Exam I Important Stuff to Know

GOUT

Risk factors for gout

Male, older, obese

Diet high in animal sources of purines

Alcohol and high-fructose corn syrup sweetened drinks (beer, not wine)

Renal insufficiency and organ transplant (especially kidneys)

How to treat gouty arthritis attacks based on patient factors

NSAIDs > Colchicine > Oral Glucocorticoids

Unapproved options: Corticotropin, IL-1 inhibitors

Use topical ice as adjuvant

What makes patient candidate for Urate Lowering Therapy (ULT)

Only if one of three options below are true:

≥ 1 SQ tophus

Evidence of radiographic damage attributable to gout

≥ 2 gout flares annually

Allopurinol (1st line) > Febuxostat (alternative)

Only use Probenecid if 1st line and alternative are not appropriate or as add on

Only use Pegloticase as alternative for refractory gout

Other adjunct drugs to lower urate in gout

Losartan (only ARB/ACEi used in gout)

Fenofibrate

SGLT2

Single most important factor that decreases incidence in gouty arthritis attacks

Keep serum uric acid levels < 6 mg/dL

RHEUMATOID ARTHRITIS/OA

How to treat acute RA flares

NSAIDs (mild and for occasional symptoms)

Corticosteroids (usually only for flares)

Continue DMARD therapy and adjust if disease is not controlled

What does + RA factor and + anti CCP antibodies mean

+RF

• Higher titers correlate to worse disease

• Not specific to RA

+anti-CCP antibodies

• Very high specificity

• associated with more aggressive RA

TNF Inhibitors - MOA (Adalimumab, Infliximab, Etanercept, Golimumab, Certolizumab)

Block TNF-α (used to trigger inflammation)

Common biologic side effects

Increased infection risk

Reactivate Hep B and TB (chance)

TB screening before treatment

Rituximab - MOA

Depletes B cells, Anti CD20 monoclonal antibody

Rituximab - Side Effects

Infusion reactions, increased risk of infection

Abatacept - MOA

Prevents T cell activation, CTLA-4 agonist

Abatacept - Side Effects

Infection risk, IV form has high risk of anaphylaxis

Tocilizumab - MOA

IL-6 receptor blocker

Tocilizumab - Side Effects

GI perforation, neutropenia, thrombocytopenia, hypertriglyceridemia

Jak Inhibitors - MOA (Tofacitinib, Baricitinib, Upadacitinib)

Inhibit JAK-STAT signaling pathway

Jak Inhibitors - Side Effects (Tofacitinib, Baricitinib, Upadacitinib)

Herpes Zoster reactivation, infections, malignancy, diarrhea, headache,

higher doses linked to thrombosis and death

Synthetic DMARDS

Methotrexate

Hydroxychloroquine

Sulfasalazine

Leflunomide

Methotrexate

Initial dose: 7.5 mg once weekly

Max dose: 25 mg once weekly

Must take folic acid 1mg/day

ADRs: Stomatitis, alopecia, hepatic (LFTS q 6 weeks), pulmonary, teratogenic, hematologic

Leflunomide

Dose: 100 mg for 3 days then 10-20 mg daily

Monitor CBC and LFTS

ADRs: teratogenic, less nausea, oral ulcers and liver problems

More expensive and not any more effective than MTX

Hydroxychloroquine

Initial dose: 400 - 600 mg daily

Maintenance: 200 mg daily

ADRs: GI, retinopathy (rare)

Sulfasalazine

Dose: 2-3 g in 2-3 divided doses

ADRs: hematologic, hepatic, nausea, renal dysfunction,

C/I: sulfonamide allergy

DRUG-INDUCED DISEASES

How would you assess somebody with HIT

Magnitude of platelet drop

Timing of thrombocytopenia in relation to heparin exposure

Presence of new thrombosis

Other possible reasons for thrombocytopenia

Based on the 4T score, what do you do with it? What does it tell you?

Score 0-3 (low risk): continue heparin and monitor

Score 4-5 (intermediate risk): stop or change anticoagulant and check Ab

Score 6-8 (high risk): change to argatroban/fondapiranux and check HIT Ab

Patient risk factors for Torsades

Age > 65

Female

Sepsis, congenital long QT syndrome, bradyarrhythmias

Electrolyte and metabolic disorders (hypokalemia, -magnesia, -calcemia, hypothyroidism, anorexia, hypo/hyperglycemia)

Cardiac abnormalities (MI, HF, ventricular hypertrophy, previous anti-arrhythmic therapy)

Drug risk factors for Torsades

increase QTc interval 60 ms from pre-drug baseline

Prolong QTc administered IV with rapid infusion rate

High drug doses/concentrations (except quinidine)

Chronic hepatic and renal insufficiency

First line treatment for Torsades

Magnesium Sulfate

Second line treatment for Torsades

Isoproterenol

Sodium Bicarbonate (quinidine-mediated arryhtmias)

Steroid sparing agents in DILD

Mycophenolate, azathioprine, N-acetylcysteine

PEPTIC ULCER DISEASE

What kind of ulcers does H. Pylori cause

Duodenal Ulcers (90% of them!)

Complications of H. Pylori

Degrades gastric mucosa (leads to ulcers)

Increases gastric acid production

Associated with certain gastric cancers

Easy v. Hard to treat H. Pylori

Hard: very resistant

Requires multiple antibiotics as well as raising gastric pH to a level where growth is inhibited

Tests for H. Pylori

Stool antigen testing and urea breath test

Most definitive test for PUD

Upper GI Endoscopy

Primary treatment for H. Pylori

Bismuth Quad Therapy:

PPI, Bismuth, Metronidazole, Tetracycline

GERD

Typical GERD symptoms

Heartburn (warmth and pressure/pain to neck)

Waterbrash (hypersalivation)

Belching and regurgitation

Atypical GERD symptoms

Asthma-like wheezing

Chronic cough

Dental erosions

Non-cardiac chest pain

Daytime sleepiness

Lifestyle modifications to decrease risk of GERD

Elevate head of bed to 30 degrees

Avoid foods that lower LES tone (fats, chocolate, alcohol, mints)

Avoid irritating foods (spicy, acidic foods, coffee)

Eat small portions

Avoid eating within 3 hours of sleep

Stop smoking, lose weight

Alginic Antacids

Create foamy barrier that floats on stomach contents (mild symptoms; not severe GERD)

Non-Alginic Antacids

Neutralizes stomach acid

IRRITABLE BOWEL DISEASE (Ulcerative Colitis)

Mild UC

< 4 stools a day

normal ESR

no systemic toxicity

Moderate UC

6-10 bloody stools/day

Abdominal pain but can eat

Fecal calprotection

Severe UC

>10 blood stools a day

Fever, tachycardia, anemia

+CRP and FCP

UC symptoms

Bloody stools

Tenesmus (urge to defecate)

Smoking in UC

decreases risk

Proctitis treatment

All severity

Topical 5-ASA suppository

Distal Colitis treatment

Mild-moderate: Topical 5-ASA enema

Severe: 5-ASA enema + oral 5-ASA or Budesonide

Pancolitis treatment

Mild-moderate: oral 5-ASA or budesonide

Severe: oral or IV steroids (thiopurines for maintenance)

Pancolitis treatment if not responsive to non-biologic therapy

Anti-TNF (preferred)

S1P receptor modulators, IL-12/23 blockers, Vedolizumab, JAK inhbitiors

IRRITABLE BOWEL DISEASE (Crohn’s)

Mild-moderate Crohn’s

Ambulatory pts who are able to orally feed without signs of systemic toxicity

Moderate-severe Crohn’s

Fever, weight loss, abdominal pain, N/V and/or significant anemia

Severe-fulminant Crohn’s

Pts with persistent symptoms, signs of severe toxicity

Crohn’s symptoms

Less bloody stools

Fatigue, malaise, nausea, fever

Smoking in Crohn’s

Increases severity

Mild-moderate CD treatment

Oral steroid

Enteral nutrition

5-ASA

Anti-TNF if refractory

Moderate-severe CD treatment

Oral steroid

Enteral nutrition

Combined use of GMA (colonic lesions)

Anti-TNF if refractory

Severe-fulminant CD treatment

Hospitalization

IV nutrition and steroids

Surgery??

Anti-TNF MOA and ADRs

Blocks TNF-a (reduces inflammation)

ADRs: infection, infusion reactions, autoimmune arthritis

Vedolizumab MOA and ADRs

α4β7 integrin blocker (does not penetrate BBB)

ADRs: infection risk

IL-12/23 inhibitor MOA and ADRs

Blocks cytokines that drive inflammation

ADRs: infection, increased risk of Hep B

JAK inhibitor MOA and ADRs

Block JAK-STAT signaling pathway

ADRs: infection, shingles reactivation, increased LDL

S1P modulator MOA and ADRs

Prevents lymphocyte egress from lymph nodes

ADRs: bradycardia, increased LFTs

CHRONIC LIVER DISEASE

What cause of CLD is increasing the most rapid in the US

Non-alcoholic fatty liver disease (NAFLD)

Ascites treatment

Spironolactone (due to hyperaldosteronism with ascites)

Loop diuretics (works quicker than spironolactone)

40:100 ratio furosemide:Spironolactone

TIPS if refractory

Hepatic Encephalopathy treatment

Lactulose (titrate to 3-4 stools/day)

Other local antibiotics (neomycin, metronidazole, rifaximin (preferred))

Flumazenil for HE coma?

Spontaneous Bacterial Peritonitis treatment

Cefotaxime (preferred), but can use ceftriaxone x 5 days (if allergic use levo)

Add albumin 1.5 g/kg on day 1 then 1 g/kg on day 3

Autoanticoagulation treatment

High dose of vit k (meh)

Cryoprecipitate (for low serum fibrinogen)

Alcoholic Hepatitis treatment

Use MELD score (% risk of death within 3 months to prioritize organ transplant)

Methylprednisolone 32mg daily for 28 days

Add N-acetylcysteine if MELD > 30

DRUG ALLERGY

Drug Allergy

Not an expected pharmacological effect

Typical symptoms of allergy (skin rxns, anaphylaxis)

Occurs at dose below therapeutic levels

Can resolve fairly quickly after D/C agent

Chemical cross-reactivity possible

Adverse Drug Reaction

Predictable effects

Dose-dependent

Not mediated by IgE, IgG or T-cells

Gell and Coombs Classifications

Anaphylaxis treatment (initial)

Maintain airway with 100% oxygen

Administer IV fluids, Epi for shock

Anaphylaxis treatment (secondary)

Administer antihistamines and/or corticosteroids

Cross-reactivity Penicillins and Cephalosporins

Early generation: 5-10%

Later generation: 1-4%

Cross-reactivity with other beta lactams

Carbapenems: meropenem and imipenem have little to no cross reactivity in PCN allergic patients

Aztreonam safe in PCN allergy

Cross-reactivity with quinolone

Low % chance

Protocols prior to starting biologics

TB, Hep B/C and chronic infection screening

CBCs and LFTs

Live vaccines should be 4 weeks before starting treatment