Anti-Psychotics Flashcards
(38 cards)
What is the mechanism of action of BOTH typical and atypical anti-psychotics?
Competitively ANTAGONIZES post-synaptic dopamine D2 receptors of the CNS (especially in the mesolimbic-frontal system)
What is the difference between atypical and typical drugs? Do they have different mechanisms of action?
SAME mechanism of D2 blockade
DIFFERENT in terms of:
1) side effects - Atypical have LESS typical EPS side effects
2) Additional blockade - Atypical have HIGHER serotonin:DA blockade ratio than typical
How are dosages and affinity properties of an anti-psychotic related to achieve therapeutic efficacy, specifically at the D2 receptor level?
HIGH AFFINITY anti-psychotics require LOW doses HIGHER POTENCY - achieve efficacy X (decrease DA)
LOW AFFINITY anti-psychotics require HIGHER dose LOWER POTENCY- achieve efficacy X (decrease DA)
How are dosage and affinity properties of an anti-psychotic related, specifically in the D1 receptor level?
NO correlation between potency and affinity in the D1 level
RESULT: D2 receptor targeting = Most important for schizophrenia treatment
Describe the pharmacokinetic properties (ADME) of anti-psychotics.
A - High first-pass transformation, lipid-soluble and enters CNS, crosses placental + BBB
D - Bound extensively to plasma proteins, High Vd as it sequesters in lipid compartments
M - HIGH metabolism: Oxidative (Cyp3A4, Cyp2D6) + glucuronidation/sulfation/other conjugation to create more polar metabolites
E - LITTLE excretion unchanged bec of extensive metabolism
What is the clearance property of MOST of the anti-psychotics?
SLOW clearance due to LONG HALF-LIVES (12-75hrs) due to sequestration in lipid compartments
How can the variable side effects of anti-psychotics be explained?
1) Anti-psychosis: All target D2 receptors
2) Variable Side effects: Different anti-psychotics also act on various receptors [serotonin, alpha-adrenergic, muscarinic, histamine receptors
What are the two classes of anti-psychotics?
ATYPICAL
TYPICAL
What drug interactions do you have to be careful when administering?
Other drugs that are either CYP3A4 or CYP2D6 inhibitors/inducers
CYP3A4 Inhibitors - GRAPEFRUIT JUICE, AZOLE anti-fungals, HIV protease inhibitors
CYP2D6 Inhibitors - SSRIs (FLUOXETINE, PAROXETINE) + BUPROPRION
CLINICAL TOXICOLOGY: What are Extrapyramidal effects (EPS)? Which class of anti-psychotics presents EPS more?
Parkinson-like syndrome: Bradykinesia + Rigidity + Tremor
TYPICAL anti-psychotics = MORE EPS
MOST SEVERE EPS - Tardive dyskinesia
CLINICAL TOXICOLOGY: A common side effect of anti-psychotics is DYSTONIA. What is DYSTONIA and what are 2 possible treatments for ACUTE, PAINFUL DYSTONIA?
DYSTONIA = twisting motions resulting from severe muscle contractions
TREATMENTS
1) DIPHENHYDRAMINE (Benadryl) - Sedative anti-histamine with anti-cholinergic properties
2) BENZTROPINE - Anti-muscarinic agent
CLINICAL TOXICOLOGY: What is the MOST UNWANTED effect of anti-psychotic drugs? Is it reversible or irreversible? When does this side effect present itself (immediately after onset of treatment or later)?
TARDIVE DYSKINESIAS (EPS symptom) = Choreoathetoid movements of LIP muscles + buccal cavity
May be IRREVERSIBLE
Presents itself after SEVERAL YEARS of treatment but may also present as early as 6mo after initiation
CLINICAL TOXICOLOGY: What is the most likely treatment plan of TARDIVE DYSKINESIAS?
DISCONTINUE or REDUCE current anti-psychotic dosage
CLINICAL TOXICOLOGY: Which class of anti-psychotics presents more intermediate autonomic effects?
ATYPICAL - While it shows less EPS and less hyperprolactinemia, autonomic effects are more likely to present
CLINICAL TOXICOLOGY: What are the adverse side effects of autonomic blockade when taking anti-psychotics?
ALPHA-BLOCKADE: Postural HYPOTENSION + EJACULATION failure
MUSCARINIC-BLOCKADE:
1) Atropine-Like Effects: Dry as a bone, Blind as a bat, Mad as a hatter, Hot as hell, Red as a beet, Full as a flask
2) CNS Toxic effects: Confusional states
3) URINARY RETENTION
What other disorders can anti-psychotics treat short-term?
MAJOR DEPRESSION - Depression/Mood
MANIA - Depression/Mood
DELIRIUM/DEMENTIA - Cognitive
SCHIZOPHRENIA - Psychosis
CLASS 1 ATYPICAL: Name the 6 ATYPICAL anti-psychotics.
“CORZAQ - Sounds like Coors, Zack - Zack likes drinking Coors”
1) CLOZAPINE
2) OLANZAPINE
3) RISPERIDONE
4) ZIPRASIDONE
5) ARIPRAZOLE
6) QUETIAPINE
CLASS 2 TYPICAL: Name the 3 TYPICAL Anti-psychotics.
“T for typical, HC”
1) THIORIDAZINE
2) HALOPERIDOL
3) CHLORPROMRAXINE
CLASS 1 ATYPICAL: Explain how ATYPICAL anti-psychotics REDUCE + sx and “APPEAR to reduce” - sx
ATYPICAL ANTI-PSYCHOTICS = Anti-D2 receptors + EVEN GREATER anti-5HT2 (serotonin) receptors
CLASS 1 ATYPICAL: What are the general side effects? (*Hint: extrapyramidal symptoms [EPS], neurologic, cardiac, and body mass)
1) LESS EPS than TYPICAL (older drugs)
2) Seizures - Neurologic
3) Hypotension + Conduction deficits + Prolonged QT - Cardiac
4) Increased risk of Type 2 Diabetes, Hyperlipidemia, Weight Gain - Body Mass
CLASS 1 ATYPICAL: What two activities does ARIPIPRAZOLE have?
1) PARTIAL agonist at D2 receptor
2) COMPETITIVE antagonist at D2 receptor UNTIL the partial agonist Emax is achieved
CLASS 1 ATYPICAL: What is the proposed explanation for why ATYPICAL anti-psychotics present LESS EPS?
Atypical anti-psychotics are thought to produce GREATER DA blockade in MESOLIMBIC compared to nigrostriatal (nigrostriatal blockade = EPS)
CLASS 1 ATYPICAL: What makes CLOZAPINE different from all other atypical anti-psychotics (CORZAQ)
(*Hint: Mechanism of action)
CLOZAPINE barely has any D2 receptor blockade
Instead, it has HIGH D4 blockade - D4 receptors are HIGHLY expressed in the MESOLIMBIC system (attributes for + sx)
CLASS 1 ATYPICAL: Which atypical anti-psychotic particularly has lower EPS side effects (i.e. anti-D2 activity in the NIGROSTRIATAL system)?
CLOZAPINE - since it is not as good of a anti-D2 agent
Very good anti-D4 agent
