Pharmacokinetics Flashcards
Pharmacokinetics describes the fate of a drug within the body
-It simple refers to “what the body does to the drug”
-These fate includes
_____
______
_____
______
ABSORPTION
DISTRIBUTION
METABOLISM
EXCRETION
Administration of a drug
-is the initial introduction of a drug into the body
-Drugs are introduced into the body either
______ or ______
Enterally or Parenterally
ENTERAL means of administering drugs
____
Oral
PARENTERAL means of administering drugs
Mention 7
Intravenous
Intramuscular
Subcutaneous
Inhalational
Topical
Transdermal
Intrathecal/Intraventricular
Absorption
-is the transfer of drug from the _____ to ____
site of administration to the bloodstream
MEASURE OF DRUG ABSORPTION
Bioavailability
- is the ______
relative amount of the administered drug that reach the systemic circulation
Drugs administered through Intravenous (IV) route have ____% bioavailability
100
Formula for bioavailability of drugs:
Absolute bioavailability = _____/ ____ × —-
Relative bioavailability =_____/ ______ × 100
AUC Oral
AUC IV
100
AUC (test)
AUC (standard)
Bioequivalence
Two drug formulations with _________ as well as the _______ are bioequivalent
the same bioavailability
same rate of absorption
Distribution
is the delivery of a drug from the _____ to ______
systemic circulation to tissues
MEASURE OF DRUG DISTRIBUTION
Volume of distribution (Vd)
-It is the _______
Formula:
Vd = _____/Co
Co is the _______
fluid volume in the body into which the drug is contained
Dose
concentration of the drug in the plasma at time 0
Tissues that store large concentration of drugs are
____
_____
Fat
Bones
Metabolism Of drugs
-Characterized by the conversion of drugs from its ___PHILIC nature to execrable ___PHILIC products, through specialized enzymatic systems
LIPO
HYDRO
SITES OF DRUG METABOLISM
Mention 4
Liver
Kidney
Small Intestine
Lungs
PRODUCTS OF DRUG METABOLISM
Mention 4 scenarios
Inactive to active
Active to inactive
Active to active
Active to toxic
PHASES OF DRUG METABOLISM
Phase I
FUNCTIONALIZATION REACTION
-A ___ is introduced into the drug to make it ____
-Enzymes involved a special enzymes called _____ enzymes found in the ____
functional group
more polar
CYTOCHROME P-450
SER
Examples of Phase I reaction includes:
____
_____
_____
Oxidation
Reduction
Hydrolysis
Enzymes involved in phase 1 oxidation reactions
CytochromeP450 Oxidase
dehydrogenase
Enzymes involved in phase 1 reduction reactions
Cytochrome p450 reductase
Decarboxylase
Enzymes involved in phase 1 hydrolysis reactions
Estarase
Amidase
Phase II
CONJUGATION REACTION
-An _____ substance is added to the drug to make it hydrophilic
-Examples of Phase II reaction
Mention 5
endogenous
Glucuronidation
*Sulfation
*Methylation
*Acetylation
*Glutathione conjugation
Glucuronidation
Sulfation
Methylation
Acetylation
Glutathione conjugation
Glycine conjugation
Mention the enzymes involved in the reactions
Glucoronyl Transferase
N-acetyl Transferase
Sulfo Transferase
Methyl Transferase
Glutathione conjugation
Glycine conjugase
Enzyme Induction
-Induces Microsomal Cytochrome P-450 enzyme
-___eases metabolism of co-administered drugs
-May lead to _____
Incr
therapeutic failure
Enzyme Inhibition
Inhibitors of Cytochrome P-450
___eases metabolism of co-administered drugs
May lead to ____
Decr
drug toxicity
MECHANISM OF HEPATIC EXCRETION
_______
_______
Hepatic secretion
Enterohepatic circulation
Enterohepatic circulation
-from ______ to ____ to ___ to ____ to ____
duodenum to ileum
capillary bed to portal vein to liver
__% bile salts is excreted into faeces
5
a charged drug can cross the plasma membranes
T/F
F
can’t
for absorption, acidic drug wants ____ environment. Basic drugs wants ____
for excretion, acidic drugs wants ___ environment, basic drugs wants ____ environment
acidic
basic
basic
acidic
MEASURE OF DRUG EXCRETION
Half-life (t1/2)
-It is the time taken for ______
Elimination rate (Kel)
-It is the ________
Clearance (CL)
-It is the _______
the concentration of drug in the blood to fall by half its original value.
fraction of drug that is eliminated at a given time
volume of blood or plasma cleared of a drug in unit time
ELIMINATION KINETICS
Zero-order kinetics
-Elimination of ________ per unit time
-Rate of elimination is (dependent or independent?) of drug concentration
-Half-life is ( dependent or independent?) to the drug concentration
constant amount of a drug
independent
dependent
Zero-order kinetics Examples
Mention 4
Ethanol
Heparin
Phenytoin
Aspirin
First-order kinetics
-Elimination of ____ of a drug per time
-Rate of elimination is (dependent or independent?) of the drug concentration
-Half-life is (dependent or independent?) of drug concentration
Examples
____
constant percentage
Dependent
independent
MOST DRUGS
PARACETAMOL
Administration-
Bioavailability-
Metabolism in the liver - phase 1:
phase 2:
Half-life-
Elimination kinetics- zero or first
Excretion is by??
Oral
63-89%
Oxidation
Sulphation and glucoronidation
1.9-2.5 hours
First order
Kidney
Enteral administration is administering a drug by ______
mouth
______ administration is the safest and most common, convenient, and economical method of drug
administration.
Enteral
The drug may be swallowed, allowing oral delivery, or it may be placed _________ (sublingual), or _____ (buccal), facilitating direct absorption into the bloodstream
under the tongue
between the gums and cheek
A wide range of oral preparations is available for drugs that can’t withstand the low ph of the stomach including
______ and ______ preparations.
enteric-coated and extended-release
Enteric coating is useful for
certain drugs (for example, ______) that are acid unstable.
Drugs that are irritating to the stomach, such as _______, can
be formulated with an enteric coating that only dissolves in the
small intestine, thereby protecting the stomach.
omeprazole
aspirin
the half-life of oral morphine is ___
2 to 4 hours
Example of a drug poorly absorbed in the GIT
Heparin
Example of a drug that is unstable in the GIT
Insulin, omeprazole
________ is the most common parenteral
route
IV injection
Injected drugs can be recalled by activated charcoal
T/F
F
Subcutaneous injection route should not be used with drugs that cause
_______, because ______ and ______ may occur.
tissue irritation
severe pain and necrosis
Drugs commonly administered via the subcutaneous route include
______ and ______
insulin and heparin.
Examples of drugs administered via Oral inhalation include bronchodilators, such as ______, and corticosteroids, such as _____.
albuterol
fluticasone
Desmopressin is administered ______
in the treatment of _________
intranasally
diabetes insipidus.
Topical application is used when _____________
a local effect of the drug
is desired.
Transdermal: This route of administration achieves systemic
effects by application of drugs to ______, usually via a ______
the skin
transdermal patch
Rectal: Because 50% of the drainage of the rectal region ________, the ___________ is minimized with rectal administration.
bypasses the portal circulation
biotransformation of drugs by
the liver
The vast majority of drugs
are absorbed by ____ mechanism
Passive diffusion
_____-soluble drugs penetrate the cell membrane through aqueous channels or pores, whereas ____-soluble drugs readily move across most biologic
membranes
Water
lipid
Mechanisms of absorption of drugs from the GI tract
Passive diffusion can be saturated
Facilitated diffusion can be saturated
Active transport can be saturated
T/F
F
T
T
The lower the pKa of a drug, the more _____ it is
acidic
Which has more blood flow and hence better for absorption?
Stomach or small intestine?
Small intestine
First-pass hepatic metabolism: When a drug is absorbed from the GI tract, it enters the _____ before entering the _____
portal circulation
systemic circulation
more than 90% of _______ is cleared during first-pass metabolism.
nitroglycerin
rocuronium, a _________ is administered by ______ route
Neuromuscular blocker
IV
if the medication is delivered too rapidly and high concentrations are reached too quickly , It may also ______, induce ______, or cause other adverse reactions
precipitate blood constituents
hemolysis
Drugs administered IM can be in ______, which are absorbed rapidly, or in specialized ______, which are absorbed slowly.
aqueous solutions
depot preparations
Depot preparations often consist of a _____ of the drug in a ______
vehicle such as polyethylene glycol.
As the vehicle diffuses out of the muscle, the drug ______ at the site of injection. The drug then _______, providing a ________ over an extended period of time.
suspension; nonaqueous
Precipitates ; dissolves slowly
sustained dose
Subcutaneous administration route should not be used with drugs that cause _______, because ________ and _______ may occur.
Drugs commonly administered via the subcutaneous route include ______ and _____
tissue irritation
severe pain and necrosis
insulin and heparin.
The _____ typically delays or prevents the absorption of drugs into the central nervous system (CNS). When local, rapid effects are needed, it is necessary to introduce drugs directly into the _________
blood–brain barrier
cerebrospinal fluid.
A drug passes through membranes more readily if it is (charged or uncharged ?)
Uncharged
Factors that affect route of administration
______ of Drug
________ of treatment
_____ of action
Desired _______
_________
Nature
Duration
Site
onset of action
Consciousness
FACTORS AFFECTING DRUG ABSORPTION
_______ of Administration
_________ of drug
_______
______
_____ flow
_______ of absorption site
_________ at absorption site
Presence of ______
Route
Solubility
Concentration
pH
Blood
Surface area
Contact time
P-glycoprotein
Out of AADME, which ones do age affect
Distribution
Metabolism
Out of AADME, which ones do PH affect
Absorption
Distribution
Excretion
Arrange in terms of decreasing absorption rate
Skin; gut; muscle
Muscle, skin, gut
FACTORS AFFECTING DRUG DISTRIBUTION
______ of drug
____
Binding to ______
Binding to _____
Organ or tissue size and perfusion
_____
______
____
_______
______ state
Drug ______
Lipophilicity
pH
plasma proteins
Tissues
Age
Pregnancy
Obesity
Diet
Disease
interaction
MEASURE OF DRUG DISTRIBUTION
__________
Volume of distribution (Vd)
Levodopa is converted from _____ to _____
Inactive to active
Epinephrine is from active to _____
Panadol is from active to_____
Inactive
Toxic
Salivary excretion is by _______
Pulmonary excretion is by _______________
Tears excretion is by _________
Sweat excretion is by ________
Hair excretion is by _________
Breast excretion is by __________
Passive diffusion
Passive diffusion and expiration
Passive diffusion
Passive diffusion
Unknown…maybe deposition from the capillaries
Passive diffusion
Codeine
Weak acid or weak base?
Weak base
Most rapid route of absorption is IV
T or F
F
Inhalational
