Exam 1 - Key Concepts RW

What are risk factors for gout?

Typical patient: older, male, obese

Diet high in animal sources of purines

Consumption of alcohol and high-fructose corn-syrup sweetened drinks (Beer but NOT wine)

Renal insufficiency and CKD

Organ transplantation - especially kidney

Diuretic use (HBP, CHF)

Cytotoxic use (lymphoma/leukemia)

Cyclosporine use

Obesity, T2DM, metabolic syndrome

What are options for treating acute gout?

NSAIDs

Colchicine

Steroids

ICE

IV fluids

When are NSAIDs used for acute gout?

Drug of choice for most patients

When should use of NSAIDs be avoided?

Hx. PUD or GI bleed

Warfarin use

Acute/chronic kidney dysfunction

When is Colchicine used for acute gout?

Used primarily if intolerant to or have a GI C/I for NSAIDs

When are steroids used for acute gout?

Intraarticular injections can provide rapid relief IF one or two easily accessible joints are affected

Systemic steroids used if patients have significant history of PUD and/or has renal insufficiency

How do you decide if a gout patient is a candidate for ULT?

Initiating ULT recommended for patients who have:

≥1 SubQ tophi

Evidence of radiographic damage attributable to gout

Frequent gout flares (≥2 annual flares)

(Or more than one attack in lifetime)

What drugs can be used to achieve target SUA level?

Allopurinol - 1st line

Febuxostat

Probenecid - if can't use XOI's or as add-on therapy

Pegloticase - for refractory gout

Losartan - add on for pt.'s with HTN

Fenofibrate - add on for pt.'s with high triglycerides

What lifestyle modifications are most important to prevent recurrence of gouty arthritis?

Lose weight if obese

Avoid beer/spirits

Sensible diet (Avoid high fructose corn syrup, Avoid lots of animal purines; Decrease protein consumption, IBW)

Hydrate with 2-3 liters of water per day

What pharmacologic treatments are there for OA?

Acetaminophen

NSAIDs

COX-2 inhibitors

Duloxetine

Opioids

Glucocorticoid injections

Hyaluronans injections

When is Acetaminophen used for OA?

Indicated for mild-moderate pain

NSAIDs > Acetaminophen > Placebo

When are NSAIDs used for OA?

Topical if knee or shoulder is preferred for less toxicity

Variable efficacy and toxicity

When is Duloxetine used for OA?

Recommended for patients not getting enough relief from APAP/NSAIDs

When are Opioids used for OA?

Last resort meds before surgery or if surgery is not indicated

Use low dose as needed if possible

When are glucocorticoid injections used for OA?

Indicated if pain persists despite oral analgesics

Effective for short term pain relief (<12 weeks)

Limit to every 3 months for up to 2 years

When are hyaluronans used for OA?

Indicated if pain persists despite other agents

Pain relief probably worse than steroid injections

What is the general MOA of biologics in RA?

Inhibition of cytokines

VIA:

Neutralization of cytokines

Receptor blockade

Activation of anti-inflammatory pathways

What is the MOA of TNF-a inhibitors?

Prevent TNF-a mediated inflammatory actions

What is the MOA of Rituximab?

Anti-CD20 Antibody

Causes B-Cell Depletion

What is the MOA of Abatacept?

T-Cell Modulator

Inhibits activation of T-cells

What is the MOA of Toxlizumab?

Anti-IL-6 medication

IL-6 is pro-inflammatory

Blockade reduces inflammation

What is the MOA of JAK inhibitors?

JAK system involved in immune cell function

Inhibition suppresses the cytokine-mediated inflammatory response

What are options for immediate treatments of RA flares?

NSAIDs

Glucocorticoids

What does a rheumatoid factor (RF) level mean in RA patients? Is higher or lower worse?

Higher titers correlated with worse disease

Detect IgM RF, seen in 60-70% of RA patients

What does a anti-CCP level mean in RA patients? Is higher or lower worse?

Linked to most erosive forms of disease

Which DMARD is associated with herpes reactivation?

Janus-Kinase (JAK) inhibitors (-nib's)

Carry BBW for herpes infection/reactivation

Must test for TB and Hep B/C before initiating

What are the components of the 4T score?

Magnitude of platelet drop

Timing of thrombocytopenia in relation to heparin exposure (5-10 days)

Presence of new thrombosis

Other possible reasons for thrombocytopenia

What should be done if the T score is 1-3?

Continue heparin and monitor platelets

What should be done if the T score is 4-5?

Stop or change anticoags, and check Ab

What should be done if the T score is 7-8?

Change to Argatroban/Fondaparinux and check HIT Ab

What patient factors predispose patients to TdP/QT-prolongation?

Age >65

HF

Electrolyte abnormalities - Hypokalemia or Hypomagnesia

Female gender

What are pharmacologic treatment options for TdP?

Magnesium Sulfate (1st line)

Isoproterenol

Sodium bicarbonate (for quinidine-mediated arrythmias)

If somebody on high dose long-term steroids for drug-induced lung disease, what immunomodulators could you use to reduce the steroid dose?

Steroid-Sparing agents:

Mycophenolate, Azathioprine

NAC

Who should receive gastroprotection prophylaxis, in someone who requires NSAIDs or other anti-inflammatory agents?

Indicated in patients with:

GI bleeding

Dual antiplatelet therapy

Concomitant anticoagulant use

Indicated if have more than one risk factor:

≥60 yr old

Corticosteroid use

Dyspepsia or GERD symptoms

How does atypical GERD present?

Asthma like wheezing

Chronic cough

Dental erosions

Non-cardiac chest pain

Daytime sleepiness

How does complicated GERD present?

Severe symptoms, and usually severe or erosive esophagitis

Continual pain

Odynophagia

Esophageal stricture/spasm

What are lifestyle modifications for GERD to counsel patients on?

Elevate head of bed by 30 degrees

Avoid food that lower LES: Fats, Chocolate, Alcohol, Mints

Avoid irritating foods: Spicy or acidic foods, Coffee

Eat small meals and avoid eating within 3 hours of going to bed

Stop smoking

Lose weight if obese

Are any antacids preferred over other ones for treating GERD?

Antacids containing alginic acid are superior

Otherwise all antacids work the same

What is the first line treatment for mild (<2x/wk) GERD?

OTC Tx.

What is the refractory treatment for mild (<2x/wk) GERD?

PPI

What is the first line treatment for moderate (>2x/wk) GERD?

PPI

What is the refractory treatment for moderate (>2x/wk) GERD?

High dose (BID) PPI

What is the first line treatment for severe (daily) GERD?

PPI

What is the refractory treatment for severe (daily) GERD?

BID PPI or Vonoprazan

Or surgery

What part of the GI tract is affected by UC?

Colon and rectum

What part of the GI tract is affected by CD?

Any part of GI tract

What are symptoms of UC?

Chronic, loose bloody stools

Tenesmus

Abdominal pain

What are symptoms of CD?

Diarrhea

Abdominal pain and tenderness (worse pain)

Weight loss

Fever

Nausea

Anorexia

Before starting a biologic, what testing and preparations should be done?

Screen for TB and Hep B/C

Vaccinations (Give any vaccine possible before starting therapy)

Screen for any active infections

What is the MOA for Vedolizumab?

a4B7 Integrin Blocker

Blocks inflammatory pathway in gut and brain

What is the MOA for Ustekinumab?

IL-12/23 blocker

Inhibits IL-12 and IL-23 mediated signaling, cellular activation, and downstream cytokine production Reduces pro-inflammatory signaling

What is the MOA for Ozanimod/Etrasimod?

S1PR

Blocks lymphocytes from leaving lymph nodes

Decreases immune cells to prevent inflammatory responses

What should be done if someone is on a drug that has elevated LFTs 3x ULN?

Increase in AST/ALT >3x ULN: D/C Drug

What should be done if someone is on a drug that has elevated LFTs 2x ULN?

If increase in AST/ALT <3x ULN:

May reduce dose or hold

Best to monitor LFTs more frequently (Before deciding to change therapy)

What is the treatment for SBP?

Ceftriaxone or Cefotaxime for 5-7 days

Add albumin (to improve response and prevent HRS)

How is SBP prevented?

Ciprofloxacin or Bactrim

(Cipro preferred (due to resistance))

What are treatment options for ascites?

Spironolactone + Loop

Paracentesis

TIPS Shunt

How is HE treated?

Lactulose is primary treatment

IF Lactulose not effective/tolerated: Rifaximin

How is variceal bleeding treated?

Endoscopic treatment (banding, sclerotherapy)

Octreotide in severe cases (IV)

3rd gen cephalosporins (Cefotaxime or ceftriaxone) for 5 days due to SBP risk

How is variceal bleeding prevented?

NON-selective B-blockers (Propranolol, nadolol, or carvedilol)

Can use nitrates if B-blockers not tolerated

What is the fastest growing cause of CLD in the US?

Non-Alcoholic Liver Disease (NAFLD)

Incidence rapidly rising due to obesity

If patient has a type 4-C reaction to a drug, can they receive that drug again?

NO, if have 4-C reaction future use is C/I

SJS/TEN reactions are an absolute C/I to future use

What is the definition of a drug allergy?

Reaction is NOT an expected pharmacologic effect

Clinical symptoms resemble an allergic reaction

Reaction can occur at a dose below that needed for pharmacologic effect

Resolution occurs within days/weeks of D/C'ing agent

Chemical cross-reactivity can occur

What are characteristics of a quinolone allergy?

IgE mediated reactions

Due to covalent coupling with sites on molecules common to all quinolones

Low risk cross-reactivity

65-75% of pt.'s with immediate-type reactions to fluroquinolones tolerate the culprit when re-challenged

(Safe option is just to use a different quinolone)

What are characteristics of cross-reactivity between ACE/ARB?

10% cross reactivity to cause ARB-induced angioedema

Use depends on how badly need ARB

Reaction can be life threatening

Best to avoid use if possible

How is anaphylaxis treated?

EPINEPHRINE!!!

Initial: oxygen, IV fluids, epinephrine

Secondary: antihistamines, corticosteroids

When should penicillin skin testing be done?

If history of anaphylaxis or recent reaction suspected to be IgE mediated

Safe even in extremely allergic patients IF scratch testing used first

Can only assess Type 1 (IgE) reactions

WHen should direct oral challenge be done?

Adults with history of distant (>5 yrs) and benign cutaneous (MDE/Urticaria) reaction

When should desensitization be done?

Only for IgE reactions (NOT SJS/TEN)

Only considered when PCN/Beta Lactam antibiotic is absolutely necessary

What are characteristics of cross reactivity between PCN and cephalosporins?

Reactions are mainly side chain-specific

Earlier "generation" cephalosporins have a higher chance of cross reactivity (5-10%) than later "generations" (1-4%)

What are characteristics of cross reactivity between PCN and other beta-lactams?

Carbapenems: little or no cross-reactivity

Monopenems (Aztreonam): safe in PCN allergy