I hope you had a great weekend. Today will be our “week in review” where we review last weeks material as well as past materials. I have received positive feedback about last weeks quiz format, so we will continue that format today.
1) Antipsychotic medications block dopamine (D2) receptors throughout the brain. The blockade of dopamine in which neural pathway is likely responsible for reduction in the positive symptoms of schizophrenia?
a) Tuberoinfundibular pathway
b) Nigrostriatal pathway
c) Mesolimbic pathway
d) Mesocortical pathway
2) One day after starting an antipsychotic medication your patient presents to clinic stating that he feels irritable and suicidal. During the interview he is sitting down but looks very anxious and is stamping his feet and constantly crossing and uncrossing his legs. What drug reaction might be going on?
a) Dystonic reaction
d) Tardive dyskinesia
3) Name a memory aid (mnemonic) that we discussed to help remember the range of presentations for a patient with neuroleptic malignant syndrome (NMS)?
4) Some antipsychotics block cardiac potassium channels and are linked to the prolongation of the cardiac QT interval. This is a risk factor for the ventricular arrhythmia torsades de pointes which is often fatal. Which of the following medications has the least effect on prolonging the QTc?
5) All antipsychotics have been associated with weight gain although mean weight gained varies substantially between drugs. Which antipsychotic medication is NOT considered low risk in regards to its potential for weight gain.
DON'T LOOK UNTIL YOU HAVE FINISHED THE ENTIRE QUIZ
From Day 12
•Dopamine (D2) blockade in the Tuberoinfundibular pathway -> stimulates prolactin secretion -> (women) breast discharge [galactorrhea], amenorrhea, sexual dysfunction -> (men) enlargement of breast tissue [gynecomastia], sexual dysfunction. This same mechanism can lead to changes in bone metabolism and increase incidence of osteoporosis and risk of fractures if taken for prolonged period of time.
•Antipsychotic medications can also block dopamine receptors in an area of the brain that is vital for the production of movement. Disruption in this pathway leads to movement disorders. This pathway is called the nigrostriatum which is neuron tract in the basal ganglia that connects the substantia nigra pars compacta to the dorsal striatum and the caudate nuceli. The nigrostriatum is apart of the extrapyramidal system, which is responsible for the modulation and regulation of motor signals.
•The positive symptoms of schizophrenia (hallucinations, delusions, disorganized speech, etc...) are treated by reducing dopamine in the mesolimbic dopamine pathway (nucleus accumbens, fornix, amygdala, and the hippocampus).
•The negative symptoms of schizophrenia (anhedonia, apathy, flat affect, etc.) are thought to occur due to (decreased) dopaminergic action in the mesocortical pathway (cerebral cortex). It makes sense, then, that treating with antipsychotics (blocking dopamine) can actually worsen negative symptoms in some cases.
From Day 13
•Dystonic reaction = sustained painful contraction of muscles. Timing: can occur within hours of starting antipsychotics (minutes if the IM or IV route is used). Can include muscles of the neck (head twisting to the side called torticollis), tongue, eyes (rolling upwards called oculogyric crisis), or back (arching back called opisthotonos), airways, or diaphragm. Spasms of the airways (larygospasm) and diaphragm (cause asphyxiation) can be life threatening. The patient may be unable to speak or swallow clearly.
•Akathisia = intense sense of restlessness, strong urge to move lower extremities. Can include foot stamping when seated, constantly crossing/uncrossing legs, rocking from foot to foot, or constantly pacing up and down. Must include akathisia on differential diagnosis of an agitated patient. Akathisia can be mistaken for psychotic agitation and has been linked with suicidal ideation and aggression towards others.
•Parkinsonism = symptom cluster that includes resting tremor, slowed movements (bradykinesia), expressionless face (masked facies), flat monotone voice, walking gait with short steps + trunk flexed forward + stiff legs (festinating gait), and cogwheel rigidity in the extremities. Can also include slowed thinking (bradyphrenia) and salivation. Can be mistaken for depression or the negative symptoms of schizophrenia. Timing: days to weeks after antipsychotics are started or the dose is increased.
•Tardive dyskinesia = involuntary twitching or writhing (choreoathetoid) movements of the face, neck, trunk, and extremities.May include a wide variety of movements such as lip smacking or chewing, tongue protrusion, choreiform hand movements (pill rolling or piano playing), or pelvic thrusting. Severe orofacial movements can lead to difficulty speaking, eating, or breathing.
From Day 14
Fever (most common presenting symptom)
Autonomic instability (BP, HR)
Excessive sweating (diaphoresis)
•The clinical presentation of NMS varies considerably, however the following can be seen:
Fever, diaphoresis, rigidity ("lead-pipe rigidity")
Lead-Pipe rigidity = uniform increase in tone throughout entire range of motion)
Confusion, fluctuating level of consciousness (delirium)
"Autonomic instability" = labile blood pressure, tachycardia
Labs: elevated creatinine kinase (CK), elevated white blood cell count (WBC), altered liver function tests (LFTs)
If not intervened upon the condition can progress to rhabdomyolysis (muscle breakdown), renal failure, metabolic derangement, end-organ failure, and even death.
From Day 15
•Risk increases beyond normal limits (440ms for men, 470 for women) however stronger evidence links values over 500ms to be clearly increased risk.
•No effect: Brexpiprazole, Lurasidone
•Low effect (<10 ms): Aripiprazole, Asenapine, Clozapine, Perphanazine, Fluphenazine, Olanzapine, Paliperidone, Risperidone, Loxapine
•Moderate effect (>10 ms): Chlorpromazine, Haloperidol, Iloperidone, Quetiapine, Ziprasidone
•High effect (>20 ms): any IV antipsychotic or drug combination in doses exceeding recommended maximum
•Note that effect on QTc may not necessarily equate directly to risk of torsades de pointes or sudden death, although this is often assumed.
From Day 15
Risk of weight gain
•High risk: Clozapine, Olanzapine
•Moderate risk: Chlorpromazine, Iloperidone, Quetiapine, Risperidone, Paliperidone
•Low risk: Amisulpride, Asenapine, Brexpiprazole, Aripiprazole, Haloperidol, Lurasidone, Ziprasidone
I hope you got them all correct. If not... no stress! That's why we are here. We are here to slowly build our knowledge base day by day. Tune back in tomorrow as we start our last week of our "Intro to Psychotic Disorders" theme. Tomorrow we will discuss some of the classic or "don’t miss" side effects of specific drugs.