Unit 1 Lectures Flashcards
1
Q
pharmacotherapeutics
A
dose regimen
2
Q
pharmacokinetics
A
how plasma concentration changes over time (what the body does to drug)
3
Q
pharmacodynamics
A
what the drug does to the body
4
Q
pharmacotherapeutics can use a drug for…(4)
A
prevention, diagnosis, treatment, cure
5
Q
In a dosage regimen, select drug and dose based on…
A
pharmacodynamics, disease target, drug regulation
6
Q
In a dosage regimen, select route of administration based on…
A
pharmacokinetics (absorption and distribution)
7
Q
In a dosage regimen, select dosage frequency based on…
A
pharmacokinetics (metabolism and excretion)
8
Q
In a dosage regimen, select duration based on…
A
disease pathophysiology
9
Q
Physiology identifies _________ for drug action
A
potential targets
10
Q
Pathophysiology determines how the _________ should be _________ in a disease
A
targets, manipulated
11
Q
bioavailability
A
how much drug reaches a target
12
Q
volume of distribution
A
what is the drug dose for a desired Cp?
13
Q
The major organ of metabolism is the ________
A
liver
14
Q
The major organ of excretion is the _________
A
kidney
15
Q
Therapeutic uses of drugs act via enhancement or blockade of _______________________
A
normal physiological pathways
16
Q
Idiosyncratic reactions are adverse drug reactions that occur ____________
A
not at target site (peculiar to an individual, less common, less predictable)
17
Q
ke is the _____________ and is used to determine __________
A
elimination rate constant (slope of ln Cp vs. time), half-life
18
Q
factors influencing drug membrane passage (4)
A
- molecular size
- concentration
- lipid solubility
- degree of ionization
19
Q
bioavailability equation (F)
A
F = AUC(oral)/AUC(IV)
20
Q
Bioavailability with oral administration varies based on…
A
- survival of drug in GI (acidity, digestive enzymes)
- ability to cross membrane (small, uncharged, lipid soluble)
- efficiency of metabolism (first pass effect)
21
Q
Rate of onset of drug effect is determined primarily by…
A
route (rather than individual drug characteristic)
22
Q
The major equivalency test required for generic drugs is…
A
bioequivalency (therapeutic equivalency)
23
Q
Generic drugs are bioequivalent to brand name if…
A
rate (Cmax, Tmax) and extent (AUC-bioavailability) of absorption are within set parameters
24
Q
factors affecting drug absorption
A
- drug solubility
- rate of dissolution (concentration of drug at site, circulation, area of absorbing surface)
25
If you take a drug on an empty stomach, you're protecting the _______
drug
26
Subcutaneous route provides a ____________ rate of absorption
slower, more constant
27
Injection volume of __________ route is more limited than ________ route
subcutaneous, intramuscular
28
Injection of (solution/suspension) provides rapid onset of action
solution
29
The sublingual route of drug administration is useful if the drug is __________________
lipid soluble and potent
30
One advantage of a transdermal patch is that it...
avoids first-pass metabolism
31
With local effects, the response (is/is not) proportional to plasma concentration
is not
32
slow speed of onset of drug effect (4)
- oral
- intramuscular
- subcutaneous
- transdermal
33
Depo-provera lasts...
3 months (IM)
34
NPH insulin lasts...
10-12 hours (SC)
35
Duragesic lasts...
72 hours (transdermal)
36
Depakote ER (seizures) lasts...
24 hours (oral)
37
Henderson-Hasselbach equation
10^pH-pKa = non-protonated/protonated
38
Henderson-Hasselbach allows prediction of... (2)
- % of total amount of drug that is ionized
| - prediction of pH where absorption will be favored
39
Protein-binding _________ elimination rate, ___________ half-life, and ________ Vd
decreases, increases, decreases
40
protein-binding displacement may be problematic if...(4)
- displaced drug has narrow therapeutic index
- displaced drug is started in high dose
- Vd of displaced drug is small
- response to drug occurs more rapidly than redistribution
41
Vd represents the relationship between ___________ and ____________
dose of a drug, resulting Cp
42
Vd equation
Vd = dose (amt drug in body)/Cp (concentration drug in plasma)
43
drugs highly bound to plasma
warfarin, heparin
44
drugs highly water soluble (don't enter cells, found in extracellular water)
gentamicin, ibuprofin
45
drugs that freely enter cells (total body water)
lithium, ethanol
46
drugs highly lipid-soluble sequestered at tissue sites
amitriptyline, fluoxetine
47
Vd varies between patients based on... (3)
- body composition (fat vs. lean)
- body size
- changes in protein binding
48
Loading Dose equation
LD = Cp (desired) x Vd
49
phase I reaction types
- oxidations
- hydrolysis
- reductions
50
phase II reaction types
conjugations
51
phase I enzymes
- CYP450
- esterases-amidases
- reductases
52
phase II enzymes
transferases
53
phase I and II genetic polymorphisms are (significant/insignificant)
significant
54
phase I induce-inhibit
significant
55
phase II induce-inhibit
possible-less
56
phase I and II development patterns
variable
57
phase I age changes
decrease in 1/3
58
phase II age changes
minimal
59
phase I saturability
minimal
60
phase II saturability
substantial
61
T/F: There is cytochrome P450 development in neonates
true
62
Drugs that are metabolized by the __________ system are usually highly lipid-soluble
CYP450
63
Drugs metabolized by the CYP450 system are usually metabolized in the ___________________
smooth ER
64
CYP3A4
major; gastric mucosa but not large intestine
65
CYP2E1
turns acetaminophen into a metabolite that destroys liver
66
CYP2D6
metabolite of opioids, antipsychotics; genetic polymorphisms
67
CYP2C9
warfarin
68
The amplichip test detects polymorphisms in __________ and ___________
CYP2D6, CYP2C19
69
Caucasians tend to be _________ poor-metabolizers which Asians tend to be ___________ poor-metabolizers
CYP2D6, CYP2C19
70
Some examples of CYP450-dependent phase I oxidations are...
- aromatic hydroxylations
- aliphatic hydroxylations
- oxidative dealkylation
71
Some examples of CYP450-independent phase I oxidations are...
- monoamine oxidase
| - dehydrogenases (alcohol, aldehyde)
72
Phase I reductions
- azo
- nitro (can produce toxic intermediates)
- carbonyl
73
Valacyclovir undergoes phase ___ __________
phase I hydrolysis
74
The products of phase II conjugations are often...
highly water-soluble, readily excreted
75
Hydrolysis by bacterial B-glucuronidase can lead to ____________
enterohepatic recirculation
76
Characteristics of N-acetylation (Phase II conjugation)
- some products are less water-soluble
| - marked genetic variation
77
Alcohol dehydrogenation is a ______________
non-P450 oxidation
78
The mechanism of induction of drug metabolism is mainly due to _________________
increased synthesis of enzyme production (and some decreased turnover)
79
Which phase enzymes are more prone to inhibition?
phase I
80
Drug interactions effects are most obvious when...
drugs are given orally (via first-pass effect)
81
Rifampin interacts with _____________ because it ___________ clearance, thus altering ____
oral contraceptives, increases, Cp (decreased, unplanned pregnancy)
82
Erythromycin interacts with _________ because it ___________ clearance, thus altering ____
lipitor, decreases, Cp (increased, myopathy)
83
Saturation is less likely to occur with ____________ than ___________
renal excretory process, metabolism
84
P-glycoprotein transporters in the GI tract _________________
decrease oral absorption
85
P-glycoprotein transporters in the liver-kidney _________________
enhance biliary and renal excretion
86
P-glycoprotein transporters in the blood-brain barrier _________________
limit distribution of drugs
87
Adult levels of glucuronyl transferases are reached by age ____
3-4
88
What is the best documented and clinically most important mechanism of drug-drug interaction?
inhibition or induction of metabolism of the drug
89
Rate of elimination of first order kinetics is proportional to ______________
plasma concentration (constant %/time eliminated)
90
With half-life, a constant __________ is eliminated per unit time and is ___________ of the total amount of drug present
fraction, independent
| *half-life is the same regardless of Cp
91
equation for clearance
```
CL = Vd x ke
CL = (maintenance dose/tau)/Cp(ss)
```
92
Clearance
- volume of plasma that is completely cleared in a given period of time
- proportionality constant that makes Cp(ss) equal to rate of administration
93
The half-life of a drug depends on ______________
CL (inversely proportional) and Vd (directly proportional)
94
(Free drug/protein-bound drug) can be metabolized
free drug
95
The time it takes to reach steady state is independent of ___________
drug dosage
96
The time it takes to reach steady state depends entirely on ___________
half-life
97
Loading dose equation
LD = Cp x Vd
98
tau
time between doses
99
Steady state level depends on __________
MD/tau
100
fold-fluctuations
2^n (n=tau/half-life)
101
More _________ in a dosing interval means greater fluctuation
half-lives, not hours
102
The amount of fluctuation in Cp that can be tolerated by a drug is determined by its _________________
therapeutic index
103
Saturation is more likely to occur with __________ than _________ processes
hepatic metabolic, renal excretory
104
When giving a single dose, what equation do you use to determine plasma concentration?
Cp = dose/Vd
105
Steady-state is proportional to ...
dose/dosage interval
106
Fluctuations are proportional to ...
dosage interval/(t(1/2))
107
Types of protein receptors (4)
- hormone and neurotransmitter
- receptor, voltage-gated ion channel
- enzymes
- transport proteins
108
What 3 factors determine binding affinity to a receptor?
size, shape, electrical charge
109
What effect does a pharmacologic antagonist have in the absence of agonist?
none
110
Potency depends on ... (2)
- affinity (Kd) of receptors for binding drug
| - efficiency of drug-receptor complex to generate response
111
The power of a drug to bring about a response is related to ...
Emax
112
Physiological antagonists act on ______________
a different receptor than agonist
113
What happens to EC50, Emax, and potency with competitive, reversible inhibitors?
- EC50 increases
- Emax unchanged (surmountable)
- potency decreases
114
What happens to EC50, Emax, and potency with noncompetitive inhibitors?
- EC50 unchanged
- Emax reduced
- potency unchanged
115
Quantal dose-response curves can provide information on dose __________ but not dose ___________
potency, efficacy
116
Idiosyncratic drug reactions
genetically-determined abnormal response to drug (unpredictable)
117
Pharmacokinetic drug interactions can result in...
- elevated drug concentrations (toxicity)
| - decreased plasma concentrations (sub therapeutic)
118
Pharmacodynamic drug interactions can result in...
- pharmacologic enhancement or antagonism via same drug target
- physiologic enhancement or antagonism via different effector system
119
What is an indirect pharmacodynamic effect?
pharmacologic effect of one drug indirectly affects second
120
Half-life may be (prolonged/shortened) with toxicity
prolonged
121
When poisoned, how do you decrease absorption?
- gastric lavage
- emesis
- activated charcoal
- whole-bowl irrigation
- cathartics
122
When poisoned, how do you enhance elimination?
- inhibit toxication or enhance detoxication (give antidote)
- hemodialysis
- manipulate urine pH
123
(Ipecac/activated charcoal) must be given before (ipecac/activated charcoal)
ipecac, activated charcoal
124
What is the most rapid and complete method of emptying the stomach?
gastric lavage
125
How does activated charcoal work to treat toxicity?
binds drug in gut to limit absorption (ion-trapping in stomach)
126
When should magnesium citrate or sulfate be avoided?
- renal disease
| - poisoning with nephrotoxic agents
127
When should sodium sulfate be avoided?
-CHF
-hypertension
(systemic Na+ absorption leads to edema)
128
methanol toxication
methanol, alcohol dehydrogenase, formic acid, retinal damage
| -inhibit alcohol dehydrogenase with ethanol (substrate and competitive inhibitor)
129
ethylene glycol toxication
ethylene glycol, alcohol dehydrogenase, oxalic acid, acute renal failure
-inhibit alcohol dehydrogenase with fomepizole (specific inhibitor)
130
How does hemodialysis inhibit toxication?
removes parent compounds/metabolites
| -best for toxins with small Vd and low protein-binding capacity
131
Acetaminophen is normally eliminated by (Phase I/Phase II) mechanism
phase II (gets saturated with toxic dose)
132
What is the treatment for acetaminophen toxication?
gastric lavage, supportive therapy, N-acetylcysteine (replenishes GSH)
133
Treatment for methanol and ethylene glycol toxication act by...
inhibiting toxication
134
Treatment for acetaminophen toxicity acts by...
enhancing detoxication
135
Hemodialysis, hemoperfusion , chelation of heavy metals, and forced diuresis act by...
enhancing elimination
136
What enzyme is responsible for producing the hepatotoxic metabolite of acetaminophen?
CYP2E1
137
Pre-clinical testing
5-8 years
- acute-chronic toxicity in rodent and non-rodent species
- determine safe dosage range for humans
138
Phase I drug trial
2-10 years
- Is it safe? toxicity
- pharmacokinetics: absorption, half-life, elimination-metabolism
139
Phase II drug trial
2 years
- Does it work in patients?
- safety and efficacy, final dosing and regimens
140
Phase III drug trials
3 years
- Does it work double blind?
- efficacy measured against established therapy
141
Phase IV
-post-marketing surveillance (include omitted study groups, document low-incidence drug effects
142
Patents expire ____ years after application
20
143
What is the difference between pharmaceutical equivalence, bioequivalence, and therapeutic equivalence>?
- pharmaceutical equivalence: drug formulation (ingredients, dose, route of administration, strength)
- bioequivalence: drug molecules
- therapeutic equivalence: therapeutic effect
144
Bioequivalence
rate (Cp max, Tmax) and extent (bioavailability) that active ingredient is absorbed and becomes available
145
What is considered a supplement? (4)
vitamins*, minerals*, amino acids*, herbal medicine
| *molecular entity and safe dosage range known
146
Which drug studies involve testing safety?
Phase I, II, and III
147
Which are required for determining generic drug equivalence with brand names?
therapeutic equivalence, pharmaceutical equivalence, bioequivalence
Pharmaceutical equivalence, bioequivalence
148
Criteria for classifying drugs with abuse potential
medical use, physical/physiological dependence, abuse potential
149
When are drugs required to go through cells as opposed to between? (3)
absorption into small intestine, blood-brain barrier, kidneys
150
Rate of absorption of a drug is estimated as ________
peak Cp (Cmax) or time to attain peak Cp (Tmax)
151
_____________ route of administration can only be used with potent drugs
Transdermal
152
Cp vs. time graphs determine ___________
pharmacokinetics
153
What type of phase II conjugation does morphine undergo?
glucuronidation
154
What type of phase II conjugation does acetaminophen undergo?
sulfate conjugation
155
____________ is the only factor that will keep a drug from being filtered at the glomerulus
protein binding
