NR 565 Advanced Pharmacology Midterm
Week 1: Principles of Pharmacology
Pharmacokinetics, pharmacodynamics, and drug interactions
o Pharmacokinetics is the study of drug absorption, distribution, metabolism, and
excretion in the body.
o For drug absorption to occur, a drug must penetrate cellular membranes to cross
biological barriers. The process entails passive diffusion whereby drugs move
from a higher concentration area to a lower concentration area by diffusing
through cell membranes.
o Membranes within the body are primarily made up of lipids, and for drugs to
cross they must be lipid soluble. Drugs that are not lipid soluble rely on chemical
characteristics that result in reactions between drugs and molecules that exist
within the body such as water.
Factors affection absorption
o Rate of dissolution
o Surface area
o Blood flow
o Lipid solubility
o pH partitioning
Factors affecting distribution
o Blood flow to tissues
o Ability to exit the vascular system
o Blood-brain barrier
o Protein-binding capacity
Drug metabolism and the CYP450 system
o Xenobiotics are substances that are foreign to the body, such as medications
o All xenobiotics or medications have the potential to adversely affect the body,
the extent of the adverse effect correlates to the rate of absorption, distribution,
metabolism, and excretion, these determine the degree of chemical exposure in
the body
o Cytochrome P450 (CYP450) are xenobiotic-metabolizing enzymes necessary for
the production of cholesterol and steroids and the detoxification of chemicals
and drug metabolism.
These enzymes are bound to a cell membrane (cyto) and contain a heme
pigment (chrome and P) that absorbs light at a wavelength of 450nm
when exposed to carbon monoxide, hence the name CYP450.
These enzymes are thought to be the major family or system of enzymes
responsible for phase 1 metabolism in which drugs are oxidized, reduced,
or hydrolyzed.
The CYP450 system is comprised of 12 enzymes that are made up of 3
families (CYP1, CYP2, CYP3) that metabolize drugs and nine families that
metabolize endogenous compounds.
, Many medication interactions are the result of an alteration in CYP450
metabolism.
Medication responses vary based on enzyme inhibition, enzyme
induction, and or genetic difference.
An inducing agent can increase the rate of another drugs metabolism,
therefore when an inducing agent is prescribed with another medication,
the dosage of the other medication may require adjustment given the
increased rate of metabolism and the reduced effect of the medication.
On the other hand, if a medication is taken with an inhibitor the level of
the drug can increase and cause adverse side effects.
Substrates are drugs metabolized by CYP450
Inhibitors
o Inhibitors are medications that inhibit the metabolic activity of one or more of
the CYP450 enzymes
o Medications that inhibit an enzyme potentially slows that enzyme’s activity or
blocks the activity required for the metabolism of other medications thereby
increasing the levels of medications dependent on that particular enzyme for
biotransformation.
o This inhibition prolongs the pharmacological effect, which may result in toxicity
o Factors that affect inhibition include the dose and capacity to bind to the enzyme
Inducers
o Inducers are xenobiotics (medications and environmental agents) that elevate
CYP450 enzyme activity by increasing enzyme synthesis.
o The increased number of sites enhances medication metabolism, decreasing the
concentration of the “parent drug” while increasing metabolite production.
o The half-life of the inducing drug may cause a delay before enzyme activity
increases.
o A decrease in the concentration of a medication metabolized by CYP2C9
(responsible for 10% of drug metabolism) usually occurs 24 hours after the
administration of the medication.
, Substrates
o Substrates are Xenobiotics that require the metabolic process of the body to
either activate or de-activate the drug.
o Knowing the CYP enzyme and whether it will increase or decrease the substrate
(causing it to exit the body faster or have prolonged excretion) is critical to avoid
adverse effects
Prescribing during pregnancy and breastfeeding
o During the first trimester, the fetus is most at risk due to the occurrence of rapid
growth. During the third trimester, drugs are likely to cross over from the
circulation of the mother to that of the child.
o Teratogenesis or prenatal toxicity is a drug effect of the highest concern that
causes structural or functional defects, intrauterine growth retardation, or fetal
death. Teratogens can be difficult to identify.
Drugs with highest teratogenic potential: neuro antiepileptic drugs,
antimicrobials, vit. A, some anticoags, hormonal medications.
Prescribing drugs for infant and pediatric patients
o Can be tricky
o Dosages are based on weight and body surface area
o Children metabolize drugs faster than adults
o Absorption in neonates and infants
Transdermal: infants have thin skin with higher rates of blood flow,
increased absorption, increased risk for toxicity
IM: neonate (slow and erratic due to blood flow in muscles first few days
of life), Infancy (increased absorption than in neonates and adults due to
increased blood flow)
Oral:
Delayed gastric emptying
Increased absorption for drugs that absorb into the stomach
Decreased absorption for drugs that absorb into the intestines
Low gastric acidity for 24 hours after birth
Increased absorption of acid-labile drugs
Prescribing for older adult patients
o Experience more adverse drug reactions and drug-drug interactions
Beers criteria
o The beers criteria includes five lists that describe certain medications and
situations and include:
potentially Inappropriate Medication (PIM) use in older adults
potentially Inappropriate Medication (PIM) use in older adults due
to medication-disease or medication-syndrome interactions that
may exacerbate the disease or syndrome
medications to be used cautiously in older adults
Week 1: Principles of Pharmacology
Pharmacokinetics, pharmacodynamics, and drug interactions
o Pharmacokinetics is the study of drug absorption, distribution, metabolism, and
excretion in the body.
o For drug absorption to occur, a drug must penetrate cellular membranes to cross
biological barriers. The process entails passive diffusion whereby drugs move
from a higher concentration area to a lower concentration area by diffusing
through cell membranes.
o Membranes within the body are primarily made up of lipids, and for drugs to
cross they must be lipid soluble. Drugs that are not lipid soluble rely on chemical
characteristics that result in reactions between drugs and molecules that exist
within the body such as water.
Factors affection absorption
o Rate of dissolution
o Surface area
o Blood flow
o Lipid solubility
o pH partitioning
Factors affecting distribution
o Blood flow to tissues
o Ability to exit the vascular system
o Blood-brain barrier
o Protein-binding capacity
Drug metabolism and the CYP450 system
o Xenobiotics are substances that are foreign to the body, such as medications
o All xenobiotics or medications have the potential to adversely affect the body,
the extent of the adverse effect correlates to the rate of absorption, distribution,
metabolism, and excretion, these determine the degree of chemical exposure in
the body
o Cytochrome P450 (CYP450) are xenobiotic-metabolizing enzymes necessary for
the production of cholesterol and steroids and the detoxification of chemicals
and drug metabolism.
These enzymes are bound to a cell membrane (cyto) and contain a heme
pigment (chrome and P) that absorbs light at a wavelength of 450nm
when exposed to carbon monoxide, hence the name CYP450.
These enzymes are thought to be the major family or system of enzymes
responsible for phase 1 metabolism in which drugs are oxidized, reduced,
or hydrolyzed.
The CYP450 system is comprised of 12 enzymes that are made up of 3
families (CYP1, CYP2, CYP3) that metabolize drugs and nine families that
metabolize endogenous compounds.
, Many medication interactions are the result of an alteration in CYP450
metabolism.
Medication responses vary based on enzyme inhibition, enzyme
induction, and or genetic difference.
An inducing agent can increase the rate of another drugs metabolism,
therefore when an inducing agent is prescribed with another medication,
the dosage of the other medication may require adjustment given the
increased rate of metabolism and the reduced effect of the medication.
On the other hand, if a medication is taken with an inhibitor the level of
the drug can increase and cause adverse side effects.
Substrates are drugs metabolized by CYP450
Inhibitors
o Inhibitors are medications that inhibit the metabolic activity of one or more of
the CYP450 enzymes
o Medications that inhibit an enzyme potentially slows that enzyme’s activity or
blocks the activity required for the metabolism of other medications thereby
increasing the levels of medications dependent on that particular enzyme for
biotransformation.
o This inhibition prolongs the pharmacological effect, which may result in toxicity
o Factors that affect inhibition include the dose and capacity to bind to the enzyme
Inducers
o Inducers are xenobiotics (medications and environmental agents) that elevate
CYP450 enzyme activity by increasing enzyme synthesis.
o The increased number of sites enhances medication metabolism, decreasing the
concentration of the “parent drug” while increasing metabolite production.
o The half-life of the inducing drug may cause a delay before enzyme activity
increases.
o A decrease in the concentration of a medication metabolized by CYP2C9
(responsible for 10% of drug metabolism) usually occurs 24 hours after the
administration of the medication.
, Substrates
o Substrates are Xenobiotics that require the metabolic process of the body to
either activate or de-activate the drug.
o Knowing the CYP enzyme and whether it will increase or decrease the substrate
(causing it to exit the body faster or have prolonged excretion) is critical to avoid
adverse effects
Prescribing during pregnancy and breastfeeding
o During the first trimester, the fetus is most at risk due to the occurrence of rapid
growth. During the third trimester, drugs are likely to cross over from the
circulation of the mother to that of the child.
o Teratogenesis or prenatal toxicity is a drug effect of the highest concern that
causes structural or functional defects, intrauterine growth retardation, or fetal
death. Teratogens can be difficult to identify.
Drugs with highest teratogenic potential: neuro antiepileptic drugs,
antimicrobials, vit. A, some anticoags, hormonal medications.
Prescribing drugs for infant and pediatric patients
o Can be tricky
o Dosages are based on weight and body surface area
o Children metabolize drugs faster than adults
o Absorption in neonates and infants
Transdermal: infants have thin skin with higher rates of blood flow,
increased absorption, increased risk for toxicity
IM: neonate (slow and erratic due to blood flow in muscles first few days
of life), Infancy (increased absorption than in neonates and adults due to
increased blood flow)
Oral:
Delayed gastric emptying
Increased absorption for drugs that absorb into the stomach
Decreased absorption for drugs that absorb into the intestines
Low gastric acidity for 24 hours after birth
Increased absorption of acid-labile drugs
Prescribing for older adult patients
o Experience more adverse drug reactions and drug-drug interactions
Beers criteria
o The beers criteria includes five lists that describe certain medications and
situations and include:
potentially Inappropriate Medication (PIM) use in older adults
potentially Inappropriate Medication (PIM) use in older adults due
to medication-disease or medication-syndrome interactions that
may exacerbate the disease or syndrome
medications to be used cautiously in older adults
