(6) Neuro & Psych: Antipsych/Parkinsons (5.1-5.3) Flashcards
Suffix: First-generation antipsychotics
“-azine”
(Don’t confuse the “-zine” of H1 receptor blockers with the “-azine” of typical antipsychotics)
Name a first-generation antipsychotic without the suffix “-zine”
Haloperidol
MOA: First-generation antipsychotics
Inhibit central D2 receptors
(Its primary mechanism of action)
What are the high potency first-generation antipsychotics?
(1) Trifluoperazine/Fluphenazine
(2) Haloperidol
What are the low potency first-generation antipsychotics?
(1) Thioridazine
(2) Chlorpromazine
Indications (4) : First-generation antipsychotics
(1) Schizophrenia
(2) Acute psychosis
(3) Acute aggression/agitation
(4) Tourette’s syndrome
Do first-generation antipsychotics have a short or long half-life?
Long
Other than D2 receptors, what receptors do first-generation antipsychotics inhibit?
(1) Muscarinic receptors
(2) α1 receptors
(3) H1 receptors
* (Note: this occurs predominantly in the LOW potency first-generation antipsychotics)*
What type of side effects are more common in first-generation antipsychotics compared to second generation?
Extra pyramidal symptoms
What type of extrapyramidal symptoms can occur within minutes of starting a high potency first-generation antipsychotics?
Acute dystonia
What type of extrapyramidal symptoms can occur within days of starting a high potency first-generation antipsychotics?
Akathisia
(movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still)
What type of extrapyramidal symptoms can occur within weeks of starting a high potency first-generation antipsychotics?
(1) Drug-induced Parkinson
(2) Tardive dyskinesia
Name 2 endocrine abnormalities that can occur secondary to high potency first-generation antipsychotic use
(1) ↓ Dopamine ⇒ ↑ Prolactin
(2) ↑ Prolactin ⇒ ↓ GnRH
Adverse Effects - Non-endocrine (3) : Typical antipsychotics
(1) Neuroleptic malignant syndrome
(2) Torsades de pointes
(3) Seizures
What are the symptoms of neuroleptic malignant syndrome?
(1) Lead-pipe rigidity
(2) Autonomic instability
(3) Rhabdomyolysis
What is the distinctive side effect of Thioridazine?
Retinal deposits
What is the distinctive side effect of Chlorpromazine?
Yellow corneal deposits
Do first-generation antipsychotics better treat positive or negative symptoms of schizophrenia?
Positive symptoms of schizophrenia
Name 6 atypical antipsychotics
(1) Quetiapine
(2) Olanzapine
(3) Risperidone
(4) Aripiprazole
(5) Ziprasidone
(6) Clozapine
MOA: Atypical antipsychotics
(1) Central D2-receptor antagonist
(2) 5-HT2A receptor antagonist
Do atypical psychotics treat the positive or negative symptoms of schizophrenia?
Both
Indications (3) : Atypical antipsychotics
(1) Schizophrenia
(2) Resistant depression
(3) OCD (with SSRI)
Which atypical antipsychotic has been used to treat Tourettes?
Risperidone
Other than D2 and 5-HT2A receptors, what receptors do atypical antipsychotics block?
(1) H1 receptors
(2) α1 receptors
(3) Muscarinic
Which atypical antipsychotic most strongly blocks muscarinic receptors?
Clozapine
What side effects distinguish atypical antipsychotics from first-generation?
(1) Weight gain
(2) Dyslipidemia
(3) Hyperglycemia
* (These occur in Second Generation, not first generation)*
What are the potential adverse effects most associated with Clozapine?
(1) Agranulocytosis
(2) Myocarditis/cardiomyopathy
(3) Seizures
Which atypical antipsychotic is most associated with extrapyramidal side effects?
Risperidone
Are atypical antipsychotics associated with neuroleptic malignant syndrome?
Yes
(Although less than first generation)
What adverse cardiac effect is associated with atypical antipsychotics?
Torsades de pointes
What is the immediate precursor to dopamine?
L-DOPA
(Which is able to cross the BBB)
Adverse Effects - Acute therapy (4) : L-DOPA
Due to increased PERIPHERAL Dopamine:
- (1) GI distress
- (2) Cardiac arrhythmia
- (3) Orthostatic hypotension
Due to increased CENTRAL Dopamine:
(4) Neuropsychiatric symptoms
* (↑ Dopamine in chemotrigger zone outside BBB ⇒ Nausea. Antipsychotics can be used to treat CNS symptoms)*
Adverse Effects - Chronic therapy (2) : L-DOPA
(1) Response fluctuations (Wearing-off effect)
(2) Dyskinesias (i.e., choreoathetosis)
Contraindication: L-DOPA
Psychosis
MOA: Carbidopa
Peripheral DOPA decarboxylase inhibitor
(⇒ ↓ Peripheral adverse effects + ↑ Bioavailability)
What drug can be used to alleviate the peripheral side effects of L-DOPA?
Carbidopa
Name 3 enzymes which metabolize peripheral L-DOPA
(1) DOPA decarboxylase
(2) COMT
(3) MAO
Suffix: COMT inhibitor
“-capone”
What’s the difference between Tolcapone and Entacapone?
Entacapone is NOT active in CNS
(Notice Tall Al Capone is in the vault ∴ can cross BBB)
Which Parkinson’s drug is associated with liver failure?
Tolcapone
(∴ Entacapone is usually preferred)
MOA: Ropinirole
D2 receptor agonist
MOA: Pramipexole
D3 receptor agonist
Indications - Non-endocrine (2) : Dopamine receptor agonists
(1) Parkinsons
(2) Restless leg syndrome
* (Usually, initial therapy for Parkinson’s, as they are less likely to produce an on-off effect)*
What drug can exacerbate impulse control disorders?
Ropinirole
(“Just think ‘rock and roll’ Ropinirole!”)
MOA: Amantadine (in treating Parkinson’s)
(1) ↑ Endogenous release
(2) Inhibiting reuptake
* (Very similar to amphetamines, it even sounds similar)*
Which symptom of Parkinson’s is NOT treated by centrally acting antimuscarinics?
Bradykinesia
