Pharmacokinetics/Dynamics EXAM REVIEW

Question 1

What is the definition of oxidation?

Answer 1

Loss of electrons; phase I reaction

Question 2

What is reduction?

Answer 2

Gain of electrons: Phase I reaction

Question 3

What is Hoffman degradation?

Answer 3

Example of non-organ metabolism

Site of metabolism is PLASMA

Question 4

What is Hydrolysis ?

Answer 4

Splitting molecule with the addition of water/ PHASE I

Question 5

What is the relationship between ph and pKa.

Answer 5

When pH=pKa, 50% of the drug is ionized and 50% in non- ionized.
Lower pKa stronger acid, Higher pKa stronger base.

Question 6

How does ph and pKa relationship affect weak bases and weak acids?

Answer 6

• A general rule with weak bases states when the pKa minus pH < 0, then most of the drug will be in the non-ionized form.
• With weak acids the opposite is true. pKa minus pH < 0 then most of the drug will be in the ionized form.

Question 7

What percentage of cardiac output is distributed to each tissue compartment?

Answer 7

HIGHLY PERFUSED (lungs, heart, brain, kidneys, liver) ~ 75%

Question 8

4. Explain when protein binding becomes a concern to the clinician?
5. Protein binding and Vd
6. Protein binding and metabolism
7. Protein binding and lipid solubility
8. when is alteration important

Answer 8

1. Protein binding effects Vd because only
   unbound drug can cross cell membranes.
   Therefore the Vd is inversely related to
   protein binding.
2. Only unbound drug can undergo
   metabolism and glomerular filtration
3. Extent of protein binding directly related to
   the lipid solubility
4. Alterations in protein binding are only
   important for drugs that are highly
   protein bound.

Question 9

5. What are methods of metabolism? What are considered to be phase 1? What are considered to be phase 2

Answer 9

Phase 1 (ORH)
Oxidation, reduction and hydrolysis are
Phase II reaction –> CONJUGATION

Question 10

6.Which routes of drug administration undergo hepatic first pass effect? Which do not?

Answer 10

1.Drugs that undergo large first pass hepatic
effect (lidocaine, propranolol) PO and IV doses very different
2. AVOID first pass effect
Include sublingual, buccal and nasal route, IV
3. Drugs administered into to LOWER RECTUM avoid the first pass effect

Question 11

7. What drug characteristics will affect Vd?

Answer 11

Lipid solubility, protein binding, molecular
size.
• Drug with LOW LIPID SOLUBILITY and HIGH PROTEIN BINDING will have a LOW Vd

Question 12

Vd is _______to protein binding

Answer 12

Inversely proportional

Question 13

8. Define zero order kinetics?
   Definition
   When does it occur?
   Result of

Answer 13

A constant amount of drug in cleared per unit of time regardless of plasma concentration
Occurs when the plasma concentration of
drug exceeds the capacity of metabolizing
enzymes.
• Result of saturating the available enzymes
at high drug concentrations of some
compounds.

Question 14

What drugs undergo zero order kinetics?

Answer 14

Alcohol, Aspirin, and Phenytoin

Question 15

9. Define first order kinetics? What drugs undergo first order kinetics?

Answer 15

Most drugs will follow linear of first-order
kinetics.
• Constant fraction of drug is metabolized
per unit of time.

Question 16

In first order kinetics the metabolism of a drug is highest when?

Answer 16

when the drug concentration is greatest.

Question 17

In first order kinetic; The fraction of drug eliminated is_________

Answer 17

independent of the drug concentration

Question 18

For first order kinetic, It will take 1 half-life for the plasma________
At 5 half-lives the drug plasma
concentration declines by_______

Answer 18

concentration to decline by 50%.

96.9 %

Question 19

10. What are the mechanism for renal excretion of drugs? (3)

Answer 19

Glomerular filtration.
Passive tubular secretion.
Passive tubular reabsorption.

Question 20

11. What organ is responsible for drug metabolism

Answer 20

Liver

plasma for hoffman degradation

Question 21

12. Why do the elderly respond to drugs differently than younger patients? (DED-DI)
    They all lead to ________and _________

Answer 21

Decreased cardiac output
Enlarged fat content
Decreased protein binding
Decreased renal function

all lead to drug accumulation and increased risk of toxicity

Question 22

13. What is the principal effect of metabolism?

Answer 22

The role of metabolism is to convert
pharmacologically active, lipid-soluble drugs
into water soluble inactive compounds that
can be easily excreted.

Question 23

14a Define Enantiomer?

Answer 23

A pair of molecules existing in two forms
that are mirror images of one another but
cannot be superimposed. All contain a chiral carbon

Question 24

Define stereoisomer

Answer 24

are a particular kind of isomer that are different from each other only in the way the atoms are oriented in space (but are like one another with respect to which atoms are joined to which other atoms)

Question 25

Define Chiral Carbon

Answer 25

Chiral is a term used to describe a molecule | that has a center (or centers) of threedimensional asymmetry

Question 26

Enzyme inducers drugs RPPCAC

Answer 26

``` Rifampin Phenobarbital Phenytoin, cigarette smoking Alcohol Chronic carbamazepine. ```

Question 27

Enzyme Inhibitors drugs are | ProDiVE - CANVA

Answer 27

``` Protease inhibitors DI- ltiazem Verapamil Erythromycin Cimetidine Acute alcohol ingestion Nefazodone Valproic acid Amiodarone ```

Question 28

16. What affect will ionization, molecular size, lipid solubility, protein binding have on Vd?

Answer 28

the NON-IONIZED portion of the drug is more lipid soluble and therefore crosses the cell membrane better (higher Vd) HIGHER IONIZED --> Lower Vd Molecular size: higher molecular weight, low Vd Lower molecular size: HIGH Vd Therefore the Vd is INVERSELY related to protein binding. Low lipid solubility + high protein binding-->low Vd(locked in vessels) High lipid solubility + low protein binding --> High Vd (distributes easily)

Question 29

17. Define pharmacokinetic.

Answer 29

The quantitative study of absorption, distribution, metabolism, and excretion of drugs and their metabolites The movement of a drug through the body over time. “What the body does to a drug

Question 30

Define pharmacodynamics.

Answer 30

The study of the intrinsic sensitivity of responsiveness of receptors to a drug and the mechanism by which these effects occur. "What the drug does to the body”

Question 31

18. Weak BASE given pKa and ph when will non-ionized or ionized from (general rule)

Answer 31

A general rule with WEAK BASES states when the pKa - pH < 0, then most of the drug will be in the NON-IONIZED form.

Question 32

Weak ACID given pKa and ph when will non-ionized or ionized from (general rule)

Answer 32

With weak acids the opposite is true. pKa minus pH < 0 then most of the drug will be in the ionized form

Question 33

19. Understand the principles behind calculating a creatinine clearance.

Answer 33

•{140 - age ) x IBW /72 x Serum creatinine} x (0.85 for females.) Formula used to calculate estimated creatinine clearance. • IBW male 50 +(2.3 x each inch >60) IBW in Kg • IBW female 45.5 + (2.3 x each inch >60) = IBW in Kg

Question 34

Define drug clearance.

Answer 34

The volume of plasma cleared of drug by renal excretion and/or metabolism by the liver or other organs

Question 35

Anaphylaxis

Answer 35

antigen-antibody interaction, | immune mediated and REQUIRES PRIOR EXPOSURE

Question 36

Anaphylactoid

Answer 36

no previous exposure or sensitization, not a true allergic reaction but results in histamine release, vasodilation, wheals, and welts