Exam 2: Lecture 5, DMARDs Flashcards

1
Q

DMARDs

A

Disease Modifying Slow-Acting Anti rheumatic Drugs

NSAIDS cannot reverse join damage, DMARDs are used for rheumatic disorders not responding to NSAIDs

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2
Q

Rheumatoid disease is…

A

a widespread chronic inflammatory condition

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3
Q

DMARDs info

A

operate in connective tissues

heterogeneous group of slow acting anti-inflame agents

all agents have very slow onset of effect, can take months

many do not respond to DMARDs (esp Gold Salts)

Controversy still about efficacy in arthritis

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4
Q

Gold Salts

A

Cytotoxic agent

most effective for rapidly progressive disease

cannot fix existing damage, prevent more

decrease O2 metabolites production

Suppress Phagocytosis, lysosomal enzyme activity, and histamine release

taken up by macrophages

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5
Q

Gold Salt Toxicity

A

observed in 1/3 pt, 1/10 have severe symptoms

skin rashes, occasionally severe
mouth ulcers
proteinuria
encephalopathy
peripheral neuropathy
Hepatitis
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6
Q

Methotrexate (rheumatrex)

A

First line

Anti-cancer med
cytotoxic immunosuppressant agent

reduce number of immune cells for inflammation response, actively dividing inflammatory cells vulnerable to effects of drug

inhibit enzyme essential for NA synth/cell rep

doses smaller than those for anticancer therapy, for sever rheumatoid arthritis

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7
Q

Methotrexate Toxicity

A
Bone marrow suppresion
Leucopenia,thrombocytopenia,anemia
GI toxic
Hepatic toxicity
Pulmonary fibrosis
Renal Dysfunction
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8
Q

Sulfasalazine (Azulfidine)

A

Second line

Mechanism poorly understood, thought to be scavenger of free radicals

Drug is combo sulfonamide + salicylate, split not 2 In colon

used to treat RA. Ulcer colitis, Inflammatory Bowel disease

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9
Q

Sulfasalazine (Azulfidine) Toxicity

A

Gi Disturbance
Headache
Reversible drop in Sperm count
Possible anaphylaxis, dyscrasia (unspecified blood disorder)….this possible with other sulfonamides too

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10
Q

Penicillamine (Cuprimine, Depen)

A

A Chelating agent used in the treatment of poisoning by heavy metals

An analog of cysteine + substances that produced by penicillin hydrolysis

decrease progression of bone destruction

mechanism not clear, suggested the decrease of IL-1 formation and collagen synthesis

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11
Q

Penicillamine Toxicity

A
Anorexia
Nausea
Rashes
Stomatitis
Bone-Marrow disorders

Chelator, so don’t give with gold compounds

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12
Q

Hydroxychloroquine (Plaquenil)

A

Antimalarial drug
Usually, Well tolerated
Used to treat RA

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13
Q

Hydroxychloroquine (Plaquenil) Mechanism

A

Depress activity of T-lymphocytes
Decrease leucocytes chemotaxis
Interferes with RNA/DNA synthesis

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14
Q

Hydroxychloroquine (Plaquenil) Toxicity

A
Headache
Tinnitus
Arrhythmias
Nausea,Vomiting
Rashes
Possible retina damage = streaks/flashes
Eye swelling + color change
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15
Q

All DMARDs are related to….

A

Severe and Fatal Toxicities

Require monitoring

Danger of mixing DMARDs together, severe kidney damage.

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16
Q

Gold Salts severe toxicity

A

fatal dermatitis and bone marrow depression

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17
Q

Methotrexate severe toxicity

A

bone marrow depression and teratogenic fetal damage/abortion

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18
Q

D-Penicillamine severe toxicity

A

renal damage and aplastic anemia

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19
Q

Hydrochloroquine severe toxicity

A

dermatitis,bone marrow depression and RETINAL DEGENERATION

20
Q

Combo Therapy with DMARDs

A

high toxicity, but used to treat RA

plan is designed rationally,

use non-overlapping toxicities and pharmacokinetics

21
Q

Biological DMARDs

A

breakthrough in treatment

engineered recombinant antibodies and other proteins

hard + expensive to make

for patients that don’t respond to other DMARDs

admin with specialist supervision

22
Q

Immunoglobulin Structure

A

produced by specific activated B cell against particular antigen, 10^20 antibody molecules in individual

Heavy + Light Chain (H+L)
Antigen binding Frag (Fab)
Constant region (Fc)
N-terminal ends of H/L chain form Ag-binding site
Single antibody can bind 2 Ag
23
Q

Variable region Antibody

A

Top portion of the Y structure

24
Q

Constant region Antibody

A

Bottom portion of the Y structure

25
Anakinra Dosing
Given daily
26
Etanercept Dosing
Given once or twice per week.
27
Abatacept and Golimumab Dosing
Given once monthly
28
Adalimumab, Certolizumab, Infliximab, Rituximab Dosing
Given every two weeks.
29
Biopharmaceuticals Therapy Limitations
only given to severely affected patients, when other therapy failed. ~30% don't respond to them Discontinued if no benefit seen 2/4 weeks combo of drugs is more effective
30
Biopharmaceutical Adverse effects
Precipitate latent infections (Tuberculosis/Hep B) Encourage opportunistic infections Provoke onset of psoriasis-like syndrome (Rare) Hypersensitivity, injection site reactions and mild GI symptoms
31
Gout is a
genetically determined metabolic disorder characterized by high conc of uric acid in the blood
32
Chronic Gout causes
Genetic defect = increase purine synthesis Renal Deficiency (genetic or caused by thiazides) Lesch-Nyhan Syndrome (Excessive uric acid synthesis)
33
Acute gout attacks can be provoked by...
Excessive Alcohol consumption, diet rich in purines or kidney disease
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Mechanism for Gout Attack
Purines -> Xanthine -> Uric Acid ->Uric Acid Crystals -> Phagocytosis by Neutrophils -> Inflammation Mediators Release -> Lysosomal Enzyme release ->Acute inflammation
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Gout Treatment Strategies
Reduce Inflammation (Indomethacin/ Colchicine) reduce conversion of purines to uric acid (Allopurinol) Increase uric acid excretion (Probenecid,Sulfinpyrazone)
36
Colchicine (Colchrys)
Plant alkaloid, reserved for acute gout attacks Mitotic Poison can be used to treat Mediterranean fever
37
Colchicine Mechanism
Selective inhibitor of microtubule assembly, bind to tubulin Disrupts mobility of granulocytes into affected area blocks cell division by binding mitotic spindles reduces production of Leukotrienes (LTB4)/ Reduce inflammation
38
Mediterranean fever
Fever, Hepatitis, peritonitis, arthritis
39
Colchicine Toxicity
Nausea/Vomiting/Abdominal Pain/ Sever Diarrhea Possible sever liver/kidney damage * Not to be used during pregnancy * Fatal dose as little as 8mg in 24hrs, close monitoring IV no longer approved
40
Allopurinol (Zyloprim)
1st line agent for chronic gout treatment not effective in acute attack Purine Analog
41
Allopurinol Mechanism
Competitive inhibits last two steps in uric acid biosynthesis Inhibit Xanthine Oxidase Decrease uric acid conc, precipitation of uric acid crystals in joints and tissues * Selective in humans but can severely impair purine metabolism in some protozoa*
42
Allopurinol Toxicity
Well tolerated in most patients, oral admin skin rashes in 3% of patients Bone marrow depression Hepatic Toxicity and Nephrotoxicity ** Rare peripheral neuritis/ vasculitis, very rare bind to lens resulting in cataracts **
43
Uricosuric Agent
Reduce inflammation Block proximal tubule reabsorption of uric acid Uricosuric agents are organic acids - increase uric acid secretion
44
Uricosuric Agents examples
Probenecid (Generic) | Sulfinpyrazone (Anturane)
45
Uricosuric Agent Toxicity (of the 2 examples)
Both agents similar toxicity rarely aplastic anemia Gi irritation more active (sulfinpyrazone) Nephrotic syndrome mostly (probenecid)
46
Probenecid (Generic)
blocks kidney tubule secretion of penicillin was developed to prolong penicillin level in blood used occasionally to increase antibiotic conc