Final Exam Flashcards
(152 cards)
1
Q
Choosing diseases
A
-government incentives target orphan diseases
-target diseases that have a large market (make profit; cancer, heart disease)–rare diseases won’t make money
-pharma is made of companies and the first order of buisness is money
2
Q
drug target (most common)
A
enzymes
receptors
2
Q
Drug target
A
enzymes
receptor
other proteins
dna
rna
3
Q
selectivity
A
target determines side effects
BEST=bacterial
-easier to target non-human proteins & mutated cancer proteins (make sure normal protein is unaffected)
4
Q
Assay development
A
-test drugs to see if they work
in vitro
in vivo
ex vivo
5
Q
in vitro
A
-test tube
-cell culture (not an entire organism)
FAST & INEXPENSIVE
-clean system (test just what is in tube)
Disadvantage: test tube not a cell or animal
–1st round of testing
6
Q
in vivo
A
living animals (mice, rats, rabbits)
Disadvantage: expensive, animals may suffer, regulations, complex systems
7
Q
ex vivo
A
tissues out of living animals
8
Q
lead compound
A
natural products
chemical banks
rational drug design
9
Q
natural products
A
plants
algae
bacteria
fungi
10
Q
chemical banks
A
thousands/ millions
-pharma companies
11
Q
rational drug design
A
use logic to cut down brute work
-utilize side effect
-alter natural ligand (antihistamine)
12
Q
Molecular Docking
A
-fast, cheap (free)
-crystal structures of proteins known
-program calculates chemical attraction
disadvantage: skips ALOT of details like
conformations-proteins changing shape
cell membrane-cant cross, can never go inside cell and hep protein
13
Q
Structural Activity Relationships (SAR)
A
-optimize lead compound
-makes drug better
-eliminates unneeded functionalization
14
Q
pharmokinetics
A
absorption
distribution
metabolism
excretion
what body does to drug
(dosage, circulation, and site of action)
15
Q
Hepatitis C virus
A
old treatment cheap, less effective and toxic
–new treatment is effective, safe but very expensive
16
Q
cancer treatments
A
increases life by days, costs hundreds to thousands
17
Q
pharma companies
A
motivated by money
-may not have patients best interest at heart
18
Q
pharmacology
A
study of how chemical substances interact and modulate living systems
19
Q
pharmacodynamics
A
what it does to biologic system of body (ex: relieve pain, etc.)
pharmacological effect
—mechanism
—potency
—efficacy
—toxicity
20
Q
pharmacogenetics
A
how genetic makeup impacts interaction of drug
-each person’s unique reaction
21
Q
toxicology
A
adverse effects of drug and molecules
22
Q
drug
A
any substance that interacts and modulates a living system
23
Q
agonist
A
drug ACTIVATES biologic response
24
antagonist
drug INHIBITS biologic response (NO response)
-by binding to receptor it will prevent binding of agonist
25
drug action targets
receptors
enzymes
26
pharmacotherapeutics
clinical response
-efficacy and toxicology
27
chemical name
chemical structure
ex: n-acetyl-p-aminophenol
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non-proprietary name
chemical or pharmacological class
-generic name
ex: acetaminophen
29
proprietary name
trade name
-marketing name (catchy)
--made once determined medicine is profitable
ex: tylenol, tempra (can have several)
30
drug classification
chemical properties
mechanism of action
disease/ condition
abuse potential
--otc drugs
--prescription drugs
--orphan drugs
31
chemical properties
benzodiazepines
sulfonamides
32
mechanism of action
-ACE inhibitor (angiotensin converting enzyme)
-calcium channel blocker
-carbonic anhydrase inhibitors
33
disease/condition
analgesics
antidepressants
antihypertensives
34
Drug classification
Schedule I-V
35
schedule I
HIGH
-heroin, LSD, marijuana
-no currently accepted medical use
-CANNOT BE PRESCRIBED
36
schedule II
HIGH
-morphine, amphetamines, high dose, codeine
-no refills, requires written prescription (IN PERSON)
37
schedule III
MODERATE
-ketamine, low dose codeine
-5 refills max within 6 months
38
schedule IV
LOW
-benzodiazepines
-5 refills max, within 6 months
39
schedule V
LOWEST
diphenoxylate
40
translational research
moving knowledge and discovery gained from basic sciences to application in clinical and community settings
-encompasses a bidirectional continuum (move around and follow trajectory)
t0-t4
41
translational research continuum
public health
basic research
pre-clinical research
clinical research
clinic implementation
ALL CENTERED AROUND PATIENT INVOLVEMENT
42
t0
define mechanisms underlying health or disease (identify opportunities and approaches to a health problem)
--yields knowledge about defining mechanisms targets or lead molecules
BASIC RESEARCH QUESTION
43
t1
test basic research findings for clinical effect (discovery of candidate health application)
--yields knowledge about new methods of diagnosis, treatment, and prevention
PHASE I AND II CLINICAL TRIALS, OBSERVATIONAL STUDIES
44
t2
test new inventions under controlled environments (health application to evidence based practice guidelines)
--yields knowledge about efficacy of interventions in optimal settings
PHASE III CLINICAL TRIALS--OBSERVATIONAL STUDIES--EVIDENCE SYNTHESIS AND GUIDELINE DEVELOPMENT
45
t3
explore ways of applying guidelines in general practice (practice guidelines to health practices)
--yields knowledge about how interventions work in REAL WORLD settings
46
t4
study influences on the health of populations (practice to population health impact)
--research ultimately results in improved global health
47
multidisciplinary
diverse backgrounds
-additive, complementary, independent, sequential
48
interdisciplinary
different expertise working together to integrate knowledge
-interactive, combine, integrate
49
transdisciplinary
holistic
-new methodologic or conceptual frameworks
50
unmet health need
FDA: condition whose treatment or diagnosis is not addressed adequately by available therapy
-does not need to have a treatment for a disease
-immediate need for defined population and long-term need for society
-may arise due to budget constraints, low socioeconomic status (underserved individuals)
51
determining treatment unment health need
priority
-treating patients not on any other treatments
-treating patients who will get the largest health gain
52
t0 objectives
identify functional significance of genomic polymorphisms
try preclinical methods: animal modes/ human physiological studies, human blood or cell lines, computational models
53
therapeutic modalities
intervention used to heal someone
Drugs: small molecules, biologics, devices, diagnostics
54
Drug (FDA)
substance recognized by official pharmacopoeia/ formulary
-intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease
-substance intended to affect the structure or any function of body
-substance intended for use as component of medicine NOT device, component, part or accessory of device
-biological products
55
small molecules
most drugs are
-weight 900 Da
-organic molecules, natural products, full/semi synthetic
-have oral bioavailability, cross biological membranes
--have well defined chemical structure
56
Biologics
vaccines, blood & blood components, allergenics, somatic cells, gene therapy, tissues, recombinant and therapeutic proteins
-isolated from variety of natural sources and produce what small molecules cant provide
57
proteins
antibody, large proteins
58
biologics delivery method
-viral vectors (gene therapies)
-nanoparticles
59
top selling
humira- adalimumab
enbrel- etanercept
remicade- imflixamab
60
medical device
instrument, apparatus, implement, machine, contrivance, implant which is:
-intended for use in the diagnosis of disease or other conditions, or in cure, mitigation, treatment, or prevention of disease, in man or other animals
-affect the structure or any function of the body of man or other animals which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals NOT DEPENDENT UPON being metabolized for treatment of any of its primary intended purposes
61
Class I
least regulatory control (general controls)
-bandages, exam gloves
62
Class II
general controls with special controls
-acupuncture needles, powered wheelchair, infusion pump, surgical drapes
63
Class III
above & requires pre-market approval (PMA)
supports or sustains life
-pacemaker, defibrillators
64
premarket notification
"similar devices"
-how does it differ and is it safe & effective
-documented lab data but human data not required
-clearance v approval (cant say FDA approved)
65
pre-market approval
completely new or Class III
-laboratory and clinical data needed
-more time, money, and documentation
66
diagnostics
used to determine whether or not a condition is present in an individual
tissue biopsy: detect tumor, analyze drug response
breathalyzer: alcohol
blood: PSA, glucose, electrolytes
urine: hCG (pregnancy)
considerations:
qualitative v quantitative
invasive v non invasive
accuracy v precision
sensitivity v specificity
67
invasive v non invasive
stand alone or part of series of tests
68
accuracy
how close measured value to standard or known value
69
precision
degree to which several measurements provide answers very close to each other
70
sensitivity
probability that individual with disease tests positive
71
specificity
probability individual without the disease will test negative
72
efficacy
maximum response produced by a drug
73
potency
concentration or dose of drug that produces 50% maximal response
74
partial agonist
will not produce an effect as large as a full agonist
-more potent agonist (lower log value) but will produce a response larger than less potent
75
competitive antagonist inhibition
competes with agonist for a spot
-affinity of drug for receptor decreases as well as potency
--if you add more agonists (more potent) they will outcompete the antagonists
76
non-competitive (allosteric) inhibition
bind at different site (besides main site) which may change the receptors response to the agonist
CHANGES EFFICACY OF THE RECEPTOR
-no competition so potency of agonist WILL NOT CHANGE
-
77
Desensitization (chronic agonist)
receptor continually activated by agonist and internalized by cells causing the receptors to get degraded (less available) causing down regulated
gonadotropin releasing hormone (GnRH)
78
Supersensitivity (chronic agonist)
to compensate for continuous blocking ( & lack of activation) cell will put more receptors on its surface
causing receptors to get up regulate
ex: propranolol
79
Gonadotropin
-downregulation
-controls release of lutenizing hormone (LH)
-has pulsatile release
-continuous treatment of leuprolide will cause desensitization (decrease in testosterone= prostate cancer growth)
80
leuprolide
agonist for GnRH receptor used to treat prostatic cancer
-get constant activation of receptors, which they will eventually downregulate (degradation) producing less of the lutenizing hormone
81
luteinizing hormone
stimulates testosterone synthesis
82
graded concentration response
for therapeutic efficacy, which is important for clinical use
83
quantal dose response
all or none response
-take number of responders out of study and give those who didn't have a higher dosage (add accumulated of responders)
84
quantal dose responsive curve
therapeutic index
-effective dose: which 50% of individuals exhibit the therapeutic effect (increases heart rate)
toxid dose: which 50% of individuals exhibit toxic effect vomiting
85
therapeutic index (TI)
TD50/ED50
86
enteral administration
-oral
-sublingual
-rectal
87
oral
non-invasive (excellent for repeating dosing)
-undergoes first-pass metabolism (digestive)
88
sublingual
place under tongue and is absorbed
-rapid entry of permeable drugs
--NO FIRST PASS metabolism
89
Rectal
oral administration is impractical
partial first pass metabolism
90
parenteral administration
intravenous
subcutaneous
intramuscular
topical
transdermal
inhalation
91
intravenous
rapid and complete distribution (go everywhere quickly)
92
subcutaneous
slow absorption
-hypodermis injection
93
intramuscular
larger volume than subcutaneous
-use slow release formulations (if you want absorbed slow)
if muscle has larger blood supply drugs will be absorbed quicker
94
topical
directly where we want it
-localized
-rapid reuptake through mucous membranes
95
transdermal
eyes, skin, etc.
-sustained release
-potential for irritation
96
inhalatation
-efficient for anesthesia
-initially localized to pulmonary system
97
bioavailability
-absorbability of a drug
-usually measured in percentage
100% bioavailability will never happen with oral formulation
compared to IV, oral has a delay in plasma concentration and it does not get as high
98
passive absorption
diffusion (high to low concentration)
-dependent on membrane permeability and concentration gradient
99
membrane permeability
smaller drugs are reabsorbed faster
-lipophilicity increases absorption
-
100
neutral molecules
absorbed faster than ionized
101
factors influencing absorption
-membrane permeability
-gastric emptying
-formulation
102
gastric emptying
fatty foods will delay gastric emptying
103
formulation
-coatings (enteric ones abosorbed in intestine not stomach)
-hydrogels
-sustained v controlled release
104
sustained release
constant, same amount released overtime
105
controlled release
over a period of time amount tapers off
106
single compartment (drug distribution)
distribute evenly throughout body
107
unequal distribution
-between organs
-metabolize before pure equilibrium
-many drugs bind to plasma proteins
-sequesters drug in plasma
-potential for drug interactions
108
Phase 1
usually involves "activation" of molecule so it can be conjugated with more polar group (liver ER but can occur in other tissues such as GI tract)
-oxidation
-epoxidation
-o and n dealkylation
-reduction
-dehalogenation (Br and Cl)
-hydrolysis (esters and amides)
109
Phase II (conjugation)
biotransformation into more polar form, readily excreted in urine and feces
-Acetylation
-Glucouronidation
-Sulfation
-Glutathionation
110
factors affecting drug metabolism
-age (max efficacy at 50)
-change in diet
-chronic drug use cause synthesis of larger amounts of biotransformation
-genetic differences
111
non renal excretion
-bile (largest non-renal route)
-lung
-saliva
-milk
-sweat
112
renal excretion
-glomerular filtration
-active tubular secretion (ion secretion)
-passive reabsorption: (drugs in top 2 steps reach the distal tubule and passively diffuse out of kidney into blood supply and get remetabolized
113
glomerular filtration
most drugs are passively filtered into nephron
-renal blood flow (20% cardiac output)
-Plasma protein binding
-such drug is not reabsorbed or additionally secreted, then its clearance would be about 125 ml/minute (GFR)
114
active tubular secretion
some drugs are secreted into nephron
-the clearance of such drug can be as high as 600ml/minute
-OAT and OCT (non-specific)
-important for protein bound drugs
115
passive reabsoprtion
many drugs passively reabsorbed in the course of urine formation
-drug ionization will affect the extent of this passive reabsorption (move to from higher to lower concentration)
ion trapping (trapping ionized drug can be exploited to speed up removal)
116
biliary excretion
active transport systems for basic and acidic compounds are an elimination of ionized compounds and their metabolites
-glucuronides
-high MW weight conjugates
117
entero heptatic recycling
-gut bacteria unconjugate metabolites which get transported back to liver
(similar to recovery of bile salts drugs excreted in bile)
activated charcoal interrupts recycling (speed up removal of drug)
118
lungs
eliminates gases and volatile substances
ex: gas anesthetics, alcohol
119
factors affecting lung excretion
blood flow
rate of respiration
solubility in blood
120
milk
-lactic secretions rich in fat and protein
-unionized drug diffuses through mammary epithelium
ex: anti-cancer drugs, lithium
121
saliva
-unionized drug secreted passively
-cause bitter taste in mouth
ex: caffeine, alcohol
122
sweat
-very minor
-alcohol, salicylic acid
123
steady state
rate of drug infusion= rate of elimination at therapeutic dose
124
non-saturating elimination
first order (reverse linear)
-more drug in body, elimination will be faster
-glomerular filtration
-diffusion and ion trapping
-active renal secretion
-metabolic enzymatic processes
elimination= -kel[drug]
follows an exponential decay
125
half life (t1/2)
0.693/kel
126
Vd (volume of distribution)
dose (mg) /plasma concentration (mg/L)
127
doubling dosage
increases duration of time by approximately one half life
128
saturating elimination
zero order (completely linear, as time increases drug concentration decreases)
RARE
catalysis= kcat[enzyme]
129
first order processes
reach a plateau with repeated doses, avoid reaching toxic levels
130
zero order processes
start constant and go above toxic level with repeated dosages, very unpredictable and cannot reach plateau
131
plateau
time determined by Kel
-describes the decrease in drug when the drug administration is haltered
132
loading dose
avoids slow rise of drug to therapeutic level
-most stable for it to be the largest dose and then give smaller maintenance doses
=Vd*[drugs]
133
clearance
the relationship between drug concentration and rate of drug elimination from the body
=kel * Vd or (0.693/t(1/2))*Vd
134
maintenance dose
Cl*[drugs]*Tm
135
phase IV variability
-due to large population of patients studied
-increased diversity/ heterogeneity in patient population (variation in drug pharmacokinetics and pharmacodynamics)
136
sources of individuality
condition of state of being
environmental
genetic
drug combinations (drug interactions)
137
children
newborn/ infants
-drug distribution
-lower plasma proteins (more free drug availabile)
-lower P450 enzymes
-lower GFR
138
elderly
-lower GFR
-lower P450
-changes in PD
139
p450 induction
charcoal broiled foods
-broccoli/sprouts
140
p450 inhibitors
grape fruit juice, topical fruits
-higher levels of drug in patient
-prevents activation of drug from pro-active state
141
Codeine
prodrug conversion to morphine
-poor metabolizer (low analgesia)
-ultra rapid metabolizer
142
drugs may
-inhibit metabolism of other drugs (increase half life)
-stimulate metabolism of other drugs
-displace other drugs from albumin binding sites (increase in free v bound drug)
-inhibit oral absorption of other drugs
143
pharmacokinetics
study of genetic basis for variation in drug response
affects:
-pharmacokinetics
-pharmacodynamics
144
isoniazid
treatment of tuberculosis
-modification of drug by acetylation (phase II liver metabolism)
-variation in genetic alleles for NAT affecting drug half life
-can alter therapeutic and adverse reactions
145
primaquine
antimalarial drug forms reactive metabolites inactivated by reduced form of GSH
-can cause hemolytic anemia (lysis of red blood cells)
occurs primarily in patients with deficiency in glucose-6-phosphate dehydrogenase
146
warfarin
inhibitor of vitamin K epoxide reductase (VKORC1)
-recycles oxidized vitamin K to its reduced form
147
chronic myelogenous leukemia
malignant hematopoietic stem cell disorder
-expression of tyrosine kinase essential for maintaining oncogenic state
-95% cases associated with Philadelphia chromosome
148
imatinib
inhibits Bcr-Abl tyrosine kinase present in philadelphia chromosome
149
tamoxifen
prodrug
-polymorphism in CYP2D6 lead to lower therapeutic levels of active drug causing relapse
pharmacodynamic: missing estrogen receptor
150
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