Drug Induced Disorders ES

Treatment of TdP

- d/c QT prolonging drugs

- balance pt electrolytes

- IV magnesium

What is Torsades de Pointes (TdP)?

- rapid ventricular arrhythmia

- manifests as a "twisting" pattern of QRS complexes and prolonged QT intervals

What is the main marker in an EKG reading that increases risk of TdP?

lengthening of QT interval

What drug classes are considered high risk for QT prolongation and TdP?

- cardiac drugs

- antidepressants

- antipsychotics

- antihistamines

- antimicrobials (some abx and azoles)

Patient risk factors for QT prolongation/TdP

- certain genetic mutations

- female

- older age

What are some conditions that put patients at higher risk for QT prolongation/TdP?

- hypocalcemia/magnesaemia/kalemia

- myocardial ischemia

- cardiomyopathies

- hypothyroidism

- obesity

- HTN

What is the 4T score?

- used to assess risk of HIT in patients on heparin

- low risk (0-3), intermediate risk (4-5), high risk (6-8)

What is heparin induced thrombocytopenia (HIT)?

Development of antibodies against heparin- bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets thrombosis and thrombocytopenia.

What can HIT cause?

thrombosis and potentially fatal clots

Which is more likely to cause HIT-- UFH, LMWH?

UFH

Diagnosis of HIT

- temporal association with heparin therapy

- laboratory evidence of anti-PF4/heparin antibodies

- major decrease in platelets

Laboratory tests used to identify HIT

- platelet activation assays ("functional" assays)

- immunoassays

Pros of platelet activation assays for HIT

high specificity (will identify HIT very well)

Cons of platelet activation assays for HIT

- low sensitivity

- more technically challenging

Platelet activation assays

detect antibodies capable of binding and cross-linking platelet FcyRIIA

Pros of immunoassays for HIT

- technically simple

- high sensitivity

Cons of immunoassays for HIT

lack specificity (due to potential for asymptomatic seroconversion)

Immunoassays

measure presence of anti-PF4/heparin antibodies using variety of antibody capture platforms

Treatment of HIT

- D/C all sources of heparin

- start alternative anticoagulation therapy (direct thrombin inhibitors, VKA)

- **Argatroban

Treatment of ILD

- remove offending agents

- corticosteroids

What is ILD?

exposure to drug causes inflammation and fibrosis of lung interstitium

Diagnosis of ILD

- temporal relationship between onset of symptoms and drug exposure

- absence of a more likely cause

- improvement upon withdrawal of causative agent

Drugs likely to cause ILD

- cancer drugs

- rheumatology drugs (DMARDs)

- amiodarone

- antibiotics

How does amiodarone cause ILD?

- cytotoxic to alveolar epithelial cells and other cells that maintain interstitial space in the lungs

- high dose for a long time

What kind of ILD does amiodarone cause?

normally subacute (can cause acute)