ICL 3.6: Principles of PNS Pharmacology Flashcards
what are NSAIDs?
NSAIDs = Non-Steroidal anti-Inflammatory Drugs
the nomenclature NSAID was given to this class of drug to distinguish them from the anti-inflammatory activity of glucocorticoids
NSAIDs are primarily used to treat inflammation in addition to mild or moderate pain and fever
what are the 3 therapeutic effects of NSAIDs?
- regulate body temperature
- reduce inflammation
- reduce pain
what is the immune response to tissue damage?
tissue damage is accompanied by the release of several biochemical mediators such as histamine, bradykinin, platelet activating factor, and a group of lipid materials known as prostaglandins and leukotrienes
histamine, bradykinin, and leukotrienes cause the swelling and redness of the inflamed area due to vasodilatation and increased capillary permeability
prostaglandins, on the other hand, increase tissue sensitivity to pain and cause elevation of body temperature
so NSAIDs are used in the treatment of inflammation, pain and fever!
what musculoskeletal disorders are NSAIDs used to treat?
- rheumatoid arthritis
- osteoarthritis
NSAIDs provide symptomatic relief from pain and inflammation
how do NSAIDs reduce pain?
they have analgesic activity that lowers prostaglandin levels by blocking their synthesis
normally, prostaglandins are increased in response to neuropeptides and cytokines associated with inflammation
so NSAIDs are effective against pain of low-to-moderate intensity
what kind of pain are NSAIDs useful for treating?
they are effective in treating somatic pain
they are also effective in treating menstrual pain, and a type of visceral pain associated with increased prostaglandin release
somatic pain comes from the skin. muscles, and soft tissues
visceral pain comes from the internal organs
how do NSAIDs reduce fever?
your body temperature is controlled by hypothalamus and during fever, the set point is elevated
this happens because cytokines increase prostaglandin E2 (PGE2) levels in circumventricular organs, leading to changes in hypothalamic function
NSAIDs block PGE2 synthesis!
NSAIDs reduce fever without impacting normal variations in temperature associated with the circadian rhythm
what is Reye’s syndrome?
Reye’s syndrome is characterized by encephalopathy, liver dysfunction and fatty infiltration of the liver
aspirin and other salicylates are associated with Reye’s syndrome so aspirin is contraindicated in children and adults under 20 years old that have a fever associated with a viral illness
NEVER prescribe aspirin to children and teenagers recovering from chickenpox or flu-like symptoms
which NSAID is a salicylates?
aspirin
which NSAIDs are propionic acids?
- ibuprofen (advil, motrin)
2. naproxen (alleve)
which NSAIDs is COX-2 inhibitors?
celecoxib
what are the categories of NSAIDs?
- salicylates
- propionic acids
- acetic acids
- oxicams
- fenamates
- COX2 inhibitors
what is the MOA of NSAIDs?
- injury to tissue
- phospholipase A2 acts on the phospholipids in the cell membrane and releases arachidonic acid
- arachidonic acid then makes leukotriene via the lipoxygenase pathway
or arachidonic acid can make prostanoids (prostacyclin, prostaglandin E2, or thromboxane) via COX1 or CO2 in the cyclooxyrgenase pathway
so what NSAIDs do is inhibit COX1 and COX2!
what is the function of COX1?
COX-1 is responsible for the physiologic production of prostanoids = prostacyclin, prostaglandin E2, or thromboxane
it’s present in most tissues, especially in the GI tract; it maintains the normal lining of the stomach via mucous! –> this is why if you give too many NSAIDs you can cause stomach ulcers because you’re breaking down the stomach lining
it’s involved in kidney and platelet aggregation
COX-1 is “housekeeping enzyme” that regulates normal cellular process, such as gastric cytoprotection, vascular homeostasis, platelet aggregation, and kidney function
most NSAIDs target COX1
what is the function of COX2?
COX-2 causes the elevated production of prostanoids that occurs in sites of disease and inflammation
it’s present in macrophages and monocytes
it’s responsible for pain and inflammation
what class of drugs can inhibit COX2?
glucocorticoids!!
the structural differences between COX-1 and COX-2 permitted the development of COX-2 selective inhibitors
where is COX2 expressed in the body?
- brain
- kidney
- bone
what are the 2 mechanisms of aspirin?
- inhibits transcription of the COX-2 mRNA preventing more prostaglandin production
- aspirin is an acetylated form of salicylic acid
and it *irreversibly alters the COX-1 or COX-2 enzyme responsible for production of prostaglandins by donating an acetyl group to a serine residue, thus inactivating COX-1 or COX-2
what are the uses of aspirin?
- regulates body temperature = aspirin inhibits cyclooxygenase activity which decreases the formation of prostaglandins (PGE2)
- anti-inflamatory
- anti-pain = decreases prostaglandin E2 synthesis which represses the sensation of pain usually arising from musculoskeletal disorders rather than that arising from the viscera
what are the uses of acetaminophen?
great of anti-pain and anti-fever but it is NOT good at anti-inflammatory effects
what respiratory effect does aspirin have?
at therapeutic doses, aspirin can increase ventilation
however, higher doses work directly on the respiratory center in the medulla, resulting in hyperventilation
what are the GI effects of aspirin?
normally, prostacyclin (PGI2) inhibits gastric acid secretion, whereas PGE2 stimulates synthesis of protective mucus in both the stomach and small intestine
in the presence of aspirin, these prostanoids are not formed resulting in increased gastric acid secretion and diminished mucus protection = stomach ulcers
what are the adverse effects of aspirin on the kidney?
COX-inhibitors prevent the synthesis of prostaglandins that are responsible for maintaining renal blood flow
decreased synthesis of prostaglandins can result in retention of sodium and water, and may cause edema and hyperkalemia
this is bad because this can in turn effect the heart!!
which conditions is aspirin used to treat?
salicylic acid derivatives are used in the treatment of gout, rheumatic fever, and osteoarthritis