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*Pharmacology > Apex-Pharmacokinetics > Flashcards

Apex-Pharmacokinetics Flashcards

1
Q

What measures the relationship between a drug dose and a drugs plasma concentration?

A

Volume of Distribution

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2
Q

What is a theoretical measure of how a drug distributes throughout the body?

A

Volume of distribution

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3
Q

What does Vd (volume of distribution) assume? (2)

A
  1. That the drug distributes instantaneously &
  2. That the drug is not subject to biotransformation or elimination before it’s fully absorbed
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4
Q

Do hydrophilic drugs have a low or high Vd?

A

Low > they distribute into some or all of the total body water but don’t distribute into fat

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5
Q

Do hydrophilic drugs require higher or lower doses to achieve a given plasma concentration?

A

Lower doses (they are restricted to the ECF and stay there - don’t have to worry about their distribution into fat which would require more drug to get to a certain plasma concentration)

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6
Q

Example of high vs low Vd drugs? (1 each)

A

High = propofol (distributes into fat, lipophillic)
Low = neuromuscular blockers (stays in the ECF)

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7
Q

Volume of Distribution = (2 calculations)

A

Amount of drug/Desired plasma concentration

Patients weight x Vd of a given drug

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8
Q

How to calculate a loading dose

A

Vd x Desired plasma concentration/Bioavailability

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9
Q

What is the bioavailability of all IV drugs?

A

1

> bc 100% of it is immediately available in the ECF (doesn’t have to go through 1st pass metabolism in the liver)

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10
Q

Total Body Water = ____L or _____L/kg

A

42 L
0.6L/kg

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11
Q

(High/low) Vd drugs exceed total body water

A

High (Lipophilic)

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12
Q

What makes up total body water?

A

The ECF - 14L & ICF 28L

60%/40%/20% (15%/5%)
T-I-E
70kg always normal reference
40% x 70kg = 28L
20% x 70kg = 14L

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13
Q

What makes up ECF?

A

60/40/20 (15/5)

Intesistial = 15% (10.5L)
Plasma = 5% (3.5L)

% of 70kg

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14
Q

Define drug clearance

A

The volume of PLASMA that is cleared of the drug over time

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15
Q

What are the major clearing organs? How are drugs cleared in the plasma?

A

Liver and Kidney

Hoffmann elimination and ester hydrolysis in the plasma

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16
Q

What is the term for when the amount of drug entering the body = the amount of drug leaving the body

A

Steady state

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17
Q

How many half-times must elapse to achieve steady state?

A

5

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18
Q

Clearance is directly proportional to (3)

A
  1. Blood flow to the clearing organ
    >more blood flow to the kidney = faster the drug can be cleared
  2. Extraction ratio
    >more extraction = more cleared
  3. Drug dose
    >increased drug = increased clearance
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19
Q

Clearance is (indirectly/directly) proportional to:

Half life vs drug concentration in the central compartment

A

Both inversely related

  1. Half-life
    >increased 1/2 life = decreased clearance
  2. Drug concentration in the central compartment
    >more drug in the central compartment = less being cleared
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20
Q

In multi-compartment models, what do the Alpha and Beta phases represent ?

A

Alpha phase = distribution (plasma concentration decreases)
Beta phase - represents drug elimination from the central compartment

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21
Q

Elimination half-life vs half-time

A

Half life = time required for a drugs plasma concentration to decrease 50%
>the time it takes for 50% of the drug to be removed from the body

Half-time = The time it takes for 50% of the drug to be removed from the PLASMA during the elimination phase (think- watch 1/2 TIME show on PLASMA tv)

> this oversimplifies the movement of drug inside the body and is clinically meaningless

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22
Q

What is the term for the time required for the plasma concentration to decrease 50% after an infusion has stopped?

A

Context-sensitive half-time

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23
Q

When is a drug considered to be cleared from the body?

A

When 96.9% of it has been eliminated from the plasma (5 half-times)

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24
Q

Filling out half-time table

A

First row 0-5
%Drug eliminated
%Drug remaining

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25
Q

Label the opioids on the context-sensitive half time chart

A

FASteR

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26
Q

A weak acid/base is where the pH of a solution is (>) the pKa of the drug?

A

Weak acid : pH of solution < pKa of the drug (decreased pH =acidic)
Weak base: pH of solution > pKa of the drug (increased pH = basic)

*more likely to pass through a lipid membrane

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27
Q

What is the difference between a weak acid and a weak base?

A

Weak acids donate a H+
Weak bases donate OH-

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28
Q

What happens when the pKa & pH of the drug are the same?

A

50% will be ionized and 50% will be unionized

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29
Q

What is ionization?

A

The process where a molecule gains a positive or negative charge, affecting it’s ability to diffuse through lipid membranes

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30
Q

Amount of ionization a drug undergoes depends on what 2 factors?

A

The solutions pH and the pKa of the drug

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31
Q

Another name for pKa

A

Disassociation constant

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32
Q

Ionized vs un-ionized:
Water/lipid soluble
Pharmacologically active/inactive
Hepatic biotransformation vs renal elimination more likely
Diffuse across lipid bilayers - yes/no

A

Ionized = water soluble , pharmacologically inactive, renal elimination more likely, does not diffuse across lipid bilayers (likes the water and stays there)

Un-ionized = lipid soluble, pharmacologically active, hepatic biotransformation more likely, yes diffuses across lipid bilayers (BBB, GI tract, Placenta)

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33
Q

Does albumin carry a positive or negative charge?
Will it primarily bind acidic or basic drugs?

A

Negative charge
-will primarily bind acidic drugs (+/-)

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34
Q

Does alpha-1 acid glycoprotein primary bind basic or acidic drugs?

A

Basic drugs

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35
Q

Does beta-globulin bind acid or basic drugs?

A

Basic
(Beta, Basic)

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36
Q

5 circumstances where albumin will be decreased (increased risk of toxicity)

A
  1. Liver disease (liver makes albumin)
  2. Renal disease (albumin passes through diseased kidneys)
  3. Old age
  4. Malnutrition (ETOH)
  5. Pregnancy (altered distribution)
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37
Q

5 circumstances where alpha-1 acid glycoprotein would be increased and 2 for decreased states

A

Increased = surgical stress, MI, chronic pain, RA, old age
Decreased = neonates and pregnancy

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38
Q

If a drug is 98% bound and the bound fraction decreases to 96%, how much has the unbound or free-fraction of the drug increased by?

A

100%
(2% free increases to 4% free)
(4-2)/2 x 100 = 100%

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39
Q

Zero order kinetics vs First-order kinetics

A

Zero order = a constant AMOUNT of a drug is metabolized over time
First- order = a constant FRACTION (F/F) of a drug is metabolized over time

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40
Q

The majority of our drugs follow first-order kinetics, which drug follows zero-order kinetics? (6)

A

WAP HAT

Warfarin
Alcohol
Phenotoin
Heparin
Aspirin
Theophylline

41
Q

What is the enzymatic process of altering the chemical structure of a molecule?

A

Biotransformation/Metabolism

42
Q

What are the 3 phases of metabolism/biotransformation?

A
  1. Modification
  2. Conjugation
  3. Elimination
43
Q

What is the primary goal of metabolism?

A

To change a lipid-soluble, pharmacologically active compound into a water-soluble, pharmacologically inactive byproduct so it can be excreted

44
Q

What is a prodrug? Example?

A

When the body converts and inactive molecule into a pharmacologically active one

(The body is a Pro at making drugs)

Fospropofol is metabolized by alkaline phosphatases to it’s active metabolite > propofol

45
Q

Jeopardy-style: When you administer the drug, how much of it will end up in the bloodstream?

A

What is Bioavailability

46
Q

In order for a drug to diffuse across the lipid bilayer of cells, does it have to be ionized or unionized?

A

Un-ionized (the cell membrane is negatively charged and if an ionized (+) drug tries to cross, it can’t. It will just stick to it.

47
Q

Is morphine sulfate an acid or a base and why?

A

Morphine is a base, it is combined with sulfuric acid to be a stable compound (which can be stored)

(acid + base = salt > water)
(add water(what our body is made of)) to the salt and acid and base will dissociate into it’s two seperate parts) i think

Demerol hydrocholide - hydrochloronic acid = acid, so demorol is a base.

48
Q

What is the pKa of a drug?

A

A pH in which that drug would be 50% ionized and 50%unionized

49
Q

pH of CSF?

A

7.3 (slightly more acidic than blood)

50
Q

Which equation is used to determine the pKa of a drug?

A

Henderson-Hasselbalch

51
Q

Phase I, II, & III reactions are associated with which terms?

A

I- modification
II- conjugation
III- elimination

52
Q

Which type of reaction results in small, molecular changes that increase the polarity (water solubility) of a molecule?

A

Phase I

> it does this to prepare it for phase II reactions (Conjugation)

53
Q

Most Phase I reactions are carried out by what?

A

The P450 system

54
Q

What are 3 elements of phase I reactions and what do they mean?

A
  1. Oxidation - removes electrons from a compound
  2. Reduction- adds electrons to a compound
  3. Hydrolysis- adds water to a compound to split it apart (usually an ester)
55
Q

What phase reaction results in a water-soluble, biologically inactive molecule ready for excretion?

A

II

56
Q

What does conjugation mean?

(what phase reaction)

A

Phase II - it adds on an endogenous, highly polar, water-soluble substrate to the molecule to inactivate it so it can be excreted.

57
Q

What drug works via enterohepatic circulation and what does that mean?

A

Diazepam - some conjugated compounds are excreted in the bile, reactivated in the intestine, and reabsorbed into systemic circulation

58
Q

What phase of metabolism involves ATP-dependent carrier proteins that transport drugs across all cell membranes that are present in the kidney, liver, and GI tract?

A

Phase III - elimination

59
Q

Hepatic clearance is a product of what 2 things?

A
  1. Liver blood flow - how much blood is delivered to the liver
  2. Hepatic extraction ratio- how much drug is removed by the liver
60
Q

Hepatic extraction ratio - what is it?

A

A measure of how much drug is delivered to a clearing organ vs how much is removed by that organ.

61
Q

How is the extraction ratio calculated?

A

Arterial concentration - venous concentration
/arterial concentration

62
Q

What do extraction ratios of 1.0 and 0.5 mean?

A

1.0 = 100% of the drug delivered to the clearing organ is removed

0.5 = 50% is removed

63
Q

Extraction ratios of flow limited elimination and capacity limited elimination

A

flow limited = ER > 0.7
(clearance is dependent on liver blood flow)
(increased blood flow = increased clearance)

capacity limited = ER < 0.3
(clearance is dependent on the ability of the liver to extract the drug from the blood)
& since only a small amount of drug is removed per unit of time, alterations in blood flow minimally effect the clearence

64
Q

Does enzyme induction result in increased or decreased clearance from the liver?

A

induction = INcreased

65
Q

Does enzyme inhibition result in increased or decreased clearance from the liver?

A

inhibition = decreased

66
Q

6 drugs with low ER’s (liver depedent)

A

PTT, MLD (PTT and MELD score) LOW ER

Phenytoin
Theophylline
Thiopentyl

Methadone
Lorazepam
Diazepam

67
Q

15 drugs with high ER’s (blood flow dependent)
(5 groups of drugs)

A

Opioids (5)
1. Fentanyl
2. Sufentanil
3. Morphine
4. Meperidine
5. Naloxone
(fent and su, M&M, and the reversal)

Induction drugs (2)
6-7. Propofol & Ketamine

Locals (2)
8-9. Lidocaine & BPV

Beta-blockers (3) MAP (blood blow)
10. Metoprolol
11. Alprenolol
12. Propanolol

CCBs (3)
13. Nifideipine
14. Diltiazem
15. Verapamil

68
Q

4 intermediate ER drugs

A

eating M&M’s in Virginia (VA)

  1. Midazolam
  2. Methohexital
  3. Vecuronium
  4. Alfentanyl
69
Q

2 other names for P450 isoenzymes

Where are they located?

A
  1. Mixed-function oxidase system
  2. Monooxygenases

In the smooth ER of the hepatocyte
(also in lungs, kidney, skin, adrenals, GI tract)

70
Q

What is the most important cytochrome P450 enzyme?

What’s the second most important?

A

-CYP 3A4 (3 Ashleys, how about 4)
(metabolizes nearly 50% of drugs we administer)

-CYP 2D6 (2 dicks sux)

71
Q

What do enzyme inducers do?

A

Stimulates the synthesis of additional enzymes
-increased clearance
-decreased drug plasma level (t1/2 life)

72
Q

What do enzyme inhibitors do?

A

Competes for binding sites on the enzyme –> fewer binding sites to clear the drug
-decreased clearance
-increased drug plasma level (t 1/2 life)

73
Q

6 Enzyme inducers

A
  1. Alcohol (ethanol)
  2. Tobacco

Smokers (love) A Cold PBR

Smokers (love)
Alcohol
Carbamazepine
Phenytoin
Barbituates
Rifampin

*may require increased doses)

74
Q

7 Enzyme inhibitors

A

(I [love] Geckos)

Isoniazid (TB)
Grapefruit juice
Erythromycin
Cimetidine
Ketoconazole (antifungal)
Omeprazole
SSRIs

75
Q

3 categories of CYP 3A4 substrates and the (4-3-2) drugs in each category

A
  1. Opioids
    >Fent, Su, Al ,
    >Methadone
  2. Locals
    >Lido, BPV, Ropi
  3. Benzos
    >midaz, diazepam
76
Q

Inducers of CYP 3A4 (6)

A

(ERS has TB - see! (C))
Ethanol
Rifampin
St. Johns Wart *

Tamoxifen*
Barbituates

Carbamazepine

77
Q

Inhibitors of CYP 3A4 (5)

A

(CAGES)
Cimetidine
“A”-zole antifungals
Grapefruit Juice
Erythromycin
SSRIs

78
Q

Substrates of CYP 2D6 (4)

A

Codeine –> Morphine
Oxycodone
Hydrocodone

79
Q

Inducers of CYP 2D6 (3)

A

(Pat Casey likes dexamethasone)
Phenytoin
Carbamazepine
Dexamethasone

80
Q

Inhibitors of CYP 2D6 (3)

A

(SIsQo)
SSRIs
Isoniazid
Quinidine*

81
Q

Substrate of CYP 1A2 (1)
it’s inducers (3) and inhibitors (2)

A

Theophylline (small therapeutic index)
> tobacco, cannabis, ethanol
>erythromycin, ciprofloxacin

82
Q

What is the primary function of the kidney

A

To eliminate metabolic waste into the urine

83
Q

What happens to lipophilic drugs that have not undergone biotransformation?

A

They will be re-absorbed into the peri-tubular fluid by diffusion

84
Q

What are the 2 processes that deliver drug into the urine?

A

-Glomeular filtration & Organic ion transporters

85
Q

Where are organic anion and cation transporters located and what do they do?

A

They are transport proteins located in the proximal renal tubules
>secrete organic acid and bases into the urine

86
Q

Organic anion transporter drugs (3)
Organic Cation transporter drugs (3)

A

Anion transporter - furosemide, thiazides, PCN
Cation transporters - Morphine, meperidine, dopamine

87
Q

What influences whether drugs are excreted in the urine or reabsorbed into the peritubular capillaries?

A

The urine pH (like dissolves like)

88
Q

Acid urine favors reabsorption of (acid/basic) drugs and excretion of (acid/basic) drugs

A

reabsorption of acidic drugs
excretion of basic drugs

***AAA: Acid drugs are better Absorbed in an Acidic environment

89
Q

Basic urine favors reabsorption of (acid/basic) drugs and excretion of (acid/basic) drugs

A

reabsorption of basic drugs
excretion of acidic drugs

***BBB: Basic drugs are Better absorbed in a Basic medium

90
Q

What will help acidify the urine to help eliminate basic drugs? (2)

A

-Ammonium chloride (A)
-Cranberry juice

91
Q

What will help alkalize the urine to help eliminate acidic drugs? (2)

A
  1. sodium Bicarb (B)
  2. Acetazolamide (Diamox)
92
Q

All metabolic pathways involve enzymes for metabolism except what?

A

Hoffmans elimination (pH and temp)

93
Q

Do plasma enzymes undergo enzyme induction?

A

No

94
Q

Pseudocholinesterase deficiency extends the duration of action of what 3 drugs?

A
  1. Sux
  2. Mivacurium
  3. Ester local anesthetics (one i)
95
Q

What are the 3 groups of esterases?

A
  1. Pseudocholinesterase
    (Sux, mivacurium, ester local anesthetics)
  2. Nonspeicfici esterases
    (Esmolol, Remifent, etomidate, atricurium)
  3. Alkaline Phosphatase
    (Fospropofol) > prodrug concerted to propofol by alkaline phosphatase
96
Q

What 2 drugs are eliminated by Hoffman elimination?

A
  1. Cisatracurium (Chuck Norris)
  2. AHHHHtracurium (+nonspecific esterases)
97
Q

Scenario:

You ran propofol gtt and waited too long to shut it off bc u were nervous they were gonna move too soon…..
what can you do to try and facilitate them clearing the drug?

A

Increase their blood pressure!

  • propofol has a high extraction ratio meaning it’s depedent on blood flow to the liver to be cleared; increase blood flow to the liver, more drug will be cleared and well-a! (i’ma try this)

and if someone gives pushback saying your giving another drug…. well i’m giving a drug with a relatively safe profile that will clear the anesthetic from their body faster - they will be able to breathe more effectively, eat sooner, and leave the hospital sooner; decrease LOS and increased production time

98
Q

Do you need to reduce the amount of propofol in someone with hepatic failure?

A

Probably not- it has a high ER - meaning it’s clearence is depedent on blood flow to the liver

99
Q

You think you gave too much narcotic, pt is VERY comfortable and doesn’t want to breathe; what can you try doing before giving narcan?

A

Increasing their BP
-fentanyl has a high ER meaning it is depedent on blood flow to the liver for elimation
-more blood flow to the liver = more drug able to be eliminated

(no idea if this is clinically significant but it sounds like a good idea)

*Pharmacology (25 decks)

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