Core Principles of Drug Action Flashcards
1
Q
what drugs do to your body
A
pharmacodynamics
2
Q
what your body does to drugs
A
pharmacokinetics
3
Q
_____ is the chemical control of physiology
A
pharmacology
4
Q
binding of drug and protein results in a
A
complex
5
Q
ligand refers to
A
any small molecule that binds to a protein
6
Q
allosteric effect
A
a drug that binds to the target at a different site from the endogenous ligant and affects the protein’s ability to respond
7
Q
NAMs
A
negative allosteric modulators
8
Q
ligand that binds but doesn’t activate the receptor, just prevents agonist binding
A
antagonist
9
Q
the majority of drugs that bind to receptors are
A
antagonists
10
Q
almost all endogenous ligands are
A
agonists
11
Q
most ligands bind ____ to proteins
A
reversibly
12
Q
most irreversible drugs are
A
enzyme inhibitors
13
Q
aspirin targets
A
COX
irrev
14
Q
omeprazol targets
A
H”K” ATPase
irrev
15
Q
tranylcypromine targets
A
MAO- antidepressant
irrev
16
Q
higher affinity means
A
tighter binding = effective at lower concentrations = more potent
17
Q
drugs with different affinities have ______ number of collisions
A
the same
18
Q
drug concentration and target occupation have a _________ relationship
A
hyperbolic
19
Q
a lower Kd means
A
higher affinity
20
Q
Hill-langmr equation
A
b/Bmax = [L]/(Kd+[L])
21
Q
diphenhydramine is a
A
histamine antagonist
22
Q
diphenhydramine has side effects due to
A
small affinity for ACh receptors (binds preferentially to H receptors (lower Kd))
- more side effects seen with higher concentratiosn
23
Q
when there is competition for a common binding site, there is a _____ in collisions of each ligand, but an _____ in total number of collisions
A
decrease for each
increase for total
24
Q
if the drug is an agonist, then the overall effect of natural agonist + drug is
A
increased receptor stimulation
25
if the drug is an antagonist then the overall effect of natural agonist + drug is
decreased receptor stimulation
26
drugs competing for binding site results in
increased levels of both drugs
| - not being metabolised as fast because need to share binding site
27
how can you reduce inactivation of an expensive drug
put in another drug that competes with it for the same enzyme
28
ability of agonist to evoke a response in a tissue
efficacy
29
angatonists have ___, while agonists have _____ and ____
affinity
affinity and efficacy
30
receptors that are not required are called
spare receptors
31
what is the function of spare receptors
so that the cell can generate the same response with less endogenous ligand release = metabolic efficacy
32
agonist binds to receptor, isomerisation to form higher affinity bonds, then isomerised receptor is active
two state induced fit model
can also happen with antagonists
33
conformational selection
agonist binds preferentially to active conformation and shifts the equilibrium so that more receptor exists in the activated conformation
proteins are not static
34
tachyphylaxis is
receptor desensitisation
35
rebound vasodilation is a result of
receptor desensitisation
36
partial agonists elicits a ___ than maximal effect even when all receptors are occupied
smaller
37
partial agonists can behave as both
agonists and antagonists
38
inverse agonists have a higher affinity for the
inactive form of the receptor
39
most drugs classed as antagonists at receptors that show conformational selection behaviour are probably
inverse agonists
40
prolonged therapeutic effects happen when
drugs are irreversible
| typically TE mirrors amount of drug in the body
41
net movement of drug frm site of admin into bloodstream
absorption
42
net movement of drug from bloodstream into organs and tissues
distribution
43
enteral
PO or PR
| - has first pass loss
44
parenteral
bypassing the intesting
| IV, IM, SC, topical, transdermal, inhalation, buccal, sublingual
45
drugs with high lipid solubility pass cell membranes quickly because of ___ law of ____
fick's law of diffusion
| - larger concentration gradient in cell membrane
46
Pka is the pH at
which 50% of the drug is ionised
47
formulation used to optimise absorption include
drug size
protective coatings
sustained release pellets
depot injections
48
a formulation of larger # of small particles results in
faster higher peak
49
all drugs absorbed from the stomach and intestines must enter the
portal vein to go to the liver
50
after first pass metabolism, oral drugs may pass through the liver once every ___ circults
4
51
the fraction of an oral dose of drug that reaches the systemic circulation as an intact drug
oral bioavailability
52
what causes a higher apparent volume of blood
more drug distribution
53
the larger the volume of distribution, or the smaller the fraction of the dose that remains in the blood, the ____ it takes to remove the drug from the body
longer
54
AVd
apaprent volume of plasma
55
plasma albumin has __ drug binding sites
2
56
alpha1-acid glycoprotein has ___ drug binding site
1
57
competition for plasma protein binding results in
drug-drug interactions + can't diffuse into cell
| - may cause side effects as less of singular drug can be bound when there're 2
58
majority of drug elimination is from
urine and feces
59
3 parts of renal drug elimination
1. bowman's capsule
2. acid/ base transporter pumps
3. lipid soluble drug reabsorbed at descending loop onwards
60
lipid soluble drug srequire metabolism by
helatic metabolism
61
metabolism does deactivate/ detoxify drugs T or F
F- not necessarily
62
phase 1 metabolism is
functionalization
63
phase 2 metabolism is
connjugation
64
where does hepatic metabolism occur
hepatocytes
65
phase 1 reactions include
oxidations, reductions, hydrolysis, hydration, isomerisations, dealkylations
66
cytochrome P450 enzymes are used in which phase
1
67
most prominant cyp450 enzymes
3A4/5/7 and 2D6- most drugs metabolized
68
conjugation reactions usually involve
attaching a large, water soluble molecule to a drug or phase 1 metabolite
69
glucuronidation enzyme
UDP glucuronyl transferase- adds glucuronic acid (a sugar)
70
sulfation enzyme
sulfotransferase - adds sulfate
71
acetylation enzyme
N-acetyl transferase - adds acetyl
72
glutathionylation enzyme
glutathione S transferase- adds glutathione (tripeptide)
73
which predominantes at low [drug] glucuronidation or sulfation
sulfation
74
where is UGT found
throughout body- high levels in liver smooth ER
75
where are SULTs found
mainly in cytosol of hepatocytes
76
N-acetyl transferases (NAT1 and NAT2 are found)
in Kupffer cells of the liver
77
acetylation is a common conjugation pathway for
aromatic amines, hydrazines, and sulfonamide antibacterial drugs
78
which NAT is an example of genetic polymorphism
NAT2
79
which phase 2 metabolism makes drugs less water soluble
acetylation
80
which phase 2 reaction is a protective mechanism against electrophilic species
glutathione conjugation
81
glutathione is made of
glu-cys-gly
82
NAPQI is the
hepatotoxic metabolite of acetaminophen
83
what part of glutathione reacts with electrophilic species
thiol
84
N acetyl cysteine and methionine are added with acetaminophen to
protect against overdose- reacts nonenzymatically at high concentrations with NAPQI
85
elimination can be an unchanged drug or a drug's enzymeatic metabolite
T
86
efficacy of drug elimination is measured as
drug clearance
87
first order drug elimination is ______ and has an ___ curve
concentration dependent
exponential
88
Kel
first order elimination rate constant
89
Kel=
Ln2/T1/2
90
clearance =
ADv * Kel
91
the ____ curve is a mirror image to the first order elimination curve for the same drug
infusion
92
how many half lives to reach steady state
5
93
Css is an ____
average
94
IV injections have ___ where as smoothing is seen with ___ dosing
spikes
| oral
95
smoothing is exaggerated with
sustained release preparation
96
a range of plasma concentratiosn within which a TR is obtained but without serious side effects
therapeutic window
97
if cyp is irreversibly inhibited
increased bioavailability and Css
| decreased clearance, Kel
98
to reduce fluctuations without changing dosing rate
choose a different dosing regimen- shorter time between each dose + smaller doses
99
drugs that are rapidly metabolized by the kidneys have a ____ clearance rate
higher
