7: Pharmacology, Pharmacokinetics, Metabolism Flashcards
drugs not synthesized within the body
xenobiotics
Who said the dose makes the poison?
Theophrastus Von Hohenheim (Paracelsus)
actions of the drug on the body; group in which drug belongs
pharmacodynamics
*think Drug’s effect on the body = D
actions of the body on the drug (absorption, distribution, metabolism, and elimination ) aka ADME
pharmacokinetics
Flux (molecules per unit time) = (c1-c2) x ((area x permeability coefficient))/thickeness
Fick’s Law of Diffusion
category of drug absorption expressed as fraction of dose administered; also known as the fraction of unchanged drug reaching circulation
Oral Bioavalability (F)
(area under curve)
How are most toxicants absorbed by the body?
Simple diffusion
True/False:
Only the unbound drugs (those not bound to proteins) distribute into tissues and receptors, exert pharmacological effects, and are metabolized
True
The elimination rate constant; a function of clearance and volume of distribution
KEL
Cl = Vd x KEL
A constant relating to drugs rate of transfer/elimination from plasma; units are mL/min
Clearance
Cl = kel/Cp
Is clearance used for zero order or first order eliminated drugs?
first-order
Type of elimination where processes are saturated (going as fast as they can
-Constant rate of elimination; think of a tub; linear
zero-order elimination
i.e. Ethanol
Type of elimination where processes are not saturated; not linear
first-order elimination
Time for plasma concentrations to become ½
half life, T1/2
Is clearance used for zero order or first order eliminated drugs?
first-order
Calculation for half-life
T1/2 = 0.693/KEL
hypothetical volume of body fluid (plasma) necessary to contain all of the drug at a concentration equal to the plasma concentration
Apparent Volume of Distribution, Vd
Vd of drugs that distribute in total body water (plasma + water)
0.7 L/kg male and 0.55 L/kg females (EtOH**)
Route of Administration –>
Put in order of speed of delivery starting w/ fastest:
subcutaneous, IM, IV, Oral
(fastest) IV, Intramuscular, subcutaneous, oral (slowest)
when the quantity of drug eliminated in the unit of time equals the quantity of the drug that reaches the systemic circulation in the unit of time.
Steady State
How much accumulation/loss is achieved in 1 half life?
4 half lives?
5-6 half lives?
1 = 50%
1 = 90%
5-6 = 95-99%
What three factors influence clearance?
1) dose (timing, was absorption complete)
2) organ blood flow
3) intrinsic function of liver and kidneys
range of target plasma concentrations effective for most patients;
Therapeutic Range
chemical transformation of any xenobiotic
Biotransformation
Where does biotransformation primarily occur?
Liver
Step in biotransformation where drugs are converted to more polar metabolite (oxidation, reduction, hydrolysis)
Phase I
Step in biotransformation where drugs are conjugated w/ larger molecule (endogenous substance) to yield a more easily excreted conjugate; examples: glucuronidation acetylation, sulfation, methylation
Phase II
*Most common is glucuronidation
Where are drug metabolizing enzymes primarily located?
endoplasmic reticulum of liver
Common enzymes responsible for biotransformation of drugs
Cytochrome p450 familt
CYP 1-3 w/ different isoforms
CYP3A inhibition: grapefruit juice
The two most important sits for drug elimination are:
Liver and Kidney
An antagonist is a type of drug that:
Has maximal efficacy
Has affinity for a receptor but poor efficacy
Binds to a receptor and activates it
Has efficacy but poor affinity
Decreases the concentration of an agonist required to produce
an effect
Has affinity for a receptor but poor efficacy
An agonist is a type of drug that:
Prevents the metabolism of other drugs
Binds to a receptor without activating it
Simulates the metabolism of other drugs
Competes noncompetitively
Binds to a receptor and activates it
Binds to a receptor and activates it
True or False: Most drugs are either strong acids or strong bases.
False. Most are weakly basic or acidic
True or False: In alkaline urine, acidic drugs are more readily ionized.
True.
True or False: Ionized substances are also referred to as polar substances.
True.
True or False: The plasma half-life of a drug is directly proportional to total clearance.
False.
Think of this equation –> T1/2 = 0.693/KEL
True or False: Drugs bound to albumin are inactive
True.
A classic example of a drug with a high Vd is:
Cocaine
THC
Alprazolam
Ethanol
Isopropanol
THC
One of the major physiological factors that determines the variability in the rate of drug excretion into the urine is its:
pH
Protein content
Temperature
Volume
pH
In biotransformation, Oxidation, hydroxylation, dealkylation and sulfoxide formation are examples of…
Phase I reactions
With few exceptions, the metabolites of drugs are more __________ than the parent drug.
Polar or Non-Polar
Polar
The primary site for drug absorption is:
Stomach
Small intestine
Muscle
Kidney
Liver
Small Intestine
Metabolism is the __________ conversion of one chemical substance to another.
Chemical
This metabolite is highly reactive and responsible for acetaminophen-induced hepatotoxicity:
NAPQI
The following is an inactive metabolite:
Dihydrocodeine
Delta-9-Carboxy-THC
Morphine 6-glucuronide
11-OH-THC
Nordiazepam
Delta-9-Carboxy-THC
In contrast to drugs after phase I biotransformation, drugs after phase II have:
Less pharmacological activity and lower water solubility
More pharmacological activity and greater water solubility
Less pharmacological activity and greater water solubility
More pharmacological activity and less water solubility
Less pharmacological activity and greater water solubility
Cocaine undergoes this to form benzoylecgonine:
Demethylation
Reduction
Hydrolysis
Glucuronidation
Oxidation
Hydrolysis
Cytochrome p450 is a family of:
Mixed function monoamine oxidase inhibitors
Mixed function glutathione transferases
Mixed function transferases
Mixed function oxidases
Mixed function isozymes
Mixed function oxidases
True or False: Lorazepam has no active metabolites.
True
1,4-butanediol is a metabolic precursor to:
GHB
PCP
LSD
GBL
alpha-PVP
GHB
