M6 L2 Non-narcotic Analgesics Flashcards
COX-1
widely distributed enzyme
- has all effects
COX-2
limited distribution enzyme
(macrophages and at sites of inflammation)
- for inflammatory processes
what does “COX” stand for
cyclooxygenase enzyme
COX-3
mainly in brain
3 isoenzymes of cyclooxygenase enzyme
COX-1, COX-2, COX-3
3 types of antipyretics
- non-steroidal anti-inflammatory drugs (NSAIDS)
- Acetaminophen (tylenol)
- Selective COX-2 inhibitors
NSAIDS examples
aspirin, ibuprofen
example of selective COX-2 inhibitor
celecoxib
how does acetylsalicylic acid (aspirin) work
- irreversible inhibition of COX -1 and -2 (decreases production of prostaglandins and thromboxanes
- other NSAIDs cause reversible inhibition of COX enzyme
pharmacological action of acetylsalicylic acid
- analgesic
- antipyretic
- antiplatelet
- anti inflammatory (high dose)
NSAIDS in general are used for…
mild to moderate pain (less effective than opioids)
- do this through inhibition of PG’s synthesis
1. peripheral action: prevents sensation of pain-transmitting nerve fibres to chem mediators released by tissue injury
2. central action: inhibits action of transmitters involved in pain pathways
- no tolerance, addiction, or dependence
what do NSAIDs do for fever
by inhibition of PG’s synthesis
- reset temp center in hypothalamus
- no effect on normal body temp
what do NSAIDS do on thromboembolic disease
- through antiplatelet effect
- treatment or prophylaxis
how do NSAIDS help inflammation
need a high dose
- rheumatic fever
- rheumatoid arthritis
- gout (high dose)
adverse effects of NSAIDs
- bleedings (commonly GI)
- GI upset (when you block the prostaglandins this can affect the mucosa of the stomach)
- bronchial asthma
- tinnitus (ringing of ears)
- acid base imbalance
- chronic nephritis
- hypersensitivity
- reyes syndrome
adverse effects of aspirin
- swelling of eyes, face, lips, tongue, or throat
- wheezing, diff breathing, hoarseness, fast breathing
- tachycardia
- cold, clammy skin
- hives/rash
- ear ringing
- bloody vomit
- bleeding
contraindications of using aspirin and other NSAIDS
- bleeding tendencies
- peptic ulcer
- bronchial asthma
- allergy to aspirin or other NSAIDs
- chronic renal disease
- children or adolescents w fever and viral infection
absorption, protein bound, metabolism, and excretion of aspirin
absorption: stomach - small intestine
protein bound: 50-80%
metabolism: liver (80%)
excretion: kidney
acute aspirin toxicity manifestations
- vomiting, abdominal pain
- tinnitus
- hypoglycemia, hypokalemia
- hyperthermia, hyperventilation
- metabolic acidosis, respiratory alkalosis
- confusion, seizures, coma
- pulmonary edema, hypotension, CV collapse } cause death
acute aspirin toxicity treatment
- no specific antidote
- provide supportive measures: ABC’s, fluids and electrolytes, restore pH, glucose
- alkalinization of urine
Commonly used other NSAIDs besides aspirin
- ibuprofen (advil) } OTC
- naproxen (aleve) } OTC
- indomethacin
- ketorolac
- diclofenac (can be linked to heart attack and stroke risk)
acetaminophen
(not an acid, not an NSAID)
- mech of action is not fully understood (inhibits COX enzyme…but has other unknown actions ?? COX-3 inhibition
- no anti-inflammatory or anti-platelet action
- safe if you have a bleeding tendency, or pregnancy
- absorption: GIT
- metabolism: liver
- excretion: kidney
adverse effects/pros of acetaminophen
- safe if taken in proper dose
- safe in preg
- causes liver and renal damage possibly
end products of acetaminophen metabolism
NAPQI: N-acetyl-p-benzoquinoneimine (bad for liver)
GSH: glutathione
acute acetaminophen toxicity
- commonly due to suicide
- acute liver damage (may be fatal)
- antidote: N-acetylcysteine (NAC)
- supportive measures
- +/- charcoal ingestion
- +/- gastric lavage
N-acetylcysteine (NAC)
- antidote of acetaminophen
- source of glutathione -> decreased NAPQI -> decreased liver damage
- most effective within 8 hrs of exposure
- oral or IV
COX-2 inhibitors
- selective inhibitors of COX-2 isozyme
- less COX-1 induced side effects: asthma, gastric irritation and bleeding, more theoretical!!
- more risk of thrombosis and cardiovascular morbidity and mortality
- ex: celecoxib
