First Aid 221-244 Flashcards
What is defective in Leukocyte adhesion deficiency type 2
Low amounts of sial-lewis-x
What is the role of metalloproteinases in wound healing?
tissue remodeling
What is the role of FGF in wound healing?
stimulates angiogenesis (VEGF also does this)
Pathogenesis of granuloma formation
Th1 cells secrete IFN-gamma –> macrophages activated
TNF-alpha from macrophages induces and maintains granuloma
Type of amyloid found in chronic inflammatory conditions
AA (secondary)
Deposition of proteins from Ig light chains is what kind of amyloid?
Primary - AL
Fibrils composed of beta-2-microglobulin in patients with ESRD or long-term dialysis;
May present at carpal tunnel syndrome;
Dx?
Dialysis-related amyloidosis
Transthyretin mutations result in what kind of heritable disorder?
Amyloidosis
What kind of cancer is implicated by:
ALK
Oncogene - need to damage only one allele
Receptor tyrosine kinase
Lung adenocarcinoma
What kind of cancer is implicated by:
BRAF
Oncogene - need to damage only one allele
serine/threonine kinase
melanoma, non-Hodgkin lymphoma
What kind of cancer is implicated by:
c-KIT
Oncogene - need to damage only one allele
cytokine receptor
Gastrointestinal stromal tumor
What kind of cancer is implicated by:
KRAS
Oncogene - need to damage only one allele
GTPase
Colon cancer, lung cancer, pancreatic cancer
What kind of cancer is implicated by:
MYCL1
Oncogene - need to damage only one allele
TF
Lung tumor
What kind of cancer is implicated by:
MYCN
Oncogene - need to damage only one allele
TF
Neuroblastoma
What kind of cancer is implicated by:
JAK2
Oncogene - need to damage only one allele
TK
chronic myeloproliferative disorders
What kind of cancer is implicated by:
HER2/neu (c-erbB2)
Oncogene - need to damage only one allele
TK
breast and gastric carcinomas
Psammoma bodies are seen in:
PSaMMoma bodies: Papillary carcinoma of the thyroid Serous papillary cystadenocarcinoma of the ovary Meningioma Malignant mesothelioma
Serum tumor marker for Paget’s disease and mets to liver and bone:
alk phos
Serum tumor marker for seminoma
placental alk phos
Serum tumor marker for: hepatocellular carcinoma hepatoblastoma yolk sac (endodermal sinus) tumor mixed germ cell tumor
alpha-fetoprotein
CA 15-3
CA 27-29
serum tumor markers for
breast cancer
CA 19-9
serum tumor marker for
pancreatic adenocarcinoma
CA 125
serum tumor marker for
ovarian cancer
Calcitonin
serum tumor marker for
medullary thyroid carcinoma
Carcinoembryonicantigen (CEA)
serum tumor marker for
non-specific - colorectal, pancreatic, gastric, breast, medullary thyroid carcinomas
P-glycoprotein is aka multidrug resistance protein 1 (MDR1). What is its function and in what conditions is it seen?
Used to pump out toxins ie chemotherapy agents
Seen in adrenal cell carcinoma, also seen in colon and liver cancer
Explain “lead kettle” - Pb-KTL
Prostate breast lung thyroid kidney all produce bone mets
Most common cancer to metastasize to the liver
colon
Km is inversely related to
the affinity of the enzyme for its substrate
Vmax is directly proportional to
enzyme concentration
Why does a competitive inhibitor not change Vmax?
Because Vmax only depends on the enzyme concentration and so an inhibitor can be overcome
How does a noncompetitive inhibitor influence Vmax?
Lowers it
So does a competitive inhibitor but only if it is irreversible
Equation for Loading Dose
LD = Css x Vd
MD = Css x CL
Maintenance dose equation
Km changes with what kind of inhibitor?
Competitive inhibitor
Slope of a Lineweaver-Burk plot
Km/Vmax
Y-intercept of a Lineweaver-Burk plot
1/Vmax
y-int is inversely proportional to the Vmax
X-intercept of a Lineweaver-Burk plot
1/-Km
What is the effect of an irreversible competitive inhibitor on Km?
No effect
Km =
[S] at 0.5Vmax
Vd =
Drug / [ ] plasma
What is a permissive drug interaction?
Presence of substance A is required for the full effects of substance B
ie cortisol on catecholamine responsiveness
Clopidogrel and aspiring given together represents:
Synergistic drug effect
effect of substance A and B together is greater than the sum of their individual effects (ie additive would be aspirin and acetominophen)
What is a tachyphylactic drug interaction?
Acute decrease in response to a drug after initial/repeated administration
MDMA and LSD
PEA for zero-order elimination drugs
Phenytoin
Ethanol
Aspirin
What are examples of Phase II drug metabolism (conjugation)
Methylation
Glucuronidation
Acetylation
Sulfation
The efficacy of a drug is proportional to
Vmax
What is the effect on potency of a competitive antagonist?
Lowers potency
No change in efficacy (bc can be overcome)
MOA Flumezenil
competitive GABA antagonist
for benzodiazepine overdose
MOA Phenoxybenzamine
noncompetitive alpha-receptor antagonist
MOA Buprenorphine
Partial agonist at opioid mu receptors
“After QISSeS you get a QIQ out of SIQ Super Qinky Sex”
GPCRS and pathways --Sympathetic q - alpha 1 i - alpha 2 s - beta 1,2,3 --Parasympathetic M1 - q M2 - i M3 - q --Dopamine D1 - s D2 - i --Histamine H1 - q H2 - s --Vasopressin V1 - q V2 - s
M1, M3, H1, alpha-1, V1
pathway
Gq –> PLC (DAG –> PKC or IPS –> increase in Ca)
M2, alpha-2, D2
pathway
Gi –> inhibits AC
Cholinomimetics are aka
parasympathomimetics
Bethanechol Carbachol Methacholine Pilocarpine drug class?
Bethanechol - activates bowel and bladder
Carbachol - same as acetylcholine
Methacholine - contracts bronchial SM
Pilocarpine - contracts ciliary muscle of eye
DIRECT cholinomimetics
Cholinomimetic used in tx of Sjogrens bc it causes salivation
Pilocarpine
Challenge test in asthma drug
Methacholine
Cholinomimetic can exacerbate COPD/asthma
Treatment of open angle glaucoma
Direct cholinomimetic
Carbachol
Donepezil
Galantamine
Rivastigmine
drug class
Indirect cholinomimetic agonists
Increase ACh
Tx Alzheimer disease
Edrophonium
drug class
Indirect cholinomimetic agonists
Increase ACh for 5-15 min
Diagnosis of MG
Neostigmine
CNS penetration?
Neostigmine - NO CNS penetration bc quarternary amine;
Indirect cholinomimetic agonist
Increase ACh
reversal of neuromuscular junction blockade
Physostigmine
CNS penetration?
YES - Physo phyxes atroping OD
tertiary
Indirect cholinomimetic agonist
Increase ACh
Pyridostigmine
Use
Indirect cholinomimetic agonist
Increase ACh - treat MG
does not cross BBB (quarternary amine)
With all cholinomimetic agents, be careful for:
peptic ulcers
exacerbation of COPD, asthma
DUMBBELSS pneumonic
DUMBBELSS
Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation Lacrimation Sweating Salivation
Cholinesterase inhibitor poisoning (ie insecticides)
Can become irreversible if prolonged (“aging”)
Cholinergic/Parasympathomimetic toxidrome
