Pharmacokinetic Principles of Pharmacology Flashcards by Desiree Namou

what the body does to the drug

pharmacokinetics

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what the drug does to the body

pharmacodynamics

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clinical pharmacokinetics is the discipline that describes the 
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absorption, distribution, metabolism, excretion

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half life is the time required for serum concentration of a drug to decrease by ____ after absorption and distribution are complete

example drug A half life is 2 hours - 100%
1 hour is 50%

50%

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a drug given orally has to first pass through this organ _____________ before it reaches its site of action

hepatic first pass effect

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___________ is a generic name for the group of enzymes that are responsible for most drug metabolism _______ reactions. They are produced in the _______

cytochrome p450

oxidation

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physiologic barriers
physical, chemical and biological barriers

epithelial lining of GIT is a __________
pH difference between stomach and fundal veins is a _________

blood barrier/blood placental barrier is a _________

bi-lipid layer: _________, ______, ________
transmembrane proteins (__ proteins)
___________ core and 2 _______ surfaces

physical barrier
chemical barrier
biological barrier
phospholipids, sterols, glycolipids
G proteins
hydrophobic
hydrophilic

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drug concentration at sites of action influenced by several factors such as:
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route of administration
dose
characteristics of drug molecules

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drug absorption
routes of drug administration
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2
- vapors, gases, smoke
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- \_\_\_\_\_\_\_
-  \_\_\_\_\_\_\_\_
-\_\_\_\_\_ suppositories
4. injection (parenteral)
- \_\_\_\_\_\_\_
-\_\_\_\_\_\_\_\_
-\_\_\_\_\_\_
-\_\_\_\_\_\_\_\_
-\_\_\_\_\_\_
-\_\_\_\_\_\_\_\_
5. \_\_\_\_\_\_\_\_\_

oral
inhalation
mucous membranews
intranasal 
sulingual
rectal 
intravenous 
intramuscular
subcutaneous
intraperitoneal
intra-arterial
intra-articular
transdermal

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drug absorption
lipid solubility
pKa = pH at which __% of drug molecules are ionized
-uncharged (_______) molecules are lipid ______
-the pKa of a molecule influences its rate of ________ through tissues into the blood stream
-pH trapping (___________ equation)
-consider a weakly acidic drug ___

pH trapping

aspirin is _______ in an acidic environment and 1000x faster in diffused through the GI mucosa into the plasma which has a pH of 7.4
- once in the plasma, this acidic drug is _______ and cannot reneter the GI trapped

pH varies: _______ (1-2), intestines (6-7)

50
unprontonated
soluble
absorption
henderson-hasselbalch equation
neutral
pH trapped
stomach
intestines

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routes of drug administration
oral drug administration:

advantages:
safe, economical, convenient, practical

disadvantages

___________
_____ levels are difficult to predict due to multiple factors that limit absorption
some drugs are destroyed by _________
drugs may get activated and then broken down
some drugs irritate the ___ system

first pass effect
blood
stomach acids
GI

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routes of drug administration
advantages of injection routs
- absorption is more ____ than with oral administration
-rate of absorption depends on blood flow to particular tissue site (___> ___ > ___)

advantages specific to IV injection

no absorption involved ( inject directly into blood)
rate of _____ can be controlled
a more accurate prediction of ____ is obtained

rapid
IP, IM, SC
infusion
dose

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routes of drug administration
disadvantages/risks of injection
-a rapid onset of action can be dangerous if _______ occurs
-recovery from ________ or shock
-if administered too fast, ____ and ____ function could be compromised
-drugs insoluble in water or dissolved in oily liquids can not be given ___
-_______ techniques are neccessary

overdosing
dehydration
heart, respiratory
IV
sterile

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______: the fraction of an administered dose of drug that reaches the blood stream

physical properties of the drug (______, ______, ________)
drug formulation (_______, ______, ______)
_____ state
_______ emptying rate
interactions with other drugs
____ and ___
_____
genetic, disease, ethnocultural, socioeconomic

bioavailability
hydrophobicity, pKA, solubility
sustained release, troche, pessary
fasting 
gastric
age, gender
diet

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__________: the passage of drug from site of administration into the circulation

__________: drugs given in solid form muset dissolve in the _______ bio-phase before they are absorbed. poorly water soluble drugs (______)

passive transport depends on the _________ gradient
area of absorbing surface: if the area is _____, the absorption is faster
________ of absorbing surface. Blood circulation _____ the drug from the site of absorption and maintains concentration gradient across the ________. _____ blood flow hastens drug absorption

absorption
aqueous solubility
aqueous
Griseofulvin
concentration
larger
vascularity
membrane
increased

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route of administration affects drug absorption because each route has its own pecularities

oral application

unionized lipid soluble drugs (______) are readily absorbed from GIT
acid drugs (____) acid drug absorption from the stomach is faster due to non-ionized properties
basic drugs (______, ______) are largely ionized in the _______ and are absorbed only from the ______

ethanol
aspirin
atropine, morphine
stomach
duodenum

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presence of food
-dilutes the ____ and retards ______
-_______ with calcium present in milk
-_______ hormone (_______: synthroid USP)
-food delays gastric _______. Most drugs are absorbed better if taken on an empty stomach
-certain drugs are degraded in the GIT _______ by acid, _____ by peptidases - ineffective _____
-enteric coated tablets (______ coating)
and sustained released preparations can be used to overcome ______ ability, _____ irritancy and ____ duration of action

drug, absorption
tetracyclines
thyroxine
levothyroxine
emptying
penicillin G, insulin
orally
acid resistant
acid, gastric, brief

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presence of other drugs
-drugs can also alter absorption by gut wall:
altering motility (_______, ________)
-causing mucosal damage (_______)
-alteration of gut flora by _______ may disrupt the __________ circulation

intestinal absorption
-ileum (_, _, _, _)

motility
atropine, metoclopramide
methotrexate
antibiotics
enterohepatic
ADEK

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Subcutaneous and IM

drug deposited in the vicinity of the _________
_______ drugs pass readily across the surface of the capillary endothelium
absorption from SC site is ______ than that from IM
application of ___ and ______ accelerate drug absorption by increasing blood flow
_____ preparations (preparations with a long action) such as _______ and __________ can be given by these routes

vaccines

capillaries
lipid soluble
slower
heat, muscular exercise
depot
benzyl penicillin
protamine zinc insulin

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topical application
(skin, cornea, mucous membrane)
systemic absorption depends on ________
only a few drugs significantly penetrate intact skin
-_______, ______, and _______
-______ applied over extensive areas can produce systemic effects and ________ suppression
-mucous membranes of the mouth, rectum, and vagina absorb ______ drugs (example: ______)

lipid solubility
nitroglycerine, scopolamine, estradiol
glucocorticosteroids
estrogen creams

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______: passage of a drug from the circulation to the tissue and the site of its action
-the extent of distribution of a drug depends on its _______, _______ at physiological pH, extent of binding to _____ and ________, and differences in regional _______

movement of a drug proceeds until an ______ is established between unbound drug in plasma and tissue fluids

distribution
lipid solubility
ionization
plasma, tissue proteins
blood flow
equilibrium

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the total body water as a perccentage of body mass varies from __ to __%, being rather less in _____ than ____
body water is distributed into the following main compartments
1. _______ (20% of body mass)
2. _______ fluid (15%)
3. ______ fluid (35%)
4. _________ fluid (__%)
5. ___ (20%)

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50, 70 
plasma
intestinal
intracellular
transcellular 
fat

apparrent volume of distribution
if drug given IV the body behaves as a single ______ compartment with a volume (Vd) where the drug gets immediately distributed
vd = _________/_________

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homogenous
dose administered
plasma concentration

drugs extensively bound to plasma proteins are largely restricted to the _______ compartment and have low __ (______ is 99% bound to plasma proteins therefore its Vd is 0.1)

drugs sequestrated in other tissues may have Vd much more than the ___ or even body mass (________)

drugs may be present in other tissues, and the plasma concentration is low (___________)
drug poisoning: Drugs with large Vd are not easily removed by ___________ and need a plasma antidote to chelate them
chelating agents: _________ for Lead
_________ for copper (______ disease)

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vascular compartment
Vd
TBW
Digoxin
biphosphonates
hemodialysis
Ca++ EDTA
penicillamine 
Wilson's disease

Blood Brain Barrier - Lipid based and limits the entry of non-lipid soluble drugs (_______) - efflux carriers like P-gp (_______) present in brain capillary endothelial cells extrude drugs that enter the brain by other processes - inflammation of the meninges of the brain ______ permeability of the BBB - Drugs: ________ does not enter the brain, but its precursor ______ does - use in _________

``` amoxicillin glycoprotein increases dopamine parkinsonism ```

blood placental barrier - _________. Placental membranes are _____ soluble and allow free passage of ________ drug, while restricting ______ drugs - the placental P-gp also serves to limit fetal exposure to maternally administered drugs - _______ amounts of non-lipid soluble drugs when present in high concentration gain access to the fetus - it is an ______ barrier - ________, ________, ______ cross easily - _______, _______, and _______ do not affect the fetus and may be used during pregnancy

``` placental barrier lipid lipophilic hydrophilic restricted incomplete benzodiazepines, alcohol, cannabis penicillins, azithromycin, erythromycin ```

storage of drugs -drugs may also accumulate in specific organs or get bound to specific tissue constituents 1. heart and skeletal muscles - ______ 2. liver - _______ 3. kidney - ______ 4. thyroid gland - _______ 5. brain - _________ 6. retina - ________ 7. bones and teeth - _______, _______ 8. Adipose tissue - _______

``` digoxin chloroquine NSAIDs iodine isoniazid chloroquine tetracyclines, heavy metals DDT ```

Metabolism (biotransformation) -chemical alteration of the drugs in the body - the primary sites for drug metabolism is the ______, ______, ______, _____, and _______ metabolism of drugs may lead to the following: a) ______ - most drugs are converted to less active or inactive metabolites (_______) b active ______ from an active drug - many drugs are converted to one or more active metabolites (______, ______) c) activation of ________ drug - _____ are inactive and need conversion to one or more active metabolites (_____ to ______) their active forms may be more stable; have better _______ less side effects and toxicity

``` liver, kidney, intestine, lungs and plasma inactivation morphine metabolite diazepam, codeine inactive prodrugs levodopa to dopamine bioavailability ```

``` biotransformation reactions can be classified into two phases Phase I (_______) and II (_____, _______) ``` Phase I a) _______ is the most important drug metabolizing reaction - various oxidation reactions are ________; oxygenation at __, __ or __ atoms - oxidative reactions are mostly carried out by ______ enzymes in the liver (___________) - there are more than 200 cytochrome p450 isoenzyes, differing in their affinity for various substances

``` non-synthetic synthetic, conjugation oxidation hydroxylation C-, N-, S- atoms cytochrome cytochrome p450 reductase ```

cytochrome p450 - ______/_______ carry out biotransformationo f the largest number (=50%) of drugs - in addition to the . liver, these isoforms are expressed in the ______ and the _____ - inhibition of CYP ___ by _______, _______, ______, ______, ______ and a constituent of _______ are responsible for unwanted interactions - _______, _____, _________ - inducers of the _______

``` CYP 3A4, CYP3A5 intestine, kidney 3A4 erythromycin, clarithromycin, ketoconazole, ltraconazole, diltiazem, grapefruit juice rifampicin, phenytoin, carbamazepine ```

cyp3a4/5 inhibitors slide 30

ketoconazole, gestodene

b) Reduction. this reaction is the converse of oxidation and involves _____ enzyme in working in the opposite direction -drugs, primarily reduced are ______, ______

CYP450 | levodopa, halothane

c) _______ - this is cleavage of a drug molecule by raking up a molecule of water ester + h20 ----> (esterase) acid + alcohol similarly _____ and ______ are hydrolyzed by _______ and _______. Hydrolysis occurs in the ______, ______, ____ and other tissues (_______, ______)

``` hydrolsis amides, polypeptides amidase, peptidases liver, intestines, plasma lidocaine, oxytocin ```

d) _______ - opening up of a ring structure of the cyclic molecule (_______)

decyclization | phenytoin

Phase II - synthetic (conjugation) reaction these involve conjugation of the drug or its phase I metabolite with an _______ substrate to form a ____, highly _____ compound, excreted in ____ or ___ -conjugation reactions have ____ energy requirements 1) ___________ is the most important synthetic reaction. Compounds with a ________ or ________ group are easily conjugated with glucoronic acid (ex. _______) - the liberated drug is reabsorbed and underrgoes the same fate. This _________________ of some drugs (__________) prolongs their actions

``` endogenous polar, ionized urine, bile high glucuronide conjugation hydroxyl, carboxylic bile salts enterohepatic recirculation oral contraceptives ```

phase II - synthetic (________) reactions 2) ________. compounds having ____ residues are conjugated with the help of _________ (ex. _______) multiple genes control the ________ and rate of acetylation shows genetic _______ (slow and fast acetylators) 3) _________/________ synthesis is important for the activation of many ____ and ______ antimetabolites used in ________ (ex ________) 4) __________ - alcohol by __________ - epinephrine by ____________ (__)

``` conjugation acetylation amino acetyl coA isoniazid acetyl transferases polymorphism ribonuceloside/nucleotide purine, pyrimidine cancer chemotherapy 5-fluroacil dehydrogenases monoamine oxidase (MAO) ```

first pass (presystemic) metabolism - metabolism of a drug during its passage from the site of absorption into the systemic circulation - all orally administered drugs are exposed to drug metabolism in the __________ and ____ in different extent - _______, _______, ______, _______ - oral dose of these drugs is higher than _______ dose - there is individual variation in the oral dose due to differences in the extent of first pass metabolism - oral _________ is _______ patients with severe liver disease

``` intestinal wall, liver propranolol, verapamil, albuterol, nitroglycerine parenteral bioavailability increased ```

``` iv ______ - the passage of systemically absorbed drugs out of the body drugs and their metabolites are excreted by: 1 2 3 4 5 6 ```

``` excretion urine (kidney) bile and feces exhaled air saliva sweat milk skin ```

``` urinary/renal excretion 1 2 3 4 5 - urinary antiseptic ```

``` aminoglycosides beta-lactams sulfonamides quinolones nitrofurantoin (Macrobid) ```

``` hepatic excretion 1 2 3 4 ```

macrolides lincosamines rifampicin tetracyclines

``` pulmonary excretion 1. general ___________ 2 3 4 5 ```

``` inhalation anesthetics nicotine albuterol deriphylline alcohol ```

salivary excretion 1 2 3

nicotine phenytoin nifedipine

first order (exponential kinetics) - this occurs for ________ of drugs - the processes involved involved in elimination are not ______ over the clinically obtained concentrations - their rate of elimination is directly proportional to the _________ concentration - drugs are ______ at the rate at which they are ______

``` majority saturated plasma drug removed absorbed ```

zero order (linear) kinetics - some drugs are inactivated by metabolic degradation (_______, ______, _______ and _______) - time-course elimination of drug from plasma is initially ____ and then the ________ get saturated - these drugs are removed at constant rate of which is ________ of plasma concentration

ethanol, phenytoin, theophylline, warfarin linear excretory mechanisms independent

first order elimination - drug decreases _______ with time - rate of elimination is _______ to drug - t 1/2 is _______ regardless of drug zero order elimination - drug decreases ______ with time - rate of elimanation is ______ - rate of elimination is _______ of a drug - no true t 1/2

``` exponentially proportional constant linearly constant independent ```

__________ is the time in which the plasma concentration of a drug declines by 1/2. drugs with long t 1/2 can ______ _______ < 2 sec ________ up to 8-10 years

plasma half life t1/2 accumulate adenosine alendronate

tolerance (desensitization)/tachyphylaxis - rapid tolerance development: ________ - ______ response to same dose with repeated (______) exposure - or more drug needed to achieve same effect - may occur with an acute dose (ex. ______) - can develop across drugs (_________) - caused by ________ mechanisms that oppose the effects of the drug - ________ and ______

``` tachyphylaxis decreased constant alcohol cross-tolerance compensatory nitroglycerine, nicotine ```

drug-drug interactions pharmacokinetic, pharmacodynamic _________ drug interactions - one drug affects the absorptionl distribution metabolism or excretion of another _________ drug interactions: two drugs have interactive effects at the site of drug action (___ and ______) either type of drug interaction can result in adverse effects in individuals -________, _____, _______ and _________

pharmacokinetic pharmacodynamic BZDs and alcohol cumulative, additive, synergistic, antagonistic

______ effects the condition in which repeated admin of a drug may produce effects that are more pronounced than those produced by the fiirst dose ________: ______

cumulative antipsychotics haloperidol

_______ effects the effect of two chemicals is equal to the sum of the effect of the two chemicals taken separately ex _______ and _____

additive | acetominophen, ibuprofen

________ effects the effect of two chemic als taken together is greater than the sum of the separate effect at the same doses ex:

alcohol and marijuana

________ effects the effects of two chemicals taken together is less than the sum of their separate effect at the same doses (_______ drugs such as ______ may antagonize effects of _____ drugs such as _______)

antagonistic bacteriostatic, macrolides bactericidal, vancomycin

_____ - median ____ ____ 50: the dose at which 50% of the population or sample manifests the desired effect ____ - median _______ ___ 50 - dose which kills or causes toxicity in 50% of the subject

ED50, median effective | LD50, median lethal

therapeutic index equation:

TD50 or LD50/ ED50

Pharmacokinetic Principles of Pharmacology Flashcards

(54 cards)