Immunology Block: Pharmacology 9 - Clinical Pharm With Steroids, Nsaids And Acetaminophen

Front 1

Nsaids! which ones should we know about, and how do they work? which non-specific ones should we know?

Back 1

tehy all work by inhibiting cox, though their concentrations and specifities and chemical families can all vary.

the non-specific NSAIDS we need to know are aspirin, ibuprofen, naproxen, nabumetone, and diclofenac.

Front 2

what are the effects of NSAIDS?

Back 2

antiinflammatory, analgesics (remember that prostiglandins sensitize noceptors),

antipyretics

Front 3

adverse effects of nsaids?

Back 3

platelet dysfunction,

gastritis/peptic ulcers

renal failure (remember that prostiglandins are vasodilatory, and that for people with kidney disease, they might be depending on those to keep their GFR up.

also can inhibit labor (PG's are pro-smooth muscle constriction, including the uterus).

water/sodium retention, swelling.

Front 4

what's asprin allergy and aspirin resistance?

Back 4

allergy is because you stop all that AA going to PgH, it gets shunted over to the leukotriene pathway. Get bronchoconstriction and vasoconstriction, bad news.

diminishing returns = aspirin resistance. once you knock out all the platelet cox, there's no more to do. just have left over salicates.

Front 5

what are the dose dependent signs of aspirin toxicity?

Back 5

low levels, have GI problems. nausea vomiting.

mild toxic = tinnitus, hyperventilation (from your acidosis) leads to respiratory alkalosis.

then get vasomotor collapse, coma, hypoprothrombinemia

lethal - renal and respitory collapse.

Front 6

how does tylenol work, what are the signs of its toxcisity, and what do you do about it?

Back 6

don't know how tyolenol works. weakly inhibits Cox1 and Cox 2, may inhibit cox 3.

doesn't do much to the kidneys or to the Gi system.

but very hepatoxic - so careful with liver disease.

large dose can cause dizziness, excitement, disorientation.

big time dose can cause liver problems. see vomiting and diarrhea and abdominal pain.

need to give SULFHYDRYL GROUPS in the form of N-Acetyl-Cystine to neutralize the toxic metabolites.

Front 7

why are Cox-2 drugs bad?

Back 7

some people constitutively express Cox-2 in their endothelia and heart, where they're making prostiglandins.

Remember that PG's are pro-bleeding normally. If you inhibit here, more likely to form clots and have heart attacks.

Front 8

what prostiglandin has a lot to do with fever?

Back 8

PgE2. It's what tells the hypothalamus to up its setpoint, and why aspirin (which inhbits it) stops fevers.

Front 9

when can prostiglandins be used as a therapy?

Back 9

think diseases of high pressure. Hypertension and glaucoma.

drops are given in the eyes

PGi2 is given to hypertensives during catheterisation.

remember that prostiglandins are dilators and are natural diuretics - they increase GFR and fluid loss, bringing down internal pressure.

also, can use for peripheral vascular disease, including reynaud's phenomenon.

also can use for abortion (PGF) and for quickening birth (remember that NSAIDS are used for painful periods and to keep babies inside).

also treat erectile dysfunction.

Front 10

What do leukotrienes have to do with asthma?

Back 10

remember that leukotrines are broncho-spastic and vasocontstricting.

so, it's a good thing to bring down leukotrienes.

can do this by stopping lipoxygenase (zileuton)

can do this by antagonizing the leukotriene receptors (Kasts)
= montelukast, zafirlukast

or, you can again stop everything with corticosteroids, which inhibit phospholipase A2.

Front 11

what's the difference in mechanism between steroids and NSAIDS?

Back 11

steroids tend to function on phospholipase A2, which prevents the formation of AA.

NSAIDS like aspirin attack COX, which turns AA into PGH2.

also remember that corticosteroids are essentially glucocorticoids, so they cause transcription of lots of GRE's, including IkB, which is an antagonist of NFkB (a necessary molecule in many cytokine/IL pathways).

Front 12

do nsaids stop the progression of disease? what shoul dyou use?

Back 12

no - use DMD's - or disease modifying drugs.

aspirin won't stop erison of bone or cartilege. DMD's might.

Front 13

what are the disease modifying drugs we should know about?

Back 13

methotrexate - inhibits dihydro folate reductase, so you don't get DNA synthesis, stops erosion. stops fast growing cells


gold salts - immunosupressive, work on macrophages, not used anymore

azathioprine - purine anti-metabolite, so it works to stop the proliferation of fast growing cells (especially blood cells). remember that cyclophosmoamide works like this too.

Chloroquine - works like a steroid

sulfasalazine - anti B/T cell, used in IBD.

penacillamine - immune modulatory metabolite of penacillin. not used much 'cause it's bad for bones. Wilson's disease treatment.

Front 14

there are a few more disease modifying drugs...

Back 14

the anti-TNFalpha antibodies!

etanercept -

infliximab, bind sTNFalpha receptors.

adailmumab

Front 15

where does gout come from? what's the metabolic pathway?

Back 15

xanthine goes to uric acid via xanthine oxidase.

remember that xanthine is a purine breakdown product.

uric acid crystals precipitate out in the joints, get partially phacocytosed, those cells send out chemoattractants, get inflammatory response.

this includes leukotrine B4, which is a big time chemoattractant.

Front 16

what drugs do we use to treat gout? talk about acute attacks vs. chronic.

Back 16

Chocicine - inhibits PMN tubules so they don't move right. Used for acute attacks and profilacctially. Stops B4 formation.

also, NON ASPIRIN-NSAIDS.

remmeber that aspirin has variable effects on uric acid excretion.


if it's chronic, think about ALLOPURINOL - inhibits xanthine oxidase. used if very severee. lots of side effects in the GI, and get cataractsand gouty flareups.

PROBENICID - it's uricosuric, so that's good.

Sulfinpyrazone - uricosuric too, but not as good.

Pegloticase - recombinate uricase to get rid of uric acid.

Front 17

so we use choclicine for acute gout and allopurinol for chronic gout, but we just learned that allopurinol causes gouty flare ups. what's that and what should we use?

Back 17

if you use allopurinol, remember your'e killing xanthine oxidase. really making no uric acid.

now, the uric acid in the gouty joints falls back into the blood and deposits in good joints. = acute gouty flareup.

treat like it's an acute symptom -chococine and non aspirin NSAIDS.

Front 18

what's reye's syndrome?

Back 18

affects all organs simultaneously.

mostly liver and brain. can start with a viral infection first, then gets worse. weird fat deposits and high ICP. therapy is designed to stop brain swelling.

90 to 95% of pts have taken aspirin. not sure why. kids under 19 shouldn't take aspirin.