Exam 2- studyguide

What are ADME properties and what do they determine

A: Absorption: how well the drug enters the body

D: Distribution: how well the drug is distributed to the organs/tissue

M: Metabolism: How the drug us broken down to be eliminated

E: Elimination: how the drug exits the body

What properties determine the nature of drug action

Binding activity and activity at the therapeutic target

What is absorption?

movement of a drug from its site administration into the blood stream from the site of delivery, this indicates the blood is the main space where a drug will go first after its absorbed, and from there it can move to the rest of the body

Which of these is a factor that affects absorption

all are correct

3 multiple choice options

which molecule, hydrophilic or lipophilic molecules penetrate the lipid bilayer more readily

lipophilic

Transport that requires energy

Active

1 multiple choice option

transport that does not require energy

Passive

1 multiple choice option

Type of passive transport that goes through cells with no transporter

diffusion

2 multiple choice options

Type of passive transport that goes through cells mediated by SLC transporter

facilitated diffusion

2 multiple choice options

Type of passive transport that goes around cells with no transporter

Paracellular transport

2 multiple choice options

Passive transport moves with a concentration gradient from _ to __.

High to low

Active transporters use __ to move drugs against the concentration gradient

energy

1 multiple choice option

Active transporters use __ to move ion against the concentration gradient

ATP

1 multiple choice option

true/false In terms of ionization, charged forms do not readily cross the membrane

true

true/false in terms of ionization, uncharged forms do not penetrate membranes

false

What is pka

the ph at which half the drug is in its ionized and unionized form

ph

protonated

ph>pka

which form will predominate

un/deprotonated

Do ionized or unionized forms cross membranes more easily

unionized

Where do more basic drugs get absorbed and why

they are unionized at its higher pH env. small intestine because it has a high surface area

What is the fractional extent to which a dose of a drug reaches the systemic circulation

bioavailability

3 multiple choice options

Which of the following situations would be expected to decrease the oral bioavailability of a drug

The drug undergoes extensive first-pass metabolism in the liver

3 multiple choice options

What symbol is used for bioavailability

F

3 multiple choice options

What does the area under the curve represent?

AUC represents the overall amount of drug in the blood after a given dose over time

which of these is NOT a parenteral ROA

Oral ingestion and transdermal

3 multiple choice options

True/false accelerating gastric emptying will increase rate of absorption from the upper intestine

true

What four properties make a drug bioequivalent

1. Same active form

2. concentration

3. dosage form

4. ROA

What phase of distribution passes through well-perfused organs such as the brain, kidneys, lungs, and liver

FIrst phase

1 multiple choice option

What phase of distribution passes through muscle, viscera, and fat

second phase

1 multiple choice option

In terms of protein binding drugs acidic drugs bind to _

albumin

In terms of protein binding drugs basic drugs bind to _

a-acid glycoprotein

Why does protein binding limit the availability of drugs

Because only unbound drugs can cross membranes

which of the following statements about tissue binding of drugs is correct

Amino-glycoside antibiotics can accumulate in tissues, leading to renal and ear toxicity

3 multiple choice options

_ transporters move drugs into the brain

influx

1 multiple choice option

_ transporters move drugs away from the brain

efflux

1 multiple choice option

true/false drugs never can cross the placenta, making most drugs safe in fetal development

false

1. introduce or expose functional groups

2. example CYP450 enzymes

3. result in both active and inactive compounds

which phase of metabolism?

Phase 1 of metabolism

1 multiple choice option

1. Polar conjugates are usually inactive and excreted rapidly

2. covalent linkage between functional groups on drugs/metabolite and glucuronic acid, sulfate, or glutathione

3. example: UPD-glucuronosyl transferases and sulfotransferases

which phase of metabolism?

Phase 2 of metabolism

1 multiple choice option

What is a prodrug

A drug given in an inactive form and once inside the body, enzymes or chemical changes converts it to an active drug that actually produces and affect like for example, Codeine, the body changes it into morphine

Which of the following statements it true about drug-drug interactions

enzyme induction increases metabolism, lowering drug levels and potentially reducing effectiveness

3 multiple choice options

what is the main route of elimination/excretion

Urine and feces

what are examples of other routes of elimination/excretion

Minor: lungs, sweat, saliva, tears and breast milk

In first order kinetics, there is a constant _ of drug metabolized per unit time, while in zero order kinetics there is a constant _ of drug metabolized per unit time

fraction and amount

A measure of the bodys efficiency in eliminating a drug from systemic circulation

Clearance

3 multiple choice options

a measure of the rate of removal of a drug form systemic circulation

Half life

3 multiple choice options

fraction of a drug absorbed into the systemic circulation

Bioavailability

3 multiple choice options

Apparent space of body available to contain a drug based on a mount given and concentration in systemic circulation

Volume of distribution

3 multiple choice options

true/ false in terms of clearance, first order clearance has a nonlinear relationship between concentration and elimination, while zero order has a linear relationship between concentration and elimination

false

what can limit hepatic clearance

reduces hepatic blood blow, the blood flow can be impacted by hypotension or heart failure

The clearance of drugs by the kidney depends on

1. Glomular filtration

2. secretion

3. reabsorption

4. glomular blood flood

series of repetitive doses or continuous injection to maintain steady state

maintenance dose

1 multiple choice option

a dose used to achieve target concentration rapidly

loading dose

1 multiple choice option

what are some disadvantages of a loading dose

prolonged exposure to drugs with long half -lives and potential to reach toxic concentration rapidly

what is the genetic mutation variation that occurs at a frequency of at least 1% in the human population

polymorphism

3 multiple choice options

True/false if someone has a gene duplication of CYP2D6 they should be considered an ultra rapid metabolizer

true

What type of coding region SNPs impacts the protein sequence which leads to amino acid substitution or stop translation

non-synonymous (missense)

3 multiple choice options

what are three type of polymorphisms

1. single nucleotide polymorphism

2. insertions/deleltions (indels)

3. copy number variation

genetic variation that occurs in at least 1% of the human population

Polymorphism

inherited trait from one parent

Dominant trait

segment of gene that does not code for protein and interrupts gene sequence

intron

mutations or genes on the X chromosome

X-Linked

pertaining to non-sex chromosomes

Autosomal

inherited trait from both parents

Recessive trait

two different alleles that can be expressed with mixed phenotypic patterns

Co dominant trait

segment of gene containing coding information

Exon

Which molecules will most readily cross cell membranes

unionized molecules

Which of the following ROA is not a type of parental administration

Transdermal and oral injestion

3 multiple choice options

Immediate onset of action, utility in emergency situations, easy dose adjustment and low first pass hepatic metabolism are characteristics of this ROA

intravenous

3 multiple choice options

true/false the oral route is generally considered the easiest and most convenient ROA for drugs

true

which of the following ROA's is most subject to first pass metabolism

oral

3 multiple choice options

true/ false a drug with a f value of 0.9 would be considered to have low bioavailability

false

dose dumping failure of a dosage form is a potential limitation for this ROA

oral controlled released formulation

3 multiple choice options

if a weak base has a pka value of 9.4, what will the ratio of ionized vs unionized drug at a ph of 7.4

100:1

true/ false with zero order pharmacokinetics, a constant amount of drug is eliminated per unit time

true

true/ false protein binding in plasma has an impact on both drug distribution and elimination by limiting both drug availability and glomuar filtration

true

1. functions to restrict access of chemicals to the brain on the basis of charge, size and lipid solubility

2. composed of tight junctions between capillary endothelial cells

3. is augmented by membrane transporters

blood brain barrier

A process that results in a covalent linkage between a functional group on a drug or metabolite and glucuronic acid, sulfate, or glutathione

phase 2 biosynthetic reaction

3 multiple choice options

A Term that relates the amount of drug in the body to the plasma concentration and also reflects the extent to which a drug is present in extravascular tissue and not in plasma

volume of distribution

3 multiple choice options

a measure of the bodys efficiency in elimination drugs that is measured in units of volume per unit time

clearance

3 multiple choice options

true/ false to rapidly achieve and maintain a desires plasma concentration, a dosing regimen that includes both a loading and maintenance dose should be utilized

true

Drugs such as verapamil, morphine, propanalol have high inartistic clearance and are readily metabolized in the liver. Systemic clearance of such drugs will be impacted most by

reduced blood flow due to hypotension or heart failure

3 multiple choice options

gene duplications of the CYP2D6 gene resulting variability in drug metabolism represent this type of polymorphism

Copy variation number

Genetic variations occurring at a frequency of at least 1% un the human population are referred to as

polymorphism

The segment of a gene containing coding information

exon

The gene for ABCB1 transporter may contain a C or a T as the base in positions 3435, such genetic variability is known as

single nucleotide polymorphism

A patient whose genome lacks copies of GYP2D6 gene, and thus lacks GYP2D6 function would be considered

poor or null metabolizer

true/false a synonymous (sense) SNP in the coding region of a gene would alter the AA sequence of the gene product, potentially leading to changes in the structure or function of the protein

false

A glutathione-S-transferase M1 (GSTM1) polymorphism associated with a loss of 50 kilobases, resulting in reduced glutothione conjugating capacity

deletion

Midazolam is metabolized by CYP3A5, which is expressed in a higher percentage of African-Americans (55%) than in Japanese (33%) or Caucasians (10-20%). The source of this variability is a SNP in intron 3 that encodes a stop codon and truncates the protein, thereby reducing expression of CYP3A5. Based on this information, which patient population would exhibit higher levels of hydroxylated midazolam (a metabolite of midazolam)?

african americans

Can you calculate half life based on a zero order graph

no

Can you calculate volume of distribution based of a first order with multiple compartments graph

no

how do you calculate the clearance based off a first order multiple compartment graph

from the AUC

How to calculate K

0.693/T0.5

how to calculate clearance

CL=kVd

how to calculate Vd

Vd= Dose/concentration of plasma @ time 0