Drug Mechanisms Flashcards
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
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)
3 receptors (besides DA) antagonized by typical antipsychotics
Anti:
- histamine-1
- alpha-adrenergic
- muscarinic (type of cholinergic)
General mechanism of atypical antipsychotics
Antagonism of D2 and 5HT2 receptors
dopamine D2 and serotonin 2A receptors
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
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
Mechanism of clozapine
Atypical antipsychotic
-wide antagonism: 5HT2A, D1, D2, D4, H1, muscarinic, and alpha1
Mechanism of risperidone
Atypical antipsychotic
-antagonism: 5HT2A, D2, alpha1
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
Mechanism of quetipaine
Atypical antipsychotic (quetiapine = Seroquel) -antagonism: 5HT2A, D2, alpha1, alpha2, H1
Mechanism of ziprasidone
Atypical antipsychotic
(ziprasidone = Geodon)
-antagonism: 5HT1A, 5HT2A, D2, D3, and monoamine reuptake pumps (NE, 5HT, DA)
Which antipsychotic inhibits monoamine reuptake pumps?
Ziprasidone (= Geodon)
Which atypical antipsychotics antagonize muscarinic receptors?
- clozapine
- olanzapine
Mechanism of aripiprazole
Aripiprazole (Abilify) = atypical antipsychotic
- antagonism: 5HT2A
- partial agonism: D2, 5HT1A
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
Name all the receptors blocked by TCAs
Therapeutically block reuptake pumps: 5HT and NE
Block receptors: muscarinic, alpha-adrenergic, H1
Latency period of TCA activity
3-4 weeks of administration for therapeutic effect to begin
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
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
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
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
