Therapeutics And Drug-Drug Interaction

Front 1

Most common Drug Reaction

Back 1

Predictable extension of pharmacology (70-80%) >> hypersensitivity (6-10%) > Idiosyncratic (~5%)

Front 2

Deaths per year due to adverse drug reactions?

Back 2

>100,000

Front 3

Thyroxine (hypothyroid medication)'s absorption is inhibited by __________?

Back 3

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

Front 4

Phenytoin (antiepileptic) and the effects of kidney failure

Back 4

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.

Front 5

Digitalis (cardiac contractility) and effect of renal failure or disease

Back 5

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.

Front 6

P-glycoprotein

Back 6

Membrane pump. Tumor cells may over-express this protein as a mechanism of chemo resistance.

Front 7

Imipramine (TCA) interacts with what anti-hypertensive? How?

Back 7

Guanethedine.
TCAs blocks reuptake receptors on pre-synaptic neurons. Guanethedine cannot get into the cell.

Front 8

Propanolol and asthma

Back 8

Propanolol is a Beta 1 and 2 blocker. Will inhibit a beta 2 agonist like albuterol (dangerous for asthmatics)

Front 9

Lidocaine dangers with heart disease

Back 9

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.

Front 10

Leukemia interaction:
Allopurinol inhibition of metabolism pathway (in a chemo agent)

Back 10

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.

Front 11

Statins compete for metabolism with what drug?

Back 11

Conazole (anti-fungal) and Statins (hypercholesterolemia) are both metabolized by CYP3A4. Statins accumulate, cause muscle lysis and renal failure.

Front 12

Grapefruit juice inhibits what?

Back 12

CYP3A4

Front 13

Number one cause of acute liver failure in US?

Back 13

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....

Front 14

Treatment of Acetaminophen OD?

Back 14

Acteylcysteine (Mucomist, a sulf-compound). Acts as a replacement for glutathione.

Tylenol --> p-450 --> toxic --> glutathione --> non-toxic end product.

Front 15

Thalidomide
(sedative and multiple myloma patients)

Back 15

Leads to limb defects in babies if given to a mother during her first trimester.

Front 16

Diethylstilbesterol

Back 16

Treatment for risk of miscarriages. Daughters born after this have increased risk for GU abnormalities and vaginal clear cell carcinoma

Front 17

Doxorubicin
Anthracycline.... higher risk to women or men?

Back 17

Women. Risk of cardiotoxicity through decreased contractility.

Front 18

Tamoxifen

Back 18

Must be converted to active form. 10% of Euro population lacks this enzyme.

Front 19

Succinylcholine

Back 19

short-actin muscle relaxant. Genetic polymorphisms lead to higher sensitivity due to inability to metabolize

Front 20

Seldane (antibiotic for acne) metabolism issue?

Back 20

Erythromycin outcompetes Terfenadine for metabolism by CYP34A. K+ channels are blocked, leading to prolonged QT intervals.

Front 21

What drug metabolism would you be concerned about in genetic variation of:
CYP2C9

Back 21

warfarin, phenytoin
(warfarin blocks vitamin K metabolism and therefore blocks clotting --> hemorrhagic death)

Front 22

What drug metabolism would you be concerned about in genetic variation of:
CYP2C19

Back 22

Omeprazole, Diazepam

Front 23

What drug metabolism would you be concerned about in genetic variation of:
CYP2D6

Back 23

Codeine, metroprolol

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