PRELIM 02 - Pharmacokinetics Flashcards
(197 cards)
1
Q
Refers to any set of physical properties whose value determine the pharmacokinetic characteristics or behavior of the drug
A
Pharmacokinetic parameters
2
Q
Absorption (Pharmacokinetic parameter)
A
Bioavailability
3
Q
Distribution (Pharmacokinetic parameter)
A
Volume of distribution
4
Q
Metabolism and excretion (2 pharmacokinetic parameters) (HC)
A
Half-life, Clearance
5
Q
An organelle is that semipermeable; follows the fluid mosaic model
A
Cell membrane
6
Q
A double layer of amphiphilic phospholipids; found in the cell membrane
A
Lipid bilayer
7
Q
Proteins that span the cell membrane
A
Integral proteins
8
Q
Proteins that are attached to the cell membrane; modules function of integral proteins
A
Peripheral proteins
9
Q
Refers to spontaneous movement of molecules across a concentration gradient; no energy required
A
Diffusion/Passive transport
10
Q
Refers to transport of molecules against a concentration gradient; requires energy
A
Active transport
11
Q
Diffusion through the cell membrane or between cells; major process for transport of most drugs (Types of diffusion)
A
Simple diffusion
12
Q
2 types of simple diffusion (TP)
A
Transcellular, Paracellular
13
Q
Most drugs that undergo transcellular diffusion through the lipid bilayer are __________, __________, and __________ (HUN)
A
Hydrophobic, Unionized, Nonpolar
14
Q
Done by carrier proteins; saturation may occur (Types of diffusion)
A
Facilitated diffusion
15
Q
Glucose, and vitamins B1, B2, and B12 undergo __________ diffusion
A
Facilitated
16
Q
Transport that is carrier-mediated and is accompanied by an energy-producing process
A
Active transport
17
Q
Moves substances by using energy produced by ATP hydrolysis; pumps coupled to ATPase (Types of active transport)
A
Primary active transport
18
Q
Moves substances by using kinetic energy from the concentration gradient established by primary active transport (Types of active transport)
A
Secondary active transport
19
Q
5-fluorouracil, methyldopa, levodopa, methotrexate, and iron salts undergo __________ transport
A
Active
20
Q
Transport the involves vesicles and requires energy
A
Vesicular transport
21
Q
Engulfment by the cell membrane of particles larger than 500 nm (Types of endocytosis)
A
Phagocytosis
22
Q
Polio and other vaccines undergo __________ (Types of endocytosis)
A
Phagocytosis
23
Q
Engulfment of small droplets of extracellular fluid by membrane vesicles (Types of endocytosis)
A
Pinocytosis
24
Q
Vitamins A, D, E, K undergo __________ (Types of endocytosis)
A
Phagocytosis
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Receptors on cell surfaces bind with ligands to form ligand-receptor complexes on cell surfaces (Types of endocytosis)
Receptor-mediated endocytosis
26
The material internalized by the membrane domain is transported through the cell and secreted on the opposite side (Types of endocytosis)
Transcytosis
27
Refers to the movement of solvent from a less concentrated solution to a more concentrated solution through pores
Osmosis
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Refers to the movement of small molecules with the solvent during osmosis
Solvent drag
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Water, sugars, and urea undergo __________ and __________ (SO)
Solvent drag, Osmosis
30
Transport wherein oppositely charged molecules interact and form a neutral complex
Ion-pair transport
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Quaternary ammonium compounds and sulfonic acids undergo __________ transport
Ion-pair
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Refers to the process of movement of unchanged drug from the site of administration to systemic circulation
Absorption
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Effects that involves the metabolism of drug before it reaches the circulation
First pass effect
34
Intestinal metabolism is due to __________ enzymes (mainly CYP3A4)
CYP450
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Primary site of drug metabolism
Liver
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A measure of the extent to which the drug reaches the systemic circulation following administration by any route
Bioavailability (F)
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Compares the amount of the active drug reaching the systemic circulation following extravascular administration with the amount of the same drug following intravenous administration (Types of bioavailability)
Absolute bioavailability
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Compares the amount of the active drug reaching the systemic circulation following administration of a test formulation with the amount of the same drug following administration from a reference formulation (Types of bioavailability)
Relative bioavailability
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A measure that compares the bioavailability of multisource drug products with the innovator drug product
Bioequivalence
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Drug products that contain the same active drug substance; marketed by more than one pharmaceutical manufacturer; examples include generic drug products
Multisource drug products
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Drug products that are marketed as new chemical entities
Innovator drug products
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Means that there is no clinically significant difference in bioavailability
Bioequivalent
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Bioavailability and bioequivalence testing may be __________ or __________ (II)
In vivo, In vitro
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Refers to the maximum concentration of drug in the plasma
Peak plasma concentration (Cmax)
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Unit of peak plasma concentration (Cmax)
mcg/mL
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Refers to the time for a drug to reach peak plasma concentration after administration
Time of peak concentration (Tmax)
47
Unit of time of peak concentration (Tmax)
Hours
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Refers to the total integrated area under the plasma drug concentration-time profile
Area under the curve (AUC)
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Unit of area under the curve (AUC)
mcg-h/mL
50
Refers to the minimum concentration of drug in the plasma required to produce the therapeutic effect
Minimum effective concentration (MEC)
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The level of plasma drug concentration below MEC
Subtherapeutic level
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Refers to the minimum concentration of drug in the plasma that produces adverse or unwanted effects
Minimum toxic concentration (MTC) or Maximum safe concentration (MSC)
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The time required for the drug to start producing pharmacologic response
Onset of action
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F=1 by definition (Route of administration)
Intravenous
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0.75 < F < 1 (2 routes of administration) (SI)
Subcutaneous, Intramuscular
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0.05 < F < 1 (Route of administration)
Oral ingestion
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Bioavailability is complete (F=1); distribution is rapid (Route of administration)
Intravenous (IV)
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The rate of absorption via simple diffusion is constant and slow to provide a sustained effect (Route of administration)
Subcutaneous (SC)
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Drugs can be in aqueous solutions (absorbed rapidly) or in specialized depot preparations (absorbed slowly) (Route of administration)
Intramuscular (IM)
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A drug is injected directly into an artery to localize its effect in a particular tissue or organ (Route of administration)
Intra-arterial (IA)
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Produces local and rapid effects of drugs on the meninges or cerebrospinal axis (Route of administration)
Intrathecal
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Access to the circulation is rapid by this route because the lung's surface area is large (Route of administration)
Inhalational
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It achieves a local and direct effect (Route of administration)
Topical
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This route is most often used for the sustained delivery of drugs (Route of administration)
Transdermal
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It is the safest and most common, convenient, and economical method of drug administration (Route of administration)
Oral (PO)
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Venous drainage from the mouth is to the superior vena cava, bypassing the portal circulation (Route of administration)
Sublingual (SL)
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Approximately 50% of the drug that is absorbed from the rectum will bypass the liver (Route of administration)
Rectal
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pH range of the stomach
pH 1-3.5
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pH range of the small intestine
pH 6-7.5
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According to this theory, the unionized form of an acidic or basic drug, if sufficiently lipid soluble, is absorbed but the ionized form is not
pH partition theory
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The higher the surface area, the __________ the extent and rate of absorption
Greater
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Most drugs are absorbed in the __________ because of its large surface area and gradually changing pH
Small intestine
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Refers to the distribution of the drug into interstitial and intracellular fluids
Distribution
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A __________ is not a real physiologic or anatomic region but is considered a tissue or group of tissues that have similar blood flow and drug affinity
Compartment
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The body is a single homogenous compartment; most drugs follow this model (Types of compartment models)
One-compartment model
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Its subtypes include central compartment and tissue compartment (Types of compartment models)
Two-compartment model
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Includes the blood and highly perfused lean organs such as the heart, brain, liver, lung, and kidneys (Types of two-compartment models)
Central compartment
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Includes the slowly perfused tissues such as muscle, skin, fat, and bone (Types of two-compartment model)
Tissue compartment
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Refers to the measure of the apparent space in the body available to contain the drug
Volume of distribution (Vd)
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Humans are ___________% water
60%
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The Vd of the plasma compartment for a 70 kg man or 6% of body weight is __________ L
4
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Drugs with ___________ are too large to move out through the endothelial slit junctions and are effectively trapped within the plasma compartment
Very large molecular weight
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The Vd of the extracellular fluid for a 70 kg man or 20% of body weight is __________ L
14
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In extracellular fluid, drugs with low molecular weight and are __________ can move through the endothelial slit junctions of the capillaries into the interstitial fluid
Hydrophilic
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The Vd of the total body water for a 70 kg man or 60% body weight is __________ L
42 L
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In total body water, drugs with low molecular weight and are __________ can move into the interstitium through the slit junctions
Hydrophobic
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Small water-soluble molecules: eg, ethanol (Fluid compartment in the body)
Total body water
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Larger water-soluble molecules: eg, gentamicin (Fluid compartment in the body)
Extracellular fluid/water
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Larger protein molecules: eg, antibodies (Fluid compartment in the body)
Plasma compartment
90
Highly lipid-soluble molecules: eg, diazepam (Fluid compartment in the body)
Fat
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Certain ions: eg, lead, fluoride (Fluid compartment in the body)
Bone
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Refers to the volume of blood that circulates in the cardiovascular system and reaches different organs and tissues in the body per unit of time
Blood flow
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Unit of blood flow
mL/min
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Refers to the amount of xenobiotic that can be stored or distributed in a tissue that depends on the mass of tissue or size of organ
Tissue size
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Refers to the distribution of a compound in a region of the body that depends on the blood flow to that region
Tissue perfusion
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Refers to the diffusion of drug into extravascular tissues
Tissue diffusion
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Are proteins that are neutral molecules and are highly lipophilic
Lipoproteins
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Are proteins that are acidic/weakly acidic compounds in ionized form with moderate or marked lipophilicity
Albumin
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Are proteins that are ionized, basic compounds with moderate lipophilicity
α-1-acid glycoprotein (AGP)
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Phenytoin, salicylates, phenylbutazone, disopyramide, and penicillins bind to ___________
Albumin
101
Propanolol, saquinavir, imipramine, quinidine, and lidocaine bind to ____________
α-1-acid glycoprotein (AGP)
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Chlorpromazine binds to ___________
Lipoproteins
103
Happens when drugs with the same binding site compete for interaction
Drug displacement
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Refers to a barrier composed of tight junctions of endothelial cells of cerebral capillaries; drug distribution is highly regulated and limited here
Blood-brain barrier (BBB)
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Cells that form a solid envelope around the brain capillaries
Astrocytes
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Most antibiotics like __________ cannot penetrate the blood-brain barrier (BBB)
Penicillins
107
One must use ___________ for parkinsonism instead of dopamine
Levodopa
108
A barrier that is not effective as the blood-brain barrier (BBB)
Placental barrier
109
Many drugs such as ethanol, sulfonamides, barbiturates, gaseous anesthetics, and some antibiotics cross the placental barrier by __________
Simple diffusion
110
Nutrients for fetal growth such as glucose, amino acids, minerals, some vitamins, purines, and pyrimidines cross the placental barrier by __________
Carrier-mediated/Energy requiring process
111
Drugs such as thalidomide, phenytoin, isotretinoin, testosterone, and methotrexate show teratogenic effects during the __________, which is the stage where fetal organs develop
1st trimester
112
Refers to the conversion of drugs into more hydrophilic metabolites for elimination and termination of biological and pharmacological activity
Metabolism/Biotransformation
113
Primary organ for drug metabolism
Liver
114
Lungs, kidneys, intestine, placenta, adrenals, and skin are organs that perform __________ metabolism
Extrahepatic
115
Are enzymes that are different from the enzymes that metabolize food
Drug metabolizing enzymes
116
Enzymes that metabolize the majority of drugs; catalyze oxidation, reduction, hydrolysis, and glucuronidation reactions (Types of drug metabolizing enzymes)
Microsomal enzymes
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Microsomes (fragments that contain microsomal enzymes) are derived from __________
Rough endoplasmic reticulum
118
Enzymes that include those that are present in the cytoplasm and those attached to the mitochondria but not to the RER (Types of drug metabolizing enzymes)
Non-microsomal enzymes
119
2 phases of metabolism
Phase I, Phase II
120
A polar functional group is introduced/unmasked on the otherwise lipid-soluble substrate; include oxidation, reduction, and hydrolysis (Phases of metabolism)
Phase I
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Products of Phase I metabolism
Primary metabolites
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A flavoprotein; contains FMN and FAD; a monooxygenase in Phase I metabolism
NADPH CYP450 oxidoreductase
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A hemeprotein; a monooxygenase in Phase I metabolism
Cytochrome P450 (CYP450)
124
Represents a superfamily of heme containing enzymes; involved in Phase I metabolism
Cytochrome P450 (CYP450)
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A member of the oxidoreductase family; present in high concentrations in the liver and kidney; involved in metabolism of alcohols (Other Phase I enzymes)
Alcohol dehydrogenase
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Metabolize aldehydes to less reactive forms (Other Phase I enzymes)
Aldehyde dehydrogenase
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Deamination of diamines not monoamines (Other Phase I enzymes)
Diamine oxidase (Histaminase)
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Metabolism of purine bases and hypoxanthine to xanthine and finally to uric acid (Other Phase I enzymes)
Xanthine oxidase (XOD)
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Catalyze the hydrolysis of a large number of structurally diverse esters, aides, thioesters, and carbamates in humans (Other Phase I enzymes)
Carboxylesterases (CES)
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Hydrolyze the peptide bonds of proteins and peptides (Other Phase I enzymes)
Peptidase (Protease/Proteinase)
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Small polar endogenous compounds are covalently attached to the unchanged drug or products of Phase I metabolism; involves conjugation or synthetic reactions (Phases of metabolism)
Phase II
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Enzymes involved in Phase II metabolism
Transferases
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Refers to the increased drug metabolizing ability of the enzymes by drugs and other substances
Enzyme induction
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The agent that brings about enzyme induction
Inducers
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Most inducers are __________ with long elimination half lives
Lipophilic
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Includes several drugs and pesticides (Types of inducers)
Phenobarbital type inducers
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Includes 3-methyl cholanthrene and cigarette smoke (Types of inducers)
Polycyclic hydrocarbon type inducers
138
Carbamazepine, meprobamate, cyclophosphamide, and rifampicin are capable of __________ or __________ (AS)
Auto-induction/Self-induction
139
Result from interaction at the enzymatic site, the net outcome being a change in enzyme activity (Type of enzyme inhibition)
Direct inhibition
140
Structurally similar compounds compete for the same site (Type of direct inhibition)
Competitive inhibition
141
A structurally unrelated compound interacts with the enzyme at a different site from the drug being metabolized (Type of direct inhibition)
Noncompetitive inhibition
142
Metabolic products compete with the substrate for the same enzyme (Type of direct inhibition)
Product inhibition
143
Involves decrease in enzyme content (Type of indirect inhibition)
Repression
144
Ethionine, puromycin, and actinomycin D results in __________
Decreased synthesis
145
CCl4, CS2, and disulfiram results in __________
Increased degradation
146
Involves nutritional deficiency or hormonal balance (Type of indirect inhibition)
Altered physiology
147
Metabolism is __________ related to volume of distribution (Vd)
Inversely
148
The microsomal enzyme system is not fully developed up to __________ months
2
149
__________ is well developed in newborns (e.g. sulfate conjugation of paracetamol)
Sulfation
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__________ is not developed in newborns (e.g. chloramphenicol in newborns lead to kernicterus and gray baby syndrome)
Glucuronidation
151
Infants _________ months to __________ year old have similar profile as neonates in metabolizing drugs with improvement as age advances and as enzyme activity increases
2 months - 1 year old
152
Children that are __________ to __________ years old metabolize several drugs faster than adults
1-12
153
In the __________, liver size is reduced, microsomal enzyme activity is decreased, and hepatic blood flow declines; overall metabolism is slow
Elderly
154
A __________ protein diet decreases metabolizing activity
Low
155
A __________ protein diet increases metabolizing activity
High
156
__________ alcoholism decreases enzyme activity
Acute
157
__________ alcoholism increases enzyme activity
Chronic
158
____________ disease leads to increased half life of drugs
Liver
159
__________ disease leads to decrease of glycine conjugation of salicylates, oxidation of vitamin D, and hydrolysis of procaine
Kidney
160
__________ and __________ leads to decreased blood flow to the liver and decreased metabolism (CM)
Congestive heart failure (CHF), Myocardial infarction (MI)
161
__________ leads to decreased UDPGA and glucuronidation
Diabetes
162
Refers to the removal of the drug from the body either as the unchanged drug or as a metabolite
Excretion
163
Principal organ of excretion
Kidneys
164
Basic unit of the kidneys
Nephron
165
3 steps in renal excretion (GTT)
Glomerular filtration, Tubular reabsorption, Tubular secretion
166
A nonselective, unidirectional process whereby most compounds, ionized or unionized, are filtered
Glomerular filtration
167
Refers to the volume of blood that is filtered per unit time
Glomerular filtration rate (GFR)
168
Glomerular filtration rate (GFR) is around __________% of renal blood flow
20%
169
Normal glomerular filtration rate
125 mL/min
170
A carrier mediated process which requires energy for transport of substances against a concentration gradient
Tubular secretion
171
Tubular secretion occurs primarily in the __________
Proximal tubule
172
Happens with endogenous substances that are needed by the body such as electrolytes, glucose, vitamins, amino acids, and uric acid (Types of tubular reabsorption)
Active tubular reabsorption
173
Happens with exogenous substances; driven by the concentration gradient established by back diffusion of water, sodium, and inorganic ions (Types of tubular reabsorption)
Passive tubular reabsorption
174
Clearance is __________ proportional to plasma drug concentration
Directly
175
Clearance is __________ related to volume of distribution
Inversely
176
Example of acidic drug
Penicillin
177
Example of basic drug
Gentamicin
178
Example of very weakly acidic, nonpolar drug (pKa >8)
Phenytoin
179
Example of very weakly basic, nonpolar drug (pKa <6)
Propoxyphene
180
Example of a strongly acidic drug (pKa≤2)
Cromoglycic acid
181
Example of a strongly basic drug (pKa≥12)
Guanethidine
182
Example of acidic drugs with pKa 3-8
NSAIDs
183
2 examples of basic drugs with pKa 6-12 (MT)
Morphine analogs, Tricyclic antidepressants
184
__________ causes hypertension, DM, hypovolemia, pyelonephritis, and buildup of nephrotoxic agents
Renal impairment
185
Function that can be determined by measuring the GFR
Renal function (RF)
186
Is exogenous and tedious; used to determine renal function (RF)
Inulin
187
Is endogenous and is the most widely used to determine renal function (RF)
Creatinine
188
Involves the measurement of serum creatinine
Creatinine clearance
189
Bile is synthesized in the __________
Liver
190
Bile is stored in the __________
Gallbladder
191
Bile is secreted in the __________
Duodenum
192
Rate of elimination is convenient because it is constant (Types of elimination)
Zero-order elimination
193
Rate of elimination changes with respect to drug plasma concentration (Types of elimination)
First-order elimination
194
Refers to the factor that predicts the rate of elimination in relation to the drug concentration
Clearance (CL)
195
Unit of clearance
Volume/time
196
Clearance of drug by several organs is __________
Additive
197
Refers to the time required to change the amount of drug in the body by one-half during elimination
Half-life (t1/2)
