Term
| What is the fraction of administered drug that reaches systemic circulation? |
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Definition
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Term
| What will the bioavailability of an IV be? |
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Definition
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Term
| What 4 factors influence bioavailabilit? |
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Definition
Solubility of drug
Chemical instability
Formulation
First-pass hepatic metabolism |
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Term
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Definition
| The binders or dispersing agents used in some drugs |
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Term
| If drugs contain the same active ingredients and are identicle in dose, dosage form, and route of administration then the drugs are said to be? |
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Definition
| Pharmaceutical equivalents |
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Term
| When 2 drugs have the same rate and extent of bioavailability of their active ingredients, which cannot be signifigantly diffent then these drugs are said to have? |
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Definition
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Term
| When 2 drugs have comparable efficacy and safety they are said to have? |
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Definition
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Term
| What 3 factors are drug distribution dependent upon? |
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Definition
Blood flow
Capillary permeability
Binding of drug to protein |
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Term
| Blood flow reflects what 2 things? |
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Definition
Cardiac output
Regional blood flow |
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Term
| What 4 organs recieve most of a drug once it has been absorbed? |
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Definition
Heart
Liver
Kidneys
Brain |
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Term
| What 4 places are not going to recieve drug quickly after being absorbed? |
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Definition
Muscle
Most viscera
Skin
Adipose
<all due to lack of vascularizaion compared to other organs> |
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Term
| Talking about capillary permeability, in the capillary structure of the liver and spleen what kind of junctions do they have? |
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Definition
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Term
| Talking about capillary permeability, the capillary structure of the blood brain barrier is made up of what kind of junctions? |
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Definition
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Term
| In Parkinson's Disease, we cannot give someone dopamine but instead give leodopa why is this? |
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Definition
| Dopamine is a charged cannot cross the blood brain barrier, but Levodopa depends upon the "neutral amino acid transporter" for brain entry |
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Term
| What are drug resivoirs and what do they have an impact on? |
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Definition
Body compartments that a drug can accumulate in
They have a dynamic effect on drug availability |
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Term
| What are 2 examples of drug resivoirs? |
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Definition
Plasma proteins<Albumin>
Cellular resivoirs<Adipose tissue and Bone> |
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Term
| A resivoir would have a _________ effect on some drugs. |
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Definition
| Pharmacokinetic <body on drug> |
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Term
| What type of transport of drugs across biological membranes is influenced by protein binding? |
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Definition
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Term
| Binding may occur at what 3 places? |
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Definition
Plasma proteins
Non-specific tissue proteins
Drug's receptors |
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Term
| Only a drug that is _________ to proteins can diffuse across membranes. |
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Definition
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Term
| Talking about drug binding in plasma proteins, Albumin can bind what? |
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Definition
Weak acids
Hydrophobic drugs |
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Term
| Talking about drug binding to plasma proteins, α1-acid glycoprotein can bind what? |
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Definition
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Term
| Talking about drug binding to plasma protein, is the binding reversible/irreversible and selectiv/nonselective? |
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Definition
| Reversible & Nonselective |
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Term
| The fraction of total drug in plasma that is bound is determined by what 3 factors? |
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Definition
Drug concentration
Drug affinity for binding sites
Number of binding sites |
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Term
| At low concentration, binding is a function of what? |
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Definition
| Kd, or affinity of drug to the binding site |
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Term
| At high concentration, binding is a function of what? |
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Definition
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Term
| What class of drugs have a low dose/capacity<most drug is bound> level? |
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Definition
Class I Drugs
ex. Warfarin, only 3% of drug is free for use |
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Term
| What class of drugs have a high dose/capacity<all sites occupied and most drug is free> level? |
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Definition
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Term
| What 4 drugs primarily bind to Albumin? |
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Definition
Bilirubin (class I)
Warfarin (class I)
Sulfonamides (class II)
Tetracycline (class II) |
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Term
| What drug primarily binds to α1-acid glycoprotein? |
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Definition
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Term
| What drug is readily stored in fat and acts as a short-lived anesthetic? |
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Definition
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Term
| Termination of drug action occurs as a result of what? (Particularly true for lipid-soluble drugs that affect brain and heart) |
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Definition
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Term
| Why do you want to avoid giving pregnant women and young children tetracycline antibiotics? |
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Definition
| They are ADSORBED into the bone crystal surface and become incorporated as rings into the teeth. |
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Term
| True/False: Bone can become a resivoir for slow release of toxic agents (e.g. lead, radium) and release these back into the blood. |
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Definition
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Term
| Drugs cross the placental barrier primarily by simple passive diffusion, 2 types of drugs that readily enter the fetal bloodstream from maternal ciculation are? |
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Definition
Lipid-soluble drugs
Nonionized drugs |
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Term
| Rates of drug movement across the placenta tend to increase/decrease towards term as the tissue layer between maternal blood and fetal capillaries thin. |
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Definition
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Term
| _________ are passively concentrated in the stomach from the blood because of the large pH differential. |
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Definition
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Term
| True/False: The GI tract can serve as a reservoir. |
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Definition
| TRUE; some drugs are excreted in the bile in active form or as conjugates that can be hydrolyzed in the intestine and reabsorbed |
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Term
| What is the equation for volume distribution (Vd)? |
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Definition
Vd=(total amount of drug)/(Concentration of drug in plasma)
Vd=D/Cp |
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Term
| In a 70Kg person what is the total amount of body water? |
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Definition
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Term
| The plasma compartment is how many liters? and drugs that get trapped there exhibit what 2 characteristics? |
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Definition
4Liters
Large molecular weight
Extensive protein binding |
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Term
| What makes up the extracellular fluid compartment? how many liters is it? and drugs that show up there have what 2 characteristics? |
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Definition
Includes plasma compartment and all fluid outside of cells
14Liters
Low molecular weight & Hydrophilic
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Term
| What makes up the intracellular compartment? how many liters is it? drugs found there must exhibit what 2 characteristics? |
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Definition
all the fluid within all the cells
28Liters
Low molecular weight & hydrophobic |
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Term
| Assuming complete bioavailability, steady-state will be achieved when? |
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Definition
The rate of drug elimination=the rate of administration &
when Vd=D/Cp |
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Term
| What are some things that may lead to volume distribution varying widely? |
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Definition
pKa of drug
Drug's degree of plasma binding
Drug's lipid solubility
Drug's binding to other tissues
Patient
Age
Gender
Disease(s) |
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Term
| In relation to volume of distribution (Vd) and plasma concentration (Cp), the smaller the Vd the ______plasma concentration |
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Definition
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Term
| In relation to volume of distribution (Vd) and plasma concentration (Cp), the larger the Vd the ________plasma concentration. |
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Definition
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Term
| Digoxin is hydrophobic and distributes preferentially to muscle and fat leaving very little drug in plasma, therefore the digoxin dose required therapeutically depends on what? |
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Definition
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Term
| What is the ultimate goal of metabolism and elimination? |
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Definition
| Make compounds more water soluble to allow excretion by kidneys |
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Term
| What order of kinetics metabolizes a FRACTION of the drug per unit time? |
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Definition
| First-Order Kinetics; the rate of drug metabolism is directly proportional to the free drug concentration |
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Term
| What order of kinetics metabolizes a CONSTANT AMOUNT of drug per unit time? |
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Definition
| Zero-Order Kinetics; the rate of drug metabolism remains constant |
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Term
| Where are cyctochrome P450 mixed function oxidases (MFOs) found? |
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Definition
| Smooth endoplasmic reticulum in the liver |
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Term
| What are some functions of cytochrome P450 mixed function oxidases (MFOs)? |
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Definition
Hydroxylations
N-, O-, S-dealkylations
Deamination
Desulfuration
Dehalogenation |
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Term
| What are some requirements of cytochrome P450 mixed function oxidases (MFOs)? |
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Definition
Oxygen
NADPH
Hemoprotein
reductase (Flavoprotein) |
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Term
| True/False: Cytochrome P450 mixed function oxidases (MFOs) are susceptible to induction. |
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Definition
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Term
| Families of cytochrome P450 enzymes (CYPs) are based on what similarities? |
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Definition
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Term
| What CYP metabolizes 40% of all drugs? |
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Definition
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Term
| Important information pertaining to mechanism of drug oxidation in the cytochrome P450 cycle. |
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Definition
| Parental drug enters with an attached -H and leave the cycle with a -OH which makes the drug water soluble and the cycle needs Fe to work |
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Term
| What causes increase in cytochrome enzyme syntheses fo the MFO system? |
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Definition
| INDUCTION (ex. sedatives, tranquilizers, analgesics, some antihistamines) |
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Term
| What causes a decrease in cytochrome activity of existing enzyme of the MFO system? |
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Definition
| INHIBITION (ex. cimetadine--antihistamine, secobarbital) |
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Term
| When adding a water soluble molecule to a parental drug via glucuronidation, glutathion, amino acid, sulfate, acetylation, or methylation, this is know as what? |
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Definition
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Term
| Elimination of a large fraction of drug during first passage through gut wall and then through liver is know as? |
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Definition
First Pass Effect
(ex. nitroglycerin, propranolol, imipramine acetylsalicylic acid) |
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Term
| The first-pass effect occurs when there is a high ______ ratio. |
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Definition
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Term
| TRUE/FALSE: The first-pass effect is an unsaturable process. |
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Definition
| FALSE, the system can be saturated |
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Term
| Drug elimination in the form of metabolism takes place where? |
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Definition
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|
Term
| Drug elimination in the form of excretion takes place where? |
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Definition
Kidneys
Liver (bile)
Lungs |
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Term
| In renal excretion of drugs filtration takes place where? |
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Definition
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|
Term
| In renal excretion reabsorption via passive transport happens where? |
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Definition
| Proximal & Distal Tubules |
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|
Term
| In renal excretion secretion via active transport happens where? |
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Definition
| Proximal Tubule; both organic acids and bases are filtered and protein binding has no effect on this process |
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Term
| TRUE/FALSE: In glomerular filtration only bound drug is filtered. |
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Definition
| FALSE, only unbound drug is filtered, plasma protein binding of drug prevents filtration (ex. thyroxine 99% is bound so continually recycled) |
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Term
| What can be used to estimate glomerular filtration rate (GFR)? |
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Definition
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Term
| In the distal tubular reabsorption, passive transport depends on what 5 factors? |
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Definition
pH
Concentration
Size
Lipid solubility
Ionization |
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Term
| In distal tubular reabsorption acid urine favors reabsorption of weak _________? |
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Definition
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|
Term
| In distal tubular reabsorption basic urine favors reabsorption of weak ______? |
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Definition
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|
Term
| The net of filtration, reabsorption, and secretion depends on what? |
|
Definition
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|
Term
| What is the equation for clearance (CL)? |
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Definition
| CL=([drug] in urine x Urinary Blood Flow)/[drug] in plasma |
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Term
|
Definition
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|
Term
|
Definition
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|
Term
| What 3 things are secreted into the bile for excretion? |
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Definition
Organic acids
Organic bases
Some drugs
(ex. glucuronides of steroids and morphine) |
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Term
| What 3 factors effect pulmonary excretion? |
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Definition
Plasma solubility of drug
Cardiac output
Respiration |
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Term
| What factors could lead to normal dose regimen becoming toxic or decrease the overall effectiveness? |
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Definition
Age (with age comes decrease renal/hepatic metabolism)
Renal disease
Liver disease
Drug Interactions |
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Term
| A drug has a low therapeutic index when renal function drops below what? |
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Definition
| 50% of normal adult value |
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Term
| Liver diseases such as parenchymal liver disease, hepatic profusion, and cirrhosis affect drugs with high/low extraction ratios? |
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Definition
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|
Term
| In liver metabolism what drug enhances via induction the overall metabolism? |
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Definition
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|
Term
| In liver metabolism what drug directly inhibits overall metabolism? |
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Definition
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|
Term
| In renal tubular secretion what drug inhibits secretion of weak acids? |
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Definition
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|
Term
| In renal tubular secretion what drug inhibits secretion of weak bases? |
|
Definition
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|
Term
| In drugs with first pass elimination by CYP3A4 why should you not take them with grapfruit juice? |
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Definition
| Grapefruit juice inhibits the metabolism by CYP3A4 which metabolizes 40% of all drugs passing through |
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Term
|
Definition
| The volume of blood cleared of drug per unit time |
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|
Term
| What is the equation for loading dose? |
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Definition
| Loading Dose= (Concentration of drug in plasma wanted) x (Vd) |
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Term
| What is the equation for calculating Concentration of Drug in plasma needed? |
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Definition
| Plasma concentration needed= (drug dose) / (Vd) |
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Term
| Some drugs switch from zero-order to first-order as plasma levels fall, these are known as what? |
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Definition
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Term
| The time required to change the amount of drug in the body by 1/2 during elimination is known as? |
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Definition
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