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Flashcards in Antipsychotics Deck (43):
1

also known as ------- drugs

neuroleptic and anti-schizophrenic drugs.

2

Psychosis


• Persons experiencing a psychotic episode may have a constellation of symptoms such as disorganized thinking, personality changes, paranoid or delusional beliefs, and hallucinations.
Psychosis has been traditionally linked to the neurotransmitter dopamine. maybe psychosis results from an over activity of dopamine particularly in the mesolimbic pathway.

3

Hallucinations

defined as sensory perception in the absence of external stimuli. They are different from illusions, which are the misperception of external stimuli.

4

term psychosis is particularly associated with ---------

schizophrenia, bipolar disorder (manic depressive disease) and severe depression.

5

secondary psychosis

Psychosis arising from non-psychological conditions:

• Neurological disorders
• Electrolyte disorders
• Multiple medical conditions
• Drugs – use, abuse or withdrawal

6

Neurological disorders associated with psychosis

Brain tumors
• Alzheimer's Disease
• Multi-infarct dementia
• Dementia with Lewy bodies • Multiple sclerosis
• Syphilis
• Parkinson's Disease
• Pick’s disease (robin williams)

7

Electrolyte disorders associated with psychosis

• Hypo/hyper calcemia

• Hypo/hyper natremia

• Hypokalemia

• Hypo/hyper magnesemia

• Hypophosphatemia

• Hypoglycemia

8

Medical conditions associated with psychosis

• AIDS
• Lupus
• Lyme Disease
• Sarcoidosis
• Leprosy
• Malaria

9

Drugs whose use, abuse or withdrawal have been associated with psychosis include:

• OTC drugs such as Dextromethorphan at high doses and antihistamines at high doses
• Atropine
• Antidepressants
• Antiepileptics
• Barbiturates
• Benzodiazepines
• L-dopa
• Narcotic analgesics
• Alcohol
• Amphetamines • Cannabis
• Cocaine
• LSD
• MDMA (ecstasy) • Mescaline
• PCP
• Psilocybin

10

Neuroleptic drugs


• The neuroleptic or antipsychotic drugs are currently categorized and referred to as being either:

• Typical or first generation neuroleptic
• Atypical or second generation neuroleptic

11

first generation antipsychotics:

Phenothiazines:
Chlorpromazine (Thorazine)
Fluphenazine (Prolixin)
Perphenazine (Trilafon)
Prochlorperazine (Compazine)
Thioridazine (Mellaril)
Trifluoperazine (Stelazine)
Triflupromazine (Vesprin)
Levomepromazine (Nozinan)

Thioxanthenes:
Flupenthixol (Depixol)
Thiothixene (Navane)
Zuclopenthixol (Clopixol)

Butyrophenones:
(See note below)
Haloperidol (Haldol)
Droperidol

12

Atypical antipsychotic medications include

Butyrophenone class: (To further confuse matters, this class of drugs is occasionally listed under the typical antipsychotics as well.
Haloperidol (Haldol)
Droperidol (Inapsine)
Pimozide (Orap) – also indicated for the treatment of Tourette’s syndrome
Melperone

Dibenzodazepine class:
Clozapine (Clozaril)
Quetiapine fumarate (Seroquel)

Thienobenzodiazepine class:
Olanzapine (Zyprexa)

Benzisoxazole class:
Respiradone (Risperdal)

13

general Neuroleptic drugs MOA

• The main mechanism of action of both the typical and the atypical neuroleptic drugs is blockade of dopamine receptors in the brain.

• The atypical neuroleptic drugs also serve as antagonists or partial antagonists to serotonin receptors.

• Both typical and atypical neuroleptic drugs may affect various receptor subtypes of norepinephrine, acetylcholine, and histamine as well.

14

The atypical neuroleptic MOA

these drugs also serve as antagonists or partial antagonists to serotonin receptors.

Both typical and atypical neuroleptic drugs may affect various receptor subtypes of norepinephrine, acetylcholine, and histamine as well.

15

benefits of atypical neurleptics

considered first line tx now
Two of the defining characteristic of an atypical antipsychotic is the

-decreased propensity of these agents to cause extrapyramidal side effects
-and an absence of sustained prolactin elevation.

** the Blocking D2 receptors in these other pathways is thought to produce many of the unwanted side effects that often accompany the use of the **typical** antipsychotics.

16

major dopamine receptor for neuroleptic MOA


• Five dopamine receptors have been identified and the chief antipsychotic effects of the neuroleptics appears related to dopamine blockade at the D2 receptors.

• Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences and it is the blockade of dopamine receptors in this pathway that is thought to control psychotic experiences.


17

typical antipsychotics and dopamine receptors

Typical antipsychotics are relatively non- selective in regards to the mesolimbic pathway and also block dopamine receptors in the mesocortical pathway,
tuberoinfundibular pathway, and the nigrostriatal pathway.

• Blocking D2 receptors in these other pathways is thought to produce many of the unwanted side effects that often accompany the use of the typical antipsychotics.

18

What does dopamine regulate?

1. Movement Via the dopamine receptors D1, D2, D3, D4 and D5
2. Cognition and frontal cortex
3. Regulating prolactin secretion
4. Motivation and pleasure
5. Sociability

19

Adverse effects commonly observed with the use of neuroleptics include:

• Tremors/ Parkinsonian effects
• Tardive dyskinesia (atypicals less so)
• Postural hypotension
• Blurred vision, dry mouth, constipation and urinary retention
• Sexual dysfunction
• Increased prolactin release
• Drowsiness

20

extrapyramidal signs associated with typical neuroleptics

akinesia (inability to initiate movement),
akathisia (inability to remain motionless),
and tardive dyskinesia (facial grimacing and inappropriate posturing of the tongue, neck, trunk and limbs).

cannabis helps!!

21

Tardive dyskinesia

Dyskinesia refers to an involuntary movement. Facial grimacing and involuntary movements of limbs are examples of dyskinesias.

• The effect of these drugs can be tardive, meaning the dyskinesia continues on or first appears after the drugs are no longer being taken.

22

neuroleptic malignant syndrome.

rare

Neuroleptic malignant syndrome is characterized by
1. catatonia,
2. fluctuating blood pressure
3.dysarthria and
4. fever.
• This syndrome may be fatal if the antipsychotic drug is not immediately discontinued and the patient receives treatment with a dopamine agonist such as Bromocriptine.

23

dopamine agonist

Bromocriptine.
used to counter neuroleptic malignant syndrome

24

anti- emetic effects MOA

mediated by blocking D2 dopaminergic receptors in the chemoreceptor trigger zone (CTZ) of the medulla.

• Several neuroleptics are useful in the treatment of the severe nausea that occurs as result of cancer chemotherapy.

25

Chlorpromazine/ Thorazine

• Class: Typical neuroleptic
• Indication: Psychosis, mania,
schizophrenia as well as nausea and
vomiting and intractable hiccoughs.
• MOA: Chiefly D2 dopaminergic receptor
site blockade. Also alpha-adrenergic blockade and H1 blockade (anti-histamine effects).

26

Chlorpromazine/ Thorazine SE


• Side effects: As noted in prior slides, significant side effects include onset of Parkinsonian symptoms and extrapyramidal signs such as tardive dyskinesia. Increased release of prolactin commonly occurs as a result of dopamine blockade. Increased prolactin can result in galactorrhea and amenorrhea in women and infertility in both men and women.


27

Prochlorperazine/ Compazine


• Class: Typical neuroleptic
• Indication: Psychosis as well as vertigo and nausea and vomiting, particularly when associated with migraine headaches.
• MOA: Primarily H1-histamine receptor antagonist as well as alpha-adrenergic receptor antagonist and D2 dopaminergic receptor antagonist.
***perhaps 10 to 20 times more potent than chlorpromazine in terms of its antipsychotic effects.

• Char: Less orthostatic hypotension and fewer extrapyramidal signs then chlorpromazine. Better anti-emetic agent than many of the other neuroleptics.

28

Prochlorperazine/ Compazine SE



• Side effects: As noted previously. Significant drowsiness, dry mouth, constipation and urinary retention. Lowers seizure threshold. Extrapyramidal side effects generally seen only when Prochlorperazine is given at high doses over long periods of time.

29

Haloperidol/ Haldol



• Class: Typical neuroleptic
• Indication: Psychosis, Tourette’s syndrome, Huntington’s disease, acute agitated behavior.
• MOA: Chiefly D2 dopaminergic receptor site blockade.
• Char: Careful administration so as to reduce excessive sedation and tardive dyskinesia.

30

Haloperidol/ Haldol SE


• Side effects: Chiefly Parkinsonian-like symptoms and extrapyramidal effects, which may be very dramatic. Tremors very common. Less blockade of the muscarinic and the alpha-adrenergic receptors compared to other neuroleptic agents such as Chlorpromazine. The potentially fatal neuroleptic malignant syndrome (NMS) is a significant possible side effect

31

Clozapine/ Clozaril


• Class: Atypical neuroleptic
• Indication: Schizophrenia, especially when other anti-psychotic agents have failed or have produced undesirable side effects.
• MOA: Multiple receptor site blockade yet greatest effects at D2 and 5-HT2 (serotonin) receptor sites.
• Char: PO. Rapid absorption and extensive metabolism

*** first of the atypical antipsychotics to be developed for schizo

32

Clozapine/ Clozaril SE

the rare but potentially lethal side effects of agranulocytosis and myocarditis relegate it to third-line use.


• Side effects: Relatively diminished extra- pyramidal side effects compared to other neuroleptic agents. Agranulocytosis has been reported in 1 to 2% of patients. (Clozapine should be withheld if granulocyte count is

33

Respiradone/ Risperdal

• Class: Atypical neuroleptic
• Indication: Psychosis
• MOA: Exact mechanism of action is
unknown yet presumed to be a combination of dopamine and serotonin receptor blockade.
• Char: Metabolized in liver by P450 enzyme and metabolites are active. Dose must be reduced in patients with liver dysfunction.


34

Respiradone/ Risperdal

• Side effects: Extrapyramidal effects, tardive dyskinesia, constipation, sedation. Slow withdrawal is recommended to reduce the incidence of acute psychosis. Weight gain, hyperglycemia and diabetes. Increased risk for stroke in elderly patients.

***incr risk for type 2 DBM

35

Olanzapine/ Zyprexa


• Class: Atypical neuroleptic
• Indication: Schizophrenia, especially when
other antipsychotic agents have failed or
have produced undesirable side effects.
• MOA: Multiple receptor site blockade yet
greatest effects at D2 and 5-HT2 receptor
sites.
• Char: PO. Rapid absorption and extensive
metabolism

**Olanzapine is structurally similar to Clozapine. Olanzapine has a higher affinity for 5- HT2 serotonin receptors than D2 dopamine receptors.

36

Olanzapine/ Zyprexa SE


• Side effects: Relatively diminished extra- pyramidal side effects compared to other neuroleptic agents. Weight gain, hyperglycemia and diabetes. Increased risk for stroke in elderly patients.

MAJOR weight gain and DBM

**Olanzapine and Risperidone, should not be given to elderly patients with dementia. dt stroke risk

37

Mania

• Mania is another affective disorder, characterized by elevated, expansive or irritable moods accompanied by increased activity, rapid speech, thoughts and feelings of grandiosity, distractibility and decreased need for sleep.

• Patients that cycle between periods of depression and mania carry the diagnosis of bipolar disorder.

increased high risk activities

38

Lithium salts

• Lithium salts are used prophylactically in treating bipolar disorder and in the treatment of manic episodes.
• Lithium is widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing norepinephrine release and increasing serotonin synthesis.

39

Lithium salts proposed MOA


• The exact MOA of lithium as a drug is not known but it may serve to dampen transmission by norepinephrine as well as acting to diminish response to glutamate, an excitatory neurotransmitter.

40

Lithium carbonate/ Eskalith


• Class: Lithium salt
• Indication: Bipolar disorder and manic
episodes. Lithium has also being used in
the treatment of schizophrenia.
• MOA: As previously noted.
• Char: PO. Cleared by kidneys. Very small
therapeutic index such that therapeutic serum levels may be extremely close to toxic levels. Blood levels of lithium must be frequently checked.

41

Lithium carbonate/ Eskalith dosing

Doses are adjusted to achieve plasma concentrations of 0.6 to 1.2 mmol Li+ on samples taken 12 hours after the preceding dose.

Overdosage, usually with plasma concentrations over 1.5 mmol of Li+, may be fatal and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment, and convulsions

42

Lithium carbonate/ Eskalith SE

• Side effects: A major problem with lithium treatment is lack of compliance, especially due to the side effects of weight gain, cognitive impairment and short-term memory deficits.

• The most common renal effect of lithium is impaired concentration capacity due to reduced renal response to antidiuretic hormone (ADH).

• The incidence of polyuria due to nephrogenic diabetes insipidus is approximately up to 20% of patients receiving chronic treatment.

Hypothyroidism may occur in 5% to 35% of patients on long term lithium therapy.
• Signs that lithium levels may be too high
include: lethargy, confusion, diarrhea, abdominal pain, nausea and vomiting ataxia and severe tremors.
• As lithium levels increase, seizures develop and cardiotoxicity can occur.

43

lithium tx initiation and dosing

1. administering a single dose of lithium, obtaining a serum level 24 hours later, and using a nomogram to predict the appropriate daily dose.
2. Alternatively, lithium may be started in low, divided doses (i.e. 300 mg or less) to minimize side effects, depending on the patient's weight and age, and then the dose should be titrated upward to a serum concentration of .5 mEq/L.

xThe optimal maintenance levels vary from patient to patient but usually range from .6 to 1.2 mEq/L.