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Principles of drug Action II > principles of drug action psychosis exam 3 > Flashcards

principles of drug action psychosis exam 3 Flashcards

1
Q

WHAT IS PSYCHOSIS?

A

“Psychotic” means out of touch with reality, or unable to separate real from unreal experiences.

 Psychoses may include hallucinations and / or delusions.

Diagnosis based on degree and length of symptoms:

 Reactive or Brief Psychotic Disorders  Schizoaffective Disorder
 Schizophreniform Disorder
 Schizophrenia

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2
Q

what are the positve and negative symtoms of schiz

A

negative :

Flattened affect
 Social withdraw
 Lack of motivation
 Poverty of speech (alogia)  Anhedonia

Positive

Hallucinations

Negative Symptoms
 Flattened affect
 Social withdraw
 Lack of motivation
 Poverty of speech (alogia)  Anhedonia

  • Delusions
  • Agitation
  • BizarreBehavior • Catatonia*
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3
Q

DOPAMINERGIC HYPOTHESIS:

A

dopaminergic antagonists to treat psychotic symptoms

Classical Neuroleptics block dopamine D2 receptors

 Reduces symptoms of schizophrenia

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4
Q

what drugs increase dopmaine and causes positive symptoms?

A

L-dopa

amphetamine

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5
Q

SEROTONERGIC HYPOTHESIS

A

Based on the serotonergic receptor (blocks the 5HT2A receptor) binding profile of the atypical antipsychotics, and serotonergic interactions with dopaminergic neurotransmission.

 Serotonin stimulation decreases DA release in striatum

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6
Q

Administration of m-chlorophenylpiperazine (mCPP) a 5-HT agonist:

A

Exacerbates symptoms in unmedicated schizophrenics - Has no effect in healthy volunteers

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7
Q

D1-Like Receptors (Increase cAMP)

A

Increases cAMP by activation of adenylyl cyclase.  Increases PKA activity in cell
 Long carboxyterminal sequence

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8
Q

 D1 Receptors

A

Localized in Striatum (putamen, nuclelus accumbens) &

olfactory tubercle
 Renal and enteric NS (GI tract)

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9
Q

 D5 Receptors

A

Localized in Limbic system (hippocampus) & hypothalamus  Vasculature and heart

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10
Q

D2 - Like Receptors (Decrease cAMP)

A

Decreases cAMP by inhibiting adenylyl cyclase

 Opens potassium channels (What effect?)

 Blocks calcium channels (What effect?)

 Long cytoplasmic loop sequence  G-protein binding site

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11
Q

d2 receptor

A

Localized in striatum, substantia nigra, and pituitary

 Kidney and presynaptic nerve terminals in vasculature

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12
Q

d3 receptor

A

 Localized in N. accumbens, olfactory tubercle, hypothalamus.

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13
Q

d4 receptor

A

Localized in frontal cortex, substantia nigra, medulla  & midbrain
 Highly polymorphic, but not associated with disease

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14
Q

Mesolimbic System:

A

Dopaminergic neurons originating in the ventral tegmental area (VTA) and terminating in the nucleus accumbens, amygdala, and hippocampus.

 Influences limbic and cognitive function, and behavior

 Hyperactivity in this pathway is associated with positive symptoms of schizophrenia

Ventral tegmental area

 Associated with BEHAVIOR

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15
Q

Mesocortical System:

A

Hyperactivity may cause

Mesocortical Pathway

psychomotor agitation

 Hypoactivity may cause slowed thinking in Parkinson’s disease, reduced concentration in patients with ADHD, and negative symptoms of schizophrenia

 Provides negative feedback to the
mesolimbic pathway to the nucleus
accumbens. Diminished activity may
cause overactivity of limbic system, tegmental causing or exacerbating the positive

symptoms of schizophrenia

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16
Q

Nigrostriatal system

A

Dopamine neurons originating in substantia nigra and terminating in corpus striatum (basal ganglia).

controls motor function

Deficiency of dopamine associated with MOVEMENT Disruptions

Dopamine D2 receptor antagonists cause side effects of extrapyramidal reactions (EPS):

 Produces a movement disorder similar to Parkinson’s disease (pseudoparkinsonism)

Substantia nigra

 Muscle spasms or dystonias

 Hyperkinetic movements seen as akathisia and tardive dyskinesia

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17
Q

Tuberoinfundibular pathway

A

uberoinfundibular pathway is one of the major dopamine pathways in the brain originating from hypothalamus. The release of dopamine in this pathway regulates prolactin secretion by the pituitary gland

Blockade of D2 receptors (as seen with the use of antipsychotic medications) increases prolactin secretion and may cause:

 Females: Galactorrhea (breast engorgement), lactation (inappropriate milk production), amenorrhea, and infertility

 Males: Gynecomastia and impotence
 Prolactinomas: Most Common Hyperfunctioning Pituitary

Adenoma
 Hypersecretion

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18
Q

Hypofrontality

A

is a state of decreased cerebral blood flow (CBF) in the prefrontal cortex of the brain. Hypofrontality is symptomatic of several neurological medical conditions, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and major depressive disorder.

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19
Q

The most prominent neurochemical entity associated with schizophrenia is

A

the monoamine neurotransmitter dopamine.

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20
Q

 Dopamine hypothesis of __schizophrenia_________

A

Symptoms of schizophrenia are due to INCREASED dopamine

transmission

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21
Q

 Dopamine hypothesis of ________________

A

Therapeutic effects of anti-psychotics result from their action on dopamine transmission

 Not all anti-psychotics are created equal

 Regional selectivity and differential effects on dopaminergic systems

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22
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

Pharmacological Actions

A

Block dopamine D2 receptors, as well as

cholinergic muscarinic,  adrenergic, and

histaminergic receptors

 Blockade of D2 receptors in the mesolimbic track, decreases positive symptoms.

 Blockade of D2 receptors in the mesocortical track which is already deficient in schizophrenia, may increase negative symptoms.

 Blocks D2 receptors in the extrapyramidal motor system, resulting in extrapyramidal symptoms.

 Blockade of other receptors subtypes associated with ADRs

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23
Q

how is negative symptoms worsened

A

Negative symptoms may be worsened or caused by higher doses of medications which decrease dopamine activity in the prefrontal areas

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24
Q

TYPICAL ANTIPSYCHOTICS:

THERAPEUTIC INDICATIONS

 Second line agents

A

for treatment of schizophrenia and other psychotic disorders

Approximately one-third of schizophrenic patients fail to respond to typicals

Limited efficacy against negative symptoms and cognitive deficitsHigh proportion of patient relapse (see earlier graph)
Side effects and compliance issues

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25
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

Low Potency Agents (100mg equivalents)

A

Bind to dopamine D2 receptors at ≈60-70%

occupancy

Produce higher incidence of anticholinergic side effects (muscarinic), sedation (histamine) and orthostatic hypotension ( adrenergic)

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26
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

High Potency Agents (1-10mg equivalents)

A

Bind to dopamine D2 receptors at >80% occupancy

High incidence of extrapyramidal symptomsFewer non-dopaminergic side effects

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27
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

Phenothiazines (D2 vs D1: 5x selectivity)

list the three categories of phenothiazine and drugs of each category

A

Aliphatic :
Chlorpromazine (Thorazine)

Triflupromazine (Vesprin)

Piperidines

Thoridizine (Mellaril)

Piperizines
Fluphenazine (Prolixin)

Perphenazine (Trilafon)

Trifluoperazine (Stelazine)

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28
Q

Low potency typical antipsychotics have significant

A

histamine, muscarinic, and  adrenergic receptor activity, leading to many of the undesired ADRs with these drugs

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29
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

Thioxanthenes and Butyrophenones

list subcategories and slectivity to which dopamine receptor

A

Aliphatic (Selective for D2 vs D1)

Chlorprothixene (Taractan)

Piperizines (Selective for D2 vs D1)

Thiothixene (Navane)

Butyrophenones (HIGHLY D2 selective)

Haloperidol (Haldol)

30
Q

High potency typical antipsychotics have significant dopamine______ receptor activity, leading to the extrapyramidal side effects of these drugs

A

D2

31
Q

TYPICAL ANTIPSYCHOTICS: DOPAMINE RECEPTOR ANTAGONISTS

Others

A

Dibenzodiazapines:

High potency (10 mg eq) Loxapine (Loxitane)

Low Potency (100 mg eq) Clozapine (Clozaril)

 Indolone:
Low potency: Molindone (Moban)

 Diphenylbutylpiperidine: High potency:

Pimozide (Orap)

32
Q

a1 agrenergic receptor antagonism adverse reaction

A

Orthostatic hypotension, dizziness, reflex tachycardia

33
Q

D2 receptor antagonism

teraputic and adverse reactions

A

t_eraputic actions_ :Alleviation of positive symptoms of schizophrenia

_adverse reaction:_Extrapyramidal side effects (akathisia, pseudoparkinsonism dystonia), elevated serum prolactin

34
Q

Muscarinic antagonism

A

Blurred vision, constipation, dry mouth, urinary retention, cognitive effects, sinus tachycardia

35
Q

H1 receptor antagonism

A

Sedation, increased appetite and weight gain

36
Q

EXTRAPYRAMIDAL MOTOR TRACTS

A
  • Include all motor pathways NOT part of the corticospinal tract (aka “pyramidal” tract”)
  • Motor neurons that are part of the extrapyramidal tracts descend to spinal cord but do NOT pass through the pyramids
  • Descending motor neuron tracts that control or regulate
  • Axial muscles responsible for balance and posture
  • Muscles controlling movements of proximal portions of limbs

Head, neck and eye movements

37
Q

TWO MAJOR DESCENDING PATHWAYS

A

PYRAMIDAL VS. EXTRAPYRAMIDAL

Pyramidal system

  • Pathway for voluntary movement Brain stem centers
  • Most fibers originate in motor cortex and cross to contralateral side in the medulla to affect voluntary movement

Extrapyramidal system

•Pathways for postural control / certain reflex movements

  • Originates in brainstem
  • Fibers do not cross
  • Cortex can influence this system via inputs to brain stem
38
Q

MOST COMMON NON-NEUROLOGICAL SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS

A

Sedation (serotonin and antihistamine activity) 70%

  • More common with low potency agents

-Orthostatic Hypotension (1 anti-adrenergic activity) 10-30%

  • More common with low potency agents
  • Patients should be advised to get up slowly from recumbent positions

 Anticholinergic reactions (anti-muscarinic activity) >60%

-Constipation, tachycardia, dry mouth, urinary retention, blurred vision

Cardiac Toxicity
 Can occur with several neuroleptics
 Causes cardiac conduction delays
 Can cause arrhythmias, QT prolongation, and tachycardia

39
Q

SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS

A

{Extrapyramidal effects - motor}

Dystonic reactions - Slow sustained contractions or spasms that result in involuntary movement, mostly seen in face, neck, tongue, back spasm

Akathisia –

 Subjective or observable restlessness & urge to move  “Ants in the Pants”

 May persist until the AP dose is lowered, or treated with propranolol

 Anticholinergic and antiparkinsonian drugs are less effective

(Pseudo) Parkinsonian symptoms - shuffle, tremor, facial rigidity,

bradykinesia, cogwheel rigidity

40
Q

ANTIPSYCHOTICS - TYPICAL ADRS

Tardive Dyskinesia

A

The risk of tardive dyskinesia increases with duration of neuroleptics exposure

  • Syndrome of abnormal involuntary movements
  • Buccolingual masticatory movements
  • Involuntary movement involving the tongue and mouth (NOT A DYSTONIA)
  • Choreoathetoid movements of limbs or trunk / neck
  • Facial grimacing or tics
  • Can affect respiration

Treatment includes discontinuation and often switching to clozapine

  • Temporarily masked by increasing dose of AP and worsens acutely with decreased dosage
  • Antiparkinsonian drugs are of no benefit and may actually increase symptoms of tardive dyskinesia.
41
Q

SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS

Neuroleptic Malignant Syndrome

A

Characterized by:

 Fever >38, and up to 42°C

 Autonomic dysfunction, tachycardia, labile BP, respiratory distress, arrhythmias

 Altered level of consciousness

 Severe muscle rigidity

Usually within two wks of initiation or dose change
 risk factors: high-potency antipsychotics; recent increase in drug dosage;

previous episodes of NMS

Treatment involves discontinuing the neuroleptics immediately along with supportive treatment:

Aggressive cooling

 IV benzodiazepines for agitation, psychomotor hyperactivity, and muscular rigidity

Dopamine agonists (bromocriptine and amantadine) or dantrolene

42
Q

SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS

A
  • Galactorrhea, gynecomastia, menstrual irregularities*
  • Due to elevated prolactin levels due to DA blockade
  • Greatest risk with typical antipsychotics and risperidone

Sexual Side Effects
 Retrograde ejaculation, erectile dysfunction, and inhibition of orgasm are common side effects

 Photosensitivity

 Photosensitivity and a predisposition to sunburn is not uncommon

 Chlorpromazine
 Seen more with low potency agents

 Retinitis Pigmentosa
 irreversible blindness seen with high dose thioridazine

43
Q

TYPICAL ANTIPSYCHOTICS – ADME

A
  • Protein binding ranges from 90 to 99%
  • Peak levels in 1-4 hr; half-lives from 8-36 hr
  • Extensively metabolized in the liver

 Many have active metabolites

  • Variable oral bioavailability (first pass effect), therefore IM doses can result in 2 - 3X higher blood levels

Haloperidol ≈ 60% AND Loxapine ≈ 30%

44
Q

DEPOT INJECTABLE ANTIPSYCHOTICS

A

Haloperidol decanoate
 Use an immediate-release antipsychotic before

considering a conversion to haloperidol decanoate

 Recommended that patients be treated with and tolerate short-acting haloperidol due to adverse reactions

Fluphenazine decanoate
 Initial 12.5-25 mg for IM or SC use
 Subsequently administered every 2 to 3 weeks  Fluphenazine PO overlap for 1 week

 Hypersensitivity reactions:
 Test orally BEFORE administering decanoate

45
Q

ATYPICAL ANTIPSYCHOTICS

A

-Generally bind to D2 receptors with lower affinity than typicals (≈ 50-70% occupancy).

  • Drugs have a higher affinity for 5-HT2 compared to the dopamine D2 receptors. A low ratio of [5HT2A binding affinity] / [D2 binding affinity] is predictive of atypical antipsychotic activity

 Haloperidol = ~3.9

 Clozapine = 0.02;

 Olanzapine = 0.2;

 Risperdal = 0.25

46
Q

RECEPTOR BINDING PROFILES RESPONSIBLE FOR THERAPEUTIC RESPONSE AND ADVERSE DRUG REACTIONS

A
47
Q

ATYPICAL ANTIPSYCHOTICS

Therapeutic Indications

A

First-line agents for the initial and maintenance treatment of schizophrenia and psychotic symptoms of any cause, in both adolescents and adults

Also effective for:

mood disorders with psychotic or manic features; psychosis secondary to head trauma;

psychosis and aggressiveness secondary to dementia; agitation and aggression;

drug-induced psychoses

48
Q

ATYPICAL ANTIPSYCHOTICS

Improve positive symptoms of schizophrenia

May improve negative symptoms of schizophrenia

May improve cognitive impairment

A

Improve positive symptoms of schizophrenia

 Hallucinations

 Delusions
 Disordered thoughts

 Agitation

May improve negative symptoms of schizophrenia

 Withdrawal

 Flat affect

 Anhedonia

 Catatonia

May improve cognitive impairment

 Perceptual distortions

 Memory deficits  Inattentiveness

49
Q

ATYPICAL ANTIPSYCHOTICS VERSES TYPICALANTIPSYCHOTICS

A

Adverse Effect profiles
 Relatively small risk for extrapyramidal symptoms

 Mostly with risperidone when used at higher doses (>8 mg/day)

Neuroleptic malignant syndrome

 Rarely seen compared to typical APs

Anticholinergic effects

 Seen mostly with clozapine and olanzapine

Tardive dyskinesia

 Some atypical agents can reduce the risk and symptoms of TD, unlike typical agents that have a high incidence of TD.

 Caution should be exerted with higher doses of risperidone.

50
Q

EVIDENCE FOR SEROTONIN-DOPAMINEINTERACTION IN PSYCHOSIS

A

Clozapine

 binds with high affinity to 5-HT2A receptors

 increases dopamine levels in the mouse PFC with smaller increases in subcortical regions

  • Mixed 5-HT2A/D2 receptor antagonists, cause a marked rise extracellular dopamine concentrations in mesocortical projection regions
  • This finding suggests that concomitant blockade of 5-HT2A and D2 receptors may prominently stimulate the mesocortical dopamine pathway compared to the nigrostriatal and mesolimbic pathways.
51
Q

ATYPICAL ANTIPSYCHOTICS: CLOZAPINE (CLOZARIL)

A

Clozapine titrated slower than other antipsychotics due to risk of orthostatic hypotension

 Initiate at low dose (12.5 mg qd or bid) and raise dose gradually by 25-50mg/day as tolerated until a target dose of 300-450mg/day is reached (~2 weeks)

 Predominantly metabolized by the CYP3A4 and CYP1A2.

 Risk of cardiomyopathy & agranulocytosis… (Block Box Warning)

52
Q

ATYPICAL ANTIPSYCHOTICS: RISPERIDONE (RISPERDAL)

A

Potent antagonist at 5-HT2A and D2 receptors

 Affinity for alpha-1 adrenergic and H1 receptors
 Low affinity for beta-adrenergic and muscarinic receptors

 Typically dosed bid or qd (4-6mg/day)

Dose dependent risk for EPS

 Dose dependent risk for prolactin elevation (especially at

higher doses)
 Minimal anticholinergic side effects

 Fatigue and sedation are most commonly reported side effects.

 Metabolized by CYP2D6

 Likely to interact with SSRIs and other antidepressants.

53
Q

PALIPERIDONE (INVEGA®)

A

9-OH risperidone = principal active metabolite of risperidone

 80% renally eliminated, <10% metabolized through CYP2D6 hence fewer drug interactions expected

 Effects similar to Risperidone…

 Potent antagonist at 5-HT2A and D2 receptors

Affinity for alpha-1, alpha-2 adrenergic and H1 receptors
 Low affinity for beta-adrenergic and muscarinic receptors
 Dose dependent risk for EPS (similar to risperidone)
 High risk for elevated prolactin levels (similar to risperidone)

54
Q

LURASIDONE (LATUDA®)

A

Potent antagonist at 5HT2A and D2 receptors

◦ Alsobindα1,α2receptors

◦ NoaffinityforH1andmuscarinicreceptors

◦ Highaffinityatthe5-HT7receptor,andmaythereforehavea unique effect on cognition

 Half-live ~ 18 hrs, Css ~ 7 days  Metabolized by CYP3A4

55
Q

ILOPERIDONE (FANAPT®)

Potent antagonist at 5-HT2A and D2 receptors

 Low to moderate affinity for alpha-1, alpha-2 adrenergic and H1 receptors

 No discernable affinity for mAChRs
 Metabolized through P450 2D6 and 3A4

 T1⁄2 ~ 18 hr, Css ~ 3 - 4 days

 Available in 1, 2, 4,6, 8, 10 and 12mg tablets

A

Potent antagonist at 5-HT2A and D2 receptors

 Low to moderate affinity for alpha-1, alpha-2 adrenergic and H1 receptors

 No discernable affinity for mAChRs
 Metabolized through P450 2D6 and 3A4

 T1⁄2 ~ 18 hr, Css ~ 3 - 4 days

 Available in 1, 2, 4,6, 8, 10 and 12mg tablets

Minimal ADRs:
 extrapyramidal side effects,  weight gain
 prolactin elevation dizziness,  dry mouth, fatigue
 orthostatic hypotension
 somnolence
 tachycardia

56
Q

ATYPICAL ANTIPSYCHOTICS: ZIPRASIDONE (GEODON)

A

Low incidence of EPS

 Somnolence, dizziness, nausea, and postural hypotension are most common side effects

 May raise prolactin

 Low weight gain liability

 Cardiac conduction problems (↑QTc interval).  EKG Recommended for examination of QT interval  Torsade de Pointes (ventricular tachycardia)

 Metabolized by CYP3A4

 Available as Capsules and an IM injectable formulation

57
Q

ATYPICAL ANTIPSYCHOTICS: OLANZAPINE (ZYPREXA)

A

Chemical analogue of clozapine without the ADR liability of clozapine (e.g. agranulocytosis)

 Substantial affinity for 5-HT2A, alpha1, D2, D4, M1, and H1 receptors

 Typically dosed qd due to drowsiness (10-20mg) & long half-life.

 Relatively free of serious side effects: Most common side effects include drowsiness, dry mouth, weight gain and development of type-2 diabetes, and insomnia. Less common side effects include orthostatic hypotension, and nausea.

 Low incidence of EPS.

 Mainly direct glucuronidation with minor metabolism by the CYP1A2

and CYP2D6.
 Drug-drug interactions are less likely to occur with this medication

58
Q

ATYPICAL ANTIPSYCHOTICS: QUETIAPINE (SEROQUEL)

A

Dosed bid or tid (50-250mg; most effective at 300mg/day)  Short half-life (~6 hours)

 Drug has a remarkable absence of binding preference to any of the receptor systems thought to correlate with clinical efficacy

 Low incidence of EPS.

 Side effects include orthostatic hypotension, somnolence, and weight gain. Dyspepsia, abdominal pain and dry mouth may also occur

 Can cause cataracts in very high doses so initial and periodic eye exams are recommended

 Predominantly metabolized by sulfoxidation and CYP3A4 (minor).

59
Q

ASENAPINE (SAPHRIS®)

A

Potent antagonist at 5-HT2A and D2 receptors

 Affinity for alpha-1, alpha-2 adrenergic and H1 receptors

 Metabolized through P450 1A2 and 3A4 (Minor)

T1⁄2 ~ 24 hr, Css ~ 3 days with BID dosing

 Available in 5 and 10mg sublingual tablets
 5mg PO BID for schizophrenia; 10mg PO BID for bipolar D/O

 Place under tongue…
 Do NOT swallow and do NOT eat/drink for 10 min

 Side effects: See antipsychotic comparison chart

60
Q

ARIPIPRAZOLE (ABILIFY®)

A 
Partial agonists:
 Different class of antipsychotic agent

 Classified as a partial dopamine agonist

 ~90% D2 occupancy; 20-30% partial agonist activity

 Ki~0.5nMatD2andD3

 D2 receptor blockade is considered necessary and sufficient for antipsychotic activity

 Also has 5-HT2A antagonist activity (Ki ~3.4 nM)

61
Q

WHY MIGHT ARIPIPRAZOLE’SDOPAMINE STABILIZING PROPERTY BE IMPORTANT?

A

-Theories suggest schizophrenia is a problem with both too much and too little dopamine

 In the hypodopaminergic environment, aripiprazole increases dopaminergic tone in areas where neurotransmitters are LOW (acts as an agonist).

 In the hyperdopaminergic environment, aripiprazole decreases dopaminergic tone in areas where transmission excessive (acts as an antagonist).

62
Q

WHY IS ARIPIPRAZOLE DOPAMINE STABILIZING PROPERTY IMPORTANT?

A

In the hyperdopaminergic environment, aripiprazole decreases dopaminergic activity by acting as an functional antagonist, reducing psychosis.

In the hypodopaminergic environment, aripiprazole increases dopaminergic action when it binds to the D2 receptor (acts as an agonist), reducing EPS and hyperprolactinemia.

63
Q

BREXPIPRAZOLE (REXULTI®)

A

Approved for psychosis for Sz and bipolar

 Provides alternative to D2 selective FGA and SGAs

 Classified as a partial dopamine agonist

64
Q

CARIPRAZINE (VRAYLAR®)

A

-approved for psychosis for Sz and bipolar
 Classified as a partial dopamine agonist with selectivity

for D3 vs D2 receptors ( as opposed to Abilify and Rexulti)  Provides alternative to D2 selective FGA and SGAs

 minimal effect on prolactin

 relative lack of effect on metabolic parameters, including weight

65
Q

PIMAVANSERIN (NUPLAZIC)

A

For use with psychosis in Parkinson’s Disease

 Classified as a partial inverse agonist and antagonist at

5HT-2A

 Approved for delusions and hallucinations associated with Parkinson’s Disease

 Limited affinity at dopamine receptor

66
Q

study second generation antipsychotics table

A
67
Q

ESTIMATED MEAN WEIGHT GAIN (at 10 weeks)

A

Some atypical agents can increase appetite and cause weight gain Antipsychotic drugs may have direct actions on glucose metabolism, causing or exacerbating diabetes

agents include

clozapine

olanzapine

quetiapine

68
Q

effects WEIGHT GAIN WITH ANTIPSYCHOTICS

A
  • Increased risk of morbidity and mortality
  • Type-2 Diabetes
  • Cardiovascular disease
  • Hypertension
  • Increased cholesterol
  • LDL increase, triglycerides increase, HDL decrease
  • Dissatisfaction with medication and problems with adherence
  • Diminished self esteem
69
Q

summary

A

Atypicals, pioneered by Clozapine, have mixed pharmacology profiles targeting primarily dopamine and 5-HT2 receptors

 Atypicals are as good as typicals at alleviating positive symptoms of psychosis and MAY be more effective with negative symptoms

 Atypicals are generally safer and less likely to induce neurological side effects common of high potency typicals

 Aripiprizole is a neuromodulator and is theorized to work by partial agonism at different dopaminergic terminal fields in the CNS

 Clozapine is clinically determined to be the most effective atypical but severe side effects dictate it be reserved for refractory symptoms and requires regular WBC monitoring

70
Q
A

Principles of drug Action II (10 decks)

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