(6) Neuro & Psych: Antipsych/Parkinsons (5.1-5.3)

Question 1

Suffix: First-generation antipsychotics

Answer 1

“-azine”

(Don’t confuse the “-zine” of H1 receptor blockers with the “-azine” of typical antipsychotics)

Question 2

Name a first-generation antipsychotic without the suffix “-zine”

Answer 2

Haloperidol

Question 3

MOA: First-generation antipsychotics

Answer 3

Inhibit central D2 receptors

(Its primary mechanism of action)

Question 4

What are the high potency first-generation antipsychotics?

Answer 4

(1) Trifluoperazine/Fluphenazine
(2) Haloperidol

Question 5

What are the low potency first-generation antipsychotics?

Answer 5

(1) Thioridazine
(2) Chlorpromazine

Question 6

Indications (4) : First-generation antipsychotics

Answer 6

(1) Schizophrenia
(2) Acute psychosis
(3) Acute aggression/agitation
(4) Tourette’s syndrome

Question 7

Do first-generation antipsychotics have a short or long half-life?

Answer 7

Long

Question 8

Other than D₂ receptors, what receptors do first-generation antipsychotics inhibit?

Answer 8

(1) Muscarinic receptors
(2) α1 receptors
(3) H1 receptors
* (Note: this occurs predominantly in the LOW potency first-generation antipsychotics)*

Question 9

What type of side effects are more common in first-generation antipsychotics compared to second generation?

Answer 9

Extra pyramidal symptoms

Question 10

What type of extrapyramidal symptoms can occur within minutes of starting a high potency first-generation antipsychotics?

Answer 10

Acute dystonia

Question 11

What type of extrapyramidal symptoms can occur within days of starting a high potency first-generation antipsychotics?

Answer 11

Akathisia

(movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still)

Question 12

What type of extrapyramidal symptoms can occur within weeks of starting a high potency first-generation antipsychotics?

Answer 12

(1) Drug-induced Parkinson
(2) Tardive dyskinesia

Question 13

Name 2 endocrine abnormalities that can occur secondary to high potency first-generation antipsychotic use

Answer 13

(1) ↓ Dopamine ⇒ ↑ Prolactin
(2) ↑ Prolactin ⇒ ↓ GnRH

Question 14

Adverse Effects - Non-endocrine (3) : Typical antipsychotics

Answer 14

(1) Neuroleptic malignant syndrome
(2) Torsades de pointes
(3) Seizures

Question 15

What are the symptoms of neuroleptic malignant syndrome?

Answer 15

(1) Lead-pipe rigidity
(2) Autonomic instability
(3) Rhabdomyolysis

Question 16

What is the distinctive side effect of Thioridazine?

Answer 16

Retinal deposits

Question 17

What is the distinctive side effect of Chlorpromazine?

Answer 17

Yellow corneal deposits

Question 18

Do first-generation antipsychotics better treat positive or negative symptoms of schizophrenia?

Answer 18

Positive symptoms of schizophrenia

Question 19

Name 6 atypical antipsychotics

Answer 19

(1) Quetiapine
(2) Olanzapine
(3) Risperidone
(4) Aripiprazole
(5) Ziprasidone
(6) Clozapine

Question 20

MOA: Atypical antipsychotics

Answer 20

(1) Central D₂-receptor antagonist
(2) 5-HT_2A receptor antagonist

Question 21

Do atypical psychotics treat the positive or negative symptoms of schizophrenia?

Answer 21

Both

Question 22

Indications (3) : Atypical antipsychotics

Answer 22

(1) Schizophrenia
(2) Resistant depression
(3) OCD (with SSRI)

Question 23

Which atypical antipsychotic has been used to treat Tourettes?

Answer 23

Risperidone

Question 24

Other than D₂ and 5-HT_2A receptors, what receptors do atypical antipsychotics block?

Answer 24

(1) H₁ receptors
(2) α₁ receptors
(3) Muscarinic

Question 25

Which atypical antipsychotic most strongly blocks muscarinic receptors?

Answer 25

Clozapine

Question 26

What side effects distinguish atypical antipsychotics from first-generation?

Answer 26

(1) Weight gain (2) Dyslipidemia (3) Hyperglycemia * (These occur in Second Generation, not first generation)*

Question 27

What are the potential adverse effects most associated with Clozapine?

Answer 27

(1) Agranulocytosis (2) Myocarditis/cardiomyopathy (3) Seizures

Question 28

Which atypical antipsychotic is most associated with extrapyramidal side effects?

Answer 28

Risperidone

Question 29

Are atypical antipsychotics associated with neuroleptic malignant syndrome?

Answer 29

Yes *(Although less than first generation)*

Question 30

What adverse cardiac effect is associated with atypical antipsychotics?

Answer 30

Torsades de pointes

Question 31

What is the immediate precursor to dopamine?

Answer 31

L-DOPA (*Which is able to cross the BBB)*

Question 32

**Adverse Effects** - Acute therapy (4) : L-DOPA

Answer 32

**_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)*

Question 33

**Adverse Effects** - Chronic therapy (2) : L-DOPA

Answer 33

(1) Response fluctuations (Wearing-off effect) (2) Dyskinesias (i.e., choreoathetosis)

Question 34

**Contraindication**: L-DOPA

Answer 34

Psychosis

Question 35

**MOA**: Carbidopa

Answer 35

Peripheral DOPA decarboxylase inhibitor *(⇒ ↓ Peripheral adverse effects + ↑ Bioavailability)*

Question 36

What drug can be used to alleviate the peripheral side effects of L-DOPA?

Answer 36

Carbidopa

Question 37

Name 3 enzymes which metabolize peripheral L-DOPA

Answer 37

(1) DOPA decarboxylase (2) COMT (3) MAO

Question 38

**Suffix**: COMT inhibitor

Answer 38

"-capone"

Question 39

What's the difference between Tolcapone and Entacapone?

Answer 39

Entacapone is NOT active in CNS *(Notice Tall Al Capone is in the vault ∴ can cross BBB)*

Question 40

Which Parkinson's drug is associated with liver failure?

Answer 40

Tolcapone *(∴ Entacapone is usually preferred)*

Question 41

**MOA**: Ropinirole

Answer 41

D₂ receptor agonist

Question 42

**MOA**: Pramipexole

Answer 42

D₃ receptor agonist

Question 43

**Indications** - Non-endocrine (2) : Dopamine receptor agonists

Answer 43

(1) Parkinsons (2) Restless leg syndrome * (Usually, initial therapy for Parkinson's, as they are less likely to produce an on-off effect)*

Question 44

What drug can exacerbate impulse control disorders?

Answer 44

Ropinirole *("Just think 'rock and roll' Ropinirole!")*

Question 45

**MOA**: Amantadine (in treating Parkinson's)

Answer 45

(1) ↑ Endogenous release (2) Inhibiting reuptake * (Very similar to amphetamines, it even sounds similar)*

Question 46

Which symptom of Parkinson's is NOT treated by centrally acting antimuscarinics?

Answer 46

Bradykinesia