LAB_Anti-Inflam and Analgesics Flashcards
a response intended to eliminate the initial cause of cell injury,
remove the damaged tissue, and generate new tissue
Inflammation
Cardinal signs of inflammation:
- rubor (redness)
- tumor (swelling)
- calor (heat)
- dolor (pain)
- functio laesa (loss of function)
Materials needed for inflammatory activity
- Plethysmometer
- Tuberculin syringes
- Intubation needles
- Individual Observation Cages
- 24 or 26 gauge 1” syringes
Anti-inflamm drugs
Diclofenac
Carrageenan
It is a highly sensitive and reproducible test for nonsteroidal antiinflammatory drugs and has long been established as a valid model to
study new anti-inflammatory drugs
Carrageenan-Induced Paw Edema
The development of edema induced by carrageenan injection causes
an _____ and ______ inflammatory response
acute and local
In the early phase (0-1h), ________, ________, and _________ are
the first mediators involved
histamine, serotonin, and bradykinin
In the second phase - ________ and various _______ such as
IL-1β, IL-6, IL-10, and TNF-α are implicated
Prostaglandins ; cytokines
Used to suppress the symptoms of inflammation and relieve pain
(analgesic action) and fever (antipyretic action)
Non-Steroidal Anti-inflammatory Drugs
(NSAIDS)
Anti-inflammatory effect of nsaids:
inhibition of COX-1 and COX-2
NSAID that inhibits COX-1 and COX-2
Aspirin
Inhibit COX-2>COX-1
COX-2 selective agents
_____ reduce the inflammatory response and pain but not the cytoprotective action of
prostaglandins in the stomach
COX-2
Analgesic effect of NSAIDs
Inhibition of PGE2 and PGI2
: inhibition of production of prostaglandins induced by IL1 and IL-6 in the hypothalamus and the ‘resetting’ of the thermoregulatory
system leading to vasodilation and increased heat loss
Antipyretic effect of NSAIDs
First-line drugs to arrest inflammation and accompanying pain of
rheumatic and non-rheumatic diseases
NSAIDs
NSAIDs alleviate __________ pain
mild-moderate
T/F: NSAIDs reduce elevated body temperature
T
Ibuprofen, fenoprofen, ketoprofen flurbiprofen, oxaprozin, naproxen
Propionic acid derivatives
Indomethacin, tolemtin, sulindac, ketorolac
Acetic acid derivatives
Piroxicam, tenoxicam
Oxicam
Celecoxib, parecoxib etoricoxib
Selective Cox-2 Inhibitors
better tolerated than ASA
Ibuprofen
Analgesic, antipyretic, anti-inflammatory efficacy less than ASA
Ibuprofen
T/F: Ibuprofen is well-absorbed, >90% bound to plasma proteins and cross BBB
T
Ibuprofen is metabolized in the ______, excreted in ________
liver; bile and kidneys
Ibuprofen dosage forms
Oral, parenteral, topical use (gel, cream)
available as patch, capsule, tablet
Ketoprofen
used in the eye for anti-inflammatory property
Flurbiprofen
longer acting
Naproxen
Propionic Acid ADR
nausea, vomiting, GI discomfort, fluid retention
This Acetic Acid derivative has analgesic property to relieve postoperative pain
Ketorolac
Acetic Acid derivative that is a potent anti-inflammatory, agent, antipyretic,
analgesic effect
Indomethacin
ADR of Indomethacin:
headache, dizziness, ataxia, confusion, hallucinations, psychosis,
hypersensitivity reaction
CI of Indomethacin
renal failure, thrombocytopenia, elevated bilirubin
used as closure of PDA, pain in laminectomy, eye drops for inflammation
Indomethacin
Indomethacin _________ action of furosemide, thiazides, beta blockers, and ACE
inhibitors by salt and water retention ; ____________ bleeding with warfarin
decreases; increases
weaker actions than others but less toxic, not antagonize
diuretic and antihypertensive actions of thiazides
Sulindac
are more toxic, contraindicated in children, and not
to be used for more than one week
Mefenamic Acid
Mefenamic Acid ADR
GI side effects (diarrhea)
used in analgesic in myalgias, dysmenorrhea
Mefenamic Acid
good anti-inflammatory activity, more potent,
poorer analgesic and antipyretic activity
Phenylbutazone
less likely to cause agranulocytosis
Azapropazone
poor anti-inflammatory agent
Metamizol
good anti-inflammatory, analgesic and antipyretic
activit
Piroxicam
similar to Metamizol
Propiphenazone
significant effect on RA and OA
Nabumetone
less gastric irritation than piroxicam; preferentially
binds to COX-2
Meloxicam
preferentially inhibits COX-2, antihistaminic and antallergic properties
Nimesulide
Acetic acid derivative that is relatively
nonselective COX inhibitor
DICLOFENAC
DICLOFENAC has a half life of _______;
1.9 to 2.3 hours
Co-administration of
____________ may increase the toxicity of diclofenac.
voriconazole
Diclofenac ADE
GI ulceration
Elevation of serum aminotransferases
Selective COX-2 Inhibitors prototype
Celecoxib
Celecoxib can cause
HTN and edema
ADR of Selective Cox 2 inhibitors
increase risk for cardiovascular and cerebrovascular thrombotic
events -> increase risk for MI and stroke
highly selective for COX-2 and longer acting (given once a day)
Etoricoxib
Materials included in analgesic activity
Hot plate analgesia apparatus
* Weighing scale
* Stopwatches
* Tuberculin syringe
a condition of enhanced sensitivity to painful stimu
Hyperalgesia
Mice treated with test compound -> ______________ latencies to respond
to thermal stimulation compared to mice treated with vehicle.
increased
Pharmacological test for evaluating the analgesic potential of test
compounds
Hot Plate Method
Acts peripherally (inhibit COX1 or
COX2)
Non- Opioid Analgesics
Has ceiling effect
Non- Opioid Analgesics
Used as analgesic, anti-inflammatory,
antipyretic and antiplatelet
Non- Opioid Analgesics
Interact with mu, delta, kappa opioid
receptors, act mostly on SC and brain
Opioid Analgesics
May have a capacity for dependence,
withdrawal and abuse
Opioid Analgesics
Used as analgesic
Opioid Analgesics
Does not have analgesic ceiling
effect; dose escalation is limited by
incidence and severity of ADRS
Opioid Analgesics
Used in moderate to severe pain,
neuropathic pain
Opioid Analgesics
SE: constipation, nausea, vomiting,
respiratory depression, urinary
retention, withdrawal symptoms
Opioid Analgesics
SE: GI, renal, cardiovascular (see
previous slides)
Non- Opioid Analgesics
acute and chronic inflammatory
diseases (eg. RA, OA, gout)
Non- Opioid Analgesics
relieves pain without loss of consciousness
Analgesia
T/F: Analgesia alters both perception and reaction to pain
T
presynaptic inhibition of the reuptake of serotonin
and NE in pain inhibitory pathways
Antidepressants
: deplete local neurons of Substance P, which is required in
the transmission of nociceptive inpu
Capsaicin
lowering NT release or reducing neuronal firing
Anticonvulsants
clock nerve signals that send the feeling of pain
from site of injury to the brain
Topical lidocaine