Week 5 Al-Mehdi ILAs Flashcards
What are the major causes of relative and absolute hypovolemia?
relative- third space loss (fluid changes places), sepsis, edema states (heart failure, cirrhosis); nephrotic syndrome
absolute- hemorrhage, GI fluid loss (diarrhea, etc), fluid loss from skin (burns, sweating) ; diuretics, endocrine diseases
Why is 5% glucose in water (D5W) ineffective for replacement of lost fluid?
if 1000mL is given, ~70mL will be intravascular and the rest will be added to ICF or ECF
Why is 3 L of normal saline (NS) or Ringer’s lactate needed to replace 1 L of blood loss?
they are isotonic solutions of electrolytes in water and they distribute rapidly through ECF compartment, they contain NaCl and lactate, K+ and Ca2+
Why is lactate better than bicarbonate in solution to replace plasma bicarbonate?
bicarbonate is unstable in solution. Once lactate is metabolized, it results in bicarbonate
How does administration of hypertonic NaCl solution reduce brain edema?
induces a shift of fluid from ICF to ECF –> reducing brain water and Inc intravascular volume
Why are colloids NOT used frequently for volume resuscitation despite their theoretical advantages over crystalloids?
HES in particular appears associated with a risk of renal failure when used for resuscitation in patients with septic shock
What are the major phases of drug metabolism?
Phase 1- OXIDATION, REDUCTION, AND HYDROLYSIS, of the parent molecule
goal: WATER SOLUBILITY + drug activation sometimes
Phase 2- CONJUGATION
Goal: DRUG INACTIVATION + water solubility
Phase 3: EXCRETION INTO BILE
Which cell is the major site for drug metabolism?
Hepatocytes
What are the goals of phase 1 of metabolism?
make water soluble for urine excretion; activate prodrugs, inactivate some drugs
What are the major reactions in phase 1?
OXIDATION, REDUCTION, HYDROLYSIS
bile acid oxidation by specific CYPs
testosterone –> estrogen by CYP 19 (aromatase)
CYP2E1 catalyzes ACETAMINOPHEN to NAPQI –> hepatotoxicity
How do the cytochrome P450 enzymes metabolize drugs?
inducers - DEC effectiveness
inhibitors- INC toxicity
What are the typical reactions in phase 2 metabolism?
conjugation
What is the goal of phase II?
inactivation of drugs and glucuronidation
List drugs and other products that inhibit or induce cytochrome P450 enzymes. How can they affect the effectiveness or toxicity of other drugs?
CYP3A4 inducers (DEC effectiveness) - St. Johns Wort, Rifampin, Griseofulvin
CYP3A4 inhibitors (INC toxicity) - grapefruit juice, Cimetidine, Ciprofloxacin, Erythromycin, Ketoconazole
Where is the subcellular location of CYPs?
within the endoplasmic reticulum and mitochondria of liver cells
What happens to smooth ER after barbiturate treatment?
induce the proliferation of the smooth ER and its associated detoxification enzymes, thus increasing the rate of detoxification
What is the mechanism of CYP induction by drugs?
What 2 drugs metabolize/inactivates CYP2C9 that leads to bleeding
WARFARIN + CIMETIDINE
What 2 drugs metabolize/inactivates CYP3A4 that leads to bleeding
WARFARIN + ERYTHROMYCIN
What 2 drugs inhibit CYP3A4 = metabolized by CYP3A4, and prolongs QT leading to arrhythmia and cardiac arrest? and what is it called just before the heart goes into ventricular fibrillation?
ERYTHROMYCIN + KETOCONAZOLE
Torsades de Pointes
What 2 drugs are activated/inactivated by CYP2C19 leading to platelet aggregation
CLOPIDOGREL + OMEPRAZOLE
What drugs metabolize and inhibits CYP3A4 leading to myopathy, including rhabdomyolysis
STATINS + Grapefruit juice
What 2 drugs induce/ degrade CYP34A that leads to a baby?
RIFAMPIN + Oral contraceptive
What 2 drugs compete for UDP-glucuronosyltransferase for inactivation (phase 2 metabolism) leading to myoglobinuria
GEMFIBROZIL + SIMVASTATIN
