Psychopharmacology: Antipsychotic and Antidepressant Drugs Flashcards
Study of the drugs that affect cognition, affect, and behavior of an individual
Psychopharmacology
Inability to distinguish between what is real and what is not real
psychosis
most common psychotic disorder
Schizophrenia
Structural and functional changes in the brain
Schizophrenia
Dysregulated neurotransmitters
Schizophrenia
Hyperactive dopamine in the mesolimbic pathway theory
Dopamine theory
NMDA receptor hypofunction
NMDA theory
5 HT2A receptor hyperfunction in the cortex
Serotonin theory
what were were the first drugs found to be useful to reduce psychotic symptoms in schizophrenia
Reserpine and chlorpromazine
a neuroleptic agent; that is, it produces catalepsy in rodents and EPS in humans
Chlorpromazine
In the dopamine hypothesis of psychosis Increasing evidence implicates both ________ and ________ networks
serotonin and glutamate
antipsychotic drug with high incidence of EPS
Neuroleptic
D2»_space; 5-HT 2 receptors
Typical / Classic Drugs
Phenothiazine
Thioxanthine
Butyrophenone
Typical / Classic Drugs
5-HT 2»_space; D2 receptors
Atypical / Newer Agents
Clozapine
Olanzapine
Risperidone
Quetiapine
Ziprasidone
Aripiprazole
Atypical / Newer Agents
antipsychotic drugs are well absorbed _____
orally
True or False: antipsychotic drugs are
true
True or False: antipsychotic drugs are
true
True or False: antipsychotic drugs have short half lives
false, long
in this theory, Schizophrenia is due to excess of functional DA in mesocortical tracts in the brain
Dopamine hypothesis
Dopamine receptors
GPCR, D1- D5
Dopamine receptors in the caudate, putamen, cortex, hypothalamus negatively
coupled to adenylyl cyclase
D2
Blockade of D2
EPS (tremor, slurred speech, akathisia, dystonia)
has affinity for other receptors, Less EPS than first generation drugs
Atypical antipsychotics
All antipsychotic drugs block H1 receptor to some degree except:
- Haloperidol
- Iloperidone
- Lurasidone
First generation drugs:
dopamine receptor blockade
____________ path underlies its antipsychotic effect
Mesocortical-mesolimbic
this effect is due to the blockade of the chemoreceptor trigger zone
Antiemetic effect
Common adverse effects of Antipsychotics
Extrapyramidal symptoms, hyperprolactinemia (1st Generation)
Antipsychotics works by blocking
dopamine
histamine works as a
sedative
1st gen or 2nd gen: lower cost, EPS
1st
1st gen or 2nd gen: improves negative symptoms (emotional blunting,
social withdrawal, lack of motivation)
2nd
antipsychotic drugs are used together with ______ and _________ to treat mania
lithium, benzodiazapine
benzodiazepine works as a
sedative
Prevention of manic phase of bipolar disorder:
Aripiprazole, olanzapine, asenapine
Prevention of bipolar depression:
Quetiapine, lurasidone, olanzapine, carizapine
Meds for Tourette syndrome
Molindone
antipsychotics can be also used for
Alzheimer and Parkinsonism
Common with Haloperidol and more potent piperazine derivatives (Fluphenazine, trifluoperazine)
Dose dependent EPS : Parkinson like symptoms
how to manage Dose dependent EPS : Parkinson like symptoms
Mx: reduce dose, use of antimuscarinic agents
Also respond to antimuscarinic agents, or diphenhydramine
Movement problems akathisia, dystonia
autonomic effects are due to
blockade of peripheral muscarinic and alpha receptors
autonomic effects are seen more in:
Thioridazine»clozapine and atypicals»_space;haloperidol
this is due to alpha blockade common in elderly esp with phenothiazines
Postural hypotension
Hyperprolactinemia, gynecomastia, infertility is the effect of
D2 blockade in pituitary, prominent with Risperidone
Treat with dantrolene, diazepam, dopamine agonists
Neuroleptic malignant syndrome hyperthermia
chlorpromazine work as
sedative
Visual: retinal deposits with
thioridazine
Cardiac rhythm abnormalities:
thioridazine, quetiapine, ziprasidone
heals Agranulocytosis
Clozapine
Commonly used for manic phase of bipolar disorder
Lithium
Used in bipolar disorder to decrease manic behavior and reduces frequency and magnitude of mood swings
Lithium
Toxicity
̶ Tremor, sedation, ataxia, aphasia
̶ Thyroid enlargement
̶ Cardiac abnormalities in the fetus
Lithium
Prolongs inactivation of voltage gated Na channels, GABA A agonist
Valproic acid
antimanic effects when failed to respond to lithium
Valproic acid
Prolongs inactivation of voltage gated Na channels
Carbamazepine and lamotrigine
drugs for for mania and prophylaxis of depressive phase
Carbamazepine and lamotrigine
Feelings of sadness and or loss of interest in normally pleasurable activities, leading to emotional and physical problems, with resulting impairment in social, occupational and other areas of functioning for 2 weeks
Depression
Monoamine Hypothesis:
- compulsion
- sleep
- memory
- impulse
- repetitive and stereotypical behavior
Serotonin
Monoamine Hypothesis:
- pleasure
- reward seeking
- drive
Dopamine
Monoamine Hypothesis:
- energy
- alertness
- concentration
- vigilance
noradrenaline
Monoamine Hypothesis:
- anxiety
- irritability
serotonin + noradrenaline
Monoamine Hypothesis:
- sex
- appetite
- aggression
serotonin + dopamine
Monoamine Hypothesis:
- attention
- motivation
dopamine + noradrenaline
drug that depletes monoamines
reserpine
this drug was used as an antituberculosis drug, was found to reverse reserpine induced depression
iproniazid
Depression is associated with loss of neurotrophic support
Neurotrophic hypothesis
for neural plasticity, resilience, and neurogenesis
Brain derived neurotrophic factor (BDNF)
Phenelzine
Selegiline
Tranylcypromine
Monoamine Oxidase Inhibitors
Amitryiptyline
Clomipramine
imipramine
Tricyclic antidepressants
Amoxapine
Bupropion
mirtazapine
Heterocyclic
antidepressants
Duloxetine
venlafaxine
5-HT NE reuptake inhibitors
Nefazodone
Trazodone
5-HT antagonists
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Selective Serotonin reuptake inhibitors
- Related to phenothiazine antipsychotics
- Well absorbed orally, but undergo first pass effect
- Excessive hepatic metabolism required
- Forms active metabolites
- Long half life (OD dosing)
Tricyclic antidepressants
- Require hepatic metabolism
- Fluoxetine half life of several days once a week dosing
Selective serotonin reuptake inhibitors
Pharmacokinetics similar to TCA
Heterocyclics
- Related to amphetamines and orally active
- Inhibitors of hepatic drug metabolizing enzymes
Monoamine oxidase inhibitor
NMDA antagonist
Ketamine
anesthetic agent that has antidepressant action as long as 1 wk.
Ketamine
modulator of GABA A receptors
Brexanolone
for postpartum depression
Brexanolone
- Inhibit the reuptake transporters that terminate the actions of NE and 5 HT
- Blocks H receptors and α adrenoceptors
Tricyclic antidepressants
- Highly selective on Serotonin Transporter (SERT) allosterically inhibit the transporter
- Minimal inhibitory effects on NE
SSRI
Bind to transporters for both serotonin and NE
SNRI
- Increase brain amine levels, interfering with metabolism
- increase in vesicular stores of NE and 5 HT
MAO Inhibitor
increase amine release by antagonism of α 2 receptors
Mirtazapine
no effect on 5 HT or NE amine transporters
Bupropion
increase NE in nerve endings; inhibit
reuptake of NE in nerve endings
Amine uptake blockade (Sympathomimetic effects)
Common in TCA and heterocyclic (mirtazapine) and 5 HT2 blockers
(nefazodone and trazodone)
Sedation
Occurs with all TCA esp. amitriptyline and doxepine ; also with nefazodone , amoxapine, amprotiline
Muscarinic blockade
Atropine like effects minimal with SSRI and bupropion
Muscarinic blockade
for patients withdrawing from nicotine dependence
Bupropion
Stress incontinence and vasomotor menopausal symptoms
SNRI
OCD
Clomipramine and SSRI
Neuropathic pain
Duloxetine, venlafaxine
interaction of fluoxetine and MAOI
Serotonin syndrome
Severe muscle rigidity, myoclonus, hyperthermia, cardiac instability,
seizures
Serotonin syndrome