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Holistic Pain Management

Focus on Codeine

Jacques Snyman (MD)

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DISCLAIMER

The views and opinions expressed in and during this presentation are those of the author and do not necessarily reflect the official policy or position of the South African Health Products Regulatory Authority (SAHPRA) or the Codeine Care Initiative (CCI). Any content provided by the presenter are of their opinion and are not intended to malign any religion, ethnic group, club, organization, company, individual or anyone or anything.

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Pain? �The current IASP definition of pain “An unpleasant sensory and emotional experience �associated with actual or potential tissue damage, or described in terms of such damage”

It is an unpleasant feeling that can range from mild, localized discomfort to agony. Pain has both physical and emotional components. – Clearly a subjective and individual experience!

Pain. 2020 September 01; 161(9): 1976–1982. doi:10.1097/j.pain.0000000000001939

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Strategies in pain management

Pain management is determined by the cause and perception of pain i.e.

Origin

Musculoskeletal – bone, joints and muscle
Organ e.g. abdomen
Undefined
Inflammatory

Time

Chronic
Acute

Intensity

Severe to mild

This often determines choice of medicine and or combination used

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Selection of Analgesics

NSAIDS

Non – selective COX inhibitors
Selective COX₂

Opioids based on perceived potency and side effect profile

Strong
Medium
Mild

Combination Analgesics

Opioid plus NSAID

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Common Pain Flow charts

Clinical Medicine and Research 2007;5; 19-34

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Codeine only beneficial in combination

High Individual Variability and response needs titration

NNT indicative of 50% effect

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Opioid Receptors and Pain

Mu, Kappa, Delta and Sigma
Not all associated with pain relief
Dysphoria associated with Sigma
While Kappa associated with pain relief at spinal level without euphoria – central dysphoria
Delta – peripheral analgesia
Mu1 – Brain – analgesia and euphoria
Mu2 – Brain = GIT – analgesia, Resp depression and constipation

Schedule 2 medicines may only be sold under personal supervision of a pharmacist and may not be kept in an open shop. Every sale of a schedule 2 medicine must be recorded in a prescription book, thus ensuring the pharmacy has details of patients to whom the medicines are sold.

Schedule 2 medicines are not to be sold to anyone younger than 12, unless there is a prescription issued by a registered medical practitioner.

She adds: “Furthermore, the Medicine Act has scheduling regulations, which are used to ‘schedule’ a medicine when registered with the SAHPRA. In these regulations, products containing codeine are allowed to be sold as schedule 2 medicines in the permissible quantities.”

Cough syrup with codeine is sold in 100ml bottles. When more than 100ml is sold, it is no longer considered a schedule 2 medicine and the higher volume may not be sold without a prescription. This, in effect, implies that a pharmacy may not sell more than one bottle of 100ml cough syrup with codeine to a patient without a valid prescription,” Singh says.

influenza and the common cold. As healthcare professionals we have to consider the treatment of the whole person, taking into account mental and social factors, rather than just the symptoms of an illness.

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Opioid Receptor Subtypes

Peripheral effect

Sigma

Dysphoria and anxiety

Pain is the antidote for opioid effects and side effects and as pain subsides unwanted effects increase

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Codeine: Focus

Natural Product – alkaloid in Poppy plant
Methyl-morphine = codeine i.e. replacing the OH group with a OCH₃ group
Binding to receptor: phenyl –N-methyl piperidine part of molecule
Low potency relative to morphine
CYP450 enzymes in liver metabolises to active metabolites – variable in individuals (demethylation in liver and brain to morphine)
Presynaptic binding to opioid receptors

Stimulation results in reduced impulse conduction (decrease cAMP, closing voltage gated Calcium and opening Potassium channels = reduction in release of excitatory transmitters)

High potential for histamine release compared to other opioids

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Codeine: Focus

Relieves dull ill-defined pain
Paleospinothalamic pain pathway – substantia gelatinosa, amygdala and hypothalamus

Limbic system involvement - emotional behaviour effects

The resultant effect is not so much analgesia but the creation of indifference to painful stimuli
The euphoric effect drives the abuse potential

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Summary Notes on Codeine

Codeine is a low potency opioid with little if any benefit when dosed as single analgesic
Combination with NSAID and or Paracetamol demonstrates additive effect – lower NNT
Short term use low abuse potential
Risk of abuse increase with longer term use and when used in inappropriate high dosages
If pain is not adequately controlled with combination therapy – reassessment is required, and another product should be used

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Thank You