Pharmacokinetics

Question 1

What is the equation for volume of distribution?

Answer 1

Vd = amount of drug/desired plasma concentration

Question 2

What is the total distribution of body water in a 70 kg patient?

Answer 2

42L

Question 3

How many liters of fluid are located in the intracellular region?

Answer 3

28

Question 4

How many liters of fluid are located in the extracellular fluid?

Answer 4

14L

Question 5

Of the extracellular fluid, how many liters are located in the interstitial fluid?

Answer 5

10L

Question 6

Of the extracellular fluid, how many are located in the plasma volume?

Answer 6

4L

Question 7

A drug with a Vd that > TBW (> 0.6 L/kg or > 42L) is assumed to be what?

Answer 7

Lipophilic

Question 8

A drug with a Vd < TBW (<0.6 L/kg or < 42L) is assumed to be what?

Answer 8

Hydrophilic

Question 9

What are some key traits about a drug that is lipophilic with a high Vd (>42L)?

Answer 9

It distributes into the total body water as well as into the fat

Question 10

What is the equation for the loading dose of a drug?

Answer 10

Loading dose = Vd x desired plasma concentration/ 1

(this is assuming it is an IV drug with 100% bioavailability)

Question 11

What are the most important clearing organs?

Answer 11

Liver
Kidney
Organ independent (Hoffman)

Question 12

What is clearance directly proportional to?

Answer 12

Blood flow to cleaning organ
Extraction ratio
Drug dose

Question 13

What is clearance inversely proportional to?

Answer 13

Half-life
Drug concentration in the central compartment

Question 14

What does a steady state mean?

Answer 14

The amount of drug entering body = amount of drug eliminated from body

Question 15

As a general rule, when is steady state achieved?

Answer 15

5 half-lives

Question 16

When looking at the plasma concentration curve, what does the alpha phase represent?

Answer 16

Distribution

Question 17

What looking at the plasma concentration curve, what does the beta phase represent?

Answer 17

Elimination

Question 18

What is the concept of context sensitive half-time?

Answer 18

It’s the time required for the plasma concentration to decline by 50% after the infusion is stopped

Question 19

What is the Ionization of a drug is dependent on what two factors?

Answer 19

The pH of the solution
The pKa of the drug

Question 20

What exactly is pKa?

Answer 20

It’s a constant property of a molecule

A drug’s pKa equals the pH where 50% of the drug is ionized and the other 50% is non-ionized.

Question 21

What is the Henderson-Hasselbach equation?

Answer 21

pH= pKa + log (base) / conjugate acid

Question 22

What are some properties of an ionized molecule? Traits

Answer 22

Solubility: water (hydrophilic)
Pharmacological effect: not active
Hepatic Biotransformation: less likely
Renal Elimination: More likely
Diffuses across lipid bilayer: BBB, GI tract, or placenta —> no

Question 23

What are some properties of a non-ionized molecule?

Answer 23

Solubility: lipophilic
Pharmacologic effect: yes, active
Hepatic bio transformation: more likely
Renal elimination: no
Diffuse across a lipid bilayer: BBB, GI tract, Placenta —> yes

Question 24

Which local anesthetic is most likely to undergo fetal ion trapping? Which is the least likely?

Answer 24

Most likely: Lidocaine
Least likely: chloroprocaine (d/t it’s high pKa and rapid metabolism)

Question 25

What are some key facts about albumin in terms of plasma protein binding?

Answer 25

Most plentiful plasma protein Determines oncotic pressure 1/2 life: 3 weeks Negative charge Primarily binds to ACIDIC drugs

Question 26

In what conditions is albumin decreased?

Answer 26

Liver disease Malnutrition Renal dx Old age PREGNANCY

Question 27

What are some key facts about a1- Acid Glycoprotein?

Answer 27

Binds with basic drugs

Question 28

When is a1 acid Glycoprotein increased? What decreases it?

Answer 28

Increased: surgical stress MI chronic pain RA Advanced age When is it decreased: pregnancy neonates

Question 29

What is the equation to determine changes in plasma protein binding?

Answer 29

Percent change= New value - Old Value / old value x 100%

Question 30

What is zero order kinetics? What are some examples?

Answer 30

A constant AMOUNT of the drug is metabolized per unit time Ex: asa, phenytoin, alcohol, warfarin, heparin, theophylline

Question 31

What is first order kinetics?

Answer 31

A constant FRACTION of the drug is metabolized per unit time Most of our drugs are this.

Question 32

What is the key organ for metabolism? What is another important site?

Answer 32

Key: Liver Plasma

Question 33

What is the primary role of metabolism?

Answer 33

Change a lipid-soluble, active compound to a water soluble, inactive compound

Question 34

What is it called when the body converts an inactive molecule into a pharmacologically active molecule?

Answer 34

Prodrug!

Question 35

What are the 3 phases of metabolism?

Answer 35

Phase 1: Modification Phase 2: Conjugation Phase 3: Elimination

Question 36

What are the three types of phase 1 reactions?

Answer 36

Oxidation —> removes electrons Reduction —> adds elections Hydrolysis —> adds water to split

Question 37

What does it mean to be perfusion dependent?m in terms of hepatic elimination?

Answer 37

This is for drugs with a high hepatic extraction ratio (> 0.7) ~ clearance depends on liver blood flow. ^ liver blood flow = ^ clearance Decrease in blood flow = decrease in clearance

Question 38

What does it mean to be capacity dependent on terms of hepatic elimination?

Answer 38

Drugs that have a low hepatic extraction ratio (< 0.3). Clearance is dependent on the ability of the liver to extract the drug from blood. Changes in hepatic enzymes and/or protein binding affect clearance ^ enzyme induction = ^ clearance Enzyme inhibition = decrease clearance

Question 39

What are examples of high hepatic extraction rations and/or perfusion-dependent drugs?

Answer 39

Most anesthetics/opioids Propofol Fent Ketamine Morphine Lidocaine BBS CCBs

Question 40

What are examples of low hepatic extraction ratio? An/or drugs that are capacity-dependent?

Answer 40

Roc Diazepam Lorazepam Methadone Thiopental Theophylline Phenytoin

Question 41

What are two specific enzymes of the P450 system that pertain to anesthesia? They are important

Answer 41

CYP 3A4 (most of our anesthetics) CYP 2D6 (some opioids) morphine, oxycodone, hydrocodone

Question 42

Name some examples of enzyme inducers? What do these do?

Answer 42

Increase clearance —> decrease drug level —> may need increased dose Tobacco Barbiturates Ethanol Phenytoin Rifampin Carbamazepine St. John’s Wort

Question 43

What are examples of an enzyme inhibitor? What does it do?

Answer 43

Inhibits enzyme activity —> decreases clearance —> increased plasma levels—> smaller dose may be required Grapefruit juice Cimetidine Omeprazole Isonaizid SSRIs Erythromycin Ketoconazole Cipro

Question 44

Acidic urine favors what? Think elimination

Answer 44

Reabsorption of acidic drugs Excretion of basic drugs AAA (Acids are better Absorbed in an Acid medium)

Question 45

Basic urine favors what? Think elimination

Answer 45

Reabsorption of basic drugs Excretion of acidic drugs BBB: Basic drugs are Better absorbed in a Basic medium)

Question 46

What drugs are metabolized by pseudocholinesterases?

Answer 46

Sux Mivacurium Ester local anesthetics (cocaine, tetracaine)

Question 47

What drugs are eliminates by non-specific esterases?

Answer 47

Esmolol Remi Atracurium (+ Hoffman) Etomidate Clevidipine

Question 48

What describes the relationship b/t effect-site concentration and the clinic effect?

Answer 48

Pharmacodynamics “What the drug does to the body”

Question 49

What describes the relationship b/t the drug dose and plasma concentration?

Answer 49

Pharmacokinetics “What the body does to the drug” (Think absorption, distribution, metabolism, elimination)

Question 50

What is one the x axis when looking at the dose-response curve?

Answer 50

Potency

Question 51

What is on the y axis is on dose-response curve?

Answer 51

Efficacy

Question 52

What is the ED50? What is the ED90?

Answer 52

ED 50 —> dose required to achieve a given affect in 50% of the population ED 90 —> dose required to achieve a given affect in 90% of the population

Question 53

When considering the dose-response curve, what does a left-shift mean?

Answer 53

Increased potency —> lower dose required

Question 54

When considering the dose-response curve, what does a right shift mean?

Answer 54

Lower potency —> higher dose is required.

Question 55

What is efficacy?

Answer 55

Measure of the intrinsic ability of a drug to elicit a given clinical effect

Question 56

What does the slope on the dose response curve indicate?!

Answer 56

Slope tells you how many receptors must be occupied to elicit a clinical effect. Steep slope: most receptors must be fully occupied

Question 57

What is an example of addition?

Answer 57

Effect of two drugs given at the same time are added to each other (1+1=2) Morphine + hydromorphone

Question 58

What is an example of synergism?

Answer 58

The effect of two drugs given at the same time is greater than their individual effects. (1+1=3) Propofol and midazolam

Question 59

What is potentiation?

Answer 59

Effect of one drug is enhanced by a drug that has no effect of its own 1+0=3 PCN and probenecid

Question 60

What is antagonism?

Answer 60

Simultaneous administration of one drug negates the effect of a second drug 1+1=0 Fent and naloxone

Question 61

How do you calculate therapeutic index?

Answer 61

Therapeutic index= LD50 / ED50

Question 62

What is the TD50?

Answer 62

The dose that will produce toxicity in 50% of the population

Question 63

What is the LD50?

Answer 63

The dose that produces death in 50% of the population.

Question 64

What is a racemic mixture?

Answer 64

It’s a mixture that contains two enantiomers in equal amounts.

Question 65

What are some examples of enantiomers?

Answer 65

Ketamine Thiopental Isoflurane Desflurane Mepivacaine

Question 66

What are two exceptions that are prepared as single enantiomers instead of as racemic mixture?

Answer 66

Ropivacaine Levobupivacaine

Question 67

What are ways you can acidify the urine? What are ways you can alkaline the urine?

Answer 67

Acidify: ammonium chloride or cranberry Alkalize: acetazolamide