8: Organ Toxicity Flashcards
5 types of hepatotoxiicty
hepatocellular necrosis
steatosis
chronic hepatitis
cholestasis
fibrosis/ cirrhosis
what is hepatocellular necrosis
ncrotic cell loss
what is steatosis
abnormal accumulation of fat in hepatocytes
what is chronic hepatitis
hepatic inflammation
what is cholestasis
obstruction of the flow of bile salts
what is fibrosis/ cirrhosis
pathological wound healing, scarring, increased connective tissue
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
which of the following is dose related and predictable
1. direct hepatotox
2. idiosyncratic hepatotox
3. indirect hepatotox
1
causes of direct hepatotoxicity
intrinsic hepatotoxicity when agent given in high doses
causes of idioxyncratic hepatotoxicity
indiosyncratic metabolic or immunologic reaction
causes of indirect hepatotoxicity
indirect action of agent on liver/ immune system
T or F: toxins can affect any part of the kidney but not all result in decreased GFR
T
nephrotoxicity results ini
AKI, CKD, and functional kidney disorders
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)
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
4
neuropathies =
degeneration of neurons
peripheral neuropathy is
damage to sensory, motor, or autonomic PNS
what is excitotoxicity
energy needs exceeds production = no ATP to restore or maintain ion gradients
demyelination impacts
the production and maintenance of myelin
MAOi inhibits
presynaptic metabolism
amphetamimnes stimulate
neuronal release of NT
ACh esterase inhibitors inhibit
synaptic degradation of ACh
botulinum toxins inhibit
release of neurotransmitters
respiratory toxicity can manifest as
pulmonary irritation, asthma/ bronchitis, reactive airway disease, emphysema, allergic alveolitis, fibrotic lung disease, pneumoconiosis, lung cancer
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
4
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
T
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%)
