Pharmacodynamics intro Flashcards
1
Q
extent of pharm response based on
A
affinity of active receptor for ligand
2
Q
drug-receptor complex strength is measure of
A
affinity
3
Q
characteristics that influence affinity
A
molecular size, shape, and electrical charge of drug
4
Q
binding of drug to receptor often exhibits
A
stereospecificity–i.e. one enantiomer will form stronger attachment than other–R/L handed molecules may have varying side-effects
5
Q
stereoisomer aka
A
enantiomer
6
Q
pharmacologic response based on
A
change to system related to receptor
7
Q
acetaminophen binds to receptor in brain
A
receptor (cyclooxygenase) won’t produce prostaglandins at site –> analgesia
8
Q
receptor that when bound drug result in no physiologic change
A
inert receptor–i.e. albumin although some indirect effects–
9
Q
Drug-receptor bonds–strong–>weak
A
- covalent–share e- –IRREVERSIBLE @ body temp–drug effect lasts much longer–
- electrostatic or ionic bond–more common reversible bond
- hydrogen bond–dipole-dipole +_-
- hydrophobic–very weak–imp in LIPID SOLUBLE d-r interactions
10
Q
time it takes for drug concentration in plasma to be reduced by 50%
A
elimination half-life–if sustained response likely covalent–aspirin covalent to COX on platelet inhibit clotting
11
Q
All drug receptor bonds reversible except
A
covalent – at body temp
12
Q
nonpolar substances as lipid tend to
A
clmp together rather than distribute in water–so minimal contact w/ water–reversible bond
13
Q
drug receptor interactions often involve
A
multiple bond types simultanious
14
Q
body’s response to drug concentration changes is _______
A
nonlinear in progression–more change at lower concentrations
15
Q
nonlinear progression of drug response due to
A
receptors become saturated–plateau reached at max response
16
Q
time before drug takes effect
A
lag period
17
Q
maximum response of drug
A
“peak effect”–top of curve builds and tapers (symptoms return)
18
Q
Maximum effective concentration MEC
A
between desired and adverse responses is THERAPEUTIC WINDOW
19
Q
measurable PARAMETERS of drug effect
A
- symptom–i.e. pain
- sign– i.e. BP
- Biological marker
20
Q
time range during which drug concentration exceeds MEC for desired response
A
Duration of action
21
Q
dose that results in death of 50% of study population
A
LD50
22
Q
dose necessary to establish effectiveness in 50% of population
A
ED50
23
Q
Therapeutic index TI =
A
LD50 / ED50
24
Q
LD50 sometimes replaced with
A
toxic dose TD
TI = TD50 / ED50
25
Wide TI implies
drug is generally safe--or large dif btwn lethal/toxic dose and ED
26
narrow TI implies
drug has safety concerns-- will need close monitoring
27
Can there be more than one therapeutic index TI for a drug?
Yes--for drugs with multiple drug effects (i.e. ibuprofen for pain IN ADDITION TO inflammation) ED may be different depending on symp being treated--window may be narrower
28
measure for comparing 2+ drugs with equivalent pharm responses
Relative potency
29
refering to pharmacologic response generated at given receptor occupancy
potency of drug--EC50 compared
30
when 2 drugs produce equivalent responses the more potent drug on dose response curve is
the drug whose dose response curve lies to the left of the other--less drug required for same effect
31
chemical termed a "drug" when
supplied exogenously
32
#1 receptor-- lipid-soluble ligand--pg7 of outline
crosses plasma membrane to interact w/ intracellular receptor (enzyme or gene transcription regulator)
33
#2 R--Ligand (drug) binds extracellularly to transmembrane protein
activates enzymatic activity within cytoplasm--internal and external domains attached by hydrophobic segment.
34
enzyme that can transfer a P group from ATP to protein in cell
tyrosine kinase-- on/off switch for cellular functions
35
tyrosine kinase subclass of
protein kinase
36
#3 R--ligand (drug) binds extracell to transmem protein structurally bound to protein tyrosine kinase
becomes activated--same as #2 but tyrosine kinase not intrinsic w/ receptor
37
#4 R--Ligand binds to ion channel
activation = opening
1. mimic endogenous ligands--nt's
2. alter membrane potential
3. work quickly
38
#5 R--metabotropic--ligand attaches to receptor linked to G-protein--components:
1. surface receptor
2. G protein at cytoplasmic face
3. change to effector system (ion channel, 2nd mess)
39
second messenger ex's: _____, _______, and _______
cAMP, calcium, cGMP
40
affinity analogy
lock and key--skeleton keys (some keys fit into many locks)
41
if drug-receptor complex is irreversible its likely
covalent bond--
42
- molecule donates e- to + molecule -- treatment with "salt"
most drugs ionic
43
H+ on molecule attracted to negative on receptor
hydrogen bonding--
44
pregnancy risks
```
A: no risk
B: remote risk
C: benefits outweigh risks
D: evidence of risk--benefits may outweigh risks
X: Contraindicated
```
45
MEC
minimum effective concentration
46
only dif btwn transmembrane proteins 2 & 3
"machinery" integrated vs. separate, connected molecule that can detach respectively
47
ionotropic speed
miliseconds
48
metabotropic speed
fractions of second
49
#1 receptor ex
lipid soluble--ex. steroid-- approx 30 min lag for protein synth
50
agonist broken into
full and partial agonist--spectrum
51
partial agonist elicits
less than MAXIMUM EFFECT from same tissue as would elicited from total occupancy by full agonis
52
types of antagonists _______ and _______
competitive (reversible)--
| noncompetitive (irreversible)-- typically covalent
53
drug that causes an action opposite to that of the agonist when bound
inverse agonist
54
antagonist type that will disallow full agonist rxn despite dose
noncompetitive--irreversible
55
iris sphincter muscle activation by parasymp NS
miosis--contriction
56
ANS integrated for male sexual function
symp=ejaculation
| parasymp=erection
57
Always signals coming from ANS but which branch _____ will be based on internal and external environment
predominates
58
pt w/ tachicardia give
beta blocker--IV--antagonize of sympathetic NS
59
atropine for bradycardia--too much parasympathetic tone on SA node
antagonise parasympathetic w/ competitive antagonist for cholinergic muscarinic receptor
60
drug similar to normal functioning of involved receptors
-mimetic
61
drug that inhibits or blocks normal functioning of receptors involved
-lytic ("destroys")
62
______ can play part in pharmacokinetics of drug
Gender--sexual dimorphism
63
down-regulation of receptors
agonist given--body perceives strong signal
64
up-regulation of receptors
antagonist given--body perceives weak signal
65
rapid drug tolerance =
tachyphylaxis--rapid decrease in effectiveness of drug
66
exaggerated response, respectively, in pt when compared to most ppl
hyperreactivity
67
diminished response, respectively, in pt when compared to most ppl
hyporeactivity
68
"start low, go slow"
titration--when drug has ADR's that decrease tolerability of drug
69
titration leads to better _______ of drug
tolerance-- for drugs with low toxic level--i.e. anticoagulants
70
slowing weaning a patient off medication by lowering dose over time
tapering--avoid withdrawals--i.e. systemic steroids
71
if tapering pt off drug and symptoms emerge
slow taper--same for titration
72
mitigate tolerance by
1. taking break from drug
| 2. switch to drug with same effect by dif mechanism
73
Most drugs produce several effects, _____ _______, is wanted for treatment
therapeutic effect
74
tolerance vs tachyphalaxis
tolerance is blanket term for effect over time--tachyphalaxis happens w/in hours/ days/ mins
75
adverse drug rxns ADR's most appropriately for ________ as opposed to side effects which may be benign
unwanted, unpleasant, noxious, or potentially harmful drug effects
76
2 most common ADRs
* 1. GI disturbance (mostly PO drugs)
| 2. Allergic rxn
77
GI drug disturbances
exs. loss of apetite, nausea, bloating, constipation, and diarrhea --should be considered for ALL ORAL DRUGS
78
Allergic rxn to drug aka
hypersensitivity rxn
79
types of hypersensistivity drug rxn's -- all involve immune system
type ONE: rapid/immediate after 1st exposure-- mast-cell derived--IgE antibodies attach to drug--anaphylactic
type FOUR: rxn delayed--antigen presented to T helper cells-->macrophages and T killer cells destroy target cell.
80
Type four rxn to drug
Steven-Johnson syndrome & toxic epidermal necrosis presentation--deadly like burn--happens w/ 1st exposure but slow
81
Type one rxn to drug
IgE antibody--requires 1st exposure--presentation w/ urticaria, angioedema, and ANAPHYLAXIS
82
Drug-drug interaction
may increase or decrease concentration of other drug in body
83
D-D interaction--increase drug concentration as found by drug plasma concentration
1. inhibit liver enzyme production
2. slowing excretion by kidney
- -drugs given based on normal liver function
84
D-D interaction--decreased drug concentration
1. decrease absorption of drug--i.e. lower stomach pH
2. increase metabolism-- ^ liver enzyme--may look like drug tolerance to clinician (dangerous)
3. increase excretion--
85
smoking can ________ activity of some ______ ________, thus decreasing effectiveness of some drugs
increase, liver enzymes
86
increasing urine acidity will
1. decrease acidic drug excretion
| 2. increase basic drug excretion
87
decreasing urine acidity will
1. increase acidic drug excretion
| 2. decrease basic drug excretion
88
drug-drug interaction in terms of pharmacodynamics
are those where the magnitude of the drug effect is changed
89
2+ drugs with same ingredient have added effect/ADR adverse drug rxn
DUPLICATING effect--particularly dangers with OTC drugs--risk toxicity
90
2+ drugs with same effect taken
DUPLICATING effect-- D-D interaction
91
2+ drugs taken with opposite action
OPPOSING effect--decreased efficacy of one or both
92
Anticholinergic side effects
```
hot as a hare
dry as a bone
blind as a bat
red as a beet
mad as a hatter
```
93
a ________ __________ or ________ _________ book can be checked for drug-drug interaction
reference book or computer program
94
most important drug-drug interaction DDI to think abt
hepatic enzyme INDUCTION or INHIBITION
95
pt taking multiple drugs--increase DDI risk
polypharmacy
96
age risk for DDI
newborns and elderly have lower physiological function
97
________and _________ diseases will greatly effect drug's ________and ________
liver and renal
| metabolism and excretion
