Neuroanatomy Block 4 Antipsychotics

neuroleptic

become less withdrawn or less excited agitated and hostile
less irritable
anxious
suspicious
more cooperative
begin to participate in activities
with continued therapy, delusions, halucinations, paranoia, and disordered thought processes diminish and may disappear
*onset of tx benefit may be prolonged

manic phase of bipolar affective disorder

conventional antipsychotic drugs

schizophrenia
psychotic depression
drug-induced psychosis

maintenance pharmacotherapy to prevent relapse of psychosis

decrease delusions/hallucination
quiet agitation
sedation
movement (extrapuramidal) disorders
antiemetic
anticholinergic
orthostatic hypotension
quinidine-like effects
depressed T-wave
prolonged Q-t interval (irreversible)
increase prolactin, decrease secretion of gonadotropin/GH/ACTH
poikilothermic effect

phenothiazines (chloropromazine)
butyrophenones (halperidol)
thioxanthenes (thiothixene)
miscellaneous (loxapine)

clozapine
riserpidone
olanzapine
quetiapine
sertindole

1. parental administration of acute agitation
2. lack of benefit or intolerance to novel agents
3. special populations (eg pregnant patients)
4. noncompliant patients for whom depot medication may be indicated

phenothiazine structure forms basic nucleus of this group
substitution at position (2) imparts antipsychotic activity
substitution on nitrogen at position (10) alters potency and adverse effects; the principal substitutions are: aliphatic, piperdine, piperazine

schizophrenia
psychotic depression
drug-induced psychosis

aliphatic and piperidine substitutd compounds

thioridazine

piperazine substituted compounds

fluphenazine
trifluoperazine

haloperidol

thiothizene

loxapine

molindone

molindone

parenteral administration for acute agitation
lack of benefit/intolerance to novel agent
special populations (pregnant)
noncompliant patients who depot meds may be indicated

atypical

various dopamine (D1 and D2), adrenergic, muscarinic receptors, have lesser degree of activity at serotonin receptors

D2 receptors

chlorpromazine

thioridazine

fluophenazine
trifluoperazine

MORE likely to cause sedation, orthostatic hypotension, hypersensitivity
LESS likely to induce parkinsonism/EPS

MORE likely to cause sedation, orthostatic hypotension, hypersensitivity
LESS likely to induce parkinsonism/EPS

EPS, antiemetic activity
less hypotension and sedation

1. reduced hallucinations/delusions
2. quieting of agitated patients
3. sedation - helps in agitated pts
4. decreased spontaneous activity (cataleptic state in high doses)

dopamine receptor blockade in mesolimbic-mesocortical dopaminergic system
1. lowers seizure threshold
2. toxic confusional state: due to central anticholinergic effects especially troubling in older patients

type of mvmt disorder confusing and methods of treatment vary
-Parkinsonism, akinesia, tremor, rigidity
-acute dystonia
-akathisia
-tardive dyskinesia
-perioral tremor

reduce dose or change drug, anticholinergic antiparkinson drugs
amantadine

spasms involving head, neck, trunk, extremities

bextropine, diphenyhydramine
due to dopamine receptor blockade

state of extreme motor restless and drive to move

reduce dose, switch to low potency or atypical
propranolol, benzodiazepines, amantadine
Mech is uncertain

stereotyped, repetitive involuntary mvmts of mouth, lips, tongue, choreiform mvmts of limbs and body

gradual reduction of dose
avoid anticholinergic drugs
switch to atypical
mech: dev supersensitivity of dopamine receptors as a consequences of long term blockade

rabbit syndrome, late appearing
cyclical mvmt of body part

responds to anticholinergic antiparkinson drugs or reduction in dose of antipsychotic agents
uncertain mech, dopamine receptor blockade

blockade of chemoreceptor trigger zone
phenothiazines - not effective against motion sickness

promethazin

alpha adrenergic blockade results in orthostatic hypotension
muscarinic blockade: anticholinergic side effects are frequent and troublesome causing dry mouth, blurred vision, urinary retention in males with prostatism, aggravation of glaucoma

antihistaminic
antiserotonergic activity

local anesthetics
anticholinergic
quinidine-like effects
depressed T waves and prolonged Q-T interval, reversible on discontinuation of drug

increases prolactin secretion
produces lactation females
gynecomastia in males
ovulation and menstruation disturbances
decreased secretion of gonadotropin, GH, ACTH

poikilothermic effect: decreased temperature regulating and vasomotor mechanisms
have either hypothermia or hyperthermia
preanesthetic medication to facilitate hypothermia for certain type of surgery

CNS: drowsy, Parkinsonism, akathisia, dystonia, lowered seizure threshold, oculogyric crisis, tardive dyskinesia, confusional state, depressive state
Autonomic: hypotension, orthostatic hypotention, anticholinerfic effects, ECG changes, hyperpyrexia, impaired ejaculation
endocrine
hypersensitivity, photosensitivity, allergic rashes, blood dyscriasis, cholestatic jaundice
eye -toxic retinopathy
weight gain: molindone seems to be least troublesome

neuroleptic malignant syndrome

respiratory or renal failure

stop antipsychotic
cool pt
bromocriptine -D agonist
L-dopa and amantadine
dont give neuroleptic for at least 2 wks
dantrolene to decrease rigidity
begin with low doses and increment slowly using low potency neuroleptics

potentiate CNS depressant and opiods
synergistic depression w/ ethanol; inhibits alcohol metabolism
reduce tx effectiveness of L-dopa in PD
additive anticholinergic and alpha-blocking effects
interfere with antihypertensive of guanthedine
may potentiate cardiotoxicity (quinidine-like)
inhibit phenytoin metabolism

agranulocytosis

EPS
no tardive dyskinesia

D2, 5HT, alpha1 receptors

D2, 5HT, D1, D4, 5HT2, alpha2, muscarinic, H1

5HT, D2, alpha1 receptors
side effects: nasal congestion, sexual dysfunction, dry mouth, orthostatic hypotension, dizziness

haloperidol
used to gain rapid control due to the slow onset of lithium

haloperidol - effective and most used
pimozide - approved for Tourette's

lithium, a mood stabilizer
prevent both epressive and mani episodes

recurrent endogenous depression

7-10 days

2.0 mEq/L

sodium intake
in sodium deficiency, lithium ion may accumulate to toxic levels
also NSAIDS

cause lithium retention and toxicity

0.6-1.2 mEq/L

pregnancy

fluid and electrolyte replacement
saline infusion
osmotic diuretics
peritoneal dialysis or hemodialysis
tx thiazide diuetics
necessary to follow cardiac and renal status
anticonvulsants for seizures

valproic acid-best alternative for mania or maintenance of bipolar disorder

carbamazepine: an alternative to lithium in treatment of bipolar disorder