topical & transdermal medications in palliative medicine
DESCRIPTION
DISCLAIMER: This slideset does not constitute medical advice. References are provided through out, please discuss with your own doctor or consult your own references before utilizing any information found in this slideset. Presented to the University of Kansas Palliative Medicine Fellowship lecture group.TRANSCRIPT
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Topical & Transdermal Medications
Christian Sinclair, MD
Kansas City Hospice & Palliative Care
October 8, 2008
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Medication Routes
• Oral• Intravenous• Rectal• Intraosseous• Intrathecal• Inhaled• Optical• Topical
• Sublingual/Buccal• Subcutaneous• Intravesical• Intramuscular• Epidural• Insuffluation• Intravitreal• Transdermal
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Indications for Alternate Route
• Unwilling or unable to swallow meds• Cancers of the head, neck and GI tract• Compromise of the GI tract
– Mucositis– Bowel obstruction
• Intolerable side effects during administration• Treating localized pain• Avoiding systemic side effects• Neonatal/pediatric populations
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Topical versus Transdermal
• Topical– Treats at the site of medication placement
– Usually compounded, often non-branded
– Antibiotics for skin infection
– Steroid creams for rashes
• Transdermal– Treats via systemic delivery of the medication
– Usually branded and not compounded
– Hormone replacement, nicotine addiction, Duragesic
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Variations
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Factors affecting absorption
• Flow increases with– Increased concentration– Increased surface area– Decreasing skin thickness– Lipophillic compounds– Low molecular weights
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Available Brand Medications
• Contraceptives/HRT
• Lidocaine
• Clonidine
• Nicotine
• EMLA
• Nitroglycerin
• Methylphenidate
• Estradiol
• Oxybutynin
• Estrogen
• Scopolamine
• Fentanyl
• Testosterone
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Compounding Vehicles
• PLO – Pluronic Lecithin Organogel
• Can hold guest molecules which are solubilized in the gel
• DMSO
• Other proprietary gels
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Other topical meds in Pubmed• Hormones-estriol and estradiol, DHEA, progesterone,
testosterone• NSAIDs-ketoprofen, diclofenac, piroxicam • SSRIs –fluoxetine, paroxetine • Antipsychotics-haloperidol, prochlorperazine • Levodopa• Morphine• Dexamethasone • Calcium channel blockers-diltiazem, nifedipine • Clonidine with gabapentin and ketamine• Lidocaine, tetracaine
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Evidence for Topical Meds
• Poor to Fair
• Animal studies (cats) in small numbers
• Many are single dose studies
• Rare human drug level studies
• Rare human symptom studies
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Topical Diclofenac
• OA, lateral epicondylitis
• 2% topical dicoflenac
• n=74, 14
• Improved pain, stiffness, physical function
• J Rheum 1999, Clin J Sport Med 1998
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Topical NSAIDs
• Stay mostly in the dermis
• Can reach synovial fluid
• Efficacy ranges from 18-92%
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EMLA Cream/Disc
• Typically used in the pediatric population
• 1G for 60 mins before efficacy
• Localized effect
• 5% emulsion preparation
• Combination of lidocaine and prilocaine
• Strong evidence base
• Patch 60 minutes provides 2 hours of relief
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Amethocaine
• 1G amethocaine gel 30 mins
• Better results then EMLA in less time
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Topical Ketamine
• No to minimal effect – With neuropathic or capsacin induced pain
• Ionotopheresis assisted delivery
• Open label showed long term effectiveness
• Often combined with amitriptyline
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Lidocaine Patch
• 5% Lidocaine
• Topical not transdermal
• Indicated for Post-herpetic Neuralgia
• Tried in – CTS, OA, vaccinations, venipuncture
• Also available as lidocaine gel
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Topical Opioids
• Opioid receptors on:– Peripheral nerves– Inflammed skin
• Morphine and metabolites not found systemically
• ? Wound healing mechanism– Up-regulate nitric oxide synthase
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Topical Opioids
• Skin infiltration of tumor
• Nonmalignant skin ulcers
• Severe oral mucositis
• Knee arthritis
• Tenesmoid pain.
Pain. 1999 Mar;80(1-2):121-5.
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Topical Opioids
• Mostly used for pressure ulcer pain• Relief modest for about 7-8 hours• Gel form
– 10 mg of morphine sulfate injection (10mg/ml)– in 8 gm of Intrasite gel– or gel infused dressing
• Also for burn wounds– MISS->Morphine Infused Silver Sulfadiazene
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http://www.supportiveoncology.net/journal/articles/0506289.pdf
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Topical Methadone
• Methadone 100mg in 10g Stomadhesive powder
• Varied results in wound application
• Analgesic effects of topical methadone: a report of four cases.
Clin J Pain. 2005 Mar-Apr;21(2):190-2.
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Topical antidepressants
• Topical Doxepin combined with capsacin for chronic neuropathic pain
• Doxepin mouthwash improved oral mucosal pain in cancer patients
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Transdermal Medications
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Testosterone
• Transdermal Patch• Transdermal Cream/Gel
– Testim or Androgel 1% QD
• Injectable, oral, and buccal forms• Indicated for testosterone replacement therapy
– Increased lean body mass, decreased fat mass, increased bone mineral density, increased sexual activity and desire
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Transdermal Nicotine
• Approved for nicotine replacement therapy
• Effects of nicotine– Increases glucose, epinephrine– Enhances serotonin and opiate receptors?– Stimulant, but also anxiolytic– Appetite suppressant
• Not indicated in naïve patients
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Fentanyl Transdermal Patch
• Well studied
• 92% bioavailable
• Strong mu opioid agonist
• Lipophillic -> High CNS Concentration
• Reservoir and Matrix patches
• Affected by skin thickness and temperature
• Less constipating
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Fentanyl Transdermal Patch
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Source: Duragesic package insert
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Source: Duragesic package insert
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Scopolamine Transdermal Patch
• Motion sickness
• Opioid induced nausea
• Smooth muscle spasm
• Parkinson’s
• Drying secretions
• Pyrexia/Sweating
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Scopolamine Transdermal Patch
• Belladonna alkaloid (Hyoscine)• Anti-cholinergic• Side effects:
– Drowsiness, dilated pupils, increased HR
• Initial bolus, then 120mcg/d x 3d• Plasma – 4hrs, Peak 24hrs• Post-auricular?• Cost: $8/patch
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Transdermal ABHR
• Ativan (lorazepam)– 2 articles
• Benadryl (diphenhydramine)– Case reports
• Haldol (haloperidol)– One study
• Reglan (metoclopramide)– No studies
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“Yes, you’re changed; you’ve got new ideas over here,” her friend continued.
“I hope so,” said Isabel; “one should get as many new ideas as possible.”
“Yes; but they shouldn’t interfere with the old ones when the old ones have been the right ones.”
Henry James, Portrait of a Lady
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The Future
• More studies
• Med-Tats
• Micro-needles
• Needless jet injectors
• Ionotophoresis
• Phonophoresis
• Liposomal delivery
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Review
• Topical vs. Transdermal
• Know the drug
• If it is branded, likely some efficacy
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Bibliography
• Carnel SB, Blakesless DB, Oswald SG, Barnes M. Treatment of radiation and chemotherapy-induced stomatitis. Otolaryngol Head Neck Surg. 1990;102:326-30.
• Cerchietti LC, Navigante AH, Bonomi MR et al. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002;95:2230-2236.
• Flock P. Pilot study to determine the effectiveness of diamorphine gel to control pressure ulcer pain. J Pain and Symptom Management. 2003;25:547-554.
• Gallagher RE, Arndt DR, Hunt K. Analgesic effects of topical methadone; a report of four cases. Clin J Pain. 2005;21:190-192.
• 5. Kalso E, Tramer MR, Carroll D et al. Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Pain. 1997;71:127-34.
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Bibliography
• Krajnik M, Zylicz Z, Finlay I et al. Potential uses of topical opioids in palliative care – report of 6 cases. Pain. 1999;80:121-125.
• Picard PR, Tramer MR, McQuay HJ et al. Analgesic efficacy of peripheral opioids (all except intra-articular): a qualitative systematic review of randomized controlled trials. Pain. 1997;72:309-318.
• Poonawala T, Levay-young BK, Hebbel RP, Gupta K. Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005;13:165-74.
• Porzio G, Marchetti P. Topical morphine in the treatment of painful ulcers. J Pain and Symptom Management. 2005;30:304-305.
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Bibliography
• Twillman RK, Long TD, Cathers TA. Treatment of painful skin ulcers with topical opioids. J Pain and Symptom Management. 1999;17:288-292.
• Vernassiere C, Cornet C, Trechot P et al. Study to determine the efficacy of topical morphine on painful chronic skin ulcers. J Wound Care. 2005;14:289-93.
• Zeppetella G, Paul J, Ribeiro MDC. Analgesic efficacy of morphine applied topically to painful ulcers. J Pain and Symptom Management. 2003;25:555-558.
• Zeppetella G, Joel SP, Ribeiro MD. Stability of morphine sulphate and diamorphine hydrochloride in intrasite gel. Palliat Med. 2005;19:131-6.
• Zeppetella G, Ribeiro MDC. Morphine in Intrasite gel applied topically to painful ulcers. J Pain and Symptom Management. 2005;29:118-119.
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Topical CCB
• Diltiazem with lidocaine (PLO) for anal fissures
• Also for anal fissures/hemorrhoids– Preparation H (phenylepherine)– 0.2% glyceryl trinitrate
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Topical Capsacin• Topical capsaicin preparations of 0.025 and 0.075%
• Postherpetic neuralgia
• Diabetic neuropathy
• Postmastectomy pain syndrome
• Oral neuropathic pain, Trigeminal neuralgia, and TMJ disorders
• Cluster headache (following intranasal application)
• Osteoarthritis
• Dermatological/cutaneous conditions