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Topical Pain Control Medication

Topical Pain Control Medication. Gregory Harochaw Pharmacy Manager Tache Pharmacy Phone 204-233-3469 tache@mts.net. Goals and Objectives. Understand the pharmacokinetics of transdermal delivery Advantages/disadvantages of transdermal route Medications used for some different situations .

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Topical Pain Control Medication

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  1. Topical Pain Control Medication Gregory Harochaw Pharmacy Manager Tache Pharmacy Phone 204-233-3469 tache@mts.net

  2. Goals and Objectives • Understand the pharmacokinetics of transdermal delivery • Advantages/disadvantages of transdermal route • Medications used for some different situations

  3. Metabolism Cytochromes

  4. Parenteral Routes • Intradermal • Small volumes  0.1ml • Absorption is slow  slow onset of action • Subcutaneous • <2ml volumes • Much more rapid absorption than ID • Intramuscular • 2 – 5ml volumes • More rapid absorption than by SC • Can formulate a delayed response • Intravenous • Small to large volumes • No absorption of drug  directly in vein Sterile Dosage Forms: S. Turco, R. King

  5. Pharmacokinetics for Absorption • IV route  immediate & total access to active drug molecules • IM, SC, ID  require an absorption step • The vascularity of the IM route is greater than the SC route   absorption Sterile Dosage Forms: S. Turco, R. King

  6. SC injections  active drug absorbed by diffusion of drug into the capillary network • The greater the blood flow in the capillary network the greater the absorption of the drug • Epinephrine  vasoconstriction   drug absorption • Heat  blood flow   drug absorption

  7. Stratum Corneum (horny layer) • Compared to “bricks & mortar” • 10-15 layers of flattened cornified cells constitute the bricks • Lipid-rich intercellular matrix constitutes the mortar • form an effective barrier to transdermal water loss & external chemical access • If a drug is to pass through the skin & into general circulation, it must 1st traverse this barrier

  8. Factors for Drug Absorption • Transcutaneous flow of compounds across the stratum corneum is directly proportional to the concentration gradient & therefore can be attributed to passive diffusion • As surface area  & thickness of epidermis , the rate of transdermal flux  • The underlying epidermal layers & the dermis area are an aqueous environment

  9. Factors for Drug Absorption • Highly hydrophilic drugs will absorb poorly through the stratum corneum but better in the aqueous layers of the epidermis • Highly lipophilic drugs will absorb better through the stratum corneum but slowed when they reach the aqueous layers of epidermis

  10. Finding a Suitable Carrier • For compounds used exclusively for the treatment of a skin condition, passive diffusion into the superficial epidermis may be sufficient • Using a vehicle such as Glaxal Base or Vaseline • For a drug to be delivered to the general circulation, the drug/vehicle must maintain affinity for both aqueous and lipid environments to absorb effectively

  11. Site Permeability • Generalized rank order of site permeabilities: • genitals > head/neck > trunk > arm > leg • Preterm infant > term infant > young adult > elderly Klein & collegues,. Transdermal Clonidine Therapy in Elderly Mild Hypertensives; Hypertension Suppl 1985:3;581-584

  12. Vehicles Used1 • PLO – Pluronic Lecithin Organobase • Pluronic  hydrophilic phase • Lecithin Isopropyl Palmitate  lipophilic phase • Mixing Pluronic Gel & Lecithin Isopropyl Palmitate under pressure (with the drug) will form an amphiphilic phase containing drug micelles • Gold standard available most Rx • Provides good penetration into skin • Works well with a variety of lipophilic/hydrophilic agents • Need to rub in well??? • “Greasy” base • The 2 phases can separate under cold conditions

  13. Electronic and Electro Mortar & Pestles The electronic mortar & pestle provide pharmacists with the modern way to compound creams,gels, ointments and suspensions.

  14. Ointment Mill The ointment mill mixes powders, crystals and creams into a smooth, finished product

  15. Bases To Be Used1 • Lipoderm • Creamier base than PLO • Cosmetically more elegant • Less sticky • Less smell • Not as temperature sensitive as PLO • Cold temperatures PLO may separate • Less chance of rash vs PLO • Only compounding pharmacies can make

  16. Bases To Be Used1 • Penetration rates: • Pentravan,VanPen, PLO  5-20mm • PCCA Gel 2058  1-3mm (Intradermal) • PCCA Gel 4038  10-20mm • PCCA Gel 6633  +30mm • Speed Gel  up to 50mm

  17. Sports Medicine • Iontophoresis • Enhance absorption of ions by the use of an electrical current • Anti-inflammatory’s, dexamethasone, lidocaine • Phonophoresis • Uses ultrasound to  transcutaneous drug absorption • NSAID’s, dexamethasone

  18. Reasons for Topical Route Oral route not desirable Mucositis Inability to swallow Nausea/vomiting Obstruction Poor taste of product Dry mouth Can produce a more localized action Also can be used for systemic use GH

  19. Topical Route: Advantages Avoids the GI tract and hepatic first-pass metabolism Reduces systemic side effects Improves compliance Allows ↑ concentration of Rx at site of application Plasma concentrations of <10% compared to oral route Heir, Gary DMD, et al. IJPC 2004; 8:337-343

  20. Topical Route: Drawbacks Variations in the stratum corneum barrier • Delivery dosing may require adjustment • Rate of absorption may vary Rash most common SE May be incumbent when using larger areas Heir, Gary DMD, et al. IJPC 2004; 8:337-343

  21. + + - - Prostaglandins Bradykinin Histamine Leukotrienes Step 1: Peripheral Stimulation & Nociceptor Sensitization Substance P Glutamate Aspartic Acid Nitric Oxide Step 2: Signal Transmission Enkephalins Endorphins Medication Step 3: Pain Perception

  22. NMDA and AMPA Receptors Na+ influx exacerbates the Ca++ influx in absence of Mg++ This results in “wind up” pain, LTP and Allodynia

  23. Drugs That Effect Ion Channels • NMDA-Ca++ channel blockers: • Ketamine, orphenadrine, amantadine,DM, magnesium, haloperidol, nylidrin, methadone • AMPA-Na+ channel blockers: • Anticonvulsants • Gabapentin, carbamazepine • Antiarrythmics: • Lidocaine, mexilitine

  24. Ketamine • Widely used as an anesthetic agent • Given IV, IM, PO, PR, intranasally or spinally (Chia et al., 1998; Gehling and Tryba, 1998; Malinovsky et al., 1996; Mercandante et al., 2000; Walker et al., 2002) • Safety and efficacy of ketamine and analgesic well documented (Malinovsky et al., 1996; Reich & Silvay. 1989; White et al., 1982) • Tx in neuropathic pain (Edie et al., 1994, 1995; Jackson et al., 2001; Kannan et al., 2002; Kjepstad & Borchgrevnik., 1997; Mercandante et al., 1995, 2000; Mercandante & Arcuri, 1998) • Phantom limb pain (Knox et al., 1995) • Post-operative pain and other post-traumatic pain (Dick-Neilsen et al.,1992; Gurmani et al., 1996; Hirlinger & Dick, 1984; Hirlinger & Pfenninger, 1987; Lauretti & Azevedo, 1996; Owen et al., 1987) • Control control pain during dressing changes (Bookwalter, 1994; Humphries et al, 1997; Kulbe, 1998; Pal et al, 1997) • Low doses of ketamine have minimal adverse effects on cardiovascular or respiratory function(Miller et al., 2000)

  25. Ketamine2 REQUIRES A TRIPLICATE

  26. Medications Used in Transdermal Delivery Drugs listed in percentages 1% Solution = 1000mg/100ml OR 10mg/ml Hydromorphone 1% solution 10mg/ml

  27. Medications Used in Transdermal Delivery

  28. Medications Used in Transdermal Delivery

  29. Quirks • Ketamine has highest affinity for NMDA receptors of products given • Amitriptyline has a synergistic effect with ketamine • Fibromyalgia baclofen works well as an add on • Complex regional pain amitriptyline and bretylium • Diclofenac > pruritis than ketoprofen

  30. Arthritic Pain • Diclofenac 2 – 4 % used for years • Pennsaid 1.5% • Add • Amitriptyline 2 – 5%  bone pain • Capsaicin 0.025 – 1%  Substance P blocker • Gabapentin 6 – 10%  Neuropathic pain • Lidocaine 2-10%  Na channel blocker

  31. Sciatica • Gabapentin 6%, Clonidine 0.1%, Diclofenac 2% & Lidocaine 2% • Above mixture + Pentoxyfylline 5% • May prevent sciatica caused by a herniated disc Yabuki et al. Prevention of compartment syndrome in dorsal root ganglia caused by exposure to nucleus pulposus. Spine 2001;26:870-875

  32. Shingles • Ketamine 15%, amitriptyline 2-5%, loperamide 5-10%, lidocaine 2-10% • Topical spray • Ketamine 10%, bupivicaine 0.3-0.75% • Ketamine 4%, morphine sulfate 4% • 2-Deoxy-D-Glucose 2%, Diphenhydramine 2%, Lidocaine 4%

  33. Shingles • Capsaicin 0.025-0.1%  substance P blockade • Speed gel??? • Penetration depth up to 50mm • Tx may take up to 8 weeks to get maximum relief

  34. Sensory Neuropathy“Tingling” Sensation • Gabapentin 6%, loperamide 10% & lidocaine 2% • Amitriptyline 2% • Clonidine 0.1% • Apply to affected areas for 2 – 4 weeks

  35. Treatment of Anal Fissures • Nitroglycerin 0.2% Ointment • Success rates 48-78% in treating anal fissures • NTG metabolized it releases nitric oxide  an inhibitory neurotransmitter for smooth muscle • Given 3 – 5 times daily • Nifedipine 0.2% Ointment • Less side effects than NTG • HA’s, dizziness, lightheadedness hypotension • Ca++ antagonist   O2 demand and mechanical contraction of smooth muscle • One study 95% complete healing rate in 21 days

  36. Myofascial Pain

  37. Topical Magnesium • Magnesium Chloride 10% PLO • Use twice daily • Applied across whole “taught” band • Can cause diarrhea • Magnesium 10%/ Pyridoxine 5% PLO • Pyridoxine   pain thresholds and  serotonin levels

  38. Diabetic Neuropathy • Ketamine 15%, Amitriptyline 2-5%, Clonidine 0.1-0.3%%, Nifedipine 2-10%,  Diclofenac 2-4% • Burning sensation  Alpha Lipoic Acid PO 600-1800mg/day Topically 0.5-3%

  39. Fibromyalgia • Ketoprofen 10%, cyclobenzaprine 3%, lidocaine 5% • Amitriptyline 5%, baclofen 2%, diclofenac 2%, lidocaine 2% • Ketoprofen 10% & baclofen 5%  lidocaine 5%

  40. Base:□ Lipoderm □ PLO □ Speed Gel □ Other (specify)_________________ Check the Ingredient & Strength: Other Strength: □ Ketamine __5% __10% __15% ______% (requires a triplicate Rx with this Rx) □ Gabapentin __6% __8% __10% ______% □ Clonidine __0.1% __0.2% ______% □ Lidocaine __2% __4% __5% __10% ______% □ Loperamide __5% __10% ______% □ Ketoprofen __5% __10% __20% ______% □ Diclofenac __2% __4% __5% ______% □ Carbamazepine __2% __5% __10% ______% □ Baclofen __2% __5% ______% □ Amitriptyline __2% __5% ______% □ Pentoxifylline __5% __10% __15% ______% □ Bretylium __1% __2% ______% □ Nifedipine __2% __5% __10% ______% □ Dextromethorphan __10% □ Guaifenesin __5% __10% □ Menthol __ 0.5% □ Camphor __0.25% Additional Ingredients: _________________ _____% _________________ _____% Directions: Apply _____mL to affected area(s) (specify) ________________________ (frequency) _______________________. Mitte: _______mL Refill x _______

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