G-Protien coupled receptors and how they interact with drugs
Ans: G-protein coupled receptors (GPCR) interact with drugs through 7 regions of proteins that span
and innervate the cell membrane and trap the molecule into the receptor site like an interwoven basket
(Insel & Sriram, 2018). Drugs can then enter this space and interact with the GRCP. A specific interaction
and binding with a site on one or more of the regions of proteins within the GPCR, and drugs bound with
the GRCP can stimulate the release of G proteins that can interact with various effector proteins to
create physiological responses within the body (Insel & Sriram, 2018). This process occurs through
secondary messengers (such as cAMP) which creates the extracellular interactions produced by the drug
binding to the GRCP.
What neurotransmitters are excitatory?
Ans: amino acids such as glycine, aspartate, and glutamate are excitatory (Woo & Robinson, p.16,
2016).
,Which is the most common CYP enzyme in the body? What role does it play?
Ans: According to the textbook, the CYP3A4 is the most important enzyme in the body. CYP3A4 is
responsible for the metabolism of more than 50% of medications and is considered a major drug
metabolizing enzyme. CYP3A4 can be found in the liver, as well as the lining of the GI tract. Due to this
location, food can also influence this CYP. One example of this is grapefruit juice, which can inhibit
CYP3A4. Medications that are metabolized by CYP3A4 include antimicrobials, calcium channel blockers,
antihistamines, anticonvulsants, azole antifungals, and corticosteroids (Woo, & Robinson, 2016).
What is the clinical significance of being an ultra-rapid CYP2D6 metabolizer?
Ans: People who are ultra-rapid metabolizers have high activity of CYP2D6 enzymes that break down
certain medicines rapidly and are likely to need different doses or even a different medicine. Drug dose,
response, and toxicity risk of beta-blockers, antidepressants, antiarrhythmics, and opioid analgesics are
dependent on CYP2D6 pharmacogenetics (Ayazseven et al., 2020). Knowing the result of the CYP2D6
test and which group the patient falls into such as poor metabolizers, intermediate metabolizers, or
ultra-rapid metabolizers, will help nurse practitioners prescribe the right medication and dosage for the
patient.
What would be the concern if a drug is a CYP450indicer? How that might affect the metabolism of
another drug the patient is taking?
Ans: Cytochrome P450 enzymes are in cells throughout the body, primarily found in liver cells (Girvan &
Munro, 2016). These enzymes are essential for the metabolism of many medications. Cytochrome P450
enzymes can act as an inducer or inhibitor of metabolism. When a medication induces the CYP450
enzyme that increases the rate of metabolism (Girvan & Munro, 2016). This can impact the effectiveness
of other medications. For example, medication A induces CYP450 enzyme activity, therefore medication
B will be metabolized quicker and have a less therapeutic effect.
Explain the significance of a drug being an inhibitor of P-glycoprotein? (see text)
, Ans: P-glycoprotein (P-gp) is the main barrier of the body and it affects the proper delivery of drugs and
causes drug resistance in our body. P-gp is an efflux membrane transporter, that can be found
throughout the body and it controls the cellular uptake and the distribution of synthetic substances,
chemicals, and toxins. Drugs are chemicals and P-gp hinders the absorption, permeability, and retention
of the drugs, extruding them out of the cells. This adversely affects drug therapies and fails to yield good
results, for example in therapies like using chemo agents in cancer treatments. In this case, proper
inhibition of P-gp is important to increase cellular uptake, transport, and half-lives of drugs. The drug is
an inhibitor of P-gp that would help in the cost-effective treatment for disease conditions without
wasting an extra amount of medicines. It will help to shorten the treatment time and speedy recovery of
the patient (Abebe et al., 2019; Woo & Robinson, 2016).
Significance of a VCORC1 mutation for patients taking warfarin?
Ans: In 2008, the U.S Food and Drug Administration updated the dosing of warfarin to include the
application of pharmacogenomics. Variable metabolism by CYP2C9 was once known as the major
contributor to the variable response to warfarin. However, a mutation in VCORC1 has been found to
account for much more variability in warfarin responses and can cause a rare syndrome of warfarin
resistance. A mutation in VCORC1 encodes a subunit of the vitamin K epoxide reductase complex ,the
pharmacological target for warfarin, and increases the chances of uncontrolled bleeding (Woo &
Robinson, 2016). Therefore, if providers have information about the presence of this mutation, they
may decide to decrease the dosage of Coumadin for their patient.
What out text has to say about National Standards of Culturally and Linguistically Appropriate Services?
Ans: In 2012, the institute of medicine identified that the main factor affecting health disparity is
cultural competency of the health practitioner (Woo & Robinson, 2016). The National Standard for
Culturally and Linguistically Appropriate Services in health and health care (CLAS) standards were
created as a way to address and correct these inequities (Woo & Robinson, 2016). Originally established
in 2000, the CLAS standards provided a blueprint for providers to implement services that were
culturally and linguistically appropriate, however, over the years they have evolved (Woo & Robinson,
2016). They have undergone review and have been revised in 2013 and will continue to evolve in
response to research and changing demographics (Woo & Robinson, 2016).
What are some differences in drug metabolism in Asian populations?
Ans: G-protein coupled receptors (GPCR) interact with drugs through 7 regions of proteins that span
and innervate the cell membrane and trap the molecule into the receptor site like an interwoven basket
(Insel & Sriram, 2018). Drugs can then enter this space and interact with the GRCP. A specific interaction
and binding with a site on one or more of the regions of proteins within the GPCR, and drugs bound with
the GRCP can stimulate the release of G proteins that can interact with various effector proteins to
create physiological responses within the body (Insel & Sriram, 2018). This process occurs through
secondary messengers (such as cAMP) which creates the extracellular interactions produced by the drug
binding to the GRCP.
What neurotransmitters are excitatory?
Ans: amino acids such as glycine, aspartate, and glutamate are excitatory (Woo & Robinson, p.16,
2016).
,Which is the most common CYP enzyme in the body? What role does it play?
Ans: According to the textbook, the CYP3A4 is the most important enzyme in the body. CYP3A4 is
responsible for the metabolism of more than 50% of medications and is considered a major drug
metabolizing enzyme. CYP3A4 can be found in the liver, as well as the lining of the GI tract. Due to this
location, food can also influence this CYP. One example of this is grapefruit juice, which can inhibit
CYP3A4. Medications that are metabolized by CYP3A4 include antimicrobials, calcium channel blockers,
antihistamines, anticonvulsants, azole antifungals, and corticosteroids (Woo, & Robinson, 2016).
What is the clinical significance of being an ultra-rapid CYP2D6 metabolizer?
Ans: People who are ultra-rapid metabolizers have high activity of CYP2D6 enzymes that break down
certain medicines rapidly and are likely to need different doses or even a different medicine. Drug dose,
response, and toxicity risk of beta-blockers, antidepressants, antiarrhythmics, and opioid analgesics are
dependent on CYP2D6 pharmacogenetics (Ayazseven et al., 2020). Knowing the result of the CYP2D6
test and which group the patient falls into such as poor metabolizers, intermediate metabolizers, or
ultra-rapid metabolizers, will help nurse practitioners prescribe the right medication and dosage for the
patient.
What would be the concern if a drug is a CYP450indicer? How that might affect the metabolism of
another drug the patient is taking?
Ans: Cytochrome P450 enzymes are in cells throughout the body, primarily found in liver cells (Girvan &
Munro, 2016). These enzymes are essential for the metabolism of many medications. Cytochrome P450
enzymes can act as an inducer or inhibitor of metabolism. When a medication induces the CYP450
enzyme that increases the rate of metabolism (Girvan & Munro, 2016). This can impact the effectiveness
of other medications. For example, medication A induces CYP450 enzyme activity, therefore medication
B will be metabolized quicker and have a less therapeutic effect.
Explain the significance of a drug being an inhibitor of P-glycoprotein? (see text)
, Ans: P-glycoprotein (P-gp) is the main barrier of the body and it affects the proper delivery of drugs and
causes drug resistance in our body. P-gp is an efflux membrane transporter, that can be found
throughout the body and it controls the cellular uptake and the distribution of synthetic substances,
chemicals, and toxins. Drugs are chemicals and P-gp hinders the absorption, permeability, and retention
of the drugs, extruding them out of the cells. This adversely affects drug therapies and fails to yield good
results, for example in therapies like using chemo agents in cancer treatments. In this case, proper
inhibition of P-gp is important to increase cellular uptake, transport, and half-lives of drugs. The drug is
an inhibitor of P-gp that would help in the cost-effective treatment for disease conditions without
wasting an extra amount of medicines. It will help to shorten the treatment time and speedy recovery of
the patient (Abebe et al., 2019; Woo & Robinson, 2016).
Significance of a VCORC1 mutation for patients taking warfarin?
Ans: In 2008, the U.S Food and Drug Administration updated the dosing of warfarin to include the
application of pharmacogenomics. Variable metabolism by CYP2C9 was once known as the major
contributor to the variable response to warfarin. However, a mutation in VCORC1 has been found to
account for much more variability in warfarin responses and can cause a rare syndrome of warfarin
resistance. A mutation in VCORC1 encodes a subunit of the vitamin K epoxide reductase complex ,the
pharmacological target for warfarin, and increases the chances of uncontrolled bleeding (Woo &
Robinson, 2016). Therefore, if providers have information about the presence of this mutation, they
may decide to decrease the dosage of Coumadin for their patient.
What out text has to say about National Standards of Culturally and Linguistically Appropriate Services?
Ans: In 2012, the institute of medicine identified that the main factor affecting health disparity is
cultural competency of the health practitioner (Woo & Robinson, 2016). The National Standard for
Culturally and Linguistically Appropriate Services in health and health care (CLAS) standards were
created as a way to address and correct these inequities (Woo & Robinson, 2016). Originally established
in 2000, the CLAS standards provided a blueprint for providers to implement services that were
culturally and linguistically appropriate, however, over the years they have evolved (Woo & Robinson,
2016). They have undergone review and have been revised in 2013 and will continue to evolve in
response to research and changing demographics (Woo & Robinson, 2016).
What are some differences in drug metabolism in Asian populations?
