Term
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Definition
Class: glucocorticoid, immunosuppressant
Mechanism: pass through membrane bind receptor in cytosol (releases hsps), homodimerization of receptors, translocate to nucleus, active TF to induce transcription of anti-inflammatory gene products
Indication: prevent and treat transplant rejection, graft vs. host disease, autoimmune disorders
Adverse Effects: increased susceptibility to infection, increased glucose elvels and DM, secondary hyperparathyroidism, osteoporosis, edema, suppression of linear bone growth (in children), steroid psychosis, Cushing's-like effects, withdrawal adrenal insufficiency, myopathy |
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Term
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Definition
Class: glucocorticoid
Mechanism: pass through membrane bind receptor in cytosol (releases hsps), homodimerization of receptors, translocate to nucleus, active TF to induce translation of anti-inflammatory gene products
Indication: prevent and treat transplant rejection, graft vs. host disease, autoimmune disorders
Adverse Effects: increased susceptibility to infection, increased glucose elvels and DM, secondary hyperparathyroidism, osteoporosis, edema, suppression of linear bone growth (in children), steroid psychosis, Cushing's-like effects, withdrawal adrenal insufficiency, myopathy |
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Term
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Definition
Class: calcineurin inhibitor, immunosuppressant
Mechanism: bind cyclophilin, block dephosphorylation of NFAT by calcineurin, thus NFAT doesn't enter nucleus and this blocks the production of IL-2
Indication: organ transplant (in combo)
Adverse Effect: NEPHROTOXICITY (majority of pt), HTN (~50% of renal transplants), tremor, (hepatotoxicity, hyperlipidemia, hirsutism, gum hyperplasia)
Pharmacokinetics:
Admin - oral or iv
Absorb - slow, 20-50% bioavail
Metab - extensive by CYP3A, drug interactions |
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Term
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Definition
Class: calcineurin inhibitor, immunosuppressant
Mechanism: binds FK binding protein (FKBP), prevents dephosphorylation of NFAT by calcineurin, prevents production of IL-2
Indication: prevent and treat transplant rejection [use therapeutic drug monitoring b/c of nephrotoxicity]
Adverse effects: NEPHROTOXICITY, neurotoxicity (HA, tremor, seizures), (hepatoxicity, hyperlipidemia, hirsutism, gum hyperplasia)
Pharmacokinetics: metabolized by CYP3A (drug interactions) |
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Term
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Definition
Class: immunosuppressant
Mechanism: binds FKBP, blocks the IL-2 receptor signaling and arrests cell division by blockin mTOR (a kinase)
Indication: prophylaxis in organ transplant rejection (ESP. PT WITH HIGH RISK FOR NEPHROTOXICITY)
Adverse effects: hyperlipidemia, leukopenia, thrombocytopenia
Drug interaction: aggravates cyclosprine renal dysfx so do not combine |
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Term
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Definition
Class: anti-metabolite, immunosuppressant
Mechanism: prodrug analog of mercaptopurine, inhibits gene translation; more effective than mercaptopurine (due to pharmacokinetics)
Indication:
Adverse effect: BONE MARROW SUPPRESSION, increased susceptibility to infection |
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Term
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Definition
Class: anti-metabolite, immunosuppressant
Mechanism: folate analog, inhibits dihydrofolate reductase; cytotoxic and anti-inflammatory effects
Indication: cancer, rheumatoid arthritis, graft vs. host dz
Adverse effect: IMMUNOSUPPRESSION, fasting grow cell effects (hair loss, GI stuff) |
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Term
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Definition
Class: anti-metabolite, mycophenolic acid
Mechanism: inhibits inosine monophosphate dehydrogenase (IMPDH) the rate limiting enzyme in guanosine formation; preferentially acts in lymphocytes (more dependent on IMPDH for purines, isoform II used by lymphocytes is specifically targeted)
Indication: combo for transplant rejection (glucocorticoids and calcineurin inhibitors, NOT with azathioprine)
Adverse effects: vomit, diarrhea, leukopenia, increased risk of infection |
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Term
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Definition
Class: humanized Ab, immunosuppressant
Mechanism: anti-CD25 mouse monoclonal Ab; binds IL-2 receptor on activated T cells; LOWER AFFINITY
Indication: prophylaxis for renal transplants in combo w/ other immunsuppressants
Adverse effects: infection, anaphylactic rxn |
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Term
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Definition
Class: humanized Ab, immunosuppressant
Mechanism: anti-CD25 mouse monoclonal Ab; binds IL-2 receptor on activated T cells; HIGHER AFFINITY
Indication: prophylaxis for renal transplants in combo w/ other immunsuppressants
Adverse effects: infection, anaphylactic rxn |
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Term
| inflammatory mediators - vasodilation |
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Definition
prostaglandins (PG..)
nitric oxide
CGRP
histamine |
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Term
| inflammatory mediators - increased vascular permeability |
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Definition
histamine
C3a, C5a - complement components
bradykinin
leukotrienes (LT)
platelet-activating factor |
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Term
| inflammatory mediators - chemotaxis and leukocyte activation |
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Definition
C5a
LTG4, lipoxins (LX)
bacterial antigens |
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Term
| inflammatory mediators - tissue damage |
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Definition
PMN and macrophage
lysosomal products
oxygen radicals
nitrous oxide |
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Term
| inflammatory mediators - fever |
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Definition
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Term
| inflammatory mediators - pain/hypersensitivty |
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Definition
PGE2, PGI2
bradykinin
tryptase
ATP |
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Term
define cytokine/chemokine
(what they are, when released, bind to what, special note) |
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Definition
protein hormones produced as part of innate
immunity by multiple cells
released or activated by cell injury
bind to specific tyrosine kinase receptors or GPCRs
cytokine actions are redundant and can influence synthesis of other cytokines |
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Term
alprostadil
(class, mechanism, indication) |
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Definition
Class: prostaglandin
Mechanism: PGE1 analog
Indication: maintain ductus arteriosus (i.e. when need to perform cardiac procedures post-birth) |
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Term
misoprostrol
(class, mechanism, indication) |
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Definition
Class: prostaglandin
Mechanism: PGE1 analog, inhibits gastric acid secretion, inhibits pepsin secretion, increases mucus secretion in GI tract
Indication: promote ulcer healing |
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Term
dinoprostone
(class, mechanism, indication) |
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Definition
Class: prostaglandin
Mechanism: PGE2 analog
Indication: suppositories for parturition |
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Term
acetylsalicylic acid (aspirin)
(class, mechanism, indication, contraindiction) |
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Definition
Class: NSAID
Mechanism: COX-1 inhibitor, irreversible
Indication: pain, osteoarthritis, RA
Contraindication: ulcer, allergic, clotting disorders, pregnancy (3rd trimester esp.), gout, viral infections in kids/young adults
Adverse Effects: see NSAID flashcards |
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Term
acetaminophen
(class, mechanism, effects, indication, adverse effects) |
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Definition
Class: pseudo-NSAID
Mechanism: COX1 inhibitor
Effects: analgesic, antipyretic, no anti-inflam action, weak platelet effects, no uricosuric effects, no alterations in acid-base, minimal GI effects at therapeutic doses
Indication: pain, osteoarthritis, gout, RA
(esp. with benefits from above)
Adverse Effects: overdose can cause fatal hepatic necrosis |
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Term
n-acetylcysteine
(mechanism, indication) |
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Definition
Mechanism: recycles glutathione
Indication: treatment of acetaminophen poisoning |
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Term
celecoxib
(class, mechanism, benefits, indication, contraindication, adverse effects) |
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Definition
Class: NSAID, Cox2 inhibitor
Mechanism: inhibits COX2
Benefits: less GI side effects, less renal toxicity, no platelet effects
Indication: pain, OSTEOARTHRITIS
Contraindications: sulfa sensitivity, GI bleeding or ulceration
Adverse Effects: MI AND STROKE RISK IN PT WITH UNDERLYING CVD |
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Term
adalimumab
(class, mechanism, indication) |
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Definition
Class: biologic modifier, arthritic
Mechanism: antibody to TNF-alpha
Indication: Crohn's, RA, psoriasis, ankylosing spondylitis
Adverse effects: see biologic flash card |
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Term
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Definition
Class: NSAID, arylproprionic acid
less GI side effects |
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Term
|
Definition
Class: NSAID, arylpriopioinic acid
twice daily dosing |
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Term
| contraindication for biologic modifiers |
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Definition
active infection
traveling to area with certain risk of infection
more susceptible to infection already |
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Term
entanercept
(class, mechanisum, indication) |
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Definition
Class: biologic modifier, arthritic
Mechanism: fusion protein to TNF-alpha receptor binding site; false receptor that binds up TRF-alpha in circulation thus decreases its effects in inflammatory dz
Indication: RA, Crohn's disease
Adverse effect: see biologic flash card |
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Term
infliximab
(class, mechanism, indication) |
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Definition
Class: biologic modifier, arthritic
Mechanism: antibody to TNF-alpha
Indication: Crohn's, RA
Adverse effects: see biologic flash card |
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Term
natalizumab
(class, mechanism, indication) |
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Definition
Class: biologic modifiers, arthritic
Mechanism: humanized monocolonal antibody to alpha4 integrin; blocks migration of T cells into gut
Indication: Crohn's
Adverse effects: see biologic flash card |
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Term
golimumab
(class, mechanism, indication) |
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Definition
Class: biologic modifiers, arthritic
Mechanism: antibody to TNF-alpha
Indication: RA, psoriatic arthritis, ankylosing spondylitis |
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Term
colchicine
(class, mechanism, indication, adverse effects) |
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Definition
Class: arthritic drug
Mechanism: inhibits cell migration and thus decreases inflammatory response
Indication: gout (when NSAID not effective)
Adverse effects: GI distress, abdominall pain, myopathy & neuropathy -> weakness, blood dyscrasias |
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Term
probenecid
(class, mechanism, indication, adverse effects) |
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Definition
Class: arthritic
Mechanism: compete with reabsorption of uric acid from urine, thus increase uric acid exretion
Indication: gout (prevent hyperuricemia)
Adverse effects: precipitate uric acid crystals in renal tubules, rash, hypersensitivty rxn, GI irritation in pt w/ peptic ulcers |
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Term
sulfinpyrazone
(class, mechanism, indication, adverse effect) |
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Definition
Class: artrhitic
Mechanism: compete with reabsorption of uric acid from urine, thus increase uric acid exretion
Indication: gout (prevent hyperuricemia)
Adverse effects: precipitate uric acid crystals in renal tubules, rash, hypersensitivty rxn, GI irritation in pt w/ peptic ulcers |
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Term
allopurinol
(class, mechanism, indication, adverse effects) |
|
Definition
Class: arthritic
Mechanism: decrease uric acid production, inhibits xanthine oxidase
Indication: gout
Adverse effects: rash, hypersensitivity rxn, fever, malaise, muscle aches, rarely leukopenia |
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Term
abtacept
(class, mechanism, indication) |
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Definition
Class: biologic modifiers, arthritis
Mechanism: fusion protein to CTLA-4, costimulation modulator
Indication: inflammatory diseases
Adverse effect: see biologic flash card |
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Term
febuxostat
(class, mechanism, indication, adverse effects) |
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Definition
Class: arthritic
Mechanism: decrease uric acid production, inhibits xanthine oxidase
Indication: gout
Adverse effects: rash, hypersensitivity rxn, fever, malaise, muscle aches, rarely leukopenia |
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Term
tofacitinib
(class, mechanism, indication, adverse effects) |
|
Definition
Class: biologic modifiers, arthritic
Mechanism: JAK1 and JAK3 inhibitors, blocks STAT-1 dependent gene expression, intracellular signaling block of cytokines
Indication: inflammatory diseases
Adverse effects: see biologic flash card |
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Term
| treatment of pain - classes used |
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Definition
NSAIDs
acetaminophen
COX2 inihbitors |
|
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Term
| treatment of osteoarthritis - classes used |
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Definition
NSAIDs
capsaicin
glucosamine/chondroitin - not proved by NIH
glucocorticoids
COX2 inhibitors |
|
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Term
| treatment of gout - classes used |
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Definition
NSAIDs
glucocorticoids
xanthine oxidase inhibitors (allopurinol, febuxostat)
colchicine |
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Term
| treatment of rheumatoid arthritis - classes used |
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Definition
NSAIDs
immunosuppressants
biologic modifiers |
|
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Term
| treatment of IBD/Crohn's Dz - classes used |
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Definition
mesalmine (5-ASA)-based therapies
glucocorticoids
antibiotics
immunosuppressants
biologic modifiers |
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Term
| treatment of psoriasis - classes used |
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Definition
topical agents (glucocorticoids, Vit D analogs, retinoids)
light therapy
immunosuppressants
biologic modifiers |
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Term
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Definition
| class of molecules produced endogenously through the metabolism of arachidonic acid |
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Term
| prostaglandin - CV effects |
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Definition
Blood pressure - PGE and PGI2 decrease it, thromboxane A2 increases
Heart - PGE and PGI2 dilate coronary vessels, TXA2 constricts them
TXA2 stimulates platelet aggregation
PGI2 (prostacyclin) inhibits platelet aggregation |
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Term
| prostaglandin - renal effects |
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Definition
| PGE and PGI2 cause vasodilation, natriuresis, diuresis and renin release |
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Term
| prostaglandin - resp. effects |
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Definition
PGE and PGI2 dilate bronchioles
TXA2 and PGF2alpha constrict bronchioles
PGE2 used as aerosol for asthma, but too short duration for clinical popularity |
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Term
| prostaglandin - GI effects |
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Definition
| PGE2 and PGI2 inhibit gastric acid and pepsin secretion, icnrease mucous secretion |
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Term
| prostaglandin - reproductive effects |
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Definition
PGE2 relaxes non-pregnant, but contracts pregnant uterus
PGF2alpha contracts pregnant and non-pregnant and causes lysis of corpus luteum
PGE2 and PGF2alpha used as contraceptive/induce abortion/control post-partum hemorrhage |
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Term
| prostaglandin - pain and inflammation |
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Definition
synthesized and found in synovial fluid in inflammation
produce pain or hyperalgesia |
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Term
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Definition
| central admin esp. into hypothalamus produces it |
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Term
| clinical uses of prostanoids |
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Definition
1. promotes dilation of cervix, facilitates labor - PGE2
2. gastric protection - misoprostol
3. improve harvesting and storage of platelets (PGG, PGI2)
4. impotence? - alprostadil (PGE1)
5. dilate pulmonary vessels - epoprostenol PGI1
6. maintenance of patent ductus arteriosus - alprostadil |
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Term
|
Definition
no tolerance develops
reduce symptoms, doesn't affect underlying dz
choice of which one is largely empirical
Benefits: analgesic, antipyretic, anti-inflammatory (except acetaminophen)
Adverse: gastric irritation, altered respiration, disturbs acid-base balance, increased bleeding, prolongation of gestation, potential renal damage |
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Term
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Definition
epigastric distress
nausea
vomiting
gastric ulceration
hemorrhage
exacerbate ulcers
hepatotoxicity |
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Term
| NSAID adverse - cardiovascular |
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Definition
inhibit platelet aggregation
prolong bleeding
toxic conc. can depress circulation |
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Term
|
Definition
aspirin intolerance
hypersensitivity (skin, astham, anaphylaxis) |
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Term
|
Definition
recurrent vomiting
listlessness
irritability
combativeness
disorientation or confusion
delirium
convulsions
loss of consciousness
prognosis linked to brain swelling - increased intracranial pressure
assoc. between young kids/adults with viral infection and treated with aspirin |
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Term
|
Definition
| acute renal insufficiency w/ underlying disease (liver disease + ascites, CHF, renal disease) |
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Term
|
Definition
low dose decrease urate excretion
antagonize uricosurics
worsen gout |
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Term
| aspirin poisoning - 1* effects |
|
Definition
CNS - tinnitus, mental confusion, hearing loss, convulsions, coma; stimulate respiratory center
GI - nausea, vomiting
General - hyperthermia, dehydration, uncouples oxidative phosphorylation |
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Term
| aspirin poisoning - 2* effects |
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Definition
respiratory alkalosis
metabolic acidosis
water and electrolyte loss
cardio and respiratory arrest w/ severe intoxication |
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Term
|
Definition
produces thromboxanes in platelets
(vasoconstriction and platelet aggregation results) |
|
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Term
|
Definition
produces prostacyclin in endothelial cells
(vasodilation and blocking of platelet aggregation result) |
|
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Term
| adverse effects of biologic modifiers |
|
Definition
2* to injection - pain, swell, itch, fever, chills, rash
INFECTION - compromised immune state
nausea, vomiting, HA, abdominal pain
potential for malignacies
CYTOKINE RELEASE SYNDROME - reduced by humanization
infiximab - reproted to cause anaphylaxis or lupus-like syndrome on rare occasion
very expensive |
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