Lecture 11 - pain and inflammation Flashcards
what is pain ?
“ an unpleasant sensory and emotional experience associated with actual or potential tissue damage”
often tired as acute or chronic >3 months
acute pain is often as a result of inflammation or damage to tissues and. nerves
Chronic pain is more likely to be influenced by central nervous system mediation
what are the 3 pain classifications?
- physiological pain. also called nociceptive pain. caused by stimulation of pain receptors by tissues damage eg in inflammation
- Pathological pain. also called neuropathic pain. caused by damage of nerve pathway
- psychologic pain. in depression and anxiety. difficult to differentiate whether secondary to or actual cause of pain
descried nociceptive pain
Injury: When there is an injury, various substances are released from the damaged tissue.
Substances Released: These include:
Bradykinincauases vasolidialtion leading to inflammation and pain
Prostaglandins: Lipid compounds that intensify the pain sensation and inflammatory resposne
.
Serotonin (5-HT): A neurotransmitter that can contribute to pain signals and inflammation.
Histamine: Released from mast cells, causing vasodilation and increased blood flow, which contributes to inflammation and pain.
Nerve Growth Factor (NGF): A molecule that may play a role in the sensitization of pain pathways.
ATP: Serves as an energy molecule but can also act as a neurotransmitter in the pain pathway.
Hydrogen ions (H+): The accumulation of which can lead to acidosis and associated pain.
Edema: The accumulation of fluid in tissues, leading to swelling, is often a consequence of inflammation and contributes to the pain sensation.
Neuronal Activation: The primary afferent neuron, which carries the pain signal, is activated by these substances.
Neuropeptides Released: In response to the activation, the neuron releases neuropeptides like Substance P and Calcitonin Gene-Related Peptide (CGRP).
Signal Transmission: The neuron then transmits the signal towards the dorsal horn of the spinal cord, where the pain signal is processed and relayed to the brain for the perception of pain.
what are the pain pathways in the brain and meds site of action
brain pain - paracetamol, morphine-like drugs, neuropathic pain drugs
spoil cord - morphine-like drugs and neuropathic pain drugs
peripheral nerve injury - bone, skin, other tissues; morphine-like drugs and anti-inflammatory drugs
what is the time to effect of taking NSAIDS?
Pain relief starts soon after taking the first dose
Full analgesic effect should normally be obtained within a week
Anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks.
If appropriate responses are not obtained within these times, try another NSAID
About 60% of patients will respond to any NSAID
what are the choice of NSAIDS ?
Ibuprofen - anti-inflammatory, analgesic, and antipyretic properties. Fewer side-effects than other non-selective NSAIDs but its anti-inflammatory properties are weaker. Poor choice in gout
Naproxen is one of the first choices because it combines good efficacy with a low incidence of side-effects (but more than ibuprofen).
Diclofenac sodium are similar in efficacy to naproxen – higher CV risk
The selective inhibitors of cyclo-oxygenase-2, etoricoxib and celecoxib, are as effective as non-selective NSAIDs such as diclofenac sodium and naproxen.
Consider topicals
describe Gi toxicity associated with NSAIDS
When it comes to GI adverse effects not all NSAIDs are equal.
Ibuprofen (≤400mg tds) has a placebo like G.I. adverse event rate
For all the others and high dose ibuprofen the risk ratio increases significantly (generally in the order of 5x)
PPIs are the most effective strategy for preventing ulcers
COX II inhibitors are slightly safer, but far more expensive, therefore are not predominantly used despite this safety difference
how do nasals and acoocited ends cause gu toxicity
nsaids inhibit PGE2 and PG12 leading to less gastric mcuus and more acid related damage
H2 antagonists inhibit the action of h2 receptors on parietal cells reducing acid secretion
H. pylori Treatment: Helicobacter pylori infection is treated with a combination of bismuth, metronidazole, tetracycline, clarithromycin, and amoxicillin to reduce GI toxicity and ulcers.
describe cardiac toxicity associated with NSAIDs
ALL NSAIDs, except Naproxen, have consistently shown a tendency towards higher cardiovascular event rates (heart attacks and strokes, and heart failure exacerbations)
This must be contextualised for an individuals risk and the patient informed and counselled on this
No drugs are totally safe, you should only be deploying an NSAID to provide effective relief for day-to-day symptoms, therefore this small risk should not matter greatly
what are other side effects of NSAIDs?
Kidneys
prostaglandins - mainly prostacyclins, PGE2, PGD2 - act as vasodilators in the afferent arteriole, increasing renal perfusion, with distribution of the cortex flow to the nephrons in the renal medullary region.
Lungs
Pregnancy
ED
descried different types of opioids
mild to moderate
Codeine
Dihydrocodeine
Tramadol
strong
Morphine
Buprenorphine
Diamorphine
Alfentanil
Oxycodone
Methadone
Hydromorphone
what are adjuvant agents used in
Tricyclic anti-depressants, anti-epileptics deployed if there is a peripheral neuropathic component to the pain or a central nervous system component to the pain or its modulation
Amitriptyline is very commonly used, and can be deployed at doses of 10 -50mg daily
Gabapentin is the next most common and is slowly titrated, sometimes up to high doses
Steroids are particularly useful as adjuvant therapy for metastatic bone pain, neuropathic pain, and visceral pain
Irritant creams and patches are often tried but rarely bring success (capsaicin)
Use of SNRI’s, lignocaine patches, alpha blockers and cannibinoids is reserved for specialist use.
