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Rheumatology > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Effects of Glucocorticosteroids

A

Anti-inflammatory
Bind & block promoter sites of proinflammatorty genes IL-1 alpha & IL-2 beta
Decreased production of TNF alpha
Multiple cell specific effects

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2
Q

Proinflammatory Mediators Glucocorticosteroids Inhibits

A 
Phospholipase A2
Cyclooxygenase 2
Nitric oxide synthetase
Prostaglandins
Leukotrienes
Thromboxanes
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3
Q

Effect of Glucocorticosteroids on Leukocytes

A

Can’t exit circulation as readily

Entry to site of infection & tissues injury impaired

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4
Q

Glucocorticosteroids & Suppression of Inflammatory Response

A

Increased neutrophils
Decreased eosinophils
Decreased monocytes
Decrease lymphocytes

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5
Q

Glucocorticosteroids & Effects of Acquired Immunity

A

Decreased APCs
Decreased T cells
Decreased B cells

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6
Q

Increased Infection Risk with Glucocorticosteroids

A

Immediate reduction of phagocytic responses

Main infections on long term therapy: herpes zoster, staph, candida

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7
Q

Monitoring for Toxicity of Glucocorticosteroids

A 
BP
Serum glucose
Lipid profile
Eye exam
Bone density
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8
Q

Pros of Steroids

A

No dose adjustment in renal impairment

Good symptom relief of pain secondary to inflammation

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9
Q

Short Term Symptom Management for RA

A

NSAIDs

Steroids

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10
Q

NSAIDs & RA

A

May alleviate the symptoms

Do not prevent irreversible joint damage

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11
Q

Glucocorticoids & RA

A

Quick symptoms relief
Avoid long term administration due to toxicities
Not a profound effect on decreasing joint destruction

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12
Q

DMARDs & RA

A

Variable response
Discontinuation rate high
Continued indefinitely unless significant toxicity
Biological & non-biological

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13
Q

Non-Biological DMARDs

A 
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
D-penicillamine
Gold salt
Azithroprine
Cyclosporine
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14
Q

Biological DMARDs

A 
Etanercept (Enbrel)
Adilimumab (Humira)
Infliximab (Remicade)
Aakinra (Kineret)
Abatacept (Orencia)
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15
Q

2nd Line if Failure to Achieve RA Remission in 3 Months

A

Change DMARD

Go to combination therapy

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16
Q

How to decide on which drug for RA?

A

Disease severity
Prognostic factors
Patient preference

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17
Q

Methotrexate (Rheumatrex)

A

DMARD of choice for RA

Generally well tolerated

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18
Q

MOA of Methotrexate (Rheumatrex)

A

Stimulates adenosine release
Reduced neutrophil adhesion
Suppression of cell mediated immunity
Anti proliferative effect on synovial fibroblasts & endothelial
Inhibition of IL-1, IL-6, & IL-8
Inhibits synovial collegenase gene suppression

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19
Q

What do all patients on methotrexate need?

A

Folic acid supplemet

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20
Q

Contraindications of Methotrexate (Rheumatrex)

A

Women contemplating pregnancy
Pregnancy
Liver disease or excessive ETOH intake
GFR less than 30 mL/min

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21
Q

SE of Methotrexate (Rheumatrex)

A 
Hepatotoxicity
Pulmonary toxicity
Myelosuppression
Nephrotoxicity
Fatigue
Decreased ability to concentrate
Alopecia
Nausea
Stomach upset
Loos stools
Soreness of the mouth
Rash on the extremities
Headache
Fever
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22
Q

Toxicities of Methotrexate (Rheumatrex)

A

Myelosuppression
Hepatotoxicity including cirrhosis
Pulmonary toxicity

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23
Q

Monitoring of Methotrexate (Rheumatrex)

A 
CBC
LFTs
Albumin
Creatinine
Pre treatment CXR
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24
Q

2nd Line Drug for RA

A

Sulfasalazine (Azulfidine)

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25
MOA of Sulfasalazine (Azulfidine)
Inhibition of PMN cell migration Reduced lymphocyte responses Inhibits angiogenesis Decreases inflammatory cytokines & IgM RF production
26
Contraindications of Sulfasalazine (Azulfidine)
``` Sulfa allergy Pregnancy category D GI or GU tract obstruction Porphyria Platelet count less than 50K LFTs > 2x ULN Hepatitis Men wanting to conceive ```
27
SE of Sulfasalazine (Azulfidine)
``` Nausea & diarrhea Intestinal or urinary obstruction Oral ulcers Orange-yellow pigmentation of the skin Headache Depression Neutropenia Thrombocytopenia Agranulocytosis ```
28
Toxicity of Sulfasalazine (Azulfidine)
Myelosuppression
29
Monitoring of Sulfasalazine (Azulfidine)
CBC monthly x3 | CBC every 3 months
30
Effects Leflunomide (Avara)
Anti-inflammatory Antiproliferative Decreases progression of joint erosions & joint space narrowing
31
MOA of Leflunomide (Avara)
Competitive inhibitor of dihydrofolate reductase Decreases production of pyrimidine Inhibits pyrimidine synthesis
32
Contraindications to Leflunomide (Avara)
Pregnancy Preexisting liver disease Alcoholism
33
SE of Leflunomide (Avara)
``` Diarrhea Rash Reversible alopecia Hepatotoxicity Weight loss HTN Bone marrow suppression ```
34
Leflunomide (Avara) Toxicities
Hepatotoxicity | Bone marrow suppression
35
Monitoring of Leflunomide (Avara)
Monthly x 6 then every 2 months CBC Liver enzymes Creatinine
36
Interactions with Leflunomide (Avara)
Weak inhibitor of CYP2C9 Increase warfarin levels Rifampin may increase levels of leflunomide Bile acid sequesterants decrease effectiveness of leflunomide
37
Hydroxychloroquine (Plaquenil) & RA
Antimalarial | Does not limit progression of RA
38
Use of Hydroxychloroquine (Plaquenil)
Mild RA with no evidence of joint destruction & no inflammatory markers or autoimmune markers Add-on to methotrexate
39
MOA of Hydroxychloroquine (Plaquenil)
Interferes with normal antigen processing Inhibits lysosomal enzymes & IL-1 release Inhibition of PMNs & lymphocyte responses
40
Toxicity of Hydroxychloroquine (Plaquenil)
Macular damage
41
Monitoring with Hydroxychloroquine (Plaquenil)
Fundoscopic & visual field exams every 6-12 months
42
SE of Hydroxychloroquine (Plaquenil)
``` Nausea Diarrhea Abdominal discomfort Photosnsitivity Skin pigmentation changes Rash Macular damage ```
43
Drug Interactions with Hydroxychloroquine (Plaquenil)
Decreased metabolism of beta blockers | May increase cyclosporine & digoxin levels
44
Treatment of Severe RA
Combination of DMARD therapy Switch to another TNF inhibitor with different mechanism Ongoing glucocorticoid therapy Ongoing NSAIDs
45
TNF Inhibitors
Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira)
46
MOA of TNF Inhibitors
Bind to TNF-alpha, cell lysis occurs | Interferes with inflammatory activity
47
SE of TNF Inhibitors
``` Injection site infections Infusion reaction (infliximab-Remicade) Serious infections leading to sepsis Do not administer live vaccine Response to other vaccines may be diminished ```
48
Contraindications of TNF Inhibitors
Latent TB infection | High risk for opportunistic infections
49
Interactions of Infliximab (Remicade)
Abatacept (Orencia) Anakinra (Kineret) Increased risk of infection
50
Methotrexate & Infliximab (Remicade)
Decreases development of infliximab antibodies
51
Toxicity of TNF Inhibitors
Injection site reaction | Increased risk of local or systemic infection
52
Monitoring of TNF Inhibitors
PPD prior to therapy | Periodic CBC
53
MOA of Anakinra (Kineret)
Blocks IL-1 receptor to decrease degree of joint destruction & inflammation
54
Anakinra (Kineret) & GFR less than 30 mL/min
Decrease dose
55
Contraindications of Anakinra (Kineret)
Sensitivity to E. coli-derived proteins Preexisting infection or high risk for infection Not to be used in combination with TNF inhibitors
56
SE of Anakinra (Kineret)
Skin irruption at injection site Infection Possible angioedema & anaphylaxis Decrease in WBCs
57
Monitoring in Anakinra (kineret) Use
CBC monthly x3 | CBC Q4 months x 1 year
58
Non-preferred DMARDS
D-penicillamine Azithroprine Cyclosporine A Gold compounds
59
D-Penicillamine
Chelating agent for metal poisoning, arsenic poisoning, or Wilson's disease Depresses T cell activity Pregnancy category D
60
Aithroprine (Imuran)
Inhibits enzymatic activity required for DNA synthesis Adjust dose for decreased renal clearance Pregnancy category D Major toxicity = bone marrow suppression Carcinogenic
61
Cyclosporine A
Blocks activation of T cells & IL-2 Follow blood levels Many drug interactions Toxicity: renal failure
62
Gold Compounds
Decreases prostaglandin production Add-on therapy Greater toxicity than DMARDs
63
Medications that May Lead to a SLE Exacerbation
Sulfa containing antibiotics Minocycline OCPs
64
Medication that May Lead to Drug Induced Lupus
Procainamide Hydralazine Griseofulvin
65
Medications that Work for Cutaneous & Musculoskeletal Involvement of SLE
Anti-malarials | Hydroxychloroqine (Plaquenil)
66
Medications for Cutaneous Involvement of SLE
Topical therapies
67
Medication for Musculoskeletal Involvement of SLE
NSAIDs
68
Medications for Significant Organ Involvement in SLE
Glucocorticoids
69
Immune Modulators for Severe SLE When Steroid Resistent
``` Methotrexate Cyclophosphamide Azathiprine Mycophenolate Rituximab ```
70
Medication When Antiphospholipid Antibody Positive in SLE
Warfarin
71
Medications to Treat Acute Attacks of Gout
NSAIDs Colchicine Steroids
72
Medications for Prevention of Gout
``` Xanthine oxidase inhibitors: allopurinol (Zyloprim), febuxostat Uricosuric drugs (Probenecid) ```
73
MOA of NSAIDs
Inhibit cyclooxygenase & production of mediators of inflammation
74
Contraindications of NSAIDs
``` CrCl less than 60 mL/min Active duodenal or gastric ulcers HF Uncontrolled HTN Allergy Chronic anticoagulation ```
75
NSAIDs Increase Risk of
``` CVA MI CHF A-fib CV death ```
76
Aspirin & NSAIDs
Take aspirin 2 hours prior to NSAIDs
77
NSAIDs Acute Gout
Indomethacin (Indocin) Naproxen Celecoxib (Celebrex)
78
Colchicine for Acute Gout Attacks
NSAID intolerance | NSAID contraindication
79
MOA of Colchicine
Prevents activation degranulation & migration of neutrophils associated with mediating some gout symptoms
80
Pregnancy Category of Colchicine
Category C
81
SE of Colchicine
``` Diarrhea N/V Reversible peripheral neuropathy Bone marrow suppression Myopathy ```
82
Dose Adjustment Needed in Colchicine
``` >70 years old CrCl less than 30 mL/min Avoid in dialysis patients Strong CYP3A4 inhibitors Moderate CYP3A4 inhibitors P-glycoprotein inhibitors ```
83
Examples of Strong CYP 3A4 Inhibitors
``` Clarithromycin Itraconozaole Ketoconazole Nefazodone HIV protease inhibitors ```
84
Examples of Moderate CYP3A4 Inhibitors
``` Diltiazem Erythromycin Fluconazole Grape fruit juice Verapamil ```
85
Examples of P-Glycoprotein Inhibitors
Cyclosporine Ranolazine Amiodarone
86
Contraindications to Colchicine
Renal impairment | Hepatic impairment
87
No Relief of Symptoms on Colchicine After 24 Hours
+ glucocorticoid | Cautiously in conjunction with an NSAID
88
Management Between Gout Attacks
Avoid thiazides & loop diuretics Avoid niacin Avoid aspirin
89
Medications to Reduce Serum Uric Acid Indications
2+ episodes a year Tophi CKD Stage II+
90
Allopurinol (Zyloprim)
Agent of choice for lowering rate Xanthine oxidase inhibitor Goal level: less than 6
91
MOA of Allopurinol (Zyloprim)
Inhibits xanthine oxidase needed for eventual conversion of hypoxanthine to uric acid
92
Necessary Dose Adjustment in Allopurinol (Zyloprim)
Renal Failure: less than 60 mL/min
93
SE of Allopurinol (Zyloprim)
``` Skin rash Gout attack Diarrhea Nausea Elevated liver enzymes Hypersensitivity reactions Bone marrow suppression Hepatotoxicity ```
94
2nd Line Therapy for Prevention of Gout
Probenecid
95
MOA of Probenecid
Blocks tubular reabsorption of filtered rate & increases uric acid excretion by the kidney
96
When is probenecid not effective?
CrCl less than 50 mL/min
97
Contraindications of Probenecid
Hx of nephrolithiasis
98
Prevention of Uric Acid Stones with Use of Probenecid
Increase fluid intake | Need agent to alkalinize the urine
99
Other Medications that can Decrease Uric Acid Levels
Losartan Fenofibrate Vitamin C 500mg daily Cherries

Rheumatology (8 decks)

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