Study Guide NURS517
Exam 1 – Summer 2022
2025
Week 1:
First-pass Effect
Definition: Metabolism by the liver following oral administration and determines whether
a drug can be orally administered.
- When a drug is taken orally, it goes through the liver first and metabolizes the
medication. After liver metabolism the concentration of the drug is less.
- enzymes in the liver break down the drug. Avoiding first-pass metabolism allows a
much larger proportion of the dose to reach the brain or other organs.
Half-Life
- Definition: The time period over which the drug concentration will decrease by half.
- Blood levels decrease by 50% in one half-life, 75% in two half-lives, and 87.5% in three half-lives. As
a general rule, drugs tend to be administered at dosing intervals that are close to their half-life
-The dose–response curve and half-life will determine the dosing schedule, with fewer doses per day
encouraging adherence to the drug regimen
Toxicity
-Ideally, drugs will produce their desired effects at dosages well below toxicity.
-The speed at which drugs enter the bloodstream affects the maximum blood level that is achieved.
Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side effects. EX:
rapid IV administration= IV push drugs. For these reasons, some medications are administered by
slow IV infusion
over 30 to 60 minutes. This allows distribution to occur, keeps the blood level from getting too high,
and minimizes toxicity.
-Metabolism can increase or decrease the onset, duration of action, and toxicity of a medication
-Drugs with a low or narrow therapeutic index may require close monitoring for toxicity
-Patients at the extremes of age, either the very young or the very old, have developmental
pharmacokinetic differences that warrant careful prescribing. Infants have immature liver and renal
functions that place them at risk for toxicity. The older adult population has decreased liver and
renal functions, resulting in decreased metabolism and clearance, which can cause drug
accumulation and toxicity.
, -Genetic differences may account in part for some of the well-documented variability in response to
drug therapy. Obviously, many factors other than genetics—such as age, sex, other drugs
administered, and underlying disease states—also contribute to variation in drug response.
However, inherited differences in the metabolism and disposition of drugs and genetic
polymorphisms in the targets of drug therapy (e.g., metabolizing enzymes or protein receptors) can
have an even greater influence on the efficacy and toxicity of medications. Individuals known as slow
acetylators will metabolize the drug slowly, allowing greater residence time in the body and
enhanced toxicity.
-CYP3A4 isoenzyme is responsible for metabolism of several important classes of drugs that are
commonly used in primary care (see Table 6-1). Examples of these classes include -azole antifungals,
calcium channel blockers, antihistamines, anticonvulsants, antimicrobials, and corticosteroids. Both
drug-related induction or inhibition of CYP450 3A4 isoenzyme may complicate drug therapy in
patients
Steady state
Steady-state concentration occurs when the amount of a drug being absorbed is the same
amount that’s being cleared from the body when the drug is given continuously or repeatedly
(rate of the drug entering the systemic circulation equals the rate of elimination )
- drug molecules are being replaced at the same rate, through new doses, that they’re being
removed from the body. Steady-state concentration is the time during which the concentration
of the drug in the body stays consistent.
- For most drugs, the time to reach steady state is four to five half-lives to reach steady state
blood levels if the drug is given at regular intervals
Upregulation
increase in a cellular response to a molecular stimulus due to increase in the number of receptors on
the cell surface.
Treatment with some agonist drugs can cause the receptors to downregulate, or decrease, in
response to receptor stimulation; this can limit the duration over which the drug can be clinically
useful.
Treatment with some antagonist drugs can cause receptors to upregulate (increase) in response to
the decrease in receptor stimulation, which can produce rebound effects if the antagonists is
abruptly withdrawn.
An increase in the number of receptors on the surface of target cells, making the cells more sensitive
to a hormone or another agent.
Disease states or drug treatment can selectively alter the number of receptors in various tissues
throughout the body.
o Ex: hyperthyroidism upregulates or increases the number of beta-adrenoceptors, making
hyperthyroid pt more likely to have HTN and a rapid HR.
, Regulation of a drug after being on a drug for a long time such as beta-blockers and opiates may
cause a change in amount or dose given
Gender Differences in Pharmacokinetics
Gender differences: child vs adult, childbearing, across the lifespan and drugs to avoid in certain
populations like older adults
Infants have immature liver and renal functions that put them at risk for toxicity and adverse drug
reactions and may require dosage adjustments based on age.
Older adults have decreased liver and renal functions r/t aging and place them at increased risk for
ADRs.
o Pts over 65 required hospitalization r/t ADRs 7 times more often.
o Take care to minimize polypharmacy.
Most phase 2 enzymes have a faster clearance in men than women.
pregnancy, oral contraceptive use, and hormonal replacement therapy can significantly change drug
metabolism and drug clearance.
Pharmacokinetics in women is affected by lower body weight, slower gastrointestinal motility, less
intestinal enzymatic activity, and slower glomerular filtration rate.
Women have more ADRs than men r/t differences in body composition and hormonal fluctuation.
ADRs may also be related to pregnancy and lactation.
Pharmacokinetics and Prescribing
Metabolism, know the renal function and pharmacokinetics of the drug.
The movement of drugs through the body
deals with (ADME) absorption, distribution through the body, metabolism, and excretion of drugs.
How medications are presented to the body affects the speed, extent, and duration of drug
absorption.
When deciding which drug in a class to prescribe, the pharmacokinetic properties of a drug may
influence drug selection.
For example, drugs within a drug class may differ in their ability to cross the blood–brain barrier,
either being more effective (i.e., antiseizure medications) or causing more adverse central nervous
system effects (i.e., first generation antihistamines).
Another consideration is metabolism. Different drugs in a class may use different cytochrome P450
(CYP450) enzymes, which may influence metabolism or drug interactions.
Drugs that are excreted almost exclusively by the kidneys may not be appropriate for a patient with
decreased renal function, such as an older adult.
Absorption
The way in which medications are presented to the body affects the speed, extent, and duration
of drug absorption.
Route may also affect adherence.
Bedpan bullet= a poorly formulated dosage that travels through the intestines and arrives
unchanged in the toilet. There is little biological effect if the active medication never reaches its site of
action.
Parenteral= by injection. (IV, IM, SC) Used when immediate effect is needed, when active
ingredients are destroyed or not absorbed by GI tract, or if pt is unable to take PO meds.
Limitation= requires needles, syringes, and sterile technique.
, Drug absorption is greatest for IV injection.
IV=all the drug enters the blood stream immediately.
IV route= serves as standard of comparison for bioavailability (percentage of administered drug
that is absorbed) compared to other routes
Major disadvantage is once given, absorption cannot be slowed, and the drug cannot be
removed.
Oral= most common and convenient. Must pass through lining of intestines to enter systemic
circulation. Then travels to liver to be metabolized on their way to the blood stream.
Sublingual and buccal allow quicker onset of action and avoid liver metabolism.
SL for nitroglycerin. Works in 1-2 minutes and stop anginal attack.
Buccal is less common. Used with nicotine/chewing tobacco and methyltestosterone.
Enteric coated/extended release=do not crush. This leads to higher blood levels than
anticipated.
Use of oral meds is limited if nausea, vomiting, uncooperative.
Rectal administration is absorbed similar timeframe as oral preparations.
Giving meds close to site of action allows higher concentration of med while minimizing other
unwanted effects.
Topical meds go directly on damaged areas of skin, inhalers go directly to lungs.
Ophthalmic meds are buffered and isotonic to reduce discomfort to the eye. Aural meds do not
require buffering and isotonicity.
Bioavailability
Not all administered doses may be dissolved, absorbed, or survive liver metabolism, only fraction
makes it to bloodstream
The percentage of admin dose that does enter bloodstream = Bioavailability
o Parenteral administration= 100%.
o Ranges from 10-90% for oral dosing. If bioavailability is low, a higher dose is given.
Peak Blood Levels
The speed which drugs enter bloodstream affects maximum blood levels that is achieved
Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side
effects.
o Aminoglycoside antibiotics are given IV over 30-60 minutes. This allows distribution to occur,
keeps blood level from being too high, and minimizes toxicity.
Distribution
Once drug is absorbed, still must reach site of action to produce an effect. Distribution is the
process of drugs moving throughout the body
movement of absorbed drug in bodily fluids throughout the body to target tissues. Requires
adequate blood supply.
Drugs passively diffuse most readily when they are small and uncharged and have the right
balance between lipid and water solubility.
pH in the body affects the ionization of the drug.
Drugs may bind to proteins. Molecular weight of 500 or less are best candidates for passive
diffusion. >5000 diffuse poorly.
Henderson-Hasselbalch Relationship= passive diffusion through biological barriers, such as cell
membrane or layer of cells, occurs most readily when drugs are in the uncharged state.
Passive diffusion proceeds until the concentration of unionized drug is the same on both sides.
Exam 1 – Summer 2022
2025
Week 1:
First-pass Effect
Definition: Metabolism by the liver following oral administration and determines whether
a drug can be orally administered.
- When a drug is taken orally, it goes through the liver first and metabolizes the
medication. After liver metabolism the concentration of the drug is less.
- enzymes in the liver break down the drug. Avoiding first-pass metabolism allows a
much larger proportion of the dose to reach the brain or other organs.
Half-Life
- Definition: The time period over which the drug concentration will decrease by half.
- Blood levels decrease by 50% in one half-life, 75% in two half-lives, and 87.5% in three half-lives. As
a general rule, drugs tend to be administered at dosing intervals that are close to their half-life
-The dose–response curve and half-life will determine the dosing schedule, with fewer doses per day
encouraging adherence to the drug regimen
Toxicity
-Ideally, drugs will produce their desired effects at dosages well below toxicity.
-The speed at which drugs enter the bloodstream affects the maximum blood level that is achieved.
Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side effects. EX:
rapid IV administration= IV push drugs. For these reasons, some medications are administered by
slow IV infusion
over 30 to 60 minutes. This allows distribution to occur, keeps the blood level from getting too high,
and minimizes toxicity.
-Metabolism can increase or decrease the onset, duration of action, and toxicity of a medication
-Drugs with a low or narrow therapeutic index may require close monitoring for toxicity
-Patients at the extremes of age, either the very young or the very old, have developmental
pharmacokinetic differences that warrant careful prescribing. Infants have immature liver and renal
functions that place them at risk for toxicity. The older adult population has decreased liver and
renal functions, resulting in decreased metabolism and clearance, which can cause drug
accumulation and toxicity.
, -Genetic differences may account in part for some of the well-documented variability in response to
drug therapy. Obviously, many factors other than genetics—such as age, sex, other drugs
administered, and underlying disease states—also contribute to variation in drug response.
However, inherited differences in the metabolism and disposition of drugs and genetic
polymorphisms in the targets of drug therapy (e.g., metabolizing enzymes or protein receptors) can
have an even greater influence on the efficacy and toxicity of medications. Individuals known as slow
acetylators will metabolize the drug slowly, allowing greater residence time in the body and
enhanced toxicity.
-CYP3A4 isoenzyme is responsible for metabolism of several important classes of drugs that are
commonly used in primary care (see Table 6-1). Examples of these classes include -azole antifungals,
calcium channel blockers, antihistamines, anticonvulsants, antimicrobials, and corticosteroids. Both
drug-related induction or inhibition of CYP450 3A4 isoenzyme may complicate drug therapy in
patients
Steady state
Steady-state concentration occurs when the amount of a drug being absorbed is the same
amount that’s being cleared from the body when the drug is given continuously or repeatedly
(rate of the drug entering the systemic circulation equals the rate of elimination )
- drug molecules are being replaced at the same rate, through new doses, that they’re being
removed from the body. Steady-state concentration is the time during which the concentration
of the drug in the body stays consistent.
- For most drugs, the time to reach steady state is four to five half-lives to reach steady state
blood levels if the drug is given at regular intervals
Upregulation
increase in a cellular response to a molecular stimulus due to increase in the number of receptors on
the cell surface.
Treatment with some agonist drugs can cause the receptors to downregulate, or decrease, in
response to receptor stimulation; this can limit the duration over which the drug can be clinically
useful.
Treatment with some antagonist drugs can cause receptors to upregulate (increase) in response to
the decrease in receptor stimulation, which can produce rebound effects if the antagonists is
abruptly withdrawn.
An increase in the number of receptors on the surface of target cells, making the cells more sensitive
to a hormone or another agent.
Disease states or drug treatment can selectively alter the number of receptors in various tissues
throughout the body.
o Ex: hyperthyroidism upregulates or increases the number of beta-adrenoceptors, making
hyperthyroid pt more likely to have HTN and a rapid HR.
, Regulation of a drug after being on a drug for a long time such as beta-blockers and opiates may
cause a change in amount or dose given
Gender Differences in Pharmacokinetics
Gender differences: child vs adult, childbearing, across the lifespan and drugs to avoid in certain
populations like older adults
Infants have immature liver and renal functions that put them at risk for toxicity and adverse drug
reactions and may require dosage adjustments based on age.
Older adults have decreased liver and renal functions r/t aging and place them at increased risk for
ADRs.
o Pts over 65 required hospitalization r/t ADRs 7 times more often.
o Take care to minimize polypharmacy.
Most phase 2 enzymes have a faster clearance in men than women.
pregnancy, oral contraceptive use, and hormonal replacement therapy can significantly change drug
metabolism and drug clearance.
Pharmacokinetics in women is affected by lower body weight, slower gastrointestinal motility, less
intestinal enzymatic activity, and slower glomerular filtration rate.
Women have more ADRs than men r/t differences in body composition and hormonal fluctuation.
ADRs may also be related to pregnancy and lactation.
Pharmacokinetics and Prescribing
Metabolism, know the renal function and pharmacokinetics of the drug.
The movement of drugs through the body
deals with (ADME) absorption, distribution through the body, metabolism, and excretion of drugs.
How medications are presented to the body affects the speed, extent, and duration of drug
absorption.
When deciding which drug in a class to prescribe, the pharmacokinetic properties of a drug may
influence drug selection.
For example, drugs within a drug class may differ in their ability to cross the blood–brain barrier,
either being more effective (i.e., antiseizure medications) or causing more adverse central nervous
system effects (i.e., first generation antihistamines).
Another consideration is metabolism. Different drugs in a class may use different cytochrome P450
(CYP450) enzymes, which may influence metabolism or drug interactions.
Drugs that are excreted almost exclusively by the kidneys may not be appropriate for a patient with
decreased renal function, such as an older adult.
Absorption
The way in which medications are presented to the body affects the speed, extent, and duration
of drug absorption.
Route may also affect adherence.
Bedpan bullet= a poorly formulated dosage that travels through the intestines and arrives
unchanged in the toilet. There is little biological effect if the active medication never reaches its site of
action.
Parenteral= by injection. (IV, IM, SC) Used when immediate effect is needed, when active
ingredients are destroyed or not absorbed by GI tract, or if pt is unable to take PO meds.
Limitation= requires needles, syringes, and sterile technique.
, Drug absorption is greatest for IV injection.
IV=all the drug enters the blood stream immediately.
IV route= serves as standard of comparison for bioavailability (percentage of administered drug
that is absorbed) compared to other routes
Major disadvantage is once given, absorption cannot be slowed, and the drug cannot be
removed.
Oral= most common and convenient. Must pass through lining of intestines to enter systemic
circulation. Then travels to liver to be metabolized on their way to the blood stream.
Sublingual and buccal allow quicker onset of action and avoid liver metabolism.
SL for nitroglycerin. Works in 1-2 minutes and stop anginal attack.
Buccal is less common. Used with nicotine/chewing tobacco and methyltestosterone.
Enteric coated/extended release=do not crush. This leads to higher blood levels than
anticipated.
Use of oral meds is limited if nausea, vomiting, uncooperative.
Rectal administration is absorbed similar timeframe as oral preparations.
Giving meds close to site of action allows higher concentration of med while minimizing other
unwanted effects.
Topical meds go directly on damaged areas of skin, inhalers go directly to lungs.
Ophthalmic meds are buffered and isotonic to reduce discomfort to the eye. Aural meds do not
require buffering and isotonicity.
Bioavailability
Not all administered doses may be dissolved, absorbed, or survive liver metabolism, only fraction
makes it to bloodstream
The percentage of admin dose that does enter bloodstream = Bioavailability
o Parenteral administration= 100%.
o Ranges from 10-90% for oral dosing. If bioavailability is low, a higher dose is given.
Peak Blood Levels
The speed which drugs enter bloodstream affects maximum blood levels that is achieved
Rapid absorption leads to higher peak blood levels, with a risk of greater toxicity and side
effects.
o Aminoglycoside antibiotics are given IV over 30-60 minutes. This allows distribution to occur,
keeps blood level from being too high, and minimizes toxicity.
Distribution
Once drug is absorbed, still must reach site of action to produce an effect. Distribution is the
process of drugs moving throughout the body
movement of absorbed drug in bodily fluids throughout the body to target tissues. Requires
adequate blood supply.
Drugs passively diffuse most readily when they are small and uncharged and have the right
balance between lipid and water solubility.
pH in the body affects the ionization of the drug.
Drugs may bind to proteins. Molecular weight of 500 or less are best candidates for passive
diffusion. >5000 diffuse poorly.
Henderson-Hasselbalch Relationship= passive diffusion through biological barriers, such as cell
membrane or layer of cells, occurs most readily when drugs are in the uncharged state.
Passive diffusion proceeds until the concentration of unionized drug is the same on both sides.
