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MSK II Exam 2 > Linger Rheumatic Pharm > Flashcards

Linger Rheumatic Pharm Flashcards

1
Q

Basic Principles of RA Treatment

A

Early and aggressive use of DMARDs for all patients
Tight control is important
- Goal should be remission or low disease activity
- Frequent reassessment of response
- Monitoring and prevention of drug toxicity

Response time

  • Nonbiologic DMARDs are slower (1-6 months)
  • Biologic DMARDs are faster (1-2 weeks); some patients report improvement after the first dose

Use of NSAIDs and glucocorticoids as adjunct therapy

  • To control symptoms during initial DMARD treatment, regimen modification, or disease flares
  • Provide immediate pain relief
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2
Q

Standard Approach for Pharmacologic Treatment of RA

A
  1. DMARD + NSAID ± corticosteroid
    - Methotrexate (MTX) is used in 50-70% of cases
    - Hydroxychloroquine (HCQ) or sulfasalazine (SSZ) are safer alternatives for mild disease
    - If response is inadequate, second or third DMARD can be added
  2. TNF-α inhibitor (monotherapy or with nonbiologic DMARD)
    - More effective and faster response than nonbiologic DMARDs
    - Second-line due to long-term adverse effects (1st line after inadequate response to nonbiologics)
  3. Switch to a different TNF-α inhibitor or a non-TNF biologic
    - Patients who do not respond to one TNF inhibitor may respond to another TNF inhibitor or a non-TNF inhibitor
    - Currently no evidence that any one TNF inhibitor is more effective than any other
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3
Q

Combination DMARD Therapy

A

Combinations of 2 or even 3 DMARDs are often used

  • Complementary mechanisms of action
  • Non-overlapping pharmacokinetics
  • Non-overlapping toxicities

Most combinations are methotrexate-based

Combinations of two drugs can include MTX and another nonbiologic DMARD or MTX and a biologic DMARD

Triple therapy: MTX + HCQ + SSZ

Combining different biologic DMARDs is not recommended
- Increases risk of infection without significant benefit

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4
Q

Treatment of Acute Gout

A

NSAIDs

  • First-line therapy for acute gout
  • MOA: inhibit urate crystal phagocytosis and PG synthesis
  • Common choices: indomethacin, naproxen, sulindac, celecoxib
  • Aspirin, salicylates, and tolmetin are not used

Colchicine

  • Formerly primary therapy; now rarely used due to toxicity
  • Can be used in patients with NSAID contraindications

Glucocorticoids

  • Sometimes used for severe gout
  • Administered intraarticularly, orally, or parenterally depending on the number of joints involved
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5
Q

Prevention of Recurrent Gout

A

Antihyperuricemic (urate-lowering) therapy

  • Xanthine Oxidase Inhibitors
  • — Decrease urate synthesis
  • — Allopurinol and febuxostat
  • Uricosuric Agents
  • — Enhance renal excretion of uric acid
  • — Probenecid (antihypertensive losartan has uricosuric effects)

Anti-inflammatory drugs (NSAIDs or colchicine)
- Used early in urate-lowering therapy when mobilization of uric acid is associated with a temporary increase in the risk of acute gout

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6
Q

Gout- where it comes from

A

Gout results from precipitation of urate crystals in the tissues

An inflammatory response is caused by phagocytosis of urate crystals

Hyperuricemia is a prerequisite, but does not always result in gout

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7
Q

how gout drugs work

A

Synoviocytes phagocytose urate crystals and then secrete inflammatory mediators, which attract and activate polymorphonuclear leukocytes (PMN) and mononuclear phagocytes (MNP) (macrophages). Drugs active in gout inhibit crystal phagocytosis and polymorphonuclear leukocyte and macrophage release of inflammatory mediators. PG, prostaglandin; IL-1, interleukin-1; LTB4, leukotriene B4.

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8
Q

Lady has morning stiffness, fatigue, body aches, weight loss, sweeling, tenderness and warmth in the MCP and PIP joints.
Joint erosions
High RF
Anti CCP antibody

What’s she got?

A

rheumatoid arthritis

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9
Q

Lady has RA and we start her on methotrexate. What’s the main purpose of that?

A

Slow, stop, and possibly reverse joint pathology in RA

Disease-Modifying Antirheumatic Drugs = DMARDs

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10
Q

Which of the following adverse effects is most likely following administration of MTX for RA?

Myelosuppression
Nephrotoxicity
Ocular toxicity
Stomatitis
Viral infection
A

Stomatitis

in doses for cancer you’d have nephrotoxicity and myelosuppression too, but not here for RA as much

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11
Q

Methotrexate (MTX)

A

Doses used in rheumatic diseases are much lower than those used for cancer

  • Different primary mechanism of action (MOA)
  • Reduced toxicity compared to use in cancer chemotherapy

Response time: 4-6 weeks or longer

Clinical Uses

  • First-line DMARD for RA; used in 50%-70% of cases
  • Psoriasis; unlabeled use in Crohn’s diseases
  • Used at much higher doses in many cancer chemotherapy regimens (inhibits dihydrofolate reductase)
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12
Q

Methotrexate Adverse Effects

A

Common side effects

  • Nausea, upset stomach, loose stools
  • Stomatitis or soreness of the mouth
  • Alopecia
  • Fever
  • Macular punctate rash (usually on the extremities)
  • Headache, fatigue, or impaired ability to concentrate

Hepatic enzymes are frequently elevated, but cirrhosis is rare (< 1%)

Myelosuppression and nephrotoxicity are much less frequent with low-dose therapy than high-dose MTX

Lung damage may be due to inflammation, infection, or MTX-related neoplasia

Contraindicated in pregnancy (teratogenic)

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13
Q

Which of the following agent(s) may be used to reduce the side effects of methotrexate?

Calcium
Folic acid
Folinic acid
Pyridoxine
Vitamin C
A 
Folic acid- cheap
Folinic acid (leucovorin)- expensive (rescue from high dose)

Pyridoxine is vitamin B6- anti-emetic effects for morning sickness, helps against isoniazid induced peripheral neuropathy.

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14
Q

The patient’s multidrug regimen also includes an agent that will provide immediate pain relief due to its analgesic and anti-inflammatory effects. Which drug best meets this description?

Acetaminophen
Hydroxychloroquine
Ibuprofen
Oxycodone
Sulfasalazine
A

Ibuprofen

Acetominophen is just analgesic but NOT anti-inflammatory
hydroxychloroquine is a DMARD, not imediate effect

Oxycodone- opiate agonist, analgesic but not anti-inflammatory

Sulfasalazine- DMARD

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15
Q

Role of NSAIDs in Treatment of RA

A

NSAIDs have immediate analgesic and anti-inflammatory effects, but usually do not affect disease progression

Typically used during DMARD induction, during transition to a different DMARD, or during disease flares

Some commonly used agents: ibuprofen, naproxen, diclofenac

Aspirin is not typically used due to GI toxicity; COX-2-selective celecoxib exhibits less GI irritation

No oral NSAID is consistently more effective than any other for treatment of RA; choice based on efficacy/toxicity (varies by patient)

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16
Q

For additional analgesic and anti-inflammatory effects, the patient is scheduled to receive an intra articular injection of methylprednisolone acetate in one joint. Which condition, if present, would contraindicate administration of this agent?

Asthma
Diabetes mellitus
Hepatocellular adenoma
Plaque psoriasis
Infection in or around the joint
A

Infection in or around the joint

this is a corticosteroid, don’t want to prevent the immune system from dealing with the infection

glucocorticoids are helpful in asthma and psoriasis

in DM single injections are not an issue at local joints

17
Q

Role of Corticosteroids in Treatment of RA

A

Short course of low-dose corticosteroids are often used for symptomatic relief (avoid long-term use; Cushings, etc.)

Effects are prompt and dramatic

Can slow progression of RA, but long-term use is limited by serious adverse effects

Short course of high-dose corticosteroids is sometimes required to control severe systemic manifestations of RA, such as pericarditis or vasculitis

Intra-articular injection of a corticosteroid can relieve an acutely inflamed rheumatoid joint with minimal adverse effects

18
Q

Nonbiologic DMARDs

A 
Prototype: Methotrexate (MTX)
Other frequently used agents:
- Leflunomide (LEF)
-  Hydroxychloroquine (HCQ)
- Sulfasalazine (SSZ)

First-line therapy for all RA patients

Rarely used agents:
Azathioprine	•	
Gold Salts
Cyclophosphamide	•	
Minocycline
Cyclosporine	•	
Mycophenolate mofetil
19
Q

Leflunomide (LEF)

A

As effective as MTX in preventing RA-associated bone damage
Can be used as monotherapy or in combination with MTX
Diarrhea is very common; elevation of liver enzymes may also occur; contraindicated in pregnancy

20
Q

Hydroxychloroquine (HCQ)

A

Best known as an antimalarial drug
Frequently used in combination with MTX and/or SSZ
Monitor for ocular toxicity every 12 months

21
Q

Sulfasalazine (SSZ)

A

Used in a variety of rheumatic and autoimmune diseases
More toxic than HCQ, ~30% of patients are intolerant
Nausea, vomiting, anorexia, headache, and rash are common

22
Q

a rheumatologist decides to stop the sulfasalazine and prescribes a TNF-α inhibitor. Which agent is most likely prescribed?

Adalimumab
Certolizumab
Etanercept
Infliximab
Golimumab
A

All of them are TNF alpha inhibitors.

none is more efficacious than the rest

23
Q

a patient is started on infliximab. Which adverse effect is most likely to occur?

Congestive heart failure
Hodgkin lymphoma
Opportunistic infection
Reversible infertility
Systemic lupus erythematosus
A

Opportunistic infection

24
Q

TNF Inhibitors - Clinical Uses

A

Used as monotherapy or in combination with nonbiologic agents for treatment of RA and other rheumatic diseases
Not all agents are labeled for all indications

25
Q

TNF Inhibitors - Adverse Effects

A

Increased susceptibility to serious infections, including bacterial sepsis and reactivation of tuberculosis (TB); patients should be screened for latent TB infection prior to and during treatment
Reactivation of hepatitis B can also occur
Injection/infusion reactions can occur (sometimes severe)
May be associated with certain malignancies, especially lymphoma
May be associated with heart failure; not recommended for use in patients with class III/IV CHF

26
Q

Other Biologic DMARDs

A

Abatacept: Fc fusion protein containing the extracellular domain of the CTLA-4 receptor; prevent T-cell activation
Rituximab: targets CD20, resulting in depletion of B-cells
Tocilizumab: binds to and inhibits signaling of IL-6 receptors
Tofacitinib: oral inhibitor of Janus Kinase (technically not a biologic)

These agents are typically reserved for patients refractory to nonbiologic DMARDs and TNF inhibitors
Used as monotherapy or in combination with nonbiologic DMARDs
Infusion reactions are common (sometimes severe)
Likely increases susceptibility to infection, but association with TB has not been demonstrated

27
Q

Which class of drugs is considered first-line therapy for treatment acute gout symptoms?

Glucocorticoids
NSAIDs
Opioids
Uricosuric agents
Xanthine oxidase inhibitors
A

NSAIDs

28
Q

NSAIDs for Gout

A

First-line therapy; they inhibit urate crystal phagocytosis
Some commonly used agents: naproxen, indomethacin, sulindac
Celecoxib is often used (off-label) to treat gout due to decreased incidence of GI adverse effects
All other NSAIDs (except aspirin, salicylates, and tolmetin) have been successfully used to treat gout
Aspirin is not used because it can inhibit urate excretion at low doses and can inhibit the action of uricosuric agents

29
Q

NSAIDs: Adverse Effects

A

Some patients who do not respond to or tolerate one NSAID may tolerate or respond to another
GI upset with progression to ulcers
- GI toxicity can be reduced by concomitant use of additional agents (misoprostol, proton pump inhibitors)
Increased bleeding time due to platelet inhibition
Renal insufficiency in susceptible individuals
Restricted during pregnancy

30
Q

The patient has active peptic ulcer disease and cannot tolerate non-selective NSAIDs. An alternative agent is prescribed to treat the acute attack that acts by inhibiting microtubule polymerization. Which agent best fits this description?

Allopurinol
Colchicine
Indomethacin
Probenecid
Triamcinolone
A

Colchicine

31
Q

Colchicine

A

MOA: binds to tubulin and prevents its polymerization into microtubules, leading to inhibition of leukocyte migration and phagocytosis

Clinical Uses

  • Second-line therapy for acute gout (narrow therapeutic index)
  • Used at low doses between attacks for prevention

Adverse Effects

  • Often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain
  • Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures can occur
  • Treatment with colchicine should not be repeated within 14 days to avoid cumulative toxicity
32
Q

Glucocorticoids for Gout

A

Sometimes used in the treatment of severe gout (particularly in patients with contraindications to both NSAIDs and colchicine)

Intraarticular, oral, or parenteral administration may be used, depending on the number of joints involved

Provide rapid relief within hours of therapy

Intra-articular injections are useful if only a few joints are involved and septic arthritis has been ruled out

33
Q

Urate-lowering therapy is initiated to reduce the probability of gout recurrence. Which agent is most likely to be effective in all cases, regardless of the pathophysiology underlying the hyperuricemia?

Allopurinol
Colchicine
Mycophenolate
Prevacid
Probenecid
A

Allopurinol

34
Q

Xanthine Oxidase Inhibitors

A

Prototype: Allopurinol
MOA: results in decreased uric acid production
First-line therapy for prevention of recurrent gout
Febuxostat is a newer drug that may be more effective, but it is also much more expensive

35
Q

Uricosuric Agents

A

Prototype: Probenecid
MOA: inhibits reabsorption of uric acic
Indicated for treatment of hyperuricemia associated with gout when use of allopurinol or febuxostat aren’t tolerated, or when tophi are present

36
Q

stuff that lowers urate

A

Xanthine Oxidase Inhibitors
Uricosuric Agents

don’t start these during an acute attack

37
Q

adverse effects of xanthine oxidase inhibitors

A

GI intolerance including nausea, vomiting, and diarrhea
Allergic rash
Dosage reduction of chemotherapeutic purines (6-mercaptopurine, azathioprine) is required
Febuxostat is generally well tolerated, even in patients with a history of allopurinol intolerance

38
Q

adverse effects of uricosuric agents

A

Generally well tolerated; mild GI irritation and rash are common
Reduces excretion of numerous therapeutic agents (e.g., penicillin)
Increased uric acid secretion increases the likelihood of renal stone formation; contraindicated in patients with uric acid stones
Uricosuric effects diminished by aspirin and other salicylates

39
Q

Drugs for RA vs Drugs for Gout

A 
Drugs for RA:
	DMARDs
		Nonbiologic
		Biologic
			TNF
			Non-TNF

Drugs for Gout:
Colchicine
Xanthine oxidase inhibitors
Uricosuric Agents

Anti-inflammatory drugs are for both:
NSAIDs
Corticosteroids

MSK II Exam 2 (16 decks)

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