AntipsychoticDrugs

Antipsychotic DrugsStudy this se t online at: http://www.cram.com/flashcards/935151

What are thefunctions impaired

in Psychosis?

Mental capacityAffective response

Capacity to recognize realityCommunication

Relating to others

What isSchizophrenia?

Breakdown of integrationbetween EmotionsThoughtActions

What are POSITIVESymptoms of

Schizophrenia?

Posit ive symptoms -An EXCESS of normalfunct ions

DelusionThought disorder

Perceptual disturbancesIncongruous mood

Increased motor funct ion

A dimunition or lossof normal functions in

Schizophrenia istermed?

NEGATIVE Symptoms

Poverty of SpeechLoss of emotional responsiveness

Reduced motor functionSocial withdrawal


What is the biologicalbasis of the Positive

symptoms inSchizophrenia?

Overactivity ofDOPAMINE neuronsin - MESO-LIMBICDopamine Pathway

What evidencesupports this

Dopaminergic activityin Schiz?

Drugs that Increase DopaminergicActivity - Increase or ProducePosit ive psychotic symptoms

Drugs that Decrease DopaminergicActivity - Decrease or Stop Posit ive

symptoms

Which 2 drugs can causea Paranoid psychosisindistinguishable from

Schiz?

Amphetaminesand Cocaine

If given repeatedly

Which receptordoes Antipsychotics

block?D2 recptors


Name the 4 welldefined Dopamine

pathways in the brain

MesolimbicNIgrostriatalMesocortical

Tuberoinfundibular

The MesolimbicPathway

involves ..?

It projects from theBrainstem to the Limbic

area

Controls BEHAVIOUR

Overactivity of theMesolimbic pathway

produces..?

Delusions Hallucinat ions

These symptoms are decreasedwhen the Mesolimbic pathway is shut

down by blocking Post synapticdopamine receptors (hypothesized)

The NigrostriatalPathway

projects from...?

the Substantia Nigra tothe Corpus Striatum

Controls MOVEMENT


Blocking thedopamine receptorsin the NigrostriatalPathway causes?

Disorders ofmovement like those

in Parkinson's disease

How are the side effectsof blocking post synaptic

dopamine receptors in theNigrostriatal Pathway

caused?

The Nigrostriatal Pathway projects to theBasal Ganglia which forms part of the

Extrapyramidal nueronal system of the CNS

Side ef fects are called EXTRA PYRAMIDALsymptoms - a set of movement disorders

How is theMesocortical Pathway

involved in Schiz?

It may be involved inmediating..

Positive and perharpsNegative symptoms

How does Classical orTypical antipsychoticsaffect the Mesocortical

Pathway?

Blockade of dopamine receptors inthe pathway

They produce Blunt ing of emotionsand various Cognit ive side effects

They are not useful for negativesymptoms


How does blockade ofdopamine receptors affect

the Tuberoinfundibularpathway?

When dopamine receptors areblocked...

They cause Prolactin levels to rise -Galactorrhea

Dopamine released f rom neurons in thispathway INHIBITS Prolactin secretion

What are the othernames for

antipsychotic drugs?

NEUROLEPTICdrugs

MAJORTRANQUILIZERS

List the Classicalor Typical

antipsychotics.

ChlopromazineFluphenazineHaloperidolThioridazineThiothixene

Two famous drugs are Chlopromazine andHaloperidol

List the Atypicalantipsychotics

ClozapineRisperidoneOlanzapineQuetiopineZiprasidoneAripiprazolePaliperidone


What is the efficacyof Classical

antiphych. drugsrelated to?

The efficacy is closelyrelated to their ability toblock D2 receptors in -Mesolimbic pathway

How are the Atypicalantiphych. drugs

different to Classical?

They have Higher af f init ies for otherreceptors part icularly 5-HT than D2

They appear to exert part of their act ion byblocking 5-HT receptors

They are MUCH less likely to causeExtrapyramidal symptoms

Clozapine an atypicalantiphych. drugs has

a high affinity forwhich receptors?

D1, D4, 5HT2, M,Alpha adrenergic

But it also blocks D2

Risperidone blockswhich recptor to a

greater extent thanD2?

5HT2

Unlike Clozipine it cancause EPS but this is rare

at normal therapeutic doses


Most of the Atypicalshave High affinity for

which 5-HTreceptors?

'5-HT2A'

List the differences ofClozapine from

Typical antipsychoticagents.

*Minimal. if any, ExtrapyramidalSymptoms (EPS)

*Essentially, NO Tardive dyskinesia*Minimal Increases in Prolact in*Negative symptom eff icacy

*Eff icacy in treatment of refractorypopulat ions

What is the minimaldefinition for an

Atypicalantipsychotic?

*Dual antagonism ofSerotonin 5-HT2A andDopamine D2 receptors

*Reduced propensity for EPS

What effect does Classicalantipsych. have on the

Mesolimbic andNigrostriatal system?

D2 blockade of the Mesolimbic -Relieves the Posit ive symptoms of

Schizophreniabut....

D2 blockade of the Nigrostriatalsystem causes Extrapyramidal side

effects


How does SDAs(serotonin-dopamine

antagonists) affect theMesolimbic and

Nigrostriatal system?

D2 blockade of the Mesolimbic -Relieves thePosit ive symptoms of Schizophrenia (same

as classical)however.....

They are Compet it ive Antagonists at Presynapt ic 5HT2 receptors in the Nigrostriatal

pathway

How does the CompetitiveAntagonism at Pre synaptic 5-

HT2 receptors in theNigrostriatal pathway assist inreducing the EPS effects by

SDAs?

5-HT2 receptors function like alpha 2 receptos onpresyaptic neurons

They inhibit the re lease o f Dopamine when acted on bySerotonin

butSDAs block this inhibition and so Dopamine is re leased

This decreases the Dopamine blockade and preventsthe EPS

What are the 2major actions ofantipsychotics?

*Antips ychotics (as the name s ugges ts ) - they reduce halucination and agitation

they have a calming effect

*Antiemetics -mediated by blockade of D2 at the chemoreceptor trigger

z one(mos t older antps ychotics hve this effect)

Many als o block Mus carinic, alpha 1 adrenergic, and H1receptors

this caus es a variety of s ide effects

What are the Extrapyramidal effectsassociated with?

High potency of the drugfor D2 receptors

The more potent the drugfor D2, the more EPS


What r the 2 drugsthat have a highaffinity for D2

receptors?

HaloperidolFluphenazine

both are Classical antipsychoticswith High Potency

Which classicalantipsych. is lowpotency at D2

receptors?

Thiorizadine

EPS are less likely tooccur

Which 2 classicalantipsych. are Stong

anticholinergics?

ThiorizadineChlopromazine

EPS are less likely tooccur because of this

Which 2antipsych. has no

Antiemetic effects?

AripiprazoleThioridazine

Clopromazine is useful aspharmacological antiemetic


How are antipsych.different frombarbituates?

Antipsych. DO NOTdepress intellectual

function Motor incoordination is

minimal

Antipsych. that haveLow Potency at D2

also have what effecton EPS?

They have low Extra-pyramidal symptoms

Remember this is the samefor High potency at 5HT2

Which drugcauses the

worse EPS?

Haloperidol

High potency at D2 -High EPSLow potency at M or 5HT2

No sedation

The Bestantipsych.

drug?

Clozapine

Medium potency D2Medium potency M

High potency at 5HT2 - NO EPS


Which 2 antipsych.drugs cause

Hypotension?

Chlopromazine Thioridazine

They block alpha 1receptors

Which receptor actedon by antipsych.

drugs causessedation?

5HT1

Rispiridone has Highpotency at D2 and at

5HT2. It thus haswhat effect on EPS?

Low EPS

What is the Mostimportant unwanted

AE of antipsych.drugs?

Tardive dyskinesia late occuring syndrome ofabnormal choreoathetoid

movements


What is the possiblecause of Tardive

dyskinesia ?

May be due to UP-regulation of Dopamine

receptors - due tolongterm blockade

Which antipsych.causes

Agronulocytosis in 1-2% of patients?

ClozapineThis makes it a 2ndline drug NOT the

DOC

What causesGalactorrhea fromuse of antipsych.?

Blockade of D2 in PituitaryIncrease Prolactin secretion

In women- amenorrhea-galactorrhea syndrome and

infertility

What are theendocrine effects ofantipsych. in men?

ImpotenceLoss of Libido

Infertility


Which group ofantipsych. is less likelyto produce elevations

in Prolactin?

Atypicals

They cause more Weightgain and incr. in Lipids

than some Typical agents

Which 2 Atypicalscause the worse

Weight gain?

ClozapineOlanzipine

Consequence of Wt gain: HTN,DM type 2, Hyperlipidemia

Which Atypical drugcauses the LEAST

Weight gain?ZIPRASID

ONE

Blockade ofMuscarinic receptors

can cause..?

Anticholinergic effectsbut...

This antimuscarinic effectmay be beneficial in

relation to EPS


Beside orthostaticHypotension, blockade

of alpha 1 cancause........in men?

ImpairedEjaculation

What effect doesThioridazine

have on the eye?

Thioridazine cause Retinaldeposits

Chlopromazine causesCornea and Lens deposits

Which drug causesreversible

abnormalities in Twaves?

Thiorazidine -at High doses

Which Atypical hasthe Greatest risk ofQT prolongation?

Ziprasidone


What is the Rare butlife-threatning

disorder ofantipsych.?

Neuroleptic Malignant Syndrome

Occurs in patients who areextremely sensitive to the EPS

of antipsych.

What are thesymptoms of

Neuroleptic MalignantSyndrome?

Muscle rigidityFever

altered mental statusStupor

Unstable BPMyoglobinemia

Apart fromSchizophrenia whatare the other clinicaluses of antipsych.?

Bipolar disorderTourette's syndrome

Huntington's disease -paranoidbehaviour

Alzheimer's Dementia-Control ofdisturbed behaviour

What are Non-pyschyatric uses

of antipsych.?

Nausea, vomiting

Droperidol is used incombo with Fentanyl inNeuroleptic -anesthesia


2 antipsychpromoted solelyas antiemetics?

Prochloperazine

Benzquinamide

Which antipsychis Category B in

pregnancy?

Only Clopazine

all others areCategory C

Why are Atypicalsprefered as DOC?

*Benefit for Negative symptomsand cognition

*Diminished risk of TardiveDyskinesia, EPS

*Lesser incr. of prolactin levels

Clozapine is reservedfor refractory

patients, why?

Potential forAgranulocytosi

s


Antipsych may beused to control

Agitation or psychosisin ....?

Depressedpatients

Jaundice iscaused by

which drug?Chloproma

zine

AE ofParkinsonism canbe treated with?

ConventionalantiParkinson's drugs of

the Muscarinic type

Never Levadopa

What aresome EPS?

ParkinsonismAkathisia -uncontrollable

restlessnessacute Dystonic Reactions -

spastic retrocollis or torticollis


Whose realityis 'The realreality" ??

Us or them

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