B5-6: 1st (typical) and 2nd (atypical) Generation Antipsychotics Flashcards
What is Schizophrenia?
What are the 3 major categories of pathological features of schizophrenia?
Chronic psychosis with delusions, hallucinations, thinking/speech disturbances. Neurodevelopmental / genetic disorder, 1% prevalence. Dysfunction of mesolimbic or mesocortical dopaminergic neuronal pathways
Features: Positive symptoms (e.g. hallucinations), Negative symptoms (e.g. apathy), and Cognitive Deficit (impaired memory and attention).
What are positive and negative symptoms in Schizophrenia?
- Positive: something “added” to the normal, e.g. hallucinations, delusions, aggressiveness. Related more to mesolimbic / mesocortical D2 receptors and some 5-HT receptors.
- Negative: lack of something that would be normal in behavior, e.g. decreased affection, anhedonia, ambivalence, catatonia. Also autism (extreme introversion), alogia (cannot project thoughts into reality). Related more to 5-HT2A, 5-HT7, α2, D3 (From Riba but who really knows with specific serotonin receptors)
Changes in which three neurotransmitters are believed to be responsible for schizophrenia? What evidence supports this?
- Excessive Dopamine: Most antipsychotics have effect via blockade of D2 receptors. Drugs that increase dopamine aggravate schizophrenia. High density of DA receptors found in schizophrenic brains.
- 5-HT alterations: serotonin regulates DA. Hallucinogenic drugs act on 5-HT system in similar ways to what cause hallucinations in schizophrenics. Most 2nd generation antipsychotics are inverse agonists of 5-HT2 receptors.
- Glutamate: NMDA hypofunction may have role in cognitive deficit.
What are the differences between first and second generation antipsychotics?
- First gen: older, mainly suppress positive symptoms of schizophrenia (mesolimbic D2 blockade), and have high incidence of extrapyramidal symptoms (EPS) due to nigrostriatal D2 blockade.
- 2nd gen: Suppress positive symptoms + improve negative symptoms. Have less EPS. Still have cognitive deficit. Usually antagonize 5-HT2 more than D2.
- (3rd gen may come soon to address cognitive deficit. May act on NMDA Glu receptors)
What is the general order of extrapyramidal symptoms (EPS), from early symptoms to late?
[Mostly just including the names of the effects, but details will be on earlier slides]
- Acute dystonia
- Parkinson Syndrome (drug-induced)
- Neuroleptic Malignant Syndrome
- Uncontrollable restlessness (acathisia).
- Perioral tremor
- Tardive dyskinesia (all the above can respond to treatment, except this one. It’s usually late effect but not always; this order is in general but it doesn’t occur like this all the time)
What are some of the symptoms of acute dystonia?
What can be used to treat them?
- Strong rigidity of neck muscles, can’t move head
- Oculogyria: can’t move eyes, they get stuck in one position
- Tics: sudden, repetitive, nonrhythmic motor movement or vocalization
- Automatic tongue movements
Treat with antihistamines, cholinolytics, maybe even calcium (I think Riba said something about this). Probably benzos too. Not harmful but annoying. Tend to resolve spontaneously during treatment.
What are the 4 basic symptoms of Parkinson’s Syndrome? (relevant to drug-induced form in these topics)
- Resting tremor
- Hypoknesia or akinesia: cannot move despite motivation, and movement is slow
- Muscle rigidity in extensor and flexor muscles. Mask-like face
- Unstable posture
Usually give centrally-acting antimuscarinic drugs as treatment (will be in other card decks)
What are the 3 main symptoms of Neuroleptic Malignant Syndrome (NMS)?
What drugs can be used to treat it?
- Extreme catatonia (pt is locked in)
- Malignant hyperthermia (muscles shiver and body temp rises)
- Autonomic instability (low BP, etc.)
[Most dangerous of the extrapyramidal symptoms]
Treatments: dopamine agonist (Bromocriptine), physical cooling, Dantrolene (for malignant hyperthermia), Diazepam, give anti-hypotensives if necessary
What is Tardive Dyskinesia?
What are the symptoms?
- Frequently irreversible dopaminergic hypersensitivity that is usually a late sign from chronic anti-psychotic use (hypersensitive dopamine receptors due to long DA blockade).
- Involuntary movements, notably in the mouth (e.g. “fly-catching” motions of tongue, smacking lips). May also be slow writhing movements or rapid jerking movements.
What should be done to a patient showing signs of Tardive Dyskinesia?
Reduce dose or cut off completely, switch to a different antipsychotic. Other anti-EPS meds like anticholinergics may worsen the condition. Sedatives like clonidine, propranolol, or benzos may alleviate symptoms.
Antipsychotics often have varying degrees of H1, α1, and muscarinic receptor inhibition.
What are some typical side effects related to inhibition of each of these 3 receptors?
- H1 antagonism: sedation, dizziness, confusion, weight gain
- α1 blockade: dizziness, hypotension, reflex tachycardia
- M inhibition: peripheral parasympatholytic symptoms (dry mouth, constipation, difficult urination), delirium, impaired memory
[Note I’m not putting the receptor inhibition profiles for every drug bc Riba said we don’t need to know]
What are the two most important 1st generation antipsychotics to know?
[I will include others, but just want to focus on these right now]
- Chlorpromazine: oldest. highly sedative, less EPS.
- Haloperidol: strongest, good for acute psychosis. Less sedative, more EPS.
[extra: Chlorpromazine has the brand name Thorazine. The zombie-like walk of patients medicated with Thorazine is called the Thorazine Shuffle. Chlorpromazine also has the brand name Hibernol because it is thought to keep your body temperature closer to that of the environment]
What is a depot injection of antipsychotics?
In which population might this be useful?
- Intramuscular injection of antipsychotic that causes a slow, 2-week effect.
- Useful in non-compliant schizophrenics. Schizophrenics often hate taking their pills. (2nd generation antipsychotics available in pills that immediately dissolve, so they can’t hide it under their tongue and spit it out later)
In which types of patients might antipsychotics be at risk of causing a stroke?
In elderly people with cerebral atrophy that is the cause of their psychosis. Should not give them antipsychotics.
(Don’t give them benzos either, can make them agitated)
D2 blockade from antipsychotics has what adverse effect on the endocrine system?
Hyperprolactinemia (DA inhibits prolactin)
