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23 Cards in this Set

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Most common Drug Reaction
Predictable extension of pharmacology (70-80%) >> hypersensitivity (6-10%) > Idiosyncratic (~5%)
Deaths per year due to adverse drug reactions?
>100,000
Thyroxine (hypothyroid medication)'s absorption is inhibited by __________?
FeSO4 (iron supplement) as well as other metals such as antiacids (due to the Mg+ component)

Pituitary will sense low thyroid function and will increase TSH in the blood
Phenytoin (antiepileptic) and the effects of kidney failure
Phenytoin is normally bound to serum protein. As the serum creatinine levels rise, less phenytoin is bound to the plasma proteins so more is bioavailable. "Normal" dose becomes an overdose.
Digitalis (cardiac contractility) and effect of renal failure or disease
Digitalis increases heart contractility by inhibiting the Na/K ATP-ase. It is metabolized by the kidney. Kidney failure causes a rise in levels in the body and therefore heart failure.
P-glycoprotein
Membrane pump. Tumor cells may over-express this protein as a mechanism of chemo resistance.
Imipramine (TCA) interacts with what anti-hypertensive? How?
Guanethedine.
TCAs blocks reuptake receptors on pre-synaptic neurons. Guanethedine cannot get into the cell.
Propanolol and asthma
Propanolol is a Beta 1 and 2 blocker. Will inhibit a beta 2 agonist like albuterol (dangerous for asthmatics)
Lidocaine dangers with heart disease
Lidocaine is metabolized by the liver. clearance is realted to cardiac output. If the heart is pumping insufficiently, the lidocaine will accumulate and cause seizures.
Leukemia interaction:
Allopurinol inhibition of metabolism pathway (in a chemo agent)
6-MP metabolism is inhibited by allopurinol (prevent uric acid formation and gout from death of WBC in leukemia treatment). If both are given, 6-MP will become toxic. Decrease the dose for safety.
Statins compete for metabolism with what drug?
Conazole (anti-fungal) and Statins (hypercholesterolemia) are both metabolized by CYP3A4. Statins accumulate, cause muscle lysis and renal failure.
Grapefruit juice inhibits what?
CYP3A4
Number one cause of acute liver failure in US?
Acetaminophen OD. In itself, not toxic. Metabolism makes it toxic.
Tylenol --> p-450 --> toxic --> glutathione --> non-toxic end product.

note implication of delpleted gluathione levels....
Treatment of Acetaminophen OD?
Acteylcysteine (Mucomist, a sulf-compound). Acts as a replacement for glutathione.

Tylenol --> p-450 --> toxic --> glutathione --> non-toxic end product.
Thalidomide
(sedative and multiple myloma patients)
Leads to limb defects in babies if given to a mother during her first trimester.
Diethylstilbesterol
Treatment for risk of miscarriages. Daughters born after this have increased risk for GU abnormalities and vaginal clear cell carcinoma
Doxorubicin
Anthracycline.... higher risk to women or men?
Women. Risk of cardiotoxicity through decreased contractility.
Tamoxifen
Must be converted to active form. 10% of Euro population lacks this enzyme.
Succinylcholine
short-actin muscle relaxant. Genetic polymorphisms lead to higher sensitivity due to inability to metabolize
Seldane (antibiotic for acne) metabolism issue?
Erythromycin outcompetes Terfenadine for metabolism by CYP34A. K+ channels are blocked, leading to prolonged QT intervals.
What drug metabolism would you be concerned about in genetic variation of:
CYP2C9
warfarin, phenytoin
(warfarin blocks vitamin K metabolism and therefore blocks clotting --> hemorrhagic death)
What drug metabolism would you be concerned about in genetic variation of:
CYP2C19
Omeprazole, Diazepam
What drug metabolism would you be concerned about in genetic variation of:
CYP2D6
Codeine, metroprolol

• 10% of native Africans are ultra-rapid metabolizers of CYP2D6 drugs because of gene duplications. More genes → more enzymes → faster drug breakdown.