Lec 16 Pain & Inflammation Flashcards Preview

Pharm Exam 2 > Lec 16 Pain & Inflammation > Flashcards

Flashcards in Lec 16 Pain & Inflammation Deck (21):

Aspirin-Like Analgesics

-selectively inhibit cyclooxygenase, blocking synthesis of prostaglandins and thromboxanes from arachadonic acid


COX1 vs COX2

COX1: constitutively expressed
COX2: induced by pro-inflammatory stimuli


Aspirin-Like Analgesics
(side-effects, 4)

-increased bleeding time
-gastic ulcers
-reyes syndrome (encephalopathy)
-hepatotoxicity (acetominaphen)


Increased Bleeding Time w/ Asprin

-aspirin irreversibly inhibits COX1/2
-in order for metabolites, especially thromboxanes to rebuild stores, have to resynthesize proteins, which takes time
-without thromboxanes, loose ability to properly and effectively clot


Opioid Analgesics
(vs. aspirin-like)

-much higher analgesic efficacy and more potent


Opioid Analgesics
(mechanism at sensory afferent fibers Ad, C)

-opioid binding to MOR on presynaptic blocks opening of VGCaC, prohibiting NT release
-binding to MOR on postsynaptic enhances K+ channel opening, hyper-polarizing the membrane and preventing transmission of any signal that may arrive
-overall attenuates afferent evoked excitation of the neuron


Opioid Analgesics
(mechanism at brain nuclei)

-binds to MOR, increasing descending inhibitory neuron signaling on pain transmission
-NTs: 5HT, NE


Opioid Receptor Signaling & Desensitization

-activation of receptor (GPCR) causes arrestin to bind which signals internalization of the receptor and loss of response to the agonist
-easy to build up tolerance


Narcan (Naloxone)

-addition of alkyl chain to agonist, forming an antagonist with high affinity for the MOR, blocking binding of the agonist
-antagonist has no efficacy, but has short duration of action


Opioid Analgesic Side Effects

-psychological/physical dependence (addictive)
-pinpoint pupils, sedation, constipation, respiratory depression (life threatening)


Local Anesthetics

-selective inhibition of nerve conduction by binding to a site within Na+ channel protein in nerve membrane, inhibiting the Na+ flux necessary for AP propagation
-injected directly into the site, often with an alpha-agonist for vasoconstriction. also safety to prevent build up in circulation (can have cardiac and CNS effects)
-along nodes of ranvier (myelinated) or evenly spaced (non-myelinated)


General Anesthetics

-nonselective loss of neuronal activity in the brain leading to analgesia and loss of consciousness
-inhaled vapors of gas, low therapeutic index
-potentiate inhibitory GABA synapses (Cl- channel open), inhibit excitatory ACh synapses (block ion pore)

inc oil:water =dec Panesthetic = inc potency = dec MAC (median alveolar conc, 50%)


Inflammatory Response Characteristics (4)

1. increased blood flow
2. exudation of vascular fluid and proteins into tissue (increased vascular permeability)
3. chemoattraction of leukocytes and migration of blood into tissue
4. proliferative phase w/ tissue degeneration and fibrosis


Mediators of Acute Inflammation (3)

1. Histamine
-vasodilation, vascular permeability
-from mast cells with tissue injury or antigen activation
2. Bradykinin
-vasodilation, vascular permeability, pain
-released with tissue injury
3. Prostaglandins & Leukotriens
-vasodilation, vascular permeability, chemotaxis, pain


Mediators of Chronic Inflammation (2)

[lead to fever, sleep, b- and t-cell activation, COX2 and lipoxygenase induction, fibroblast proliferation
1. IL-1, IL-2
-from macrophages, t-cells
-inflammation from b- and t-cell activation
2. TNF-a
-from macrophages
-inflammations via NF-kB singaling


(histamine receptors and antagonists)

1. H1 Receptor
-itching, vasodilation, vascular permeability
-histamine released by proinflammatory stimuli
-antagonist: antihistamines, antagonize vascular permeability and vasodilation at nerve endings (1st gen: sedating, 2nd gen: nonsedating)
2. H2 Receptor
-mediates gastric acid secretion
-antagonist: anti-ulcer drugs



[non-steroidal anti-inflammatory drugs]
-inhibit COX2, and thus PGs
ex. aspirin, ibuprofen, celecoxib (NOT acetaminophen)


Glucocorticoids & NF-kB
(anti-inflammatory and immunosuppressant effects)

1. antagonism of NF-kB
-increased translocation of gene for I-kB (inhibitor of NF-kB)
-nuclear binding by ligand-bound GC receptor
2. block release of arachidonic acid and its metabolites
-increased transcription of gene for lipocortin, which inhibits phospholipase two, thus
-decreasing COX2 transcription


Cytotoxic Drugs
(ex and mech)

ex. methotrexate
-inhibit cell replication, block t- and b-cell replication


T-cell Specific Inhibitors
(ex and mech)

ex. cyclosporine
bind cytosolic proteins that blood transcription required for t-cell activation, thus:
-block antigen-triggered t-cell activation
-inhibit cellular immunity
-prevent transplant rejection


TNF-a antagonists

monoclonal antibodies and receptor analogues that bind to the cytokine TNF-a
(cytokine antagonists, NOT receptor)