Med Chem Lecture 13 Spring

Front 1

What does DMARDs stand for?

Back 1

disease-modifying antirheumatic drugs

Front 2

disease-modifying antirheumatic drugs (DMARDs) however, which seem to be effective in the treatment of _____disorders yet fail to exhibit activity in standard assays for _____ drugs

Back 2

arthritic

antiarthritic

Front 3

Both DMARDs and NSAIDS improve symptoms of ___ ___

Back 3

rheumatoid arthritis

Front 4

Both DMARDs and NSAIDS improve symptoms of rheumatoid arthritis, only ______ have been shown to alter the progression of the disease and reduce destruction of the joints

Back 4

DMARDs

Front 5

DMARDs are typically used along with an __ or __ in comboination

Back 5

NSAID or steroid in combination

Front 6

DMARDs are typically used along with an NSAID or steroid in combination. The ______ treats the immediate symptoms, while the ____ gets to work on the disease itself

Back 6

NSAID/steroid

DMARDS

Front 7

DMARDs have a ____onset of action, taking up to ____months to show a measurable benefit, and their long term use can involve ____ ___ __

Back 7

DMARDs have a very slow onset of action, taking up to three months to show a measurable benefit, and their long term use can involve dangerous side effects.

Front 8

DMARDs can be divided into two general categories?

Back 8

Synthetic chemical DMARDs

Biological DMARDs

Front 9

Synthetic chemical DMARDsare drugs that may either treat what or what?

Back 9

the disease or act as immunosuppressants.

Front 10

Biological DMARDs are dosed how? What do they target?

Back 10

subQ or IV, and target inflammatory cytokines (TNFα) and T lymphocytes (T cells).

Front 11

what are 2 Chemical DMARDs?

Back 11

gold compounds
hydroxychloroquine

Front 12

what are 2 Biological DMARDS?

Back 12

soluble TNF receptors (Etanercept)
anti-TNFα-antibodies (Infliximab)

Front 13

___ and __ ___ are highly water soluble gold-conatining polymers and decompose upon standing at room temp

Back 13

Aurothioglucose (aka thioglucose) and sodium aurothiomalate

Front 14

The only effective DMARD gold compounds have __-__ bonds within

Back 14

gold-sulfur bonds

Front 15

Aurothioglucose (aka thioglucose) and sodium aurothiomalate these drugs are rapidly converted to a ____ state from ___ state

Back 15

a +3 oxidation state (“auric”) or to metallic gold

+1 oxidation state (“aurous”)

Front 16

Aurothioglucose therapeutic effect is correlated with accumulated ____, not ___ levels

Back 16

gold, not with serum plasma gold levels.

Front 17

Aurothiomalate is also ____ water soluble and is also _____ and light _____.

Back 17

highly

unstable

sensitive

Front 18

Aurothiomalate is also highly water soluble and is also unstable and light sensitive. It is administered IM and the patient must be in the what position for how long?

Back 18

in the supine position for 10 min following injection.

Front 19

is an acetylated thioglucose derivative that contains a phosphine ligand attached to the gold atom

Back 19

Auranofin

Front 20

Auranofin is an acetylated thioglucose derivative that contains a phosphine ligand attached to the gold atom. This drug is orally ____

Back 20

bioavaliable

Front 21

Auranofin


The_____ ligand stabilizes the lower oxidation state of the gold and allows the drug to exist in _____ form

Back 21

Phospine

momoneric

Front 22

The phosphine ligand stabilizes the lower oxidation state of the gold and allows the drug to exist in momoneric form. Changes made to the substituents on the ______atom will effect activity

Back 22

phosphorous

Front 23

. Changes made to the substituents on the phosphorous atom will effect activity, and the phosphine plays a role in ____ activity

Back 23

anti-arthritic

Front 24

Auranofin plasma gold level are lower for the ___ ____ compounds

Back 24

parenterally administered compounds

Front 25

The ____are antimarial drugs, but their antirheumatic effects are not associated with antimalarial activity

Back 25

aminoquinolines

Front 26

aminoquinoline accumate in ___ and inhibit certain ___ enzymes

Back 26

lysosomes and inhibit certain lysosomal enzymes.

Front 27

_____ is less toxic, but also less effective as an antirheumatic

Back 27

Hydroxychloroquine

Front 28

when Hydroxychloroquine is dosed with aurothio glucose there is an increased risk of ____ damage

Back 28

liver

Front 29

Chloroquine itself has both ___and _____ toxicities, so it is only used for ______ treatment

Back 29

Chloroquine itself has both corneal and renal toxicities, so it is only used for antimalarial treatment

Front 30

Sulfasalazine is a ____ drug

Back 30

codrug

Front 31

Sulfasalazine is a codrug, or a mutual prodrug of ___ and _-___ ___ acid coupled with an ____ linkage

Back 31

sulfapyridine and 5-amino salicylic acid coupled with an azo linkage

Front 32

Sulfasalazine is a codrug, or a mutual prodrug of sulfapyridine and 5-amino salicylic acid coupled with an azo linkage. It is broken down by __ in the ___ to give the individual components

Back 32

. It is broken down by bacteria in the colon to give the individual components.

Front 33

Sulfasalazine is a codrug, or a mutual prodrug of sulfapyridine and 5-amino salicylic acid coupled with an azo linkage. It is broken down by bacteria in the colon to give the individual components. The beneficial effects are believed to result from the local effect of this drug in the ___ although what plays a role?

Back 33

bowel

bowel, although systemic immunosuppressive effects play a role.

Front 34

Sulfasalazine is utilized for the treatment of what?

Back 34

for the treatment of Crohn’s disease as well as for rheumatoid arthritis

Front 35

Leflunomide is a ____ that is almost completely metabolised to ______, the pharmacologically active ____ metabolite.

Back 35

prodrug

teriflunomide

a-cyanoenol

Front 36

Leflunomide is a prodrug that is almost completely metabolised to teriflunomide, the pharmacologically active α-cyanoenol metabolite. The ___ hydrogen of the ____ ring in lefunomide is necessary for this ring-opening transformation to occur.

Back 36

C3

isoxazole ring

Front 37

Leflunomide is inactive, but teriflunomide inhibits ___ ___ at low therapeutic doses by inhibiting ____ decreasing ___ ans ____ synthesis and arresting ___ and ___

Back 37

inhibits pyrimidine synthesis at low therapeutic doses by inhibiting dihydroorotatedehydrogenase(DHODH - the rate-determining enzyme for the synthesis of UMP), decreasing DNA and RNA synthesis, and arresting the cell proliferation cycle and production of antibodies

Front 38

The reduction of dihydroorotate to orotate occurs concurrently with the reduc-tion of its cofactor ___

Back 38

ubiquinone(coenzyme Q).

Front 39

The inhibition of dihydroorotatedehydrogenase by teriflunomide demonstrates ___ and ___ kinetics

Back 39

noncompetitive and uncompetitive kinetics

Front 40

Azathioprine is a ____ metabolized to ____

Back 40

Azathioprine is a prodrug metabolized to 6-mercaptopurine

Front 41

Azathioprine is a prodrug metabolized to 6-mercaptopurine. It inhibits what? Prevents what? Especially in what?

Back 41

purine biosynthesis and prevents cell proliferation, especially in fast growing T-lymphocyte cells.

Front 42

Methotrexate ______inhibits _______, an enzyme that participates in ______ synthesis

Back 42

Methotrexate competitively inhibits dihydrofolatereductase (DHFR), an enzyme that participates in tetrahydrofolate synthesis

Front 43

Lower doses of methotrexate have been shown to be very effective for the management of __ ___

Back 43

rheumatoid arthritis

Front 44

In the treatment of rheumatoid arthritis, patients should supplement their diet with ____

Back 44

folate

Front 45

patients should supplement their diet with folate. Inhibition of DHFR is not thought to be the main mechanism, but rather the inhibition of enymes involved in ___ metabolism, leading to accumulation of ___ or the inhibition of ___ ___

Back 45

purine metabolism, leading to accumulation of adenosine, or the inhibition of T-cell activation

Front 46

Penicillins and related antibiotics decrease renal excretion of ___, causing a buildup of ____ in the blood

Back 46

methotexate

methotexate

Front 47

____ is an inflammatory disease characterized by the buildup of uric acid (as urate ion) in the plasma and urine, and may show up as both acute and chronic conditions

Back 47

gout

Front 48

Acute gouty arthritis results from the accumulation of ___ ___ within the ___ and ___ fluid

Back 48

monosodium urate within the joints and synovial fluid

Front 49

Uric acid exists primarily as what?

Back 49

as the monsodium salt at physiologic pH

Front 50

When uric acid formation is elevated, or uric acid excretion is reduced, the solubility limits of uric acid are ____ and the uric acid ____ from biological fluids, depositing in ____

Back 50

are exceeded and the uric acid crystallizes from biological fluids, depositing in tissues.

Front 51

____ gout symptoms develop as permanent erosive joint damage occurs.

Back 51

chronic

Front 52

Treatment of gout may include what 3 components?

Back 52

Control of acute attacks by drugs that reduce inflammation caused by the urate crystals.
Control of chronic gout by increasing the rate of uric acid excretion (uricosuricdrugs).
Inhibiting the biosynthesis of uric acid by inhibiting the enzyme xanthineoxidase

Front 53

The increase in extracellular urate may result from increased what? Decreased what?

Back 53

increased uric acid biosynthesis, decreased urinary excretion of uric acid, or perhaps, a combination of both.

Front 54

. Uric acid is formed by the oxidation of ___ by the enzyme ___

Back 54

xanthine by the enzyme xanthineoxidase

Front 55

Xanthine is a metabolic product of ___

Back 55

adenine

Front 56

Xanthine is a metabolic product of adenine (via hypoxanthine) and guanine formed by the enzymes ____ ___and ___ ___

Back 56

adenine deaminase and guanine deaminase, respectively.

Front 57

Uric acid is the excretory product of ____ metabolism

Back 57

purine metabolism

Front 58

_____ inhibits the deposition of urate crystals

Back 58

Colchicine

Front 59

Colchicine inhibits the deposition of urate crystals. Since the formation of such crystals is enhanced by a low pH in the tissues, it is surmised that colchicine raises the tissue pH by what? What does this than reduce the production of?

Back 59

inhibiting the oxidation of glucose, thereby reducing the production of lactic acid in leukocytes.

Front 60

Probencid is a ____ ___ (pKa = 3.4) is insoluble in ____ and ___ solutions

Back 60

caboxylic acid

acidic and neutral solutions

Front 61

Probencid is a caboxylic acid (pKa = 3.4) is insoluble in acidic and neutral solutions, but is administered as a slightly ___ solution and is copletely absorded by the __ __

Back 61

basic solution (pH 7.4) and is completely absorbed by the GI tract

Front 62

Probenecid is used for what purpose?

Back 62

sulfonamides decreased the renal clearance of penicillin, extending the half-life of penicillin as supplies diminished

Front 63

. Probenecid promotes the excretion of uric acid by inhibiting what?

Back 63

the urate anion exchange transporter (URAT1

Front 64

. Probenecid promotes the excretion of uric acid by inhibiting the urate anion exchange transporter (URAT1), decreasing the reabsorption of ____ __ in the ___ ___

Back 64

uric acid in the proximal tubules.

Front 65

Probenecid overall effect is to decrease what? There by decreasing the rate and extent of what?

Back 65

to decrease plasma uric acid concentrations, thereby decreasing the rate and extent of urate crystal deposition in joints and synnovial fluids.

Front 66

_____ produces a uricosuric effect similar to that of probenecid

Back 66

Sulfinpyrazone

Front 67

Sulfinpyrazone is strongly what? What does this factor play a role in? Because why?

Back 67

. It is a strongly acidic compound (pKa = 2.8), and this factor plays a role in the uricosuric effect, because within a series of these pyrazolidinedione derivatives, the stronger the acid, the more potent the uricosuric effect.

Front 68

One of the main metabolites of Sulfinpyrazone has a ______attached at the acidic carbon.

Back 68

glucoronide

Front 69

Allopurinol is a purine _____ and it’s major oxidative metabolite is _______.

Back 69

purine antagonist

alloxanthine(oxypurinol).

Front 70

Allopurinol inhibits ____

Back 70

xanthineoxidase

Front 71

Allopurinol inhibits xanthineoxidase, slowing ___ ___ formation

Back 71

uric acid

Front 72

, inhibition of xanthineoxidase causes an increase in ___ and ___

Back 72

hypoxanthine and xanthine

Front 73

xanthineoxidase causes an increase in hypoxanthine and xanthine, which are converted to closely related purines ___ and __

Back 73

adenosine and guanosine

Front 74

increased levels of hypoxanthine and xanthine causes feedback inhibition of what?

Back 74

causes feedback inhibition of amidophosphoribosyltransferase

Front 75

allopurinol therefore decreases both ___ and ___

Back 75

uric acid formation and purine synthesis