Intro to Pharm Flashcards
Week 1
1
Q
What do pharmacokinetic, dynamic, and genetic principles explain in the context of drug response?
A
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.
2
Q
What does pharmacokinetics study?
A
The influence of bodily processes on drug effect
This includes how drugs are absorbed, distributed, metabolized, and excreted by the body.
3
Q
What is pharmacodynamics?
A
The influence of drug on body processes
It examines how drugs exert their effects on the body, including mechanisms of action.
4
Q
What does pharmacogenomics/pharmacogenetics focus on?
A
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.
5
Q
What is the impact of a single nucleotide variant or altered gene coding?
A
It can significantly influence drug response
Variants can affect how drugs are metabolized and their therapeutic effects.
6
Q
What are some confounding variables that can influence desired drug response?
A
- Age
- Co-morbidities
These factors can affect drug pharmacokinetics and pharmacodynamics, leading to variability in treatment outcomes.
7
Q
Relationship b/t Pharmacokinetics and Pharmacobiophysics
A
Kinetics = The drug dose
Biophysics = the concentration of the drug in the plasma over time
“What the drug does to the body”
8
Q
Relationship b/t Pharmacobiophysics and Pharmacodynamics
A
Biophysics = Drug concentration at the site of action “Effect site” or “biophase”
Dynamics- the pharmacological effect
“What the drug does to the body”
9
Q
What is the biophase
A
The relationship b/t drug concentration in the plasma and effect site
10
Q
Name the 4 phases of pharmacokinetics
A
absorption
distribution
metabolism
excretion
11
Q
Where does metabolism or biotransformation occur
A
Either Liver or the kidney
12
Q
What is the first step in passage of a drug through the body?
A
absorption
13
Q
What does the rate of systemic absorption determine?
A
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
14
Q
T/F: IMV drugs bypass absorption
A
True: They go directly into the bloodstream
15
Q
What key factors impact the degree of drug absorption (5)
A
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
16
Q
What are the routes of drug administration
A
Oral/Enteral: PO, NGT, Rectal
Parental: SC, IM, IV, Intrathecal
Inhalational
Sublingual
Intranasal/Topical
Transdermal
17
Q
Name the onset of drug routes from fastest to slowest
A
IV > IM > SC > PO
18
Q
Name drug routes from longest to shortest for drug duration
A
Longest: PO > SC > IM > IV (Shortest)
19
Q
Advantages of Oral/ Enteral Administration
A
convienent
Larger margin of safety
economical (cheaper)
20
Q
What is the biggest disadvantage of oral administration and other disadvantages?
A
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)
21
Q
What 2 things impact absorption
A
Lipid solubility and Ionization
22
Q
T/F Hydrophilic drugs pass the CWM greater than Hydrophobic drugs
A
False
Hydrophilic = ionized = water soluble = electrical charge which is repelled by the CWM
Hydrophobic= lipophilic
23
Q
What is bioavailability
A
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
24
Q
Name some factors that decrease bioavailability
A
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
25
What is the First Pass Effect?
Drugs absorbed from the GI tract enter the portal vein and pass through the liver before entering circulation.
26
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.
27
What accounts for the large difference between oral and IV dosages?
The First Pass Effect.
28
Name drugs that exhibit significant First Pass Effect.
Inderal, Morphine, Lidocaine, Metoprolol.
so the Oral dose is WAY BIGGER than the IV dose
29
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
30
How can EHRC impact drug elimination?
If EHRC is blocked, the elimination of drugs undergoing EHRC may be increased.
31
Give an example of a drug that can block EHRC.
Antibiotics that decrease gut flora and deconjugating enzymes.
32
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
33
What are some common drugs that block enterohepatic recirculation
Antibiotics
NSAIDS
Warfarin
Hormones
opioids
digoxin
34
What is a key benefit of sublingual administration?
Rapid onset of drug effect.
35
What is the bioavailability of drugs administered sublingually?
100% bioavailability.
36
How does sublingual administration bypass the First Pass Effect?
It drains directly into the superior vena cava.
37
What is a common drug administered sublingually?
Nitroglycerine.
38
Why is rectal administration losing popularity?
It is less preferred for most patients. lol
sometime used in quick pediatric procedures to avoid an IV
39
What factors affect absorption in rectal administration?
Proximal versus distal rectum.
40
If inserted to the proximal rectum: a drug undergoes a ____________________
first pass effect
41
What can result in unpredictable absoprtion of a rectally administered medication
shit
42
What is a benefit of transdermal administration?
Sustained release provides steady plasma concentration.
avoids peaks and valleys
43
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
44
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
45
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
46
What are 5 meds that you can administer transdermally
fentanyl
scopolamine
clonidine
NTG
Nicotene
47
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
48
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
49
Name the med for the CTZ Zone:
5HT3
Ondansetron- 5HT3 antagonist
50
Name the med for the CTZ Zone:
Histamine blocker
Benadryl for H1
Famotidine for H2
51
Name the med for the CTZ Zone:
muscarinic blocker
Scopalamine
52
Name the med for the CTZ Zone:
Dopamine
Reglan
Droperidol
53
How long does a transdermal fentanyl patch take to achieve therapeutic levels
24 hours
patch changed q3days
54
What is the primary advantage of inhalation administration?
Lungs provide large surface area for absorption
## Footnote
This allows for efficient uptake of inhaled agents.
55
What characteristic of inhalational agents allows for rapid uptake?
Agents are highly lipid soluble and diffusible
## Footnote
This property facilitates quick blood-brain equilibration.
56
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
## Footnote
This method minimizes systemic effects.
57
What is Ventolin and its mechanism of action?
Beta-2 agonist that acts on the β2 adrenergic receptor
## Footnote
It produces relaxation of the airway smooth muscle. (bronchodilation)
58
What is the role of Atrovent in inhalation therapy?
Blocks parasympathetic nervous system and acts on muscarinic receptors
g-coupled protein receptor
## Footnote
It also produces relaxation of the airway smooth muscle and dries secretions.
59
What is a key benefit of topical administration?
Avoids first pass effect
## Footnote
This enhances local effects and increases bioavailability.
60
What type of administration allows for rapid absorption and is comparable to IV administration?
Intranasal administration
avoids first pas
## Footnote
It provides effective delivery through mucous membranes.
61
What is a potential risk associated with topical administration of a med like benzocaine spray?
Potential for systemic toxicity
## Footnote
This can occur if the drug is absorbed beyond the intended local effects.
62
What is intranasal fentanyl used for?
Used in both pediatric and adult patients
## Footnote
It is an alternative to IV access for pain management.
63
T/F you should give intranasal medications equally to both nares
True: makes for better, more equal absorption
64
4 major routes of parental administration
IV
SC
IM
Intrathecal
65
Intrathecal medications are directly administered into CSF and bypassess _______________________
the BBB
local anesthetics and opioids
66
What impacts SC and IM absorption
degree of blood flow and the site
lipid solubility of the drug
67
What is the rate of absorption in intramuscular administration dependent on?
Local blood flow
68
Which muscle site has faster absorption for intramuscular injections?
Deltoid faster than glute
69
How does the absorption rate in females compare to males in intramuscular administration?
Slower due to higher percentage of subcutaneous fat
70
In what scenario is intramuscular administration particularly useful?
When pediatric IV access is difficult
atropine and succ mday be given IM
71
who would you give IM ketamine to
special needs patients who need to be sedated prior to induction
72
What is the IM dose for Atropine?
0.01-0.02 mg/kg
73
What is the IM dose for Succinylcholine in pediatric patients?
4-5 mg/kg
74
What condition is Methergine contraindicated in?
Hypertension
75
What is a potential side effect of Methergine?
Coronary vasospasm
76
What is the IM dose for Ketamine for sedation?
3-5 mg/kg
77
What is Hemabate used to treat?
Postpartum hemorrhage
78
What is the initial IM dose of Hemabate?
1 mL (250mcg)
79
What is Methergine used for and what is the dose ?
Treatment of postpartum hemorrhage
.2 mg IM
80
Contraiindications for Hemabate
asthmatics
may cause bronchospasm
81
What characterizes absorption in subcutaneous administration?
Constant and slow absorption with sustained effect
82
What is a benefit of using a vasoconstrictor in subcutaneous administration?
Slows absorption and prolongs effect
83
What is a common medication administered subcutaneously?
Insulin
84
True or False: Absorption is faster from the gluteus than the deltoid in intramuscular administration.
False
85
Fill in the blank: Methergine is contraindicated in patients with _______.
[hypertension]
86
Fill in the blank: Ketamine may be used for sedation in patients with _______.
[special needs]
87
Fill in the blank: Subcutaneous administration provides a _______ effect.
[sustained]
88
What are 2 major advantages of intravenous administration?
100% bioavailability
rapid and accurate delivery of drug
## Footnote
This means the entire dose of the drug reaches systemic circulation immediately.
89
What is a disadvantage of intravenous administration?
Possible adverse reaction due to high plasma drug levels
requires vigilance!
## Footnote
High concentrations can lead to toxicity or other side effects.
90
What does rapid and accurate plasma drug level delivery refer to in intravenous administration?
The ability to achieve desired drug concentrations quickly and precisely
## Footnote
This is crucial for medications that require tight control of plasma levels.
91
What is required to avert adverse responses during intravenous administration?
Vigilance to patient response
## Footnote
Continuous monitoring is essential to adjust dosing as needed.
92
What is the route of choice for anesthesia?
Intravenous administration
## Footnote
This method allows for quick onset and control of anesthesia depth.
93
What does the first pass effect of the lungs refer to?
Percentage of drug taken up by the lungs after IV administration
## Footnote
This occurs before the drug is distributed to the rest of the body.
94
How does the first pass effect influence arterial plasma concentration?
It delays the release of the drug from the lungs
## Footnote
This can affect the overall effectiveness and timing of the drug.
95
What do pharmacologists measure to determine the degree of pulmonary uptake of a drug?
The difference in arteriovenous plasma concentration after IV administration
## Footnote
This measurement helps assess how much of the drug is absorbed by the lungs.
96
What is the typical uptake percentage of the initial drug dose by the lungs?
65-70%
## Footnote
This uptake is incorporated into the drug's dosing profile so you don't have to adjust dose
97
What major factor impacts the degree of pulmonary uptake?
pKa of the drug
## Footnote
The pKa influences how well the drug is absorbed in the lungs.
98
What type of drugs have a high degree of pulmonary uptake?
Basic lipophilic amines (pKa>8)
## Footnote
These drugs tend to be more readily absorbed by lung tissue.
99
Name two examples of drugs with high pulmonary uptake.
* Lidocaine
* Fentanyl
## Footnote
Other examples include propanolol, sufentanil, alfentanil, propofol, catecholamines, and ketamine.
100
What is a clinical significance of the first pass effect of the lungs?
Temporary reservoir of drug
## Footnote
The lungs can release the drug back into circulation as plasma concentrations decrease.
101
What can cause loss of pulmonary uptake?
Increased plasma levels and potential for toxicity
## Footnote
High drug concentrations can overwhelm the lung's capacity to uptake the drug.
102
What is the effect of competitive medications on pulmonary uptake?
They can alter the degree of uptake
## Footnote
For example, Lidocaine and Inderal can compete for uptake, affecting drug levels.
103
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
104
What is the structure of the cell wall membrane?
Bilipid layer composed of cholesterol and phospholipids
105
What is the function of transmembrane proteins in the cell wall membrane?
Facilitate transport across the membrane
106
True or False: The cell wall membrane is permeable to water-soluble drugs.
False
107
What types of drugs easily dissolve in the cell wall membrane?
Lipid soluble drugs
108
What does the sodium-potassium pump require to function?
ATP
109
What is the primary function of the sodium-potassium pump?
Moves Na+ out of the cell and K+ into the cell against concentration gradients
110
How many molecules of Na+ are pumped out of the cell by the sodium-potassium pump?
3 molecules
111
How many molecules of K+ are pumped into the cell by the sodium-potassium pump?
2 molecules
112
What is the resting potential inside the cell maintained by the sodium-potassium pump?
-70 to -90 millivolts (Mv)
113
Concentrations of Na and K inside and outside the CWM
Inside cell
Na+10mEq
K+160mEq
Outside cell
Na+140mEq
K+ 4mEq
114
What factors determine the transfer of drugs across cell membranes?
* Molecular size
* Degree of ionization
* Relative lipid solubility
* Binding to tissue proteins
115
Fill in the blank: Only _______ drug can enter the cell.
unbound
116
What influences drug uptake across cell membranes?
Regional blood flow and concentration gradient
117
How does molecular size affect the transfer of drugs across cell membranes?
Greater impact on water-soluble molecules; smaller agents traverse easier
118
What is the molecular weight threshold for easy transfer of drugs?
Less than 200 daltons
119
What factor affects the transfer of drugs across cell membranes related to their solubility?
Lipid solubility
## Footnote
High lipid solubility (lipid soluble) allows drugs to easily cross cell membranes, while low lipid solubility (water soluble) makes traversal difficult.
120
What is the term for drugs that easily cross the cell membrane due to high lipid solubility?
Lipophilic drugs
## Footnote
An example of a lipophilic drug is Propofol.
121
What type of drug is difficult to traverse cell membranes due to low lipid solubility?
Water soluble drugs
## Footnote
These drugs are often referred to as hydrophilic.
122
How does the degree of ionization influence drug transfer across cell membranes?
It affects how easily a drug crosses the cell membrane
## Footnote
Ionized drugs (water soluble) are repelled by the cell membrane, while nonionized drugs (lipid soluble) can cross more easily.
123
What is the characteristic of an ionized drug?
Water soluble and possesses an electrical charge
## Footnote
This charge repels ionized drugs from easily entering cells.
124
Where do ionized drugs tend to remain in the body?
Central circulation (blood/plasma)
## Footnote
Ionized drugs are often excreted unchanged by the kidneys.
125
What type of drug is easily able to cross the cell membrane?
Nonionized drug
## Footnote
Nonionized drugs are lipid soluble and have a more rapid onset of action.
126
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
## Footnote
The pKa is a numerical value that indicates how a drug will dissociate in solution.
127
What does the pKa of a drug measure?
The rate at which a drug will dissociate into its ion form
## Footnote
The pKa is a constant that does not change.
128
What type of drug are barbiturates, propofol, and acetaminophen classified as?
Weak acids
## Footnote
These drugs interact with charged ions.
129
What ions do acids combine with?
+ charged ions
Na, Mg, Ca
Sodium pentathol
## Footnote
This is a characteristic of acidic drugs.
130
Name two types of drugs that are considered bases.
Local anesthetics, opioids, benzo, vasopressors
131
What ions do bases combine with?
- charged ions
morphine sulfate, lidocaine Hydrochloride
## Footnote
This is a characteristic of basic drugs.
132
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
## Footnote
Drug-protein complexes are too large to bind to receptors.
133
What is Vd in pharmacology?
Volume of distribution
## Footnote
It is a theoretical measure of how extensively a drug distributes throughout the body.
134
Which is the most abundant and important plasma protein?
Albumin
## Footnote
It favors acidic drugs like aspirin and acetaminophen, phenytoin, barbiturates
135
What type of drugs does alpha1-acid glycoprotein favor?
Basic drugs
## Footnote
Examples include diazepam, midazolam, and opioids, locals
136
What is the effect of high protein binding on a drug's distribution?
Remains in the vascular system
## Footnote
This leads to high plasma concentration and small calculated Vd.
137
Fill in the blank: The extent of protein binding depends on the _______ for the carrier protein.
Affinity
## Footnote
This is influenced by the concentration of the drug and protein.
138
Which plasma proteins bind to basic drugs?
Beta-globulins
## Footnote
An example is plasminogen.
139
What is the effect of protein binding on drug clearance?
Highly protein bound drugs are metabolized and excreted slower
## Footnote
Only the unbound fraction of drug can enter hepatocytes and undergo biotransformation and glomerular filtration and elimination from body
140
What maintains the drug-protein complex?
Weak bonds (ionic, hydrogen, van der Waals) that are easily reversible
## Footnote
The complex dissociates when **plasma concentration** decreases after hepatic or renal clearance of unbound drug - then more drug is released to maintain homeostasis
141
What is the role of protein binding in drug concentration?
Serves as a storage reservoir to control plasma concentration of drugs
## Footnote
Binding is nonselective; drugs with similar characteristics can compete for the same binding site.
142
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
## Footnote
This increases the plasma concentration of the chronically administered drug.
143
Protein binding of drugs is _______________
nonselective- drugs w/ similar characteristics can compete for the same binding site
144
How does increased plasma concentration affect the pharmacological effect?
In theory, it increases the effect; in practice, the effect is usually small
## Footnote
The increased concentration of free drug is metabolized by the liver and excreted from the body.
145
Which drugs are significantly affected by alterations in protein binding?
| significant w/ highly bound drugs (>90%)
Warfarin, phenytoin, propranolol, propofol, fentanyl, diazepam, midazolam
## Footnote
Warfarin is 98% protein bound.
146
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
## Footnote
Although the free drug amount has doubled, it does not produce a clinical effect unless **clearance **is impaired.
147
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%
## Footnote
Example: If binding decreases from 98% to 96%, the change is 100%.
148
What patient factors can impact protein binding?
Severe hepatic or renal diseases, inflammatory diseases, pregnancy, aging
## Footnote
Examples include trauma, surgery, burns, acute MI, rheumatoid arthritis, Crohn's, and cancer.
149
Albumin levels _______ in the last stage of pregnancy
Decrease
## Footnote
This leads to increased binding of basic drugs, resulting in less free drug.
150
How does lipid solubility relate to protein binding?
Degree of protein binding parallels degree of lipid solubility
## Footnote
Increased lipid solubility results in increased protein binding.
151
Which opioids are compared in terms of protein binding?
Morphine versus fentanyl
## Footnote
Fentanyl has higher lipid solubility and protein binding compared to morphine.
152
Which local anesthetics are compared in terms of protein binding?
Lidocaine versus bupivacaine
## Footnote
Bupivacaine has higher lipid solubility and protein binding compared to lidocaine.
153
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
## Footnote
This results in a smaller volume of distribution.
154
Degree of protein binding paralles degree of _______________
lipid solubility
Increase lipid solubility = increase protein binding
155
What are examples of chronic inflammatory diseases?
Rheumatoid arthritis, Crohn's, cancer
156
What is the effect of acute/chronic inflammatory disease on alpha-1-acid glycoprotein?
Increased production of alpha-1-acid glycoprotein
## Footnote
= increased binding of basic drugs = less free drug
157
What changes occur in drug binding due to aging?
Decreased albumin
## Footnote
This results in less binding sites for acidic drugs, leading to more free drug.
158
Fill in the blank: Decreased albumin results in _______ free drug.
more
159
True or False: Increased production of alpha-1-acid glycoprotein leads to more free basic drugs in the system.
False
