General Pharmacology

Front 1

Characteristics of Competitive Inhibitors:

Back 1

1.Resemble substrate
2.Overcome by increased [S]
3.Bind to active site
4.Effect on Vmax is unchanged
5.Increased effect on Km
6.Pharmacodynamics: decreased POTENCY

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Characteristics of Noncompetitive Inhibitors:

Back 2

1.Do Not resemble substrate
2.Are Not overcome by increased [S]
3.Do Not bind to active site
4.Effect on Vmax is decreased
5. Effect on Km is Unchanged
6.Pharmacodynamics: decreased EFFICACY

Front 3

What is Km?

Back 3

1. It's the Michaelis constant.
2. Reflects the Affinity of the enzyme for its substrate.
3. It is equal numerically equal to the [S] at which the rxn velocity is equal to 1/2 Vmax.
4.Km DOES NOT vary with the concentration of enzyme.

Front 4

What does a numerically small (low) Km mean?

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This reflects a HIGH AFFINITY of the enzyme for substrate, because a low concentration of substrate is needed to 1/2 saturate the enzyme --that is, reach a velocity that is 1/2 Vmax.

Front 5

What does a numerically large (high) Km mean?

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This reflects a LOW AFFINITY of the enzyme for substrate because a high concentration of substrate is needed to 1/2 saturate the enzyme.

Front 6

Relationship of velocity to enzyme concentration :

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The rate of the rxn is DIRECTLY PROPORTIONAL to the enzyme concentration at ALL SUBSTRATE CONCENTRATIONS.
--E.g: if the enzyme concentration is halved, the INITIAL rate of the rxn, as well as that of VMAX, are reduced to 1/2 that of the original.

Front 7

Competitive Inhibition : Effect on Vmax

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The effect of a competitive inhibitor is REVERSED by INCREASING [S]. At a SUFFICIENTLY HIGH substrate concentration, the rxn velocity reaches Vmax observed in the absence of inhibitor.

Front 8

Competitive Inhibition: Effect on Km

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A competitive inhibitor increases the APPARENT Km for a given substrate. This means that in the presence of a competitive inhibitor, MORE substrate is needed to achieve 1/2 Vmax.

Front 9

Competitive Inhibition: Effect on Lineweaver-Burke plot

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Plots of the inhibited and unhibited rxns INTERSECT on the Y AXIS at 1/Vmax (Vmax is unchanged).
The inhibited and uninhibited rxns show DIFFERENT X-axis INTERCEPTS, indicating that the apparent Km is INCREASED in the presence of the COMPETITIVE INHIBITOR.

Front 10

Noncompetitive Inhibition: Effect on Vmax

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Noncompetitive inhibition CAN'T be overcome by INCREASING the concentration of substrate. Thus, noncompetitive inhibitors DECREASE the Vmax of the rxn.

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Noncompetitive Inhibition: Effect on Km

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Noncompetitive inhibitors DON'T interefer with the binding of substrate to enzyme. Thus, the enzyme shows the SAME Km in the presence or absence of the noncompetitive inhibitor.

Front 12

Noncompetitive Inhibition: Effect on Lineweaver-Burke plot

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Noncompetitive inhibition is readily differentiated from competitive inhibition by plotting 1/vo vs. 1/[S] and noting that Vmax DECREASES in the presence of a noncompetitive inhibitor, whereas Km is UNCHANGED.

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Pharmacokinetics
Volume of distribution (Vd):

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Vd = amount of drug in the body/ plasma drug concentration

Relates to the amount of drug in the body to the plasma concentration.

Vd of plasma protein-bound drugs can be ALTERED by LIVER AND KIDNEY DISEASE.

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Pharmacokinetics
Volume of distribution (Vd):

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Drugs with:
Low Vd (4-8 L) distribute in the BLOOD

Med Vd distribute in extracellular space or body water.
High Vd (> body wt.) distribute in tissues.

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Pharmacokinetics
Clearance (CL):

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Relates the rate of elimination to the plasma concentration.

CL = rate of elimination of drug/ plasma drug concentration = Vd X Ke (elimination constant)

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Pharmacokinetics
Half-life (t 1/2)

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The time required to change the amount of drug in the body by 1/2 during elimination (or during a constant infusion).
A drug infused at a constant rate reaches about 94% of steady state after 4 half-lives. PROPERTY OF FIRST-ORDER ELIMINATION.

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Drug Calculations

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Loading dose = Cp x Vd/F

Maintenance dose = Cp x CL/F where Cp = target plasma concentration and F= bioavailabilty = 1 when drug is given IV.

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Drug Calculations for Patients with impaired renal or hepatic function:

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Loading dose remains UNCHANGED, although the maintenance dose is DECREASED.

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Elimination of Drugs:
What is Zero-order elimination?

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CONSTANT AMOUNT of drug eliminated per unit time.
Example of drugs: Phenytoin, Ethanol, & Asprin (at high or toxic concentrations)

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Elimination of Drugs:
What is First-order elimination?

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Rate of elimination is PROPORTIONAL to the drug concentration. (Constant FRACTION of drug eliminated per unit time)

Front 21

How do you treat a weak acid overdose?

Examples of weak acids: Phenobarbital, methotrexate, TCA, Aspirin.

Back 21

Treat overdose with bicarbonate.

Front 22

How do you treat a weak base overdose?

Example of weak base: amphetamines

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Treat overdose with ammonium chloride.