Pharmacokinetic Principles Flashcards
(152 cards)
1
Q
Pharmacokinetics is the quantitive study of what?
A
The quantitive study of absorption, distribution, metabolism, and excretion of drugs and their metabolites.
2
Q
Define Absorption?
A
The passage of drug molecules through physiological/biological barriers BEFORE reaching the vascular system.
3
Q
(T/F?) When drugs are given extravascularly (i.e. orally, IM, transdermal, SQ, etc.), absorption MUST take place for the drug too reach systemic circulation?
A
True
4
Q
The systemic absorption of a drug is dependent upon which 3 factors?
A
1) Physiochemical properties of the drug: lipid solubility, molecular size, pKa, ionization.
2) Nature of the drug: dosage form and delivery system.
3) Anatomy and physiology functions at the site of the drug absorption: cell membrane, surface area, pH, blood flow, etc.
5
Q
Which form of a drug is able to cross the lipophilic cell membrane?
A
The Non-ionized form
6
Q
Define Passive Diffusion? Does this process require energy?
A
Passive Diffusion is the process by which drug molecules move from a region of high concentration to lower concentration. Passive Diffusion does NOT require energy.
7
Q
What is the main process by which most drugs cross cell membranes?
A
Passive Diffusion
8
Q
You can not change the lipid solubility, pKa, or molecular size of a drug. However, you can change the ionization of a drug? How and why would you do this?
A
You can do this by giving it with another drug with a different pH. You would do this so the drug crosses the lipid membrane more easily.
9
Q
The process of Passive Diffusion is governed by which Law” What is the formula that describes the Law?
A
Fick’s Principle/Law. Q/t = {K x A x (Cp - Ct)} / D
10
Q
Define the following components of Ficks Principle/Law:
1) Q/t
2) (Cp - Ct)
3) A
4) K
5) D
A
1) Q/t = Rate of diffusion across a membrane
2) (Cp - Ct) = The difference in drug concentration in the plasma and tissue.
3) A = Surface area of the membrane over which the drug may be absorbed.
4) K = Diffusion Coefficient: degree of lipid solubility of the drug.
5) D = Thickness of the membrane
11
Q
Which 2 factors, that also affect Passive Diffusion, are not included in the calculation of Fick’s Principle/Law?
A
1) Molecular size
2) Blood flow
12
Q
Define Active Transport? Does it require energy?
A
The transport of drug AGAINST a concentration gradient (from low to high), which REQUIRES the use of energy.
13
Q
(T/F?) Active Transport plays an important role in renal and billiary secretion of drugs and their metabolites?
A
True
14
Q
Define Facilitated Diffusion?
A
Process that uses a carrier to transport drug along a concentration gradient (from high to low).
15
Q
Where is the site of action for anesthetic drugs?
A
The Brain
16
Q
What is the common name for Naproxen Sodium?
A
Alieve
17
Q
(T/F?) All Opioids are weak bases?
A
True
18
Q
What happens to weak acids and weak bases during ionization?
A
Weak Acids give up a Hydrogen ion that forms a bond with positively charge ion (i.e. Na++, Ca++, Mg++) to form a salt.
Weak Bases accept a hydrogen ion to form a salt.
19
Q
(T/F?) Weak acids and Weak Bases are administered in solution as salt forms of the drugs?
A
True
20
Q
What are the characteristics Non-ionized drug molecule?
A
1) Pharmacologically active
2) Lipid soluble (crosses lipid barrier)
3) No renal excretion
4) Hepatic metabolism
21
Q
What are the characteristics Ionized drug molecule?
A
1) Pharmacologically inactive
2) Water soluble (Does not cross lipid barriers)
3) Renal excretion
4) No hepatic metabolism
22
Q
How are the salt forms of drugs made from weak acids typically named?
A
Typically with the cation listed in front of the drug name: i.e. Sodium Thiopental and Sodium Phenobarbital. Naproxen Sodium and Phenytoin Sodium are exceptions.
23
Q
How are the salt forms of drugs made from weak bases typically named?
A
Typically with the drug name listed in front of the anion: i.e. Lidocaine HCl, Mepivicaine HCl, or Bupivicaine HCl.
24
Q
What are the 2 examples of drugs made from weak bases that don’t follow the typical naming rule. i.e. Lidocaine HCl?
A
1) Propofol
2) Etomidate
25
What is the purpose of the Henderson Hasselbalch Equation? What is the formula?
The equation helps to predict the degree of ionization of a given drug in a solution, given the pH of that particular solution and the drugs pKa.
pH = pKa + log([Base] / [Acid])
26
Define pKa
pKa is defined as the pH at which a drug is will be 50% ionized and 50% non-ionized.
27
How does the value of pKa relate to the value of pH?
1) The lower the pKa, the stronger the acid
| 2) The higher the pKa, the stronger the base
28
What are the general principles relating pH to pKa?
1) When pH < pKa, the protonated/non-ionized form (HA or BH+) predominates.
2) When the pH > pKa, uprotonated/ionized form (A- or B) predominates.
29
For weak acids and weak bases, the pH where the drug is located determines the relative amounts of a drugs ______? what does this affect?
It determines the relative amounts of a drugs ionized and non-ionized forms, which affects solubility, which in turn affects absorption and onset of action.
30
Since administering a weak acid or weak base drug at normal physiologic conditions (pH 7.4) yields a a defined ratio of ionized to non-ionized drug molecules, what would happen if the patient had an altered pH?
If the PT's pH was acidic, weak acid drugs will become more non-ionized or lipid soluble and weak base drugs will become ionized.
If the PT's pH was basic, weak acid drugs will become more ionized while weak base drugs will become more non-ionized.
31
(T/F?) Barbiturates are classified as weak acid drugs?
True
32
Acetylsalicylic acid is a weak organic acid with a pKa of 3.5. What form of ionization will PREDOMINATE at physiologic pH=7. 4?
when pH > pKa in a weak acid, the uprotonated/ionized form (A- or B) predominates.
33
Explain Ion Trapping as it relates to the administration of local anesthetics in obstetrics.
Since local anesthetics are all weak bases, administration of local anesthetics via epidural can cross the placenta and become trapped in the fetus and accumulate because the fetal pH is lower (more acidic) than maternal pH. This can lead to toxicity. Remember that weak bases become ionized in acidic environments and is consequently unable to cross lipid membranes.
34
How can you utilize the Ion Trapping Mechanism in Drug Excretion?
Weak acids are excreted faster in an alkaline pH (anion favored) so you alkalinize the urine.
Weak bases are excreted faster in an acidic pH (cation form favored) so you acidify the urine.
35
Define Bioavailability?
Bioavailability is the rate and amount of therapeutically active drug that becomes available at the site of drug's action.
36
Why is it that when drugs are given extravascularly, the entire dose may not reach the systemic circulation (is not 100% bioavailable)?
Because they must be absorbed across several biologic membranes before entering the vascular system.
37
(T/F?) Drugs given via IV have a bioavailability of 100%?
True
38
Describe the "First-Pass Hepatic Effect"?
Drugs absorbed from the GI tract pass through the portal venous system then through the liver before finally going to the systemic circulation.
39
Why are there large differences in the pharmacological effect between IV and PO routes when administering lidocaine and propranolol?
Lidocaine and propranolol undergo very large first-pass effect, so they have low bioavailability by the time they reach systemic circulation if they are taking PO.
40
For most drugs, the optimum site for drug absorption after oral administration, is the duodenum region of the upper portion of the small intestine, why?
1) It has increase surface area due to presence of microvilli.
2) It is highly perfused with capillaries.
41
What are 3 examples of Transmucosal Administration? What are the advantages of this route?
1) Sublingual 2) Buccal 3) Nasal
| Advantages include rapid onset due to high blood supply and rapid absorption and bypasses first-pass effect.
42
What are the advantages of rectal administration of drugs? does this route bypass the first-pass effect?
Advantages = rapid uptake, can be used for PTs who are unconscious or who have N&V.
Bypasses first-pass effect if given in lower rectum. If given in proximal rectum, it will not bypass first-pass effect.
43
What's the major advantage of Transdermal administration?
Provides sustained therapeutic plasma concentration with decreased likelihood of loss of efficacy due to peaks and valley plasma concentration effects.
44
What makes a good transdermal medication?
1) Lipid soluble drugs
2) Molecular weight < 1,000 (low MW)
3) pH 5-9 in a saturated aqueous solution
4) Absence of histamine releasing effects
5) Daily dose requirements of < 10mg (low dose)
45
Absorption via transdermal administration is highly dependent on which factors?
1) Stratum Corneum thickness
2) Heat
3) Blood flow in the area
46
Define Distribution?
Distribution is the passage of drug molecules from the bloodstream into tissues and organs.
47
What are the determinants of drug distribution?
1) Lipid solubility
2) Protein binding
3) Blood flow rate to the tissue
4) Molecular size of the drug
5) Degree of drug ionization
48
(T/F?) After distribution, when a drug reaches its site of action (drug receptor), only the free/unbound drug is available to cross membranes into tissues.
True
49
Define Volume of Distribution
A theoretical volume that relates the amount of drug in the body to the measured concentration in the plasma.
50
(T/F?) Volume of Distribution is required to account for the total amount of drug in the body if the concentration of all tissues are the same as the plasma concentration.
True
51
What is the formula used to calculate Volume of Distribution?
Vd = (Dose/Concentration)
52
Volume of Distribution is an important pharmacokinetic parameter because it is used to determine what?
Loading Dose of a drug, which is required to achieve a steady state concentration immediately after the dose is administered.
53
Knowing the Volume of Distribution allows us to estimate which 3 things?
1) The amount of drug in the body
2) Peak serum levels of the drug after an IV bolus
3) The clearance of a drug
54
Explain why Volume of Distribution is inversely related to protein binding?
Because only unbound drug can cross cell membranes. Drugs that are highly plasma protein bound remain in the plasma as compared to drugs that are low plasma protein binding.
55
Explain why protein binding is directly related to lipid solubility?
Because only the lipid soluble drug will be absorbed into the bloodstream and is available for protein binding.
56
The fraction of total drug in plasma that is bound to protein is determined by which 3 factors?
1) Plasma concentration of the drug
2) The affinity of binding sites for the drug
3) The # of protein binding sites/protein concentration
57
How can various diseases affect drug distribution as it relates to protein binding.
Certain diseases affect protein concentration which impacts the amount of plasma protein available to bind drugs.
58
Give an example of a drug that is highly affected by protein levels?
If a PT's albumin level is low, you must reduce the dose of Phenytoin to avoid toxicity because Phenytoin is highly albumin bound.
59
How does protein binding affect drug metabolization and clearance?
1) Metabolization - Binding to proteins prevents the drug from entering hepatocytes, resulting in decreased drug metabolization.
2) Protein-bound drugs are larger molecules and cannot easily diffuse through capillary membranes in the glomeruli, resulting in decreased drug clearance.
60
What are the two main plasma drug binding proteins?
1) Albumin - Responsible for reversible drug binding and binding to most acidic drugs.
2) Alpha1 Acid Glycoprotein - Binds most basic drugs
61
Name three drugs that bind to Alpha1 Acid Glycoprotein?
1) Lipoproteins
2) Immunoglobulins
3) Erythrocytes
62
How do small changes in protein binding affect drugs that are highly protein-bound? Give examples of such drugs?
Small changes radically increases drug concentration. Examples include warfarin, propranolol, phenytoin, and diazepam.
63
How do changes in protein binding affect drugs that are low protein-bound?
Changes in protein binding in these drugs are not clinically significant.
64
Define Metabolism?
Metabolism or biotransformation is the chemical conversion of a drug into different compounds.
65
What are the possible results of drug metabolism?
Drug metabolism results in inactive metabolites OR active metabolites whose pharmacologic activity is equal to, greater than, less than or completely different from that of the parent drug.
66
The majority of drug metabolism is catalyzed by by which enzyme?
CYP 450
67
In addition to the liver, metabolism can also occur in which other organs?
1) Plasma - Hoffman elimination, nonspecific esterase enzymes, and butyrycolinoesterases.
2) Kidneys
3) Lungs
4) GI mucosal cells
5) Skin
68
What is the primary effect or net effect of drug metabolism?
Production of more polar, water-soluble metabolites that are more easily excreted from the body.
69
Since metabolism can lead to active metabolites, give two examples of drugs that have active metabolites?
1) Diazepam
| 2) Meperidine
70
What are Prodrugs? Give an example?
Certain drugs that are inactive compounds and require metabolism via liver or non liver enzymes to become active.
i.e. Clopidogrel - requires metabolism by CYP450 to become its active metabolite.
71
What are the 2 pathways to drug metabolization?
1) Phase I - Functionalization Reactions
| 2) Phase II - Conjugation Reactions
72
What happens during Phase I (Functionalization Reactions)?
Reactions are catalyzed by enzymes that introduce or expose a functional group on the drug molecule, which increases the drugs polarity and prepares it for either Phase II conjugation reactions or excretion.
73
3 Types of Phase I reactions?
Oxidation, Reduction and Hydrolysis
74
(T/F?) Phase I reactions generally result in drug inactivation?
True - but prodrugs are an exception to this rule.
75
Which enzyme is the main one responsible for phase I reactions and is essential for reduction reactions?
Cytochrome P-450
76
Phase I Oxidation Reactions involve which enzymes?
CYP 450
FMOs
Non-microsomal enzymes, i.e. alcohol dehydrogenase
77
5 examples of Phase I Oxidative Reactions?
1) Hydroxylation (addition of a water molecule) i.e. Midazolam
2) Deamination (removal of amine - NH3)
3) Desulffuration (removal of S)
4) Dealkylation (removal of CH3 i.e. demethylation of morphine to normorphine)
5) Dehalogenation
78
Halogenated volatile anesthetics are susceptible to dehalogenation, which can lead to the release of which ions?
1) Chlorine
2) Bromide
3) Fluoride
79
Describe Phase I Hydrolysis Reactions? Which enzymes are involved?
Hydrolysis is a type of reaction that adds water to molecule, making it more water soluble.
Esterase (hydrolysis of ester bonds and amides (hydrolysis of amide bonds) can carry out hydrolysis reactions.
80
Are CYP 450 enzymes involved in hydrolysis reactions?
NO - CYP450 are never a part of hydrolysis reactions.
81
Describe what happens during Phase II Conjugation Reactions?
An endogenous substrate called a conjugating agent, which is highly polar, is attached either to the drug or a phase I metabolite via a covalent link to form a more water soluble, inactive substance that is easily excreted via the kidneys or bile.
82
3 examples of phase II conjugating agents?
1) Glucuronic Acid
2) Glutathione
3) Glycine
83
(T/F?) Conjugation reactions increase hydrophilicity, detoxification and excretion of drugs?
True
84
(T/F?) Conjugation reactions are synthesis reactions?
True - Something is added to the molecule
85
5 types of Phase II Conjugation reactions?
1) Glucuronidation - most common, and important metabolic pathway for propofol, morphine, and midazolam.
2) Acetylation
3) Glutathione
4) Sulfation
5) Methylation
86
Phase II reactions generally terminate the biological activity of the drug. What is one exception to this rule?
Morphine - Undergoes a gluconidation reaction to form the 6-glucuronide metabolite, which is a more potent opiod than morphine itself.
87
What are the 5 Phase II enzymes that carry out Phase II conjugation reactions?
1) UGT - the main Phase II enzyme located in the Endoplasmic Reticulum.
2) N-acetyltransfeases
3) Glutathione-S-transferases
4) Sulfotransferases (SULTs)
5) Methyltransferases
* All the phase 2 enzymes end with "transferase"
88
Describe the Cytochrome P-450 (MFO) System?
AKA the Mixed Function Oxidase (MFO) enzyme system, it is a group of more than 50 individual enzymes primarily located in the smooth ER in the liver. They are membrane bound, heme-containing microsomal enzymes responsible for the oxidation and reduction phase I metabolic reactions of drugs.
89
(T/F?) CYP 450 enzymes are also responsible for the the metabolism of dietary supplements, and synthesis of steroid hormones.
True
90
Which CYP450 enzyme is the most abundantly expressed in the liver?
CYP 3A4
91
What are CYP450 Inducers? Give examples of drugs?
CYP450 Inducers are drugs that stimulate the activity of CYP450 microsomal enzymes. i.e.
1) Rifampin
2) Phenobarbital
3) Phenytoin
4) Carbamazepine
5) St John's Wort
6) Cigarette Smoking
92
What are CYP450 inhibiters? Give examples of drugs?
CYP450 inhibiters are drugs that inhibit the activity of CYP450 microsomal enzymes. i.e.:
1) Amioderone
2) Diltiazem, Verapamil
3) Erythromycin
4) Alcohol
5) Cimetidine
6) Valproic Acid
7) Nefazodone, Fluozetine
8) Protease Inhibiters
93
What are Non-microsomal Enzymes?
Non-CYP450 enzymes found mostly in the liver that catalyze reactions responsible for drugs by conjugation and hydrolysis.
94
6 factors that affect the metabolism of drugs?
1) Pharmacogentic factors - most important because it affects absorption, distribution, metabolism and excretion.
2) Environmental factors
3) Age
4) Gender
5) Disease state
6) Induction or inhibition of enzyme metabolism by other drugs
95
Define Excretion?
The irreversible removal of a drug from the body
96
The 3 routes by which drugs and metabolites are excreted from the body?
1) Kidney - Via glomerular filtration and tubular secretion
2) Liver - Via biliary excretion
3) Pulmonary - Via exhalation
97
Define Clearance? What is the formula for clearance?
Clearance (aka drug elimination) is the volume of plasma or blood cleared of drug from the body in a given amount of time.
Cl = Vd x Kel
*Kel = elimination constant rate or fraction of drug lost
98
Why is clearance important?
Clearance describes the body's capacity to eliminate drug and can be used to determine the maintenance dose of a drug required to obtain a given steady state serum concentration.
99
Drug Clearance is composed of which 2 major processes?
1) Metabolism
| 2) Excretion
100
What are the determinants of hepatic clearance?
1) Hepatic blood flow (Q)
| 2) Hepatic extraction rate (ER)
101
How is hepatic clearance affect by protein binding and hepatic enzyme activity?
1) A decrease in protein binding will increase hepatic clearance.
2) An increase in enzyme activity will increase hepatic clearance.
102
What are the 3 processes by which a drug is cleared through the kidney?
1) Glomerular filtration
2) Active tubular transport
3) Passive tubular reabsorption
103
Where in the renal system do the following processes take happen:
1) Filtration of unbound drug
2) Tubular secretion of drug
3) Tubular reabsorption of drug
1) Filtration of unbound drug - Glomerulus
2) Tubular secretion of drug - Proximal tubule
3) Tubular reabsorption of drug - Distal tubule
104
Give an example of a drug that is highly susceptible to passive tubular reabsorption?
Sodium Thiopental - A highly lipid-soluble agent that is reabsorbed from the nephron - minimal unchanged drug is excreted in the urine.
105
2 factors the affect passive tubular reabsorption?
1) Rate of renal tubular urine flow
| 2) pKa of the drug and the pH of the fluid in the renal tubule (pH~ 5 to 8).
106
How is the rate of excretion of weak acids and weak bases affected by the pH of urine?
1) Weak acids are excreted faster in alkaline urine since the ionized form of the drug predominates and cannot cross the renal tubular membrane.
2) Weak bases are excreted faster in acidic urine since the ionized form of the drug predominates and cannot cross the renal tubular membrane.
107
What is the formula for Cockcroft-Gault's equation? what is its significance?
Cr = {[(I40-age) x IBW] / 72 x Serum creatinine} x .85 for females only
It is used to calculate GFR.
108
Define Enterohepatic circulation?
The cycle in which the drug is absorbed, excreted into the bile, and then reabsorbed in the intestines.
109
How might enterohepatic circulation prolong the pharmacological effects of certain drugs?
a drug that is excreted in bile may be reabsorbed in the GI tract or a drug conjugate may be hydrolyzed by gut bacteria, liberating the original drug which can be returned to general circulation.
110
Give 2 examples of drugs that undergo enterohepatic circulation?
1) Morphine
2) Diazepam
3) Hormones
4) Birth Contol
111
4 Determinants of tissue uptake of drugs?
1) Blood flow
2) Concentration gradient
3) Blood brain barrier
4) Physiochemical properties of drug (i.e. ionization, lipid solubility and protein binding)
112
4 Determinants of the capacity of tissue to store drugs?
1) Lipid solubility
2) Tissue mass
3) Binding to macromolecules
4) pH of the tissue
113
Define Elimination Half-life
The time necessary for the serum (plasma) concentration to decrease by 50% AFTER absorption and distribution.
114
How is Elimination Half-Life related to Volume of Distribution and Clearance?
Elimination half-life is proportional to volume of distribution and inversely proportional to clearance
115
Elimination half-life is clinically useful for the estimation of what?
1) Time needed to reach steady state
2) An appropriate dosing interval
3) Time required for drug removal from the body after the drug is no longer being administered
116
(T/F?) Elimination half-life is NOT clinically reliable for anesthetic drugs?
True
117
How is Elimination half-life (t1/2) calculated?
```
t1/2 = 0.693/Kel; or t1/2 = (0.693 Vd) / Cl
*Cl = clearance
```
118
Define Steady State?
Steady State is when the rate of drug administration equals the rate of drug clearance.
Steady State is achieved at 4 to 5 t1/2 from the time the dosage regiments started for first order kinetic drugs?
119
Define Context-Sensitive Half-time?
The time necessary for the plasma drug concentration to decrease by 50% after discontinuing a continuous infusion of a specific duration.
120
The Context-Sensitive Half-time reflects the combined effects of which 3 parameters of drug disposition?
1) Distribution
2) Metabolism
3) Duration of continuous IV administration
121
Define Zero-order Kinetics?
Zero-order kinetics says that the elimination rate of a drug is independent of time or concentration. This happens because enzymes or transporters responsible for metabolization become saturated.
122
Define First order Kinetics?
First-order kinetics says that the rate of elimination of a drug depends on the drug's plasma concentration. The greater the concentration the greater the rate of elimination. Refers to the elimination of a constant FRACTION or PERCENTAGE of drug per unit of time.
123
(T/F?) All CYP450 enzymes are Phase I enzymes?
True
124
Examples of phase I enzymes besides CYP450?
```
Amidases
Esterase
Epoxide Hydrolyses
Alcohol Dehydrogenases
FMOs
```
125
Where are the enzymes systems involved in phase I reactions primarily located?
In the Endoplasmic Reticulum of the liver
126
How is morphine and meperidine metabolized in the body?
They undergo oxidative n-demethylation reaction to become normorphine and normeperidine in the body.
127
Where do all Phase II reactions occur in the Body?
In the Cytosol
128
While CYP450 enzymes are mainly located in the Liver, where else are they located.
Technically all over the body, but specifically in the small intestines, kidneys, brain and lungs.
129
(T/F?) Non-Microsomal enzymes cannot be induced or inhibited?
True
130
Examples of drugs that have a high hepatic extraction rate ( ER > 0.7)?
Lidocaine
Propofol
Propranolol
131
Terms that suggest that a drug has a high hepatic extraction rate?
Perfusion dependent elimination
| Flow Limited
132
What value of ER suggests that a drug has a low hepatic extraction rate?
ER < 0.3
133
Term that suggest that a drug has a low hepatic extraction rate? give an example of a drug with a low ER?
"Capacity dependent Elimination" i.e. alfentanil
134
Define Pharmacokinetic Models?
Describes a drug's fate in the body and how its effects are distributed throughout the body. Usually separated into compartment models.
135
(T/F?) You can only use the Vd = Dose/Conc formula for drugs that follow a one-compartment model form of distribution?
True
136
For a drug that follows a Two-compartment model, what are the two compartment being referred to?
1) Central compartment
| 2) Peripheral compartment
137
In a two-compartment model, how does the drug Tavel in the body between compartments?
1) The drug is introduced and distributes rapidly in the blood stream and highly perfused organs (i.e. heart , brain) - Central Compartment
2) Then slow distributes to the less well perfused body tissues - peripheral compartment
3) Drug then moves back and forth between compartments to maintain equilibrium , then returns to central compartment for clearance.
138
What are the two phases of the Two-Compartment Model?
1) Distribution or Alpha Phase - Rapid movement of drug from plasma to tissues.
2) Elimination or Beta phase - Decline of plasma concentration driven by the elimination of the drug.
139
Describe the difference between the grafts or the curves of the One-compartment model and the two-compartment model?
1) One compartment mode curve is a straight downward sloping line.
2) Two-compartment model curve looks like an upside-down hockey stick.
140
For a two-compartment model drug, you must draw half-life concentrations from plasma in which phase?
Elimination or Beta phase
141
Examples of Zero order eliminated drugs?
Aspirin, alcohol, phenytoin, heparin, warfarin, and theophylline
142
All Phase II reactions occur in the cytosol, except for which one? where does it occur instead?
Glucoronidation, which occur in the Endoplasmic Reticulium
143
Clearance is directly proportional to what?
1) Blood flow to the clearing organ
2) Extraction Ratio
3) Drug dose
144
Clearance is inversely proportional to what?
1) Half life
| 2) Drug concentration on the central compartment
145
Steady State is achieved after how many Half-lives?
5
146
Flow limited Elimination vs. Capacity limited Elimination?
1) Flow Limited Elimination - For drugs with a high ER (>0.7), clearance is dependent upon liver blood flow. high blood flow = high clearance and vice versa.
2) Capacity Limited Elimination - For drugs with a low ER (<0.3), clearance is dependent on liver enzyme activity. Since only a small amount of the drug is being removed per unit of time, alterations in liver blood flow won't affect clearance as much. Clearance is dependent on induction or inhibition of enzymes that will metabolize the drug.
147
(T/F?) The GREATER the pKa of the weak base drug, the GREATER the proportion of drug is in
the ionized form at physiologic pH=7.4. (and vice versa)
True
148
Organize the following drugs from longest context sensitive half time to the shortest:
1) Fenanyl
2) Thiopental
3) Midazolam
4) Alfentanil
5) Sufentanil
6) Propofol
1) Fenanyl
2) Thiopental
3) Midazolam
4) Alfentanil
5) Sufentanil
6) Propofol
149
(T/F?) Ephedrine is a weak base?
True
150
(T/F?) Thiopental and Methohexital are weak acids?
True
151
What can be used to acidify the urine so the body will excrete basic drugs?
Cranberry juice and ammonium chloride
152
What can be used to make the urine alkaline so the body will excrete acidic drugs?
Acetazolamide (diamox) or bicarb
