics

Antagonism of D2 and 5HT2 receptors

dopamine D2 and serotonin 2A receptors

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Describe the effect of the 2 receptors blocked by atypical antipsychotics

(i) Blocking D2 in the mesolimbic dopamine pathway = therapeutic effect against positive symptoms (ex: hallucinations, delusions)
(i) Blocking 5HT2A in mesocortical, nigrostriatal, and tuberoinfundibular pathways enhances DA transmission => mitigating ‘typical’ side effects

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What receptors do atypical antipsychotics block?

Therapeutically: D2 blockade
Decreased ‘typical’ side effects due to 5HT2A blockade

Also blocks to varying degrees:
muscarinic, alpha-adrenergic, histamine-1

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Mechanism of clozapine

Atypical antipsychotic

-wide antagonism: 5HT2A, D1, D2, D4, H1, muscarinic, and alpha1

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Mechanism of risperidone

Atypical antipsychotic

-antagonism: 5HT2A, D2, alpha1

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Mechanism of olanzapine

Atypical antipsychotic

wide antagonism: 5HT2A, D1, D2, D4, H1, muscarinic, and alpha 1 (same as clozapine)
among the atypicals, may have efficacy second only to clozapine

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Mechanism of quetipaine

Atypical antipsychotic (quetiapine = Seroquel)
-antagonism: 5HT2A, D2, alpha1, alpha2, H1

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Mechanism of ziprasidone

Atypical antipsychotic
(ziprasidone = Geodon)
-antagonism: 5HT1A, 5HT2A, D2, D3, and monoamine reuptake pumps (NE, 5HT, DA)

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Which antipsychotic inhibits monoamine reuptake pumps?

Ziprasidone (= Geodon)

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Which atypical antipsychotics antagonize muscarinic receptors?

clozapine

- olanzapine

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Mechanism of aripiprazole

Aripiprazole (Abilify) = atypical antipsychotic

antagonism: 5HT2A
partial agonism: D2, 5HT1A

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Mechanism of therapeutic action for TCAs

Tricyclic Antidepressants proposed mechanism:
antagonism at serotonin (5HT) and NE presynaptic reuptake pumps

-Not fully understood- may involve receptor and downstream secondary messenger transcription changes

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Name all the receptors blocked by TCAs

Therapeutically block reuptake pumps: 5HT and NE

Block receptors: muscarinic, alpha-adrenergic, H1

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Latency period of TCA activity

3-4 weeks of administration for therapeutic effect to begin

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What is the difference btwn the two groups of TCAs?

TCAs grouped into tertiary and secondary amines b/c this predicts side effect profile

Tertiary amines: greater alpha, H1, and muscarinic blockade

Newer, secondary amines: fewer side effects, less sedating, safer in OD

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Mechanism of action of MAOIs

Irreversible MAO (monoamine oxidase) inhibitors
-MAO metabolizes monoamines (5HT, DA, and NE) in the presynaptic neuron => MAO inhibition disables momamine degradation

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MAO-A vs. MAO-B

(a) Which is blocked by psychiatric drugs?
(b) Which blockade is necessary for therapeutic effect?

MAO-A vs. MAO-B

(a) Psychiatric drugs block both
(b) Only MAO-A blockade is necessary for the anti-depressant effect. MAO-A is used to break down tyramine

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What other receptors are blocked by MAOIs?

MAOIs also block these receptors:

alpha1 adrenergic
histamine1

Mechanism of patch form MAOI?

Patch form = transdermal selegiline
-MAOI that at lower doses is selectively MAO-B inhibitor => MAO-A is still around to metabolize tyramine => lower dietary restrictions when selegiline used at lower dose

Which drug is suggested to have the best efficacy for depression among all new antidepressants?

Venlafaxine (Effexor)

-SNRI

Mechanism of action of SSRIs

Selective antagonism of 5HT presynaptic reuptake pumps

Site of action of SSRIs

Thought to be frontal serotonin projections

Latency period of SSRIs

Same as TCAs: therapeutic effect begins only after 3-4 weeks of administration

Mechanism of mirtazapine

Mirtazapine (Remeron) = NaSSA = Noradrenergic and specific serotonergic antidepressant Dual mechanism - antagonism at central alpha2 autoreceptors => disinhibition of NE and 5HT release - stimulation of alpha1 somatodendritic receptors on serotonin neurons => boosts 5HT release

Name all the receptors that mirtazapine acts on

Mirtazapine (Remeron) - antagonism of central alpha2 - stimulation of alpha-1 - blocks: 5HT2A/2C/3 and H1 receptors

Mechanism of trazodone

Trazodone = SARI = serotonin antagonist and reuptake inhibitor -selective antagonism at 5HT presynaptic reuptake pump w/ simultaneous 5HT2A blockade

Mechanism of nefazodone

Nefazodone = SARI = serotonin antagonism and reuptake inhibitor - antagonism of 5HT reuptake pump - 5HT2A receptor blockade (to protect against sexual dysfxn as side effect)

Mechanism of bupropion

Bupropion = Wellbutrin = Noradrenergic and dopamine reuptake inhibitor -antagonism of presynaptic NE and DA reuptake pumps

Mechanism of Vilazodone and vortioxetine

Selective serotonin reuptake inhibitor and serotonin partial agonist

Mechanism of action of benzos

Full agonism of GABA-A receptor by increasing frequency of chloride channel openings

Which are the most addictive benzos?

High potency, short half-life (b/c rapid onset) ex: Alprazolam (Xanax) = short half-life and high potency

What drugs are helpful in EtOH withdrawal, explain the mechanism

Benzos can be used in detox in sedative and alcohol addiction due to cross tolerance w/ alcohol and barbiturates

Which benzos are safer in liver disease?

Lorazepam (Ativan), Oxazepam (Serax), and temazepam (Restoril) don't require oxidation in the liver => safer in liver disease -all 3 are short half-life benzos

Mechanism of buspirone

Buspirone = nonbenzo anxiolytic -5HT1A agonist -unclear mechanism of efficacy against anxiety

Mechanism of hydroxyzine

Hydroxyzine = nonbenzo anxiolytic | -sedating antihistamine

Mechanism of zolpidem

Zolpidem (Ambien) = GABAergic

Mechanism of zaleplon

Zaleplon (Sonata) = GABAergic | -short acting, can dose in middle of the night

Mechanism of eszopiclone

Eszopiclone (Lunesta) = GABAergic

Mechanism of diphenhydramine

Diphenhydramine (Benadryl) = sedating antihistamine

Mechansim of ramelteon

Ramelteon (Rozerem) = melatonin MT1 and MT2 receptor agonists -thought to normalize circadian rhythms

Mechanism of lithium

Unknown | -theory that has effect on modulation of secondary messenger systems

Lithium clearance

- not metabolized in the liver | - cleared almost entirely by the kidney

Carbamazepine mechanism of action

Unknown mechanism for its effects in mania | -has effect at Na/K channels, possibly enhances GABA

Valproic acid mechanism of action

Unknown mechanism for its effects in mania - inhibits Na/Ca channels => boosting GABA and decreasing glutamate (not known if this is the mechanism that provides mood stabilization) - can be rapidly loaded for quicker therapeutic effect

Gabapentin mechanism of action

GABAergic | -anticonvulsant mood stabilizer

Mechanism of action of the classic CNS stimulants

Stimulation of alpha and beta adrenergic receptors => triggers release of DA and NE from presynaptic terminals

Mechanism of atomoxetine

Atomoxetine = Strattera = novel CNS stimulant -selective inhibition of presynaptic reuptake of NE