8: Organ Toxicity Flashcards by Linda Chen

5 types of hepatotoxiicty

hepatocellular necrosis
steatosis
chronic hepatitis
cholestasis
fibrosis/ cirrhosis

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what is hepatocellular necrosis

ncrotic cell loss

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what is steatosis

abnormal accumulation of fat in hepatocytes

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what is chronic hepatitis

hepatic inflammation

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what is cholestasis

obstruction of the flow of bile salts

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what is fibrosis/ cirrhosis

pathological wound healing, scarring, increased connective tissue

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DILI is ____ but _____ and often ______ to manage/ diagnose
fill in the blanks: common/ uncommon, clinically important/ unimportant, difficult/ easy to manage

uncommon
clinically important
difficult to diagnose /manage

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which of the following is dose related and predictable
1. direct hepatotox
2. idiosyncratic hepatotox
3. indirect hepatotox

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causes of direct hepatotoxicity

intrinsic hepatotoxicity when agent given in high doses

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causes of idioxyncratic hepatotoxicity

indiosyncratic metabolic or immunologic reaction

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causes of indirect hepatotoxicity

indirect action of agent on liver/ immune system

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T or F: toxins can affect any part of the kidney but not all result in decreased GFR

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nephrotoxicity results ini

AKI, CKD, and functional kidney disorders

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damage to the kidneys, reusltilng in AKI, CKD, and others see changes such as (3)

decreased ability to excrete wastes
disruption to fluid and electrolyte homeostasis
renal hormones impacted (ex- erythropoietin)

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which of the following is false about the CNS
1. the CNS has high cellular interdependence
2. the CNS has high metabolic demant
3. there is a limited understasnding of its normal chemical and molecular function
4. it is a complex system requiring a 3 basic cell types

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neuropathies =

degeneration of neurons

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peripheral neuropathy is

damage to sensory, motor, or autonomic PNS

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what is excitotoxicity

energy needs exceeds production = no ATP to restore or maintain ion gradients

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demyelination impacts

the production and maintenance of myelin

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MAOi inhibits

presynaptic metabolism

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amphetamimnes stimulate

neuronal release of NT

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ACh esterase inhibitors inhibit

synaptic degradation of ACh

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botulinum toxins inhibit

release of neurotransmitters

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respiratory toxicity can manifest as

pulmonary irritation, asthma/ bronchitis, reactive airway disease, emphysema, allergic alveolitis, fibrotic lung disease, pneumoconiosis, lung cancer

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what is the central compartment of PK

blood

what has direct contact with every systemic xenobiotic

blood

because blood comes into contact with almost all toxins, toxins in the blood can disrupt

homeostasis

3 functions of skin

shields internal organs maintains homeostasis prevents infections

3 main components of skin

epidermis, dermis, hypodermis

what is one of the most common body systems for ADRs

skin

transdermal xenobiotic absorption depends on

passive diffusion lipid solubility concentration gradient MW skin permeability

burns are mostly ________ rather than ________

chemical reactivity rather than thermal damage

chemical reactivity burns may be caused by

oxidizing or reducing agents, corrosives, protoplasmic poisons, desiccants, or vessicants

chemical burns often appear _________ but can _________

mild/ superficial can progress in 24-36hrs to necrosis

list 3 systemic injuries/ diseases that manifest dermatologically

cyanosis xanthoderma pruritus flushing sweating dyspigmentation

urticaria is a type ___ reaction

1- IgE

bullous reactions are often _____ or _____ related

xenobiotic or autoimmune

drug induced hypersensitivity sx is characterized by

fever, skin eruptions, internal organ involvement

drug induced hypersensitivity sx is more common in patients with underlying diseases like

hepatitis, interstitial nephritis, vasculitis, pneumonitis, autoimmune hypothyroidism

anticoagulant induced skin necrosis is usually due to ______ and starts ______

warfarin 3-5 days after initiation

anticoagulant induced skin necrosis corresponds to ________________________ from warfarin tx. it results from _________________

expected early decline in protein C function results from antibodies that bind to complexes of heparin and platelet factor 4 and induce aggregation

SJS/ TENs is due to drugs activating ________________ = triggering extensive apoptosis

cytotoxic T lymphocytes + Fas ligand/ perforin granzyme pathways

SJS/ TENs is a ____ mediated, type ___ hypersensitivity

T cell mediated type 4 hypersensitivity

_______ dermatitis occurs when a xenobiotic comes into contact with skin

xenobiotic

allergic contact dermatitis is a type ___ hypersensitivity reaction

What is the difference between allergic and irritant contact dermatitis

irritant contact dermatitis does not require prior antigen sensitization

what is the pathophys of nonreversible CV toxicity

cell loss through necrosis/ apoptosis

what is usually seen on diagnosis of nonreversible CV toxicity

injury marker release, progressive contractile dysfunction, cardiac remodeling

what are some manifestations of nonrev cardio tox

cardiomyopathy, HF, MI, thrombosis- progressive in nature

what is the pathophys of reversible CV damage

cellular dysfunction

upon diagnosis of reversible CV toxicity, what is usually seen

no injury marker release, reversible contractile dysfunction, reversible arterial hypertension

reversible CV toxicity manifestations include

temporary contractile dysfunction, vasospastic angina, arterial hypertension - normalizes over time

list 3 possible characteristics of cardiotoxicity

abnormalities in repolarization reduced ventricular ejection fibrosis HF altered hemodynamics hemostasis and thrombosis

when xenobiotics imapct cardiac contractility, there are changes in

ejection fraction, CO, BP

inotrophy is dependent on

sympathetic/ parasympathetic NS, preload/ afterload, HR, catecholamines

mechs of cardiotox are usually _______ and/or _______

multifactorial unknown

Xenobiotics can directly cause dysrhythmias/ cardiac conduction abnormalities by affecting _________ or indirectly via _________

the cell membrane metabolic effects

how does atropine affect the HR + MOA

rises HR- blocks inhibitor effect of vagal influence

phenylephrine effect on HR

bradycardia

arrhythmias result from alterations of

impulse formation or conduction

what 2 drug classes cause hyperkalemia

Cardioactive steroids Beta adrenergic blockers

3 classes of drugs that cause hypokalemia

loop diuretics, insulin, thiazide diuretics

list the ECG changes that occur with increasing K+ conc

peaked T waves - PR prolongation - loss of P wave - QRS widening - sine wave

describe the ECG changes that occur with decreasing K+ conc

flattening of T wave- appearance of U waves - depression of ST segments

which 5 drugs cause hypercalcemia

All trans retinoic acid Androgens Antacids Lithium Thiazide diuretics

xenobiotics more commonly cause _______ than _________ - calcium changse

hypocalcemia > hypercalcemia

T or F: ECG abnormalities from calcium changes are common, but life threatening dysrhythmias are rare

the hERG gene encodes a _________

pore forming subunit of rapidly activating delayed rectifier cardiac K+ channel

xenobiotics cause HPTN by

CNS synpathetic overactivity increased myocardial contractility increased peripheral resistance

xenobiotics cause hypotension by

decreasing peripheral vascular resistance decreasing myocardial contractility dysrhythmias depletion of intravascular volume

the antitumor properties of anthracyclines come from

inhibition of topoisomerase and DNA synthesis

LT AEs of anthracyclines

cardiomyopahty and congestive HF

_________ is inflammation of the myocardium

myocarditis

what is the most common cause of myocarditis

viral infection

list 3 RFs for cardiotoxicity in cardiooncology

Prior anthracycline based tx or combined trastuzumab/ anthracycline Elderly (>75yrs) Prior mediastinal or chest radiotherapy HPTN, diabetes Smoker Very young (<10yrs) Elevated cardiac biomarkers Baseline abnormal LV systolic function (LVEF <50%)