Lecture 2 pharmacodynamics

Question 1

When calculating the Creatinine Clearance (CrCl), one should only use the actual body weight instead of the ideal body weight (IBW) of the patient if

Answer 1

the actual body weight is LESS than the IBW.

Question 2

T/F: For patients over age 65, the CrCl should be rounded up to 1.0 even if it is below 1.0.

Answer 2

True, but it should not be rounded any further. 1.9 should not be rounded to 2. It is assumed that by age 65, that people have a diminished CrCl.

Question 3

Dialysis will remove drugs with the following 3 characteristics.

Answer 3

• Hydrophillic (polar, ionized/charged)
• Low protein binding (if bound to albumin, it’s not leaving)
• Small molecular weight

(basically what the kidneys would favor as easy to excrete)

Question 4

Dosing regimens:

List the benefits of continuous IV infusions.

Answer 4

-Continuous will eliminate swings in level
-short half life meds make titration easier (target BP or HR)
Easier to achieve goal of remaining at target concentration

Question 5

Dosing regimens:

T/F: A loading dose with intermittent dosing with reach steady state quicker than intermittent dosing alone.

Answer 5

False.

Loading dose will place patient at therapeutic level, but will not reach steady state quicker.

Question 6

Steady state is reached after how many doses?

After how man half lives?

Answer 6

5 doses or 5 half lives.
steady states means you have reached the point where the amount in=amount out. (metabolism and dosing are at steady state.)

Question 7

T/F: Dosing interval= half-life.

Answer 7

True

Question 8

At the 5th half-life what % of medication is excreted or left?

Answer 8

96.87%

1st half life: 50%
2nd=75%
3rd=87.5%
4th=93.75%
5th=96.875%

Question 9

Does a loading dose shorten the time to steady state?

Answer 9

NO!

Therapeutic concentration is achieved, but not steady state.

Question 10

Would you reach steady state faster if the dose was given at 1 half of the medications half-life? (redosing sooner?)

Answer 10

NO!

Will cause a toxic drug level.

Question 11

Peaks and Troughs:

When measuring a peak you are measuring for:

Answer 11

Toxicity.

Question 12

Peaks and Troughs:

When measuring a trough you are checking:

Answer 12

Efficacy.

Question 13

Serum Drug Concentrations:

When should a peak be drawn?

Answer 13

1 hour post administration of a dose. (mostly for IV meds)

Question 14

Serum Drug Concentrations:

When should a trough be drawn?

Answer 14

1 hour before administration of a dose. (mostly for IV meds)

Question 15

Pharmacodynamics is

Answer 15

(sometimes described as what a drug does to the body) is the study of the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding (including receptor sensitivity), postreceptor effects, and chemical interactions.

Question 16

Receptor binding:

Affinity=

Answer 16

Strength of binding between a drug and its receptor. Some drugs or substances have a greater affinity to a receptor than others.

Question 17

Dissociation Constant (Kp) is the measurement of a drugs affinity for a given receptor. The concentration of drug required in solution to achieve _____% occupancy of it’s receptors.

Answer 17

50%

Question 18

Agonist:

Answer 18

Mimics the effects of the endogenous compound that normally binds to the site. Drugs that are agonists are given to increase the normal agonist stimulation of the receptor and block the endogenous agonist. (takes the parking spot and performs a duty)

Question 19

Strong Agonist:

Answer 19

an agonist which causes maximal effects even though it may only occupy a small fraction of the receptors.

Question 20

Weak Agonist:

Answer 20

an agonist which must be bound to many more receptors than a strong agonist to produce the same effect.

Question 21

Antagonist:

Answer 21

Inhibits or blocks the actions caused by endogenous agonists. The antagonist has little or NO intrinsic activity or effects. (Blocks/takes the parking spot, but does not get out of the car to do anything)

Question 22

Competitive antagonist:

Answer 22

• Competes with agonist for the receptors. (Affinity becomes more relevant with competition).
• When the antagonist is bound to the receptor site, the agonist cannot bind.
• the agonist can “win” the competition against the antagonist by increasing the number of agonists (more players). The competitive antagonism can be overcome and is said to be “surmountable,” the main difference between competitive and noncompetitive antagonism.

Question 23

Noncompetitive antagonist:

Answer 23

• binds to a site other than the agonist-binding domain. Induces a conformational change in the receptor such that the agonist no longer “recognizes” the agonist-binding domain.
• considered “insurmontable” because even high doses of agonist cannot over come the antagonism.

Question 24

Irreversible antagonism:

Answer 24

-agents compete with agonists for the agonist-binding site. The antagonist binds irreversibly with the receptor permanently.
-rate of antagonism can be slowed by high concentrations of antagonist.
-once an irreversible antagonist binds to a receptor, it cannot be “reclaimed” by the agonist.
(like putting the wrong key in a lock and breaking the lock so the door is permanently shut.)

(Ex. Chemical weapons)

Question 25

Efficacy:

Answer 25

The degree to which a drug is able to cause maximal effects.

If A reduces BP by 20mmHg and B reduces BP by 10mmHg, then A has a greater efficacy than B.

Efficacy is used to compare drugs of the same chemical class.

Question 26

Potency:

Answer 26

the amount of drug required to produce 50% of the maximal response that the drug is capable of causing.

ex. A smaller dose of morphine is needed to achieve the same effect as codeine. Morphine is more potent than codeine.

Potency is used most often to compare drugs with different mechanisms. Toradol vs morphine.

Question 27

Drug interactions:

Addition/Additive:

Answer 27

The response elicited by the combined drugs is EQUAL TO the combined responses of the individual drugs.

1+1=2

Question 28

Synergism:

Answer 28

The response elicited by the combined drugs is GREATER THAN the combined responses of the individual drugs.

1+1=3

Question 29

Potentiation:

Answer 29

A drug which has no effect enhances the effect of the second drug

0+1=2

ex. Antibiotics

Question 30

Antagonism:

Answer 30

Drug inhibits the effect of another drug. Usually the antagonist has no inherent activity.

1+1=0

Question 31

Midazolam is a significant substrate of CYP3A4. Erythromycin is a CYP3A4 inhibitor. What would you anticipate from this drug interaction?

Answer 31

CYP3A4 breaks down midazolam. An inhibitor will slow/inhibit the metabolic activity of the enzyme. Midazolam will be broken-down/metabolized much slower. The effects of the midazolam may be extended, the patient may have a longer recovery period.

Question 32

Carbamazepine is a very strong inducer of CYP3A4. What would you anticipate happening if patient is given midazolam?

Answer 32

Midazolam will wear off quicker, may need to redose.

Inducer = increased metabolism.

Question 33

Tolerance

Answer 33

• represents a decreased response to a drug. The dose must be increased to achieve the same effect.
• Independent of increased injury or change in painful stimulus.

Question 34

Dependence

Answer 34

• occurs when a patient needs a drug to function normally.
• cessation of the drug will produce withdrawal symptoms.
• dependence may be both physical and/or psychological.
• not the same as addition

Question 35

Withdrawal

Answer 35

• when a drug is withheld or not received by the dependent individual.
• can happen when a patient is not tapered off a medication.
• withdrawal symptoms are often the opposite of the effects achieved by the drug.