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Topical Pain Control Medication Gregory Harochaw Pharmacy Manager Tache Pharmacy Phone 204-233-3469

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Presentation on theme: "Topical Pain Control Medication Gregory Harochaw Pharmacy Manager Tache Pharmacy Phone 204-233-3469"— Presentation transcript:

1 Topical Pain Control Medication Gregory Harochaw Pharmacy Manager Tache Pharmacy Phone

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

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4 Metabolism Cytochromes

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

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

8 SC injections active drug absorbed by diffusion of drug into the capillary network 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 The greater the blood flow in the capillary network the greater the absorption of the drug Epinephrine vasoconstriction drug absorption Epinephrine vasoconstriction drug absorption Heat blood flow drug absorption Heat blood flow drug absorption

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

12 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 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 As surface area & thickness of epidermis, the rate of transdermal flux The underlying epidermal layers & the dermis area are an aqueous environment The underlying epidermal layers & the dermis area are an aqueous environment

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

14 Finding a Suitable Carrier For compounds used exclusively for the treatment of a skin condition, passive diffusion into the superficial epidermis may be sufficient 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 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 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

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

16 Vehicles Used 1 PLO – Pluronic Lecithin Organobase PLO – Pluronic Lecithin Organobase Pluronic hydrophilic phase Pluronic hydrophilic phase Lecithin Isopropyl Palmitate lipophilic 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 Mixing Pluronic Gel & Lecithin Isopropyl Palmitate under pressure (with the drug) will form an amphiphilic phase containing drug micelles Gold standard available most Rx Gold standard available most Rx Provides good penetration into skin Provides good penetration into skin Works well with a variety of lipophilic/hydrophilic agents Works well with a variety of lipophilic/hydrophilic agents Need to rub in well??? Need to rub in well??? Greasy base Greasy base The 2 phases can separate under cold conditions The 2 phases can separate under cold conditions

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

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

19 Bases To Be Used 1 Lipoderm Lipoderm Creamier base than PLO Creamier base than PLO Cosmetically more elegant Cosmetically more elegant Less sticky Less sticky Less smell Less smell Not as temperature sensitive as PLO Not as temperature sensitive as PLO Cold temperatures PLO may separate Cold temperatures PLO may separate Less chance of rash vs PLO Less chance of rash vs PLO Only compounding pharmacies can make Only compounding pharmacies can make

20 Bases To Be Used 1 Penetration rates: Penetration rates: Pentravan,VanPen, PLO 5-20mm Pentravan,VanPen, PLO 5-20mm PCCA Gel mm (Intradermal) PCCA Gel mm (Intradermal) PCCA Gel mm PCCA Gel mm PCCA Gel mm PCCA Gel mm Speed Gel up to 50mm Speed Gel up to 50mm

21 Sports Medicine Iontophoresis Iontophoresis Enhance absorption of ions by the use of an electrical current Enhance absorption of ions by the use of an electrical current Anti-inflammatorys, dexamethasone, lidocaine Anti-inflammatorys, dexamethasone, lidocaine Phonophoresis Phonophoresis Uses ultrasound to transcutaneous drug absorption Uses ultrasound to transcutaneous drug absorption NSAIDs, dexamethasone NSAIDs, dexamethasone

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

23 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:

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

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

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

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

29 Ketamine Widely used as an anesthetic agent 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) 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) 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) 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) 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) 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) 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) Low doses of ketamine have minimal adverse effects on cardiovascular or respiratory function (Miller et al., 2000)

30 Ketamine 2 REQUIRES A TRIPLICATE

31 Medications Used in Transdermal Delivery Drugs listed in percentages 1% Solution = 1000mg/100ml OR10mg/ml Hydromorphone 1% solution 10mg/ml

32 Medications Used in Transdermal Delivery DrugStrengthMechanism Amitriptyline1-5% NE Reuptake inhibitor Baclofen2-5% GABA Agonist Bretylium1-5% Sympathetic Inhibition Bupivicaine %Anesthetic Capsaicin % Substance P Blockade Carbamazepine2-5% NMDA Na + Blocker Clonidine % Alpha -2 Agonist Cyclobenzaprine1-4% Muscle Relaxant Dextromethorphan5-10% NMDA Receptor Antagonist

33 Medications Used in Transdermal Delivery DrugStrengthMechanism Diclofenac2-10% Cyclooxygenase Inhibitor Diphenhydramine5-10% Voltage Regulated Na + & Ca ++ Blockade Gabapentin5-10% Glutamate Antagonist Guaifenesin5-10% Muscle Relaxant Ibuprofen10-30% Propionic Acid NSAID Indomethacin15-20% Methylated Indole NSAID

34 DrugStrengthMechanism Ketamine5-15% NMDA Receptor Antagonist Ketoprofen5-10% Propionic Acid NSAID Lidocaine2-10%Anesthetic Lipoic Acid 2-3%Antioxidant Loperamide5-10% Mu agonist Naproxen10-20% Propionic Acid NSAID Nifedipine0.2-16% Non-NMDA Ca +2 Channel Antagonist Pentoxifylline5-15% TNF Inhibitor, Peripheral Vasodilator Phenytoin0.5-2% NMDA Na + Blocker

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

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

37 Sciatica Gabapentin 6%, Clonidine 0.1%, Diclofenac 2% & Lidocaine 2% Gabapentin 6%, Clonidine 0.1%, Diclofenac 2% & Lidocaine 2% Above mixture + Pentoxyfylline 5% Above mixture + Pentoxyfylline 5% May prevent sciatica caused by a herniated disc 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:

38 Shingles Ketamine 15%, amitriptyline 2-5%, loperamide 5-10%, lidocaine 2-10% Ketamine 15%, amitriptyline 2-5%, loperamide 5-10%, lidocaine 2-10% Topical spray Topical spray Ketamine 10%, bupivicaine % Ketamine 10%, bupivicaine % Ketamine 4%, morphine sulfate 4% Ketamine 4%, morphine sulfate 4% 2-Deoxy-D-Glucose 2%, Diphenhydramine 2%, Lidocaine 4% 2-Deoxy-D-Glucose 2%, Diphenhydramine 2%, Lidocaine 4%

39 Shingles Capsaicin % substance P blockade Capsaicin % substance P blockade Speed gel??? Speed gel??? Penetration depth up to 50mm Penetration depth up to 50mm Tx may take up to 8 weeks to get maximum relief Tx may take up to 8 weeks to get maximum relief

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

41 Treatment of Anal Fissures Nitroglycerin 0.2% Ointment Nitroglycerin 0.2% Ointment Success rates 48-78% in treating anal fissures Success rates 48-78% in treating anal fissures NTG metabolized it releases nitric oxide an inhibitory neurotransmitter for smooth muscle NTG metabolized it releases nitric oxide an inhibitory neurotransmitter for smooth muscle Given 3 – 5 times daily Given 3 – 5 times daily Nifedipine 0.2% Ointment Nifedipine 0.2% Ointment Less side effects than NTG Less side effects than NTG HAs, dizziness, lightheadedness hypotension HAs, dizziness, lightheadedness hypotension Ca ++ antagonist O 2 demand and mechanical contraction of smooth muscle Ca ++ antagonist O 2 demand and mechanical contraction of smooth muscle One study 95% complete healing rate in 21 days One study 95% complete healing rate in 21 days

42 Myofascial Pain

43 Topical Magnesium Magnesium Chloride 10% PLO Magnesium Chloride 10% PLO Use twice daily Use twice daily Applied across whole taught band Applied across whole taught band Can cause diarrhea Can cause diarrhea Magnesium 10%/ Pyridoxine 5% PLO Magnesium 10%/ Pyridoxine 5% PLO Pyridoxine pain thresholds and serotonin levels Pyridoxine pain thresholds and serotonin levels

44 Diabetic Neuropathy Ketamine 15%, Amitriptyline 2-5%, Clonidine %, Nifedipine 2-10%, Diclofenac 2-4% Ketamine 15%, Amitriptyline 2-5%, Clonidine %, Nifedipine 2-10%, Diclofenac 2-4% Burning sensation Alpha Lipoic Acid PO mg/day Burning sensation Alpha Lipoic Acid PO mg/day Topically 0.5-3%

45 Fibromyalgia Ketoprofen 10%, cyclobenzaprine 3%, lidocaine 5% Ketoprofen 10%, cyclobenzaprine 3%, lidocaine 5% Amitriptyline 5%, baclofen 2%, diclofenac 2%, lidocaine 2% Amitriptyline 5%, baclofen 2%, diclofenac 2%, lidocaine 2% Ketoprofen 10% & baclofen 5% lidocaine 5% Ketoprofen 10% & baclofen 5% lidocaine 5%

46 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: _______mLRefill x _______

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