722.724 Focused Experience and Transition to Practice
PBL Part 2
(11th – 25th August)
ADAM
Adam may be prescribed an atypical antipsychotic. One of the issues with this group of medications is the potential for substantial weight gain. Agnes identifies that there is a history of diabetes in the family.
Action points
Describe the action of atypical antipsychotics on neurotransmitters that a registered nurse needs to know in order to adequately care for a client on this group of medications.
Atypical Antipsychotics
-Atypical or second generation antipsychotics generally refers to the newer anti-psychoticsychotic medication that affect both 5-HT2 (serotonin) and D2 (Dopamine) receptors.
-Atypical antipsychotic have favourable neurological side effects that is why they are the first line agents for the treatment of psychosis.
-Atypical antipsychotic considered often as to be more effective than conventional (first-generation) anti-psychotics
-Although neurological side effects are less frequent, atypical may place some clients at risk for medical morbidity resulting from weight gain and adverse, metabolic effects. Therefore, medical choices must be individualize.
-Lower liability for EPS because they looser binding to D2 receptor
Less likely to cause problem with medication adherence (Elder et al 2009)
-They block the postsynaptic D2 receptors but also exert other synaptic effects reducing positive symptoms of schizophrenia. Atypical, on the other hand, have dopamine (D2) and serotonin (5-HT2) blocking action. They not only reduce positive symptoms of schizophrenia but also have an effect on the negative symptoms without EPS.
-more effective in reducing negative symptoms
Neurotransmitter
-allow transmission of signals from one neuron to the next across synaptics
Acetylcholine
-use to control muscles by the spinal cord neurons and to regulate memory from other neurons in the brain
Dopamine
-concerned for emotional arousal and is the neurotransmitter for the extra pyramidal system: balance, equilibrium, hand and eye coordination.
-in schizophrenia shown that there has been an excessive amount of dopamine in the frontal lobes. On the other hand, too little oxygen in the motor areas of the brain are responsible for Parkinson’s disease, w/c involves uncontrollable muscle tremors.
Serotonin
-Concerned with memory, emotional state, and wakefulness, transmission in perceptual pathways –important for sleep, mood and eating behaviour. Too little serotonin has been shown to lead to depression, problems with anger control, OCD and suicide.
Mechanism of action
All available antipsychotic antagonize D2 receptors in vitro. However, the theory that psychosis results from hyperdopaminergia is overly simplistic – under activity of dopamine in mesocortical pathways, specifically those projecting to the frontal lobes, may account for the negative symptoms of schizophrenia (e.g. anergia, apathy, lack of spontaneity). Also under activity of dopamine may serve to disinhibit mesolimbolic dopamine activity via a corticolimbic feedback loop. Over activity of mesolimbic dopamine is the result, which manifest as the positive symptoms of schizophrenia (e.g. hallucinations, delusion)
Other properties –antagonise 5-HT2 receptor, which may modify dopamine activity in regionally specific manner.
Indications and efficacy
-Common indication – treatment of acute psychosis and maintenance of psychotic symptom remission in clients with schizophrenia.
-all conventional anti-psychotic. Have comparable efficacy in schizophrenia when given in equivalent doses however differ somewhat in propensity (natural tendency) for some side effects. Atypical appear to have less side effects than conventional in treatment of schizophrenia but differ with their tolerability.
-Clozapine – shown efficacy in clients with schizophrenia after non-sense to one or more anti-psychoticsychotic medication trials, including other atypical anti-psychotic.
-atypical has become key part of pharmacological armory to treat BI-Polar. All atypical except Clozapine are approved by FDA for the treatment of acute mania.
-Olanzapine and Aripiprazole are approved as maintenance treatments for Bi-polar disorder. As of Sept. 2007, Olanzapine/Fluoxetine combination therapy and Quetiapine are meds approved by FDA specifically for treatment of acute Bi-polar depressive episodes.
-effectively target psychotic symptoms associated with drug intoxications, delusional disorders and non-specific agitation although the data supporting their use in these conditions are limited.
-low doses of anti-psychotic. May be effective in some clients with borderline or schizo-typical personality disorders, particularly when psychotic ideation is targeted
-in clients with severe OCD – used to augment treatment with anti-obsessional agents.
-anti-psychotic and other drugs with dopamine receptor-blocking action (e.g. metoclopramide) are also used for their anti-emetic effect.
-as well as la Tourette’s syndrome may be controlled with anti-psychotic.
-due to sedating properties of some anti-psychotic., these may be misused in some clinical settings, such as for their use of solely as hypnotic agents for clients with insomnia or anxiolytic for clients with anxiety. Because of both short and long term adverse event risks associated with anti-psychotic medications.
-cannot be sued solely as hypnotic or anxiolytic agents.
Guidelines for the acute use of antipsychotic drug
-Prior to treatment, obtain a medical and psychiatric history. Baseline laboratory studies are also indicated as part of the initial evaluation. An evaluation for the presence of any abnormal movements is also advisable. An electrocardiogram should be considered for patients with a history of cardiac problems.
-After discussion with the patient and family about the risks and benefit of treatment, select the appropriate anti-psychotic agent on the basis of the patients physical status, the side effect profile of the drug, and the patient’s previous responses to medication, if known.
-Educate the patient and family about the risks of developing metabolic syndrome, diabetes, obesity, dyslipidemia, neuroleptic malignant syndrome, and tardive dyskinesia. Document this discussion in the patient’s clinical notes.
-Initiate treatment with anti-psychotic medication at low to moderate doses, depending on the patient’s history and clinical presentation. Titrate as tolerated to the target dose.
-If possible administer the anti-psychoticsychotic medication at bed time to increase adherence and minimise day time side effects.
-If patient has been compliant with treatment and side effects are minimal but no or minimal response to treatment occurs, increase the dose gradually (e.g. every 2-4 weeks). Full response may be delayed for six months or longer
-if patient still has no response, is taking as adequate dose, and is compliant with treatment, consider another anti-psychoticsychotic medication.
Describe the side effects of atypical antipsychotics and the interventions for these.
Guidelines for the acute use of antipsychotic drug
-prior to treatment, obtain a medical and psychiatric history. Baseline laboratory studies are also indicated as part of the initial evaluation. An evaluation for the presence of any abnormal movements is also advisable. An electrocardiogram should be considered for patients with a history of cardiac problems.
-after discussion with the patient and family about the risks and benefit of treatment, select the appropriate anti-psychotic agent on the basis of the patients physical status, the side effect profile of the drug, and the patient’s previous responses to medication, if known.
-educate the patient and family about the risks of developing metabolic syndrome, diabetes, obesity, dyslipidemia, neuroleptic malignant syndrome, and tardive dyskinesia. Document this discussion in the patient’s clinical notes.
-Initiate treatment with anti-psychotic medication at low to moderate doses, depending on the patient’s history and clinical presentation. Titrate as tolerated to the target dose.
-if possible administer the anti-psychoticsychotic medication at bed time to increase adherence and minimise day time side effects.
-if patient has been compliant with treatment and side effects are minimal but no or minimal response to treatment occurs, increase the dose gradually (e.g. every 2-4 weeks). Full response may be delayed for six months or longer
-if patient still has no response, is taking as adequate dose, and is compliant with treatment, consider another anti-psychoticsychotic medication.
Atypical anti-psychoticsychotic Risk and side effects and their management
When anti-psychotic reduce dopamine activity in the nigrostriatal pathway (via dopamine receptor blockade), extra pyramidal signs and symptoms similar to those of Parkinson’s disease result. Another locus of dopamine receptors is in the pituitary gland and hypothalamus (the tuberoinfundibular system), where dopamine is synonymous with prolactin-inhibiting factor. Blockade of dopamine in this system results in hyperprolactinemia. Similarly, antagonism of acetylcholine receptors produces symptoms such as dry mouth, blurred vision and constipation. Antagonism of a1 –adrenergic results in hypotension, and antagonism of histamine receptors is associated with sedation.
EPS(Extra Pyramidal Syndrome) Dystonic reactions, parkisonian syndrome, akathisia, tardive dyskinesia, and NMS.
-high potency conventional more likely than low potency conventional to cause EPS. All first generation anti-psychotic drugs are equally likely to cause tardive dyskinesia.
-atypical cause fewer EPS, but careful titration of resperidone is necessary to avoid neurological side effects
-anti-cholinergic agents or amantadine may prevent or ameliorate EPS, the use of atypical is highly recommended to avoid these side effects w/out introducing additional medications. Long term use of anti-cholinergic medications should be minimised because these agents may cause memory and attention impairment.
-clozapine appears only agent that doesn’t cause tardive d.
-acute dystonic reaction – occurs w/in hours or days of initiation of treatment w/ high potency conventional anti-psychotic meds. – uncontrollable tighning of the muscles including spasms of the neck, back (opisthotonos), tongue, or muscles that control lateral eye movement (oculogyric crisis) – may jeopardise meds.
Intervention: intravenous or intramuscular administration of anticholinergic meds is a rapid and effective treatment for acute dystonia.
List of drugs use to treat dystonia
§ -amantadine – tr. Name Symmetrel dopaminergic agent for parkinsonian syndrome usual dose 100 mg po bid
§ -benztropine – tr. Name congentin anticholinergic agent for dystonia, parkinsonian syndrome, acute dystonia 1-2 mg po bid
§ -diphenhydramine – Benadryl anticholinergic agent 25-50 mg pot bid(dystonia&PS)/25 mg im or iv (acute dystonia)
§ -propranol - inderal beta blocker 20 mg pot id/1mg iv for akathisia
§ Trihexyphenidyl- artane anti-cholinergic 5-10 mg po bid dystonia, PS
-young pt. Taking high potency anti-psychotic drugs are at particular high risk for developing acute dytonia. – Prophylactic treatment be considered for pt for whom the risk of developing EPS is high, especially pt. Younger than 40. Anti-cholinergic can be tapered and stopped for 10 days.
Parkinsonian Syndrome
-Diminished range of facial expression, cogwheel rigidity, slowed movements drooling, small handwriting (microphagia) and pill rolling tremor.
Intervention: most common-restore dopamine – acetylcholine balance by increasing dopamine availability.
-The treatment of anti-psychotic medication related parkinsonism most often involves decreasing the levels of acetylcholine (although amantadine, a dopaminergic drug, often effectively attenuate parkinsonian side effects w/out exacerbating the psychotic symptoms)
The Rabbit Syndrome
-fine, rapid, consisted movements of the lips that resemble the chewing movements of a rabbit.
Often considered a subset of Parkinsonian side effects. This SE occurs after more prolonged treatment and may be confused with buccolingual tardive dyskinesia
Intervention :treated effectively with anti-cholinergic agent
Akinisia
-Behavioural state of diminished spontaneity characterised by decrease gestures, unspontaneous speech, apathy, and difficult with initiating usual activities. This may appear after several weeks of therapy and is often an element of PS
-this drug induced syndrome may be mistaken for depression or for negative symptoms of schizo.
-Akthisia consist of a subjective feeling of restless in the lower extremities, often manifested as an inability to sit still
-people who experience this find it difficult to sit or sleep, both activities are interrupted by the incessant urge to move the limb or to change position
-this is the most treatment resistant of acute EPS. Benzodiazepines are helpful in some cases.
-Interventions
-current treatment for akathisia is either a switch to an atypical agent (with the exception of aripiprazole) or the addition of a b-adrenergic blocking drug, particularly propranolol. – Several data shown that in dosages up to 120 mg/day, is an effective treatment for akathisia than hydrophilic ones
Tardive dyskinesia
-A disorder characterised by involuntary choreoathetoid (def: ceaseless occurrence of rapid, highly complex jerky movements that appear to be well coordinated but are performed involuntarily
-movements of the face, trunk, or extremities. Usually associated with prolonged exposure to dopamine receptor-blocking agents – antipsychotic drugs. However, antidepressant amoxapine and antiemetic agents metoclopramide and prochlorperazine can also cause TD.
-clozapine seems to carry little or no risk of inducing TD.
-clinicians used Abnormal Involuntary Movement Scale (AIMS) toexamine presence or emergence of TD.an evaluation should be conducted before treatment begins and every 6 or 12 months thereafter.
-in typical cases, pt are unaware of involuntary movements
-severe dyskinetic movements are less common, w/c can be disfiguring or disabling as a result of affecting the muscles involved in the production of speech or swallowing.
-although most common form is dyskenetic variety (nonrhythmic, quick choreiform movements) and other types have been identified includes: Tardive akathisia; Tardive dystonia;tardive tics.
-the most commonly accepted hypothesis of the mechanism for the development of TD is that postsynaptic dopamine receptors develop supersensitivity to dopamine after prolonged dopamine receptor blockade. Research has implicated an interaction between oxidative load (free radicals) and glutamatergic neurotoxicity.
Risk factor
§ -increasing age
§ -duration of exposure to a conventional anti-psychotic because the cumulative incidence has been shown to remain constant at about 5% for the first 8 years in non-elderly pt.
§ -women have been found to be at greater risk for severe TD, although this evidence is limited to geriatric population.
§ -EPS early in the course of the treatment, a history of drug holidays (a greatear number of drug-free periods is associated with an increased risk),
§ -presence of brain damage
§ -diabetes mellitus
§ -diagnosis of mood disorder
*treatment with conventional agent may increase the likelihood of irreversible movements compared with an atypical agent*.
Withdrawal emergent dyskinesia
-discontinuation of antipsychotic/tapering of anti-psychotic dose/ may also occur when conventional agent is replaced with atypical agent.
-typically resolves within 6 weeks, however suppressed or latent TD that has been suppressed by D2 receptor blockade may not resolved once it has appeared.
-conversely movements may be masked temporarily by increasing the dosage of anti-psychotic. Meds , but symptoms eventually re-emerge, often in more severe form.