Week 3 (Vision and Psychosis) Flashcards

Question

Controlled substances

Answer 1

**Schedule I** controlled substances: **no accepted medical use in US**, high potential for abuse (**heroine**, **LSD**, MJ, peyote, methaqualone, MDMA/ecstasy) **Schedule II** controlled substances: **high potential for abuse** which may lead to severe dependence (**hydromorphone**, **methadone**, meperidine, **oxycodone**, **fentanyl**, **morphine**, **opium**, **codeine**, **amphetamine**, **methamphetamine**, methylphenidate, amobarbital, glutethimide, pentobarbital) **Schedule III** controlled substances: **less potential for abuse**, moderate or low physical dependence, high psychological dependence (**\<15mg hydrocodone** like Vicodin, **\<90mg codeine** like Tylenol+Codeine, **buprenorphine**, benzphetamine, ketamine, depo-testosterone) **Schedule IV** controlled substances: **low potential for abuse** (alprazolam/**Xanax**, clonazepam, clorazepate, **diazepam**, lorazepam, midazolam, temazepam, triazolam) **Schedule V** controlled substances: l**ow potential for abuse** (limited quantities of certain narcotics)

Answer 2

**Indirectly acting sympathomimetics**: **release** and **block** **reuptake** of **NE**, **DA** and **5HT** so increase NT levels At high doses, **MAO activity inhibited** (to also increase NT levels) Clinical uses: **narcolepsy**, **ADD**, not for weight loss Metabolized by CYP450-mediated oxidation to phenylacetone then to benzoic acid D-methamphetamine and D-amphetamine (D-isomer more potent than L-isomer) **Adderall** (amphetamine) of **Ritalin** (methylphenidate) for ADHD

Answer 3

**Indirectly acting sympathomimetics** Alpha and beta adrenergic agonists AND block reuptake of **NE, DA** **Ephedrine** more **potent** than pseudoephedrine

Answer 4

**Indirectly acting sympathomimetics**: release and block reuptake of **NE**, **DA** and **5HT** so increase NT levels Methamphetamine metabolized to amphetamine (major) and 4-hydroxymethamphetamine (minor) **Prolonged action** due to long half life (10-12h) 25% of METH and AMPH eliminated by renal ion trapping CNS stimulant: **wakefulness**, **mood** **elevation**, improves performance on **dull repetitive tasks** (does NOT facilitate learning), **appetite** **suppression** **CV stimulation** Tolerance occurs rapidly (tachyphylaxis) Dependence: **withdrawal** includes prolonged sleep, lassitude, fatigue, depression, intense hunger (hyperphagia)

Answer 5

**Psychiatric**: dizziness, tremor, hyperirritability, insomnia, hyperthermia, chronic use can produce paranoid psychosis, addiction **Neurological**: cerebral edema, hemorrhage; chronic use associated with neurotoxicity (long-term DA deficits) **CV**: tachycardia, palpitations, **arrhythmias**, HTN, headache, stroke **GI**: anorexia, nausea, vomiting Drug interactions: **hypertensive crisis with MAO inhibitors**

Answer 6

ADHD characterized by short attention span, restlessness, impulsivity and hyperactivity **Amphetamine** (**Adderall**): psychomotor stimulant that promotes release and/or blocks reuptake of DA and NE **Methylphenidate** (**Ritalin**): psychomotor stimulant that promotes release and/or blocks reuptake of DA and NE **Atomoxetine**: non-psychomotor stimulant; selective NE reuptake inhibitor (**NRI**); less abuse potential but black box warning for increased suicidal thoughts and behaviors

Answer 7

**Ritalin** or **Concerta** (long-acting) Blocks reuptake of **DA** and **NE** Absorption orally and max plasma level 1-3 hours after ingestion Hepatic metabolism, half life of 2-7 hours Similar pharm effects to amphetamine but less potent, fewer peripheral and cardiovascular effects Adverse reactions: insomnia, restlessness, talkativeness, behavioral disturbances

Answer 8

**Phentermine**: amphetamine analog but less potent **Topiramate** + **phentermine** combination (Qsymia)

Answer 9

Mechanism unclear: increases release of **DA**, may involve **hypocretin**, **histamine**, **GABA** and **glutamate** to increase activation of NE neurons in **locus ceruleus**, leading to more "wakeful state" **Wakefulness promoting** agent (not a classic amphetamine-like stimulant) Used for **narcolepsy** and other sleep disorders; also for ADHD and Alzheimer's

Answer 10

**Indirectly acting sympathomimetic** Blocks reuptake of **DA** (centrally), **NE** (peripherally) to overall increase NT concentrations Absorption: smoking gives faster entry to brain and higher drug levels than IV administration Distribution: initially distributed to highly perfused tissues (brain) then redistributes throughout body Metabolism: **short half life 45 min** because metabolized by esterases; smoking only give 5-10 min high; major metabolites in urine (85-90% of dose) are benzoyl ecgonine and ecgonine methyl ester

Answer 11

CNS: **similar to methamphetamine**; dependence Peripheral effects: **local anesthetic, vasoconstriction** Tolerance develops rapidly to CNS effects and other effects too at different rates/degrees Only clinical use is local anesthetic

Answer 12

No correlation between euphoria and adverse effects Can occur at any time and after any route of administration **OD is fatal** **Seizures**, **hyperthermia**, **respiratory** **arrest**, **cardiac** (increased HR and BP, angina, MI, arrhythmias), **cerebral** **hemorrhage** and **stroke**, **ischemic bowel**

Answer 13

**Binge user,** not daily Less euphoria during late stages of binge: irritability, dysphoria, anxiety, paranoia, depression User may take cocaine until they run out Eventually become physically exhausted but have insomnia and take CNS depressants to fall asleep then sleep for 8-40 hours ("**crash**") and wake up extremely hungry Craving for cocaine returns, individual becomes **bored/anhedonic**, and when try to give up cocaine have cravings triggered by environmental cues

Answer 14

Releaser and/or reuptake inhibitor of presynaptic **5HT, DA, NE** 5HT probably causes pro-social, **emotional** effects and also triggers release of **oxytocin** and **vasopressin** (love, trust, sexual arousal, etc) **Synthetic**, psychoactive drug similar to stimulant amphetamine and hallucinogen mescaline Produces feelings of increased energy, euphoria, emotional warmth and empathy toward other and distortions in sensory and time perception Metabolism: half life 8-9h; 2 metabolic pathways (to MDA or to benzoic acid derivatives)

Answer 15

Many of same physical effects as cocaine and amphetamines (increase **HR** and **BP**) At high doses can cause **hyperthermia** **MDMA intoxication** (similar to serotonin syndrome): neuromuscular effects (**hyperreflexia**, clonus, tremor), autonomic effects (**hyperthermia**, tachycardia) and mental effects (**agitation**, **confusion**, **anxiety**) **Surge of serotonin caused by MDMA** reduces its brain levels causing **negative after-effects**: confusion, depression, sleep problems, drug craving, anxiety (may occur soon after taking the drug or during the days or weeks after)

Answer 16

Contain one or more **synthetic** chemicals related to cathinone (amphetamine-like stimulant found in Khat plant) Mephedrone, MDPV, methylone are three main components of bath salts (structures similar to MDMA and amphetamine) Act on **NE, DA** and **5HT** presynatptic terminals as indirectly acting agents to increase NT concentrations in the synapses Increased **energy**, **empathy**, **openness**, **increased libido** Adverse effects: cardiac, psychiatric and neurological

Answer 17

**LSD** **Psilocybin** **Mescaline**

Answer 18

**Semisynthetic** psychedelic drug of ergot family Probably mixed **5HT2/5HT1 partial agonist** Hallucinations due to high affinity for **5HT2** receptors (similar to mescaline and psilocybin) Lasts 6-12 hours; plasma half life 5h with peak plasma concentration 3 hours after Causes **sensory** **alterations**, pseudo-hallucination, alterations of affectivity (euphoria, dysphoria, anxiety, mood swing) Psychological effects: altered cognitive and emotional processes, **dilated pupils**, closed/open eye visual experiences, hallucinations, **synesthesia**, altered sense of **time**, spiritual experiences, loss of filtering, bad trip, flashbacks

Answer 19

Can result from use of stimulant drugs in **abusers** or in **patients** taking therapeutic doses under medical supervision Most common stimulants involved are **amphetamines** and **cocaine**, but **bath salts** produce severe psychotic episodes faster, more intense and longer lasting Symptoms are **similar to organic psychosis/schizophrenia**: hallucinations, delusions, thought disorders and in extreme cases catatonia

Answer 20

Generic term that describes some **impairment** in "reality testing" resulting in the inability to distinguish **reality** from **fantasy**

Answer 21

**Hallucination**: **sensory** perception that has compelling sense of reality of a true perception but that occurs **without external stimulation** of relevant sensory organ **Illusion**: **misperception** or **misinterpretation** of **real** external sensory stimulus and often occurs in relation to substance intoxication

Answer 22

Most common hallucination in psychotic disorders is **auditory verbal hallucination** (hearing a voice) Voice-hearing probably heterogeneous phenomenon with multiple mechanistic pathways Neuroimaging studies implicate **L temporal lobe** and **auditory cortex** and **R hemisphere homologue of Broca's area** in etiology of auditory verbal hallucinations Suggest abnormal generation of internal verbal experiences coupled with delateralized processing errors that result in perceptions of non-volitional, external and auditory speech

Answer 23

Inner speech, memories, thoughts may be excessive, negative or otherwise abnormal --\> **errors in processing** --\> non-volitional, non-self, auditory, external

Answer 24

Normal thoughts, inneer speech = **verbal thinking** Ruminations, obsessions = self, but **ego-dystonic** Thought insertion, illusions = **non-self**

Answer 25

**A fixed, false belief** False belief based on incorrect inference about external reality that is firmly sustained despite what almost everyone else believes and despite what constitutes incontrovertible and obvious proof or evidence to the contrary. The belief is not one ordinarily accepted by other members of the person's culture or subculture (ie not an article of religious faith)

Answer 26

**Persecution/paranoia** (ideas of reference) **Grandiosity** (special powers, spiritual, erotomania) **Somatic** (control, hypochondriacal, infection, infestation) **Misidentification**: capgras (others have been replaced by imposters), fregoli (persecutor with many faces), cotard (nihilistic/negation)

Answer 27

**Preoccupation** **Affective** **valence** (distress, worry, fear, etc) **Unwarranted** and **excessive** **conviction**: creative explanations for anomalous experiences, evaluations based on not enough evidence (increased impulsivity), evaluations based on poorly selected evidence (decreased filtering), difficulties distinguishing coincidence vs. causality, few opportunities for "social" reality testing

Answer 28

Psychosis as a state of **aberrant "salience"** mediated by **dopamine** **Excess** **mesolimbic** **DA** results in heightened "saliance" (neutral/**cold** stimula --\> relevant/**hot** stimuli) Abnormal salience of **external** stimuli --\> **delusional** thinking Abnormal salience of **internal** stimuli --\> **hallucination** DA agonists and stimulants result in psychosis **Antipsychotic** medications work by **blocking DA** transmission Salience decreased with antipsychotic therapy

Answer 29

No mental illness **Malingering** **Mania** Major depressive episode Dementia Delirium Non-psychiatric **brain disorder** (seizure, tumor, infection, endocrine, etc)

Answer 30

**Substance intoxication:** Hallucinogens (visual distortions and hallucinations) Psychostimulants (paranoia, illusions, hallucinations) Alcohol withdrawal (VH) Glutamatergic drugs (AVH, delusions) Solvents (VH) Cannabis (mild paranoia) Medications (DA agonists, steroids)

Answer 31

**Positive** **Negative**: affective flattening, alogia, avolition-apathy, anhedonia-asociality **Disorganized**: tangential, circumstantial, loosening of associations

Answer 32

Disorganization as part of **"thought disorder"** that may reflect diminished hemispheric lateralization of language and disruption of semantic networks Stilted, overly **formal** speech ("problems with anthropological friction and synchronization of the societal freeway...") **Loosening of associations**, illogicality, incoherence **Neologisms** ("dramastic," "schizophrenzyism") **Concreteness**/lack of abstractions ("the glass will break")

Answer 33

**Affective** **flattening**: poor eye contact, decreased spontaneity, emotional withdrawal **Alogia**: impoverished thinking, speech latency, thought blocking, decreased abstract thought **Avolition-apathy**: decreased motivation, anergia, passivity **Anhedonia-asociality**: decreased pleasure (anticipatory \> consummatory), decreased social drive Note: negative symptoms found in other conditions such as depression but patients with schizophrenia who have negative symptoms are not depressed

Answer 34

**Primary negative symptoms**: **core** **features** of schizophrenia and may be mediated by aberrant DA and glutamatergic neurotransmission; do not respond well to antipsychotic therapy and "deficit syndrome" associated with poorer social/occupational function, quality of life and overall outcome **Secondary negative symptoms**: can be **caused** by **positive symptom** exacerbation, **depression**, medical **illness**, **medication** side effects, **psychosocial**/**environmental** factors

Answer 35

Two of more of the following 5 symptoms: 1) **Delusions** (positive symptoms) 2) **Hallucinations** (positive symptoms) 3) **Disorganized** **speech** (disorganized thinking) 4) **Grossly** **disorganized** or **catatonic** behavior (disorganized thinking) 5) **Negative symptoms**

Answer 36

**Meningioma** (30%) Glioblastoma (20%) Pituitary adenoma (6-20%)

Answer 37

**Intra-axial** (brain **parenchyma**): **glioblastoma** **Extra-axial** (not brain parenchyma): **meningioma**

Answer 38

**Pliocytic astrocytoma** (cerebellum) **Medulloblastoma** (cerebellum) Craniopharyngiomas (suprasellar) Germinoma (pineal gland/hypothalamus) Pituitary adenomas Other gliomas

Answer 39

Mutation in **Merlin**/neurofibromin2/schwannomin which is membrane-cytoskeleton scaffolding protein that may be associated with contact-mediated growth inhibition and may be linker for outside cues to cytoskeleton On **chromosome 22** **2 cerebellopontine angle vestibular schwannomas** Bilateral CN VIII schwannomas **diagnostic** of **NF2** Can have **meningioma** (psammoma bodies), **schwannoma** (Verocay bodies), **ependymoma** (perivascular pseudorosettes) All 3 tumors can be cured by resection In contrast, NF 1 is associated with neurofibromas and pliocytic astrocytomas

Answer 40

Mostly (80%) benign **Grade I** **Extra-axial** (meningeal) Association with **NF2** Histology: **whorls**, nuclear **pseudoinclusions**, **psammoma bodies** All grades can **recur** and Grade 3 can **metastasize**

Answer 41

**Lung, breast, renal, melanoma, GI** (colon) **Carcinomas** are **epithelial** and therefore express **keratin** in contrast to GBMs which are GFAP+

Answer 42

Biomarkers can potentially be tested to determine whether **therapeutic agent will be effective** Some biomarkers are **prognostic** **MGMT** (DNA repair enzyme) is an example of a biomarker, and if low MGMT in tumor, will be susceptible to **Temodar**

Answer 43

Common to **low grade astrocytomas,** **oligodendrogliomas** and **mixed gliomas**, as well as secondary glioblastomas that devolve from low grade tumors Rare in primary GBMs but **common** in **secondary glioblastoma**

Answer 44

**Astrocytic** tumor with **necrosis, vascular proliferation, mitoses** **High grade**, **aggressive** **infiltrative** intra-axial tumor (survival only **14 months**) **Primary GBM**: patient presents as GBM **Grade IV** **Secondary GBM:** evolves from low grade glioma (**Grade II, III**) **Butterfly glioma** involves **both hemispheres**

Answer 45

\<1% of population Risk increases with **urbanicity**, migration, winter births, obstetric complications, 1st/2nd trimester **maternal** **infection** (influenza, rubella, T. gondii), **advanced** **paternal age** and **cannabis** use Slightly more **males** are schizophrenic than females

Answer 46

Heritability: most cases are sporadic (1/3 with FHx), **80%** variance due to genetics, **50% among monozygotic twins**, **10-15% with dizygotic twin** or 1st degree relative **Polygenetic** disease with evidence for many different chromosomal abnormalities and candidate genes (DRD1, NRG1, G72, COMT, DISC1, DTNBP1, RGS4) **Epigenetics** may play a role Interaction of genes with **environment** (fetal hypoxia, infection, etc)

Answer 47

**Enlarged** **ventricles**, **reduced** whole brain/**grey matter** volume, reduced hemispheric asymmetry, cortical volume loss, white matter disconnectivity, **excessive synaptic pruning**, sensory gating (P300, PPI) abnormalities, increased presyn DA synthesis, increased striatal DA receptor density, decreased N-acetyl aspartate, decreased glutamate receptors However, no single common genetic, structural, or neurochemical "lesion" has been found

Answer 48

Males: 20-24 Females: 25-29

Answer 49

**Premorbid** risk: genetic, environmental, social, etc **Prodrome**: nonspecific symptoms, functional decline **Diagnosis**: positive symptoms, chronicity By definition, symptoms must be present continuously for at least **6 months**; thought spontaneous recovery can occur, in the vast majority of cases, schizophrenia does not completely resolve, even with treatment and there is no "cure" for schizophrenia **Mortality** is increased with schizophrenia (increased **suicide**, **accidents**, and **medical** morbidity) with lifespan shortened by **10-15 years**

Answer 50

NOT schizophrenia because not for 6 months **Schizophreniform \< 6 months** **Brief psychotic disorder \< 1 month**

Answer 51

**Acute** onset Later onset Onset with **precipitating** **event** Good premorbid functioning **Lack of negative** and cognitive symptoms **Female** Mood symptoms **Psychosocial support**

Answer 52

Vigilance/sustained attention Processing speed Memory (immediate and "working" memory, secondary memory, verbal memory) Verbal fluency (word generation) Executive function (volition, planning, set-shifting) Social cognition (emotional processing, theory of mind, etc)

Answer 53

Cognitive impairment can be subtle, but deficits can be as large as 2 standard deviations from normal Cognitive deficits most predictive of functional (vocational/interpersonal) impairment and quality of life Cognitive symptoms of schizophrenia are present well before onset of the full-blown disorder Mild cognitive symptoms associated with schizophrenia also found amont non-affected first degree relatives Cognitive symptoms are therefore ideal candidates for "endophenotypes" of schizophrenia (subclinical, objectively quantifiable traits that are associated with the illness in the general population; heritable, co-segregating and increased prevalence within families) Cognitive symptoms respond only modestly to antipsychotic treatment Current drug development in schizophrenia focuses on putative "cognitive enhancers" as adjunctive interventions

Answer 54

**H&P** Basic **labs** (CBC, chemistries, RPR, TSH, U/A) **Urine drug/tox screen** (cocaine, amphetamines, cannabinoids, opiates, benzodiazepines, hallucinogens, phencyclidine, ketamine, MDMA, alcohol) **Neuroimaging** for first-episode psychosis, children and elderly

Answer 55

**Dopamine D2 antagonists** On treatment for entire life 1st and 2nd generation drugs differ in terms of side effects (more **extrapyramidal** side effects with **1st gen**) Side effects: subjective **dysphoria**, motoric toxicity (restlessness, parkinsonism, **tardive** **dyskinesia**), **metabolic** side effects; so much carefully monitor **1st gen**: **haloperidol**, **fluphenazine**, thiothixene, perphenazine, trifluoperazine, loxapine, chlorpromazine, thioridazine **2nd gen**: **clozapine**, **risperidone**, **olanzapine**, quetiapine, ziprasidone, **aripiprazole**, paliperidone, iloperidone, asenapine, lurasidone

Answer 56

"Antipsychotic response" defined as 20% reduction in symptoms Approx 30% of patients with schizophrenia do not respond to antipsychotic treatment **Clozapine** is most **effective** antipsychotic medication for non-responders, but also has most **dangerous side effects** (seizures, agranulocytosis, myocarditis, etc) Effectiveness is routinely compromised by non-adherence (due to lack of insight, side effects, resistance) and substance abuse (50% lifetime prevalence) **Positive symptoms** most responsive targets of antipsychotic therapy

Answer 57

Historically, good outcomes when patients living in **supported** **housing** and subsisting on disability income who is able to stay out of the hospital **"Recovery Model"** now challenges these expectations and emphasizes **reintegration** into community with vocational and psychosocial rehabilitation

Answer 58

For optimal outcome, must integrate **psychotherapy** with **pharmacotherapy** as well Evidence-based interventions: **social** **skill** **training**, **CBT**, cognitive remediation, compliance therapy, acceptance and commitment therapy, assertive community treatment, family based services, supported employment, yoga

Answer 59

Delusions of **at least 1 month's duration** Apart from impact of delusion(s) or its ramifications, **functioning** is not markedly impaired and behavior is not obviously odd or bizarre Lack of insight inherent to delusional thinking associated with non-treatment and poor overall prognosis

Answer 60

Comorbidity of **schizophrenia** and **mood disorder** (major depression or bipolar I disorder) Psychotic symptoms must be present for at least **2 weeks** in the absence of prominent mood symptoms

Answer 61

Remember, PDs not diagnosed if symptoms are better accounted for by an Axis I disorder (like schizophrenia) Cluster A personality disorders lack full-blown psychotic symptoms, but share some thematic features with psychotic disorders and most are found at a greater rate among relatives of patients with schizophrenia (but **schizoid PD patients do NOT have more relatives with schizophrenia**) **Paranoid** **PD** (suspicious, mistrustful, preoccupied, reads into things, bears grudges) --\> **Delusional Disorder** **Schizotypal PD** (ideas of reference, odd/magical beliefs, unusual perceptions, suspicious, inappropriate affect, social anxiety) --\> **Schizophrenia** **Schizoid PD** (solitary, detached, reclusive, anhedonic, indifferent to others, emotionally flat) --\> **negative symptoms**

Answer 62

**First** antipsychotic drug (made in 1950s)

Answer 63

Used as **generic** term for **antipsychotics** (aka **antischizophrenics** or **neuroleptics**) because many antipsychotic drugs have this chemical structure Ex: chlorpromazine (Thorazine), thioridazine (Mellaril) and fluphenazine (Prolixin)

Answer 64

**Positive** symptoms: exaggeration of normal function (abnormality, distortion, **delusions**, prominent **hallucinations**, impaired reasoning) **Negative** symptoms: loss of function (**catatonic** behavior, **flat** or grossly inappropriate affect)

Answer 65

States that hyperactivity of central DA systems is responsible for the psychiatric state observed Could be **increased synthesis or release of DA**, decreased degradation of DA cell levels, or supersensitive postsynaptic DA receptors This hypothesis supported by findings that antipsychotic drugs block dopamine D2 receptors **Inconsistencies** in this hypothesis: don't start seeing antispychotic effects until 3-6 weeks after treatment (but D2 blockage occurs right after administering drug); clozapine (doesn't have affinity for D2) still works well as antipsychotic

Answer 66

**D1** and **D5** receptors **increase** adenylyl cyclase activity **D2, 3, 4** receptors **inhibit** adenylyl cyclase activity

Answer 67

Ability to bind to **D2 receptor** (NOT ability to bind D1 receptor)

Answer 68

Based on interactions between hallucinogens (LSD) and 5HT in the brain at **5HT-2A** receptors, particularly in locus ceruleus and cerebral cortex Enhancement of glutamatergic transmission

Answer 69

Based on evidence showing **hypofunction** of **glutamatergic** signaling via NMDA receptors Antagonists of NMDA subtype of glutamate receptor (phencylidine and ketamine) cause psychotic symptoms --\> so lack of glutamate signaling may cause schizophrenia This hypothesis does not negate the DA hypothesis since the two may be brought together by circuit-based models

Answer 70

**Phenothiazines**: chlorpromazine (Thorazine), thioridazine (Mellaril), fluphenazine (Prolixin) **Butyrophenones**: haloperidol (Haldol) Note: there are the **typical antipsychotics**

Answer 71

Absorption is variable and unpredictable Highly **lipid soluble** and extensively protein bound Complicated metabolic pathways with active metabolites (can last weeks!); plasma half life 10-20h; brain half lives longer Usually administered **once-daily**

Answer 72

Block **DA**, muscarinic **cholinergic**, **alpha** **1**, **histamine** **H1** receptors Psychological effects: initial **psychomotor slowing**, **emotional quieting** (sedation and tranquilization), sleepiness, restlessness, emotional indifference (neuroleptic syndrome) Brain electrical activity slowed with increased synchronization --\> decrease seizure threshold and can elicit **seizures** in susceptible individuals **Inhibit vomiting** by blocking D2 receptors in CTZ Can produce **hypothermia** due to altered temperature regulation in hypothalamus

Answer 73

**Schizophrenia**, **schizoaffective** disorder, **schizophreniform** disorder, **brief** **psychotic** disorder: acute treatment and prophylaxis of recurrence, does not cure but reduces symptoms, can take weeks or longer to see antipsychotic activity and in most cases not completely effective **Acute** **psychotic** **episodes**: due to endocrine or metabolic disturbances or drug reactions; also used for adverse reactions to psychotomimetic drugs Other psychiatric indications: acute treatment of **manic** **episodes** in bipolar affective disorder, **psychotic** **depression**, augmentation agent in **depression**, **dementia** (Alzheimers disease), rapid control of acute violence and agitation Nonpsychiatric indications: Gilles De La Tourette's Syndrome, nausea/vomiting (prochlorperazine, promethazine), intractable hiccough (?) Note; NOT used for alcohol withdrawal or anxiety

Answer 74

Behavioral: **lethargy** and drowsiness, **pseudodepression**, toxic **confusional** states (due to antimuscarinic activity) Neurologic (extrapyramidal syndrome (**EPS**)) **early** **onset**: **parkinsonian** syndrome (sometimes goes away with time), **akathisia** (motor restlessness, not anxiety or agitation), **acute** **dystonic** reactions (abnormal contraction of muscle groups, concomitant sustained contraction of agonist and antagonist muscles including facial grimacing, torticollis, oculogyric crisis; is frightening and painful) Neurologic (extrapyramidal syndrome (**EPS**)) **late** **onset**: **tardive dyskinesia** (develops after **months** or years on drug, may be **irreversible**) consists of **lip** **smacking**, chewing and **tongue** **protrusions** (bucco-linguo-masticatory syndrome), **choreoathetoid** **limb** **movements**; treatment is to **gradually reduce dose** but may make it worse Endocrine: **gynecomastia**, galactorrhea, amenorrhea CV: **orthostatic** **hypotension**, fainting with reflex tachycardia, cardiac toxicity due to local anesthetic effects ANS: **antimuscarinic** effects (**dry mouth, blurred vision, constipation, urinary retention**), inhibition of ejaculation due to alpha 1 blockade **Weight gain** **Pigmentary retinopathy** (esp with thioridazine) Allergic reactions: **agranulocytosis**, cholestatic (obstructive) **jaundice**, dermatitis and photosensitivity reactions

Answer 75

Rare idiosyncratic response caused by adverse reaction to medication with **DA** **antagonist** or by rapid withdrawal of DA medication **Fever**, **muscle rigidity**, autonomic instability, altered mental status Treatment: stop antipsychotic medication, cool, rehydrate, administer **DA agonist** and administer **dantrolene** (direct muscle relaxant) **Fatal** (10-30%) but not when **recognized early and treated aggressively** (recovery 2-14 days)

Answer 76

Additive with other **CNS depressants** (sedative-hypnotics, antidepressants, antihistamines, opiates, ethanol)--however, **OD is rarely fatal** Check for potential P450 interactions

Answer 77

**Clozapine** (Clozaril), **risperidone** (Risperidal), olanzapine (Zyprexa), quetiapine (Seroquel), xiprasidone (Geodon), aripiprazole (Abilify) Highly **non-selective** Vary in **antagonist** activity at **D1, D2, 5HT-1A, 5HT-2A, alpha 1, alpha 2, H1, histamine** receptors (except **aripiprazole** is **partial agonist** at DA and 5HT!) Psychological: sometimes effective in patients who have not responded to typical antipsychotics, more efficacious in treating **negative symptoms** of schizophrenia

Answer 78

**Neurologic** (extrapyramidal): **less** likely to produce movement disorders and tardive dyskinesia **Endocrine**: **less** likely to increase prolactin secretion; less likely to cause gynecomastia, galactorrhea and amenorrhea CV: **orthostatic hypotension, QT lengthening** (Ziprasidon), increased risk of v-tach, torsades de pointes and sudden death (may all be due to interactions with other drugs metabolized by CYP3A4) **Weight gain** Atypical antipsychotics associated with development of **T2DM**! **Agranulocytosis** (with Clozapine)

Answer 79

For **positive** **symptoms**, **secondary negative symptoms** and **behavioral disruption**