Belovich- Antipsychotic medications I Flashcards
Main 5 indications for antipsychotics?
- Schizophrenia*- most common
- Bipolar disorder (plus mood stabilizing effect)
- Psychotic depression
- Dementia-related psychoses
- Drug-induced psychoses
Though not drug of choice for nonpsychotic patients, Can treat anxiety symptoms in
autism spectrum disorder (risperidone)
Antipsychotics can improve mood, reduce anxiety, and reduce disturbances
sleep
some antipsychotics can be used as antiemetics due to antagonism of receptors in the area postrema
dopamine
What are the 3 antipsychotics used for their antiemetic effects?
- Ondansetron (Zofran)
- Scopolamine (Transderm Scop)
- Dimenhydrinate (Dramamine)
Histamine receptor antagonism can treat which itchy disease?
Pruritis
(nerve itcthing)
What are the indications for antipsychotic agents that do not tx some kind of psychosis?
antiemetics
pruritis
preoperative sedatives
What causes the positive symptoms (hallucinations, delusions) are caused by Hyperactivity of DA in pathway
mesolimbic
D2R helps alleviate psychotic symptoms
antagonism
Levodopa, amphetamines, bromocriptine, apomorphine, etc. can schizophrenia psychosis or produce psychosis de novo in some patients. Why?
aggravate; due to increased activity of dopamine receptors
What is the assumed cause of Negative symptoms (emotional blunting, social withdrawal, lack of motivation) and cognitive impairment of schizophrenia?
DA-receptor hypofunction in the prefrontal cortex
Presynaptic D1 receptors in the prefrontal cortex thought to modulate activity, which, if impaired, can decrease the activity leading to impaired cognition and working memory.
glutamatergic
Currently, negative symptoms can/cannot be pharmacologically targeted
cannot
Which neurotransmitter pathway is affected when a D2R blockade results in:
Alleviates psychotic symptoms
• May induce other behavioral symptoms
mesocorticomesolimbic pathway
What happens with D2R blockade in nigrostriatal pathway?
Produces motor disturbances by two opposing mechanisms (Extrapyramidal Symptoms and Tardive Dyskinesia)
-imbalance of AcH and DA levels
Increases prolactin secretion
• Likely responsible for altered metabolism
occur when the D2R is blocked in which dopamine pathway?
D2R blockade tuberoinfundibular pathway
What causes Parkinsonism like symptoms because of excess acetylcholine signaling relative to dopamine signaling and what dopamine pathway is effected?
The used of antipsychotics that block D2R in the nigrostriatal pathway
Hyperprolactinemia, caused by D2R blockade in tuberoinfundibular pathway, can lead to which side effects?
increased breast tissue
lactation
gynecomastia
Antipsychotic drugs have similar/various efficacy
similar
Most important factor of successfor schizophrenia is spent on a drug
time
Combination therapy should only be used in patients
refractory
The main clinical effects of FGA typical antipsychotics is antagonism
D2R
Potency of typical antipsychotics is with ADRs
correlated
Atypical (or “second generation”) antipsychotics clincal effects are due to which 2 MOAs?
D2R antagonism and inverse agonism of 5-HT2A
Why are atypical antipsychotics more commonly presribed?
more efficacious and friendlier ADRs
What are the 3 main classes of typical antipsychotics?
Phenothiazines
• Chlorpromazine • Fluphenazine
• Thioxanthenes
• Thiothixene
• Butyrophenones
• Haloperidol
What are the 2 antipsychotics in the phenothiazine class (FGA)?
- Chlorpromazine
- Fluphenazine
What is the FGA antipsychotic in the thioxanthenes class?
thiothixene
What is the FGA antipsychotic in the butyrophenones class?
haloperidol
ANS ADRs due to antipsychotics depends on the .
potency
Neurologic effects, Neuroleptic Malignant Syndrome, and Behavioral Effects
are more commone typicals/atypicals?
typical antipsychotics
Metabolic ADRs are more common in typical/atypical agents
atypical
hyperprolactinemia is more common in atypical/typical agents
typical
Which antipsychotic is more likely to cause toxic or allergic reactions?
clozapine
Cardiac toxicity ADRs can occur with atypicals/typicals/both?
both
Typical antipsychotics can also act as antagonists for which 3 other receptor types (off target) other than dopamine receptors?
• 𝛼-adrenergic antagonists - orthostatic hypotension, light-headedness
• Muscarinic antagonists - anticholinergic effects, dry mouth, urinary retention
• H1 antagonists - sedation, weight gain
The following off target effects of typical antipsychotics is due to antagonism of
receptors?
orthostatic hypotension, light-headedness
a-adregergic
The following off target effects of typical antipsychotics is due to antagonism of
receptors?
anticholinergic effects, dry mouth, urinary retention
Muscarinic
The following off target effects of typical antipsychotics is due to antagonism of
receptors?
sedation, weight gain
H1
ADRs of Antipsychotic agents share close relationship with D2R
affinity
Potency governs ADR profiles of antipsychotics and severity more than
efficacy
more potent= higher
affinity
Typicals have a higher/lower affinity for D2 receptors
higher
In general, higher potency agents are given at doses, while lower potency agents may dosed
lower; higher
More potent antipsychotics will have less/more occurrence of off target ADRs?
less
More potent antipsychotics wil have strong on target ADRs such as :
EPS and TD
Blockade of D2 receptors alters balance
DA/ACh
Relative excess cholinergic influence results in EPS/TD?
EPS (excess Ach as compared to DA)
What are the EPS ADRs?
Dystonias (sustained contraction of muscles leading to twisting, distorted postures)
- Parkinson-like symptoms
- Akathisia (motor restlessness)
EPS/TD symptoms are generally reversible?
EPS
Drugs that have stronger/weaker anticholinergic activity have a lower risk of developing EPS
stronger as the imbalance of Ach to DA is less
“Neuroleptic” refers to potency typical antipsychotic drugs
• High incidence of extrapyramidal side effects at clinically effective doses
high
What type of drugs are effective at treating extrapyramidal symptoms acute dystonia and Parkinsonism?
Antiparkinsonian agents
• Amantadine, a prodopaminergic drug, increases effective dopamine signaling
• Benztropine, an anticholinergic drug, can counter the effects of “excess” cholinergic effects
• Antimuscarinic effects can occur
Which type of antiparkonsonian agent that is used to combat extrapyramidal symptoms caused by typical antipsychotics should not be used with an Alzheimer’s co-morbidity?
Benztropine, an anticholinergic drug, can counter the effects of “excess” cholinergic effects
Which Antiparkinsonian agents, effective for acute dystonia and Parkinsonism due to EPS from typical antipsychotics, is a prodopaminergic drug, increases effective dopamine signaling and restores the Ach/DA imbalance?
Amantadine
Which Antiparkinsonian agents is an anticholinergic drug and can counter the effects of “excess” cholinergic activity due to typical antipsychotics?
Benztropine
What non Antiparkinsonian agents is also effective for acute EPS?
Diphenhydramine
Akathesia (restlessness), an EPS symptom, a is more effectively managed with (benzodiazepines) or (ßblockers)
clonazepam
propranolol
EPS/TD symptoms are generally irreversible?
TD
Excess and Involuntary movements, bilateral and facial jaw movements, “fly-catching” or “worm-like” tongue movement
Tardive dyskinesia (TD)
TD occurs with short/long-term treatment with antipsychotic agents
long-term
Which ADR occurs when Dopaminergic receptors become sensitized due to chronic antagonism?
Also, Neuronal response to dopaminergic input overpowers response to cholinergic input cause the symptoms?
TD
Describe the Ach/DA imbalance that caused TD symptoms?
excess dopamine activity compared to Ach activity from sensitization of dopamine receptors
TD is more commonly observed with high/low potency agents (esp. haloperidol)
high
What are the 2 types of treatments for Tardive dyskinesia?
• Drug cessation • Symptoms may improve but in many cases TD is irreversible and persistent
• VMAT inhibitors • Reduce amount of DA available to release • (valbenazine and deutetrabenazine)
What are the 2 types of vesicular monoamine transporter inhibitors that are used to combat TD?
valbenazine and deutetrabenazine
What is the MOA of VMAT inhibitors?
Reduce amount of DA available to release because they inhib the vesicular monoamine transporter that packs the synaptic vescicles for release
NMS occurs due to D2R blockade in the and nigrostriatal pathways
NMS is an on/off target ADR?
on
What condtion is being described:
- Muscle rigidity (“lead-pipe rigidity”)
- Fever
- Altered mental status and stupor
- Unstable blood pressure,
- Myoglobinemia,
- Elevated serum creatine kinase
- Rare, but fatal in 10-20% of cases if untreated
NMS
Most frequent with high doses of potent agents (a.k.a. “ agents”)
neuroleptic
NMS is more/less common in atypical agents
less
What 3 things are considered in the treatment of NMS?
Discontinue use of the antipsychotic agent
dantrolene*
bromocriptine*
What 2 drugs can be used to treat NMS associated with antipsychotic agent?
dantrolene
bromocriptine
How long can NMS persist after the offending agent is discontinued?
more than a week
NMS symptom persistence is associated with
mortality
How do we distinguish neurological ADRs (most likely caused by FGAs)?
distinguish by duration of symptoms
and D2R antagonism can result in akinesia, and dysphoria
D1R
“diminished spontaneity,” apathy, withdrawal, appearance of depression
akinesia (negative symptom)
Delirium and psychosis can be induced by small/large doses of typical antipsychotics
large
Which population can develop pseudomementia (confusion and disorientation) from taking antipsychotics?
elderly
Blockade of D2Rs in pathway causes hypersecretion of prolactin by pituitary
tuberoinfundibular
can directly induce galactorrhea, and sexual dysfunction or infertility in women and men
Hyperprolactinemia
What is an effective method to treat hyperprolactinemia?
Dosage reduction/cessation (however, keep in therapeutic range)
When switching antipsychotic agents in the case of hyperprolactinemia is not feasible, which 2 drugs can be used?
bromocriptine
aripiprazole
Low-potency frequently cause orthostatic hypotension and tachycardia due to off target a-adrenergic effects
phenothiazines
What are the cardiovascular effects of FGA phenothiazines due to off target blockade of adgenergic receptors?
Mean arterial pressure, peripheral resistance, and stroke volume are decreased
Phenothiazine agents (low potency than other FGAs) produce more (H1) and weight gain than other typical antipsychotics due to off target effects.
sedation
Low potency phenothiazines associated with increased serum and hyperglycemia.
triglycerides and hyperglycemia
Chlorpromazine and are the least potent of the phenothiazine class
thioridazine
Which phenothiazine is no longer used due to being associated with torsades de pointes?
• Thioridazine
Which phenothiazine is high potent and has a high potential for EP but Low potential for weight gain, sedation, and orthostasis?
fluphenazine
Which highly potent typical antipsychotic phenothiazine is Commonly used in long-acting injectable formulation for noncompliant patients?
Fluphenazine
What is the most potent and widely used typical antipsychotic?
Haloperidol
Which FGA has Greater incidence of EPS compared to other typical antipsychotics?
haloperidol
Which FGA is described:
Greater incidence of EPS compared to other typical antipsychotics
- Low potential for orthostasis, weight gain, sedation
- Can be used to manage acute psychotic states
- Commonly used in long-acting injectable formulation for noncompliant patients
haloperidol
Which highly potent typical commonly used in long-acting injectable formulation for noncompliant patients Can be used to manage acute psychotic states?
haloperidol
