Olson, Pharm 1

Front 1

Define Pharmacokinetics.

Back 1

The quantitative study of absorption, distribution, metabolism, and excretion of drugs.
It is what the body does to a drug.

Front 2

Describe the concept of compartement models.

Back 2

Concept that describes redistribution of a drug from the central compartment to the peripheral compartment.

Front 3

True or False:
The Peripheral compartment is made up of intravascular fluid and vessel-rich groups (brain, heart, kidneys, liver, lungs).

Back 3

False, Central compartment

Front 4

What percent of body mass from the central compartment?

Back 4

10%

Front 5

True or False:
Transfer between central and peripheral compartments is irreversible.

Back 5

False, it is reversible

Front 6

True or False:
A drug must return to the central compartment for clearance from the body.

Back 6

True

Front 7

What occupies the Peripheral compartment?

Back 7

Muscles
Skin
Fat

Front 8

Plasma concentration reflects the drug concentration at the receptor site. What are the two phases?

Back 8

Distribution phase - alpha phase

Elimination phase - beta phase

Front 9

True or False:
Initially the drug plasma concentration is low in the central compartment and increases as redistribution into peripheral compartment occurs.

Back 9

False. Plasma concentration is initially high in the central compartment and decreases with redistribution into the peripheral compartment.

Front 10

What is the beta phase of plasma concentration?

Back 10

The elimination phase, which is a more gradual decrease of plasma concentration as drug is eliminated or cleared from the body.

Front 11

What is the drug half-TIME?
(t 1/2 B)

Back 11

Time necessary for plasma concentration to decrease by 50%.

Front 12

What is the drug half-LIFE?

Back 12

Time necessary for total dose of drug to be reduced by 50% in total body (from peripheral compartment, too).

Front 13

True or False:
Half-time and Half-life is not the same if the decline of drug in all tissues is not the same as the decline in plasma concentration.

Back 13

True, they are approximately equal with lipid soluble, nonionized drugs.

Front 14

What is the Volume of Distribution (Vd)?

Back 14

The volume necessary to account for the total amount of drug in the body if it were present throughout the body in the same concentration as in plasma
OR -
The volume of aqueous solution the injected drug would occupy to achieve the same concentration as in the plasma.

Front 15

True or False:
Volume of Distribution (Vd) refers to an anatomical compartment in the body.

Back 15

False, it does not refer to any anatomical or physiological compartment in the body.

Front 16

How is Vd calculated?

Back 16

By dividing dose of drug by plasma concentration before elimination begins.
- Expressed in L/Kg
- Time b/w alpha and beta phase

Vd = Q/C
Vd = amount of drug given IV in mg/kg divided by the concentration of drug in plasma

Front 17

How is Vd influenced by lipid solubility?

Back 17

Highly lipid-soluble drugs may be highly concentrated in tissues and have low plasma concentrations - Vd is HIGH

Front 18

How is Vd influenced by plasma binding?

Back 18

Highly protein-bound drugs have limited passage into tissues so plasma concentration is high - Vd is low.

Front 19

What drugs used in anesthesia have a small Vd?
(limited passage into tissues)

Back 19

Muscle relaxants
- ionized, water soluble

Front 20

What drugs used in anesthesia have large Vd?
(highly concentrated tissues)

Back 20

Induction agents
- lipid soluble, have access to all compartements

Front 21

Name the 5 body compartments.

Back 21

- plasma volume (PV)
- interstitial volume (ISV)
- intracellular volume (ICV)
- fat
- extracellular volume (PV + ISV)

Front 22

Because highly ionized drugs have small volume of distribution they are restricted to what body compartment?

Back 22

Extracellular volume (ECV = PV + ISV)

Front 23

Highly lipid-soluble drugs readily dissolve in what compartment because they have a high volume of distribution?

Back 23

Fat/Adipose tissue

Front 24

What body compartment in infants and neonates is expanded/larger and why?

Back 24

Extracellular volume (ECV = PV + ISV)

b/c they have more total body water

Front 25

Because neonates/infants have expanded extracellular volume they require MORE or LESS Sux.

Explain...

Back 25

More, becuase their NMJ is immature they need more drug to open the channels. Also the drug is diluted by the greater ECF compared to adults

They require the same amount of NDMR

Front 26

Why do infants and neonates require the same amount of NDMR?

Back 26

They require more drug because of greater ECV, but less drug because of immature NMJ. This equals out and they require the same amount.

Front 27

What is the partition coefficient (oil/water)?

What does it tell us?

Back 27

It is a measure of lipid solubility, obtained by adding drug to equal volumes of oil and water. The concentration of drug is measured in each volume and the ratio of concentration of drug in oil to concentration of drug in water is the partition coefficient.

The larger the partition coefficient the greater the lipid solubility. It affects Vd, DOA, and potency.

Front 28

True or False:
Most drugs are either weak acids or weak bases and are present as both ionized and nonionized molecules in a solution.

Back 28

True.

Front 29

Describe the properties of a nonionized molecule.

Back 29

- lipid soluble
- diffuses across a membrane
- pharmacologically active

Front 30

Describe the properties of an ionized molecule.

Back 30

- poorly lipid soluble
- can't cross membranes easily
- repelled from portions of cell with charges
- degree of ionization depends on pKa of drug and pH of surrounding fluids
- small changes in pH result in large changes in extent of ionization

Front 31

What is the pKa of a drug?

Back 31

The pH at which 50% of a drug is ionized and 50% is unionized

Front 32

True or False:
Weak acids become more ionized as pH falls.

Back 32

False, weak acids become more unionized as pH falls.

Acid + Acid (low pH) = More Unionized.

Penathol a weak acid with a pKa of 7.5 is 50% unionized at a physiologic pH of 7.5. If the pH drops to 7.3 more of the drug is unionized (works better/faster)

Front 33

Will induction with pentathol (weak acid) be faster if the patient acidotic or alkalotic?

Back 33

Faster if Acidotic

Acid + Acid = More unionized = faster b/c if diffuses across membranes

Front 34

True or False:
Weak bases (locals) become more unionized as pH increases.

Back 34

True.

Base + Base = More Unionized

Front 35

Lidocaine has a pKa of 7.7 (weak base). At a physiologic pH of 7.4 is it more or less unionized?

Back 35

It is less unionized (more ionized), meaning it is less effective.

Front 36

Is lidocaine (weak base) more or less effective in infected tissue?

Back 36

less effective.

Base + Acid = more ionized

Front 37

Acid + Base = _________

Base + Base = _________

Back 37

Acid + base = ionized

Base + Base = unionized

Front 38

True or False only the unionized form of a drug has pharmacologic effect.

Back 38

True.
Only the unionized form can undergo reabsorption across the renal tubules.
Only the unionized form is susceptible to hepatic biotransformation

Front 39

Is the pharmacologic effect of non-ionized drugs:
Active or Inactive?

Back 39

Active

Front 40

Is the solubility of ionized drugs:
Lipid soluble or Water soluble?

Back 40

Water soluble

Front 41

Do nonionized drugs cross membranes?

Back 41

Yes

Front 42

Is there renal excretion for ionized drugs?

Back 42

Yes

Front 43

Is there hepatic metabolism for ionized drugs?

Back 43

No

Front 44

If a drug is lipid soluble and predominately unionized at physiological pH is the Vd large or small?
Does it require more or less frequent dosing?

Back 44

Large Vd

More frequent dosing to maintain effect.

Front 45

Ion trapping is a result of.....

Back 45

differing pH's across cell membranes.

Front 46

Why does ion trapping occur in a fetus with local anesthetics?

Back 46

Locals used in OB can cross the placenta from mother to fetus in unionized form because the pH of the fetus is lower than the moms.
Locals are weak bases.
Base + Acid = ionized drug

Unable to cross back accross placenta to mom.

Front 47

Acids become more ________ when environment becomes more acidic.

Back 47

Unionized

Front 48

Bases become more ________ when environment becomes more basic.

Back 48

Unionized

Front 49

Which local is most un-ionized at pH 7.4?
- Mepivacaine pKa 7.6
- Procaine pKa 8.9

Back 49

Mepivacaine

Acid + Acid = unionized

Front 50

The higher the pKa of a weak acid, the greater the amount of drug in the _______ form at physiological pH.

Back 50

Unionized

Front 51

The higher the pKa of a weak base, the greater the amount of drug in the ________ form at physiological pH.

Back 51

Ionized

Front 52

List several weak bases

Back 52

Locals
Ketamine
Opioids
Benzodiazepines

Front 53

List several weak acids

Back 53

Thiopental
Other barbiturates
Propofol

Front 54

Variable amounts of most drugs are bound to proteins. Most acidic drugs bind to _______.
Most basic drugs bind to _______.

Back 54

Albumin.

Alpha1-acid glycoprotein

Front 55

True or False:
Drugs are pharmacologically inactive when bound to protein.

Back 55

True, they are resistant to biotransformation & excretion. They serve as a reservoir to maintain drug levels.
Only unbound portion crosses membranes.

Front 56

True or False:
Highly protein bound drugs have large Vd.

Back 56

False, small Vd

Front 57

True or False:
More lipid soluble drugs are less protein bound.

Back 57

False, more lipid soluble drugs are more highly protein bound.

Front 58

List several drugs that are highly protein bound.

Back 58

Thiopental
Fentanyl
Diazepam

Front 59

Describe first order clearance in terms of half-time.

Back 59

Half-time is required for one-half of available drug to be eliminated from plasma.

ex. If plasma concentration is 100mg and half time is 1hour then Concentration is decreased by 50% each hour

Front 60

Describe clearance in terms of zero order kinetics.

Back 60

A constant amount of drug (usually expressed in mg/min) is eliminated per unit of time regardless of concentration of drug.

Front 61

Give examples of drugs with zero order kinetics.

Back 61

Aspirin
Phenytoin
Alcohol

Front 62

What is the primary site for drug metabolism (biotransformation). What other areas are involved.

Back 62

Liver.

Others - GI tract, Kidneys, Plasma, Placenta, Lungs

Front 63

True or False:
Only severe hepatic disease significantly effects drug metabolism.

Back 63

True.

Front 64

What is a microsome?

Back 64

Vesicular fragment of ER formed after disruption of cells.
Includes iron-containing protein known as cytochrome P-450.

Front 65

Liver microsomal enzymes responsible for metabolism of drugs through what 4 methods?

Back 65

Oxidation
Reduction
Hydrolysis
Conduction

Front 66

Is Oxidation a result of a loss or gain of electrons?

Back 66

Loss

Front 67

Is Reduction a result of a loss or gain of electrons?

Back 67

Gain

Front 68

What three methods of metabolism comprise Phase 1 Reactions ("breaking up" of molecules)?

Back 68

Oxidation, Reduction, and Hydrolysis

Front 69

Does Phase 1 or Phase 2 reactions involve the cytochrome P-450 enzyme system?

Back 69

Phase 1 (only oxidation & reduction)

Front 70

_________ metabolizes drugs that contain ester bonds, such as sux, nimbex, sevoflurane, ester locals.

Back 70

Hydrolysis

Front 71

Does Hydrolysis involve the cytochrome P-450 system?

Back 71

No

Front 72

What method of metabolism is involved in phase 2 reaction (joining)?

Back 72

Conjugation
- enhances renal and biliary excreation

Front 73

Which methods of metabolism are usually incomplete in neonates, causing them to use lower doses?

Back 73

Conjugation and Oxidation

Front 74

Name 2 drugs used in anesthesia that have low hepatic excreation during the first pass.

Back 74

Diazepam and Thiopental

Front 75

Name 3 drugs used in anesthesia that have high hepatic excreation during the first pass.

Back 75

Etomidate
Ketamine
Propofol

Front 76

Is the Hepatic or Renal system most important for elimination of unchanged drugs or metabolites?

Back 76

Renal system

Front 77

Renal blood flow is approximately ____ ml/min

Back 77

600-700 ml/min.

Front 78

What lab value assess glomerular filtration?

Back 78

Creatinine level

Front 79

Renal excretion involves Active or Passive transport?

Back 79

Active, selective for certain drugs and metabolites.
There are a limited number of transport carriers - so they can become saturated

Front 80

Glomerular filtration cannot exceed ___ ml/min

Back 80

120 ml/min, if elimination studies show renal clearance is greater than 120 ml/min tubular secretion is involved

Front 81

True or False:
In drug ODs manipulation of blood pH may be used to prevent reabsorption.

Back 81

False, manipulation of urine pH

Front 82

True or False:
Lipid soluble drugs are poorly excreted (renally) because of the ease of absorption from renal tubules

Back 82

True

Front 83

True or False:
Without metabolism, lipid drugs like thiopental would undergo reabsorption indefinately.

Back 83

True

Front 84

Uremia associated with CNS depression does what to the requirements for sedation?

Back 84

reduces them by as much as 50%

Front 85

What occurs if your patient has a decreased albumin level? Lets say below 2.5 (norm is 3.5-5.0)

Back 85

you will see a decreased plasma protein binding of drugs, so there is an increased amount of active drug available for the tissue receptors.

Front 86

What may you see with renal failure patients when using NDMRs?

Back 86

prolonged respose to long acting NDMRs, because of a slower rate of decrease in plasma concentration.

Front 87

What percent of neostigmine is eliminated by renal excretion?

Back 87

50%

(75% for edrophonium & pyridostigmine)

Front 88

Are narcotics and/or benzos usually well tolerated with renal failure patients?

Back 88

yes, both are extensively metabolized prior to excretion.

Front 89

List several properties of neuromuscular blocking agents, in terms of pharmacokinetics.

Back 89

- Small Vd
- Poorly lipid soluble
- quarternary ammonium group
- Limited to ECF (don't easily cross membranes)
- Duration of blockade depends on redistribution to inactive sites and renal excretion

Front 90

How are atracurium and/or cisatracurium metabolized?
What is it dependant on?

Back 90

Hoffman elimination, dependant on temperature and pH

Front 91

True or False:
Short acting barbiturates have a large Vd and are highly lipid soluble.

Back 91

True

Front 92

List several properties of Thiopental.

Back 92

- Highly lipid soluble
- Highly protein bound
- 99% metabolized
- Minimal renal excretion
- slow rate of metabolism

Front 93

List several properties of Propofol.

Back 93

- Rapid hepatic metabolism
- Redistributes to inactive tissues
- Cleared from plasma (unlikely to see cumulative effect)

Front 94

Why do you see rapid awakening from Etomidate?

Back 94

B/C it undergoes nearly complete hydrolysis to inactive metabolites.

Front 95

List several properties of Ketamine.

Back 95

- Highly lipid soluble
- Extensive hepatic metabolism
- Rapid redistribution to inactive tissues

Front 96

Are Opioids weak acids or weak bases?
Do they work better in an acidic or basic environment?

Back 96

Weak bases.
Better in Basic environment, Base + Base = nonionized

Front 97

List several properties of Sufenta & Fentanyl.

Back 97

- highly lipid soluble
- short DOA (low plasma concentration)
- Saturation of distribution sites occur with high doses (plasma concentration doesnt fall = prolonged DOA)

Front 98

List several properties of Alfentanil.

Back 98

- Small Vd
- Highly protein bound
- Low partition coefficient
- Lower lipid solubility (rapidly crosses BBB)
- Short DOA (redistribution & liver metabolism)

Front 99

List several properties of Remifentanil.

Back 99

- undergoes nonspecific esterase metabolism
- onset of action and offset w/in 5 minutes
- titratable
- suitable for short procedures
- good for long cases where you want to avoid prolonged recovery of decreased cognition.

Front 100

Which benzodiazepam causes prolonged action in patients with renal disease?

Back 100

Diazepam. Minimal alteration in elimination of versed in renal insufficiency.

Front 101

Why do you see rapid awakening from Etomidate?

Back 101

B/C it undergoes nearly complete hydrolysis to inactive metabolites.

Front 102

List several properties of Ketamine.

Back 102

- Highly lipid soluble
- Extensive hepatic metabolism
- Rapid redistribution to inactive tissues

Front 103

How does age affect pharmacokinetics and metabolism?

Back 103

Affects very young and old
- slow metabolism w/old
- immature systems w/young
- decreased CO w/old causes less drug to liver for metabolism
- Increased Vd (more fat) causes prolonged elimination

Front 104

Discuss how liver, cardiac, pulmonary and endocrine diseases affect pharmacokinetics and metabolism.

Back 104

Liver - metabolism decreased
Cardiac - slow blood flow to liver
Pulmonary - impaired hydrolysis and oxidation
Endocrine - thyroid dysfunction alters metabolism

Front 105

Where is the principal site of absorption for oral drug administraiton?

Back 105

Small intestine
- lg surface area
After absorption from GI tract, drug enters portal venous blood and through liver before entering sysemic circulation.
- first pass effect
- why longer OOA for PO vs IV in some drugs

Front 106

Is there First pass effect ith sublingual or buccal routes of drug administration?

Back 106

No, venous drainage from sublingual area is into superior vena cava. Rapid OOA

Front 107

Drugs with which properties have favorable affects when given transdermally?

Back 107

- water &/or lipid soluble
- MW <1000
- Absence of histamine releasing effects
- Daily dose requirement less than 10mg

Front 108

What is the rate limiting step in absorption for the transdermal route?

Back 108

Diffusion of drug across stratum corneum of epidermis