Pharmacokinetics and Pharmacodynamics Flashcards
1
Q
pharmacokinetics
- _____: what the body does to the drug
- _____: what the drug does to the body
- clinical pharmacokinetics is the discipline that describes the _____, _____, _____, _____ of drugs
- _____ is the time required for serum concentrate of a drug to decrease by _____ after _____ and _____ are complete
- a drug given orally has to pass through this organ _____ before it reaches its site of action
- _____ is a generic name fo the group of enzymes that are responsible for most drug metabolism oxidation reactions. They are produced in the _____
A
pharmacokinetics pharmacodynamics absorption distribution metabolism excretion half life half liver cytochrome P450
2
Q
physiologic barriers
- _____, _____, _____ barriers
- epithelial lining of GIT: _____
- pH differences between stomach and fundal veins: _____
- blood brain barrier/blood placental barrier: _____
- bi-lipid layer: _____, _____, _____
- transmembrane proteins (_____)
- _____ core and 2 _____ surfaces
A
physical barriers chemical barriers biological barriers phospholipids sterols glygolipids G proteins hydrophobic hydrophilic
3
Q
_____:
- movement of drugs in the body
- four processes
- -_____
- -_____
- -_____
- -_____
drug concentration at sites of action influenced by several factors, such as:
- _____
- _____
- characteristics of _____ (e.g., _____ solubility)
A
pharmacokinetics absorption distribution metabolism excretion route of administration dose drug molecules lipid
4
Q
drug absorption
routes of drug administration
-_____ (po)
-_____: _____, gases, smoke
- mucous membranes
- _____ (sniffing)
- _____
- _____
- injection (_____)
- _____ (IV)
- _____ (IM)
- _____ (SC)
- _____ (IP)
- _____
- _____
-transdermal
A
oral inhalation vapors intranasal sublingual rectal suppositories parenteral intravenous intramuscular subcutaneous intraperitoneal intra-arterial intra-articular
5
Q
drug absorption
-lipid solubility
pKa = pH at which _____ of drug molecules are _____
–uncharged (_____) molecules are _____
–the pKa of a molecule influences its rate of _____ through _____ into the _____
–pH trapping (_____ equation)
-consider a weakly acidic drug (_____)
pH trapping:
- aspirin is _____ in an acidic environment and 1000 times faster diffused through the _____ into the _____ which as a pH of 7.4
- once in the plasma, this acidic drug is _____ and cannot re-enter the _____
- pH varies: stomach 1-2, intestines: 6-7
A
50% ionized unprotonated lipid soluble absorption tissues bloodstream henderson-hasselbalch equation ASA neutral GI mucosa plasma pH trapped GI tract
6
Q
routes of drug administration
- oral drug administration:
- advantages:
- _____, _____, convenient, practical
disadvantages:
- _____ effect
- blood levels are difficult to predict due to multiple factors that limit _____
- some drugs are destroyed by _____
- drugs may get _____ and then _____
- some drugs irritate the _____ system
A
safe economical first pass absorption stomach acids activated broken down GI
7
Q
routes of drug administration
- advantages of infection routes:
- -_____ is more rapid than with oral administration
- -rate of absorption depends on _____ to particular tissue site (_____ > _____ > _____)
- advantages specific to I.V. injection
- -no _____ involved (injects directly into _____)
- rate of _____ can be controlled
- a more accurate prediction of _____ is obtained
A
absorption blood flow IP IM SC absorption blood infusion dose
8
Q
routes of drug administration
disadvantages/risks of injection
-a rapid onset on action can be dangerous if _____ occurs
-recovery from _____ or _____
-if administered too fast, _____ and _____ function could be compromised
-drugs _____ in water or dissolved in _____ liquids can not be given IV
-_____ techniques are necessary
A
overdosing dehydration shock heart respiratory insoluble oily sterile
9
Q
_____:
- the fraction of an administered dose of drug that reaches the blood stream
- -physical properties of the drug (_____, _____, _____)
- -drug formulation (_____, _____, _____)
- -_____ state
- -_____ rate
- -interactions with other _____
- -_____ and _____
- -_____
- -_____, _____, ehtno cultural, socioeconomic
A
bioavailability hydrophobicity pKa solubility sustained release troche pessary fasting gastric emptying drug age gender diet genetic diseae
10
Q
absorption
- it is the passage of drug from the _____ into the _____
- _____: drugs given in solid form must dissolve in the aqueous _____ before they are absorbed. Poorly water soluble drugs (_____)
- _____: passive transport depends on the _____
- area of _____ surface: if the area is larger, absorption is _____
- _____ of absorbing surface: blood circulation removes the drug from the site of absorption and maintains _____ across the _____. _____ blood flow hastens drug absorption
A
site of administration circulation bio-phase Griseofulvin concentration concentration gradient absorbing faster vascularity concentration gradient membrane increase
11
Q
route of administration affects drug administration, because each route has its own peculiarities
- oral application:
- -_____ drugs (_____) are readily absorbed from GIT
- -acid drugs (_____) acid drug absorption from the _____ is faster due to _____ properties
- -basic drugs (_____, _____) are largely ionized in the _____ and are absorbed only from the _____
A
unionized lipid soluble ethanol aspirin stomach non-ionized atropine morphine stomach duodenum
12
Q
presence of food
- _____ the drug and retards _____
- _____ with calcium present in milk
- thyroxine hormone (_____: _____ USP)
- food delays _____. most drugs are absorbed better if taken on an empty stomach
- certain drugs are degraded in the _____ e.g. _____ by acid, _____ by peptidases- ineffective _____
- _____ coated tablets (_____ resistant coating) and sustained released preparations can be used to overcome acid ability, _____ irritancy, and brief duration of action
A
dilutes absorption tetracyclines levothyroxine synthroid gastric emptying GIT penicillin G insulin orally enteric acid gastric
13
Q
presence of other drugs
- drugs can also alter absorption by _____:
- altering motility (_____, _____)
- causing _____ damage (_____)
- alteration of gut flora by _____ may disrupt the _____ circulation
intestinal absorption
-ileum (_____, _____, _____, _____)
A
gut wall atropine metoclopramide mucosal methotrexate antibiotics enterohepatic ADEK
14
Q
subcutaneous and IM
- drug deposited in the vicinity of the _____
- lipid soluble drugs pass readily across the surface of the _____
- absorption from SC site is _____ than that from IM
- application of _____ and muscular exercise accelerate drug absorption by increasing _____
- _____ (preparations with a long action) such as _____ and _____ can be given by these routes
A
capillaries capillary endothelium slower heat blood flow depot preparations benzyl penicillin protamine since insulin
15
Q
topical application
(skin, _____, _____)
systemic absorption depends on _____
only a few drugs significantly _____ intact skin
-_____, _____, and _____
-_____ applied over extensive areas can produce systemic effects and _____ suppression
-mucous membrane of the mouth, _____ and _____ absorb _____ drugs, e.g. _____ cream
A
cornea mucous membranes lipid solubility penetrate nitroglycerine scopolamine estradiol glucocorticosteroids pituitary-adrenal rectum vagina lipophilic estrogen
16
Q
_____:
- it is the 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 _____ proteins, and differences in regional _____
- movement of a drug proceeds until an _____ is established between _____ drug in plasma and tissue fluids
A
distribution lipid solubility ionization plasma tissue plasma tissue blood flow equilibrium unbound
17
Q
body fluid compartments -the total body water as a percentage of body mass varies from \_\_\_\_\_ to \_\_\_\_\_, being rather less in \_\_\_\_\_ than \_\_\_\_\_ -body water is distributed into the following main compartments 1. \_\_\_\_\_ 2. \_\_\_\_\_ 3. \_\_\_\_\_ 4 \_\_\_\_\_ 5. \_\_\_\_\_
A
50% 70% women men plasma intestinal fluid intracellular fluid transcellular fluid fat
18
Q
apparent volume of distribution (Vd)
-if drug given IV the body behaves as a _____ compartment with a volume (Vd) Where the drug gets _____ distributed
Vd= _____/_____
A
single homogenous
immediately
dose administered
plasma concentration
19
Q
- drugs extensively bund to plasma proteins are largely restricted to the _____ and have low _____ (_____ is 99% bound to plasma proteins therefore its Vd is 0.1)
- drugs sequestrated in other tissues may have a Vd much more than the total _____ or even _____ (_____)
- drugs may be present in other tissues, and the _____ is low (_____)
- drug poisoning: drugs with large Vd are not easily removed by _____ and need a _____ to chelate them
- chelating agents: _____ for _____
- _____ for _____ (Wilsons disease)
A
vascular compartment Vd Warfarin body water body mass Digoxin plasma concentration bisphosphonates hemodialysis plamsa antidote Ca++ EDTA lead penicillamine copper
20
Q
blood brain barrier
- _____ based and limits the entry of non-lipid soluble drugs (_____)
- _____ carriers like _____ (glycoprotein) present in _____ cells extrude drugs that enter the brain by other processes
- inflammation of the _____ of the brain _____ permeability of the BBB
- drugs: _____ (DA) does not enter the brain, but its precursor _____ does
- used in _____
A
lipid Amoxicillin efflux P-gp brain capillary endothelial meninges increases dopamine levodopa Parkinsonism
21
Q
blood brain barrier
- placental barrier: placental membranes are _____ and allow free passage of _____ drug, while restricting _____ drugs
- the placental _____ also serves to limit fetal exposure to maternally administered drugs
- restricted amounts of _____ drugs when present in _____ concentration gain access to the fetus
- it is an _____ barrier
- _____, _____, _____ cross easily
- _____, _____, and _____ do not affect the fetus and may be used during pregnancy
A
lipid soluble lipophilic hydrophilic P-gp non-lipid high incomplete benzodiazepines alcohol cannabis penicillins azithromycin erythromycin
22
Q
storage of drugs
- drugs may also accumulate in specific organs or get bound to specific tissue constituents:
- heart and skeletal muscles: _____
- liver: _____
- kidney: _____
- thyroid gland: _____
- brain: _____
- retina: _____
- bones and teeth: _____, _____
- adipose tissues: _____
A
digoxin chloroquine NSAIDs Iodine Isoniazid Chloroquine tetracyclines, heavy metals DDT
23
Q
metabolism (_____)
- 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:
- -_____: most drugs are converted to less active to inactive metabolites (_____)
- -_____ from an active drug. Many drugs are converted to one or more active metabolites (_____, _____)
- -activation of inactive 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
A
liver kidney intestine lungs plasma inactivation morphine active metabolite diazepam codeine prodrugs levodopa dopamine bioavailability
24
Q
biotransformation reactions can be classified into two phase: I (_____) and II (_____, _____)
- phase I (non-synthetic)
- -_____ 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 (_____ reductase)
- –there are more than 200 _____, differing in their affinity for various substances (drugs)
A
non-synthetic synthetic conjugation oxidation hydroxylation C- N- S- cytochrome cytochrome P450 cytochrome P450 isoenzymes
25
cytochrome P450
- _____ carry out biotransformation of the largest number (= _____) of drugs
- in addition to the liver, these isoforms are expressed in the _____ and the _____
- inhibition of CYP 3A4 by _____, _____, _____, _____, _____ and a constituent of _____ juice are responsible for unwanted interactions
- _____, _____, _____
- inducers of the CYP 3A4
```
CYP3A4/CYP 3A5
50%
intestine
kidney
erythromycin
clarithromycin
ketoconazole
itraconazole
diltiazem
grape fruit
rifampicin
phenytoin
carbamazepine
```
26
reduction. this reaction is the converse of _____ and involves CYP450 enzymes working in the _____ direction
- drugs, primarily reduced, are _____, _____
levodopa ----> dopamine (what goes above arrow)
```
oxidation
opposite
levodopa
halothane
DOPA-decarboxylase
```
27
hydrolysis. this is _____ of a drug molecule by taking up a molecule of _____
ester + H2O ------> Acid + Alcohol (what goes above arrow)
-similarly _____ and _____ are hydrolyzed by _____ and _____. hydrolysis occurs in the _____, _____, _____, and other tissues . (_____, _____)
```
cleavage
water
amides
polypeptides
amidase
peptidases
liver
intestines
plasma
lidocaine
oxytocin
```
28
de-cyclization is opening up of a _____ structure of the cyclic molecule, e.g. _____
ring
| phenytoin
29
Phase II- synthetic (conjugation) reactions
- these involve _____ of the drug or its _____ with an _____ to form a _____, highly _____ compound, excreted in _____ or _____
- conjugation reactions have _____ energy requirements
- _____ is the most important synthetic reaction. compounds with a _____ or _____ group are easily conjugated with _____. e.g. _____
- the liberated drug is reabsorbed and undergoes the same fate. this _____ of some drugs (_____) prolongs their action
```
conjugation
phase I metabolite
endogenous substrate
polar
ionized
urine
bile
high
glucuronide conjugation
hydroxyl
carboxylic
glucuronic acid
bile salts
enterohepatic
oral contraceptives
```
30
phase II - synthetic (conjugation) reactions
-_____: compounds having amino residues are conjugated with the help of _____ e.g. _____. multiple genes control the _____ and rate of acetylation shows genetic _____ (slow and fast acetylators)
```
acetylation
acetyl CoA
isoniazid
acetyl transferases
polymorphism
```
31
phase II - synthetic (conjugation) reactions
| -_____ is important for the activation of many purine and pyrimidine _____ used in _____ e.g. _____
ribonucleoside/nucleotide synthesis
antimetabolites
cancer chemotherapy
5-Flurouracil
32
phase II - synthetic (conjugation) reactions
- enzyme metabolism
- -alcohol by _____
- -epinephrine by _____ (MAO)
dehydrogenase
| monoamine oxidase
33
first pass (presystemic) metabolism
- metabolism of a drug during its passage from the site of _____ into _____
- 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 _____ dose due to differences in the extent of _____
- oral bioavailability is increased in patients with severe _____
```
absorption
systemic circulation
intestinal wall
liver
propranolol
verapamil
albuterol
nitroglycerine
parenteral
oral
first pass metabolism
liver disease
```
34
excretion
- excretion is the passage of _____ out of the body
- drugs and their metabolites are excreted by:
- _____ (kidney)
- _____ and _____
- _____
- _____
- _____
- _____
- _____
```
systemically absorbed drugs
urine
bile
feces
exhaled air
saliva
sweat
milk
skin
```
35
urinary/renal excretion
- _____
- _____
- _____
- _____
- _____ (Macrobid): _____
```
aminoglycosides
beta-lactams
sulfonamides
quinolones
nitrofurantoin
urinary antiseptic
```
36
hepatic excretion
- _____
- _____
- _____
- _____
macrolides
lincosamines
rifampicin
tetracyclines
37
pulmonary excretion
- _____ anesthetics
- _____
- _____
- _____
- _____
```
general inhalation
nicotine
albuterol
deriphylline
alcohol
```
38
salivary excretion
- _____
- _____
- _____
nicotine
phenytoin
nifedipine
39
first order (exponential) kinetics
- this occurs for majority of drugs
- the processes involved in _____ are not saturated over the clinically obtained concentrations
- their rate of elimination is directly proportional to _____ concentration
- drugs are removed at the rate at which they are _____
elimination
plasma drug
absorbed
40
zero order (linear) kinetics)
- some drugs are inactivated by _____ (_____, _____, _____, and _____)
- time -course of elimination of drug from plasma is initially _____ and then _____ mechanisms get saturated
- these drugs are removed at constant rate which is _____ of plasma concentration
```
metabolic degradation
ethanol
phenytoin
theophylline
warfarin
linear
excretory
independent
```
41
```
comparison
first order elimination:
-drug decreases _____ with time
-rate of elimination is _____ to drug
-t1/2 is _____ regardless of drug
```
zero order elimination:
- drug decreases _____ with time
- rate of elimination is _____
- rate of elimination is _____ of drug
- no true _____
```
exponentially
proportional
constant
linearly
constant
independent
t1/2
```
42
_____ (_____) is the time in which the plasma concentration of a drug declines by one half. drugs with long t1/2 can _____.
adenosine - _____ seconds
alendronate - _____ years
plasma half life (t1/2)
accumulate
< 2
8-10
43
tolerance (desensitization) / _____
- rapid tolerance development: _____
- _____ response to same dose with repeated (_____) exposure
- or _____ drug needed to achieve same effect
- may occur with an _____ dose (e.g. _____)
- can develop across drugs (_____)
- caused by _____ mechanisms that oppose the effects of the drug
- _____ and _____
```
tachyphylaxis
tachyphylaxis
decreased
constant
more
acute dose
alcohol
cross-tolerance
compensatory
nitroglycerine
nicotine
```
44
drug-drug interactions
pharmacokinetic and pharmacodynamic
-pharmacokinetic drug interactions: one drug affects the _____, _____, _____ or _____ of another
-pharmacodynamic drug interactions: two drugs have _____ effects at the site of _____ (_____ and _____)
-either type of drug interaction can result in adverse effects in individuals
-_____, _____, _____, and _____
```
absorption
distribution
metabolism
excretion
interactive
drug action
BZDs
alcohol
cumulative
additive
synergistic
antagonistic
```
45
cumulative effects
the condition in which _____ administration of a drug may produce effects that are more _____ than those produced by the _____
-antipsychotics: _____
repeated
pronounced
first dose
haloperidol
46
additive effects
| -the effect of _____ chemicals is _____ to the sum of the effect of the two chemicals taken separately
two
equal
acetaminophen
ibuprofen
47
synergistic effects
-the effect of _____ chemicals taken together is _____ than the sum of their separate effect at the same doses e.g. _____ and _____
two
greater
alcohol
marijuana
48
antagonistic effects
-the effect of two chemicals taken together is _____ than the sum of their separate effect at the same doses (_____ drugs such as _____ may antagonize the effects of _____ drugs such as _____)
```
less
bacteriostatic
macrolides
bactericidal
vancomycin
```
49
effectiveness, toxicity, lethality
-_____- median effective dose 50; the dose at which _____ of the population to sample _____ the desired effect
-_____- median lethal dose 50; dose which _____ or causes _____ in 50% of the subjects
```
ED50
50%
manifests
LD50
kills
toxicity
```
50
quantification of drug safety
| therapeutic index= _____/_____
TD/50 or LD50
| ED50
