Pharmacology of pain

Dr. Turyahikayo jack

Palliative care unit

Clinical Terms For The Sensory Disturbances Associated With Pain • ANALGESIA: absence of pain in response to stimulation

which would normally be painful.

• ACUTE PAIN: usually due to a definable acute injury or illness.

• BREAKTHROUGH PAIN: a transitory exacerbation of pain that occurs on background of otherwise stable and controlled pain.

• CHRONIC PAIN: results from a chronic pathological process.

Pocket guide for Pain management in Africa

Clinical Terms For The Sensory Disturbances Associated With Pain • INCIDENT PAIN: pain that occurs in certain circumstances

e.g. during movement

• NEURALGIA: pain in the distribution of a nerve

• NEUROPATHY: a disturbance of function of pathological change in a nerve

• NEUROPATHIC PAIN: pain which is transmitted by a damaged nervous system; partially opioid sensitive

• NOCICEPTOR: a receptor preferentially sensitive to a noxious stimulus

Clinical Terms For The Sensory Disturbances Associated With Pain

• Dysesthesia – An unpleasant abnormal sensation, whether spontaneous or evoked.

• Allodynia – Pain due to a stimulus which does not normally provoke pain, such as pain caused by light touch to the skin

• Hyperalgesia – An increased response to a stimulus which is normally painful

• Hyperesthesia - Increased sensitivity to stimulation, excluding the special senses. Hyperesthesia includes both allodynia and hyperalgesia, but the more specific terms should be used wherever they are applicable.

Aims of chronic pain mgt

• Prompt relief of pain

• Prevention of pain recurrence

Introduction

• Optimal pain management includes drug therapy with the analgesic drugs in addition to non-pharmacological methods and addressing non-physical pain.

• Types of analgesics

• Non-opioids

• Opioids

• Adjuvants

Principles of analgesia

Correct use of analgesics should be based on the following principles;

-By the mouth

By the ladder

By the clock

cotd

-By the individual

-Use of adjuvants

By the clock

PAIN

SIDE EFFECTS: Drowsiness

PRNToo HighToo High By the clockMorphine dose

• Expert committee by the cancer and palliative care unit of WHO proposed a structured approach to drug selection for cancer pain known as the ‘WHO analgesic ladder’

• Controls pain in 70-90%

• The choice of analgesic depends on;• Type of pain i.e nociceptive vs neuropathic

pain. • Severity of pain use step 1 for mild pain , step 3

for severe pain. If you start on lower step and pain doesn’t improve go up the ladder

• Co morbidities• Reassess pain always to find out if you can go

up or down the ladder. • Treat underlying cause (eg, radiation for a

neoplasm, antibiotics, antifungal for opportunistic infections)

Pharmacology of pain

04/11/23

Nociception

Receptor

Spinal Cord

Thalamus

Cortex

• Paracetamol (step 1 analgesic)

Centrally acting non-opioid,it inhibits cyclo-oxygenase in brain and reduces production of prostanoids.

Max dose /day= 4g/day

Increased risk of hepatotoxicity in;

• old age• Poor nut.status• Fasting • Chronic alcohol use• Conc. Use of enzyme

inducing drugs

• Paracetamol (step 1 analgesic)

Centrally acting non-opioid,it inhibits cyclo-oxygenase in brain and reduces production of prostanoids.

Max dose /day= 4g/day

Increased risk of hepatotoxicity in;

• old age• Poor nut.status• Fasting • Chronic alcohol use• Conc. Use of enzyme

inducing drugs

NSAIDS

Examples of NSAIDS• Ibuprofen 400mg 8 hrly max 2.4 g/d• Diclofenac 25-50mg 8hourly max 150mg/d• Indications :As a group, NSAIDs are of benefit for pain

due to inflammation and bone pain. They also lower fever.

Side effects;• ankle oedema, renal failure, can injure the gastric

mucosa and cause platelet dysfunction • Avoid in above conditions, liver disease and bleeding.

Use with Caution in elderly. Avoid aspirin use in asthmatics

Opioids

Examples; codeine, tramadol,morphine ,fentanylMorphine pharmacology• If Taken orally, absorbed upper small bowel, under goes

first pass metabolism in liver and metabolized into M3G and M6G.Half life 2-3 hrs, duration of analgesia 4-6 hrs.

• Excreted through the kidneys• Agonist at opioid receptors (μ,κ,δ)found in the brain and

spinal cord. Analgesia is mainly mediated through the μ receptors.• Opioid receptors are found pre and post synaptically with

the former dominating and when opioids bind on the former they inhibit the release of neuro transmitters.

PlaPlasmsma a CoConcencentrntratiationon

po / prpo / pr

IVIVIVIV

SC/IMSC/IM

0Half life time

Morphine continued

Side effects• Constipation- • Nausea and vomiting• Drowsiness- may occur in

the first few days, if it does not improve after about 3 days cut down on dose of morphine.

• Itching- less common

Toxicity and over dose• Signs of morphine toxicity

and over dose include;• Drowsiness that does not

improve• Confusion• Hallucinations• Myoclonus (sudden

jerking of the limbs)• Respiratory depression

(slow breathing rate)• Pin point pupils

Myths about oral morphine

• Respiratory depression;

• This is not common if morphine doses are titrated against pain as pain is a physiological antagonist to respiratory depression.

Tolerance

“If I take it now, what will I take when I really need it?”

• The need for increasing doses of morphine is usually related to disease progression.

• Reassure the patients there is adequate scope to treat more severe pain if it occurs. There is no maximum dose of morphine.

Addiction

– Differentiate addiction from physical dependence which is a normal physiological response to chronic opioid use

– Psychological dependence

-Compulsive use

-Loss of control over drugs

-Loss of interest in pleasurable activities

…addiction

• Consider– substance use (true addiction)– pseudo-addiction (under treatment of

pain)– behavioral / family / psychological

disorder

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• Morphine hastens death;

• morphine can be used for many months and years and is compatible with a normal life style. It can only lead to death by causing respiratory depression if given not correctly and not orally.

Pain not very responsive to opioids

• 1.Neuropathic pain

• 2. Bone pain

Adjuvant analgesia

• These are drugs which were not designed as analgesics but help in some types of pain along side standard analgesics. They include;

• Antidepressants• Anticonvulsants• Corticosteroids• Antispasmodics/smooth muscle relaxants• Skeletal Muscle relaxants • bisphosphonates

corticosteroids

• Dexamethasone commonly used• Indications; bone pain, neuropathic pain from

infiltration or compression of neuronal structures, raised ICP, athralgia, pain due to obstruction of a hollow viscus.

• Mechanism of action; ↓peritumoral oedema ,may reduced concentrations of PGs and LKs

• Metabolized by cyt system. Can increase metabolism of cbz. Phenytoin increases levels of dexamethasone

antidepressants

• Amitriptilline, imipramine (start with12.5-25 mg nocte)

• Indication: neuropathic pain • Mode of action: facilitate one or both of the 2

descending spinal inhibitory pathways by blocking presynaptic re-uptake of serotonin or noradrenaline

• Sideffects; dry mouth, drowsiness,constipation,cardiac toxicity, othostatic hypotension.

• Use with caution in elderly and cardiac disease

anticonvulsants

• Indication: neuropathic pain• CBZ 100-200mg bd• Phenytoin 300mg od• CBZ induces liver enzymes that are responsible

for its metabolism• Phenytoin is a hepatic enzyme inducer • Mechanism of action; suppress paroxysmal

discharges and their spread from site of origin, and reduce neuronal hyper excitability.

• Side effects: sedation, dizziness,unsteadiness

Smooth muscle relaxants

• Hyoscine butylbromide commonly used

• Indication; colicky pain

• Mode of action: in the gut reduces the propulsive and non-propulsive gut motility and decrease intraluminal secretions.

• Side effects: anticholinergic effects

Skeletal muscle relaxants

• Indication; muscle spasms

• Drug ; baclofen

• Mode of action: agonist at the gamma aminobutyric acid receptor

• Sideeffects: sedation,drowsiness,nausea,hypotonia.

• diazepam

Bisphosphonates

• Indication: bone pain not responding to NSAIDs or radiotherapy

• Drug; pamidromate sodium

• Mode of action: reduce osteoclastic activity in bone.

The message …

• between the painful part and the patient’s experience of pain lies the nervous system• the nervous system is a learning system• pain is more than a nerve activation

• Thank you for listening