What is the definition of pharmacokinetics?
The study of the time course of drug absorption, distribution, metabolism, and excretion.
What does pharmacodynamics refer to?
The relationship between drug concentration at the site of action and the resulting effect, including time course and intensity of effects.
What is the therapeutic index?
The ratio between the effective dose (ED50) and the lethal dose (LD50) of a drug.
What is bioavailability?
The proportion of a drug that enters the circulation when introduced into the body and is available for action.
What is the difference between agonist and antagonist?
An agonist activates a receptor to produce a biological response, while an antagonist blocks or dampens that response.
What is the first pass effect?
The metabolism of a drug within the liver before it reaches systemic circulation.
What is a pro-drug?
A medication that is administered in an inactive form and is metabolized into an active form within the body.
What are Phase I reactions in hepatic metabolism?
Reactions that involve the modification of the drug molecule, often through oxidation, reduction, or hydrolysis.
What are Phase II reactions in hepatic metabolism?
Reactions that involve conjugation of the drug to form a more water-soluble compound for excretion.
What is clearance in pharmacokinetics?
The volume of plasma from which a substance is completely removed per unit time.
What is the significance of p450 enzymes?
They play a crucial role in the metabolism of many drugs and can affect drug interactions.
What does steady state mean in pharmacokinetics?
The condition where the overall intake of a drug is equal to its elimination, resulting in a stable concentration.
What factors affect drug absorption?
Ionization, polarity, membrane transporters, environmental pH, and lipid solubility.
What is the loading dose?
A higher dose of a drug given initially to quickly achieve the desired drug concentration in the body.
What is the difference between first order and zero order elimination?
First order elimination is concentration-dependent, while zero order elimination occurs at a constant rate regardless of concentration.
What is the importance of ionization in drug pharmacokinetics?
It affects drug solubility and permeability across cell membranes, influencing absorption and distribution.
What is an agonist?
A compound that binds to a receptor and causes it to carry out a function.
What is a partial agonist?
Binds to the receptor and causes a function but with a smaller effect than a full agonist.
What does an antagonist do?
Binds to a receptor and stops it from carrying out a function.
What is the difference between competitive and non-competitive antagonists?
Competitive antagonists can be overcome by increasing the dose of agonist; non-competitive antagonists cannot.
What does ED50 represent?
Dose at which 50% of subjects exhibit a therapeutic response.
What does LD50 indicate?
Dose at which 50% of subjects die.
What is the therapeutic index (TI)?
The ratio of a drug's LD50 to its ED50; reflects a drug's safety.
What does efficacy refer to in pharmacology?
The maximal response that a drug can produce.
What is potency?
A measure of the dose required to produce a response.
What is bioavailability (F)?
The fractional extent to which an administered dose of drug reaches the site of action or biological fluid.
What factors affect absorption of oral medications?
What is the relationship between pharmacokinetics and pharmacodynamics?
Pharmacokinetics describes how the body affects a drug, while pharmacodynamics describes how the drug affects the body.
What does bioavailability refer to?
The amount of drug that is absorbed after administration compared to that absorbed after IV administration.
What is the bioavailability of IV administration?
100% bioavailability.
What is Fick’s Law of Diffusion?
Rate = (C1 - C2) x area x permeability coefficient / thickness of the diffusion path.
What increases drug absorption?
Larger surface area and thinner membranes.
What is the effect of pH on weak acids?
When pH < pK, the protonated (unionized) form predominates; when pH > pK, the unprotonated (ionized) form predominates.
What type of drug is better absorbed in the stomach (pH = 2)?
Weak acid drug.
What type of drug is better absorbed in the intestine (pH = 8)?
Weak base drug.
What is the impact of environmental pH on drug diffusion?
Low pH & weakly acidic drug increases unionization; high pH & weakly basic drug also increases unionization.
What is the molecular weight limit for drugs?
Most drugs are 100-1000 Daltons; >100 daltons to bind to a receptor, <1000 daltons to diffuse across membranes.
What prevents drugs from passing through the blood-brain barrier?
Tight junctions between cells in CNS capillaries prevent drugs from passing between cells.
What is the One Compartment Model in pharmacokinetics?
It describes drug distribution and elimination using a single compartment for the entire body.
What does the Two Compartment Model represent?
It describes drug distribution and elimination using central and peripheral compartments.
In the One Compartment Model, X0 = _______, X1 = _______, K = _______.
In the One Compartment Model, X0 = dose of drug, X1 = amount of drug in body, K = elimination rate constant.
In the Two Compartment Model, X0 = _______, X1 = _______, X2 = _______.
In the Two Compartment Model, X0 = dose of drug, X1 = amount of drug in central compartment, X2 = amount of drug in peripheral compartment.
What does X0 represent in the Two Compartment Model?
Dose of drug
What does X1 represent in the Two Compartment Model?
Amount of drug in central compartment
What does X2 represent in the Two Compartment Model?
Amount of drug in the peripheral compartment
What is the elimination rate constant denoted as?
K
What is the definition of Volume of Distribution (V)?
Hypothetical volume representing the space a drug distributes into.
What is the formula for concentration of drug?
C = dose / Vd
What is the effect of plasma protein binding on drug distribution?
Only unbound (free) drug can diffuse into tissues.
Which protein is the most important for drug binding in plasma?
Albumin
What characterizes zero-order kinetics?
Constant amount of drug eliminated per unit time.
What characterizes first-order elimination?
Amount eliminated depends on the current drug amount in the body.
What is the formula for half-life?
T ½ = 0.693/K
What does K represent in first-order kinetics?
Elimination rate constant (1/time)
What does the slope represent in the context of drug concentration over time?
Rate change (K)
The Volume of Distribution (V) can be thought of as a beaker representing the space a drug distributes into. For example, one beaker represents a patient with a small volume of distribution of _______ and another with a larger volume of _______.
The Volume of Distribution (V) can be thought of as a beaker representing the space a drug distributes into. For example, one beaker represents a patient with a small volume of distribution of 10 L and another with a larger volume of 100 L.
In zero-order kinetics, the same amount of drug is eliminated from the body at a constant rate, whereas in first-order elimination, the amount eliminated is dependent on the amount of drug in the body at that time, with a constant _______ of drug lost per unit time.
In zero-order kinetics, the same amount of drug is eliminated from the body at a constant rate, whereas in first-order elimination, the amount eliminated is dependent on the amount of drug in the body at that time, with a constant % of drug lost per unit time.
The formula for the slope of a line in pharmacokinetics is given by _______, where m represents the change in concentration over the change in time.
The formula for the slope of a line in pharmacokinetics is given by m = change Y/change in X, where m represents the change in concentration over the change in time.
What does C0 represent in pharmacokinetics?
C0 = original concentration
What is the relationship at one half-life?
At one half-life, concentration = ( \frac{1}{2} C_0 )
What is the formula for half-life (T1/2)?
( T_{1/2} = \frac{0.693}{K} )
How is time to reach steady state determined?
By a drug’s half-life
What is a loading dose?
A single large dose to quickly reach therapeutic plasma concentration.
What are the two types of hepatic reactions?
Phase I: oxidation, reduction, hydrolysis; Phase II: conjugation.
What does lipophilic drugs do compared to hydrophilic drugs?
Bind more to plasma proteins and distribute more throughout the body.
What is the goal of drug metabolism?
To produce metabolites that are charged and can be renally eliminated.
What is the effect of age and liver disease on Phase I reactions?
They most affect Phase I reactions which include oxidation, reduction, and hydrolysis.
How many half-lives does it take to reach 99.25% steady state?
7 half-lives.
What is the half-life for heparin?
1.5 hours.
How long does it take for heparin concentration to drop from 10,000 units to 625 units?
It takes 6 half-lives (9 hours).
What are Phase II reactions in pharmacology?
Biosynthetic reactions that involve conjugation, forming a covalent linkage between phase I metabolite and an endogenous compound, resulting in a polar and generally inactive product eliminated in urine or feces.
What is the role of the Cytochrome P-450 enzyme system?
It is a family of iron-containing hepatic isoenzymes involved in oxidative metabolism (phase I) and requires NADPH and O2.
How are CYP enzymes named?
CYP enzymes are named with the root 'CYP' followed by a number for the family, a letter for the subfamily, and another number for the specific form, e.g., CYP3A4.
What factors affect biotransformation in hepatic metabolism?
Alcohol, smoking, disease states, concomitant drugs, and genetics.
What is the difference between pharmacogenetics and pharmacogenomics?
Pharmacogenetics studies variability in drug response due to single gene variations, while pharmacogenomics involves multiple gene variations affecting drug response.
What is precision medicine?
A medical approach that prescribes the right drug, in the right dose, at the right time, based on a patient's genomic profile and other factors.
What is the traditional paradigm in medicine regarding drug prescribing?
Diagnose the patient, select medicine, start with a standard dose, observe response, and adjust if necessary.
What percentage of asthma patients are poor/non-responders to Beta-2 adrenergic agonists?
20-75%.
What are adverse drug events (ADEs) in inpatient settings?
They account for 1 in 3 hospital adverse events, affecting about 2 million stays annually and prolonging hospital stays by 1.7 to 4.6 days.
What do ADEs account for annually in outpatient settings?
What are the types of Drug Metabolism P450 Genotypes?
What is the pharmacogenetic effect of Cytochrome P450 Genotype for Poor Metabolizer?
A = Poor Metabolizer
What happened in the case of Michael Adams-Conroy?
He was a nine-year-old boy who died from a toxic accumulation of Prozac due to being a CYP2D6 poor metabolizer.
How many patients use warfarin daily?
Over 30 million patients
What genes are associated with impaired elimination of warfarin?
What are the three physiological processes involved in renal elimination?
What is the Cockcroft-Gault Equation used for?
To estimate creatinine clearance in patients with stable renal function.
What factors affect hemodialysis of drugs?
What are the pediatric pharmacokinetic differences at birth?
How does body fat change in infants?
What are the body fat percentages in infants at different ages?
How does protein binding differ in neonates?
Reduced due to lower levels of albumin and α-1 glycoprotein.
What is the half-life of phenytoin in premature neonates?
72 hours
What is the half-life of phenytoin in term infants?
20 hours
What is the half-life of phenytoin in 2-week-old infants?
8 hours
How does morphine glucuronidation compare in children and adults?
Much slower in children until age 3.
How do kidneys develop after birth?
Not fully developed at birth; rapidly increase in function over the first months.
What do BUN and Scr indicate in neonates?
They may reflect the mother's labs, not the neonate's kidney function.
What happens to receptor conformation with maturation?
Increases in conformation, density, and affinity, altering medication response.
What changes occur in renal blood flow during pregnancy?
Increased by the third trimester.
What is the effect of increased estrogen during pregnancy?
Influences hepatic induction of enzymes, e.g., CYP 3A4 for midazolam.
What is the teratogenic risk associated with drug transfer?
Drugs can cross the placenta and may pose risks to the developing fetus.
What are the effects of aging on renal function?
Reduced renal function and decreased liver blood flow.
What is the impact of aging on lipid-soluble drugs?
Increased volume of distribution due to increased body fat.
What are the types of chemical bonds in drugs?
What are stereoisomers?
Compounds with the same molecular formula but different spatial arrangements.
What are the two types of stereoisomers mentioned?
Which drugs are examples of stereoisomers?
What is the significance of quaternary structures in drug design?
They cannot cross the blood-brain barrier.
What are the second messengers in cell signaling?
What occurs with continued stimulation of receptors by agonists?
Desensitization or down-regulation of receptors.
What is the role of the FDA?
Oversees food, cosmetics, drugs, biologics, and medical devices.
What is the purpose of the Pure Food & Drug Act of 1906?
Required drugs to meet official standards of strength and purity.
What must the FDA prove to remove a drug from the market?
That labeling is false or fraudulent.
What must the FDA prove before removing a drug from the market?
The FDA must prove that labeling is false or fraudulent.
What did the Federal Food Drug and Cosmetics Act of 1938 require?
It required manufacturers to submit a New Drug Application (NDA).
What must drugs approved by an NDA be proven to be?
Safe before marketing.
What significant addition did the Kefauver-Harris Amendment make to the FDA regulations?
It added 'efficacy' to the Federal Food Drug & Cosmetics Act of 1938.
What must drugs approved by an NDA be proven to be according to the Kefauver-Harris Amendment?
Safe and effective before marketing.
What are the stages of the New Drug Approval Process?
What must an industry sponsor file before human testing in the USA?
File an Investigational New Drug (IND) application.
What is the focus of Phase 1 clinical testing?
First time in man with 20-100 healthy volunteers to determine safe dose range and pharmacokinetics.
What is the goal of Phase 2 clinical testing?
To assess short-term effectiveness and safety in selected patients with the disease.
What happens during Phase 3 clinical testing?
Expanded trials with controls to compare effectiveness against industry standards.
What is the focus of Phase 4 clinical testing?
Post marketing surveillance for adverse reactions and drug uses.
What is the therapeutic index (TI) formula?
TI = LD50 / ED50
What is the bioavailability of intravenous drug administration?
100% (by definition).
What is a characteristic of intramuscular drug administration?
Moderate volumes feasible; may be painful.
What is a characteristic of subcutaneous drug administration?
Smaller volumes than intramuscular; may be painful; suitable for pellet implantation.
What is the volume range for intramuscular administration?
75 to 100 mL
What is a drawback of subcutaneous administration?
Smaller volumes than intramuscular; may be painful
What is the primary advantage of oral administration?
Most convenient and economical
What is a significant effect of oral administration?
First-pass effect may be significant
What is a key benefit of rectal administration?
Less first-pass effect than oral
What is the volume range for inhalation administration?
5 to 100 mL
What is a notable characteristic of inhalation drugs?
Very rapid onset, parallels intravenous administration
What is the volume range for sublingual administration?
60 to 100 mL
What is a key feature of sublingual administration?
Lack of first-pass effect; absorbed directly into systemic circulation
What is the volume range for intrathecal administration?
Low (intentionally)
What is the purpose of intrathecal administration?
Circumvents blood-brain barrier
What is the volume range for topical administration?
80 to 100 mL
What is a characteristic of topical administration?
Dermal application results in slow absorption
The titration curve of a weak acid shows the relationship between pH and the forms of the acid. At pH 2, the weak acid is mostly in its _______ form, while at pH 7.4, it is in its _______ form.
The titration curve of a weak acid shows the relationship between pH and the forms of the acid. At pH 2, the weak acid is mostly in its protonated form, while at pH 7.4, it is in its unprotonated form.
In the one compartment model, drug distribution is assumed to occur uniformly throughout the body. This model is used before and immediately after _______.
In the one compartment model, drug distribution is assumed to occur uniformly throughout the body. This model is used before and immediately after administration.
The two compartment model describes drug distribution in two phases: the initial distribution phase and the _______ phase after administration.
The two compartment model describes drug distribution in two phases: the initial distribution phase and the equilibrium phase after administration.
What happens to protein-bound drugs within the vasculature?
They are retained within the vasculature
What are the phases of drug metabolism?
What are the two phases of drug metabolism?
What is an example of a phase I enzyme?
CYP3A4/5
What type of reactions occur in phase I of drug metabolism?
Oxidations, P450 dependent
What is an example of a phase II reaction?
Methylation
What are common inducers of CYP1A2?
What is the effect of inducers on drug metabolism?
They increase metabolism of drugs.
What are the typical substrates for glucuronidation?
What is the role of NADPH in drug metabolism?
It provides electrons for cytochrome P-450 reactions.
What is the elimination phase in drug metabolism?
The phase where the drug concentration decreases over time.
What is the plasma concentration (Cp) in pharmacokinetics?
The amount of drug present in the plasma at a given time.
What is the distribution phase in drug metabolism?
The phase where the drug disperses throughout the body.
What is the teratogenic risk category for drugs with controlled studies showing no risk in the first trimester?
Category A: Controlled studies in women fail to demonstrate risk to the fetus in the first trimester.
What does Category B indicate in FDA teratogenic risk categories?
Either animal studies have shown adverse effects not confirmed in women, or no controlled studies in pregnant women.
What does Category C signify regarding drug use during pregnancy?
Studies in animals have shown adverse effects, and there are no controlled studies in women. Use only if benefits justify risks.
What is indicated by Category D in teratogenic risk categories?
There is positive evidence of human fetal risk, but benefits may be acceptable in life-threatening situations.
What does Category X indicate in terms of drug use during pregnancy?
Studies demonstrate fetal abnormalities, and the risks clearly outweigh any possible benefits. Contraindicated in pregnancy.
What are some drugs that affect CYP1A2?
Cimetidine, fluoroquinolones, grapefruit juice.
What drugs are known to affect CYP3A4?
Amiodarone, azole antifungals, clarithromycin, erythromycin, protease inhibitors.
What is the effect of grapefruit juice on drug metabolism?
Grapefruit juice inhibits CYP enzymes, affecting the metabolism of various drugs.
What is the significance of maternal and fetal blood circulation in pharmacology?
Understanding maternal-fetal circulation helps assess drug transfer and potential effects on the fetus.
What are the primary components of maternal-fetal circulation?
Maternal artery, capillary in fetal placental circulation, maternal vein, umbilical artery, umbilical vein.
What is the bond strength range for covalent bonds?
Covalent bonds have a bond strength of 40-140 kcal/mol.
What is the bond strength range for ionic bonds?
Ionic bonds have a bond strength of 5-10 kcal/mol in solution.
What is the bond strength range for hydrogen bonds?
Hydrogen bonds have a bond strength of 1-7 kcal/mol.
What is the bond strength range for dipole-dipole interactions?
Dipole-dipole interactions have a bond strength of 1-7 kcal/mol.
What is the bond strength range for hydrophobic interactions?
Hydrophobic interactions have a bond strength of approximately 1 kcal/mol.
What is the effect of stereochemistry on drug activity?
Different isomers can have significantly different biological activities.
Which isomer of ascorbic acid has major activity?
L-Ascorbic acid has major activity.
What is a common effect of chloramphenicol stereochemistry?
Chloramphenicol has major activity as one isomer.
What is the stereochemical designation for diethylstilbestrol?
Diethylstilbestrol has one isomer with major activity.
Which isomer of L-Ascorbic acid has antiscorbutic activity?
Only the (−) isomer has antiscorbutic activity.
Which isomer of Chloramphenicol has high antibacterial activity?
Only the D (−) threo isomer has high antibacterial activity.
Which isomer of Diethylstilbestrol has higher estrogenic activity?
The trans isomer has 10 times the estrogenic activity of the cis isomer.
Which isomers show high affinity for the human red blood cell sugar transfer system?
Only the D isomers show high affinity for the human red blood cell sugar transfer system.
Which isomer has anti-inflammatory activity?
Only the S (+) isomer has anti-inflammatory activity.
Which isomer has hypotensive activity?
Only the (−) isomer has hypotensive activity.
Which isomers of Methylphenidate have central stimulant activity?
Only the (+) threo isomers have central stimulant activity.
Which isomer of Morphine has analgesic activity?
Only the natural (−) isomer has analgesic activity.
What does the B-Adrenergic receptor signal through?
Adenylyl cyclase > cAMP.
What does the Gi protein do?
Inhibits adenylyl cyclase > decreases cAMP.
What is the effect of Go protein?
Not yet clear.
What does the Gq protein signal through?
Phospholipase C > IP3, diacylglycerol, cytoplasmic Ca2+.
What does the Gs protein signal through?
Adenylyl cyclase > increases cAMP.
What did the Pure Food and Drug Act of 1906 prohibit?
Prohibited mislabeling and adulteration of drugs.
What did the Harrison Narcotic Act of 1914 establish?
Established regulations for use of opium, opiates, and cocaine.
What did the Food, Drug, and Cosmetic Act of 1938 require?
Required that new drugs be safe as well as pure.
What did the Kefauver-Harris Amendments (1962) require?
Required proof of efficacy as well as safety for new drugs.
What did the Orphan Drug Amendments of 1983 provide?
Incentives for the development of drugs that treat diseases with less than 200,000 patients.
What does the Drug Price Competition and Patent Restoration Act of 1984 require?
Required bioequivalence data for generic drugs.
What did the Expedited Drug Approval Act (1992) allow?
Allowed accelerated FDA approval for drugs of high medical need.
What did the Dietary Supplement Health and Education Act of 1994 amend?
It amended the Federal Food, Drug, and Cosmetic Act of 1938 to establish standards for dietary supplements.
What is the purpose of the Bioterrorism Act of 2002?
To enhance controls on dangerous biologic agents and toxins, protecting food, water, and drug supply safety.
What are the phases of clinical testing?
What is the average duration for NDA review?
The average duration is 2.6 years for safety review and 5.6 years for NDA submission.
What is the purpose of postmarketing surveillance in Phase 4?
To monitor adverse reactions, drug utilization patterns, and discover additional indications.
What are the criteria for Fast Track designation?
What does the Accelerated Review procedure involve?
Manufacturer requests review; FDA determines whether to grant based on criteria.
What is required during the development phase for drug approval?
Adequate and well-controlled studies supporting use of surrogate outcomes.
What does Phase 1 clinical testing focus on?
Safety, biological effects, metabolism, kinetics, and drug interactions.
Who conducts Phase 2 clinical testing?
Clinical pharmacologists and clinical investigators.
Who are the participants in Phase 3 clinical testing?
A large sample of selected patients.
What is the definition of pharmacokinetics?
The study of the time course of drug absorption, distribution, metabolism, and excretion.
What does pharmacodynamics refer to?
The relationship between drug concentration at the site of action and the resulting effect, including time course and intensity of effects.
What is the therapeutic index?
The ratio between the effective dose (ED50) and the lethal dose (LD50) of a drug.
What is bioavailability?
The proportion of a drug that enters the circulation when introduced into the body and is available for action.
What is the difference between agonist and antagonist?
An agonist activates a receptor to produce a biological response, while an antagonist blocks or dampens that response.
What is the first pass effect?
The metabolism of a drug within the liver before it reaches systemic circulation.
What is a pro-drug?
A medication that is administered in an inactive form and is metabolized into an active form within the body.
What are Phase I reactions in hepatic metabolism?
Reactions that involve the modification of the drug molecule, often through oxidation, reduction, or hydrolysis.
What are Phase II reactions in hepatic metabolism?
Reactions that involve conjugation of the drug to form a more water-soluble compound for excretion.
What is clearance in pharmacokinetics?
The volume of plasma from which a substance is completely removed per unit time.
What is the significance of p450 enzymes?
They play a crucial role in the metabolism of many drugs and can affect drug interactions.
What does steady state mean in pharmacokinetics?
The condition where the overall intake of a drug is equal to its elimination, resulting in a stable concentration.
What factors affect drug absorption?
Ionization, polarity, membrane transporters, environmental pH, and lipid solubility.
What is the loading dose?
A higher dose of a drug given initially to quickly achieve the desired drug concentration in the body.
What is the difference between first order and zero order elimination?
First order elimination is concentration-dependent, while zero order elimination occurs at a constant rate regardless of concentration.
What is the importance of ionization in drug pharmacokinetics?
It affects drug solubility and permeability across cell membranes, influencing absorption and distribution.
What is a partial agonist?
Binds to the receptor and causes a function but with a smaller effect than a full agonist.
What is the difference between competitive and non-competitive antagonists?
Competitive antagonists can be overcome by increasing the dose of agonist; non-competitive antagonists cannot.
What is the therapeutic index (TI)?
The ratio of a drug's LD50 to its ED50; reflects a drug's safety.
What is bioavailability (F)?
The fractional extent to which an administered dose of drug reaches the site of action or biological fluid.
What factors affect absorption of oral medications?
What is the relationship between pharmacokinetics and pharmacodynamics?
Pharmacokinetics describes how the body affects a drug, while pharmacodynamics describes how the drug affects the body.
What does bioavailability refer to?
The amount of drug that is absorbed after administration compared to that absorbed after IV administration.
What is Fick’s Law of Diffusion?
Rate = (C1 - C2) x area x permeability coefficient / thickness of the diffusion path.
What is the effect of pH on weak acids?
When pH < pK, the protonated (unionized) form predominates; when pH > pK, the unprotonated (ionized) form predominates.
What is the impact of environmental pH on drug diffusion?
Low pH & weakly acidic drug increases unionization; high pH & weakly basic drug also increases unionization.
What is the molecular weight limit for drugs?
Most drugs are 100-1000 Daltons; >100 daltons to bind to a receptor, <1000 daltons to diffuse across membranes.
What prevents drugs from passing through the blood-brain barrier?
Tight junctions between cells in CNS capillaries prevent drugs from passing between cells.
What is the One Compartment Model in pharmacokinetics?
It describes drug distribution and elimination using a single compartment for the entire body.
What does the Two Compartment Model represent?
It describes drug distribution and elimination using central and peripheral compartments.
In the One Compartment Model, X0 = dose of drug, X1 = amount of drug in body, K = elimination rate constant.
In the Two Compartment Model, X0 = dose of drug, X1 = amount of drug in central compartment, X2 = amount of drug in peripheral compartment.
What is the definition of Volume of Distribution (V)?
Hypothetical volume representing the space a drug distributes into.
What is the effect of plasma protein binding on drug distribution?
Only unbound (free) drug can diffuse into tissues.
What characterizes first-order elimination?
Amount eliminated depends on the current drug amount in the body.
The Volume of Distribution (V) can be thought of as a beaker representing the space a drug distributes into. For example, one beaker represents a patient with a small volume of distribution of 10 L and another with a larger volume of 100 L.
In zero-order kinetics, the same amount of drug is eliminated from the body at a constant rate, whereas in first-order elimination, the amount eliminated is dependent on the amount of drug in the body at that time, with a constant % of drug lost per unit time.
The formula for the slope of a line in pharmacokinetics is given by m = change Y/change in X, where m represents the change in concentration over the change in time.
What are the two types of hepatic reactions?
Phase I: oxidation, reduction, hydrolysis; Phase II: conjugation.
What does lipophilic drugs do compared to hydrophilic drugs?
Bind more to plasma proteins and distribute more throughout the body.
What is the goal of drug metabolism?
To produce metabolites that are charged and can be renally eliminated.
What is the effect of age and liver disease on Phase I reactions?
They most affect Phase I reactions which include oxidation, reduction, and hydrolysis.
How long does it take for heparin concentration to drop from 10,000 units to 625 units?
It takes 6 half-lives (9 hours).
What are Phase II reactions in pharmacology?
Biosynthetic reactions that involve conjugation, forming a covalent linkage between phase I metabolite and an endogenous compound, resulting in a polar and generally inactive product eliminated in urine or feces.
What is the role of the Cytochrome P-450 enzyme system?
It is a family of iron-containing hepatic isoenzymes involved in oxidative metabolism (phase I) and requires NADPH and O2.
How are CYP enzymes named?
CYP enzymes are named with the root 'CYP' followed by a number for the family, a letter for the subfamily, and another number for the specific form, e.g., CYP3A4.
What factors affect biotransformation in hepatic metabolism?
Alcohol, smoking, disease states, concomitant drugs, and genetics.
What is the difference between pharmacogenetics and pharmacogenomics?
Pharmacogenetics studies variability in drug response due to single gene variations, while pharmacogenomics involves multiple gene variations affecting drug response.
What is precision medicine?
A medical approach that prescribes the right drug, in the right dose, at the right time, based on a patient's genomic profile and other factors.
What is the traditional paradigm in medicine regarding drug prescribing?
Diagnose the patient, select medicine, start with a standard dose, observe response, and adjust if necessary.
What are adverse drug events (ADEs) in inpatient settings?
They account for 1 in 3 hospital adverse events, affecting about 2 million stays annually and prolonging hospital stays by 1.7 to 4.6 days.
What do ADEs account for annually in outpatient settings?
What are the types of Drug Metabolism P450 Genotypes?
What is the pharmacogenetic effect of Cytochrome P450 Genotype for Poor Metabolizer?
A = Poor Metabolizer
What happened in the case of Michael Adams-Conroy?
He was a nine-year-old boy who died from a toxic accumulation of Prozac due to being a CYP2D6 poor metabolizer.
What are the three physiological processes involved in renal elimination?
What is the Cockcroft-Gault Equation used for?
To estimate creatinine clearance in patients with stable renal function.
What factors affect hemodialysis of drugs?
What are the pediatric pharmacokinetic differences at birth?
What are the body fat percentages in infants at different ages?
How does protein binding differ in neonates?
Reduced due to lower levels of albumin and α-1 glycoprotein.
How does morphine glucuronidation compare in children and adults?
Much slower in children until age 3.
How do kidneys develop after birth?
Not fully developed at birth; rapidly increase in function over the first months.
What do BUN and Scr indicate in neonates?
They may reflect the mother's labs, not the neonate's kidney function.
What happens to receptor conformation with maturation?
Increases in conformation, density, and affinity, altering medication response.
What is the effect of increased estrogen during pregnancy?
Influences hepatic induction of enzymes, e.g., CYP 3A4 for midazolam.
What is the teratogenic risk associated with drug transfer?
Drugs can cross the placenta and may pose risks to the developing fetus.
What are the effects of aging on renal function?
Reduced renal function and decreased liver blood flow.
What is the impact of aging on lipid-soluble drugs?
Increased volume of distribution due to increased body fat.
What are stereoisomers?
Compounds with the same molecular formula but different spatial arrangements.
Which drugs are examples of stereoisomers?
What is the significance of quaternary structures in drug design?
They cannot cross the blood-brain barrier.
What are the second messengers in cell signaling?
What occurs with continued stimulation of receptors by agonists?
Desensitization or down-regulation of receptors.
What is the purpose of the Pure Food & Drug Act of 1906?
Required drugs to meet official standards of strength and purity.
What must the FDA prove before removing a drug from the market?
The FDA must prove that labeling is false or fraudulent.
What did the Federal Food Drug and Cosmetics Act of 1938 require?
It required manufacturers to submit a New Drug Application (NDA).
What significant addition did the Kefauver-Harris Amendment make to the FDA regulations?
It added 'efficacy' to the Federal Food Drug & Cosmetics Act of 1938.
What must drugs approved by an NDA be proven to be according to the Kefauver-Harris Amendment?
Safe and effective before marketing.
What are the stages of the New Drug Approval Process?
What must an industry sponsor file before human testing in the USA?
File an Investigational New Drug (IND) application.
What is the focus of Phase 1 clinical testing?
First time in man with 20-100 healthy volunteers to determine safe dose range and pharmacokinetics.
What is the goal of Phase 2 clinical testing?
To assess short-term effectiveness and safety in selected patients with the disease.
What happens during Phase 3 clinical testing?
Expanded trials with controls to compare effectiveness against industry standards.
What is the focus of Phase 4 clinical testing?
Post marketing surveillance for adverse reactions and drug uses.
What is a characteristic of intramuscular drug administration?
Moderate volumes feasible; may be painful.
What is a characteristic of subcutaneous drug administration?
Smaller volumes than intramuscular; may be painful; suitable for pellet implantation.
What is a drawback of subcutaneous administration?
Smaller volumes than intramuscular; may be painful
What is a notable characteristic of inhalation drugs?
Very rapid onset, parallels intravenous administration
What is a key feature of sublingual administration?
Lack of first-pass effect; absorbed directly into systemic circulation
The titration curve of a weak acid shows the relationship between pH and the forms of the acid. At pH 2, the weak acid is mostly in its protonated form, while at pH 7.4, it is in its unprotonated form.
In the one compartment model, drug distribution is assumed to occur uniformly throughout the body. This model is used before and immediately after administration.
The two compartment model describes drug distribution in two phases: the initial distribution phase and the equilibrium phase after administration.
What happens to protein-bound drugs within the vasculature?
They are retained within the vasculature
What is the elimination phase in drug metabolism?
The phase where the drug concentration decreases over time.
What is the plasma concentration (Cp) in pharmacokinetics?
The amount of drug present in the plasma at a given time.
What is the distribution phase in drug metabolism?
The phase where the drug disperses throughout the body.
What is the teratogenic risk category for drugs with controlled studies showing no risk in the first trimester?
Category A: Controlled studies in women fail to demonstrate risk to the fetus in the first trimester.
What does Category B indicate in FDA teratogenic risk categories?
Either animal studies have shown adverse effects not confirmed in women, or no controlled studies in pregnant women.
What does Category C signify regarding drug use during pregnancy?
Studies in animals have shown adverse effects, and there are no controlled studies in women. Use only if benefits justify risks.
What is indicated by Category D in teratogenic risk categories?
There is positive evidence of human fetal risk, but benefits may be acceptable in life-threatening situations.
What does Category X indicate in terms of drug use during pregnancy?
Studies demonstrate fetal abnormalities, and the risks clearly outweigh any possible benefits. Contraindicated in pregnancy.
What drugs are known to affect CYP3A4?
Amiodarone, azole antifungals, clarithromycin, erythromycin, protease inhibitors.
What is the effect of grapefruit juice on drug metabolism?
Grapefruit juice inhibits CYP enzymes, affecting the metabolism of various drugs.
What is the significance of maternal and fetal blood circulation in pharmacology?
Understanding maternal-fetal circulation helps assess drug transfer and potential effects on the fetus.
What are the primary components of maternal-fetal circulation?
Maternal artery, capillary in fetal placental circulation, maternal vein, umbilical artery, umbilical vein.
What is the bond strength range for covalent bonds?
Covalent bonds have a bond strength of 40-140 kcal/mol.
What is the bond strength range for ionic bonds?
Ionic bonds have a bond strength of 5-10 kcal/mol in solution.
What is the bond strength range for hydrogen bonds?
Hydrogen bonds have a bond strength of 1-7 kcal/mol.
What is the bond strength range for dipole-dipole interactions?
Dipole-dipole interactions have a bond strength of 1-7 kcal/mol.
What is the bond strength range for hydrophobic interactions?
Hydrophobic interactions have a bond strength of approximately 1 kcal/mol.
What is the effect of stereochemistry on drug activity?
Different isomers can have significantly different biological activities.
What is a common effect of chloramphenicol stereochemistry?
Chloramphenicol has major activity as one isomer.
What is the stereochemical designation for diethylstilbestrol?
Diethylstilbestrol has one isomer with major activity.
Which isomer of L-Ascorbic acid has antiscorbutic activity?
Only the (−) isomer has antiscorbutic activity.
Which isomer of Chloramphenicol has high antibacterial activity?
Only the D (−) threo isomer has high antibacterial activity.
Which isomer of Diethylstilbestrol has higher estrogenic activity?
The trans isomer has 10 times the estrogenic activity of the cis isomer.
Which isomers show high affinity for the human red blood cell sugar transfer system?
Only the D isomers show high affinity for the human red blood cell sugar transfer system.
Which isomers of Methylphenidate have central stimulant activity?
Only the (+) threo isomers have central stimulant activity.
Which isomer of Morphine has analgesic activity?
Only the natural (−) isomer has analgesic activity.
What did the Pure Food and Drug Act of 1906 prohibit?
Prohibited mislabeling and adulteration of drugs.
What did the Harrison Narcotic Act of 1914 establish?
Established regulations for use of opium, opiates, and cocaine.
What did the Food, Drug, and Cosmetic Act of 1938 require?
Required that new drugs be safe as well as pure.
What did the Kefauver-Harris Amendments (1962) require?
Required proof of efficacy as well as safety for new drugs.
What did the Orphan Drug Amendments of 1983 provide?
Incentives for the development of drugs that treat diseases with less than 200,000 patients.
What does the Drug Price Competition and Patent Restoration Act of 1984 require?
Required bioequivalence data for generic drugs.
What did the Expedited Drug Approval Act (1992) allow?
Allowed accelerated FDA approval for drugs of high medical need.
What did the Dietary Supplement Health and Education Act of 1994 amend?
It amended the Federal Food, Drug, and Cosmetic Act of 1938 to establish standards for dietary supplements.
What is the purpose of the Bioterrorism Act of 2002?
To enhance controls on dangerous biologic agents and toxins, protecting food, water, and drug supply safety.
What are the phases of clinical testing?
What is the average duration for NDA review?
The average duration is 2.6 years for safety review and 5.6 years for NDA submission.
What is the purpose of postmarketing surveillance in Phase 4?
To monitor adverse reactions, drug utilization patterns, and discover additional indications.
What are the criteria for Fast Track designation?
What does the Accelerated Review procedure involve?
Manufacturer requests review; FDA determines whether to grant based on criteria.
What is required during the development phase for drug approval?
Adequate and well-controlled studies supporting use of surrogate outcomes.
What does Phase 1 clinical testing focus on?
Safety, biological effects, metabolism, kinetics, and drug interactions.
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