Commonly encountered medications and their side effects - what the generalist needs to know

Transcription

1 Commonly encountered medications and their side effects - what the generalist needs to know Jeremy Cosgrove Consultant Neurologist Leeds Teaching Hospitals NHS Trust

2 Outline: Parkinson s medications and their mechanisms Altering dopaminergic medications as disease advances Important complications and interactions Medications to avoid What to do when the oral route is unavailable

3 Medication classes: Dopamine replacement: Levodopa + dopa decarboxylase inhibitor Co-careldopa (Sinemet) Co-beneldopa (Madopar) Duodopa Monoamine oxidase inhibition (MAO-B): Rasagaline (Azilect) Selegiline Safinamide (Xadago) Dopamine agonists: Ropinerole (Requip) Pramipexole (Mirapexin) Rotigotine (Neupro) Apomorphine Catechol-O-methyl transferase (COMT) Inhibitors Entacapone (with carbidopa/levodopa= e.g. Stalevo) Tolcapone Opicapone (Ongentys)

4 Pre-synaptic terminal Peripheral blood vessel Tyrosine Dopamine Levodopa Dopamine agonists MAO HVA MAO-B inhibitors Blood- brain barrier DaT COMT HVA DA receptor Alty et al., 2016 DCI COMT-I DA 3-0-MD Post-synaptic neuron

5 Medication side effects: Levodopa + dopa decarboxylase inhibitor Nausea, GI issues Sleep disturbance Impulse control disorders Hypotension Hallucinations, confusion Wearing off, dyskinesia Dopamine agonists: Nausea, GI issues Sleep problems including sudden onset sleep Monoamine oxidase inhibition (MAO-B): Headaches, joint pains, GI Low mood Catechol-O-methyl transferase (COMT) Inhibitors Liver damage Tolcapone only Nausea, GI issues Sleep disturbance Hallucinations, confusion Urine discoluration Impulse control disorders Hallucinations, confusion

6 The natural progression of PD: Diagnosis Prodrome before diagnosis Easy Hard Kalia and Lang, 2015 RBD = REM sleep behaviour disorder, EDS = Excessive daytime sleepiness

7 Linking progression to pathology: Mild cognitive impairment (MCI) Parietal cortex Motor symptoms Frontal cortex Dementia Hallucinations Occipital cortex Prodrome RBD, EDS, Low mood Mid-brain Pons Cerebellum Loss of smell Medulla

8 Number of cases Age at onset Events heralding the palliative stage: Residen al care Falls Visual hallucina ons Cogni ve impairment Kempster et al., 2010

9 Age, hallucination and dementia: Reid et al., 2011 Hely et al., 2008

10 Balancing things out...

11 Withdrawing medications: Cognitive decline? Rivastigmine? Hallucinations and delusions? - Quetiapine? Clozapine? Dopamine agonist MAO-B COMT Wean down levodopa Balance mobility versus mental state

12 1) Impulse control disorders (ICDs): 14 17% - dopamine agonists 0.7-7% - levodopa

13 2) Dopamine agonist withdrawal syndrome (DAWS): A severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors Nirenberg, 2013 ICD 100% in some studies DA dosage? mesocortical variant

14 Nirenberg, 2013

15 3) Neuroleptic malignant like syndrome: Sudden withdrawal of dopaminergic drugs Other potential risk factors: Advanced disease, dehydration, infection, constipation, enteral feeding 10-30% mortality Hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated CK IV fluids, cooling, reinstate dopaminergic therapy

16 4) Serotonin syndrome Cognitive: headache, agitation, confusion, hallucinations, coma Autonomic: shivering, sweating, hyperthermia, vasoconstriction, tachycardia, nausea, diarrhoea Somatic: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor, seizures

17 . in Parkinson s: MAO-B (rasagaline, selegiline, safinamide) + SSRI, TCA, SNRI (venlafaxine, duloxetine), mirtazapine, trazadone Or Opioids

18 Drugs to avoid - Antiemetics Avoid Prochlorperazine Levomepromazine Chlorpromazine Metoclopramide Cinnarizine Better options Ondansetron Cyclizine

19 Drugs to avoid Antipsychotics: Avoid Amisulpride Haloperidol All others bar quetiapine and clozapine Better options Benzodiazepine Quetiapine Mirtazapine

20 Providing medication when the oral route is not possible: Why? Infection, constipation, diarrhoea, missed doses Gradual decline disease progression Mechanisms to help: 1. Dispersible preparations 2. NG tube or PEG 3. Transdermal medication (rotigotine patch) 4. Subcutaneous (apomorphine)

21 Dispersible preparations: Levodopa: Switch to dispersible co-beneldopa 1:1 for co-careldopa Carbidopa/levodopa/entacapone (e.g Stalevo) Switch to dispersible co-beneldopa - 1:1.3 ratio Crush + 15ml water Off license Dopamine agonists Switch to equivalent co-beneldopa? Rotigotine patch? Switch to normal release, crush + 15ml water Off license for NG

22 Transdermal patch: Alty et al., 2016

23 Questions:

24 References: Alty JE, Robson J, Duggan-Carter P, et al. Pract Neurol 2016;16: Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord; 2008: 23, Kalia LV and Lang AE. Parkinson's disease. The Lancet; 2015:386: Kemspter P et al Relationships between age and late progression of Parkinson's disease: a clinico-pathological study. Brain; 133 : Nireberg MJ. Dopamine agonist withdrawal syndrome: implications for patient care. Drugs Aging. 2013;30: Reid WG, Hely MA, Morris JG, Loy C, Halliday GM. Dementia in Parkinson s disease: a 20-year neuropsychological study (Sydney Multicentre Study). J Neurol Neurosurg Psychiatry 2011;82: