[Project Name] Post-Mortem

Pain & Analgesics

Dr.Kumarasingam

Pain is an unpleasant sensation occurring in varying degrees of severity as a consequence of injury, disease, or emotional disorderHyperalgesia increased the pain sensitivity to noxious stimuli.Allodynia - phenomenon characterised by painful sensations provoked by non-noxious stimuli, (e.g. touch), transmitted by fast conducting nerve fibers

Pathophysiology of Pain

Pain perceptions are,Peripheral componentThe central component

Afferent pathways

ImpulseSpinal cordBrain stemThalamusCentral structures of brainPain is processed.

*Transmission through the larger, myelinated A- delta fibers occurs much more quickly. A - fibers carry well-localized, sharp pain sensations

*The small unmyelinated C- neurons are responsible for the transmission of diffuse burning or aching sensations

Descending pathwayIts role: - inhibition of afferent pain signals

There they inhibit or block transmission of nociceptive signals at the level of dorsal horn

Nociceptive pain (stimuli from somatic and visceral structures)Neuropathic pain (stimuli abnormally processed by the nervous system) by injury, surgery & damaged nerves.

AnalgesicsPain relieving properties by acting in the CNS or on peripheral pain receptor without significantly affecting consciousness.Narcotic / opioidNon-narcotic / NSAIDs

Mild Pain 1-3/10

Moderate Pain 4-6/10

Severe Pain 7-10/10ASA, NSAIDSWeak opioids +/- non-opioidsPotent opioids +/-non-opioids

OpioidsOriginally derived from poppiesBody possesses endogenous opioidsOpiate Receptorsmu ()delta ()kappa ()NOP

Papaver somniferum

10

Pharmacology of Opioids1: inhibit transmission of pain2: respiratory depression, euphoria, constipation, physical dependence: inhibit transmission of pain: inhibit transmission of pain: autonomic effects, dysphoria, hallucinations

PHARMACOLOGICAL ACTIONCNSEndocrineCVSGITOtherBiliaryUrinaryBronchiUterus

Transducer mechanismsACk+Ca2+

Adverse effects

Classification of NSAIDs1.Nonselective Irreversible inhibitors of COX Aspirin, Sodium salicylate,Sulfasalazine, Olsalazine, Methyl salicylate.2.Nonselective reversible inhibitors of COX Oxyphenbutazone, Indomethacin, Sulindac, Ibuprofen, Flurbiprofen, Naproxen, Mefenamic acid, Tenoxicam, Piroxicam, ketorolac, Tolmetin, Oxaprozin, Diflunisal, Diclofenac, Aceclofenac.3.Weak inhibitor of COX-1< COX-2 plus other modes of Anti-inflammatory action. Nimesulide

4.Preferential COX-2 inhibitors Meloxicam, Etodolac, Nabumetone5.Selective COX-2 inhibitors Rofecoxib, Celecoxib, Valdecoxib, Etoricoxib, Parecoxib6.COX-3 inhibitor or Reversible inhibitors of Hypothalamic COX-1 Paracetamol, Metamizol7.NSAIDs Which do not inhibit PG synthesis Nefopam , Diacerein.

LeukotrienesProstaglandins, thromboxanesCyclo-oxygenaseLipoxygenaseMembrane phospholipidsArachidonic AcidPhospholipase A2biosynthesis of Prostaglandin

PHARMACOLOGICAL ACTIONAnalgesicsAntipyreticAnti-inflammatoryPlatelet aggregationDysmenorrhoeaClosure of DAOthersColonic CA- FCPPre eclampsia- Niacin Alzheimer - Cataract

Adverse effects

Gastric mucosal damageAcid-base balanceBleeding tendencyHypersensitivityRenal

COX-2 InhibitorsSelectively inhibit cyclooxygenase-2less GI irritation; less platelet effectsother side effects similar to NSAIDsRole: patients with low cardiovascular risk who require NSAID therapy & are at increased risk for GI toxicity

21