Anti-Psychotic & Anti-Manic Drugs Part 2 Flashcards
1
Q
What are the available Typical Antipsychotic Drugs?
A
-
Phenothiazines
- Chlorpromazine, Triflupromazine
- Thioridazine, Mesoridazine
- Trifluoperazine, Fluphenazine, Perphenazine, Prochlorperazine
-
Thioxanthine derivatives
- Chlorprothixene, Thiothixene
- **Butyrophenone derivative **
- Haloperidol
- Pimozide
2
Q
What are the 3 types of Phenothiazines?
A
- Aliphatic side chain
- Piperidine side chain
- Piperazine side chain
3
Q
**Phenothiazines: Aliphatic side chain **
Examples
Potency
Actions
A
- **Chlorpromazine, Triflupromazine **
- Low to medium potency
- Sedative
- Pronounced anti-cholinergic actions
4
Q
Phenothiazines: Piperidine side chain
Examples
Potency
Actions
A
- Thioridazine, Mesoridazine
- Low potency
- Sedative
- Less extrapyramidal actions, anti-cholinergic
5
Q
**Phenothiazines: Piperazine side chain **
Examples
Potency
Actions
A
- **Trifluoperazine, Fluphenazine, Perphenazine, Prochlorperazine **
- High potency
- Less sedative
- More extrapyramidal actions, less anticholinergic
6
Q
Thioxanthine Derivatives
Examples
Pharmacology
A
- Chlorprothixene, Thiothixene
- Non-nitrogen containing analogs of the phenothiazines
- Pharmacology is similar to their equivalent phenothiazines
7
Q
**Butyrophenone Derivative **
Example
Pharmacology
A
- Haloperidol
- Not chemically related to phenothiazines
- Pharmacologically similar to high-potency piperazine derivatives
8
Q
Pimozide
Mechanism of Action
Use
A
- **Potent neuroleptic **
- Many side effects
- Approved for treatment of Tourette’s
- Commonly used when haloperidol doesn’t
9
Q
What are the Atypical Antipsychotic Agents? (10)
A
- Clozapine
- Olanzapine
- Risperidone
- Quetiapine
- Aripiprazole
- Ziprasidone
- Paliperidone
- Asenapine
- Iloperidone
- Lurasidone
10
Q
Clozapine
Mechanism of Action
Side effects
A
- Blocks D4 & 5-HT2 receptors
- Little effect on D2
- Muscarinic antagonist
- Improves positive symptoms even in patients not helped by other drugs
- Improves negative symptoms
- Lowers seizure thresholds more than other antipsychotics (5-10%)
- Can cause fatal agranulocytosis (monitor)
11
Q
Olanzapine
Mechanism of Action
Side Effects
A
- Related to clozapine
- **Potent 5-HT2 antagonist **
- D1 & D2 antagonist, some D4
- Side effects
- Few extrapyramidal symptoms (5-HT>D)
- Less seizure incidence than clozapine
- No agranulocytosis
- **Weight gain & diabetes related adverse events **
- Reports of olanzapine abuse
12
Q
Risperidone
Mechanism of Action
Side Effects
Pharmacokinetics
A
- **Combined D2 & 5-HT2 antagonist **
- Greater reduction in negative symptoms & less extrapyramidal symptoms than traditional antipsychotics
- Less seizure activity & less antimuscarinic than clozapine
-
Paliperidone is the active metabolite of risperidone
- Both available as IM depot preparations
13
Q
Quetiapine
Mechanism of Action
Pharmacokinetics
Use
Side Effects
A
- Mechanism of Action
- Structurally related to clozapine
- Similar to risperidone & olanzapine in effects on schizophrenia symptoms & side effects
- Pharmacokinetics: shorter t1/2
- Use
- Approved for augmentation in depression
- Side Effects
- Some reports of abuse
14
Q
Ziprasidone
Mechanism of Action
Side effects
A
- **5-HT2 & D2 antagonist **
- May have 5-HT1a activity (anxiolytic?)
- No weight gain
15
Q
Aripiprazole
Mechanism of Action
Use
A
- **Partial D2 agonist **
- 5-HT2 antagonist
- Approved as an adjunct in depression (augmentation)
16
Q
What is the mechanism of action of Lithium?
A
- monovalent cation of the lightest alkali metal
- one of few psychotherapeutic drugs that have no behavioral effects in “normals”
- blocks manic behavior
- Mechanism
- inhibits phosphatase that converts IP2 to IP1
- inhibits recycling of inositol substrates
- causes depletion of second-messenger source PIP2 & therefore reduces release of IP3 & DAG
17
Q
Pharmacokinetics of Lithium
- complete absorption = ____ hrs
- peak serum levels = ____ hrs
- serum t1/2 = ____ hrs (young adults); _____ hrs (elderly)
- ________ to plasma proteins
- volume of distribution = ____
- CSF conc = _____% of plasma concentration
- ____% of single dose eliminated in urine
A
- complete absorption = 6-8 hrs
- peak serum levels = 2-4 hrs
- serum t1/2 = 18-24 hrs (young adults); 30-36 hrs (elderly)
- unbound to plasma proteins
- volume of distribution = TBW
- CSF conc = 40-50% of plasma concentration
- 95% of single dose eliminated in urine
18
Q
Na+ levels (do/don’t) affect Li levels
A
DO
- increased Na excretion = clinically significant increases in Li levels
- thiazide diuretics, losses of fluids or electrolytes
19
Q
Lithium has a ______ therapeutic window.
A
narrow
important to monitor
20
Q
What 2 classes of drugs raise Li levels?
A
- ACE inhibitors
- AngII receptor blockers
21
Q
What is Lithium used for?
A
- treat mania & prevent recurrences of bipolar disease
- may be useful in preventing recurrences of unipolar depression in some patients
- Schizoaffective disorder (off-label)
- Cluster headaches (off-label)
22
Q
What are some side effects & toxic reactions of Lithium? (8)
A
- fatigue & muscular weakness
- tremor (treated w/ β-blockers)
- GI symptoms
- slurred speech & ataxia
- serious toxicity at plasma levels 2-3X (impaired consciousness, rigidity & hyperactive deep reflexes, coma)
- lithium levels affected by plasma Na levels –> interactions w/ diuretics & anti-hypertensives
- narrow therapeutic window – monitor Li levels
- use in caution w/ pregnant women
23
Q
What are the alternatives the treatment w/ Lithium? (4)
A
-
Carbamazepine
- Na+ channel
- CNS side effects: sedation, confusion, ataxia
-
Valproic acid & divalproex sodium
- 1st line drug in bipolar disorder
- Sedating
-
Lamotrigene & topiramate
- Antiseizure agents
- Na+ channels or glutamate receptors
- Warning: suicidal ideation
- **Symbyax **
- Combination of olanzapine & fluoxetine
- Bipolar disorder, depressive & treatment resistant major depressive disorder
- Initial control of manic symptoms
- Haloperidol
- Clonazepam (off label)
