Compounding for Pain Managment

Mina Bashta. R.Ph.
 
Skycare Pharmacy
Skycare Compounding Labs
 
540 Davis drive, unit 1,2
Newmarket, Ontario L3Y 2P3
Tel      (844) 727-4276
Fax      (844)-727-4277
www.skycarepharmacy.com
www.skycarecompoundinglabs.com
 
 
 

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Compounding for Pain Managment

 

by Mina Bashta, R.Ph.

Introduction

Major categories of pain

 

Inflammatory – Response to tissue damage that potentiates pain

Soft tissue – pressure ulcers, burns

Nociceptive – CNS and peripheral afferent pathways modulated via spinal cord

Somatic – aching, constant, localized (musculoskeletal)

Visceral – sharp, crescendo/decrescendo (cholecystitis, renal    stones, intestinal obstruction, MI)

Neuropathic – ischemia, destruction or encroachment of nerve by  disease or tumor

Paroxysmal – shooting or shock-like pain on a background of burning, aching sensation

Cost of chronic pain

Quality of life

 

Physical functioning

Ability to perform activities of daily living

Work

Recreation

Psychological Morbidity

 

Depression

Anxiety

Anger

Sleep disturbances

Loss of self?esteem

Social Consequences

 

Marital/family relations

Intimacy/sexual activity

Social isolation

Socioeconomic Consequences

 

Healthcare costs

Disability

Lost workdays

 

The Transdermal route:

 

Skin:is the bodies largest organ

Permeable membrane

Patient preference

Compliance

 

Why use the Transdermal route?

 

Oral route not desirable or not available

Inability to swallow (Mucositis or dysphagia)

Nausea/vomiting

Drug Interactions

Can be used to obtain a localized or a systemic effect

Lower systemic absorption when choosing to apply for a local effect

Drug concentration at the site of administration can be 30 fold higher than with an oral dose

Decreased potential for systemic side effects when targeting specific areas with a transdermal

Allows multimodal approach[1]

?          

Drawbacks of Transdermal route:

?          

Possible irritation at application site

Drying of the skin with transdermal products

Variations in the stratum corneum barrier may lead to variable absorption and may require adding penetration enhancers

Need to concentrate dosage form to accommodate therapeutic response[2]

 

?           

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

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

 

Choosing the best vehicle:

 

For compounds used exclusively for the treatment of a skin condition, passive diffusion into the superficial epidermis could be sufficient

Vehicle such as Glaxal Base or Petrolatum (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

Vehicles such as PLO or Lipoderm® (Gold Standard)

 

 

APIs

NMDA Antagonists / Glutamate Antagonist

 

Ketamine

 Amantidine

 Haloperidol

 Dextromethorphan

 Orphenidrine

 Magnesium Chloride

 

 

Ketamine

 

Issues surrounding the use of Ketamine

 

Dependence, hallucinations, out of body experiences

History of abuse since the seventies

Side effects include Anxiety, chest pain, palpitations, agitation, Rhabdomyolysis (muscle tissue breakdown), Urinary tract complications, renal impairment, dilated common bile duct, abnormal liver function.

 

Mechanism of action

 

NMDA / Ca++ channel blocker

Blocks a cascade of of intracellular events that inhibit the hyper excitability of the spinal cord neurons.

 

Use / Function

 

General Anesthetic

Neuropathic pain of various origins, including postherpetic neuralgia, complex regional pain syndrome, cancer pain, orofacial pain, and phantom limb pain.

Effective in treating painful neuropathy when other traditional methods have failed

Post-operative pain and other post-traumatic pain

Control of pain during dressing changes

 

Strength in transdermal cream

 

3%?30% Ketamine (alone or in combination)

 

Strength in topical spray

 

3?5% Ketamine (alone or in combination)

Strength in intranasal soultion

 

10?15% Ketamine / lidocaine 2?4%,

1 spray bilaterally PRN (0.1ml per spray,10?15mg)

Strength in Oral dosing

 

35?50mg TID as a baseline

AMPA Antagonist

 

Gabapentin

Carbamazepine

Phenytoin

Valproic Acid

 

Gabapentin

 

Mechanism of action

 

AMPA-Na+ channel blockers

Voltage Regulated Na+ & Ca++ Blockade

 

Use / Function

 

Chronic/ Neuropathic Pain

Helpful in burning, stabbing pains, feelings of electric shock

Topical could be used to wean patients off oral dosing

Great for trigger points

Indicated usage is for epileptic seizure control

Off label use neuropathic pain

Widely prescribed orally

 

Side effects at normal oral doses

 

Sedation

Dizziness

Ataxia

Fatigue

Weight gain

Flatulence

 

Transdermal application

 

Localized tissue concentration

Minimal systemic side effects, sedation and ataxia nonexistent

Start at 6% and titrate to patient response to 10%, used 12% very successfully

No conversion factors

 

 

NSAIDs

 

 

Ketoprofen

Diclofenac

Piroxicam

DMSO

Flurbiprofen

Ibuprofen

Indomethacin

Naproxen

 

Bioavailability of transdermal NSAID reported to be generally less than 5 –15 % in sites with lower absorption 

 

Mechanism of action

 

Blockade of Cox-1 and Cox-2 enzymes, these enzymes play a key role in making prostaglandins.

Decrease prostaglandin production ? less swelling and less pain

 

Uses / Function

 

Controlling inflammatory conditions such as RA, OA, tennis elbow, Soft Tissue Inflammation, Plantar Fasciitis

Effective for pain in acute injuries

 

Strength in transdermal cream

 

Ketoprofen 5 – 20%

Diclofenac 2 – 10%

Piroxicam 1 – 5%

DMSO 3 – 10%

Flurbiprofen 10%

Ibuprofen 5 – 30%

Indomethacin 5 – 20%

Naproxen 10 – 20%

 

 

 

Other APIs

Amitriptyline

 

Strengh in trasndermal cream: 2 – 10% (little benefit going beyond that)

Tri-cyclic anti?depressant

Oral side effects:

Sedation

Dry mouth

Sexual dysfunction

Off label as neuropathic pain and sleep modifier (orally)

?          

Nifedipine

 

Strength in trasndermal cream: 2?15%

Ca channel blocker, vasodilator ? great for increasing blood flow in conditions that are secondary to poor circulation such as diabetic neuropathy

Beneficial in both dermatome and trigger point creams

?          

Pentoxifylline

?                 

Strength in trasndermal cream: 2?5%

Irreversible alpha?agonist

increased blood flow

 

Clonidine

 

Strength in trasndermal cream: 0.1 – 0.3%

Alpha?2 Agonists

Beneficial in neuropathic pain 

Anti-hypertensive effects start showing at 0.4% and above

?          

Lidocaine, Tetracaine, Bupivacaine

 

AMPA?Na Channel blocker anesthetic

 

Opioids – strength in transdermal cream;

 

Morphine 1% (10mg/Gm)

Hydromorphone 0.3% (3mg/Gm)

Loperamide 2?7% (20?70mg/Gm)

[1] Reference: Sawynok J. Topical analgesics in neuropathic pain. Curr Pharm Des 2005; 11(23):2995?3004

[2] Reference: Heir, Gary DMD, et al. IJPC 2004; 8:337-343