NU 578 Exam 1 Study Guide
Difference between adverse effects, side effects, and toxicity (pg. 34)
- Adverse effects: any noxious unintended, and undesired effects that occur at a normal drug dose
- Side effects: unwanted UNAVOIDABLE effects of drugs that appear at a normal dose required for
therapeutic response o Idiosyncratic response: rare adverse drug response resulting from a genetic
predisposition (ex.
lack of metabolizing enzymes) can occur with certain anesthetics
Ultra-rapid metabolizers seen with kids and codeine; they metabolize to morphine at an
enhanced rate decreased RR
o Iatrogenic response: response where a drug can cause a disease like a state
ex. Antipsychotics can cause Parkinson’s like tremors
ex. aspirin can cause gastritis
broad-spectrum abx yeast infections
- Toxicity: unwanted effects that appear as a drug dosage are increased beyond the dose required for
therapeutic response. Detrimental physiologic effects o Usually dose-dependent, i.e. the patient takes
too much leading to extra effects o Avoided if we educate well and complete a med rec
o Sometimes toxicity is intended. For example, anticancer drugs can cause neutropenia, putting
the pt at high risk for infection even though the dose was therapeutic
Controlled substances—what are the schedules and how are they set? For instance, is a CS2 drug addicting
than a CS3 drug?
How do drugs cross membranes? What things influence this?
- All phases of pharmacokinetics involve drug movement.
- Three Ways to cross a cell membrane
1) Passage through channels and pores: very few drugs can do this because the channels are small and
specific for certain molecules.
a. Example: Potassium and sodium can pass through specific channels
2) Using a Transport System: carriers that move drugs from one side of the cell membrane to the other
side. These systems are very SELECTIVE – depending on the drugs structure
a. Example: P-glycoprotein (PGP) or multidrug transporter protein helps transport many drugs out of
cells
3) Direct penetration of membrane (most common): dependent on ability to penetrate membranes
directly “like dissolves like”
a. Membranes made of primarily lipids, to directly penetrate membranes, the drug must be
lipidsoluble (lipophilic)
What do polarity and charge (ionization) have to do with drugs crossing membranes (or not crossing them)?
- Molecules that are not lipid-soluble and cannot penetrate membranes are polar molecules and ions
- Polar Molecules: have no net charge but do have an uneven distribution of electrical charge (positive
and negative). Electrons (-) in water molecule spend more time next to the oxygen rather than the
hydrogen atoms (+)
, - Polar molecules will dissolve in polar solvents (such as water) but not in nonpolar solvents (lipids) -
Ions: molecules that have a net electrical charge (positive or negative).
- Small ions are unable to cross membranes and must become unionized to cross -Ionization is
dependent on pH.
Acids ionize is basic media. Bases ionize in acidic media drugs that are weak acids are best
absorbed in an acidic environment such as gastric acid because they remain in their
nonionized form.
o Ex. Aspirin molecules pass from the stomach into the small intestine where the
environment is basic (alkaline), more of the molecules change to their ionized form.
- pH Partitioning (ion trapping) drug accumulates on the side of the membrane where pH most favors its
ionization.
Which factors affect the major pharmacokinetic parameters: Absorption, Distribution, Metabolism and
Excretion?
- Absorption: movement of a drug from site of its administration into the systemic circulation
- Rate: dissolution helps determine rate of absorption. Drugs that have a faster dissolution have a faster
onset
- Surface area: large surface area = faster absorption. Absorption of oral medications is usually grater
from the small intestine rather than the stomach because of anatomy.
- due to microvilli lining, small intestine has a large surface area, whereas stomach = small surface area
- Blood Flow: absorbed rapidly where blood flow is high. Greater concentration gradient more rapid
absorption
- Lipid solubility: highly lipid soluble drugs are absorbed more rapidly than drugs with low lipid solubility
because lipid soluble drugs can readily cross membranes
- pH partitioning: absorption enhanced when difference between the pH of plasma and pH at the site of
administration is such that a drug molecule will have a greater tendency to be ionized in the plasma
- Distribution: movement of drugs from the systemic circulation to the site of drug action
1) Blood flow to tissues: drugs are carried by the blood to tissues and organs rate of drug delivery is
determined by blood flow to that tissue
a. Tissues are very vascular so it’s rarely an issue however abscesses and tumors can have low blood
flow affecting drug therapy.
2) The ability of a drug to exit the vascular system: after it has been delivered the next step is to exit the
vasculature. Most drugs do not produce effects in the blood so the ability to leave the vascular system
is important for a drug’s action.
a. They leave at capillary beds through pores and can move into the interstitial space
b. The blood-brain barrier (BBB): unique anatomy of capillaries into the CNS that create tight
junctions and prevent drug passage.
i. Because they are so tight only lipid-soluble drugs or have a transport system can cross the BBB
c. Placental drug transfer: membranes of the placenta separate the maternal circulation from fetal,
but membranes of the placenta do not create an absolute barrier for drugs
i. Most drugs cross via diffusion
ii. Lipid soluble, nonionized drugs cross easily
Difference between adverse effects, side effects, and toxicity (pg. 34)
- Adverse effects: any noxious unintended, and undesired effects that occur at a normal drug dose
- Side effects: unwanted UNAVOIDABLE effects of drugs that appear at a normal dose required for
therapeutic response o Idiosyncratic response: rare adverse drug response resulting from a genetic
predisposition (ex.
lack of metabolizing enzymes) can occur with certain anesthetics
Ultra-rapid metabolizers seen with kids and codeine; they metabolize to morphine at an
enhanced rate decreased RR
o Iatrogenic response: response where a drug can cause a disease like a state
ex. Antipsychotics can cause Parkinson’s like tremors
ex. aspirin can cause gastritis
broad-spectrum abx yeast infections
- Toxicity: unwanted effects that appear as a drug dosage are increased beyond the dose required for
therapeutic response. Detrimental physiologic effects o Usually dose-dependent, i.e. the patient takes
too much leading to extra effects o Avoided if we educate well and complete a med rec
o Sometimes toxicity is intended. For example, anticancer drugs can cause neutropenia, putting
the pt at high risk for infection even though the dose was therapeutic
Controlled substances—what are the schedules and how are they set? For instance, is a CS2 drug addicting
than a CS3 drug?
How do drugs cross membranes? What things influence this?
- All phases of pharmacokinetics involve drug movement.
- Three Ways to cross a cell membrane
1) Passage through channels and pores: very few drugs can do this because the channels are small and
specific for certain molecules.
a. Example: Potassium and sodium can pass through specific channels
2) Using a Transport System: carriers that move drugs from one side of the cell membrane to the other
side. These systems are very SELECTIVE – depending on the drugs structure
a. Example: P-glycoprotein (PGP) or multidrug transporter protein helps transport many drugs out of
cells
3) Direct penetration of membrane (most common): dependent on ability to penetrate membranes
directly “like dissolves like”
a. Membranes made of primarily lipids, to directly penetrate membranes, the drug must be
lipidsoluble (lipophilic)
What do polarity and charge (ionization) have to do with drugs crossing membranes (or not crossing them)?
- Molecules that are not lipid-soluble and cannot penetrate membranes are polar molecules and ions
- Polar Molecules: have no net charge but do have an uneven distribution of electrical charge (positive
and negative). Electrons (-) in water molecule spend more time next to the oxygen rather than the
hydrogen atoms (+)
, - Polar molecules will dissolve in polar solvents (such as water) but not in nonpolar solvents (lipids) -
Ions: molecules that have a net electrical charge (positive or negative).
- Small ions are unable to cross membranes and must become unionized to cross -Ionization is
dependent on pH.
Acids ionize is basic media. Bases ionize in acidic media drugs that are weak acids are best
absorbed in an acidic environment such as gastric acid because they remain in their
nonionized form.
o Ex. Aspirin molecules pass from the stomach into the small intestine where the
environment is basic (alkaline), more of the molecules change to their ionized form.
- pH Partitioning (ion trapping) drug accumulates on the side of the membrane where pH most favors its
ionization.
Which factors affect the major pharmacokinetic parameters: Absorption, Distribution, Metabolism and
Excretion?
- Absorption: movement of a drug from site of its administration into the systemic circulation
- Rate: dissolution helps determine rate of absorption. Drugs that have a faster dissolution have a faster
onset
- Surface area: large surface area = faster absorption. Absorption of oral medications is usually grater
from the small intestine rather than the stomach because of anatomy.
- due to microvilli lining, small intestine has a large surface area, whereas stomach = small surface area
- Blood Flow: absorbed rapidly where blood flow is high. Greater concentration gradient more rapid
absorption
- Lipid solubility: highly lipid soluble drugs are absorbed more rapidly than drugs with low lipid solubility
because lipid soluble drugs can readily cross membranes
- pH partitioning: absorption enhanced when difference between the pH of plasma and pH at the site of
administration is such that a drug molecule will have a greater tendency to be ionized in the plasma
- Distribution: movement of drugs from the systemic circulation to the site of drug action
1) Blood flow to tissues: drugs are carried by the blood to tissues and organs rate of drug delivery is
determined by blood flow to that tissue
a. Tissues are very vascular so it’s rarely an issue however abscesses and tumors can have low blood
flow affecting drug therapy.
2) The ability of a drug to exit the vascular system: after it has been delivered the next step is to exit the
vasculature. Most drugs do not produce effects in the blood so the ability to leave the vascular system
is important for a drug’s action.
a. They leave at capillary beds through pores and can move into the interstitial space
b. The blood-brain barrier (BBB): unique anatomy of capillaries into the CNS that create tight
junctions and prevent drug passage.
i. Because they are so tight only lipid-soluble drugs or have a transport system can cross the BBB
c. Placental drug transfer: membranes of the placenta separate the maternal circulation from fetal,
but membranes of the placenta do not create an absolute barrier for drugs
i. Most drugs cross via diffusion
ii. Lipid soluble, nonionized drugs cross easily
