NSAIDs, Acetaminophen, DMARDS and Drugs Used in Gout Flashcards by Jamaira Belmes

Acetylation of COX-1 and COX-2 results in decreased prostaglandin synthesis

Nonselective IRREVERSIBLE COX1 and COX 2

USES:
prevention of arterial thrombosis (MI, TIA, CVD)

SALICYLATE

Aspirin

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The ONLY IRREVERSIBLE INHIBITOR of COX

Aspirin

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Non-Selective COX Inhibitors

Aspirin
Ibuprofen
Ketoprofen
Furbiprofen
Naproxen
Nabumetone
Etodolac
Ketorolac
Piroxicam
Indomethacin
Sulindac

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Side effects of Non-Selective COX Inhibitors

GI bleeding

nephrotoxicity

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Propionic Acid Derivatives

Ibuprofen - less gastric irritation; NOT given w/ aspirin
Ketoprofen
Flurbiprofen - longest duration

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Side effects of Flurbiprofen

severe gastric irritation

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Only NON-ACID derived Non-Selective COX Inhibitors

Nabumetone

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Used as analgesia for post operational therapy

Etodolac

Ketorolac

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Non-Selective COX Inhibitor that is related to Sulfonamides

Sulindac

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Non-Selective COX Inhibitors that also (-) phospholipase A2

for closure of PDA

Indomethacin

Paracetamol IV - alternative

physiologic closure of DU - 14-15 hrs
anatomic closure of DU - 2-3 weeks

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COX II Selective Inhibitors

Celecoxib
Parecoxib
Etoricoxib

Lumiracoxib
Valdecoxib
Rofecoxib

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Not used COX II Selective Inhibitors d.t. THROMBOSIS, MI and HPN

Lumiracoxib
Valdecoxib
Rofecoxib

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Selective inhibits COX-3

Paracetamol (Acetaminophen)

Phenacetin

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Antidote for paracetamol toxicity

N-acetylcysteine - sulfhydryl donor

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MOA of Methotrexate

INHIBITS FOLATE SYNTHESIS BY

(-) AICAR TRANSFORMYLASE
(-) THYMIDYLATE SYNTHETASE
(-) DIHYDROFOLATE REDUCTASE

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Current DMARD of choice for the treatment of Rheumatoid Arthritis

Methotrexate

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Side effects of Methotrexate

mucositis/mucosal ulcers

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Rescue agent for Methotrexate

LEUCOVORIN (FOLINIC ACID)

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Binds to TNF-a and prevents it from activating TNF-a receptor

Infliximab
Adalimumab
Certolizumab
Golimumab
Etanercept

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Side effects of TNF-a inhibitors

TB reactivation

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MOA of Azathioprine

forms 6-THIOGUANINE –> suppresses INOSINIC ACID SYNTHESIS –> DNA synthesis

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MOA of Chloroquine

suppression of T-lymphocyte responses to mitogens

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Side effects of Chloroquine

ocular toxicity

prolonged QT interval

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MOA of Cyclophosphamide

ALKYLATING AGENT

form PHOSPHORAMIDE MUSTARD –> cross links to prevent cell replication

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Rescue agent for Cyclophosphamide

2-mercaptoethane sulfonate sodium (MESNA)

MOA of Cyclosporine

(-) IL-1 and IL-2 receptor production targets CALCINEURIN

Side effects of Cyclosporine

hirsutism | gingival hyperplasia

MOA of Mycophenolate Mofetil

(-) cytosine monophosphate (CMP) | (-) T cell lymphocyte proliferation

Side effects of Mycophenolate Mofetil

aplastic anemia

MOA of Sulfasalazine

active metabolite (SULFAPYRIDINE) --> (-) release of inflammatory cytokines

Side effects of Sulfasalazine

allergies | SJS

MOA of Abatacept

(-) activation of T cells by binding to CD80 and CD86

Side effects of Abatacept

increased risk of infections | URTI

MOA of Leflunomide

active metabolites --> (-) DIHYDROOROTATE DEHYDROGENASE --> decreased synthesis of ribonucleotide and arrest of stimulated cells in the G1 phase of cell growth

MOA of Rituximab

depletes B cells by cell mediated and complement dependent cytotoxicity and stimulation of cell apoptosis --> reduced inflammation by decreasing the presentation of antigens to T lymphocytes and (-) secretion of cytokine

MOA of Tocilizumab

binds to IL-6 --> decreased T cell activation and inflammatory process

(-) MICROTUBULE assembly and LTB4 production --> decrease macrophage migration

Colchicine for ACUTE ATTACK of GOUT

Side effects of Colchicine

diarrhea GI disturbance hepatotoxicity nephrotoxicity

The adverse which signals toxicity from colchicine

diarrhea

active metabolite ALLOXANTHINE -- irreversibly (-) XANTHINE OXIDASE

Allopurinol for CHRONIC GOUT tumor lysis syndrome

NONPURINE reversible (-) of xanthine oxidase

Febuxostat for CHRONIC GOUT tumor lysis syndrome allopurinol intolerance

URICOSURIC AGENTS

Probenecid | Sulfapyrazone

MOA of Uricosuric Agents

(-) reabsorption of uric acid in PCT

Prolongs the action of PENICILLIN by (-) tubular secretion

Probenecid

Novel urate lowering recombinant mammalian urate oxidase enzyme

Pegloticase

IL-1 pathway (-)

Anakinra Canakinumab Rilonacept

Among NSAIDs, aspirin is unique because it (A) Irreversibly inhibits its target enzyme (B) Prevents episodes of gouty arthritis with long-term use (C) Reduces fever (D) Increases the risk of colon cancer (E) Selectively inhibits the COX-2 enzyme

(A) Irreversibly inhibits its target enzyme

Which of the following is an analgesic and antipyretic drug that lacks an anti-inflammatory action? ``` (A) Acetaminophen (B) Celecoxib (C) Colchicine (D) Indomethacin (E) Probenecid ```

(A) Acetaminophen

Clinical Presentation of ASPIRIN OVERDOSE

``` HAGMA dehydration hyperthermia collapse coma ```

A 16-year-old girl comes to the emergency department suffering from the effects of an aspirin overdose. Which of the following syndromes is this patient most likely to exhibit as a result of this drug overdose? (A) Bone marrow suppression and possibly aplastic anemia (B) Fever, hepatic dysfunction, and encephalopathy (C) Hyperthermia, metabolic acidosis, and coma (D) Rapid, fulminant hepatic failure (E) Rash, interstitial nephritis, and acute renal failure

Which of the following drugs is most likely to increase serum concentrations of conventional doses of methotrexate, a weak acid that is primarily cleared in the urine? ``` (A) Acetaminophen (B) Allopurinol (C) Colchicine (D) Hydroxychloroquine (E) Probenecid ```

(E) Probenecid

The main advantage of ketorolac over aspirin is that ketorolac (A) Can be combined more safely with an opioid such as codeine (B) Can be obtained as an over-the-counter agent (C) Does not prolong the bleeding time (D) Is available in a parenteral formulation that can be injected intramuscularly or intravenously (E) Is less likely to cause acute renal failure in patients with some preexisting degree of renal impairment

(D) Is available in a parenteral formulation that can be | injected intramuscularly or intravenously

An 18-month-old boy dies from an accidental overdose of acetaminophen. Which of the following is the most likely cause of this patient’s death? ``` (A) Arrhythmia (B) Hemorrhagic stroke (C) Liver failure (D) Noncardiogenic pulmonary edema (E) Ventilatory failure ```

(C) Liver failure In overdose, acetaminophen causes fulminant liver failure as a result of its conversion by hepatic cytochrome P450 enzymes to a highly reactive metabolite

A 52-year-old woman presented with intense pain, warmth, and redness in the first toe on her left foot. Examination of fluid withdrawn from the inflamed joint revealed crystals of uric acid. In the treatment of this woman’s acute attack of gout, a high dose of colchicine will reduce the pain and inflammation. However, many physicians prefer to treat acute gout with a corticosteroid or indomethacin because high doses of colchicine are likely to cause ``` (A) Behavioral changes that include psychosis (B) High blood pressure (C) Rash (D) Severe diarrhea (E) Sudden gastrointestinal bleeding ```

(D) Severe diarrhea

Over the next 7 mo, the patient had 2 more attacks of acute gout. Her serum concentration of uric acid was elevated. The decision was made to put her on chronic drug therapy to try to prevent subsequent attacks. Which of the following drugs could be used to decrease this woman’s rate of production of uric acid? ``` (A) Allopurinol (B) Aspirin (C) Colchicine (D) Hydroxychloroquine (E) Probenecid ```

(A) Allopurinol Aspirin actually slows renal secretion of uric acid and raises uric acid blood levels. It should not be used in gout

A 54-year-old woman presented with signs and symptoms consistent with an early stage of rheumatoid arthritis. The decision was made to initiate NSAID therapy. Which of the following patient characteristics is the most compelling reason for avoiding celecoxib in the treatment of her arthritis? ``` (A) History of alcohol abuse (B) History of gout (C) History of myocardial infarction (D) History of osteoporosis (E) History of peptic ulcer disease ```

(C) History of myocardial infarction Celecoxib is a COX-2-selective inhibitor. Although the COX-2 inhibitors have the advantage over nonselective NSAIDs of reduced gastrointestinal toxicity, clinical data suggest that they are more likely to cause arterial thrombotic events. A history of myocardial infarction would be a compelling reason to avoid a COX-2 inhibitor

Although the patient’s disease was adequately controlled with an NSAID and methotrexate for some time, her symptoms began to worsen and radiologic studies of her hands indicated progressive destruction in the joints of several fingers. Treatment with another second-line agent for rheumatoid arthritis was considered. Which of the following is a parenterally administered DMARD whose mechanism of anti-inflammatory action is antagonism of tumor necrosis factor? ``` (A) Cyclosporine (B) Etanercept (C) Penicillamine (D) Phenylbutazone (E) Sulfasalazine ```

(B) Etanercept

Common NSAIDs TOXICITIES

``` GI Toxicity Nephrotoxicity Hypersensitivity Hematologic Hepatic Pulmonary CNS CVS ```

NON-SELECTIVE NSAIDS reversible COX 1 and 2 inhibition USES: analgesia antipyretic anti-inflammatory

ORAL ``` Ibuprofen Diclofenac Ketoprofen Piroxicam Mefenamic Acid Sulindac ```

NON-SELECTIVE NSAIDS reversible COX 1 and 2 inhibition USES: post surgical analgesic control for analgesia

INTRAVENOUS Ketorolac Dexketoprofen

NON-SELECTIVE NSAIDS reversible COX 1 and 2 inhibition USES: for PDA CLOSURE

Indomethacin (COX 1 > COX2)

COX 2 SELECTIVE NSAIDS Selective COX-2 Inhibitor USES: analgesia antipyretic anti-inflammatory

``` Celecoxib Etoricoxib Rofecoxib Valdecoxib Parecoxib ``` SE: MI Stroke - Rofecoxib and Valdecoxib

Selectively inhibits COX 3 Inhibits prostaglandin synthesis USES: analgesia (mild) antipyretic

Paracetamol (Acetaminophen)

DMARDS Suppression of T lymphocyte responses to mitogens Stabilization of lysosomal enzymes ``` USES: RA SLE Sjogren syndrome Malaria ```

ANTI-MALARIALS Chloroquine Hydroxychloroquine SE: CINCHONISM - headache, tinnitus, vertigo

DMARDS Binds to TNF-a and prevents it from activating TNF-a receptor USES: Crohn's disease RA

TNF-ALPHA INHIBITOR ``` Infliximab Adalimumab Etanercept Certolizumab Golimumab ```

DMARDS Forms 6- thioguanine -- suppresses inosinic acid synthesis

Azathioprine

DMARDS Inhibits IL-1 and IL-2 receptor production USES; tissue transplantation

Cyclosporine

DMARDS Active product (mycophenolic acid) inhibits inosine monophosphate dehydrogenase and (-) T cell lymphocyte proliferation

Mycophenolate Mofetil

DMARDS Active metabolites (sulfapyridine) inhibits the release of inflammatory cytokines

Sulfasalazine

DMARDS Inhibits activation of T cells by binding to CD80 and CD86 on the APC USES: moderate - severe

Abetacept

DMARDS Its active metabolite (-) dihydroorotate dehydrogenase -- decreased synthesis of ribonucleotide and arrest of stimulated cells in the G1 phase of cell growth USES: RA

Leflunomide

DMARDS CD20 Inhibitor

MONOCLONAL ANTIBODIES Rituximab

DMARDS Binds to IL-6 -- decreased T cell activation and inflammatory process

MONOCLONAL ANTIBODIES Tocilizumab SE: TB Fungal, Viral and other Opportunistic Infections