Category/Class
Salicylate (NSAID)
Drug interactions –
diphenylhydantoin, probenecid,
anticoagulants
Prototype/Pharmacodynamics
Aspirin




Absorption – oral
Metabolized – esterases in
blood, tissues (esp. liver)
Elimination – renal, esp. in
alkaline urine
T1/2 – 15-30 min
Mechanism of Action
Toxicities/Side Effects
Irreversibly inhibits prostaglandin
biosynthesis by acetylating
cyclooxygenase (block arachidonic
acid access to catalytic site)
Note: lipoxygenase pathway no
inhibited by NSAIDs
Dose-related – GI irritation,
dyspepsia, N, V, peptic ulcer,
gastric bleeding, renal toxicity,
HTN effects, hypersensitivity
reactions, CNS effects (tinnitus,
sleepiness, HA, dizziness,
confusion, visual disturbances),
hepatotoxicity, Reye’s syndrome
(kids). Acid-base disturbances
GI Side effects 5-15% lower than
aspirin
-Inhibit platelet aggregation to a
lesser extent than aspirin
-Fewer adverse effects after
overdose
-Superior analgesic for
dysmenorrhea
Prominent side effects – GI
disturbances, CNS alterations (HA,
depression)
Some fatal cases of hepatitis and
jaundice

Poorly tolerated - prominent GI
effects, salt and water retention,
fatal blood dyscrasias (aplastic
anemia, agranulocytosis)

Avoid in patients with allergies to
sulfonamides
Tx: osteoarthritis, rheumatoid
arthritis, less effective in acute pain,
like HA
Does not increase bleeding time
Lowers risk of ulcers
Well-tolerated
Allergic rxns – skin, fever
Severe hepatotoxicity in overdose
Analgesic and antipyretic actions
LACK anti-inflammatory actions
Tx: HA, fever reduction
Pts allergic to aspirin are usually
NOT allergic to acetaminophen,
DO NOT cause GI disturbances
NO effect on platelet aggregation
Tx: arthritis, can induce remissions
in active arthritic disease
Many months until see effect
Contraindicated in pts with renal or
hepatic dysfunction
NSAID – propionates
Salicylate – like anti-inflammatory
Ibuprofen

Abs – rapid oral, highly plasma
protein bound

Metab – extensive, hepatic
Similar to aspirin – inhibit
cyclooxygenase in the
prostaglandin pathway
NSAID – indoles
Salicylate – like anti-inflammatory
Indomethacin

See ibuprofen

Most potent inhibitor of the NSAIDs
but more toxic
Similar to aspirin – inhibit
cyclooxygenase in the
prostaglandin pathway
Phenylbutazone
o See ibuprofen
o T1/2 – 50-100 hrs
o Highly protein bound
Similar to aspirin – inhibit
cyclooxygenase in the
prostaglandin pathway
Chemical structure resembles
serotonin
NSAID – pyrazalones
Salicylate – like anti-inflammatory
Drug interactions – those highly
bound to plasma proteins and
metabolized by hepatic microsomes
COX-2 selective inhibitors
Analgesic-Antipyretic Drug
Para-amino phenols
DMARDs
(Disease Modifying Anti-rheumatic
Drugs)
Celecoxib

Abs – rapid orally

Metab – liver (P450) and
inhibits one of the P450
enzymes

T ½ - 11 hrs
Acetaminophen

Abs – rapid orally, less bound
than aspirin

Metab – liver conjugation

T1/2 – 1-3 hrs
Auranofin – Gold Salts

Abs – oral, extensive
distribution (2X in inflamed
joints)

T1/2 – dose-dept. 1-168 days
Potent anti-inflammatory, less
antipyretic and analgesic actions
Blocks COX-2 but not COX-1
Inhibits P450 (CYP2D6) – will
increase serum conc. of some betablockers, antidepressants and
antipsychotic agents
Weak inhibitor of cyclooxygenase
May suppress macrophage
processing of Ag, unmask T-cell
suppressor activity (suppress
production of rheumatoid factor)
↓ ICAMs and VCAMs
Toxicity – 25-50% of pts
Dermatitis – may progress to fatal
exfoliative form
Lesions in mucus membranes,
nephrotoxicity, blood dyscrasias
(agranulocytosis), ocular toxicity
Other




analgesic, antipyretic
(antagonizes ability of IL-1 to
reset the hypothalamic
thermostat) and anti-thrombic
action (inhibit synthesis of
thromboxane A2) at low
doses, anti-inflammatory at
high doses
Scavenge and neutralize free
radicals - ↓ pain and swelling
Tx: pre-eclampsia
Not recommended for general
use as an analgesic
Tx: gouty arthritis, ankylosing
spondylitis, osteoarthritis,
management of patent ductus
arteriosus
Tx: restricted to short-term tx
of acute flare-ups of arthritic
symptoms or gout
Category/Class
Prototype/Pharmacodynamics
Mechanism of Action
Toxicities/Side Effects
Methotrexate
Drug of choice for the tx of rheumatoid
arthritis
Suppresses Ab production and
purine biosynthesis by inhibiting
folate-dependent enzymes
Formidable antineoplastic side
effects – nausea, mucosal ulcers,
hematological toxicity
Hydroxychloroquine – antimalarial agent
Not clear – suppresses
responsiveness of T lymphocytes to
mitogens, inhibits DNA an RNA
synthesis
Metal chelating agent, unmask Tcell suppressor activity, interacts
with the lymphocyte membrane
receptor and may interfere with
collagen synthesis
Immunosuppressive
Ocular toxicity
Penicillamine
Cyclophosphamide
Pretty much the same as methotrexate
Dermatitis, renal toxicity, GI effects
Other
Tx: arthritis, can induce partial or
complete remissions in severely
afflicted pts
Low dose (pulse) – suppresses
arthritis in 80% of pts
Tx: arthritis, can induce remissions
in active arthritic disease
Tx: arthritis, can induce remissions
in active arthritic disease
Many months until see effect
Tx: arthritis, can induce remissions
in active arthritic disease