analgesic, antipyretic, NSAIDs and DMARDS Flashcards Preview

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Flashcards in analgesic, antipyretic, NSAIDs and DMARDS Deck (50):
1

clinical signs of inflammation (4)

erythema
edema
tenderness
pain

2

3 phases of inflammation

acute inflammation
immune response
chronic inflammation

3

Aspirin: mechanism of action

nonselective, irreversible inhibitor of COX-1 & COX-2

4

Aspirin: pharmokinetics

acid, pKa=3.5
fast oral absorbtion
[ASA] in mucosal cell=20 times [ASA] in stomach
-readily crosses placenta
-SLOWLY crosses BBB
rapidly hydrolyzed inplasema, liver & erythrocytes
binds to plasma proteins

5

ASA drug interactions

COMPETES w/T3, Pen G, thiopental, bilirubin, phenytoin, sulfinpyrazone, naproxen, etc for PROTEIN PLASMA BINDING SITES->drug interactions

6

ASA metabolism

low doses: first order kinetics
high doses: zero order kinetics (>600mg body burden; 2 ASA/day=zero order kinetics)

RENAL EXCRETION-alkalinization of urine promotes excretion

7

Aspirin effects

ANTIINFLAMMATORY- ↓sxs of inflammation
ANALGESIC: most effective in mild-moderate pain
ANTIPYRETIC:↓elevated temp
ANTIPLATELET: irreversible inhibition of platelet COX enzymes; platelets can't synthesize new enzyme, effect lasts 8-10 days

8

Aspirin uses

mild-moderate pain
antipyresis
anti-inflammatory (NSAID)
MI, thrombosis prophylaxis
long term use ↓colon CA

9

Aspirin adverse effects

respiratory alkalosis
then
metabolic & respiratory acidosis

10

ASA platelet effects

ASA (but not sodium salicylate) inhibits platelet aggregation, thereby ↑ bleeding time
single 650 mg dose of ASA DOUBLES bleeding time (may last 8-10d)

11

ASA should be avoided or d/c in which pts? (6)

hypoprothrombinemia
vitamin K deficiency
hemophilia
severe hepatic damage
prior to labor

stop AT LEAST ONE WEEK prior to elective surgery

12

Uricosuric effects of ASA

biphasic & dose dependant
LOW DOSES (1-2g/day): ASA ↓ uric acid excretion & ↑plasma urate excretion
LARGE DOSES (>5g/day): ASA ↑uric acid excretion (uricosuria) & lowers plasma urate levels
***such large doses of ASA are POORLY TOLERATED b/c ASA causes stomach irritation, gastric bleeding, etc

13

ASA effects:
Cardiovascular
Lungs
GI
renal

Cardio: minimal in regular doses

Lungs: ASA asthma due to ↑leukotriene synthesis

GI upset, gastritis, ulcer, bleeding (buffering, food, misoprostol used to reduce damage; but miso=abortion so no pregos)

Kidneys: renal damage, acute renal failure, interstitial nephritis

14

ASA & pregnancy

NO TERATOGENIC EFFECTS
withhold ASA several days prior to deliver to prevent excessive & prolonged post partum bleeding

15

salicylic acid local irritant effects

salicylic acid (but NOT ASA) irritant to skin, mucosa, epithelial cells, ketolytic effect used to remove wards, corns, funga, exzematous dermatitis
*but salts of salicyclic acid=no effect on skin
methyl salicylates (oil of Wintergreen) is irritating to skin

16

ASA should be DECREASED in whom?

↓ ASA during long term therapy w/oral anticoagulants, hypoglycemic agents, etc

17

Salicylate: fatal dose

ASA: abt 20g (10-30g)
methyl salicylate (oil of Wintergreen): 4-5mL fatal in kids

18

Reye's syndrome

cerebral edema in kids w/viral infections who take ASA

so DOC is acetaminophen

19

Nonacetylated salicylates (3)

magnesium chloine salicylate
sodium salicylate
salicyl salicylate

20

Nonacetylated salicylates: effects

effective anti-inflammatory
salicylic acid is the active drug
less effective analgesics than ASA
NO irreversible COX inhibition

21

Diflunisal: what is it, what is its action

salicylic acid derivative, but NOT metabolized to salicylic acid
does NOT have significant antipyretic effects, prob due to POOR penetration into CNS

22

NSAIDs: 2 major types based on action

1. Specific reversible inhibitors of COX-2 enzymes
2. Nonspecific reversible inhibitors of COS-1 & COX-2 enzymes

23

Celecoxib (Celebrex): class, admin, AEs, contraindication

Selective reversible COX-2 inhibitors=less gastropathy & risk of GI bleed
-but FDA says risk of GI ulceration, bleeding and perforation
ORAL admin
AEs: GI disturbances including ulceration & bleeding, ↑risk of cardiovascular dz
CONTRA: GI dz, asthma, breast feeding, prego, renal failure

24

Nonspecific reversible inhibitors of COX-1 & COX-2 effects

various chem structures
sim to ASA but NOT irreversible
variable SE frequency but basically same
variable PHK

25

Nonspecific reversible inhibitors of COX-1 & COX-2: the best (2) and the worst (2)

first DOC: ibuprofen-best SE profile

worst (but potent): Indomethacin, Phenylbutazone (not in US)

26

Nonspecific reversible inhibitors of COX-1 & COX-2 toxicities

GI: pain, bleeding, ulcer, pancreatitis, diarrhea
CNS: HA, dizziness, confusion, depression
Lung: bronchoconstriction
Bone marrow: agranulocytosis, aplastic anemia
Nephrotox: acute renal failure, interstitial nephritis, nephrotic sxs
Hepatotox: enzyme elevation, hepatitis
Hypersensitivity rxns

27

Indomethacin (Indocin)

nonselective, reversible inhibitor of COX-1 & COX-2

↓ PMN migration
inhibit phospholipase A

very potent ant-inflammatory agent, high incidence of SEs

used for patent ductus arteriosus (others work too)

28

Note that a lot of cards were lost when not saved, so I'm skipping from Indomethacin to Acetominophen now

yup, a lot
like Naproxen=long half life, no pregos
Ibuprofen (Motrin) 1st DOC b/c low SEs half life 2-4h

29

Acetominophen

often preferred to ASA b/c better tolerated
no COX inhibition so no ulvers, blood clotting defects, acid-base imbalance auditory toxicity but
OD can cause FATAL HEPATIC NECROSIS
so, be careful with kids

30

Best NSAID for
NO hx of PUD:
PUD in hx but not active:
active PUD:

NO hx: any NSAID

hx of PUD, not active: celecoxib w/or without antacids, some NSAIDS w/misoprostol or "-prazols" (PPIs)

active PUD: acetaminophen &/or opioids

31

Acetaminophen PHK

ORAL absorption
half-life: 2-3 hours (inc. w/high doses)
liver metabolism, conjugation, renal excretion
dose dependent free radical production-eliminated by GSH (reduced glutathione)

32

Acetaminophen effects

antipyretic action
analgesic action
NO ANTIINFLAMMATORY ACTION

33

Acetaminophen uses

DOC: fever in kids
mild-moderate pain
adjunct to anti-inflammatory therapy
dose not influence urate excretion
combined w/codeine & derivatives, sedatives, cough suppressants, tramadol, diphenhydramine, caffeine etc
NO anti-inflammatory effect, no platelet effects

34

Acetaminophen AEs:

occasional SKIN RASH & allergic rspsonse, CROSS-SENSITIVITY w/ salicylcates
few cases of NEUTROPENIA
****DOSE-DEPENDENT FATAL HEPATIC NECROSIS*** (in adults, 10-15g at once=hepatotoxicity, 25 g=fatal)
hepatotoxicity->encephalopathy, coma & death

↑serum transaminase, lactic acid dehydrogenase

hydroxylated INTERMEDIATE METABOLITE is rspsnble for liver damage

35

When does Acetaminophen toxicity become serious

when METABOLITES EXCEED THE AVAILABLE REDUCED GLUTATHIONE in body

chronic ETOH consumption ↑toxicity`

36

tx of acetaminophen intoxication

gastric emptying
forced diuresis
hemodialysis
SPECIFIC ANTIDOTE: N-acetylcysteine (Mucomyst)
N-acetylcysteine must be administered parenterally, ASAP within 10-12 hours after intoxication

37

Goals of therapy for Chronic Inflammatory Conditions

pain relief
↓inflammation
protect articular structures
maintain fxn
control systemic involvement

38

Gold Salts: action, toxicity

inhibit phagocytosis, inhibit cellular respiration, inhibit proteolytic eyzmyes of leukocytes, prevent PGI synthesis
SUPPRESS CELLULAR IMMUNITY

toxicity: BONE MARROW DAMAGE, dermatitis, ENTEROCOLITIS, jaundice, peripheral neuropathy

39

Penicillamine (Cuprimine): action, toxicity

chelating drug effective in RA & Wilson's
mechanism unknown, maybe it works like gold salts
TOXICITIES: high inc. of adv. rxns; pruritis, rash, alteration in taste, thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, proteinurin, hypoalbuminemia, nephrotic syndrome, lupus like dz, pemphigus, Goodpasture's syndrome, myasthenia gravis, polymyositis, stenosing alveolitis
PTs OVER 65 YEARS HAVE HIGHER RISKS

40

Hydroxychloroquine (PLaquenil)

possess antihistaminic, anticholinesterse & antiprotease props
inhibits prostaglandin synthesis
inhibits biosynth of mycopolysaccharide,
inhibits responses to chemotactic stimuli & phagocytosis
stabilizes lysosomes
REACTS w/NUCLEIC ACIDS and TISSUE PROTEINS

Toxicity: pruritus, hemolysis (G6PD deficient), ototoxicity, retinopathy, peripheral neuropathy

41

Sulfasalazine (Azulfidine): use, effectiveness, toxicities

Rheumatoid Arthritis, IBS
as effective Penicillamine, less toxic
As affective as injected gold compounds & better tolerated

TOX: Gi disturbance, rash, RARE hepatitis & blood dyscrasias
MONITORING for HEPATITIS & BONE MARROW SUPPRETION recommended for 2-3 weeks during first 3 mos of tx & less frequently therafter

42

Infliximab (Remicade): description, use, AE, contraindications

IgG1k monoclonal antibody targeted against TNFalpha

human constant + murine variable regions

use: Crohn's dz & RA
combined with methotrexate
IV admine

AE: HA & infusion rxns

Contra: prego, breast feeding, kids, infections

43

Rituximab (Rituxan): description, use, admin

IgG immunoglobin that BINDS TO CD20, a B-LYMPHOCYTE DIFFERENTIATE ANTIGEN on pre-B & mature B-lymphocyte

CD20 antigen expressed on >90% of B-cell non-Hodgkin's lymphoma (NHL), but not on hematopoietic stem cells, pro-B cells, normal plasma cells or other normal tissues

USE: NHL, other B-cell malignancies including chronic lyphocytic leukemia

ADMIN: IV

44

Adalimumab (Humira): description use, admin, AEs

recomh. HUMAN IgG1 MAB
specific for TNG-alpha

MONOTHERAPY in tx of RA (is formally approved for this, unlike infliximab)

subQ , t1/2=8-10days

AEs: rash, flu sxs, fatigue, HA, pruritis, N/V

45

Etanercept (Enbrel)

not a MAB, instead a FAKE TNFalpha receptor, so fewer can bind to real TNF receptor
-inhibits TNF

subQ

AE: injection site rxn, infections, increased incidence of antibody formation

CONTRA: bone marrow suppression, breast-feeding, kids, DM, infection, sepsis, vaccination, varicella, active TB

46

Abatacept (Orencia)

FULLY HUMAN recombinant fusion protein
2nd signal blocker of T cell activations
competes w/ CD28 (on T cell) for CD80 & CD86 (on APC) binding

Rheumatoid Arthritis

IV

mean t1/2=13.1 days

47

Leflunomide (Arava): Action, Admin, SEs, Contra

inhibits dihydrooratate dehydrogenase (DHODH)

INHIBITS INDUCTION OF COX-2

oral admin, t1/2=16 hours

SE: N/V/D, dyspepsia, abdominal pain, back pain, weight loss, anorexia, oral ulceration elevated hepatic enzymes

CONTRA: prego, breast feeding, heapatic, renal failure

48

Mycophenolate mofetil (Cellcept)

INHIBITS LYMPHOCYTE PURINE SYNTHESIS by reversible & noncompetitively inhibiting IMPDH

admin: ORAL or IV

AE: diarrhea, emesis, GI bleed

CONTRA: active GI dz, diarrhea, prego, breast feeding, infections

49

Anakinra (Kineret)

INTERLEUKIN-1 RECEPTOR AGONIST

RA

subQ
t1/2: 4-6h, eliminated renally

CONTRA: breastfeeding, kids, hypersensitivity rxns, renal dz

50

Tofacitinib (Xeljanz)

xelJANZ=janus kinase inhibitor
prim inhibits JAK1& JAK3, to a lesser extent JAK2

Use: adults MOD-SEVERE w/ACTIVE RA who have had inadequate response or intolerance to methotrexate

ORAL admin, t1/2=3h

AEs: serious infections & malignancy