Module 2 Flashcards
The insertion of a molecule of water into another molecule, which forms an unstable intermediate compound that subsequently splits apart.
Barash Ch. 11
Hydrolysis
The primary way amides, such as lidocaine and other amide local anesthetics, and esters, such as succinylcholine, are metabolized.
Barash Ch. 11
Hydrolytic reactions
Reactions that remove electrons from a molecule.
Barash Ch. 11
Oxidation
The single most important enzyme, accounting for 40% to 45% of all CYP-mediated drug metabolism.
Barash Ch. 11
CYP3A4
Enzymatic reactions that metabolize drugs can be classified into (_____) and (_____) biotransformation reactions.
Barash Ch. 11
Phase I / Phase II
True or False?
The passive elimination of drugs by passive glomerular filtration is a very efficient process.
Barash Ch. 11
False
The passive elimination of drugs by passive glomerular filtration is a very INefficient process
What determines the concentration of a drug in the plasma or at the site of drug effect?
Pharmacokinetics
[Stoelting ch 2]
A result from genetic modifications in metabolism; interactions with other drugs; or disease in the liver, kidney, or other organs of metabolism?
Pharmacokinetic Variability
[Stoelting ch2]
What is the time frame of initial distribution after bolus injection?
Within 1 minute
Stoelting ch 2
A compartment physically composed of those elements of the body that dilute the drug within the first minute after injection. Consists of Vessel Rich Group (VRG)
Central compartment
[Stoelting ch 2]
Many anesthetic drugs are highly ___________ soluble and poorly soluble in _______.
Fat; water
[Stoelting ch 2]
Protein binding affects the ________ of drugs as well as the _______.
Distribution; potency
[Stoelting ch 2]
Most acidic drugs bind to___________. while most basic drugs bind to ________.
Albumin; alpha 1 acidic glycoprotein
[ Stoelting ch 2]
The 4 basic pathways of metabolism are?
Phase 1 - oxidation - reduction - hydrolysis Phase 2 - conjugation
Stoelting ch 2
The CYP450 enzyme is involved in what phase of metabolism?
Phase 1
Stoelting ch 2
The rate of metabolism for most anesthetic drugs is proportional to drug ____________, rendering the clearance of the drug constant.
Concentration
Stoelting ch 2
The rate at which drug flows out of the liver must be the rate at which the drug flows in to the liver, minus the rate at which the liver ______ the drug.
Metabolizes
Stoelting ch 2
Renal excretion of drug involves what 3 things?
A) glomerular filtration
B) active tubular secretion
C) passive tubular reabsorption
Stoelting ch 2
Nonionized molecules are usually _______ soluble and can diffuse across cell membranes.
Lipid
[Stoelting ch 2]
The ______molecule is poorly lipid soluble and cannot penetrate lipid cell membranes easily.
Ionized
[Stoelting ch 2]
The reason for the large differences in the pharmacological effect of oral and IV drug doses.
First-pass hepatic effect
Route of drug administration that permits a rapid onset of drug effect due to bypassing the liver and preventing the first-pass hepatic effect.
Sublingual/ buccal route
Intravenous
(Stoelting ch 2)
What organ excretes the most amount of drugs?
Renal system
What is the formula for renal excretion?
Filtration - reabsorption + secretion at the level of the nephron
What is the definition of a nephron
It is the functional unit of the kidney
The liver is the most important organ for metabolism of drugs. Hepatic drug clearance depends on what three factors?
Barash Ch. 11
- The intrinsic ability of the liver to metabolize a drug
- Hepatic blood flow
- The extent of binding of the drug to blood components
Where do drugs enter the nephron?
Afferent arteriole
After a drug goes through the afferent arteriole in the nephron where does go?
Bowman’s capsule
When a drug is not filtered in the kidney where does it go?
Efferent Arteriole
Can a drug be secreted more then once in the kidney?
Yes, if the drug is not secreted it will branch to the peritubular capillaries and allows the drug to be secreted again if it was not filtered.
True/False Does filtration care if a drug is metabolized?
False, the only thing that filtration cares about is if the drug is free and not bound to anything. Generally speaking, polar and ionized.
If a drug is unbound in the kidney where can it be filtered out at?
Glomerulus site
Is albumin in the urine a good or bad thing?
Bad! It is used as a marker for diabetics to determine the progression of kidney disease in the urine. High number of albumin is bad
Is it good or bad for reabsorption of a drug at the glomerulus?
Bad, it is important not to reabsorb the drug. The point of metabolism is to process a drug in a way that is more readily eliminated.
What is the entire point of metabolism?
To prevent reabsorption, make a drug more readily eliminated.
Does the body prefer lipid soluble drugs or water soluble
- Lipid soluble drugs bypass the GI tract and allows is to get reabsorbed into the body.
- Easily passes cell membrane with increased lipophilicity.
True or False?
All else being equal, an increase in the volume of distribution of a drug will increase its elimination half-life; while an increase in elimination clearance will decrease elimination half-life.
Barash Ch. 11
True
Most drugs must pass through cell membranes to reach their sites of action. Consequently, drugs tend to be relatively (_____), rather than (____).
Barash Ch. 11
lipophilic/hydrophilic
The theoretical volume of blood from which a drug is completely and irreversibly removed in a unit of time.
Barash Ch. 11
Elimination clearance/drug clearance/ rate of elimination. Expressed as mass/time.
Which highly perfused core circulatory components receive the highest relative distribution of cardiac output, and therefore, are the initial organs to reach equilibrium with plasma drug concentrations? (Vessel Rich Group)
(five organs)
Barash Ch. 11
The brain, lungs, heart, liver and kidneys.
What does the liver do to the molecule?
The liver metabolizes molecules and makes them more polar, more readily eliminated from the body.
Why is a polar molecule good?
More polar molecules prevent reabsorption.
What is ion trapping
Systematic administration of a weak base, such as opioid, can result in accumulation of ionic drug in the environment of the stomach
(The ph and the charge can be changed to prevent reabsorption)
Is reabsorption always bad?
No, reabsorption of electrolytes is good but reabsorption of the drug is not
What is secretion
The way the body releases the drug into the urine
What is the rate of elimination
Formula
Elimination (Mass/time) = Clearance (volume/time) * (mass/volume) concentration. *Notice how units cancel to derive elimination as mass/time.
What is GFR
Flow rate of blood that is being filtered.
Where can creatine be found in the body ?
The muscles
What does creatinine measure
Kidney function
What is the best test to measure kidney function
24-hr urine collection
What is the gold standard for measuring kidney function
The measurement of inulin because it is freely filtered precise measurement of GFR. Rarely used.
What classifies chronic kidney disease
- Kidney problem > 3 months
- GFR< ml/min
- Increase in creatinine and decrease in GFR
What is the easiest way to determine kidney disease
- Decreased GFR
- Increased Serum Creatinine
What does enzyme induction do
It increases drug metabolism
What does competitive inhibition do
Decrease drug metabolism
Where does metabolism occur
At the level of the enzyme
Why do drug reactions occur
Secondary to change in enzyme activity
What enzyme is responsible for more than 50% of unexpected drug reactions
CYP3A4
What increases drug metabolism?
Enzyme inducers
What happens when you make more enzyme
Rate of drug metabolism is increased. It increases VMAX (maximum rate of metabolism). A VMAX that can no longer increase indicated enzyme saturation.
What is enzyme induction?
It increases the rate of metabolism, leads to increase in metabolites.
What happens if drug metabolism increases?
Drug concentration decreases.
Do chronic alcoholics make more or less enzymes ?
They make more so it increases the rate of metabolism.
What is competitive inhibition
Constrains drug metabolism, increases plasma drug concentration.
What happens in the presence of competitive inhibitors
Decreases the rate of drug metabolism, will decrease the dosage required.
What are two consequences of competitive inhibitor’s
- Decreases metabolism so it makes less metabolites (this is good if metabolites are toxic)
- If Metabolites are increased the drug concentration causes more side effects to occur
What is the most commonly prescribed drug in the US?
Statins
What is a statin
It is a cholesterol lowering agent
Where are statins metabolized at
CYP3A4-metabolite
What does more than one glass of grapefruit juice do to a person who is taking a Statin
Having more than one glass of grapefruit juice, especially at night, inhibits the CYP3A4 gene, which increases the amount of statin in the body
What is CYP3A4 inhibited by ?
Furanocumarins
What type of antacid should you not take with statins
H2 blockers
What do you H2 blockers do to your stomach when you’re taking a Staten
It takes the protons and pumps it out creating a hydrochloric acid
What are three molecules that bind to the Parietal cell
Histamine, acetylcholine, and gastrin
What is a specific name of an H2 blocker that inhibits the CYP3A4 gene and it increases Statin concentration in the body
Cimetidine
What do macrolides treat
Upper respiratory infections
What is MACE
Macrolides, azithromycjn, clarithromycin, erythromycin
Which mycin can you give a patient who is taking a statin and why
Azithromycin because it does not have CYP3A4 inhibition
What is Pharmogemonics
It is the study of how genetic factors affect drug metabolism. As with Asian glow
What is Asian glow
Eastern Asians have a predisposition when drinking alcohol that gives them an allergic reaction
In what regións in Asia do people commonly encounter Asian glow
Koreans, Taiwanese, and Japanese
Eastern Asian
What causes the Asian glow to occur
It is a release of histamine and prostaglandin that widen the arteries in veins causing a flushing appearance
(Vasodilation)
How can you treat Asian glow
- Avoid drinking
- Can use a anti-histamine (cimetidine)
- Before you start drinking alcohol take a Zantac, or aspirin to decrease the production of prostaglandins
Which route of a drug is able to directly enter the systemic circulation, able to bypass the metabolically active intestinal mucosa, and the hepatic first-pass metabolism?
Barash Ch. 11
- Sublingual
- Intravenous
Direct injection of local anesthetics and opioids into the intrathecal space bypasses the limitations of drug (___) and drug (___) of any other route of administration.
Barash Ch. 11
Absorption / distribution
The large surface area of the pulmonary alveoli available for exchange with the large volumetric flow of blood found in the pulmonary capillaries makes (___) administration an extremely attractive method by which to administer drugs.
Barash Ch. 11
Inhalational / Inhalation
True or False?
Once the concentration of drug in the brain tissue is higher than the plasma concentration of drug, there is a reversal of the drug concentration gradient so that the lipophilic drug readily diffuses back into the blood and is redistributed to the other tissues that are still taking up drug.
Barash Ch. 11
True
Pharmacokinetic term that describes all the processes that remove a drug from the body.
Barash Ch. 11
Elimination
Most drugs that are excreted unchanged from the body are (____) and therefore readily pass into urine or stool.
Barash Ch. 11
Hydrophilic
What enzymatic reaction that metabolizes a drug, which tends to transform a drug into one or more polar and potentially excretable compounds?
Barash Ch. 11
Phase I biotransformation reactions
What enzymatic reaction that metabolizes a drug to transform the original drug by conjugating a variety of endogenous compounds to a polar functional group of the drug, making the metabolite even more hydrophilic.
Barash Ch. 11
Phase II biotransformation reactions
Most common enzyme involved in phase 2 metabolism
UGTs- (UDP- Glucuronosyltransferase)- Glucuronidation reaction.
Enzymes involved in phase 2 metabolism.
UGTs (UDP- Glucuronosyltransferase)involved in Glucuronidation reaction., ( GSTs (Glutathione-s-transferase) involved in Glutathione conjugation, NATs(N-acetyltransferase) leads to Acetylation , SULTs (Sulfotransferase) leads to sulfation.
Acetaminophen is metabolized by which phase reaction.
95% of tylenol is metabolized by phase 2 enzymes.
Enzyme famous for polymorphism.
CYP2D6 (CODEINE)
First order kinetics.
video-9
Rate of metabolism is proportional to drug concentration. Half life(Time to metabolise 50% of drug) is constant.
What is zero order kinetics.
Rate of metabolism becomes independent of drug concentration. Rate of drug metabolism is constant. Rate of drug elimination is constant. Drug can build up in the body leads to toxicity
Name three drugs reach zero order kinetics quickly
VIDEO-9
Aspirin, phenytoin & ETOH
What is elimination half life
Time it take to eliminate 50% of the drug in the body.
95% of drug is always eliminate after 4.5 half-lives
Formula to calculate elimination half life
0.693/ke (first order elimination constant)
OR
0.693xVd/cl
Vd is volume of distribution and cl is clearance
What is clearance
Volume of plasma that gets filtered of drug/Time
unit is L/hr or ml/min
How to calculate Rate of elimination
Rate of elimination = clearancexplasma drug concentration
what is total clearance.
CL total= CL renal+ CL hepatic +CL lungs.
Clinical use of GFR (glomerular filtration rate)
GFR is used to to estimate changes in the renal clearance of drugs. Used as an indicator to select drug dose and choice .
DRUG CLEARANCE VS ELIMINATION.
Drug elimination refers to the irreversible removal of drug from the body by all routes of elimination. The declining plasma drug concentration observed after systemic drug absorption shows that the drug is being eliminated from the body but does not indicate which elimination processes are involved.
Total clearance
Renal clearance-urine
Hepatic clearance- Bile
Pulmonary clearance- Air
What are the main factors that affect tissue distribution of drugs? KT
Body composition, regional blood flow, and drug affinity for plasma proteins/tissue components.
The behavior of molecules with weak-moderate lipophilicity in obese patients is…. KT
Predictable as these drugs are mainly distributed in lean tissues and their doses based on ideal body weight. Ex: vecuronium and lithium.
Obesity can significantly alter….. KT
Tissue distribution and elimination of drugs, and may necessitate modified loading and/or maintenance doses of various drugs.
Obesity is defined as ….. KT
An excess of fat tissue compared with normal values for age and gender
An individual was said to be obese when …… KT
The actual bodyweight exceeds the IBW by more than 20%
Body mass index (BMI) is…. kT
Bodyweight (in kg) divided by the square of the height in metres
The BMI of an overweight person is…. KT
≥25 to 29.9 kg/m2
The BMI of an obese person is………. KT
≥30 kg/m2.
Obesity is divided into 3 classes: KT
Moderate (BMI 30.0 to 34.9), severe (BMI 35.0 to 39.9) and morbid (BMI ≥ 40.0).
How has the prevalence of obesity changed in the past 15 years? KT
Obesity has increased by
between 10 and 40%. Most pronounced in young women.
Obesity affects which stages of pharmacokinetics? KT
Distribution and elimination/clearance
The main factors that affect the distribution of drugs in tissues are… KT
Body composition, regional blood flow and binding to plasma proteins
Obese individuals have a larger absolute …… KT
Lean body mass (LBM), as well as fat mass, compared to normal healthy individuals of the same age, gender and height.
Anthropometric calculation of Lean Body Mass….KT
LBM (kg) = a × TBW (kg) – b × [TBW/height (cm)]2
where a and b are 1.10 and 120 for men and 1.07 and 148 for women.
Blood flow in fat is typically.. KT
Poor and accounts for only 5% of cardiac output compared to 22% in lean tissue and 73% in the viscera.
The livers of obese individuals frequently suffer from … KT
Fatty infiltration Ex: nonalcoholic steatohepatitis
Obese individuals may be at an increased risk of… KT
CYP2E1-mediated toxicity of environmental agents.
maintenance dosage of propofol for obese patients may be established on the same basis as …… KT
For lean patients, taking into account the TBW. There is no extra accumulation of Propofol in obese patients.
Fentanyl in obese patients… KT
Is distributed at least as extensively in the excess body mass as in the lean tissues, and the loading dose should account for total body mass.
The longer t1⁄2β of fentanyl elimination in obese patients suggests that …. KT
Maintenance doses should be prudently reduced in these individuals
Remefentanil doses for obese individuals should …. KT
Be calculated on the basis of IBW
Neuromuscular blockers are ….. KT
Polar and hydro- philic
IBW should be used to calculate ….. KT
doses of vecuronium in obese patients
Rocuronium should be administered to obese pa- tients on the basis of ……. KT
IBW and not TBW.
What is phase one when Asian flush occurs in the body
First the enzyme is ash (alcohol dehydrogenase)- take ethanol (ETOH)
And forms acetaldehyde, which make the molecule more polar
What is the normal gene in the body the metabolizes alcohol and is the abnormal gene for an Asian person
Normal = ALDH*1
Abnormal = ALDH*2
Why does Asian flushing occur ?
One parent has the abnormal gene ALDH*2 and passes it to the child
If only one parent passes the bad gene ALDH*2 to the child what kind of molecule is it
It is heterozygous and it is 100 times slower
What happens if both parents pass along the bad gene ALDH*2
The molecule is then homozygous and alcohol would make the child EXTREMELY sick
If someone has a heterozygous can they drink alcohol
They will still get sick but if they still drink they would be able to develop a tolerance and reaction would not be as bad
What is important to warn the patient who have a heterozygous gene and build up tolerance to alcohol?
They are at higher risk for developing esophageal cancer because they have the bad gene in their genetic makeup
What is disulfiram
It is a competitive inhibitor of the ALDH*2 gene and is used as an alcohol deterrent that will cause the person to get extremely ill if the drink alcohol.
It is used as a treatment for alcoholism
Which route of a drug is able to directly enter the systemic circulation, able to bypass the metabolically active intestinal mucosa, and the hepatic first-pass metabolism?
Barash Ch. 11
Sublingual
Direct injection of local anesthetics and opioids into the intrathecal space bypasses the limitations of drug (___) and drug (___) of any other route of administration.
Barash Ch. 11
Absorption / distribution
The large surface area of the pulmonary alveoli available for exchange with the large volumetric flow of blood found in the pulmonary capillaries makes (___) administration an extremely attractive method by which to administer drugs.
Barash Ch. 11
Inhalational / Inhalation
True or False?
Once the concentration of drug in the brain tissue is higher than the plasma concentration of drug, there is a reversal of the drug concentration gradient so that the lipophilic drug readily diffuses back into the blood and is redistributed to the other tissues that are still taking up drug.
Barash Ch. 11
True
Pharmacokinetic term that describes all the processes that remove a drug from the body.
Barash Ch. 11
Elimination
Most drugs that are excreted unchanged from the body are (____) and therefore readily pass into urine or stool.
Barash Ch. 11
Hydrophilic
What enzymatic reaction that metabolizes a drug, which tends to transform a drug into one or more polar and potentially excretable compounds?
Barash Ch. 11
Phase I biotransformation reactions
What enzymatic reaction that metabolizes a drug to transform the original drug by conjugating a variety of endogenous compounds to a polar functional group of the drug, making the metabolite even more hydrophilic.
Barash Ch. 11
Phase II biotransformation reactions
What is pharmacokinetics?
[V1-6]
How does the drug concentration change as it moves through the different compartments of your body
“what your body does to the drug”
What is absorption?
[V1-6]
The process of a substance entering the systemic circulation
Where does absorption take place in the body?
[V1-6]
Where absorption occurs depends on route of administration.
• If you take a drug orally – GI tract
• If you take an inhaler - lungs
What is distribution?
[V1-6]
The dispersion of a substance throughout fluids and tissues of the body; Process of going from vascular space to extravascular space
Where does distribution take place?
[V1-6]
Starts taking place in vascular space (plasma) and goes to extravascular space (fat, muscle, interstitial space)
What is metabolism?
[V1-6]
The irreversible transformation of parent compounds into daughter compounds.
Enzymes do this biotransformation process to transform it into a more polar molecule and get it ready for elimination
Where does metabolism take place?
[V1-6]
Liver
sometimes in the intestines as well
What is elimination?
[V1-6]
The removal of substances from the body
Where does elimination take place?
[V1-6]
Kidneys (most of the time)
What is bioavailability?
[V1-6]
The fraction of the administered dose that’s reaches the systemic circulation
What are the two main determinants of bioavailability?
[V1-6]
Properties of the drug and route of administration
What is the bioavailability of a drug given IV?
[V1-6]
1 because the drug is given directly into circulation
Volume of distribution
[V1-6]
Vd = total mass absorbed / [Concentration of plasma]
What is volume of distribution (Vd) used for in clinical practice?
[V1-6]
helps providers figure out how much total drug they need to give to reach a desired plasma concentration
Two clinical conditions that affect Vd
[V1-6]
Protein deficiency (low albumin levels) and increased capillary permeability (septic shock)
Do we measure extravascular concentration or intravascular concentration to determine Vd?
[V1-6]
Intravascular
Where in the liver cells does metabolism take place?
[V1-6]
smooth endoplasmic reticulum
Routes of administration that do NOT undergo first pass metabolism
[V1-6]
Sublingual, IM, IV
Two routes of administration that are subject to first pass metabolism
[V1-6]
oral and rectal
Three possible outcomes of metabolism
[V1-6]
1) active molecule becomes inactive and vice versa
2) toxic to nontoxic metabolite and vice versa
3) molecule becomes more water soluble
Drug properties that impact Vd
[V1-6]
Size of drug–Large drugs will stay in plasma, thus have a low Vd;
Binding–Plasma protein binding = low Vd, Extravascular protein binding = high Vd; Hydrophilic or lipophilic—Lipophilic (extravascular) = high Vd, Hydrophilic (stays in plasma) = low Vd
What the body “does” to the drug
PPT
Pharmacokinetics
Pharmacokinetics describes the __________,__________,___________, & _____________ of drugs.
PPT
Absorption, distribution, metabolism and elimination (ADME)
The plasma or serum concentration range within which a drug is likely to produce its effects.
PPt
Therapeutic Range (TR)
Describes the relationship between drug concentration and the response.
PPT
Pharmacodynamics
process by which a drug proceeds from the site of administration to the site of measurement (usually blood, plasma, or serum)
PPT
Absorption
process of reversible transfer of drug to and from the site of measurement (between blood and tissue)
PPT
Distribution
process by which a drug is structurally changed for purposes of detoxification and elimination
PPT
Metabolism
the irreversible loss of drug from site of measurement
PPT
Elimination (Excretion)
The fraction of administered drug that reaches general circulation.
PPT
- Bioavailability
Bioavailability is influenced by
PPT
gut function, gut perfusion (CHF), route of administration, first-pass metabolism
Combined action of intestinal and liver enzymes on drugs, or loss of a drug given orally, before it reaches systemic circulation.
PPT
First-Pass effect
Benefits of Oral route administration
PPT
Non-invasive, most common, increases patient compliance
Disadvantages of oral route administration
PPT
Not appropriate for all drugs, GI side effects, dosing frequency of some drugs
Benefits and disadvantages of topical route of administration.
PPT
Treats local areas, decreases systemic effects, slow onset, not useful for most drugs
Benefits and disadvantages of rectal route of administration
PPT
useful in unconscious patients, absorption is unpredictable, avoids first pass metabolism by the liver
Benefits and disadvantages of Sub cutaneous & IM injections
PPT
Provides steady absorption of drugs, limited to non-irritating compounds, can cause tissue necrosis
Affects how drugs are administered and supplied
PPT
Solubility
Solubility is measured as a ratio of
PPT
oil to water partition coefficient
Oil used in most medications is called
PPT
Octanol
Medications must be ________ to cross the lipid bilayer.
PPT
Lipophilic
The larger the solubility ratio the
PPT
More lipid soluble the substance is
Solubility of anesthetic gases is measure using what
PPT
Blood to gas partition coefficient
Most drugs are absorbed by
PPT
Passive diffusion
Most drugs are salts of
PPT
Weak acids or weak bases
Drugs are preferentially absorbed in which form
PPT
Unionized form
The fraction of the drug available in unionized form depends on
PPT
The Dissociation Constant (pKa) & the pH of the environment
The more ________, the higher the absorption
PPT
Lipophilic
The pH at which ionized and unionized forms are in a 1:1 ratio
PPT
pKa
pH is defines as
PPT
- log [H+]
pH for weak acids to be absorbed
PPT
LOW
pH for weak bases to be absorbed
PPT
High
With weak acids as pH increases, % ionized form ________
PPT
increases
With weak bases as pH increases, % ionized form __________
PPT
Decreases
The active form of the drugs
PPT
Unionized form
In weak bases if pH>pKa than what form predominates
PPT
Unionized
In weak bases if pH
Ionized
In weak acids if pH
Unionized
In weak acids if pH>pKa than what form predominates
PPT
Ionized
Most drugs move across membranes by
PPT
simple diffusion
The rate at which drugs diffuse through membranes is given by what equation
PPT
Fick’s equation
Diffusion rate is dependent on __________ and __________
- [drug]
- gradient across a membrane
(Fick’s equation)
drug properties that effect their transfer across membranes
PPT
- Molecular size
- degree of ionization
- lipid solubility
- protein binding
Other factors that effect the transfer of drugs across membranes
PPT
- Blood flow to target tissue
2. [gradient] of drug across membranes
Transports drug molecule to site of activity
PPT
Vasculature
Carrier mediated process, moves down the concentration gradient
PPT
Facilitated Diffusion
Carrier mediated, requires energy, can move against concentration gradient
PPT
Active Transport
Passive diffusion ________ be saturated
PPT
CANNOT
Two main plasma proteins that drugs bind to
PPT
Albumin & Alpha1-acid glycoprotein
Protein Bound drugs stay in
PPT
the intravascular space
Patients with hypoproteinemia are more sensitive to IV drugs as a result of
PPT
Decreased protein binding
_______% of circulation thiopental is protein-bound
PPT
65-85%
Administration route that bypasses absorption
PPT
IV
Organs that have enzymes that metabolize drugs
PPT
Liver, GI tract, Lung
Metabolites may be
PPT
active or inactive
Active metabolite of codeine
PPT
morphine
metabolism that makes the drug more polar and water soluble
PPT
Phase I Reactions
Phase 1 reactions include
PPT
oxidation, reduction, and hydrolysis
Phase II reactions are
PPT
conjugation reactions
Examples of Phase II conjugation reactions
PPT
Glucuronidation, acetylation,
sulfation
The const common phase II conjugation reaction
PPT
Glucuronidation
______ acetylators are more prone to toxicity with amides
PPT
SLOW (50% caucasians)
Population that has a high percent of fast acetylators
PPT
Asian
Phase I metabolism is enzymatic therefore it can be
PPT
Saturated
Metabolism of drugs in hepatocytes of the liver occurs in
PPT
Smooth endoplasmic reticulum (SER)
loss of electrons
PPT
Oxidation
Gain of electrons
PPT
Reduction
Addition of -OH group to a molecule
PPT
Hydroxylation
Break down of molecules by the addition of water
PPT
Hydrolysis
When a drug increases the amount of available enzymes
PPT
Induction
Induction results in
PPT
shorter half-life
Phase II reactions are also known as
PPT
synthetic reactions
Common phase II reactions involve the attachment of __________ to the molecule, rendering the compound water soluble
PPT
a sugar group
Orally given drugs are carried via portal vein circulation to the liver where they are metabolized
PPT
First Pass metabolism
What is the most important patient specific factor factor that influences elimination
PPT
Renal Function
Elimination occurs through 2 processes
PPT
Metabolism & excretion
Irreversible loss of a drug in the chemically unchanged form
PPT
Excretion
The primary site of excretion
PPT
Kidney
Rate of drug removal at a given time
PPT
Clearance (CL)
Theoretical volume of plasma that is completely cleared of drug at a given time
PPT
Clearance (CL)
Units of clearance
PPT
mL/min
formula used to calculate creatinine clearance
PPT
Cockroft-Gault equation
Creatinine clearance (CLcr) is needed in order to determine
PPT
Dosing regimen
Relates to the amount of the drug in the body to the concentration of the drug in the plasma
PPT
Volume of Distribution (Vd)
Hypothetical value that tells us about distribution characteristics of a drug
PPT
Apparent volume
Formula for Vd
PPT
Dose/Cp0
Units for Vd
L/kg
Used to determine if a drug is removed by dialysis
PPT
Vd
high Vd are not removed effectively
Time it takes for the drug concentration in the plasma to fall by one half
PPT
Elimination Half-Life (t1/2 beta)
How many half-lives does it take for a drug to reach a steady state
PPT
4 to 5 half lives (Video says 4.5)
Have a proportionally larger extracellular fluid (ECF) volume than adults
PPT
Neonates (up to 18 months)
ECF in adults
~ 20%
ECF in neonates
~ 40%
A higher Vd results in
PPT
Longer time for elimination
In the Two-compartment model the central compartment (VRG) can be sampled through
PPT
the blood
In the two compartment model, this compartment cannot usually be sampled
PPT
Peripheral compartment
In _________, a constant amount of drug is eliminated per unit time.
PPT
Zero Order Kinetics
In zero order kinetics, __________ can occur as a result of constant drug elimination regardless of drug concentration.
PPT
Accumulation
In First order Kinetics a ____________ is eliminated per unit time.
PPT
Constant fraction
Most drugs undergo which kinetics
PPT
First order Kinetics
In the first order kinetics two compartment model the fast decline in [drug plasma] represents (curvilinear part of graph)
PPT
distribution from central to peripheral compartment
In the first order kinetics two compartment model the slow decline in [drug plasma] represents (linear part of graph)
PPT
Elimination
Formula for T1/2beta
PPT
0.693Vd/Cl
What is the value for the proportionality constant
PPT
0.693
Elimination constant
PPT
Ke
Formula to T1/2
PPT
T1/2 = 0.693/Ke
Css represents where the rate of infusion = the rate of ___________
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Elimination
The time necessary for plasma drug concentration to fall by 50% or other percentage after a continuous infusion of specific duration.
PPT
Context Sensitive Half-Time
How far plasma concentration must decrease to reach levels compatible with awakening.
PPT
Time to recovery
