antipsychotics Flashcards
List the classical antipsychotics
- Chlorpromazine (Thorazine®)
- Prochlorperazine (Compazine®)
- Fluphenazine (Prolixin®)
- Haloperidol (Haldol®)
what class is Clozapine (Clozaril®) in
atypical antipsychotics
what class is Olanzapine (Zyprexa®) in
atypical antipsychotics
what class is Quetiapine (Seroquel®) in
atypical antipsychotics
what class is Aripiprazole (Abilify®) in
atypical antipsychotics
what class is Risperidone (Risperdal®) in
atypical antipsychotics
what class is Ziprisadone (Geodon®) in
atypical antipsychotics
what class is Lithium (Eskalith®) in
mood stabilizer
what class is Valproic acid (Depakene®) in
mood stabilizer
what class is Carbamazepine (Tegretol®) in
mood stabilizer
what class is Gabapentin (Neurontin®) in
mood stabilizer
what class is Lamotrigine (Lamictal®) in
mood stabilizer
What are examples positive symptoms
- hallucinations, delusions, catatonic behavior, disorganized speech and thinking
positive symptoms are due to what neurological pathway
- over active dopamine pathway in limbic system: mesolimbic
what are some examples of negative symptoms
- affective behavior, apathetic, withdrawn, anti-social, lack of motivation, depression
negative symptoms are due to what neurological pathway
- under-active dopamine pathways in frontal cortex: Mesocortical
the mesolimibic pathway goes from where to where? what is it responsible for?
- VTA (ventral tegmental area) to limbic system
- emotion
The mesocortical system travels from where to where? what is it responsible for
- VTA (ventral tegmental area) to frontal cortex
- cognition and emotion
the Nigrostriatal pathway travels from where to where? what is it responsible for
- Substantia nigra to striatum
- motor control
the Tuberoinfundibular pathway travels from where to where? what is it responsible for
- hypothalamus to pituitary
- Prolactin release
MOA of the “classical” antipsychotics (Neuroleptics)? what dopamine system do they target? What symptoms do they relieve
- block dopamine D2 receptors
- targert mesolimbic system
- alleviate positive symptoms
MOA of the “atypical” antipsychotics? what dopamine system do they target? What symptoms do they relieve
- block 5-HT2A and dopamine receptors
- target mesocortical and mesolimbic system
- alleviate both negative and positive symptoms
Dopamine D2 are highly concentrated in what area of brain
limbic system
- The potency for blocking the D2 receptor correlates well with the efficacy at relieving the “positive” symptoms of schizophrenia
effects of antipsychotics takes how long
6 weeks
general effects specific to Prochlorperazine (Compazine®)
antiemetic
most (classical and atypical) drugs also block what receptors
- muscarininc
- a-adrenergic
- histamine
**brain and periphery
antipsychotic medications have what effect on seizures
decrease seizure threshold
endocrine side effects of antipsychotic medications
- weight gain
- increased prolactin secretion
anticholinergic, anti a-adrenergic, and anti histamine effects of antipsychotic medications
- anticholinergic: dry mouth, blurred vision, tachycardia, constipation
- anti a-adrenergic: postural hypotension
- anti histamine effects: sedation
What are extrapyramidal symptoms
- parkinson’s like symptoms : tremor, rigidity, dyskinesia, rocking (akathisia), pacing, restlessless, anxiety, dystonia
why do antipsychotic medications cause extrapyramidal symptoms
- D2 antagonists block not only DA receptors in the limbic system, but also those in the nigrostriatal system (substantia nigra, striatum).
- imbalance of striatal DA and ACh
how are extrapyramidal symptoms treated
- treat with anticholinergics such as Benztropine (Cogentin) to restore ACh/DA balance
which class of antipsychotics tend to cause more EPS symptoms
- classical antipsychotics tend to cause more EPS than atypicals
- the higher the degree of anticholinergic activity of the drug, the less likely to cause EPS
15-25% of patients will have tardive dyskinesia. What is this
- uncontrollable, jerky movements of face and limbs
- occurs late in disease following long-term tx
- discontinue drug
which two antipsychotic drugs are the least likely to cause tardive dyskinesia
- Clozapine
- Olanzapine
What is Neuoleptic Malignant syndrome? what is it caused by
- life threatening, starts with muscle rigidity, fever, changes in BP and HR
- caused by block of Dopamine D2 receptors in the striatum and hypothalamus
What can be used to treat Neuoleptic Malignant syndrome
- Dantrolene (dantrium)
MOA of classical antipsychotics
- block Dopamine D2 receptors
classical antipsychotics are metabolized by
- CYP450s (2D6 and 3A4)
- high first pass metabolism
effects of classical antipsychotics last for how long
- weeks after last administration
- bad for pt compliance
Chlorpromazine has what incidence of EPS? why?
- low incidence of EPS
- High anticholinergic activity
MOA of Chlorpromazine
- blocks DA D2 receptors
- blocks a-adrenergic receptors and ACh
side effects of Chlorpromazine
- anticholinergic: blurred vision, dry mouth, constipation
- decreased sz threshold
- retinal deposits:“browning of vision”
How does Fluphenazine compare to Chlorpromazine
- both block DA D2 receptors
- has less anticholinergic activity -> more likely to cause EPS
MOA of Haloperidol “Vitamin H”
-
potent blocker of DA D2 receptor
- also affinity for DA D1, 5-HT2, and a1 receptors
when is Haloperidol “Vitamin H” used
- used frequently in acute setting (ER)
- can be injected
main side effect of Haloperidol “Vitamin H”
-
extrapyramidal symptoms
- no anticholinergic acitivity
- don’t use long term
MOA of Clozapine
-
blocks 5-HT2A and DA D4 receptors
- some affinity for D2
what happens if Clozapine is discontinued abruptly
- rapid relapse
- unique!
side effects of Clozapine
-
agranulocytosis
- makes it drug of last choice
- blood must be monitored
- EPS and tardive dyskinesia are rare
MOA of Olanzapine
- blocks 5-HT2A receptors and DA D4 and D2 receptors
- improves positive and negative symptoms
- used in tx of bipolar
side effects of Olanzapine
- hyperglycemia, type II diabetes
- extrapyramidal symptoms rare
first line drug for psychosis
Risperidone
MOA of Risperidone
- blocks 5-HT2A and DA D2 receptors
- improves both positive and negative symptoms
- no significant effect on DA neurotransmission in nigrostriatal pathway
MOA of Ziprasidone
- blocks 5-HT2A and DA D2 receptors
- some antidepressant activity
- 5HT1A agonist, inhibit 5 HT reuptake
unique side effects of Ziprasidone
- prolongs QT interval
- sedation
- Hyperprolactinemia
MOA of Quetiapine
- blocks 5-HT2A and DA D2 receptors
side effects of Quetiapine (Seroquel)
-
very sedating***
- used to promote sleep onset and maintenance
- does not elevate prolactin
MOA of Aripiprazole (abilify)
-
dopamine system stabilizer
- dopaminergic tone is low -> DA receptors are activated
- dopaminergic tone is high -> DA receptors are blocks
- partial agonist for DA D2 and 5-HT1A receptors
- antagonist for 5-HT2A
unique side effect of Aripiprazole
- decreases esophageal motility
what is thought to be a cause of bipolar affective disorder
- a lack of GABAergic activity
DOC for bipolar affective disorder
- lithium
metabolism of Lithium
- No metabolism
- excreted by kidneys
MOA of Lithium
- suppress 2nd messengers (IP3)
- may increase ACh, NE, and DA
how is lithium reabsorbed?
- reabsorbed by the proximal tubule in the kidney
-
competes with sodium for re-absorption
- Na+ decreases -> Li+ absorption increases -> toxicity
- Li+ increases -> Na+ absorption decreases -> hyponatremia
Lithium has a small therapeutic window. what plasma levels are associated with side effects and toxicity
- Plasma levels > 2 mEq/L -> N/D, tremor
- Plasma levels > 2.5 mEq/L -> confusion, slurred speech, sz, renal failure, cardiac arrhythmias
patients taking lithium can get diabetes insipidus. why? what is a tx?
- Li+ inhibits ADH
- treat with amiloride (blocks entry of Li+ into collecting duct)
lithium is contraindicated in
pregnancy
What happens when lithium + benzodiazepines or antipsychotics
SAFE
lithium + NSAIDs ->
- increase Li toxicity
if patient can not tolerate lithium for bipolar, what is the next drug of choice
-
valproic acid
- best used for rapid cycling manic/depressive phases
side effects of valproic acid
- surgical bleeding (dental)
- teratogenic
Which two anticonvulsants are useful for rapid cycling manic/depressive phases of bipolar disorder
- valproic acid
- Gabapentin
what drug is used in combination with lithium to tx refractory bipolar disorder
Carbamazepine
drug interactions with Carbamazepine
-
CYP450 inducer
- increases toxicity of isoniazid, erythromycin, cimetidine etc
unique adverse effect of Carbamazepine
-
steven’s johnson syndrome
- toxic epidermal necrolysis
