Anti-Psychotics

Question 1

Psychosisand

Answer 1

symptom of mental disease: anosognosis, cognitive deficit, major depression, apathy, aboulia, alogie, Malia with hallucinations, delusions, disorganized speaking and agitation

Question 2

Substances involved in inducing psychosis

Answer 2

Amphetamine(increase presynaptic neurotransmitter release), Methyphenidate, cocaine, amphetamine (inhibit presynaptic dopamine reuptake, levodopa (increase dopamine availability)

Question 3

Before 1950, psychosis therapy

Answer 3

sedation, shock therapy, brain surgery

Question 4

First antipsychotic

Answer 4

chlorpromazine (anesthetic), neuroleptics due to dopamine overactivity, psychomotor slowing, emotional quieting, affective indifference,

Question 5

Second generation

Answer 5

Serotonin importance, lower risk of extrapyramidal/prolactin, efficiency in treatment resistant patients but with metabolic adverse effects

Question 6

First generation antipsychotics - low potency

Answer 6

chlorpromazine, chlorprothixene, levomepromazine, melperone, perazine, pipamperone, promazine, promethazine, sulpiride, thioridazine, zuclopenthixole

Question 7

First generation antipsychotic - high potency

Answer 7

benperidol, flupenthixol, fluphenazine, haloperidol, perphenazine

Question 8

Second generation antipsychotics

Answer 8

amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, zotepine

Question 9

depot antipsychotics

Answer 9

fluphenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, fluspirilen, perphenazine, enanate, zuclopethixole decanoate

Question 10

First generation antipsychotics (classical, conventional, typical, neuroleptics, major tranquilizers)

Answer 10

block dopamine, cholinergic (muscarinic), alpha1, h1 receptors, bond tightly to dopaminergic receptors and produce neurological side effects. read more

Question 11

Second generation antipsychotics (atypical_)Antipode

Answer 11

metabolic side effects, life shortened by one decade, block serotinergic (5HT2A) and dopaminergic receptors, equally effective for reducing positive symptoms (hallucinations, delusions), better at relieving negative symptoms (withdrawal, thinking problems, lack of energy),

Question 12

Antiparkinson Drugs

Answer 12

one of most common neurological diseases, 40-60, two of three major symptoms: bradykinesia, hypertonia, and tremor. Only slows down progressive disability, does not stop the disease, usually after 10-15 years of treatment, drugs no longer effective.

Question 13

Dopamine precursor

Answer 13

Levodopa

Question 14

Inhibitors of dopamine degradation - MAO B inhibitors

Answer 14

Selegeline, rasagiline

Question 15

Inhibitors of dopamine degradation - COMT inhibitors

Answer 15

entacapone, tolcapone

Question 16

Dopamine receptor agonists

Answer 16

Bromocriptine, pramipexol, ropinirole

Question 17

NMDA antagonist

Answer 17

amantadine

Question 18

Muscarinic receptor antagonists

Answer 18

trihexyphenidyl, benztropinem, diphenhydramine

Question 19

Parkinson mechanism off action

Answer 19

The GABAergic neurons are the most important efferents from the striatum (see figures); normally they are inhibited by the dopaminergic afferents from the substantia nigra and stimulated by the glutaminergic afferents (from the cerebral cortex and thalamus) and cholinergic striatal interneurons.
The dynamic balance between dopamine and acetylcholine is required for proper initiation and integration of motor patterns; the loss of dopamine neurons in Parkinson’s disease upsets this balance; the goal of the therapy is to return the system to a balanced state by:
increasing local dopamine levels (Levodopa, MAO B inhibitors, COMT inhibitors), stimulating dopamine receptors (dopamine receptor agonists);
inhibiting the effect of cholinergic afferents (anticholinergics);
inhibiting glutaminergic NMDA receptors (Amantadine).

Question 20

Levadopa

Answer 20

Levodopa (L-3,4-dihydroxyphenylalanine), the most efficient antiparkinsonian drug, is an amino acid naturally occuring in the human body. It is the precursor of dopamine, by decarboxylation.
Mechanism of action
conversion to dopamine occcurs in the CNS and in the peripheral tissues, causing adverse effects.
Pharmacokinetics
Absorption: oral Levodopa is absorbed rapidly from the small bowel; the rate of absorption is influenced by: gastric emptying rate, local pH, meals (delays absorption);
Distribution: Levodopa crosses the BBB, but only 1-2% of the administered Levodopa reaches the brain;
Biotransformation and elimination: the t1/2 is 1-3 hours.
Interactions
Vitamine B6 increases extracerebral Levodopa metabolism;
administering Levodopa with MAO A inhibitors or within two weeks after discontinuation of these drugs increases the risk for HBP crisis;
foods rich in proteins compete with Levodopa for absorption, lowering it.
Indications
Parkinson’s disease;
dopamine-responsive dystonia.
Contraindications
psychosis;
angle-closure glaucoma;
history of melanome or suspicious undiagnosed skin lesions (Levodopa is a precursor of melanin);
first months of pregnancy.
Adverse effects
orthostatic hypotension (avoid antihypertensive drugs);
arrhythmias (low incidence);
nausea, vomiting;
confusion, anxiety, hallucinations, sleeping disturbances (insomnia in young patients, somnolence in older patients);
dyskinesias (choreoathetosis);
mydriasis;
„on/off phenomenon”.
Therapeutic notes
Levodopa is administered usually in association with a peripherally acting inhibitor of dopa-decarboxylase (synthetic catecholamines - Carbidopa, Benserazide) that does not penetrate into the CNS (see figure); this decreases the frequency of some adverse effects, because Levodopa is not converted to dopamine, noradrenaline or adrenaline in the peripheral tissue; furthermore, the quantity of Levodopa that reaches the CNS is increased from 1-2% to 10% and we can reduce the administered dose (to 25%) Levodopa does not stop the disease progression and after 5-10 years of treatment, we will encounter the „on-off phenomena”, which means sudden changes from periods of good symptom control (1 to 2 hours after the administration) to periods where symptoms (rigidity, akinesia) are less controlled; increasing the dose and frequency of administration will improve this situation.

Question 21

Selegeline

Answer 21

selective (high doses it is lost), irreversible MAO type B inhibitor, slows central degradation of dopamine because MAO B is responsible of dopamine metabolization, should not be administered if patients take Meperidine, tricyclic antidepressants, SSRIs, I: Parkinson (association w Levadopa), depression, senile dementia AE: anxiety, insomnia, hallucinations, nausea, constipation, arrhythmia
adjunsctive treatment to Levadopa, allows reduction of dose and attenuates mild on off phenomenon and end of dose akinesias

Question 22

Entacapomne

Answer 22

conjunction w levodopa - prevents Catechol-O-methyltrasnferase from metabolizing levadopa in periphery, I: Parkinson disease, same effect as Levadopa, entacapone administered at same time with each dose of Levodopa/carbidopa

Question 23

Bromocriptine

Answer 23

ergot alkaloid, dopamine agonists directly activate dopamine receptors, inhibits prolactin synthesis, D2 and partial D1 agonist, read more

Question 24

Trihexyphenidyl

Answer 24

I: early Parkinson’s, drug induced Parkinsonism in patients treated with antipsychotic agents; CI : prostatic hyperplasia, narrow angle glaucoma, obstructive GI disease; AE” sedation, confusion, hallucination, mood change, dyskinesia, dry mouth, urinary retention, blurred vision, increased ICP, arrhythmia, nausea, vomitting, less effective than Levodopa, improve rigidity and tremor but minor effect on bradykinesia, does not respond to anymuscarinic, may respond to another choice

Question 25

Amantadine

Answer 25

antiviral that also alters dopamine release, has anticholinergic properties and blocks glutamate receptors, biotransformation and elimination, t 1/2 is 2-4 hours, urinary excreted mainly unchanged, I: initial therapy of mild Parkinson’s disease, CI: seizure history, congestive heart failure, AE: dizziness, sedation, confusion, hallucinations, sleep disturbances, nausea, vomiting, dry mouth, urinary retention, constipation, less potent than LEvadopa but improves rigidity, tremor, bradykinesia

Question 26

First generation antipsychotics pharmacodynamic

Answer 26

neuroleptic: antipsychotic (decreases hallucinations, delirium, autism, agitation), major tranquilizing (reduce nervous tension, anxiety and hyperexcitability), extrapyramidal effects (undesired);
antiemetic;
sedation (Levomepromazine, Chlorpromazine, Thioridazine, Chlorprothixene, Flupenthixol);
central and peripheral depression of the vegetative nervous system (alfa 1 - adrenolytics) with orthostatic hypotension and hypothermia (Chlorpromazine, Haloperidol);
antimuscarinic action, with constipation, hyposalivation, visual disturbances (Thioridazine);
hyperprolactinemia;
hypothermia, due to thermoregulatory center inhibition and peripheral vasodilation;
antihystaminic H1 action (Chlorpromazine)

Question 27

First generation antipsychotic indications

Answer 27

schizophrenia;
maniacal psychosis;
agitation;
bipolar disorders;
senile dementia;
Huntington’s chorea;
Tourette’s syndrome (Haloperidol);
rare as antiemetics (in small doses).

Question 28

First generation antipsychotics adverse effects

Answer 28

parkinsonism in more than 80% of the patients, with rigidity, bradykinesia, tremor; appear progressive, more often in older patients; the treatment includes Trihexyphenidyl;
decreased attention, memory impairment, sedation;
extrapyramidal reactions (more often after Haloperidol): dystonia in 4 hours after administration (more often in younger patients), akathisia might appear after 4 days and akinesia, after one month of treatment;
neuroleptic malignant syndrome, rare, but lifethreatning, with: confusion, hyperthermia, muscle rigidity and seizures; the treatment includes: stop the antipsychotic administration, Dantrolene (myorelaxant) and Bromocriptine (D2 dopaminergic agonist);
tardive dyskinesia, often irreversible, in more than 25% of the patients, after at least 7 years of administration;
anticholinergic side effects;
gynecomastia, galactorrhea, amenorrhea, because of increased prolactinemia;
hypotension;
corneal deposits (Chlorpromazine);
retinal deposits (Thioridazine).

Question 29

Second generation Adverse effects

Answer 29

obesity (Olanzapine);
diabetes;
hyperlipidemia;
sedation (Quetiapine);
hyperprolactinemia (Risperidone);
agranulocytosis (Clozapine, never first line), which might lead to death;
increase in QT interval (Ziprasidone).