targeted drug therapyuse of platinum based chemotherapy agents is limited because of severe adverse effects(eg nephrotoxicity, ototoxicity, myelosuppression)
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The addition of anti-epidermal growth factor receptor (anti-EGFR) antibodies on the liposome surface results in an antibody-drug conjugate, allowing the encapsulated drug complex to selectively bind to tumor cells expressing high levels of EGFR, which is often overexpressed in non-small cell lung cancer. oncologypharmacologyUWorld HirotoShishido
pharmacologic stress testinguseful in diagnosing atherosclerotic CAD(coronary artery disease)
☆Dobutamine, a beta-1 agonist, increases heart rate and contractility to mimic the increase in myocardial oxygen demand that occurs with exercise. Myocardium that is unable to obtain sufficient blood flow to meet the increased oxygen demand typically demonstrates a ☆transient decrease in contractility . cardiologypharmacologyUWorld HirotoShishido
voltage gated sodium channel toxinsBinds to Na+ channels, ☆inhibiting Na+ influx and preventing action potential conduction
・Tetrodotoxin (puffer fish)
・Saxitoxin (dinoflagellates in "red tide")
Binds to the Na+ channel, keeping it open and causing persistent depolarization
・Ciguatoxin (exotic fish, Moray eel)
・Batrachotoxin (South American frogs) pharmacologyUWorld HirotoShishido
adverse effects of PDE-5 inhibitorssildenaFIL, avanaFIL, tadalaFIL
hydrolysis of cGMP → cGMP→ smooth muscle relaxation by enhancing NO activity → pulmonary vasodilation and ↑blood flow in corpus cavernosum FILs the penis
β-blocker withdrawal syndromeProlonged beta blockade leads to upregulation of beta-adrenergic receptors and increased sensitivity to circulating catecholamines, causing an enhanced beta-adrenergic response on abrupt beta blocker cessation (ie, beta blocker withdrawal syndrome). eg. angina can be triggered in patients with underlying coronary artery disease. pharmacologyUWorld HirotoShishido
medications for motion sicknessAntihistamines
meclizine
the reason why TCA toxicity is treated with bicarbonateto overcome the sodium channel-blocking activity of TCAs, but not for accelerating drug elimination. pharmacologypsychiatryUWorld step2CK HirotoShishido
pharmacokinetic difference between neonatal patients and adults↑Proportion of body water
Blood-brain barrier immaturity
→☆↑Distribution of water-soluble drugs(eg aminoglycosides, vancomycin) may necessitate higher mg/kg dose, ↑CNS toxicity
renal vs hepatic clearance of drugDrugs with high intrinsic hepatic clearance tend to have ☆high lipophilicity and a ☆high volume of distribution.
・Highly lipophilic drugs tend to be poorly eliminated in the kidney as these agents rapidly cross tubular cell membranes after filtration to reenter the tissues.
・High lipophilicity (lipid solubility) allows the drug to cross cellular barriers more easily and enter hepatocytes. It can then be excreted in the bile or through other methods of elimination. pharmacologyUWorld HirotoShishido
phosphatidylinositol 2nd messenger systemThe alpha subunit of the active G protein initially stimulates phospholipase C, which catalyzes the breakdown of membrane-bound inositol phospholipids into 2 second messenger products
– inositol triphosphate (IP3) and diacylglycerol (DAG).
IP3 produces most of its effects by ☆releasing stored calcium from the smooth endoplasmic reticulum.
DAG activates protein kinase C, which phosphorylates downstream regulatory proteins and transcription factors. biochemistrypharmacologyUWorld SIM2 HirotoShishido
drug eluting stent☆Everolimus and its pharmacologic counterparts (eg, sirolimus, zotarolimus) are cytostatic drugs that inhibit mTOR (mammalian target of rapamycin receptor), blocking the cell cycle between the G1 and S phase to reduce smooth muscle cell proliferation.
Coating the intracoronary stent surface with an antiproliferative agent such as everolimus creates a drug-eluting stent that helps ☆prevent neointimal hyperplasia and stent restenosis. cardiologypharmacologyUWorld SIM2 HirotoShishido
different effectiveness of codeincodein is prodrug with basically no effects by itself
it instead must be ☆metabolized (by the liver via CYP2D6) into morphine in order to provide analgesia anesthesiologypharmacologyfree120 HirotoShishido
antiretroviral therapy(ART)
the risk of HIV infection occuring in an infant born to HIV positive mother who received no prenatal ART can be as high as 35%
ART reduces the risk of prenatal transmission to 1-2%
clinical use/ side effects of erythropoiesis-stimulating agents(ESAs)(eg. darbepoetin alpha, erythropoietin)
anemia of chronic kidney disease
thromboembolic events(eg stroke, vascular graft thrombosis) due to increased blood viscosity, ☆ worsening hypertension due to activation of erythropoietin receptors on vascular endothelial and smooth muscle cells hematologypharmacologyUWorld HirotoShishido
immunologic/nervous side effects of corticosteroids☆neutrophilia (demargination of neutrophils previously attached to the vessel wall→ neutrophil recruitment to fight infection in tissues is decreased)
predictable and unpredictable factors of drug adverse effectspredictable→ pharmacologic (eg. ☆NSAIDs etc), secondary(eg. oral thrush with antibiotils)
unpredictable→ immunologic(eg. anaphylaxis, serum sickness, SJS/TEN), nonimmunologic(eg. red man syndrome, hemolysis with sulfa drugs(G6PD deficiency))
unpredictable adverse effects are usually driven by patient-specific genetics. pharmacologyUWorld HirotoShishido
administration/ elimination of monoclonal antibodids(mAbs)must be given via intravenous or subcutaneous/ intramuscular routes ×oral
mAbs are ☆not eliminated by hepatic or renal clearance, but are instead removed from the body in 2 primary ways:
・Target-mediated drug clearance: mAbs directed against cell surface antigens undergo internalization upon binding to their targets, removing them from the circulation
・Nonspecific clearance: Immunoglobulins are constitutively taken up by reticuloendothelial macrophages and vascular endothelial cells. immunologypharmacologyUWorld HirotoShishido
intoxication of benzodiazepines and opioidsbenzodiazepines→ sedation with ☆normal vital signs (☆antidote= flumazenil)
