Opiates & Analgesic Medications - Basic Science

Introduction

Indications & Special Consideratoins

Pediatric patients
- follow specific dosing guidelines for children which have been tested and recommended by the American Academy of Pediatrics
Geriatric patients
- may have increased sensitivity to opioid pain medicines with higher rates of side effects
  - decreased total body mass with increased body fat percentage
  - potentially decreased hepatic and renal function
Obese patients
- achieving adequate peri-operative pain control in the morbidly obese can be difficult
- the most accurate method to control pain and avoid respiratory depression should include patient controlled analgesia (PCA), which is based on the patient's ideal weight
- intramuscular injections should be avoided due to the difficulty of avoiding injection into muscle and the poor vascularity of the subcutaneous adipose tissue
Red-haired patients
- often require more anaesthesia to maintain MAC levels and higher opioid dosages postoperatively compared to other hair types
Chronic regional pain syndrome
- Vitamin C has been shown to possibly prevent CRPS specifically related to distal radius fractures

Acetaminophen

Mechanism
- not fully understood
- inhibits prostaglandin synthesis
- minimal antinflammatory effects
As effective for pain control as aspirin
Toxicity
- overdose leads to hepatic disfunction
- contraindicated in the setting of pre-existing hepatic dysfunction

NSAIDs

Local anesthetics

Mechanism
- decrease transduction of pain
- interfere with nerve conduction to provide a reversible loss of sensation in a specific location
  - affects the depolarization phase of action potentials (cells fail to depolarize enough to fire after excitation leading to a blocked action potential)
Examples
- amide family
  - lidocaine (Xylocaine)
  - bupivacaine (Marcaine)
- esters of p-aminobenzoic acid
  - procaine (Novocain)
  - butethamine (Monocaine)
- esters of meta-aminobenzoic acid
  - cyclomethycaine (Surfacaine)
  - metabutoxycaine (Primacaine)
- esters of benzoic acid
  - cocaine
  - ethyl aminobenzoate (Benzocaine)
Adverse effects
- FDA warning on the administration of continuous intra-articular infusion of local anesthetics for pain control
  - Some patients have been noted to have chondrolysis following infusion

Opiates

Overview
- useful in chronic nociceptive pain
Mechanism
- perispinal method affects modulation of pain
- systemic opiates change the perception and modulation of pain
Administration
- oral, IV, intraspinal
- oral administration preferred (more convenient and less costly)
  - bony procedures require more analgesia than soft tissue procedures
- patient compliance can improve with long-acting preparations that providue more uniform serum drug levels
- implantable systems are available for intrathecal administration
Prescription dosing guide for upper extremity surgery
- no narcotics
  - trigger finger release, nonop Dupuytren's release, small lumps/bumps
- 10 narcotic tablets
  - mucous cyst, carpal tunnel, deQuervain’s, Dupuytren’s releases and small joint fusion
- 20 narcotic tablets
  - wrist ganglion cysts, hand fracture ORIF, LRTI and tendon transfers
- 40 narcotic tablets
  - large trauma, wrist fusion, open carpal surgery and DRUJ reconstruction
Chronic use
- addiction occurs in a minority of patients
- chronic opiates should be prescribed by pain management specialists
- written contracts should be obtained
- prescriptions should always be refilled in person

Methadone

Synthetic diphenylheptaine-derivative opioid receptor agonist
High bioavailability (three times as much as morphine), effective, and inexpensive
Metabolism
- cytochrome P450 system
Rapid distribution phase (2-3 hours) and prolonged elimination phase (15-60 hours)
Caution
- can accumulate to high levels with repeated dosing
- rates of elimination vary considerably
- risk of respiratory depression, cardiac toxicity (torsades de pointes)
- consult with a qualified pain specialist when prescribing for the first-time

GABA agents

Agents
- Pregabalin (Lyrica)
- Gabapentin (Neurontin)
Mechanism
- decrease transduction of pain
  - reduce hyper-excitability of voltage dependent Ca2+ channels in activated neurons.
Gabapentin is an anticonvulsant also used to treat neuropathic pain
- binds presynaptic calcium channels to inhibit release of neurotransmitters
Efficacy
- evidence of effectiveness primarily for postherpetic neuralgia, diabetic nueropathy, and fibromyalgia
- little evidence for other uses, though often prescribed for other forms of chronic neuropathic pain (such as complex regional pain syndrome, CRPS)
- gabapentin has been shown to be as effective and less expensive than pregabalin
Discontinuation requires a tapering dose

Muscle relaxants

Overview
- Useful to treat pain secondary to muscle spasms
Agents
- Cyclobenzaprine (Flexeril)
  - mechnism of action not fully understood
  - centrally acting
  - potentiates norepinephrine and binds serotonin receptors
Use
- may decrease pain during first two weeks after an injury
- no proven benefit after first two weeks
- may be effective for fibromyalgia
- not effective to reduce spasticity secondary to neuromuscular disorders
Toxicity
- overdose rare
- may interact with other substances
  - MAOIs
  - alcohol

Adjuvant agents