Pharmacologic Principles 1 & 2 Flashcards
1
Q
What are pharmaceutics?
A
Designing new drugs; The study of how various dosage forms influence the way in which the drug affects the body
2
Q
What is pharmacokinetics?
A
The study of how the body interacts with administered drugs; what the body does to the drug
3
Q
What does “Pharmakon” mean?
A
It has 2 meanings: drug(remedy) and poison
4
Q
What is Pharmacodynamics?
A
The study of what the drug does to the body
5
Q
What does ADME stand for?
A
Absorption
Distribution
Metabolism
Elimination/Excretion
6
Q
What does ADME measure?
A
It is the study of what happens to a parent drug from the time it is put into the body until the parent drug and all metabolites have left the body
7
Q
How can we define how much drug you absorb that reaches the blood stream?
A
Bioavailability is the amount of the active drug that reaches the bloodstream.
Bioavailability of drugs vary. IV drugs deliver 100% of the active drug.
8
Q
What is the most common route for drug absorption?
A
Oral route - drugs SWALLOWED orally
9
Q
What can influence oral drug bioavailability?
A
pH of the GI tract (Absorption)
Co-Administration w/ Drugs or Meals (Absorption)
Drug Formulation/ Pharmaceutics (Absorption)
P-Glycoproteins (Absorption)
First Pass Effect (Metabolism)
10
Q
Where are most drugs ABSORBED?
A
Stomach or small intestine
11
Q
Why does the pH of the GI tract affect the absorption of oral drugs? Affects absorption specifically.
A
Some drugs may need a basic or an acidic environment. If the GI tract does not fit the needs of the drug, the bioavailability will decrease.
12
Q
What are factors that can influence the pH of the GI tract? Affects absorption specifically.
A
Time of day (pH can fluctuate throughout the day)
With or without food
Medications (Tums®)
Lifespan (neonates, geriatrics)
Diseases/Conditions
13
Q
Describe what steps should be taken to increase Levothyroxine, an oral drug, bioavailability.
This is an example of a how the GI tract influences oral drug bioavailability. Affects absorption specifically.
A
Given first thing in the morning
Requires acidic environment, take on an empty stomach without any food/drugs
Avoid administering near medications that may change pH of the gut (like Tums® or Prilosec®)
14
Q
How does co-administration with drugs or meals influence bioavailability of oral drugs? Affects absorption specifically.
A
A) Certain drugs may adhere to one another, others may change the pH of the GI tract
B) Food alters pH of the GI tract and transit time
15
Q
Describe what steps should be taken to increase Doxycycline (Tetracycline) antibiotic, an oral drug, bioavailability.
This is an example of a how co-administration with drugs or meals influences oral drug bioavailability. Affects absorption specifically.
A
1: In general, take medication on empty stomach with a full glass of water ( 30 min to 1 hour before food or 2 hours after food)
Avoid administering with other medications (like Tums®)
Calcium carbonate (Tums®) can stick to doxycycline and render it ineffective
16
Q
How does pharmaceutics influence bioavailability of oral drugs? Affects absorption specifically.
A
Different formulations will have different dissolution rates
Liquid vs. Enteric Coated vs. Extended-Release Tablet
17
Q
Describe Liquid vs. Enteric Coated vs. Extended-Release Tablets.
A
Oral Liquids/Suspensions
* Already in dissolved form and thus absorbed quickly
* Sometimes called IR= Immediate Release
Enteric Coated Tablets
*Extra coating on the outside prevents drug from being broken down by the acidic pH of the stomach
*Drug is not absorbed until they reach the small intestine (higher pH)
*Commonly made to PROTECT the gastric mucosa from irritation
Famous Example: Enteric Coated Aspirin (EC)
Extended Release/Sustained Release Tablets
*Release drug over a prolonged period
*Abbreviations => SR, SA, CR, XL, XT, ER, and more
18
Q
What would happen if you crushed certain release forms?
A
The whole dose will be released very quickly and could be dangerous. Release products should never be crushed or modified.
19
Q
How does P-Glycoproteins influence bioavailability of oral drugs? Affects absorption specifically.
A
P-Glycoproteins are part of our “defense system,” and they affect the absorption of oral drugs. They are located within essential areas of the body: Blood Brain Barrier, GI Tract.
P-Glycoproteins are called “Anti-absorption pumps” or Efflux Pumps because they are designed to pump out xenobiotics (toxins, drugs). Because P-Glycoproteins are designed to pump out xenobiotics, the absorption of oral drugs is decreased. There is less absorption of oral drugs into the general circulation.
20
Q
Describe what the P-Glycoproteins (Efflux Pumps) do in the intestines.
A
Hint: P-Glycoproteins affect absorption specifically.
In the intestines, they pump xenobiotics (xeno=foreign) back into the intestinal lumen.
This prevents less of the xenobiotic getting into the blood stream
21
Q
What are P-Glycoprotein Inhibitors, and how do they affect absorption of oral drugs?
A
P-Glycoprotein inhibitors inhibit P-glycoproteins. P-Glycoprotein inhibitors cause the oral drug to be absorbed more than intended.
22
Q
What food may block/prevent normal P-glycoprotein function (P-Glycoprotein inhibition)?
A
Grapefruit and Grapefruit Juice
23
Q
True or False: An example of P-Glycoprotein inhibition is the cholesterol lowering drug class commonly known as “Statins.”
A
True
24
Q
True of False: “Statins” have a risk of rhabdomyolysis or rapid muscle breakdown (risk increases based on dosage)
A
True
25
If a patient takes Atorvastatin and drinks Grapefruit Juice, the Grapefruit Juice inhibits the P-glycoproteins, allowing the body to absorb more Atorvastatin than anticipated.
How does this affect the risk of Atorvastatin toxicity?
This increases the risk of the patient reaching toxic levels of Atorvastatin.
26
What drugs are affected by the First Pass Effect?
Only oral drugs are affected by the First Pass Effect.
Please understand that Buccal & Sublingual drugs are a separate category from oral drugs which means they are not affected by the First Pass Effect.
27
How does First Pass Effect influence bioavailability of oral drugs? Affects metabolism specifically.
Drug is swallowed, goes to GI tract, gets absorbed into GI mucosa, and then 100% of that drug goes to the liver before getting into the general circulation. When the drug is in the liver, the liver destroys the drug which causes a smaller amount of the drug to pass into general circulation.
If a large proportion of a drug is chemically changed into inactive metabolites in the
liver, then a much smaller amount of drug will pass into the circulation. This is an example of a drug with a high first pass effect.
First-pass effect reduces the bioavailability of the drug to less than 100%. Many drugs
administered orally have a bioavailability of less than 100% because of this.
28
What are the steps of oral drug administration via the First Pass Effect?
1. Swallow the drug orally
2. Drug travels down the GI tract
3. Drugs can get absorbed in GI tract:
gastric mucosa (stomach) or Intestinal mucosa (small intestines)
4. The gastric/intestinal mucosal blood flow goes to portal vein
5. Portal Vein carries the blood to the Liver
6. Liver metabolizes drugs (FIRST PASS EFFECT)
7.Metabolized drug reaches general blood circulation
29
What is bioavailability, and what influences bioavailability?
Bioavailability is the term we use to measure the percentage of drug that reaches the general blood stream
Influences: Route & Pharmaceutics
30
Describe the bioavailability of IV vs Oral routes?
IV route is 100% Bioavailable while the Oral route is variable
31
Morphine oral bioavailability is ~17-33%
Oral morphine to IV morphine ratio is 3:1
Why is the dosage for oral morphine higher than the dosage for IV morphine?
Oral morphine has a lower bioavailability than IV morphine which is why a higher dose of morphine is needed to achieve an equal concentration of the morphine administered through IV. IV morphine has a bioavailability of 100% , and morphine oral bioavailability is ~17-33%
32
Naloxone oral bioavailability ~2%
Would it be appropriate to give this as an oral dose to achieve a therapeutic effect?
No because the bioavailability is way too low for it to achieve a concentration which will yield a therapeutic effect. The liver will metabolize most of the drug through the First Pass Effect which will yield it to be ineffective as an oral treatment.
33
Levofloxacin oral bioavailability ~99%
Patient on 500 mg of IV Levofloxacin every 24 hours in the hospital. What dose do we send them home on?
500 mg of oral Levofloxacin because the bioavailability between the oral and IV forms are nearly identical.
34
What are the 3 major routes of pharmacokinetic absorption?
Enteral (GI Tract)
Parenteral (Injections)
Other/Miscellaneous (Eye drops, Inhalers, etc.)
35
Describe Enteral (GI TRACT) absorption route. What are examples of common enteral routes?
The drug is absorbed into the systemic circulation through the GI tract. The Enteral route has variable Bioavailability
Common examples: Oral, Sublingual/Buccal, and Suppositories.
36
Describe the absorption sites and bioavailability of the common Enteral routes (Oral, Sublingual/Buccal, and Suppositories).
Oral: Mostly intestinal mucosa, rarely gastric mucosa
Sublingual/Buccal: Oral mucosa
Suppositories: Rectal/vaginal mucosa
Variable bioavailability for all.
37
What are sublingual drugs?
Drug is placed under the tongue, allows for rapid absorption via the oral mucosa
EXAMPLE: NitroSTAT- Nitroglycerin tablets used for acute chest pain (heart attack or angina)
38
What are buccal drugs?
Drug is placed between the cheek and gum to allow for absorption via the oral mucosa
EXAMPLE: Actiq®- A fentanyl “lollipop” for acute, extreme breakthrough cancer pain
39
What are the key points for Sublingual and Buccal drugs?
* Drug is absorbed in the oral mucosa of the mouth and goes directly into the blood stream
* Must allow the drug to dissolve
* Swallowing the medication may inactivate the medication (pH of stomach)
* Do not eat or drink until medication has dissolved
40
Do Sublingual and or Buccal drugs undergo the First Pass Effect?
No.
They do not pass through the liver to be metabolized. They are both absorbed into the oral mucosa not the gastric mucosa or intestinal mucosa.
41
Describe PARENTERAL absorption route. What are examples of common PARENTERAL routes?
Non-GI-Tract administration, aka injections. The drug is absorbed into the systemic circulation.
Common examples: Intravenous, Intramuscular/Subcutaneous/ Intradermal, Epidural
42
Describe the absorption sites and bioavailability of the common PARENTERAL routes (Intravenous, Intramuscular/Subcutaneous/ Intradermal, Epidural).
IV
Bioavailability: 100%
Absorption site: Blood stream
Intramuscular/Subcutaneous/ Intradermal
Bioavailability: Varies
Absorption site: Depends on location
Epidural
Bioavailability: Varies
Absorption site: Epidural space around the spinal cord
43
How much IV morphine do we absorb?
100%
44
Why must IV formulations have similar pH to blood?
Damage can happen to veins/arteries
45
True or False: Drugs administered through the parenteral (Injectable) absorption route need to be dissolved.
FALSE
Drug is immediately in solution (no need to dissolve). Therefore, drug is 100% absorbed and ready to work (100% bioavailable)
46
What liquid cannot be injected?
Diphenhydramine
47
What are the 3 MISCELLANEOUS ROUTES for drug absorption discussed in class? Describe absorption sites and bioavailability.
Inhalation:
Bioavailability: Varies
Absorption site: Complex
Topical/Transdermal:
Bioavailability: Varies
Absorption site: Dependent on location
Instillation (eye/ear/nose drops/sprays):
Bioavailability: Varies
Absorption site: Dependent on location
48
Describe absorption sites for Topical/Transdermal. Give an example of how Topical/Transdermal works.
Skin, Eyes, Ears, Nose, Rectum, Vagina, Lungs and more.
Absorbed through multiple surfaces. May be local or systemic.
Example: Fentanyl patch is placed on the skin. Adhesive holds the patch in place, drug reservoir allows permeation the drug through the skin
49
True or False: If the amount of a local medication is increased, local absorption and transfer to systemic absorption.
True
50
Describe the differences between hydrophilic, lipophilic, polar, and non-polar drugs?
Hydrophilic and polar drugs require a transporter to work (also can say that the cell membrane needs a receptor for the hydro and polar drugs). Hydrophilic drugs are the main way the body excretes drugs.
Lipophilic and non-polar drugs can easily cross cell membranes.
51
How does the body excrete lipophilic drugs?
Coverts the lipophilic drug into a hydrophilic drug, so that the body can excrete the drug via urine
52
Describe lipid soluble and water soluble drugs.
Lipid Soluble
* Easily distribute into fatty tissues where they may store or concentrate
* Have the potential to cross the Blood Brain Barrier (BBB) and the Placenta
* Cell membranes are made of a phospholipid bi-layer which is why lipid soluble drugs are able to easily cross the cell membrane. Like dissolves like.
*Steroids are an example of lipid drugs.
Water Soluble
* Typically remain in highly vascularized spaces and can easily leave the body via elimination (urine!)
53
Which drug type would reach a developing fetus? Cross into Breastmilk? Which type would reach the brain?
Fetus: Non-polar and lipophilic drug because they can easily cross cell membranes.
Breastmilk: Non-polar and lipophilic drug because they can easily cross cell membranes.
Reach the brain: Non-polar and lipophilic drug because they can easily cross cell membranes.
54
What is the most common blood protein?
Albumin
55
Some drugs preferentially bind to protein/albumin, and they are called ____.
Highly bound drugs
56
What are the differences between Free and Bound Drugs?
Free drug (active)
* Drug is not bound to albumin can distribute into extravascular tissue to its intended target
Bound drug (inactive)
* Stuck to albumin, stays in the bloodstream
* Cannot get to extravascular space and reach intended target
* When a drug is stuck to a protein it cannot function which is why bound drugs are inactive.
* Bound drugs are generally too large to pass through the walls of blood
capillaries into tissues which renders the bound drug to be ineffective.
57
Describe the protein bonding of the highly protein bound drug Phenytoin (seizure medication) if 100 mg of Phenytoin is given via IV.
10% Free, 90% bound
This means that on 10% of the drug is active, and 90% of the drug is inactive.
58
What are potential complications of Highly Protein Bound Drugs?
* Deficiency in Protein/Albumin may result in drug toxicity. There is not enough protein/albumin for the highly protein bound drugs to bind to which will result in a large amount of free (unbound) drug, and this raises the risk of drug toxicity.
* Competition (two drugs can result in toxicity): When an individual is taking two medications that are highly protein bound,
the medications may compete for binding sites on the albumin molecule.
Because of this competition, there is more free or unbound drug which raises the risk of drug toxicity.
59
Describe the Circulatory/Blood supply aspect of drug distribution.
Drugs distribute faster in areas with more blood flow.
Drugs distribute rapidly in vital organs like the kidneys, heart, liver and brain (more blood flow in these areas). Drugs distribute slowly in muscle, skin, and fat (less blood flow in these areas).
Lower doses of med in areas with more blood flow, and higher doses of med in areas with low blood flow.
60
What diseases or conditions affect circulation/blood supply aspect of drug distribution?
Diseases/Conditions can alter perfusion (blood flow)
-Poor perfusion
-Peripheral Vascular Disease
-Heart Diseases (Heart Failure): may not pump blood adequately, so it may be harder for drugs to reach body
-Shock (Sepsis): blood pressure is low, so blood is not pumping fast enough
Poor perfusion may cause medication to take longer to reach the area it needs to be in order to treat the issue.
61
What are the 3 parts of drug distribution? Describe how they affect drug distribution.
Protein Binding: It can cause drug toxicity, and it interferes with the amount of active drug which is able to distribute into extravascular tissue.
Circulation: Drugs will be distributed depending on the amount of blood flow to an area. High blood flow means rapid distribution and low blood flow means slow distribution of the drug. Diseases which cause poor perfusion hinder drug distribution because blood flow is decreased which causes drugs to be distributed to that area more slowly.
Permeability: Lipophilic and non polar drugs can easily cross cell membranes. Hydrophilic and polar drugs need a transporter or receptor outside of the cell to cross the membrane.
62
What organ is primarily responsible for metabolism?
Liver
63
What is a target drug?
Also called a substrate.
It is the drug that is metabolized by the liver.
64
Do all drugs go through metabolism?
No.
An example of this is UTI medications. UTI meds go directly to the kidneys without ever going to the liver.
65
What does the liver convert drugs into?
Active or inactive metabolites. Metabolites can be weaker or stronger than the original drug. Metabolites can also be toxic to the body which can cause body damage.
66
What is the ultimate goal of metabolism?
Drugs are metabolized to increase their water solubility to allow elimination in urine.
67
What groups of people may negatively affect their metabolism?
Livers in neonates are still developing. Livers in older adults are decreasing in function.
People with liver disease.
68
Why did some kids die when taking codeine for their tonsillectomies?
Some of the kids livers rapidly converted the parent drug codeine into the metabolite morphine which led to drug overdoses.
A similar phenomenon happened with breast feeding mothers. Some breast feeding mothers were taking codeine and their livers rapidly converted the codeine into the metabolite morphine. Morphine was then passed to the infant via breast milk which led to infant deaths.
69
What are the liver enzymes that metabolizes drugs? Describe the purpose of these enzymes.
Cytochrome P-450 (CYP450).
These enzymes generally target lipophilic and non-polar drugs in order to convert them into hydrophilic and polar drugs, so that they can be excreted in urine. It is important to that the liver will add groups or remove groups in order to make the drug hydrophilic and polar so that it can be excreted in urine.
70
What is the most common metabolite of CYP450? It is comprised of 50% of all metabolites.
3A4
71
What is liver enzyme induction?
Speed up liver
Shorten 1/2 life
Decreased pharmacologic effects
Drug breaks down quicker
72
What is liver enzyme inhibition?
Inhibit drug-metabolizing enzymes
Slows down liver
Decreases in drug metabolism result in the accumulation of the drug
and prolongation of the effects of the drug, which can lead to drug toxicity
73
What are some factors that influence enzyme inhibition/induction?
Other drugs
Certain Foods (Grapefruit) - Grapefruit is a liver enzyme inhibitor, so you will absorb more drug than expected AND it will stay around longer than expected.
Smoking/Alcohol
Other influences
Patient variables
Diseases (liver diseases)
Genetics*
Age
-Infants have limited liver enzymes
-Geriatric patients may have less liver enzyme activity
Younger patients need lower doses because their livers may not be able to metabolize the drug quickly. Same with geriatric patients.
74
You have a patient who takes warfarin (an anticoagulant) to prevent the inappropriate formation of blood clots.
Warfarin goes through liver metabolism via CYP1A2, CYP2C19, CYP2C9 , CYP3A4
What happens if you give Warfarin with Fluconazole?
Fluconazole is a liver enzyme inhibitor.
Because Fluconazole is a liver enzyme inhibitor, the liver enzymes will not be able to metabolize the Warfarin. The half life of Warfarin will be increased. Warfarin will continue to build in the body because the liver cannot break it down, and it may reach toxic levels.
75
You have a patient who takes warfarin (an anticoagulant) to prevent the inappropriate formation of blood clots.
Warfarin goes through liver metabolism via CYP1A2, CYP2C19, CYP2C9 , CYP3A4
What happens if you give Warfarin with Phenytoin?
Phenytoin is a liver enzyme Inducer.
Warfarin's metabolism will be sped up which will cause the drugs half life to be decreased. Patient will not be getting enough Warfarin, may need to double dose of Warfarin.
76
What are the liver enzyme inducers?
Mnemonic: PS-PORCS
No need for exam 1
P – phenytoin
S – Smoking
P – phenobarbital
O – Oxcarbazepine
R – rifampin
C –carbamazepine
S – St. John’s Wort (OTC herb)
77
What are the liver enzyme inhibitors?
Mnemonic: PACMAN loves Grapefruit juice!
No need for exam 1
P – protease inhibitor (HIV)
A – azole antifungal (fluconazole, ketoconazole)
C – cimetidine (H2RAs)
M – macrolides (ACE, Azithromycin, Clarithromycin, Erythromycin)
A – amiodarone
N – non-DHP Calcium Channel Blockers (diltiazem, verapamil)
♥’s
Grapefruit juice
78
What are Pro-Drugs?
They are inactive drugs that becomes active once metabolized by liver. They can help improve bioavailability
79
What is the role of the liver?
ROLE OF THE LIVER (HEPATOCYTES)
Metabolism of drugs (CYP enzymes)
Metabolism of hormones
Protein Synthesis and degradation
Coagulation- uses Vitamin K to make clotting factors
Albumin
Glycogen storage (Glycogenesis)
Cholesterol- Lipids + Bile Acid metabolism
80
What causes impaired liver function like cirrhosis or hepatoxicity?
DRUGS (Drug Induced Liver Injury- DILI)
Drugs that are hard on the liver (hepatotoxic)
Alcoholic Liver Disease
Hepatitis
81
What are some signs/symptoms of impaired liver function?
Dark urine- (bilirubin mixes with urine)
Jaundice (yellow eyes, liver no longer filters bilirubin from blood, or can’t conjugate it so it can’t be removed via bile)
Swelling of abdomen (no longer making sufficient albumin)
Bruising/Bleeding (lack of clotting factors)
Fatigue
Ammonia can concentrate (liver normally converts to urea)
* Ammonia accumulation- neurological changes- encephalopathy
82
What tests can be done to check liver function?
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
AST and ALT will be elevated if the patient has liver impairment
Normal ranges
AST: 0 to 35 units/L
ALT: 4 to 35 units/L
83
A patient is taking Tylenol® (acetaminophen) but has exceeded the maximum dosage. Exceeding the maximum dosage is known to harm the liver.
1. What is a medical term for this?
2. What are some lab values to observe?
3. What will the lab numbers look like?
4. Will there be any symptoms?
1. DILI or hepatoxicity
2. AST and ALT
3. Above 35 units/L
4. Dark urine, fatigue, jaundice, bruising/bleeding, abdomen swelling
84
What is the primary site of drug elimination?
Kidneys are the primary site.
Drugs may also exit through Liver, Breast milk, Sweat, Bowel (biliary excretion, enterohepatic recirculation).
85
What is serum creatinine?
What are the normal lab values?
What do abnormal lab values look like?
Definition: Byproduct of muscle break down. Looking at how well your kidneys are filtering.
Looks at muscle mass, so it may not be accurate in every situation. For ex, a 21 year old male body builder and a elderly male both have a serum creatinine of 1. It is hard to tell what that means. Younger people have better kidneys that older people. This is why its not used alone for kidney function.
Lab values:
Men= 0.6-1.2 mg/dL
Women= 0.5- 1.1 mg/dL
If patient has renal impairment, their serum creatinine will be elevated.
86
What is the study state?
Drug eliminated = drug absorbed
87
What is creatinine clearance?
What are the normal lab values?
When does the value indicate renal impairment?
How well you filter out creatinine. AKA pee out creatinine
This a calc which includes age, sex, and serum creatinine. It is a better predictor than serum creatinine alone.
Normal lab values:
90-120 ml/min*
Low creatinine clearance indicates renal impairment. High creatine clearance is normal.
88
You have a kidney injury, and your kidneys are not filtering correctly. What happens to your serum creatinine?
Increased serum creatinine because the kidneys are not able to get rid of it adequately
89
Describe creatinine filtration.
Creatinine is filtered through the glomerulus. Glomerulus also captures pre urine.
90
What happens if the glomerulus is not working?
Serum creatinine and BUN levels will increase
91
Would your creatinine clearance be low or high with normal kidney function? Abnormal kidney function?
High creatinine clearance for normal kidney function.
Low creatinine clearance for abnormal kidney function
92
Do you want a high Glomerular Filtration Rate (GFR) or low GFR?
High GFR have normal kidney functions.
Ball Park Acceptable Range is 90-120 ml/min
93
Blood Urea Nitrogen (BUN)
High BUN levels mean that pts blood urea nitrogen is not getting filtered out of the blood
Normal Levels:
8-20 mg/dl
Abnormal BUN levels are elevated which indicate renal impairement.
94
Urine output as it relates to kidney function
Low levels of urine output indicate that pt is not peeing well
Normal levels:
>30 ml/hr
Less than 30ml/hr indicates an issue with kidneys
95
What lab values should you look at for kidney function?
BUN
GFR
Creatinine clearance
Serum Creatinine
96
What does it mean if someone's Serum Creatinine and BUN increases?
Decreased kidney function
97
What does it mean if someone's GFR/CrCl decreases?
Serum creatinine has increased which is indicative of kidney injury
98
Scenario: What if someone is taking Amoxicillin 500 mg PO four times daily, but develops Acute Kidney Injury (AKI). What do you do?
Decrease dosage and frequency
99
What is Acute Kidney Injury?
Injury to the kidney which results in a sudden elevated SCr/BUN and a decreased eGFR/CrCl
High levels are able to bounce back
100
What is Chronic Kidney Disease?
chronically elevated SCr/BUN, decreased eGFR/CrCl
Basically stuck at elevated levels mentioned above - cannot bounce back like acute kidney disease; repetitive kidney damage
101
What is Nephrotoxicity?
Certain drugs may be harmful to the kidneys. We call the resulting damage, nephrotoxicity.
Hard on the nephron. Ibuprofen is nephrotoxic b/c it damages nephron in kidneys
102
Define the steps within pharmacokinetics.
Graph is in Pharm principles 1 slide 74
ONSET
The time it takes for the drug to elicit a therapeutic response
DURATION
The time a drug concentration is sufficient to elicit a therapeutic response
Minimum Effective Concentration (MEC)
Minimum concentration needed to produce desired effect
Therapeutic Index/Range
Enough drug present to produce therapeutic response, but not enough to be toxic
Toxicity
Plasma drug levels climb too high, toxicity occurs; drug concentration goes above peak
Peak
Max drug concentration in body
Narrow therapeutic window
15 drugs have a small therapeutic window
103
Most drugs DO NOT require drug level checks (thanks to clinical trial research).
However, some drugs do. What drugs require drug level checks?
NARROW THERAPEUTIC INDEX drugs require frequent/periodic level checks. They are 15 of these drugs with very small therapeutic windows.
104
What is the steady state for drugs?
30 mins pharm principles week 2 day 2
The physiologic state when amount of drug removed equals amount of drug absorbed. Drug in = drug out.
Most pharmacokinetic experts agree that steady state is achieved after four half lives
105
After patient has reached steady state, when do you check peak (highest blood level)? trough (lowest blood level)?
PEAK LEVEL
Highest blood level (drawn ~30 minutes AFTER a dose)
Do not take peak while the pt is receiving medication because that can cause abnormal readings
TROUGH LEVEL
Lowest blood level
Check 30 minutes to 1 hour prior to the next dosing interval
106
Vancomycin 1 IV every 24 hours ordered
Measure a PEAK
When? Why?
Measure a TROUGH
When? Why?
What happens if the Vancomycin trough came back elevated?
PEAK
30 mins AFTER dose is given.
minimize drug toxicity
TROUGH
verify adequate drug exposure, maximize therapeutic effects, and
minimize drug toxicity
ELEVATED TROUGH
Could indicate that the drug has reached toxic levels or half life increased for drug
-----
LOW TROUGH (just extra need to know info)
If the trough blood level is too
low, then the drug may not be at therapeutic levels to produce a response.
107
A patient is ordered Vancomycin 2000 mg IV every 36 hours (assume half life is 36 hours)
After how many half lives will it take to reach steady state?
When should a peak be checked? Clinically, we don’t check peaks for Vancomycin
When should a trough be checked?
The Narrow Therapeutic Index for Vancomycin is 10-20 mcg/ml. You check a trough, and the result comes back as 45 mcg/ml. The pharmacist calls and says they calculated a new half life of 48 hours for this patient. How long will it take for the patient’s level to get back into therapeutic range?
Check pharm principles slide 84 for answers
After how many half lives will it take to reach steady state?
ANSWER: We wait until after ~4 half lives (36 hours x 4= ~144 hours from now)
When should a peak be checked?
ANSWER: 30 minutes after the most recent dose has been given. Make sure to count 30 minutes after the end of the infusion.
When should a trough be checked?
ANSWER: The dose is being given every 36 hours. We should check 30 minutes to 1 hour prior to the next dose
Last Question Answer
Lab draw was Tuesday morning at 0900= Current level is 45 mcg/ml
1 half life (48 hours later from lab draw, its now Thursday morning @ 0900), new level is 45/2= 22.5 mcg/ml
2 half lives ( 96 hours later from lab draw, its now Saturday morning @ 0900) , new level is 22.5/2= 11.25 mcg/ml (this is within the 10-20 mcg/ml range!)
We know for sure the answer is 96 hours (2 half lives later
108
A patient has been prescribed Vancomycin, an antibiotic that is renally eliminated and known to cause kidney damage. The prescriber incorrectly orders a dose that is too high. What happens next?
1. What is a medical term for this?
2. What are some lab values to observe?
3. What will the lab numbers look like?
4.Will there be any symptoms?
1. Nephrotoxicity/Acute Kidney Injury/declined renal function
2. SCr, BUN, eGFR, CrCl, Urine Output
3. SCR,BUN will be elevated
EGFR,CrCl and Urine Output will be decreased
4. The patient may have decrease urination due to the declining renal function
109
What is pharmacodynamics?
The study of what the drug does to the body.
Drug-receptor relationships can be represented by Lock and Key mechanism. A specific substrate can bind to an enzyme to unlock a specific action. Locks are the receptors.
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What are receptors?
Receptors are a reactive site on the surface or inside of a cell
Drug or chemical binds to the receptor site and interacts creating a response
Our example was the Opioid Receptor
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Can "responses" have a positive and negative benefit?
Responses refer to cell receptor response to binding with a drug.
Yes.
Response could have positive/negative benefit (relative)
Morphine could cause pain relief (positive benefit)
Morphine could cause constipation or decreased breathing (negative benefit)
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If two drugs are fighting for the same receptor, what will determine which drug will bind to the receptor?
"Affinity" - degree to which a drug (Key) attaches to a receptor (Lock). The stronger drug will attach to the receptor.
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What is an agonist? Provide example.
Drug that binds to a receptor and causes a response. Enhances body's physiological response.
Example: Opioid
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What is an antagonist? Example?
Drugs that bind to a receptor and do not cause a response.
Example: Naloxone (Narcan)
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What is a partial agonist? How can they be used?
Agonists that are partially activated. Will not reach 100% activation of the agonist. Partial agonist will eventually plateau.
They can be used for people with drug addictions. The agonist can bind to receptors to induce a bodily responses to wean off withdrawals
Ex: methodone
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If morphine and naloxone were competing for a receptor, who would bind to the receptor?
The drug with the higher affinity
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Intended Outcome=Expected Pharmacological Action (GOAL)
If we give morphine, we should EXPECT pain relief
Clinically, we measure this as a pain score (0 through 10)
Assess: Patient reports 10/10 pain.
Implement: Give morphine
Evaluate: should EXPECT a lower number (like 3/10)
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Intended Outcome=Expected Pharmacological Action (GOAL)
If we give metoprolol tartrate, we should EXPECT a lower heart rate
Clinically, heart normal heart rate range is 60-100 beats per minute (bpm)
Assess: Patient has heart rate of 110 beats per minute
Implement: Give metoprolol
Evaluate: should EXPECT a lower number (80 bpm)
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Describe Unintended Outcome = Adverse Drug Event (ADE).
This is when someone is harmed by a medication
Can be Expected or Unexpected
Could be appropriate or inappropriate use of the drug:
1)Medication Error
-Wrong dose for example
2) Adverse Drug Reaction
-Allergic reaction
-Pharmacological Mechanism of the Drug
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What is the difference between drugs that are precaution/caution and CONTRA-INDICATION?
PRECAUTION/CAUTION
Can still use the drug, but BE CAREFUL and MONITOR (Evaluate Benefit vs Risk)
Example:
*Caution in using Morphine in patients with Obstructive Sleep Apnea
*Both can decrease breathing during the night- dangerous!
*Evaluate Benefit vs Risk- Should we give high dose opioids to a patient with sleep apnea?
CONTRA-INDICATION
*HARD RULE -DO NOT GIVE UNDER ANY CIRCUMSTANCES
*Technically, there are relative and absolute contra-indications
Example:
Patient is allergic to Morphine, giving will result in anaphylaxis, potentially death
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Your patient is ordered 4 mg of IV morphine x 1 now.
Fill out the blanks below
Pharmacodynamics:
LOCK (receptor):
KEY (drug):
Drug Type:
Action/Response?:
LOCK (receptor): Opioid receptor
KEY (drug): Morphine
Drug Type: Agonist
Action/Response?: Yes, will illicit cellular response
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APPLY THE NURSING PROCESS:
ASSESS: Before giving morphine
?
EVALUATE: After giving morphine
INTENDED OUTCOME: ?
UNINTENDED OUTCOME: ?
What does ISMP and JCAHO classify Morphine as ?
ASSESS: Before giving morphine
General:
Check Pre-cautions (certain conditions, diseases, etc.)
Check Contra-indications (allergies)
Drug Specific:
Morphine : Check Vital Signs (Respiratory Rate, Blood Pressure, Pulse)
EVALUATE: After giving morphine
INTENDED OUTCOME: Pain relief, improved Pain Score #’s
UNINTENDED OUTCOME: Adverse Drug Reaction
Pharmacological/ Drug Toxicity:
Patient receives too much Morphine and stops breathing- Respiratory Rate too low
Allergic/Hypersensitivity Reaction (Type through Type 4)= IMMUNE RESPONSE:
Patient develops HIVES when given Morphine
Drug-Drug Interactions:
Patient drank alcohol= enhanced effects (drug toxicity)
Patient received dose of naloxone (antagonist)= competition, decreased effects
JCAHO and ISMP identify Morphine (opioid) as a HIGH RISK/HIGH ALERT Drug
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EXAMPLES HIGH ALERT DRUGS/DRUG CLASSES?
Antibiotics:
Penicillin
Cardiac Medications:
Epinephrine, Metoprolol
Anticoagulants:
Warfarin, Heparin
Diabetes Medications:
Insulin
Opioids:
Morphine
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What are the following outcomes with the actions on the drugs?
1. Crushing an Immediate Release Tablet (IR)
2. Crushing an Extended Release Tablet (ER)
3. Crushing an Enteric Coated Tablet (EC)
4. Swallowing a Sublingual Tablet (SL)
1. Will not have any drastic effect on drug's absorption
2. Drug absorption rate will be altered, causing unexpected, increased levels of the drug
3. Crushing may result in irritation of the stomach lining
4. The drug may not be absorbed by the GI Tract
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Explain why clinicians often monitor plasma drug levels and describe how these levels are regulated to prevent drug toxicity (peaks and troughs).
Steady state is achieved around 4 half lives.
Important to check drug state earlier than later because the risk in delaying dose adjustments increase with time.
If the dose was toxic, we might put our patient at harm if we didn’t check until after 5 or 6 half lives. The level should clearly be too high if we check after the 4th half life
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Describe drug half lives?
The time it takes for one half of the current amount of a drug to be removed from the body
A measure of the rate at which a drug is removed from the body
Most drugs considered to be effectively removed after about five half-lives
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Identify common causes of Adverse Drug Events (ADEs)
1)Medication Error
-Wrong dose for example
2) Adverse Drug Reaction
-Allergic reaction
-Pharmacological Mechanism of the Drug
