Alternativas de administracion farmacos parkinson
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Este documento discute métodos alternativos para administrar medicamentos dopaminérgicos a pacientes con enfermedad de Parkinson que tienen dificultad para tomar medicamentos por vía oral. Describe opciones como preparaciones dispersables de levodopa, administración a través de sonda enteral, parches transdérmicos de rotigotina e inyecciones subcutáneas de apomorfina. También proporciona detalles sobre la dosificación de estos métodos y consideraciones al elegir la mejor alternativa para cada paciente.
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Alternativas de administracion farmacos parkinson
- 1. REUNIÓN CLINICA CETRAM Alty J, et al. Pract Neurol 2015;0:1–7. doi:10.1136/practneurol-2015-001267
- 2. INTRODUCCIÓN El uso irregular u omisión de medicamentos puede llevar a una rápida reducción en la estimulación dopaminérgica Deterioro en el control de la enfermedad aumentando el riesgo de complicaciones ↓↓↓ DA cerebral = Sd. Parkinsonismo Hiperpirexia (“Tipo Neuroléptico Maligno”) Fiebre y rigidez + Ck elevada y mioglobinuria
- 3. ALTERNATIVAS TERAPÉUTICAS EN ENFERMEDAD DE PARKINSON
- 5. MÉTODOS ALTERNATIVOS DE ADMINISTRACIÓN DE MEDICAMENTOS DOPAMINÉRGICOS 1. Preparaciones dispersables + Fluidos espesantes 2. Sonda Enteral 3. Parche Trans-dérmico 4. Inyección Subcutánea
- 6. PREPARACIONES DISPERSABLES LEVODOPA Paciente capaz de manejar fluidos con espesante: Levodopa Co-beneldopa dispersable Biodisponibilidad de preparaciones de liberación controlada es algo menor que liberación inmediata, pero se recomienda conversión 1:1 Carbidopa/levodopa/Entacapone contiene co- careldopa. Los autores recomiendan moler la pastilla y diluirla en 15 ml de agua
- 7. PREPARACIONES DISPERSABLES Dosis alternativa de co-beneldopa
- 8. PREPARACIONES DISPERSABLES AGONISTAS DOPAMINÉRGICOS Pramipexol y Ropirinol son los AD: liberación inmediata (administrados 3v/d) liberación modificada (1 v/d) Pramipexol de liberación inmediata puede ser molido y disperso en 15 ml de agua Ropirinol de liberación inmediata puede diluirse en 15 ml de agua sin ser molido Las formulaciones de liberación prolongada no deben ser molidas ni disueltas. El paciente puede requerir cambio a AD de liberación inmediata para dilución
- 9. TUBO ENTERAL Si el paciente no puede deglutir fluidos con espesante SNG/GTT Carbidopa/Levodopa/Entacapone y AD de liberación inmediata Pueden usarse en sistemas enterales (No aprobado) Diluir tabletas en 15 ml
- 10. PARCHES TRANSDÉRMICOS Paciente incapaz de usar vía oral o GI Rotigotina 2 mg 4 mg 6 mg 8 mg Dosis máxima 16 mg/24 hrs Usar parche con dosis cercana a la necesaria. No cortar Levodopa >500 mg/día Máximo 16 mg/24 hr rotigotina + Dosis ajustada de otros fármacos subcutaneos o por vía enteral
- 13. INYECCIONES SUBCUTÁNEAS APOMORFINA BIC Subcutanea Inyecciones
- 14. PRESCRIPCIONES FUERA DE INDICACIONES APROBADAS (“OFF- LICENSE”) Situaciones especiales que demandan medidas especiales para mantener la estimulación dopaminérgica Uso de Rotigotina >16 mg/24hr Pramipexol de liberación inmediata molido por sonda enteral
- 15. ELEGIR EL MÉTODO ALTERNATIVO DE ADMINISTRACIÓN Generalmente es mejor elegir el método menos invasivo Elegir un método rápido y fácil iniciar (prevenir retrasos >4 hrs en dosis) Ej. Imposibilidad de instalar SNG Usar parches de rotigotina
- 16. ELEGIR EL MÉTODO ALTERNATIVO DE ADMINISTRACIÓN Chequear la causa de incapacidad de uso de vía oral Disfagia puede mejorar si el paciente no ha recibido sus fármacos y se reinician correctamente (con espesantes, SNG, subcutaneo, etc). Chequear que no esté recibiendo bloqueadores dopaminérgicos
- 18. ELECCIÓN DEL MÉTODO ALTERNATIVO DE ADMINISTRACIÓN DEL FÁRMACO Gastroenteritis: Vómitos y diarrea pueden alterar la absorción. Útil utilizar parches de rotigotina Si hay antecedente de RAM con AD es razonable considerar un curso corto de antieméticos (Ej. loperamida) Trastornos de deglución de meses considerar gastrostomía Derivar a Fonoaudiologia
- 19. ELECCIÓN DEL MÉTODO ALTERNATIVO DE ADMINISTRACIÓN DEL FÁRMACO Considerar Perfil de Efectos Adversos: Alucinaciones: AD>Levodopa Delirium o Demencia Sensibilidad a efecto hipotensor de levodopa pulsátil Preferir Rotigotina en parches Evitar fármacos que previamente han sido mal tolerados por el paciente Evitar en lo posible cambios de fármaco si hay buena tolerancia Prolopa Prolopa dispersable + Líquidos c/espesante, en vez de AD
- 20. FÁRMACOS QUE PUEDEN SER OMITIDOS EN ESCENARIOS AGUDOS Rasagilina, Selegilina Amantadina Entacapone, Tolcapone Es importante estar alerta a nuevos síntomas que puedan ser efecto del retiro de fármacos La rápida suspensión de Amantadina ocasionalmente genera reacciones distónicas agudas
- 21. RESUMEN
- 22. ANEXO Dosis diaria equivalente de Levodopa (LED) mg Fármaco X =100 mg levodopa C.L. Tomlinson et al. Systematic Review of Levodopa Dose Equivalency Reporting in Parkinson’s Disease. Movement Disorders, Vol. 25, No. 15, 2010
- 23. ANEXO FACTOR DE CONVERSIÓN C.L. Tomlinson et al. Systematic Review of Levodopa Dose Equivalency Reporting in Parkinson’s Disease. Movement Disorders, Vol. 25, No. 15, 2010
Notas del editor
- Figure 1 Dopaminergic neurones are activated through a mechanism of dopamine (DA) being released from vesicles at the presynaptic terminal, crossing the synaptic cleft and then binding to postsynaptic dopamine receptors. Excess dopamine is metabolised by monoamine-oxidase-B (MAO-B) at the presynaptic terminal, after first being taken up by the dopamine active transporter (DaT), and also via catechol-O-methyltransferase (COMT) at the postsynaptic terminal. Levodopa, a dopamine precursor that can cross the blood–brain barrier, thus increases the amount of dopamine released at the presynaptic terminal, whereas dopamine agonists directly stimulate the postsynaptic dopamine receptors. MAO-B inhibitors and the COMT inhibitor tolcapone increase dopamine availability in the synaptic cleft by slowing down dopamine metabolism in the central nervous system. Dopa decarboxylase inhibitors (DCIs) and both COMT inhibitors (entacapone and tolcapone) reduce peripheral metabolism of levodopa, thus increasing the amount available to cross the blood–brain barrier, and reducing peripheral side effects. Note: This diagram outlines the main actions of Parkinson’s disease drugs on dopaminergic neurones but is not exhaustive; most of these drugs have additional roles, especially the enzyme inhibitors on other neurotransmitters’ metabolism. HVA, homovanillic acid.
- ALTERNATIVE METHODS OF GIVING DOPAMINERGIC MEDICATIONS There are four common alternative methods to consider if a person with Parkinson’s disease cannot take their usual oral medications: ▸ dispersible preparations±thickened fluids ▸ enteral tube ▸ transdermal patch ▸ subcutaneous injection.
- Levodopa Levodopa is the most potent oral medication used in Parkinson’s disease; significant delays or dose reductions are particularly likely to bring about symptoms of reduced dopaminergic stimulation. If the patient cannot swallow tablets but can manage fluids (including thickened fluids), convert their usual levodopa-containing medications to an equivalent dose of ‘co-beneldopa dispersible’ using the conversion rates outlined below: The bioavailability of levodopa from controlled release preparations is slightly lower than from immediate release levodopa but we recommend giving a 1:1 conversion rate in the acute setting to avoid a sudden drop in dopaminergic stimulation and then seek advice from pharmacy as slight reductions may be needed beyond the first 24h of therapy. Carbidopa/levodopa/entacapone contains the same active constituents as co-careldopa, plus a catechol-O-methyltransferase inhibitor called entacapone, which further increases the bioavailability of levodopa (figure 1). Although carbidopa/levodopa/ entacapone is only licensed as whole tablets given orally, we have often recommended crushing and dispersing the tablets in 15mL of water to minimise the number of drug substitutions; see ‘Prescribing drugs off-licence’ section. Alternatively, an equivalent co-beneldopa dispersible dose may be calculated as follows:
- DOPAMINE AGONISTS Pramipexole and ropinirole are the most commonly used oral dopamine agonists and there are immediate release (given three times per day) and modified release (given once daily) versions of each. Immediate release pramipexole may be crushed and dispersed in 15mL of water and immediate release ropinirole will disperse in 15mL of water without being crushed. These dispersions may then be added to thickened fluids if necessary. The once daily, modified release versions of pramipexole and ropinirole mustnot be crushed or added to water. If patients are taking these drugs, the modified release dose will first need to be split into three immediate release pramipexole or ropinirole doses per day. Each dose of immediate release pramipexole or immediate release ropinirole can then be dispersed in 15mL of water as outlined above.
- If a patient cannot safely swallow thickened fluids, they may need a nasogastric tube to receive their usual oral medications, using the conversion rates outlined above. If the patient’s swallowing remains significantly impaired in the long-term, it is worth considering a percutaneous endoscopic gastrostomy tube.23 Although carbidopa/levodopa/entacapone and immediate release pramipexole and ropinirole are not licensed for use with enteral systems, we have often done so (after first crushing and dispersing the tablets in 15mL water)—see box 1—and found this helps to keep the patient’s regimen as stable as possible, especially when patients need a short period of drug administration via nasogastric tube; see ‘Prescribing drugs off-licence’ and ‘Choosing an alternative method of drug administration’ sections for further discussion.
- If a patient with Parkinson’s disease is nil by mouth, nil by enteral tube (eg, perioperatively) or likely to have problems absorbing drugs via the gastrointestinal tract, a useful way of continuing dopaminergic stimulation is by a transdermal patch that administers the dopamine agonist, rotigotine; see box 1. The patch may also help patients with impaired swallowing, as an alternative to using dispersible preparations of levodopa or dopamine agonists in thickened fluids or via an enteral tube. Rotigotine patches are available in 2 mg/24h, 4 mg/ 24h, 6 mg/24h and 8mg/24h doses. The maximum licensed dose of rotigotine is 16mg/24h. The patches must not be cut to achieve the correct dose but rather the nearest patch dose that provides an equivalent level of dopaminergic stimulation should be chosen. Figure 2 outlines the method of calculating an equivalent rotigotine patch for levodopa-containing drugs and oral dopamine agonists. Table 1 summarises the conversion rates for commonly used doses of dopamine agonists.4 Due to the confines of the rotigotine patch dosages, it is not always possible to give the exact equivalent dose and a decision needs to be made as to whether to round the dose up or down. We discuss below some of the clinical issues to consider when making this decision. Whichever patch dose is ultimately chosen, it is important to monitor how the patient responds and to tailor further doses accordingly—so if there are side effects of too much dopaminergic stimulation such as confusion and hallucinations, the dose may need to be reduced, and if there is an increase in Parkinson’s disease signs such as rigidity and tremor, the dose may need to be increased. This principle extends to all the drug classes when calculating equivalent doses and ongoing monitoring is fundamental to achieving the best clinical outcome. As a rule of thumb, if the daily levodopa dose is over 500mg, the patient is likely to need a higher dose of rotigotine patch than the maximum licensed dose of 16mg/24h. In this circumstance additional drugs may be given via an enteral tube or if this is not feasible, then consider subcutaneous apomorphine. Alternatively, a clinician may decide to prescribe doses of rotigotine higher than 16mg/24h to give an
- SUBCUTANEOUS INJECTION Apomorphine, a potent dopamine agonist, may be given via subcutaneous injection under specialist supervision if the methods described above are not suitable, or when a rapid response is required. If a patient with Parkinson’s disease is admitted with an apomorphine pump already in situ it is very important not to stop or alter pump settings without seeking advice from the on-call neurologist or pharmacist. There is also a 24-h telephone helplinei provided by the manufacturer of apomorphine that will assist patients and clinicians on how to deal with the practicalities of the pump.
- Not infrequently we, as clinicians managing Parkinson’s disease, face a dilemma regarding whether to prescribe drugs off-licence. This may be necessary to maintain a level of dopaminergic stimulation equivalent to the usual oral regimen and hence reduce the risk of Parkinson’s disease complications and neuroleptic malignant-like syndrome. For example, clinicians may need to consider using rotigotine patch doses higher than 16 mg/24 h (see box 2) or giving crushed immediate release pramipexole via an enteral tube, both of which are not licensed. In these scenarios, the prescriber needs to recognise that this would be unlicensed and hence to take full responsibility for the prescription. However, nurses and pharmacists involved in the care of the patient may share some of the responsibility. Our advice is intended as a guide
- CHOOSING AN ALTERNATIVE METHOD OF DRUG ADMINISTRATION There are a few overarching guiding principles such as: it is generally best to choose the least invasive method and if appropriate, to revert to the patient’s usual oral regimen as soon as possible. It is also crucial to choose a method of drug administration fairly swiftly, to prevent significant (>4h) dose delays; so, for example if there were difficulties passing a nasogastric tube it would be advisable to apply a rotigotine patch, at least as an interim measure rather than waiting for another clinician to attempt passing the nasogastric tube if this meant several doses would be missed. While we cannot discuss every indication in this article, we will now outline a few general factors to consider when choosing which method to use.
- However, if patients have had a known adverse reaction to dopamine agonists, it is reasonable to consider a short course of antiemetic and/or antidiarrhoeal (eg, loperamide) drugs in order to maximise the bioavailability of their usual oral medications. This should be used cautiously—carefully observing for signs of reduced dopaminergic stimulation—and not at all if there is bloody diarrhoea.
- Second, it is important to consider the adverseeffect profiles of different drug classes and how these may relate to the individual patient. For example, dopamine agonists have an increased risk of hallucinations compared with levodopa, especially in older patients and those with delirium or dementia. Conversely, some patients are very sensitive to the hypotensive effect of pulsatile levodopa-containing drugs and may be better suited to the continuous stimulation offered by a transdermal rotigotine patch. It is helpful to find out which drugs a patient has previously not tolerated and avoid drugs in the same class if possible. Similarly it is often sensible to make as few drug switches as possible, especially if the current oral regimen is well tolerated. For example, for a patient taking levodopa, we find that it is probably best in terms of limiting drug-related adverse effects to give dispersible levodopa in thickened fluids or via nasogastric tube, rather than introduce a new dopamine agonist.
- PARKINSON’S DISEASE DRUGS THAT CAN BE OMITTED IN THE ACUTE SETTING Finally, while making every effort to avoid abruptly stopping any Parkinson’s disease medications, it is usually safe to omit the following drugs in the acute setting: rasagiline, selegiline, amantadine, entacapone and tolcapone. It is important, though, to be alert to new symptoms that could be drug withdrawal effects (eg, rapid withdrawal of amantadine occasionally causes an acute dystonic reaction) and to seek pharmacy advice within 48h.
- total daily levodopa equivalent dose (LED). LED estimates vary,