Intro to Pharm Flashcards
Week 1
What do pharmacokinetic, dynamic, and genetic principles explain in the context of drug response?
They provide the scientific theory to explain drug response which enhances the ‘art of anesthesia’
These principles are crucial for understanding how drugs interact with the body and how genetic factors can influence these interactions.
What does pharmacokinetics study?
The influence of bodily processes on drug effect
This includes how drugs are absorbed, distributed, metabolized, and excreted by the body.
What is pharmacodynamics?
The influence of drug on body processes
It examines how drugs exert their effects on the body, including mechanisms of action.
What does pharmacogenomics/pharmacogenetics focus on?
How a patient’s genetic make-up influences drug response
This field studies the role of genetics in drug metabolism and efficacy, leading to personalized medicine.
What is the impact of a single nucleotide variant or altered gene coding?
It can significantly influence drug response
Variants can affect how drugs are metabolized and their therapeutic effects.
What are some confounding variables that can influence desired drug response?
- Age
- Co-morbidities
These factors can affect drug pharmacokinetics and pharmacodynamics, leading to variability in treatment outcomes.
Relationship b/t Pharmacokinetics and Pharmacobiophysics
Kinetics = The drug dose
Biophysics = the concentration of the drug in the plasma over time
“What the drug does to the body”
Relationship b/t Pharmacobiophysics and Pharmacodynamics
Biophysics = Drug concentration at the site of action “Effect site” or “biophase”
Dynamics- the pharmacological effect
“What the drug does to the body”
What is the biophase
The relationship b/t drug concentration in the plasma and effect site
Name the 4 phases of pharmacokinetics
absorption
distribution
metabolism
excretion
Where does metabolism or biotransformation occur
Either Liver or the kidney
What is the first step in passage of a drug through the body?
absorption
What does the rate of systemic absorption determine?
A given drug’s intensity and duration of action
Incomplete absorption limits the amount of drug that
reaches the site of action to produce the pharmacological effect
T/F: IMV drugs bypass absorption
True: They go directly into the bloodstream
What key factors impact the degree of drug absorption (5)
Route: determined by desired time of onset and duration
Solubility: more lipid soluble = faster absorption
Conditions at site of absorption= more surface area for absorption and degree of blood flow
Degree of ionization
Bioavailability- fraction that reaches systemic circ
What are the routes of drug administration
Oral/Enteral: PO, NGT, Rectal
Parental: SC, IM, IV, Intrathecal
Inhalational
Sublingual
Intranasal/Topical
Transdermal
Name the onset of drug routes from fastest to slowest
IV > IM > SC > PO
Name drug routes from longest to shortest for drug duration
Longest: PO > SC > IM > IV (Shortest)
Advantages of Oral/ Enteral Administration
convienent
Larger margin of safety
economical (cheaper)
What is the biggest disadvantage of oral administration and other disadvantages?
BIGGEST: Patient Compliance (educational, financial, availability)
Emesis
Enzymatic destruction
Irregular absorption (influence on food/meds and First Pass)
Size of surface are for absoptiona nd degree of BF (stomach vs. small intestines)
What 2 things impact absorption
Lipid solubility and Ionization
T/F Hydrophilic drugs pass the CWM greater than Hydrophobic drugs
False
Hydrophilic = ionized = water soluble = electrical charge which is repelled by the CWM
Hydrophobic= lipophilic
What is bioavailability
the amount of free drug that binds to target sites and produces wanted effect
Fraction o funchanged drug that reaches systemically and the rate at which it occurs
Name some factors that decrease bioavailability
Incomplete absorption from
GI tract
Degree of blood flow to area (decreased in SHOCK, Hypotension)
Lipid solubility
Pulmonary uptake of drug
Degree of ionization
First pass effect of the liver - hepatic uptake DECREASES bioavailability
What is the First Pass Effect?
Drugs absorbed from the GI tract enter the portal vein and pass through the liver before entering circulation.
How does the First Pass Effect impact bioavailability?
If a drug undergoes extensive hepatic extraction and metabolism, only a small fraction of the drug reaches systemic circulation.
What accounts for the large difference between oral and IV dosages?
The First Pass Effect.
Name drugs that exhibit significant First Pass Effect.
Inderal, Morphine, Lidocaine, Metoprolol.
so the Oral dose is WAY BIGGER than the IV dose
What is Enterohepatic Recirculation (EHRC)?
A process where drugs are recycled through the liver and intestines, potentially prolonging the duration of action of a drug
How can EHRC impact drug elimination?
If EHRC is blocked, the elimination of drugs undergoing EHRC may be increased.
Give an example of a drug that can block EHRC.
Antibiotics that decrease gut flora and deconjugating enzymes.
What is a consequence of blocking EHRC for drugs like birth control pills?
They may be excreted more rapidly = birth control is ineffective
ex- antibiotics decrease gut flora and deconjugating enzymes, birth control pills also undergoes ERHC is excreted faster
What are some common drugs that block enterohepatic recirculation
Antibiotics
NSAIDS
Warfarin
Hormones
opioids
digoxin
What is a key benefit of sublingual administration?
Rapid onset of drug effect.
What is the bioavailability of drugs administered sublingually?
100% bioavailability.
How does sublingual administration bypass the First Pass Effect?
It drains directly into the superior vena cava.
What is a common drug administered sublingually?
Nitroglycerine.
Why is rectal administration losing popularity?
It is less preferred for most patients. lol
sometime used in quick pediatric procedures to avoid an IV
What factors affect absorption in rectal administration?
Proximal versus distal rectum.
If inserted to the proximal rectum: a drug undergoes a ____________________
first pass effect
What can result in unpredictable absoprtion of a rectally administered medication
shit
What is a benefit of transdermal administration?
Sustained release provides steady plasma concentration.
avoids peaks and valleys
What are the advantages of transdermal administration?
- Low incidence of side effects
- Fewer dosing intervals
- High patient compliance
- Avoids first pass effect of the liver b/c it bypasses the GIT
Drug characteristics required for transdermal absorption
low molecular weight (>1000?)
Absence of histamine release
Low daily dose ( <10mg/day)
combo of water and lipid soluble form
why does a transdermal medication require both water and lipid solubility
water solubility needed to enter bloodstream from skin
Lipid solubility needed to enter cell
What are 5 meds that you can administer transdermally
fentanyl
scopolamine
clonidine
NTG
Nicotene
Where should you apply a transdermal patch
somewhere with thin epidermis and good blood supply
hydrated skin is more permeable
Warm skin is more vasodilated = better blood supply = better absorption
psoriasis skin is thicker avoid areas of breakout
Scopalamine patch
dose and duration
use
location of administration
Dose: 1.5 mg patch that delivers 1 mg over 3 days
use: PONV and motion sickness
apply to post auricle area
needs to be applied atleast 4 hours before for efficacy
Name the med for the CTZ Zone:
5HT3
Ondansetron- 5HT3 antagonist
Name the med for the CTZ Zone:
Histamine blocker
Benadryl for H1
Famotidine for H2
Name the med for the CTZ Zone:
muscarinic blocker
Scopalamine
Name the med for the CTZ Zone:
Dopamine
Reglan
Droperidol
How long does a transdermal fentanyl patch take to achieve therapeutic levels
24 hours
patch changed q3days
What is the primary advantage of inhalation administration?
Lungs provide large surface area for absorption
This allows for efficient uptake of inhaled agents.
What characteristic of inhalational agents allows for rapid uptake?
Agents are highly lipid soluble and diffusible
This property facilitates quick blood-brain equilibration.
What is the function of bronchodilators delivered via nebulizer and metered-dose inhalers?
Propels aerosolized medication into alveolar sacs for targeted and rapid action with LESS SYSTEMIC EFFECTS
This method minimizes systemic effects.
What is Ventolin and its mechanism of action?
Beta-2 agonist that acts on the β2 adrenergic receptor
It produces relaxation of the airway smooth muscle. (bronchodilation)
What is the role of Atrovent in inhalation therapy?
Blocks parasympathetic nervous system and acts on muscarinic receptors
g-coupled protein receptor
It also produces relaxation of the airway smooth muscle and dries secretions.
What is a key benefit of topical administration?
Avoids first pass effect
This enhances local effects and increases bioavailability.
What type of administration allows for rapid absorption and is comparable to IV administration?
Intranasal administration
avoids first pas
It provides effective delivery through mucous membranes.
What is a potential risk associated with topical administration of a med like benzocaine spray?
Potential for systemic toxicity
This can occur if the drug is absorbed beyond the intended local effects.
What is intranasal fentanyl used for?
Used in both pediatric and adult patients
It is an alternative to IV access for pain management.
T/F you should give intranasal medications equally to both nares
True: makes for better, more equal absorption
4 major routes of parental administration
IV
SC
IM
Intrathecal
Intrathecal medications are directly administered into CSF and bypassess _______________________
the BBB
local anesthetics and opioids
What impacts SC and IM absorption
degree of blood flow and the site
lipid solubility of the drug
What is the rate of absorption in intramuscular administration dependent on?
Local blood flow
Which muscle site has faster absorption for intramuscular injections?
Deltoid faster than glute
How does the absorption rate in females compare to males in intramuscular administration?
Slower due to higher percentage of subcutaneous fat
In what scenario is intramuscular administration particularly useful?
When pediatric IV access is difficult
atropine and succ mday be given IM
who would you give IM ketamine to
special needs patients who need to be sedated prior to induction
What is the IM dose for Atropine?
0.01-0.02 mg/kg
What is the IM dose for Succinylcholine in pediatric patients?
4-5 mg/kg
What condition is Methergine contraindicated in?
Hypertension
What is a potential side effect of Methergine?
Coronary vasospasm
What is the IM dose for Ketamine for sedation?
3-5 mg/kg
What is Hemabate used to treat?
Postpartum hemorrhage
What is the initial IM dose of Hemabate?
1 mL (250mcg)
What is Methergine used for and what is the dose ?
Treatment of postpartum hemorrhage
.2 mg IM
Contraiindications for Hemabate
asthmatics
may cause bronchospasm
What characterizes absorption in subcutaneous administration?
Constant and slow absorption with sustained effect
What is a benefit of using a vasoconstrictor in subcutaneous administration?
Slows absorption and prolongs effect
What is a common medication administered subcutaneously?
Insulin
True or False: Absorption is faster from the gluteus than the deltoid in intramuscular administration.
False
Fill in the blank: Methergine is contraindicated in patients with _______.
[hypertension]
Fill in the blank: Ketamine may be used for sedation in patients with _______.
[special needs]
Fill in the blank: Subcutaneous administration provides a _______ effect.
[sustained]
What are 2 major advantages of intravenous administration?
100% bioavailability
rapid and accurate delivery of drug
This means the entire dose of the drug reaches systemic circulation immediately.
What is a disadvantage of intravenous administration?
Possible adverse reaction due to high plasma drug levels
requires vigilance!
High concentrations can lead to toxicity or other side effects.
What does rapid and accurate plasma drug level delivery refer to in intravenous administration?
The ability to achieve desired drug concentrations quickly and precisely
This is crucial for medications that require tight control of plasma levels.
What is required to avert adverse responses during intravenous administration?
Vigilance to patient response
Continuous monitoring is essential to adjust dosing as needed.
What is the route of choice for anesthesia?
Intravenous administration
This method allows for quick onset and control of anesthesia depth.
What does the first pass effect of the lungs refer to?
Percentage of drug taken up by the lungs after IV administration
This occurs before the drug is distributed to the rest of the body.
How does the first pass effect influence arterial plasma concentration?
It delays the release of the drug from the lungs
This can affect the overall effectiveness and timing of the drug.
What do pharmacologists measure to determine the degree of pulmonary uptake of a drug?
The difference in arteriovenous plasma concentration after IV administration
This measurement helps assess how much of the drug is absorbed by the lungs.
What is the typical uptake percentage of the initial drug dose by the lungs?
65-70%
This uptake is incorporated into the drug’s dosing profile so you don’t have to adjust dose
What major factor impacts the degree of pulmonary uptake?
pKa of the drug
The pKa influences how well the drug is absorbed in the lungs.
What type of drugs have a high degree of pulmonary uptake?
Basic lipophilic amines (pKa>8)
These drugs tend to be more readily absorbed by lung tissue.
Name two examples of drugs with high pulmonary uptake.
- Lidocaine
- Fentanyl
Other examples include propanolol, sufentanil, alfentanil, propofol, catecholamines, and ketamine.
What is a clinical significance of the first pass effect of the lungs?
Temporary reservoir of drug
The lungs can release the drug back into circulation as plasma concentrations decrease.
What can cause loss of pulmonary uptake?
Increased plasma levels and potential for toxicity
High drug concentrations can overwhelm the lung’s capacity to uptake the drug.
What is the effect of competitive medications on pulmonary uptake?
They can alter the degree of uptake
For example, Lidocaine and Inderal can compete for uptake, affecting drug levels.
How would a R->L left shunt affect the 1st pass in the lungs
loss of pulm uptake will increase plasma levels and cause potential toxicity
What is the structure of the cell wall membrane?
Bilipid layer composed of cholesterol and phospholipids
What is the function of transmembrane proteins in the cell wall membrane?
Facilitate transport across the membrane
True or False: The cell wall membrane is permeable to water-soluble drugs.
False
What types of drugs easily dissolve in the cell wall membrane?
Lipid soluble drugs
What does the sodium-potassium pump require to function?
ATP
What is the primary function of the sodium-potassium pump?
Moves Na+ out of the cell and K+ into the cell against concentration gradients
How many molecules of Na+ are pumped out of the cell by the sodium-potassium pump?
3 molecules
How many molecules of K+ are pumped into the cell by the sodium-potassium pump?
2 molecules
What is the resting potential inside the cell maintained by the sodium-potassium pump?
-70 to -90 millivolts (Mv)
Concentrations of Na and K inside and outside the CWM
Inside cell
Na+10mEq
K+160mEq
Outside cell
Na+140mEq
K+ 4mEq
What factors determine the transfer of drugs across cell membranes?
- Molecular size
- Degree of ionization
- Relative lipid solubility
- Binding to tissue proteins
Fill in the blank: Only _______ drug can enter the cell.
unbound
What influences drug uptake across cell membranes?
Regional blood flow and concentration gradient
How does molecular size affect the transfer of drugs across cell membranes?
Greater impact on water-soluble molecules; smaller agents traverse easier
What is the molecular weight threshold for easy transfer of drugs?
Less than 200 daltons
What factor affects the transfer of drugs across cell membranes related to their solubility?
Lipid solubility
High lipid solubility (lipid soluble) allows drugs to easily cross cell membranes, while low lipid solubility (water soluble) makes traversal difficult.
What is the term for drugs that easily cross the cell membrane due to high lipid solubility?
Lipophilic drugs
An example of a lipophilic drug is Propofol.
What type of drug is difficult to traverse cell membranes due to low lipid solubility?
Water soluble drugs
These drugs are often referred to as hydrophilic.
How does the degree of ionization influence drug transfer across cell membranes?
It affects how easily a drug crosses the cell membrane
Ionized drugs (water soluble) are repelled by the cell membrane, while nonionized drugs (lipid soluble) can cross more easily.
What is the characteristic of an ionized drug?
Water soluble and possesses an electrical charge
This charge repels ionized drugs from easily entering cells.
Where do ionized drugs tend to remain in the body?
Central circulation (blood/plasma)
Ionized drugs are often excreted unchanged by the kidneys.
What type of drug is easily able to cross the cell membrane?
Nonionized drug
Nonionized drugs are lipid soluble and have a more rapid onset of action.
What factors determine the degree of ionization of a drug?
- Whether the drug is an acid or base
- pH of the target solution (blood/plasma)
- pKa of the agent
The pKa is a numerical value that indicates how a drug will dissociate in solution.
What does the pKa of a drug measure?
The rate at which a drug will dissociate into its ion form
The pKa is a constant that does not change.
What type of drug are barbiturates, propofol, and acetaminophen classified as?
Weak acids
These drugs interact with charged ions.
What ions do acids combine with?
+ charged ions
Na, Mg, Ca
Sodium pentathol
This is a characteristic of acidic drugs.
Name two types of drugs that are considered bases.
Local anesthetics, opioids, benzo, vasopressors
What ions do bases combine with?
- charged ions
morphine sulfate, lidocaine Hydrochloride
This is a characteristic of basic drugs.
What is the impact of protein binding on drug distribution?
Only unbound drug is free to traverse the cell membrane
highly protein bound drugs remain in the vascular system= high plasma concentration
Drug-protein complexes are too large to bind to receptors.
What is Vd in pharmacology?
Volume of distribution
It is a theoretical measure of how extensively a drug distributes throughout the body.
Which is the most abundant and important plasma protein?
Albumin
It favors acidic drugs like aspirin and acetaminophen, phenytoin, barbiturates
What type of drugs does alpha1-acid glycoprotein favor?
Basic drugs
Examples include diazepam, midazolam, and opioids, locals
What is the effect of high protein binding on a drug’s distribution?
Remains in the vascular system
This leads to high plasma concentration and small calculated Vd.
Fill in the blank: The extent of protein binding depends on the _______ for the carrier protein.
Affinity
This is influenced by the concentration of the drug and protein.
Which plasma proteins bind to basic drugs?
Beta-globulins
An example is plasminogen.
What is the effect of protein binding on drug clearance?
Highly protein bound drugs are metabolized and excreted slower
Only the unbound fraction of drug can enter hepatocytes and undergo biotransformation and glomerular filtration and elimination from body
What maintains the drug-protein complex?
Weak bonds (ionic, hydrogen, van der Waals) that are easily reversible
The complex dissociates when plasma concentration decreases after hepatic or renal clearance of unbound drug - then more drug is released to maintain homeostasis
What is the role of protein binding in drug concentration?
Serves as a storage reservoir to control plasma concentration of drugs
Binding is nonselective; drugs with similar characteristics can compete for the same binding site.
What can happen with chronic administration of a highly bound drug?
It can be displaced from the binding site by a new drug with higher affinity
This increases the plasma concentration of the chronically administered drug.
Protein binding of drugs is _______________
nonselective- drugs w/ similar characteristics can compete for the same binding site
How does increased plasma concentration affect the pharmacological effect?
In theory, it increases the effect; in practice, the effect is usually small
The increased concentration of free drug is metabolized by the liver and excreted from the body.
Which drugs are significantly affected by alterations in protein binding?
significant w/ highly bound drugs (>90%)
Warfarin, phenytoin, propranolol, propofol, fentanyl, diazepam, midazolam
Warfarin is 98% protein bound.
What is the clinical impact of a competing drug on warfarin binding?
Decreases the binding of warfarin from 98% to 96%
secondary drug must also have high affinity for protein
Although the free drug amount has doubled, it does not produce a clinical effect unless **clearance **is impaired.
How do you calculate the change in free fraction of a drug?
Percent change formula: (New value - old value) / old value x 100
ex- from 98% binding to 96%
4%(new value) - 2%(old) / 2 = 1 x 100 = 100%
Example: If binding decreases from 98% to 96%, the change is 100%.
What patient factors can impact protein binding?
Severe hepatic or renal diseases, inflammatory diseases, pregnancy, aging
Examples include trauma, surgery, burns, acute MI, rheumatoid arthritis, Crohn’s, and cancer.
Albumin levels _______ in the last stage of pregnancy
Decrease
This leads to increased binding of basic drugs, resulting in less free drug.
How does lipid solubility relate to protein binding?
Degree of protein binding parallels degree of lipid solubility
Increased lipid solubility results in increased protein binding.
Which opioids are compared in terms of protein binding?
Morphine versus fentanyl
Fentanyl has higher lipid solubility and protein binding compared to morphine.
Which local anesthetics are compared in terms of protein binding?
Lidocaine versus bupivacaine
Bupivacaine has higher lipid solubility and protein binding compared to lidocaine.
How do water-soluble drugs compare to lipid-soluble drugs in terms of protein binding?
Water-soluble drugs (NMBA) are less protein bound than lipid-soluble drugs
This results in a smaller volume of distribution.
Degree of protein binding paralles degree of _______________
lipid solubility
Increase lipid solubility = increase protein binding
What are examples of chronic inflammatory diseases?
Rheumatoid arthritis, Crohn’s, cancer
What is the effect of acute/chronic inflammatory disease on alpha-1-acid glycoprotein?
Increased production of alpha-1-acid glycoprotein
= increased binding of basic drugs = less free drug
What changes occur in drug binding due to aging?
Decreased albumin
This results in less binding sites for acidic drugs, leading to more free drug.
Fill in the blank: Decreased albumin results in _______ free drug.
more
True or False: Increased production of alpha-1-acid glycoprotein leads to more free basic drugs in the system.
False
