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An overview of key concepts related to the distribution, metabolism, and elimination of drugs in the body. It covers factors that influence drug distribution, such as lipid solubility, molecular size, and protein binding. It also discusses the role of the liver in drug metabolism and the concept of first-pass effect. Additionally, the document explores how drug elimination is determined by factors like half-life and clearance. This information is crucial for understanding how drugs are transported, transformed, and removed from the body, which is essential for optimizing drug therapy and minimizing adverse effects.
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Once you graduate from an NP program, in order to prescribe you'll need: - ANS--Advanced nurse prescriber license
-DEA #
What is the purpose of a DEA #? - ANS-Needed to prescribed scheduled drugs
Rules for prescribing Schedule II drugs: - ANS--Written script needed
-1 month supply only
-No refills
What is the PDMP? - ANS-Prescription Drug Monitoring Program
Used to effectively track patient's controlled substance uses across different health facilities (in the same state)
What are clinical practice guidelines? - ANS-Recommendations that are intended to optimize patient care that are informed by a systematic review of the evidence and an assessment of the benefits/harms of alternative care practices
Ex: sepsis, CAP
Common causes of medication errors: - ANS--Illegible writing
-Drug names that sound alike
-Medications that look alike
-Administering a drug with the wrong route
What is pharmacokinetics? What are its 4 categories? - ANS-What the body does to the drug
Quickest route of absorption? Slowest? - ANS-IV = quickest
IM = slowest
What is the most common way drugs pass through cell membranes? - ANS-Passive diffusion
What characteristics of a drug allow it to pass most quickly through cell membranes (usually through passive diffusion)? - ANS-Small, uncharged (unionized), lipid soluble--pass through membrane without any energy
What does it mean when a drug is ionized? - ANS-It means that the drug is stuck in the compartment it was ionized in and has to be moved to the next compartment (cannot be absorbed into the bloodstream)
Where do weak acids absorb? - ANS-Stomach
Where do weak bases absorb? - ANS-Small intestine
pH of stomach: - ANS-2-
pH of small intestine: - ANS-6-
-Therapeutic effects
-Toxic effects
(lipid soluble, small, and non-ionized drugs will distribute more quickly)
Body factors related to distribution: - ANS--Vascularity (poor perfusion, disruption of blood flow due to trauma--difficulty distributing)
-Blood barriers (blood-brain-barrier can be problematic if we need to get drugs to the brain--will need very high dosing since only a small amount of the drug will get through)
-Transport mechanisms
-Plasma binding proteins
-Disease states
-Volume of distribution
-Drug interactions
What is the key plasma protein involved with protein binding for medications? - ANS-Albumin
Why do we monitor albumin? - ANS-Indicative of nutritional status and how well protein-bound drugs will be transported to their target locations
What happens to the therapeutic effect of a drug when the patient is elderly and has very low levels of albumin? - ANS-The drug does not bind to the protein (albumin) as much as expected, so there is a lot of free drug floating in the plasma; high risk for drug toxicity
Protein bound means: - ANS-Inactive form of the drug; does not have any therapeutic effect when bound to a protein
Free drug means: - ANS-Active form of the drug (available for therapeutic effect)
What happens when a patient is on two drugs that are competing for the same protein binding site on the albumin? - ANS-Some drug interactions can occur. Drugs fight for binding position, but both drugs do not get enough as the usually would. Leads to higher free drug levels, decreased overall albumin binding, and potential toxicity for both drugs.
Unpredictable
What is the 1st pass effect? - ANS-PO drug goes through GI tract and absorbs in the stomach or intestines into local circulation that reaches the liver. The liver inactivates portions of the drug before it goes into systemic circulation. Some drugs with a very high 1st pass effect may have to be given IV (goes directly into systemic circulation) or in higher PO doses (watch for side effects)
What does a substrate for an enzyme mean? - ANS-It needs it to undergo metabolism
What is an enzyme inducer? - ANS-It increases clearance of the drug (decreased blood levels of drug-- may need dose increase)
What is an enzyme inhibitor? - ANS-It reduces clearance (increased blood levels of drug--may need dose decrease)
Who is at risk for drug toxicity? - ANS-Elderly, those with decreased renal function
-Cannot properly excrete the drug
What are the key pharmacokinetic changes that occur during pregnancy? - ANS--Decreased absorption
-Increased hepatic metabolism
-Increased renal excretion
What is the minimum effective concentration? - ANS-The minimum amount of drug required to produce a therapeutic effect
What is receptor desensitization? - ANS-Decreased responsiveness of the receptor to the drug; decreased overall effects
How does antibiotic resistance occur? - ANS-The bacteria find a way to become resistant to the antibiotic. They multiply leading to an ineffective antibiotic
How to prevent antibiotic resistance: - ANS--Don't prescribe for viral infections
-Only prescribe when needed
-Use the right dose and duration (use guidelines)
-Utilize cultures
-Reassess treatment regime after cultures come back (don't just use broad spectrum drugs)
-Only use prophylactic antibiotics when completely necessary
Skin infections are usually caused by gram positive or gram negative organisms? - ANS-Gram positive (staph, strep, candida)
GI/GU infections are usually caused by gram positive or gram negative organisms? - ANS-Gram negative (E. coli, Klebsiella, Proteus)
What kind of drug is vancomycin? - ANS-Glycopeptide antibiotic
Why is it important to monitor vancomycin levels? - ANS-It has a narrow TI. Dose has to be adjusted according to amount of vanco in the blood serum (draw a vanco trough 1 hour before the next dose is due)
What is antibiotic synergy? - ANS-When 2 antibiotics are combined in one combination drug to improve efficacy
Ex: Bactrim, Augmentin, Zosyn
What are the components of bactrim? - ANS-Sulfamethoxazole: Disrupts production of dihydrofolic acid
Trimethoprim: Disrupts production of tetrahydrafolic acid
Together these drugs target different steps in the folic acid pathway that kills susceptible bacteria better than either drug would alone
How does Augmentin work? - ANS-Irreversibly binds to bacterial beta lactamases which protects the penicillin drugs from destruction. The clavulanic acid protects the penicillin from being broken down by the bacteria (combats bacterial resistance).
How do superinfections develop? - ANS--Broad spectrum antibiotics
-Several antibiotics over a short period of time
Major side effect of aminoglycosides (like Gentamicin): - ANS-Oto and nephrotoxicity
Major side effect of Tetracyclines: - ANS-Photosensitivity and teeth stains in kids
Major side effect of Vancomycin: - ANS-Red-man syndrome (if given too quickly)
Major side effect of Bactrim: - ANS-Kidney stones if patients don't hydrate well
D. Tetracyclines - ANS-D
You are reviewing an older patient's chart during a routine clinic visit. Which patient information is of most concern to you if they are on multiple protein-bound medications?
A. Chronic constipation
B. ow serum albumin
C. Increased body fat
D. Low serum creatinine - ANS-B
A patient has a localized skin infection, which is most likely caused by a gram positive cocci. Until the culture & sensitivity results are available, you plan to order a _________ -spectrum _________ drug.
A. broad; systemic
B. broad; topical
C. narrow; systemic
D. narrow; topical - ANS-D
Your patient is taking drug A, a pro-drug that is a substrate for the CYPA12 enzyme. You start them on drug B, which is a strong inhibitor of CYPA12. What do you anticipate will happen?
A. There will be no impact on levels of either drug
B. The therapeutic efficacy of drug A will be significantly reduced
C. The patient will be at risk for drug B toxicity
D. The patient will be at risk for drug A toxicity - ANS-B
You determine that a patient requires a prescription for a narrow-spectrum antibiotic to treat a gram positive cocci-related infection. What treatment options would you consider? (Select all that apply)
A. Erythromycin
B. Penicillin G
C. Tetracycline
D. Vancomycin
E. Amoxicillin - ANS-A, B, D
Which side effect of clindamycin causes the provider the most concern and may warrant discontinuation of the drug?
A. Diarrhea
B. Vomiting
C. Nausea
D. HA - ANS-A
A patient presents to the ER with a serum drug level of 50 g/mL. The half-life of this drug is 1 hour. With this drug, concentrations above 25 g/mL are considered toxic. How long will it take for the blood level to reach the non-toxic range?
A. 30 minutes
B. 1 hour
C. 2 hours
D. 3 hours - ANS-B
You are treating a patient who has been receiving an IM drug, but will transition to the PO route upon discharge. What is responsible for the increased dosage prescribed for the PO dose of this drug?
A. Passive diffusion
B. Glomerular filtration
C. Active transport
D. 1st pass effect - ANS-D
You are caring for a patient who is being treated with gentamicin and fluconazole. If these 2 drugs are competing with each other for protein-binding sites, what would be the result?
A. Altered efficacy of both drugs B. Counteract any positive benefit the drugs would have
C. There will be no problems giving these drugs together
D. Puts the patient at risk for an allergic reaction - ANS-A
When 2 drugs compete with each other for protein-binding sites on albumin, this alters the effectiveness of both drugs (and can also cause toxicity of both drugs) due to inconsistent binding and free drug concentrations in the plasma
A cancer patient is receiving morphine to treat their cancer-related pain. Approximately every 7 days, the medication is no longer effective in controlling her pain and a larger dose is needed to achieve the same effect. What is happening?
A. Cumulation effect
What term describes the drug level required for a medication to have a therapeutic effect in a patient?
A. Dynamic equilibrium
B. Critical concentration
C. Selective toxicity
D. Active transport - ANS-B
You have prescribed an IV aminoglycoside for a patient who has a severe infection in her leg. What would be important to monitor this patient for related to this class of antibiotics?
A. Renal dysfunction
B. Liver dysfunction
C. Serum glucose levels
D. Visual disturbances - ANS-A
You have recently graduated from an NP program and are exploring licensure in a variety of states. Prescribing authority is ...
A. determined by state law
B. the same for PAs and APRNs
C. the same in all states
D. regulated by the federal government - ANS-A
A patient is taking 2 PO drugs, A and B. Drug A absorbs well in the small intestine, but is poorly absorbed in the stomach. Drug B absorbs well in the stomach, but is poorly absorbed in the intestines. What is likely true?
A. Drug A is probably a weak acid and drug B is probably a weak base
B. Drug A is probably a weak base and drug B is probably a weak acid
C. Drug A is a weak base, but becomes an acid when in the stomach
D. Drug B is a weak acid, but becomes a base when in the intestines - ANS-B
Always remember that weak acids absorb well in the stomach & weak bases absorb well in the intestines (because they are not ionized in those body compartments)
Mr. G, PA is recent graduate of a master's degree PA program. His program has prepared him in prescribing using rational drug selection. He feels confident that he can promote positive outcomes when prescribing. He is exploring licensure in a variety of states. (Ch. 1)
A. It will be absorbed primarily in the stomach and become ionized once it reaches the small intestine.
B. it will be absorbed primarily in the small intestine and become ionized once it reaches the blood stream.
C. Whenever it becomes ionized, the drug will attach to an active transport receptor and be carried into the blood stream.
D. It will be absorbed in the small intestine and be non-ionized in the blood stream and will be able to enter into a lactating woman's breast milk and also return to the bloodstream from the breast milk. - ANS-D
It is a weak base so, in this case it is a non-ionized in any pH greater than 4 - so it will be absorbed in small intestines, stay ionized in blood (7.45-7.45) and also be able to enter breast milk; since breast milk is 7.1, it will not ionize there either; there are not transport receptors for just any drug and they would not be active transport bc it is not an up gradient situation.
Referring to the same drug above (weak base that ionizes at <4). What will happen to its absorbability if the person takes omeprazole which raises the gastric pH to 5?
A. The drug will only be absorbed in the small intestine because it is a weak base.
B. The drug will be absorbed in the stomach and the small intestines.
C. The drug will ionize in both stomach and small intestine thus increasing its total absorption.
D. The drug will become a weak acid. - ANS-B
The only that changes is that it is not ionized in the stomach so it can also be absorbed there as well as any other area with a pH of 4.
A blood pressure drug is small, lipid soluble with no charge at all times and is 99% protein bound. The patient's dose has been titrated and is at the appropriate dose maintain good control of his HTN. Recently, the patient begins to take daily high doses of an additional OTC drug that is also small, lipid soluble, carries no charge and is highly protein bound. Which of the following is likely to happen with the introduction of the second drug?
A. The absorption of the blood pressure drug will increase because it is small, lipid soluble and has no charge
B. The blood pressure drug will have decreased effectiveness.
C. The patient will need to be monitored as he may become hypotensive.
D. Since both drugs are small, lipid soluble and have no charge, the will compete with eachother at the same receptor sites on body tissues. - ANS-C
If 1 protein-bound drug's dose is titrated for a specific effect, when you add another highly protein bound drug, both of them will compete for receptor sites on the albumin and more free (think active) drug will be in the plasma - this puts the person at risk for toxicity/OD from both drugs. These drugs have different actions and are not competing for the same receptor
Drug A is an inhibitor of CYP1A2. Drug B, a prodrug, is a substrate of this enzyme. What is the result on Drug B of the introduction of Drug A?
A. Drug B will be more toxic because it is not metabolized as well.
B. Drug B will have a weakened effect.
C. Drug B will not become water-soluble
D. This question cannot be answered based on the information provided - ANS-B
Prodrugs need to be metabolized or they have no effect. So, if the enzyme is decreased, there is less active drug.
A patient has a SNP that creates greater than normal amounts of very efficient/ active forms of CYP 3A4. This is the enzyme that deactivates drug G. Which of the following is accurate?
A. This patient will need higher doses of drug G in order to have the expected reaction.
B. Because this patient is an ultra-metabolizer, they need to be monitored for drug toxicity when give standard doses of drug G.