Msi Week 1: Nsaids, Dmards, Gout...

Front 1

What is the mechanism of action of all NSAIDs?

Back 1

Blockade of COX enzymes, which reduces the production of prostanoids (prostaglandins, thromboxanes)

Front 2

Name the 3 effects of all NSAIDs.
(what is the one exception?)

Back 2

1. Anti-inflammatory
2. Analgesic
3. Antipyretic

*Exception--> Acetaminophen is not anti-inflammatory at normal dosages

Front 3

Which COX enzyme is more important in the inflammatory response?

Back 3

COX-2
(although both COX-1 and COX-2 are induced, COX-2 levels increase to a greater extent during inflammation)

Front 4

What is the primary use of NSAIDs?

Back 4

Treatment of the inflammatory component of musculoskeletal disorders such as:
1. Rheumatoid arthritis
2. Osteoarthritis

*Produce only symptomatic relief from pain and inflammation

Front 5

Name the 5 main groups of NSAIDs.

Back 5

1. Salicylic acids
2. Acetaminophen
3. Propionic acids
4. Carbo and heterocyclic acids
5. Selective COX-2 inhibitor

Front 6

Give an example of a salicylic acid.

Back 6

Asprin (acetylsalicylic acid)
(NSAID)

Front 7

Which NSAID is the only non-competitive inhibitor of COX-1 and COX-2?

Back 7

Aspirin (acetylsalicylic acid)

Front 8

What is the clinical usage of Aspirin?

Back 8

Increases bleeding time by inhibiting platelet aggregation

*Reduces the incidence of transient ischemic attacks, and thromboses after myocardial infarction and coronary artery bypass surgery.

*Also used to treat mild to moderate pain

Front 9

What can be an adverse effect of Aspirin?

Back 9

Gastric and duodenal ulcers
Reye's syndrome in children

Front 10

At usually doses, which NSAID has no anti-inflammatory effect, does not inhibit platelets, and does not affect the level of uric acid?

Back 10

Acetaminophen (Tylenol)

Front 11

What is the clinical usage of Acetaminophen?

Back 11

Antipyretic and analgesic

(*Cannot be used to treat arthritis since it has no anti-inflammatory effect)

Front 12

Which drug is the preferred analgesic/antipyretic drug for use in children?

Back 12

Acetaminophen

Front 13

What can be an adverse effect of acetaminophen?

Back 13

Hepatic damage

(With high doses= liver toxicty, renal toxicity, and death)

Front 14

Name 2 propionic acids.

Back 14

1. Ibuprofen (Advil, Motrin)
2. Naproxen

Front 15

What is the mechanism of action of acetaminophen?

Back 15

Weak competitive inhibitor of COX-1 and COX-2

Front 16

What is the mechanism of action of propionic acids?

Back 16

Competitive inhibition of COX-1 and COX-2

Front 17

What is the clinical usage of Ibuprofen?

Back 17

At high doses = anti-inflammatory effect
Low doses = analgesic and antipyretic effects
*Can be used to close the ductus arteriosus in preterm infants

Front 18

Name 2 carbo and heterocyclic acids.

Back 18

1. Indomethacin
2. Ketorolac

Front 19

What is the mechanism of action of carbo and heterocyclic acids?

Back 19

Competitive inhibition of COX-1 and COX-2.

Front 20

T or F.

Indomethacin is only available by prescription.

Back 20

TRUE.

Front 21

What are the clinical uses of Indomethacin?

Back 21

1. Gout
2. Ankylosing spondylitis
3. Close the ductus arteriosus

(Carbo or heterocyclic acid)

Front 22

What is the primary clinical usage of Keterolac?

Back 22

Post-surgical pain

(Carbo or heterocyclic acid)

Front 23

What are some adverse affects of Indomethacin at high doses?

Back 23

1. Pancreatitis
2. Thrombocytopenia
3. Aplastic anemia
4. Renal papillary necrosis

Front 24

Which NSAID is a selective COX-2 inhibitor?

Back 24

Celecoxib (Celebrex)

Front 25

T or F.

Celecoxib can effect platelet aggregation.

Back 25

FALSE.

Celecoxib has no DIRECT effect on platelet aggregation since it is a selective COX-2 inhibitor (COX-1 is responsible for the release of thromboxane A2 from platelets)

*Celecoxib does, however, inhibit the release of prostacyclin (PGI2)

Front 26

Which NSAID was developed in hope that it would blunt the occurrence of GI effects common to NSAIDs?

Back 26

Celecoxib

*GI side effects are reduced, but only to about 50%.

Front 27

Which drug is sometimes used with Celecoxib to maintain the therapeutic anti-clotting effect?

Back 27

Aspirin

(Celecoxib indirectly enhances clotting, so aspirin can counteract this tendency)

Front 28

T or F.

In general, all NSAIDs are equally effective as anti-inflammatory, analgesic, and antipyretic agents.

Back 28

TRUE.

Front 29

A person who is more susceptible to GI distress should probably take which NSAIDs?

Back 29

Celecoxib (Celebrex)

(*However, a person at high risk for cardiovascular events should avoid Celecoxib)

Front 30

Name the group of drugs that reduce or reverse the progression of rheumatoid arthritis.

Back 30

Disease-Modifying Antirheumatic Drugs (DMARDs)

Front 31

What is the general mechanism of action of DMARDs?

Back 31

Inhibit immune response that is responsible for causing rheumatic diseases.

Front 32

Name 8 DMARDs.

Back 32

1. Methotrexate
2. Cyclophasphamide
3. Cyclosporine
4. Abatacept
5. Sulfasalazine
6. Chloroquine and Hydroxychloroquine
7. TNF-a blocking agents (Adalimumab, Infliximab, Entercept)
8. Glucocorticoids-- Prednisone

Front 33

Which DMARD is an anolog of folic acid?

Back 33

Methotrexate

Front 34

What is the mechanism of action of Methotrexate for the treatment of rheumatoid arthritis?

Back 34

*Inhibits enzymes involved in purine synthesis, which results in inhibition of proliferation of immune-inflammatory cells.

Enzymes blocked:
1. Aminoimidazole carboxamide ribonucleotide trasformylase
2. Thymidylate synthetase

Front 35

Which drug is the first choice of DMARDs for treatment of rheumatoid arthritis?

Back 35

Methotrexate

Front 36

What are some adverse effects of Methotrexate?

What type of patients is this drug contraindicated for?

Back 36

Nausea and mucosal ulcers

Contraindicated in pregnant women (can induce abortions)

Front 37

Which DMARDs cross-links (alkylates) DNA, inhibiting the proliferation of T-cells?

Back 37

Cyclophosphamide

Front 38

What are some adverse effects of Cyclophosphamide?

Back 38

1. Nausea
2. Vomitting
3. Alopecia
4. Sterility
5. Leukemia
6. Hemorrhagic cystitis

Front 39

Which DMARD suppresses antigen-triggered T-cell function by inhibiting the activity of calcineurin?

Back 39

Cyclosporine

*The ultimate result is reduction in the expression of lymphokines, including IL-2

Front 40

Which DMARD is typically used for severe cases of rheumatoid arthritis?

Back 40

Cyclosporine

Front 41

What are some adverse effects of cyclosporine?

Back 41

1. *Nephrotoxicity
2. Hypertension
3. Hyperlipidemia
4. Hyperuricemia
5. Drug interactions (CYP3A)

Front 42

What is the mechanism of Abatacept?

Back 42

Inhibits the activation of T-cells
(DMARD)

Front 43

Which drug is used in patients with rheumatoid arthritis who have not responded adequately to other DMARDs?

Back 43

Abatacept

Front 44

Which DMARD inhibits the release of inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-a?

Back 44

Sulfasalazine

Front 45

Which DMARD inhibits calcineurin and ultimately reduces the expression of lymphokines including IL-2?

Back 45

Cyclosporine

Front 46

Which DMARDs are actually antimalarial drugs?

Back 46

Chloroquine and Hydroxychloroquine

Front 47

Name 3 TNF-a blocking drugs.

Back 47

1. Adalimumab
2. Infliximab
3. Etanercept

*These are all antibodies to TNF-a, a proinflammatory cytokine-- inactivation of TNF-a reduces the inflammatory response

Front 48

Name an example of a glucocorticoid.

Back 48

Prednisone
(DMARD)

Front 49

Which DMARDs depress the inflammatory response by blocking the activity of phospholipase A2, thereby reducing the production of eicosanoids?

Back 49

Glucocorticoids (prednisone)

Front 50

Gout is a form of arthritis caused by the buildup of ________ crystals in and around joints.

Back 50

Uric acid

Front 51

Uric acid is the final breakdown product of ________ metabolism

Back 51

Purine metabolism

Front 52

Which enzyme catalyzes the reactions of hypoxanthine to xanthine and xanthine to uric acid?

Back 52

Xanthine oxidase

Front 53

What condition appears to be necessary for gout to occur?

Back 53

Hyperuricemia (high plasma levels of urate)

Front 54

What are most cases of gout caused by-- an underexcretion of uric acid or an overproduction of uric acid?

Back 54

90% due underexcretion of uric acid

(10% due to overproduction)

Front 55

Uric acid is both reabsorbed and secreted in the.....?

Back 55

Proximal renal tubule

Front 56

What is the net result of uric acid reabsorption and secretion?

Back 56

10 % of filtered uric acid is excreted and the remainder is reabsorbed

Front 57

What condition develops if too little uric acid is excreted?

Back 57

Hyperuricemia

Front 58

What might happen if too much uric acid is excreted?

Back 58

Uric acid may crystallize in the kidney, producing uric acid stones and/or renal damage

Front 59

What are the 4 stages of gout?

Back 59

1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Asymptomatic intercritical period
4. Chronic tophaceous gout

Front 60

Where does the first instance of gout typically occur?

Back 60

Big toe

Front 61

Stage of gout that occurs between acute attacks.

Back 61

Asymptomatic intercritical period

Front 62

Stage of gout that is characterized by the presence of tophi in and around joints

Back 62

Chronic tophaceous gout
(tophi are crystals of uric acid along with cellular products of the inflammatory process)

Front 63

What is the pharmacologic treatment strategy for gout?

Back 63

1. Treat the symptoms
2. Reduce the risk of subsequent attacks
3. Reduce plasma level of uric acid

Front 64

Which drugs are used for the acute treatment of gout (4)

Back 64

1. Indomethacin
2. Naproxen
3. Celecoxib
4. Glucocorticoids

Front 65

Is Aspirin ever used to treat gout?

Back 65

NO.
In low doses it inhibits uric acid excretion and in high doses it increases uric acid excretion

Front 66

Which drugs are used to reduce subsequent attacks of gout?

Back 66

1. Allopurinol
2. Febuxostat
3. Colchicine
4. Probenecid
5. Sulfinpyrazone

Front 67

Name 2 inhibitors of xanthine oxidase.

Back 67

1. Allopurinol
2. Febuxostat

(Used in treatment to reduce subsequent attacks of gout)

Front 68

Which drug is an analog of hypoxanthine and blocks xanthine oxidase, thereby reducing the formation of uric acid?

Back 68

Allopurinol

Front 69

Which drug is a non-purine inhibitor of xanthine oxidase?

Back 69

Febuxostate

Front 70

T or F.

In the initial months of therapy with xanthine oxidase inhibitors, there may be an increased number of attacks of gout.

Back 70

TRUE

Front 71

Which drug is often used during the early treatment period of gout to prevent attacks that are frequent with xanthine oxidase inhibitors?

Back 71

Colchicine

Front 72

Drug that can be used in patients who can no longer take allopurinol.

Back 72

Febuxostat

Front 73

Drug used to prevent subsequent attacks of gout by inhibiting the formation of microtubules.

Back 73

Colchicine

Front 74

What is a disadvantage of using Colchicine?

Back 74

It has a narrow therapeutic index and severe toxicities.

*Very effective, but should not be used again for at least 7 days due to toxicities

Front 75

Name 2 uricosuric agents.

Back 75

1. Probenecid
2. Sulfinpyrazone

Front 76

What is the mechanism of action of uricosuric agents?

Back 76

Increase excretion of uric acid by inhibiting its reabsorption

*These drugs compete w/ uric acid for the renal organic acid transporter in the proximal tubule

Front 77

During which stage of gout are uricosuric agents typically used?

Back 77

During the intercritical period

Front 78

Name 4 spasmolytic drugs.

Back 78

1. Diazepam
2. Baclofen
3. Tizanidine
4. Dantrolene

Front 79

Name 5 miscellaneous muscle relaxants.

Back 79

1. Carisoprodol
2. Cyclobenzaprine
3. Methacarbamol
4. Orphenadrine
5. Chlorzoxazone

Front 80

An increase in tonic stretch reflexes and flexor muscle spasms

Back 80

Spasticity

Front 81

Most spasmolytics reduce the hyperactive stretch reflex in one of 2 ways. Name these MOAs.

Back 81

1. Reducing the activity of the nerve fibers that excite the motor neuron
2. Enhancing the activity of inhibitory interneurons

Front 82

Prototypical benzodiazepine

Back 82

Diazepam
(Controlled substance: C-IV in OK)

Front 83

Which spasmolytic drug is an agonist at GABAa receptors on motor neuron synapses?

Which spasmolytic is an agonist to the GABAb receptor?

Back 83

GABAa --> Diazepam

GABAb --> Baclofen

*Both drugs enhance the activity of inhibitory interneurons (since GABA is inhibitory)

Front 84

Which spasmolytic is a central acting alpha-2 adrenergic agonist?

Back 84

Tizanidine

Front 85

Which spasmolytic acts to block the ryanodrine receptor which releases Ca2+ and leads to spasticity?

Back 85

Dantrolene

Front 86

Which muscle relaxant has a fairly mild skeletal muscle relaxing activity?

Back 86

Carisoprodol

Front 87

Which muscle relaxant has a high abuse potential? (C-IV in OK)

Back 87

Carisoprodol

Front 88

Which 3 muscle relaxants may have central antihistamine and anticholinergic effects?

Back 88

1. Cyclobenzaprine
2. Methacarbamol
3. Orphenadrine