Pharm Basics - First Aid

Question 1

What is a Michaelis-Menten plot?

What is Km?

What is Km related to? How?

Answer 1

Graph of V (enzyme activity) vs. [S] (substrate available)

Km = [S] where V = 1/2 of Vmax

Km = inversely proportional to affinity of enzyme for substrate

Question 2

Competitive inhibitor…

• Change in Vmax?
• Change in Km?

Changed potency or efficacy?

Answer 2

Vmax = SAME

Km = HIGHER

Lower potency

Question 3

Noncompetitive inhibitor…

• Change in Vmax?
• Change in Km?

Changed potency or efficacy?

Answer 3

Vmax = LOWER

Km = SAME

Lower efficacy

Question 4

Axes of Lineweaver-Burk plot

Slope of line?

Y intercept?

X intercept?

Answer 4

1/V vs. 1/[S]

Slope of line = Km/Vmax

Y intercept = 1/Vmax

X intercept = 1/(-Km) – that’s NEGATIVE Km

Question 5

Competitive inhibitor…

- Changes on Lineweaver-Burk plot...
     - Slope?
     - X-intercept?
     - Y-intercept?

Answer 5

Line shifts RIGHT, and becomes MORE STEEP (higher Km)

Km increases, so 1/-Km (X-intercept) shifts RIGHT (becomes more positive)

Vmax stays the same, so Y-intercept stays the SAME

Question 6

Noncompetitive inhibitor…

• Changes on Lineweaver-Burk plot…
  - Slope?
  - X-intercept?
  - Y-intercept?

Answer 6

Line becomes MORE STEEP (lower Vmax)

Km stays the same, so X-intercept stays the same

Vmax goes down, so Y intercept goes UP (1/Vmax)

Question 7

What is volume of distribution?

Answer 7

Amount of drug in body / plasma drug concentration

Question 8

What is clearance?

Answer 8

Rate of elimination / plasma drug concentration

Volume of distribution x elimination constant (Ke)

Question 9

1/2 life equation (1st order kinetics)

Answer 9

(0.693 x Vd) / Clearance

Question 10

How long does it take to reach steady state for a drug, assuming it is infused continuously?

Answer 10

4-5 half lives

Question 11

Loading dose equation

Answer 11

LD = Cp x Vd / F (bioavailability)

Question 12

Maintenance dose equation

Answer 12

MD = (Cp x Cl x dosing interval) / F (bioavailability)

Question 13

Liver or renal disease…which dose changes (loading or maintenance)?

Answer 13

Maintenance dose decreases

Question 14

What is zero-order elimination?

How is this possible?

Answer 14

Constant elimination rate regardless of plasma concentration

Based on enzyme capacity, not blood flow

Question 15

What is first-order elimination?

Answer 15

Elimination rate from the plasma decreases by 1/2 every 1/2 life (directly proportional to plasma concentration)

Question 16

Drugs with zero-order elimination?

Answer 16

PEA (a pea is round like a zero)

• Phenytoin
• Ethanol
• Aspirin

Question 17

Drugs that are weak acids

How do you treat ODs? Why?

Answer 17

Phenobarbital, methotrexate, aspirin

Give bicarb –> proton is sucked off by high pH –> drug is charged and trapped in urine

Question 18

Drugs that are weak bases

How do you treat ODs?

Answer 18

Amphetamines, TCAs

Give ammonium chloride –> proton is put on by low pH –> drug is charged and trapped in urine

Question 19

Phase 1 vs. Phase 2 drug metabolism

Answer 19

Phase 1 = Reduction, Oxidation, Hydrolysis
–> slightly polar, maybe still active

Phase 2 = Conjucation (Methylation, Glucuronidation, Acetylation, Sulfation)
–> very polar, INACTIVE –> renal excretion

Question 20

EC50 of a drug

A higher EC50 means what?

Answer 20

Effective concentration at 50% of maximal effect
I.E. the amount of drug (Log of drug dose) that produces 50% of the maximal effect

The drug is less potent

Question 21

Therapeutic index

What do the variables mean?

Answer 21

Median toxic dose (TD50) / Median effective dose (ED50)

TD50 = drug concentration where 50% of patients have toxic effects

ED50 = drug concentration where 50% of patients have therapeutic effects