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Jessica Richards Hosgood, PharmD, RPh Clinical Pharmacist HospiScript Services, LLC A Catalyst Rx Company [email protected] Identify the most common symptoms in end of life care List assessment parameters for symptoms Discuss rationales for drug choices to provide symptom control in hospice patients Unapproved indications and routes of administration will be discussed 1 Anorexia Anxiety Constipation Delirium Depression Dyspnea Fatigue Fever Fluid Overload Infection Insomnia Muscle Spasms Nausea and Vomiting Pain Seizures Terminal Secretions What medications would you chose? 2 Acetaminophen Albuterol Atropine Oph Soln. Bisacodyl Chlorpromazine Ciprofloxacin Citalopram Dexamethasone Diphenhydramine Furosemide (KCL) Haloperidol Ibuprofen Lorazepam Methadone Methylphenidate Metoclopramide Morphine Nortriptyline Nystatin Phenobarbital Omeprazole OTC Oxycodone Senna/Docusate Spironolactone Trazodone Unlabeled use Improve quality of life Use of medication efficiently Minimize side effects Use appropriate routes of administration Keep medication dosage schedules simple Anticipate disease progression Give patient and care givers information and choices as appropriate 3 Psychosocial/ emotional/spiritual issues Depression Anxiety Delirium Bowel function Bladder function Pain Insomnia Nausea/vomiting Dyspnea Fever Terminal secretions Loss of route of administration Corticosteroids Dexamethasone* 2‐4mg daily Prednisone (more cost effective) 10mg daily Why not… Megesterol (Megace®) Dronabinol (Marinol®) Mirtazepine (Remeron®) * Unlabeled use 4 Benzodiazepines Lorazepam (Ativan®) 0.5‐2mg q4‐12 h Alternatives: Alprazolam (Xanax®) 0.25‐1mg q4‐8 h Antipsychotics?? * Unlabeled use Stimulant laxatives Especially for opioid induced constipation Senna (Senokot‐S®) Use in combination with docusate sodium (stool softener) Bisacodyl (Dulcolax®) Alternatives: Osmotic laxatives Sorbitol 30mL BID Why not Lactulose? Polyethylene glycol (Miralax®) 17 grams daily 5 Hospice Patients 30% occurrence on admission Cancer Patients 87% during course of disease Oxford Textbook of Palliative Medicine Reversible 49% of palliative care patients Terminal Delirium 88% of dying patients Lawlor, Arch. Int. Med, 2000, 160: 786‐84. Urinary retention Fatigue, sleep deprivation, Constipation altered circadian rhythms Severe anemia Nutritional deficiencies Hypoxemia Infection Metabolic abnormalities ↑ or ↓ sodium ↑ calcium Altered blood glucose Dehydration Thiamine, folate, B12 Drug and alcohol withdrawal Pain (especially uncontrolled) 6 If appropriate, treat reversible causes Reduce, eliminate, or change drugs that may be contributing to delirium Use hypnotic medication to provide adequate sleep Use antipsychotic drugs to treat confusion Add benzodiazepines only if needed for anxiety and/or restlessness Pharmacologic interventions Antipsychotics Haloperidol* (Haldol®) 0.5‐5 mg q4 h SL/PO/PR/SQ AVOID BENZODIAZEPINES! Unless in combination with neuroleptic (due to paradoxical worsening of delirium and anxiety) * Unlabeled use 7 Psychostimulant Methylphenidate* (Ritalin®) 5mg q am & q noon Selective Serotonin Reuptake Inhibitors (SSRIs) Citalopram (Celexa®) 10‐40 mg daily Generic Alternatives: Fluoxetine (Prozac®) 20‐40 mg daily (Long t1/2) Sertraline (Zoloft®) 25‐100mg daily * Unlabeled use Symptomatic management Opioids Low dose immediate release Nebulized opioids not necessarily effective Anxiolytics Low dose ATC + Breakthrough Morphine* 2.5‐ 20 mg PO/SL q1 h prn Oxycodone* 2.5‐20 mg PO/SL q1 h prn Lorazepam* (Ativan ®) 0.25‐2mg PO q6‐12 h ATC Non‐pharmacologic interventions Oxygen Only if hypoxic * Unlabeled use 8 Bronchodilators Albuterol (Proventil®) Corticosteroids Oral better than inhaled in end‐stage disease May not have adequate lung function to inhale corticosteroids Risk of oral thrush with inhaled corticosteroids Dexamethasone Prednisone Acetaminophen (Tylenol®) Available as tablets, capsules, liquid, suppositories 325‐650mg PO/PR q4‐6 h Caution use hepatic dysfunction Ibuprofen (Motrin®) 200‐400mg PO q4‐6 h 9 Diuretics Loop Diuretic Furosemide (Lasix®) + KCl if appropriate Potassium Sparing Diuretic Spironolactone (Aldactone®) Antibiotics Ciprofloxacin (Cipro®) Antifungals Nystatin (Mycostatin®) Alternatives: Based on type of infection/patient C&S 10 Antidepressants Trazodone* (Desyrel®) 25‐50 mg q HS Benzodiazepines Lorazepam (Ativan®) 0.5‐1mg q HS Barbiturate Phenobarbital 30‐120mg q HS Antihistamines Diphenhydramine (Benadryl®) 25‐50mg q HS Not recommended in elderly Avoid Zolpidem (Ambien/Ambien CR®) Eszopiclone (Lunesta®) Zaleplon (Sonata®) Ramelteon (Rozerem®) * Unlabeled use Benzodiazepines Lorazepam* (Ativan®) 0.25 ‐0.5mg q4‐12 h Alternatives: Baclofen (Lioresal®) 5‐10mg TID Tizanidine (Zanaflex®) 4mg q6‐8 h Cyclobenzaprine (Flexeril®) 10mg TID * Unlabeled use 11 Chemoreceptor Trigger Zone (CTZ) Cortex Vestibular Apparatus Neurotransmitters Serotonin Dopamine Acetylcholine Histamine GI Tract EPEC Project 1999 Mediated via Chemoreceptor Trigger Zone Gastric Stasis Vestibular Dysfunction Anxiety/Anticipation Increased Intracranial Pressure Gastric Irritants 12 Butyrophenones Promotility agents Haloperidol* (Haldol®) 0.5‐2mg BID & q4 h prn Metoclopramide (Reglan®) 10mg AC & HS What about Phenothiazines ? Promethazine (Phenergan®) Prochlorperazine (Compazine®) Chlorpromazine * (Thorazine®) Trimethobenzamide (Tigan®) Prokinetic agents Metoclopramide (Reglan®) 5‐10mg AC & HS 13 Antihistamines Diphenhydramine* (Benadryl®) 25mg q4‐6 h Alternative: Meclizine (Antivert®) 12.5‐25mg q6 h * Unlabeled use Anticipatory/Anxiety Lorazepam (Ativan®) Haloperidol* (Haldol®) Increased intracranial pressure Dexamethasone (Decadron®) * Unlabeled use 14 Proton Pump Inhibitors Omeprazole OTC (Prilosec OTC®) 20‐40mg daily Nociceptive Somatic Visceral Inflammatory Neuropathic Peripheral Central Functional Psycho/Social 15 Nociceptive Somatic Visceral Treatment options: Opioids Immediate‐release medications Morphine Oxycodone Extended‐release medications Morphine SR Oxycontin® Long‐acting medications Methadone 16 Morphine Gold Standard World Health Organization Mainly used to relieve pain and shortness of breath in palliative care/hospice Metabolite accumulation with high doses and in renal insufficiency Other opioids available when patients are unable to tolerate morphine Hydrocodone Not available as a single agent Hydromorphone Less neurotoxicity than morphine Most potent injectable solution available Good for subcutaneous injections Oxycodone May be more appropriate than morphine in patients with renal failure Various formulations available Oxycodone oral concentrate 20 mg/mL Immediate release – 5 & 15mg tablets Extended release (OxyContin®) 17 Fentanyl (Duragesic®) Transdermal Patch Alternative route Difficult to dose correctly Slow onset/offset of action Difficult to respond to changing pain Dependent on physiological state of patient Cachexia Dehydration Fever Diaphoresis Safety issues Recommended to be prescribed by experienced clinician QT prolongation Drug interactions Indications for treatment Pain refractory to other opioids Neuropathic pain Opioid adverse effects Morphine (phenanthrene) allergy Mechanism of action Mu receptor agonist Delta receptor agonist N‐methyl‐d‐aspartate (NMDA) receptor antagonist 18 Pharmacokinetics Steady state concentration occurs after 1 week Titrate slowly, monitor for accumulation Duration of action following steady state is 8‐12 hours No active metabolites Less sedation, no euphoria Inexpensive May be associated with a stigma Opioid addiction treatment Overdose and death Treatment options: Nonsteroidal anti‐inflammatory Drugs (NSAIDs) Steroids 19 Treatment Options Tricyclic antidepressants Nortriptyline (Pamelor®) 10‐25mg qHS, titrate to 150mg Antiepileptic Drugs Gabapentin (Neurontin®) 100‐300mg TID (maximum 3600mg/day) NMDA Blockers Methadone Ketamine Sodium Channel Blockers Lidocaine Acute Lorazepam (Ativan®) 2mg PO/SL/PR q15 min up to 8 mg/episode Maintenance Lorazepam 0.5‐1mg q6 h Phenobarbital 30‐120mg q8‐12h 20 Anticholinergic/Antimuscarinics Atropine 1% Ophthalmic Drops* 2‐4 drops SL q2‐4 h Titratable Alternatives: Hyoscyamine 0.25mg SL q4 h prn Why not Transderm Scop? Non‐pharmacologic Interventions Reposition patient first Suction is occasionally helpful Secretions re‐accumulate rapidly * Unlabeled use Jessica Richards Hosgood, PharmD, RPh [email protected] 21