1
Q
the cyclooxygenase (COX) pathway of arachidonate metabolism produces:
A
- PG pathway
- Leukotrienes pathway
” Dial 1 for Housekeeping”
Dial 2 for inflammatory
2
Q
prostaglandins, which have a variety of effects on
A
- blood vessels,
- on nerve endings,
- and on cells involved in inflammation.
3
Q
The______________- of arachidonate metabolism yields leukotrienes,
which have a powerful chemotactic effect on eosinophils,
neutrophils, and macrophages and promote bronchoconstriction
and alterations in vascular permeability.
A
** lipoxygenase pathway**
4
Q
THERAPEUTIC STRATEGIES
The treatment of patients with inflammation involves two primary __goals:
A
- first, the relief of symptoms and the maintenance of
function, which are usually the major continuing complaints of the patient;
- and second, the slowing or arrest of the tissue-damaging
process.
5
Q
In rheumatoid arthritis, response to therapy can be
quantitated using several measures such as the :
A
- Disease Activity
Scale (DAS),
- the Clinical Disease Activity Index (CDAI), and
- the American College of Rheumatology Response index (ACR
Response).
6
Q
The first two are continuous variables denoting both
state and change,
A
Disease Activity
Scale (DAS),
the Clinical Disease Activity Index (CDAI),
7
Q
is solely a change measure.
A
American College of Rheumatology Response index (ACR
Response).
8
Q
THERAPEUTIC STRATEGIES
A
- nonsteroidal antiinflammatory
drugs (NSAIDs) - glucocorticoids
- diseasemodifying
antirheumatic drugs (DMARDs) - biologics (a
subset of the DMARDs).
9
Q
- *Salicylates and other similar agent**s used to treat rheumatic disease
- *share the capacity to suppress the signs and symptoms** of inflammation.
These drugs also exert antipyretic and analgesic effects,
but it is their anti-inflammatory properties that make them most
useful in the management of disorders in which pain is related to
the intensity of the inflammatory process.
A
NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
Note : Since aspirin, the original NSAID, has a number of adverse
effects, many other NSAIDs have been developed in attempts to
improve upon aspirin’s efficacy and decrease its toxicity.
10
Q
Chemistry & Pharmacokinetics of NSAIDS
A
- grouped in several chemical classes
- chemical diversity yields a broad range of pharmacokinetic
characteristics - some general properties in common
- Most of these drugs are well absorbed, and food does not substantially change their bioavailability
- highly metabolized, some by phase I followed by phase II mechanisms
and others by direct glucuronidation (phase II) alone - While renal
excretion is the most important route for final elimination, nearly
all undergo varying degrees of biliary excretion and reabsorption
(enterohepatic circulation). - Most of the NSAIDs are highly protein-bound
(∼ 98%), usually to albumin.
*
11
Q
All but one of the NSAIDs are weak
organic acidsas given; the exception, ______________, is aketone prodrug that is metabolized to theacidic active drug.
A
nabumetone
12
Q
Most of the NSAIDs (eg, ibuprofen,
ketoprofen) areracemic mixtures, while one, ___________, is provided
as a single enantiomer
A
naproxen
13
Q
and a few have no chiral center
_________________
A
(eg, diclofenac).
14
Q
All NSAIDs can be found in______________after repeated dosing.
A
** synovial fluid**
Note : Drugs with short half-lives remain in the joints longer than would be predicted from their half-lives, while drugs with **longer **half-lives disappear from the synovial fluid at a rate proportionate
to their half-lives.
15
Q
Pharmacodynamics
NSAID anti-inflammatory activity
NSAID anti-inflammatory activity is mediated chiefly through
_____________________
A
inhibition of prostaglandin biosynthesis
16
Q
Various
NSAIDs have additional possible mechanisms of action, including
A
- inhibition of chemotaxis,
- down-regulation of interleukin-1 production,
- decreased production of free radicals and superoxide, and
- interference with calcium-mediated intracellular events.
17
Q
The selective COX-2 inhibitors do not affect
platelet function at their usual doses
A
18
Q
are somewhat more effective in inhibiting COX-1.
A
- aspirin,
- ibuprofen,
- indomethacin,
- piroxicam, and
- sulindac
19
Q
The
efficacy of COX-2-selective drugs equals that of the older
NSAIDs,whileGI safety may be improved. On the other hand,
selective COX-2 inhibitors may increase the incidence of
A
edema and hypertension
20
Q
As of August 2011, ____________ and _____ were the only COX-2 inhibitors marketed in the
USA.
A
celecoxib and the less selective
meloxicam
21
Q
_________________, two previously marketed, selective
COX-2 inhibitors, were withdrawn from the market because
of their association with increased cardiovascular thrombotic
events.
A
Rofecoxib and valdecoxib
22
Q
___________ has a Food and Drug Administration initiated
“black box” warning concerning cardiovascular risks. It has been
recommended that all NSAID product labels be revised to mention
cardiovascular risks.
A
Celecoxib
23
Q
To varying
degrees, all newer NSAIDs are analgesic, anti-inflammatory, and
antipyretic, and all (_________________ and the
___________________) inhibit platelet aggregation.
A
except the COX-2-selective agents
** nonacetylated salicylate**s
24
Q
NSAIDs are
all ______________ and can be associated with GI ulcers and bleeds
as well, although as a group the newer agents tend to cause less GI
irritation than aspirin.
A
gastric irritants
25
\_\_\_\_\_\_\_\_\_\_\_\_ has been observed for all of the drugs for which extensive experience has been reported.
Nephrotoxicity
26
**Nephrotoxicity** is due, in part, to\_\_\_\_\_\_\_\_\_\_\_\_\_
of renal blood flow, which is modulated by prostaglandins.
**Hepatotoxicity can also occur with any NSAID.**
interference with the autoregulation
27
Although these drugs **effectively inhibit inflammatio**n, there is
**no evidence that**—in contrast to drugs such as methotrexate and
other DMARDs—they **alter the course of any arthritic disorder.**
They can inhibit the inflammation but cant alter the arthritic disorder. :)
28
Several NSAIDs **(including aspirin)** reduce the incidence of
\_\_\_\_\_\_\_\_\_\_\_\_ when taken chronically. Several large epidemiologic
studies have shown a 50% reduction in relative risk when the drugs
are taken for 5 years or longer. The mechanism for this protective
effect is unclear.
colon cancer
29
The NSAIDs have a number of commonalities. Although not all
NSAIDs are approved by the FDA for the whole range of rheumatic
diseases, **most are probably effective in rheumatoid arthriti**s, s**eronegative
spondyloarthropathies** (eg, psoriatic arthritis and arthritis associated with inflammatory bowel disease), osteoarthritis, localized
musculoskeletal syndromes (eg, sprains and strains, low
back pain), and **gout (except** \_\_\_\_\_\_\_\_, which appears to be ineffective
in gout).
tolmetin
30
Adverse effects are generally quite similar for all of the NSAIDs:
**1. Central nervous system**: Headaches, tinnitus, and dizziness.
**2. Cardiovascular**: Fluid retention, hypertension, edema, and rarely, myocardial infarction, and congestive heart failure.
**3. Gastrointestinal**: Abdominal pain, dysplasia, nausea, vomiting, and rarely, ulcers or bleeding.
**4. Hematologic:** Rare thrombocytopenia, neutropenia, or even aplastic anemia.
**5. Hepatic**: Abnormal liver function tests and rare liver failure. **6. Pulmonary:** Asthma.
**7. Skin:** Rashes, all types, pruritus.
**8. Renal**: Renal insufficiency, renal failure, hyperkalemia, and proteinuria.
31
This long use and availability **without prescription** diminishes
its glamour compared with that of the newer NSAIDs. This is
**now rarely used** as an anti-inflammatory medication and will be
**reviewed only in terms of its anti-platelet effects** (ie, doses of
**81–325 mg once daily)**.
ASPIRIN
32
The
**salicylates are rapidly absorbed** from the stomach and upper small intestine yielding a peak plasma salicylate level within\_\_\_\_\_\_\_\_\_\_\_\_
1–2 hours.
33
Aspirin is absorbed as such and is rapidly hydrolyzed (serum **halflife**
\_\_\_\_\_\_\_\_\_\_\_) to acetic acid and salicylate by esterases in tissue
and blood ( Figure 36–3 ).
Salicylate is nonlinearly bound to albumin.
Alkalinization of the urine increases the rate of excretion of
free salicylate and its water-soluble conjugates.
15 minutes
34
**Mechanisms of Action**Aspirin
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
In other
tissues, synthesis of new COX replaces the inactivated enzyme so
that ordinary doses have a duration of action of 6–12 hours.
irreversibly inhibits platelet COX so that aspirin’s antiplatelet
effect lasts **8–10 days (the life of the platelet).**
35
Aspirin decreases the incidence of transient ischemic attacks,
unstable angina, coronary artery thrombosis with myocardial
infarction, and thrombosis after coronary artery bypass grafting
(see Chapter 34 ).
Epidemiologic studies suggest that long-term use of aspirin at
low dosage is associated with a **lower incidence of colon cancer,**
**possibly related to its COX-inhibiting effects.**
colon cancer decrease incidence
36
Adverse Effects
In addition to the common side effects listed above**, aspirin’s
main adverse effects**at**antithrombotic doses** are\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
\_\_\_\_\_\_\_\_\_\_\_\_\_ rarely if ever occur
at antithrombotic doses.
1. gastric upset (intolerance) and
2. gastric and duodenal ulcers
3. Hepatotoxicity, asthma, rashes, GI bleeding, and renal toxicity
37
The antiplatelet action of aspirin **contraindicates its use** by
patients with \_\_\_\_\_\_\_\_\_\_
hemophilia
38
. Although previously not recommended
**during pregnancy**, aspirin may be valuable in treating \_\_\_\_\_\_\_\_\_\_\_\_\_\_
preeclampsiaeclampsia.
39
These drugs include **magnesium choline salicylate**, **sodium salicylate,**
and **salicyl salicylate.** All are effective
anti-inflammatory drugs, although they **may be less effective analgesics**
**than aspirin**.
NONACETYLATED SALICYLATES
40
Because NONACETYLATED SALICYLATES they are much **less effective than
aspirin as COX inhibitors**and they**do not inhibit platelet aggregation,**
**they may be preferable** when **COX inhibition is undesirable**
such as in patients with \_\_\_\_\_\_\_\_\_\_\_\_\_\_
The nonacetylated salicylates are administered in doses up to
**3–4 g of salicylate a day** and can be **monitored using serum salicylate
measurements.**
1. asthma,
2. those with bleeding tendencies,
3. and even (under close supervision) those with renal dysfunction.
41
COX-2 SELECTIVE INHIBITORS
Celecoxib
Meloxicam
42
**\_\_\_\_\_\_\_\_\_\_\_\_\_** were developed in an attempt
to **inhibit prostaglandin synthesis** by the **COX-2 isozyme induced
at sites of inflammation without****affecting the action** of the constitutively
**active “housekeeping” COX-1 isozyme** found in the **GI
tract, kidneys, and platelets.**
**COX-2 selective inhibitors**, or** coxibs**,
43
What is the MOA of Cox 2 selective inhibitors?
Coxibs selectively bind to and block the
active site of the COX-2 enzyme much more effectively than that of
COX-1
44
COX-2 inhibitors have **analgesic, antipyretic, and anti-inflammatory**
effects **similar to those of non-selective NSAIDs** but
with an **approximate halving of GI adverse effects.**
45
Likewise, **COX-2 inhibitors at usual doses** have **no impact** on **platelet aggregation**, which is **mediated by thromboxane** produced by the **COX-1 isozyme**.
In contrast, they **do inhibit COX-2-mediated prostacyclin** synthesis in the **vascular endothelium.**
As a result, **COX-2 inhibitors do not offer the cardioprotective** effects o**f traditional nonselective NSAIDs**, which has **resulted in some patients taking low-dose aspirin in addition to a coxib regimen to maintain this effect.**
46
Unfortunately, because COX-2 is constitutively active within the kidney, **recommended doses of COX-2 inhibitors** cause **renal toxicities** similar to those associated with traditional NSAIDs. Clinical data have suggested a **higher incidence of cardiovascular** thrombotic events associated with COX-2 inhibitors such as **\_\_\_\_\_\_\_\_\_\_\_\_\_\_-**, resulting in their withdrawal from the market.
**ro**fecoxib and **valde**coxib
## Footnote
**" ROX VALDEZ"**
47
is a selective **COX-2 inhibitor—about 10–20 times**
more selective for COX-2 than for COX-1.
is associated with fewer endoscopic ulcers than most
other NSAIDs.
Celecoxib
48
Probably because it is a **sulfonamide**, celecoxib
may cause\_\_\_\_\_\_\_\_\_\_\_. It **does not affect platelet aggregation** at usual doses.
rashes
49
celecoxib interacts occasionally with warfarin— as would be expected of a drug metabolized via\_\_\_\_\_\_\_\_\_\_\_
Adverse effects are the common toxicities listed above.
CYP2C9.
50
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_is an enolcarboxamide related to piroxicam that **preferentially inhibits COX-2 over COX-1,** particularly at its **lowest therapeutic dose of 7.5 mg/d**.
It is **not as selective as celecoxib** and may be considered **“preferentially” selectiv**e rather than **“highly” selective.**
Meloxicam
51
It is associated with fewer clinical GI symptoms and complications than **piroxicam, diclofenac, and naproxen**.
Similarly, while ____________ is known to **inhibit synthesis of thromboxane A 2 ,** even at **supratherapeutic doses**, **its blockade of thromboxane A 2 does not reach levels that result in decreased in vivo platelet function** (see common adverse effects above).
meloxicam
52
NONSELECTIVE COX INHIBITORS
Diclofenac
Diflunisal
Etodolac
Flurbiprofen
Ibuprofen
Indomethacin
Ketoprofen
Ketorolac
Nabumetone
Naproxen
Oxaprozin
Piroxicam
Sulindac
Tolmetin
53
\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is a phenylacetic acid derivative that is relatively nonselective as a COX inhibitor.
Gastrointestinal ulceration may occur less frequently than with some other NSAIDs.
Diclofenac
54
A **preparation** combining\_\_\_\_\_\_\_\_\_\_\_\_ decreases upper gastrointestinal ulceration but may result in diarrhea.
diclofenac and misoprostol
55
Another combination of ____________ was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients.
diclofenac and omeprazole
56
**Diclofenac**, 150 mg/d, appears to impair renal blood flow and glomerular filtration rate.
\_\_\_\_\_\_\_\_\_\_\_\_\_ occurs more commonly with this drug than with other NSAIDs.
Elevation of serum aminotransferases
57
A **0.1% ophthalmic preparation** is promoted for **prevention of
postoperative ophthalmic inflammation** and can be used after
**intraocular lens implantation and strabismus surgery.**
Diclofenac
58
A topical gel
containing _____________ is effective for solar keratoses.
3% diclofenac
59
Diclofenac
in\_\_\_\_\_\_\_\_\_\_\_ form can be considered for **preemptive analgesia**
and **postoperative nausea**.
In Europe, diclofenac is also available
as an oral mouthwash and for intramuscular administration.
rectal suppository
60
Although ____________ is **derived from salicylic acid**, **it is not metabolized
to salicylic acid or salicylate**.
It undergoes an **enterohepatic**
**cycle** with reabsorption of its glucuronide metabolite followed by cleavage of the glucuronide to again release the active moiety.
This is subject to capacity-limited metabolism, with serum
half-lives at various dosages approximating that of salicylates
( Table 36–1 ). In rheumatoid arthritis the recommended dose is
**500–1000 mg daily in two divided doses**.
It is claimed to be particularly
* *effective for cancer pain with bone metastases** and for
* *pain control in dental (third molar) surgery.**
Diflunisal
61
A \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is a **clinically useful analgesic** for p**ainful oral lesions.**
Because its clearance depends on renal function as well as hepatic
metabolism, should be limited in patients with
**significant renal impairment.**
2% diflunisal oral
ointment
62
* **racemic acetic** acid derivative with an intermediate
half-life ( Table 36–1 )
* does not undergo chiral inversion in the body. The dosage of etodolac is 200–400 mg three to four times daily.
Etodolac
63
* is a propionic acid derivative with a possibly more
complex mechanism of action than other NSAIDs.
* Its ( S )(–) enantiomer inhibits COX nonselectively, but it has been shown in rat tissue to a**lso affect tumor necrosis factor-α (TNF-α) and nitric
oxide synthesis.**
* Hepatic metabolism is extensive; its ( R )(+) and ( S )
(–) enantiomers are metabolized differently, and it does **not undergo chiral conversion**.
* It does demonstrate enterohepaticbcirculation.
* also available in a topical ophthalmic formulation
for inhibition of **intraoperative miosis**.
* intravenously is effective for **perioperative analgesia in minor ear, neck, **and **nose surgery and in lozenge form for sore throat.**
Flurbiprofen
64
Although its **adverse effect profile is similar to that of other NSAIDs** in most ways,\_\_\_\_\_\_\_\_\_\_\_ is also rarely **associated with cogwheel rigidity**, **ataxia, tremor, and myoclonus.**
flurbiprofen
FLUR
65
\_\_\_\_\_\_\_\_\_ is a simple derivative of **phenylpropionic acid**
( Figure 36–1 ). In doses of about **2400 mg daily**
* is **equivalent to 4 g of aspirin in anti-inflammatory effect.**
* Pharmacokinetic characteristics are given in Table 36–1 .
Ibuprofen
66
* Oral ibuprofen is often prescribed in **lower doses (\<2400 mg/d)**, at which it has **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**
* It is available over the counter in low-dose forms under several trade names.
**analgesic but not anti-inflammatory efficacy.**
67
is **effective in closing patent ductus arteriosus** in
**preterm infants,** with much the s**ame efficacy and safety as indomethacin.**
The oral and intravenous routes are e**qually effective for
this indication.**
A topical cream preparation appears to be absorbed into fascia and muscle; an (S ) (–) formulation has been tested.
This was more effective than placebo cream in the
**treatment of primary knee osteoarthritis.**
Ibuprofen
68
A \_\_\_\_\_\_\_\_\_\_\_\_, 400 mg, provides prompt relief and good overall
efficacy in postsurgical dental pain.
liquid gel preparationof ibuprofen
69
In **comparison with indomethacin**, ibuprofen decreases urine output ____________ and \_\_\_\_\_\_\_\_\_\_\_.
less and also causes less fluid retention
70
Ibuprofen is relatively contraindicated in individuals with\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Aseptic meningitis (particularly in patients with systemic lupus erythematosus), and fluid retention have been reported. Interaction with anticoagulants is uncommon.
* nasal polyps,
* angioedema,
* and bronchospastic reactivity to aspirin.
71
What will happen with ibuprofen and aspiren administered together?
The concomitant administration of ibuprofen and aspirin **antagonizes the irreversible platelet inhibition induced by aspirin.**
Thus, **treatment with ibuprofen in patients with increased cardiovascular risk** may **limit the cardioprotective effects** of aspirin.
Furthermore, the use of ibuprofen concomitantly with aspirin **may decrease the total anti-inflammatory effect**.
72
Ibuprofen Common adverse effects are listed on page 638; rare hematologic effects include\_\_\_\_\_ and \_\_\_\_\_\_\_\_\_\_\_
agranulocytosis and aplastic anemia.
73
\_\_\_\_\_\_\_\_\_\_\_\_\_\_, introduced in 1963, is an **indole derivative**
( Figure 36–1 ).
* It is a **potent nonselective COX inhibitor**
* and may **also inhibit phospholipase A and C,**
* **reduce neutrophil migration,**
* **and decrease T-cell and B-cell proliferation.**
* **It differs somewhat from other NSAIDs in its indications and toxicities.**
Indomethacin
74
It has been **used to *_accelerate_* closure of patent ductus arteriosus.**
has been tried in numerous small or uncontrolled
trials for many other conditions, including **Sweet’s syndrome, juvenile **rheumatoid arthritis, pleurisy, **nephrotic syndrome,** diabetes insipidus, urticarial vasculitis, postepisiotomy pain, and prophylaxis of heterotopic ossification in arthroplasty.
Indomethacin
75
An _________ is **efficacious for conjunctival**
**inflammation** and to **reduce pain after traumatic corneal abrasion.**
Gingival inflammation is reduced after administration of indomethacin oral rinse.
Epidural injections produce a degree of pain
relief similar to that achieved with methylprednisolone in **postlaminectomy
syndrome.**
ophthalmic preparation
76
At usual doses, indomethacin has the common side effects listed above. The GI effects may include pancreatitis.
Headache is experienced by **15–25% of patients** and may be associated with dizziness, confusion, and depression.
**Rarely, psychosis with hallucinations** has been reported.
Renal papillary necrosis has also been observed. A number of interactions with other drugs have been reported (see Chapter 66 ).
Indomethacin
77
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ **prolongs indomethacin’s half-life** by **inhibiting both renal and biliary clearance.**
Probenecid
78
is a propionic acid derivative that inhibits both COX
(nonselectively) and lipoxygenase.
Its pharmacokinetic characteristics
are given in Table 36–1 . Concurrent administration of
***_probenecid_*** elevates ketoprofen levels and prolongs its plasma
half-life
Ketoprofen
79
* is an NSAID promoted for systemic use mainly as an analgesic, **not as an anti-inflammatory drug** (although it **has typical NSAID properties**).
* Pharmacokinetics are presented in Table 36–1 .
* The drug is an ***_effective analgesic and has been used successfully to replace morphine in some situations_*** involving **mild to moderate postsurgical pain**.
* It is most often given intramuscularly or intravenously, but an oral dose formulation is available. When used with an opioid, it may decrease the opioid requirement by 25–50%. An ophthalmic preparation is available for ocular inflammatory conditions. Toxicities are similar to those of other NSAIDs (see page 638), although renal toxicity may be more common with chronic use.
Ketorolac
80
* is the ***_only nonacid NSAID in current use_***;
* it is converted to the active acetic acid derivative in the body.
* It is given as a **ketone prodrug** that **resembles naproxen** in structure ( Figure 36–1 ).
* Its half-life of **more than 24 hours** ( Table 36–1 )
* permits **once-daily dosing,**
* and the drug **does not appear to undergo enterohepatic circulation**.
* Renal impairment results in a doubling of its half-life and a 30% increase in the area under the curve.
* Its properties are very similar to those of other NSAIDs, **though it may be less damaging to the stomach than some other NSAIDs when given at a dosage of 1000** mg/d.
* Unfortunately, higher dosages (eg, 1500–2000 mg/d) are often needed, and this is a very expensive NSAID. Like naproxen has been **associated with pseudoporphyria and photosensitivity** in some patients. Other adverse effects mirror those of other NSAIDs
Nabumetone
81
* is a naphthylpropionic acid derivative.
* It is the **only NSAID presently marketed as a *_single enantiomer._***
* Naproxen’s free fraction is significantly **higher in women than in men**, but half-life is similar in both sexes ( Table 36–1 ).
* Naproxen is effective for the usual rheumatologic indications and is **available in a slowrelease formulation, as an oral suspension**, and **over the counter.**
* A topical preparation and an ophthalmic solution are also available.
* The **incidence of upper GI bleeding** in **over-the-counter use is low** but still **double that of over-the-counter ibuprofen** (perhaps due to a dose effect).
* **Rare cases of allergic pneumonitis**, leukocytoclastic vasculitis, and pseudoporphyria as well as the common
NSAID-associated adverse effects have been noted.
Naproxen
82
\_\_\_\_\_\_\_\_ is another propionic acid derivative NSAID. As noted
in Table 36–1 , its **major difference from the other members of this subgroup** is a very long half-life (50–60 hours), although does **not undergo enterohepatic circulation.**
**It is mildly uricosuric,**
**making it potentially more useful in gout than some other
NSAIDs.**Otherwise, the drug has the same benefits and risks
that are associated with other NSAIDs.
Oxaprozin
83
Piroxicam
Piroxicam, an oxicam ( Figure 36–1 ), is a nonselective COX inhibitor
that at high concentrations also inhibits polymorphonuclear
leukocyte migration, decreases oxygen radical production, and
inhibits lymphocyte function. Its long half-life ( Table 36–1 )
permits once-daily dosing.
Piroxicam can be used for the usual rheumatic indications.
When piroxicam is used in dosages **higher than 20 mg/d, an
increased incidence of peptic ulcer and bleeding is encountered.**
Epidemiologic studies suggest that this risk is as much as 9.5 times
higher with piroxicam than with other NSAIDs (see common
adverse effects above).
84
is a sulfoxide prodrug.
It is reversibly metabolized to the
active sulfide metabolite, which is excreted in bile and then
reabsorbed from the intestine.
The enterohepatic cycling prolongs
the duration of action to **12–16 hours.**
In addition to its rheumatic disease indications
***_suppresses familial intestinal polyposis_*** and it ***_may inhibit the
development of colon, breast, and prostate cancer in humans._***
It
appears to inhibit the occurrence of GI cancer in rats. The latter effect may be caused by the sulfone rather than the sulfide.
Sulindac
85
Among the **more severe adverse reactions Sulindac **, \_\_\_\_\_\_\_\_\_\_\_\_\_have all been observed.
Like ***_diclofenac,_***
* *thisv may have some propensity to cause elevation of serum**
* *aminotransferases;** it is also **sometimes associated with *_cholestatic liver damage_*, which disappears when the drug is stopped**
Stevens-Johnson
epidermal necrolysis syndrome,
thrombocytopenia,
agranulocytosis,
and nephrotic syndrome
86
**All NSAIDs,** including aspirin, are **about equally efficacious with
a few exceptions**—\_\_\_\_\_\_\_\_\_\_\_\_\_\_ seems**not to be effective for gout,**
tolmetin
87
and
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is less effective than other NSAIDs (eg, indomethacin) for
**ankylosing spondylitis.**
aspirin
88
Thus, NSAIDs tend to be differentiated on the **basis of toxicity
and cost-effectiveness.**
For example, the GI and renal side effects
of\_\_\_\_\_\_\_\_\_\_\_\_ limit its use.
ketorolac
89
Some surveys suggest that ____________ and \_\_\_\_\_\_\_\_\_\_\_ are the NSAIDs associated with the ***_greatest toxicity,_***
indomethacin
and tolmetin
90
NSAIDS\_\_\_\_\_\_\_ are least toxic. The selective
COX-2 inhibitors were not included in these analyses.
salsalate, aspirin, and ibuprofen
91
For patients with **renal insufficiency**, \_\_\_\_\_\_\_\_\_\_\_\_\_\_
**may be best**.
nonacetylated salicylates
92
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are associated with more liver
**function test abnormalities than other NSAIDs.**
Diclofenac and sulindac
93
The **relatively
expensive**, selective COX-2 inhibitor \_\_\_\_\_\_\_\_\_\_\_\_is probably *_**safest
for patients at high risk for GI bleeding**_* but may have a**higher riskof cardiovascular toxicity**.
celecoxib
94
\_\_\_\_\_\_\_\_\_\_\_\_\_ ***_plus omeprazole or misoprostol_*** may be appropriate in patients at ***_highest risk for GI bleeding_***; in this subpopulation of patients, they are cost-effective despite their high acquisition costs.
Celecoxib or a nonselective NSAID
95
So that there is no best NSAID for all patients.
There may, however, be **one or two best NSAIDs for a specific
person.**
;)
96
2H. Pharmacology
flashcards
Decks in class (17)
# Cards
-
chapter2 pharmacodynamics48
-
Antimicrobial agents128
-
Principles of Antimicrobial Therapy74
-
Sulfonamides, Trimethoprim and Quinolones0
-
Aminoglycosides and Spectinomycin39
-
Tetracyclines and Chlorampenicol55
-
Macrolides, Clindamycin, Streptoramins37
-
ENDOC- Pancreatic hormone and Antidiabetic Drug1
-
Endoc- Thyroid and Antithyroid drugs0
-
Endoc- Gonadal hormones and Inhibitors35
-
Endoc- Antihyperlipid EMC agents0
-
MODULE6- ANTIINFLAMMATORY96
-
Mod 6- Introduction to the Pharmacology of CNS Drugs55
-
MOD 6- GOUT81
-
Mod6- Antiseizure Drugs68
-
AntiPARKINSONISM30
-
MOD 6- OPIOD53
