Schizophrenia 3: Meds & Side Effects Flashcards
Blockade of 5-HT2A receptors also causes an increase in dopamine in the prefrontal cortex. This is the reason that atypical antipsychotics improve ______ (2) symptoms of psychiatric illnesses.
- mood
- cognitive
(Atypicals are more potent 5-HT2A antagonists→ better tolerability & less EPS (by increasing DA). The higher the relative occupancy of 5-HT2A to D2 receptors, the greater the reduction in EPS.)
Theoretically, blockade of dopamine D2 transmission by antipsychotic drugs is responsible for the alleviation of the _____ symptoms of schizophrenia and induction of EPS.
positive
Antipsychotics may bind to the D2 receptor with similar affinities, but dissociate at different rates. The faster a drug dissociates from the receptor, the more likely it will be displaced by_________.
exogenous dopamine or other drugs
(the less tightly it binds → less EPS)
5HT2 receptors inhibit release of dopamine. Blockade of these receptors enhances ______.
release of dopamine
Mesolimbic tract projects from the_______to the nucleus accumbens
midbrain ventral tegmental area
(Involved in the positive symptoms of schizophrenia. Blocking the DA receptors here → reduction in positive symptoms)
The mesolimbic tract is involved in the regulation of ________ and believed to be the predominant pathway regulating positive symptoms of schizophrenia.
emotional behaviors
(Hyperactivity → positive symptoms of schizophrenia. Blocking DA receptors → decreased positive sx)
Blocking D2 receptors of the mesolimbic tract may result in reduction of _____
positive symptoms
Which medication has the greatest effecacy in treating schizophrenia
Clozapine
(AE: agranulocytosis)
Mesocortical tract projects from the _____ to the (limbic) prefrontal cortex
ventral tegmental area
(DA deficiency in this pathway causes negative and cognitive symptoms, possibly mood symptoms)
Dopamine deficiency in the mesocortical tract causes which symptoms in schizophrenia (3)?
- Negative
- Cognitive
- Mood
In the mesocortical pathway, there may be more 5HT2A receptors than D2 receptors. 5HT antagonism of atypical antipsychotics may be more profound than the _______.
D2 receptor blocking activity
(Could help with negative symptoms)
Nigrostriatal: Projects from the ______ to the basal ganglia.
substantia nigra
(Involved in the control of movements. Blockade of D2-dopaminergic receptors associated with this pathway has been implicated in the induction of EPS)
The Niagarostriatal tract as part of the extrapyramidal system and controls _____, as well as modulates _____.
- Motor movement
- direct and indirect basal ganglia pathways
- Blockade of the D2 receptors in the nigrostriatal tract causes:
- Blockade of the 5HT2A receptors in the nigrostriatal tract causes:
- movement disorders: parkinsonism & tardive dyskinesia
- Increases dopamine in this pathway
(second generation have less EPS symptoms bc they have more serotonergic activity, less DA blockage)
What is the Tonic Inhibition thoery of schizophrenia (pathophysiology)?
GABA neurons are not inhibiting the DA neurons as they should be ⇒ hyperactivity in mesolimbic tract ⇒ positive symptoms
What is the Tonic Excitation theory of schizophrenia (pathophysiology)?
- Typically glutamate stimulates DA neurons in the mesocortical tract
- If this does not happen, DA nuerons in the mesocortical tract = hypoactive→ negative & cognitive symptoms
Glutamate is important for which area of the brain?
Everywhere
(we can’t use it pharmacologically yet bc it is neurotoxic)
Temporal onset of EPS (antipsychotic-induced movement disorders) acute and long-term
- acute: dystonia, akathisia, parkinsonism
- long-term: tarditive dyskeinsesia (months to years)
Dystonia reaction to antispycotics: may occur during the ________
first hours of treatment, with 90% occurring within the first 3 days
Risk factors for getting an acute dystonic reaction to antipsychotics
muscular men under 40 on high-potency first-gen antipsychotics
(tx: benztropine or benadryl (diphenhydramine))
Akathisia reaction to antipsycotics: may occur within _____
2 to 3 days of treatment, but more frequently has an onset after 5 days
Parkinsonism reaction to antipsycotics: can occur _____.
during the first 5 to 30 days of treatment
Parkinsonism symptoms do to antipsychotics include bradykinesia, rigidity, cogwheeling, tremor as well as ____ (4).
- masked facies
- drooling
- stooped posture
- festinating gait
(more common in elderly & w/high-potency antipsychotics)
Treatment: parkinsonism reaction with antipsychotics
- Switch to a second-generation antipsychotic or lower dose
- Antiparkinson drugs (caution: in the elderly)
Define akathisia
An intensely unpleasant sensation of restlessness and the need to move, especially the legs
(may cause anxiety, agitation or suicide)
What is the cause of extrapyramidal symptoms (chemically)?
Stimulating dopamine receptors on a cholinergic neurons will inhibit the release of Ach → EPS
(if you block the Ach receptors → reduces EPS)
Treatment of akathisia reaction to antipsychotics (3)
- beta blocker (propranolol 10-30 mg tid)
- benzodiazepine (lorazepam 1 mg tid)
- anticholinergic (benztropine 1-2 mg bid)
(careful w/anticholinergic when they already have cognitive issues)
Treatment with dopamine facilitator (Amantadine) for extrapyramidal symptoms (antipsychotic AE) increases CNS concentrations of DA by ______.
(primarily for pseudoparkinsonism)
Blocking its reuptake and increasing release from presynaptic neurons
(Restores dopamine/acetylcholine balance in the striatum)
Side effects when treating extrapyramidal symptoms with anticholinergics:
- constipation
- dry mouth
- blurry vision
- urinary retention
“Blind as a bat (mydriasis), mad as a hatter (delirium), red as a beet (flushing), hot as a hare (hyperthermia), dry as a bone (decreased secretions and dry skin), the bowel and bladder lose their tone (urinary retention and paralytic ileus), and the heart runs alone (tachycardia).”
Treatment with anticholinergics for extrapyramidal symptoms (antipsychotic AE) (3)
- Benztropine (Cogentin)
- Diphenhydramine (Benadryl)
- Trihexyphenidyl (Artane)
(Dopamine and acetylcholine have a reciprocal relationship in the striatum)
Possible side effects of DA facilitator Amantadin (symmetrel): (3)
- Orthostatic hypotension
- Ankle edema
- GI upset
Treatment with beta-blockers for extrapyramidal symptoms (antipsychotic AE) is _______, specifically for which symptom(s)?
- Propranolol
- Akathisia
Treatment with alpha-agonists for extrapyramidal symptoms (antipsychotic AE) is ______, specifically for which symptom(s)? AE?
- Clonidine
- Akathisia
- Orthostatic hypotension or sedation
(AE of DA facilitator is Orthostatic HTN also)
acute dystonia (cramping & msk rigidity - AE to antipsychotics) treatment
anticholinergics
(benztropine, diphenhydramine/benadryl)
The AIMS scale measures ______.
Symptoms of tardive dyskinesia
Define tardive dyskinesia
Long-standing or permanent abnormal involuntary movements
(MC caused by the long-term use of typical antipsychotics, 20% will develop)
TD presents clinically as involuntary athetoid movements of the ______or occasionally muscle groups that subserve breathing and swallowing
tongue, facial and neck muscles, upper and lower extremities, truncal musculature
What is the difference between tardive dyskinesia and Parkinson’s symptoms?
- Tardive dyskinesia is irregular and fast
- Parkinson’s is slow and tremor
Tardive dyskinesia rarely develops in patients with _____. Increased risk in those _____.
- less than 3 to 6 months of antipsychotic exposure
- over 50 y.o.
When a patient has tardive dyskinesia you must consider risks versus benefits of ______.
continued antipsychotic medication when TD symptoms present
Treatment of tardive dyskinesia
VMAT2 inhibitors (Deutetrabenzine or Valbenazine)
Which 2 VMAT2 inhibitors treat TD?
- Deutetrabenzine
- Valbenazine
In the tuberoinfundibular tract DA blocks the release of _______, whereas 5HT2A causes its release.
- prolactin
(Increased neuronal activity in this pathway→ inhibits release; blockade of D2 receptor → hyperprolactinemia)
Potential consequences of prolactin elevation levels?
Black Box warning for antipsychotics (2)
- Mortality in dementia
- Suicide
(anything that treats modd may have suicide risk)
Potential side effects for antipsychotics (9)
- Neuroleptic malignant syndrome
- Cardiac toxicity
- Sedation
- Postural hypotension
- Weight gain
- Hyperglycemia/diabetes/hyperlipidemia
- Hematologic effects
- Heat intolerance
- Bowel complications (clozapine)
Neuroleptic Malignant Syndrome: symptoms (5)
- Muscle rigidity
- Fever
- Autonomic instability
- Delirium
- Seizures or coma (less likely)
(less common w/second gen; sx occur over hours to days, with rigidity typically occurring first)
Neuroleptic Malignant Syndrome treatment includes stopping the antipsychotic and _____ (2).
- Supportive care
- Dantrolene
Cardiac toxicity with antipsychotics include ______.
prolonged QT
Which two antipsychotics have the greatest risk for cardiac toxicity (prolonged QT)?
Pimozide and thioridazine
(ziprasidone have FDA caution; be especially careful w/patients co-morbid for cardiac diz)
Which are the most sedating first-generation antipsychotics? Second generation?
- Chlorpromazine and thioridazine
- Clozapine > quetiapine > olanzapine > risperidone > ziprasidone and aripiprazole
Which first gen antipsychotics have the least sedating effects? Which second gen antipsycotics have the least sedating effects?
- haloperidol and fluphenazine
- ziprasidone and aripiprazole
Postural hypotension (improves when pt is supine) when using antipsychotics is related to ______ blockage. MC with ______ (3) meds.
- alpha-adrenergic receptor
- chlorpromazine, thioridazine, clozapine
(May be associated with reflex tachycardia)
Treatment of postural hypotension secondary to antipsychotic use (2)
- Teach patient to get up from recumbency slowly
- Switching agents to higher potency med
All antipsychotics can increase appetite and cause weight gaine. Which second generation antipsychotics cause the most weight gain?
- Most: SGA’s: clozapine and olanzapine
(Monitoring at every visit is recommended)
Which antipsychotic causes the least amount of weight gain?
Ziprasidone, then quetiapine and risperidone
(monitor at every visit)
Which medication has the highest risk for diabetes and hyperlipidemia? Least?
- Olanzapine (also high risk for weight gain)
- Ziprasidone
(routine monitoring of glucose and lipid parameters)
Why are schizophrenic patients at a highter risk of Diabetes/Hyperglycemia/
Hyperlipidemia?
- often have sedentary lifestyle
(Independent risk from antipsychotic medication)
Hematologic effects reported with antipsychotic use: (3)
- neutropenia, leukopenia and agranulocytosis (severe neutropenia)
(CBC if patient has frequent infections; routine monitoring not necessary. Except : Clozapine → 1-3 % → agranulocytosis)
Why do schizophrenic patients have abnormal thermoregulation?
- Impaired heat loss through peripheral vasodilation via abnormalities in niacin and prostaglandin E1
- Disruption of the mesolimbic dopamine system responsible for temperature regulation and psychosis
Anti-psychotic medication may lead to abnormal thermoregulation. How do each of the following contribute to this phenomenon: anticholinergic, anti dopaminergic, antipsychotic?
- Anticholinergic: inhibits parasympathetic pathways, leading to inhibited sweating
- Antidopaminergic: increase the set point of the temp regulation
- Antipsychotic: reduce compensatory behaviors, such as drinking more water or removing extra clothing
Antipsychotic pharmacokinetics: when administered orally, peak plasma levels occur in _____. IM? Most are metabolised by _____.
- 1-4 hours
- 15 minutes
- cytochrome P450 system
(Nearly all have half-lives over 24 hours)
Antipsychotic plasma levels not used often, unless _____, or when _____.
- lack of response
- used in combination with other meds that can affect their pharmacokinetics
Initiating treatment of acute psychosis: administer _____
Antipsychotic meds
(effects generally start w/in a few days of onset of treatment)
____ (how many) discontinue their first-line antipsychotic meds. Most antipsychotic prescriptions are written for ______ (typical/atypical).
- 1/3 to ¾ of all patients
- atypicals
(5 of 9 branded antipsychotic meds will be generic in next 12-18 months, great news bc/brand name costs thousands of $$ /mo)
Schizophrenia maintenance treatment: why is prevention of relapse is more important than risk of side effects?
most side effects are reversible, and the consequences of relapse may be irreversible (they lose cognitive fxn each time)
Schizophrenia maintenance treatment: duration for first time, multiple of a danger to self or others
- 1-2 years of treatment following initial episode ( high risk of relapse → possibility of social deterioration)
- 5 years of treatment for multi-episode patients
- Chronic, or ongoing, treatment is recommended for patients who pose a danger to themselves or others
_______(maintenance treatment) may increase compliance in schizophrenia.
Long-acting depot injectables
(helpful for ppl who forget or have opposition from their family)
Use of Antipsychotics in Bipolar Disorder
- Bipolar mania, mixed or depression episodes
- Maintenance treatment
Second generation agents are better tolerated in ______ (2) bipolar episodes.
- mania
- mixed
(first gen also may be effective)
Most efficacious antipsychotics for bipolar depression: (2)
Olanzapine and quetiapine
Maintenance with antipsychotics for bipolar patients may have risks of long-term use should be weighed against the benefits. Addition of _______ to lithium or valproate reduces risk of relapse.
second generation antipsychotic
Use of Cannabidiol (CBD) in Schizophrenia: While THC has psychotomimietic effects, CBD may have ____
opposing properties (BUT right now there is not enough evidence against or for)
(THC can provoke psychosis)
Use of cannabidiol (CBD) in schizophrenia is not dependent on ______receptor antagonism
dopamine
Use of CBD in schizophrenia may reduce _____symptoms and improve _____performance in some patients.
- positive
- cognitive
(they must get a prep w/as little THC as possible as it has psychomimetic properties)
_________ are high potency antipsychotics.
Mn: “HAL TRIed to FLy high” : HALoperidol, TRIfluoperazine, and FLuphenazine
________ are low potency antipsychotics.
Mn: “CHarlatans and THIeves are lowlifes” : CHlorpromazine and THIoridazine
(high and low potency antipsychotics are first-gen)
