3/1/2018. Disclosures. Objectives. Clinical advisory board member- Daiichi Sankyo

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1 Adjuvant pain medications in geriatrics Thomas B. Gregory, Pharm.D., BCPS, CPE, FASPE Clinical Pharmacy Specialist Pain Management CoxHealth Springfield, MO Disclosures Clinical advisory board member- Daiichi Sankyo Off label indications will be clearly stated on individual medications as applicable Objectives Recall the pathophysiology of pain focusing on the elderly Review adjuvant medications used in the management of pain Recall dosing and management of adverse and side effects of adjuvant pain medications 1

2 Recall the pathophysiology of pain focusing on the elderly Definitions Pain- an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage Nociceptive- pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors Neuropathic- pain caused by a lesion or disease of the somatosensory nervous system accessed Epidemiology Estimated 60-75% of patients over the age of 65 report at least some persistent pain Osteoarthritis Back Neck Peripheral neuropathy Chronic joint pain Older patients generally under report or minimize pain Barriers such as cognition, hearing and communication impairments can also contribute to under treatment in the elderly Overview of persistent pain in older adults. American Psychologist Feb-March 69; 2:

3 Pain Pathway Stimulation of nociceptors causes signal transduction to the dorsal horn Transduction The spinothalamic tract transmits the signals to the brain where pain is first experienced Transmission and Perception Descending pathways from the brain alter the signals from the periphery Modulation Pain Pathway, cont. accessed Review adjuvant medications used in the management of pain 3

4 Commonly used adjuvant pain medications Anti-spasticity (muscle relaxants) Anti-epileptics Glucocorticoids Local anesthetics NSAIDs SNRIs Tricyclic antidepressants Others Anti-spasticity agents Multiple medications are included in this general taxonomy Certain agents approved for muscle spasticity Baclofen through activity on GABA Tizanidine through activity on alpha-2 Other agents are anti-spasmodic and should not be used for extended periods of time Benzodiazepines Cyclobenzaprine Cyclobenzaprine, or something else? 4

5 Anti-epileptics The primary anti-epileptics used in pain management work on calcium channels Gabapentin Pregabalin Others include Valproic acid (off label dosing) Topiramate (off label dosing) Carbamazepine for trigeminal neuralgia accessed Anti-epileptics for neuropathy For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and post-herpetic neuralgia There was little evidence and no judgement could be made about efficacy for valproic acid Low quality evidence was likely to be subject to a number of biases overestimating efficacy for carbamazepine Reasonable quality evidence exists indicating little or no effect for lamotrigine, oxcarbazepine and topiramate accessed Corticosteroids Mechanism of action leads to a decrease in production of heat shock proteins intracellularly leading to a decrease in inflammation Multiple routes of administration Oral Parenteral IV IM depot Intra-articular accessed

6 Local anesthetics Mechanism of action is through membrane stabilization of sodium channels preventing depolarization and signal transduction Acute uses for local anesthesia Topical application Cream, ointment, patch, etc. Intradermal injection Procedural joint nerve blocks Patches are indicated for the management of post herpetic neuralgia for chronic use Non-steroidal anti inflammatory agents COX 1 more specific to the GI tract and renal homeostasis GI mucous maintenance Vasodilatation in the kidneys COX 2 more specific to inflammation and platelet aggregation Mechanism of action is decreasing prostaglandins which are pro-inflammatory Decreasing platelet aggregation COX 3 is identified, but it s role is unknown NSAIDs and COX selectivity accessed

7 Serotonin norepinephrine reuptake inhibitors (SNRIs) Mechanism of action is through inhibition of norepinephrine and serotonin reuptake in peripheral nerve terminals Dosing is generally higher for treating neuropathic pain compared to treating depression accessed Tricyclic anti depressants (TCAs) Mechanism of action is through inhibition of norepinephrine and serotonin reuptake and inhibition of sodium channel action potentials The antidepressant effects and the neuropathic pain analgesia are independent Higher dosing and longer treatment time are needed for the antidepressant effects SSRIs and neuropathic pain Cochran review in 2007 reviewed the literature regarding Tricyclic antidepressants (TCA) Select serotonin reuptake inhibitors (SSRI) Serotonin norepinephrine reuptake inhibitors (SNRI) TCAs and venlafaxine have data which support their use in neuropathic pain There is limited evidence to suggest SSRIs are effective in managing neuropathic pain They were better tolerated compared to TCAs relating primarily to side effect profile accessed

8 Acetaminophen Mechanism of action is still not entirely known Thought to be a partial COX inhibitor In 2014 FDA mandated all prescription drug combination products containing acetaminophen cap the dose at 325 mg Maximum daily dose limits vary based on co-morbidities and who you ask Food and drug administration is still 4000 mg Johnson and Johnson is 3000 mg accessed accessed Section summary Medication Anti-spasticity (muscle relaxants) Anti-epileptics Glucocorticoids Local anesthetics NSAIDs SNRIs Tricyclic antidepressants Acetaminophen Pain indication Nociceptive Neuropathic Both Neuropathic Nociceptive Neuropathic Neuropathic Nociceptive Recall dosing and management of adverse and side effects of adjuvant pain medications 8

9 Morbidity and mortality Adverse drug reactions (ADR) are correlated to increases in hospitalization Top medications involved in these ADR include NSAIDs Glucocorticoids Polypharmacy and drug-drug interactions increase these risks Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features. EurJ ClinPharmacol : Effects of aging on PK/PD Advanced age leads to physiologic changes which can impact pharmacokinetics (PK) Decrease in total body water and lean muscle mass Increase in adipose tissue Decrease in albumin Decrease in renal function Pharmacodynamic (PD) changes Increased risk of sedation from CNS depressants Muscle relaxants and anti-epileptics Pain Management in the elderly. The Ochsner Journal : Anti-spasticity dosing Preferred agents with anti-spasticity properties include Baclofen 5 mg to 10 mg three times daily Decreased renal function requires a dose decrease Tizanidine 2 mg three times daily Decreased renal function requires a dose decrease 9

10 Anti-spasticity adverse effects Baclofen Urinary retention (rare) Tizanidine Hypotension Benzodiazepines and carisoprodol Abuse potential and dependence Methocarbamol Hepatotoxicity Anti-epileptic dosing Gabapentin Titration with 300 mg at bedtime and increasing the dose to a minimum of 1800 mg total daily dose For patients sensitive to sedating medications start with 100 mg at bedtime and titrate up every three days until efficacy, side effects or 3600 mg per day Decreased renal function requires a dose decrease Anti-epileptic dosing, cont. Pregabalin Titration with 75 mg twice daily and increasing to an optimal dosing of 450 mg total daily dose Maximum efficacy seen at 600 mg total daily dose however benefits did not increase compared to the 450 mg total daily dosing regimen Decreased renal function requires a dose decrease 10

11 Anti-epileptic adverse effects Gabapentin Sedation, psychiatric effects and increase in suicidal ideations Pregabalin Sedation, visual hallucinations, peripheral edema and increase in suicidal ideations Carbamazepine. Agranulocytosis, hepatotoxicity, hyponatremia, Stevens-Johnson reactions Anti-epileptic adverse effects, cont. Topiramate Sedation, hyperammonemia, metabolic acidosis, hyperthermia, renal calculus and increase in suicidal ideations Valproic Acid Hepatic failure, hyperammonemia, pancreatitis, hypothermia, thrombocytopenia and increase in suicidal ideations Corticosteroids oral dosing Prednisone Burst therapy 50 mg to 60 mg daily for five days Taper therapy with initial doses of 50 mg to 60 mg for patients with previous adverse reaction to burst therapy Methylprednisolone Dose pack instructions for titration Dexamethasone Up to 9 mg total daily dose 11

12 Corticosteroid adverse effects Caution should be exercised in patients with the following conditions Diabetes Psychiatric history Heart failure Adrenal suppression Taper needed when therapy exceeds days Immunocompromised Osteoporosis or fracture Gastrointestinal disease Corticosteroid adverse effects, cont. Use the lowest effective dose for anti-inflammatory effects Drug interactions should be taken into consideration even with short courses of systemic steroids Anticoagulants Antibiotics Anticonvulsants A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy AACI 2013, 9: Local anesthetic topical dosing Lidocaine Patch- up to 3 patches applied to the affected area On for 12 hours off for 12 hours Cream and lotion- multiple concentrations available Apply to affected area two to three times daily Ointment- apply a single application not to exceed 5 grams of ointment per day Caution when applying topical local anesthetics to open or broken skin 12

13 Local anesthetics adverse effects Lidocaine Irritation where topical preparation applied Arrhythmia, seizures and respiratory depression Only from significant systemic absorption and toxicity NSAID geriatric dosing and side effects Celecoxib 100 mg daily Ibuprofen 200 mg three times daily Naproxen 220 mg twice daily Diclofenac 50 mg twice daily or 75 mg extended release daily Diclofenac gel 2 grams, apply to affected area four times daily Certain co-morbidities limit the dosing of most NSAIDs Patients on anticoagulants Patients with renal dysfunction Pharmacological Management of Persistent Pain in Older Persons. JAGS 2009; 57: NSAIDs and GI complications(gic) Meta-analysis of GIC from individual NSAIDs GIC included ulceration, perforation, obstruction and bleeding All COX non-specific NSAIDs increase in risk of GIC when taken on a daily basis accessed March 8,

14 Considerations regarding NSAIDs and patients over 65 Prefer to use agents that are COX-2 specific (celecoxib) to avoid GI complications The concomitant use of misoprostol, H2RA (famotidine, etc.) or a proton pump inhibitor (omeprazole) may reduce the risk of GI ulcers AVOID the use of ketorolac High potential for GI complications and inappropriate for long term use Topical NSAIDS provide the same relief as the systemic agents with fewer of the GI complications Pharmacological Management of Persistent Pain in Older Persons. JAGS 2009; 57: SNRI dosing Prefer to use SNRI agents instead of Tricyclic antidepressants Select Serotonin Reuptake Inhibitors Duloxetine Fibromyalgia: 30 mg daily for 7 days then increase to 60 mg daily Diabetic neuropathy: 60 mg daily SNRI dosing, cont. Milnacipran Fibromyalgia: 12.5 mg on day 1, then 12.5 mg twice daily on days 2-3, 25 mg twice daily on days 4-7, then 50 mg twice daily thereafter Dose may be increased to 100 mg twice daily, based on individual response Venlafaxine (off label dosing) Diabetic neuropathy: 37.5 mg or 75 mg ER capsule daily and increase to a maximum dose of 225 mg ER capsule daily 14

15 SNRIs adverse effects SNRIs in general Withdrawal symptoms if medication is not tapered off when discontinuing Increase risk of suicidal ideations Increase in bleeding risk Venlafaxine and milnacipran Potential for hyponatremia/ SIADH when initiating Duloxetine Potential for exacerbation of seizures TCA dosing Nortriptyline (off label indication) 10 mg to 25 mg daily increased to a max dose of 100 mg Doses should not be increased more than every three days Desipramine (off label indication) 12.5 mg to 25 mg daily increased to a max dose of 250 mg Doses should not be increased more than every three days ECG monitoring for QTc prolongation at initiation, with other medications that can prolong QTc and every six months Anticholinergic properties among TCAs Tertiary amines are associated with more of the anticholinergic side effects compared to secondary amines Anticholinergic side effects include Sedation Dry mouth/ urinary retention Postural hypotension Arrhythmias or seizures accessed July 2, July 2,

16 Acetaminophen dosing Dosing ranges from 325 mg to 650 mg per dose Patients with hepatic insufficiency dosing should be capped at 2000 mg in 24 hours Patients on concomitant medications which can impair hepatic function dosing should be capped at 3000 mg in 24 hours For patients with no hepatic insufficiency or potential drug interactions dosing should be capped at 4000 mg in 24 hours Many medication combinations and over the counter products contain acetaminophen and should be considered in the total daily amount Acetaminophen Largest concern is unintentional overdoses Metabolism of acetaminophen by the liver is a saturable process Over the counter products and cumulative acetaminophen dosing South Med J. 2005; 98 (11): Summary There are multiple adjuvant medications used to manage pain other than opioids Most of them are able to be safely used in the elderly patient with increase in monitoring or vigilance when other medications are prescribed By matching pain indication to adjuvant you can decrease the amount of overall pain medication used by patients 16

17 Question and answers I cannot teach anybody anything. I can only make them think Socrates 17

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