Pharmacology - Sheet1 Flashcards
1
Q
pharmacokinetcs
A
What the body does to the drug
2
Q
pharmacodynamics
A
What the drug does to the body.
3
Q
Important disadvantage oral administration
A
First pass effect, variable response
4
Q
First Pass effect
A
Drug must first pass through portal vein to liver before reaching other organs. Metabolized and changed. Affects oral and to some extenct rectal. NOT sublingual
5
Q
IM aqueous advantage
A
fast onset of action
6
Q
IM non aqueous advantage
A
slow sustained response
7
Q
What determines absorption in transdermal
A
lipid solubility
8
Q
pH rule of thumb regarding absorption
A
weak acids stomach, weak bases intestine
9
Q
bioavailability formula
A
AUC oral/AUC injected x 100
10
Q
distribution
A
process of leaving blood and entering other areas. 3 main areas
11
Q
3 Compartments and relative size for distribution
A
Plasma - 4L, ECF - 14L, Total Body Water - 42L
12
Q
Factors affecting distribution
A
blood flow, capillary permeability, degree of hydrophobicity, binding to plasma proteins
13
Q
Important factor when drugs are displaced from plasma binding
A
Must assess their Volume of distribution. If small at higher risk of toxicity
14
Q
Volume of distribution equatino
A
bioavailability of dose/concentration of plasma at initial time.
hypothetical volume of fluid into which a drug is disseminated and prior to elimination.
15
Q
Phase 1 Drug Metabolism
A
oxidation involving cytochrome p450
16
Q
Phase 2 Drug metabolism
A
coupling endogenous substrate to a drug or phase 1 metabolite
17
Q
Cytochrome p450
A
made of many families of heme containing isozymes
18
Q
CYP families most involved in metabolizine enzymes
A
CYP 1,2,3 and CYP3A4
19
Q
What can increase CYP3A4
A
Rifampin (TB), St John’s Wort. Effect is increased metabolism of the drugs
20
Q
What can decrease CYP3A4
A
grapefruit juice
21
Q
Which CYP polymorphisms are important
A
CYP2D6, CYP2C19
22
Q
3 processes renal excretion
A
glomerular filtration, active tubular secretion, passive tubular transport
23
Q
clearance equation
A
rate of elimination/concentration
24
Q
Type of clearance kinetics for most drugs
A
first order so increasing amount leads to an equal increasing excretion
25
Relation of steady state to rate of elimination
Both require 4-5 half lives to reach steady state, indpeendent of dose or rate of dosing
26
Graded dose response
increase dose - increase response
27
quantal
all or none resopnse
28
Intrinsic activity vs potency
Potency has to do with how much you must give to get 100% response. intrinsic activity has to do with highest % response you can achieve
29
Agonist K3 value
1, antagonist is 0
30
Muscarininc chlinergic agonist
ACH, muscarine, pilocarpine
31
Muscarininc cholinergic antagonist
Atrpoine, Scopolamine
32
Nicotinic chlinergic agonist
ACH, nicotine
33
Nictinic cholinergic antagonist
Curare, succinylcholine
34
Alpha- adrenergic agonists
norepinephrine, epinephrine
35
Alpha 1 adrenergic antagonists
Prazosin, phentolamine
36
Beta 1 adrenergic agonists
Epinephrine
37
Beta 1 adrenergic antagonists
propranolol, metoprolol
38
4 Types of antagonism
competitive, noncompetitive, chemical, physiologic
39
Physiologic antagonism
One drug does exact opposite of another and works on entirely separate mechanism
40
Therapeutic index
Take the 50 cumulative percent of negative outcom/positive outcome
41
Safety Index Formula
Lethal Dose 01%/Effective Dose 99%
42
Mineralcorticoids, location and function
Zona glomerulosa adrenal cortex - salt and water regulation
43
Glucocorticoids location
Zona fasiculata
44
Androgen/estrogen location
Zona reticularis
45
Which two chaperone proteins does GR interact with LBD
Hsp90 and Hsp56
46
Which end is AF2
C terminal
47
AF2 function
ligand dependent transactivation domain. Only recruit co-regulators after steroid binds GR
48
Which end is AF1
N terminal
49
AF1 Function
ligand independent transactivation domain
50
role of Heat shock proteins in Glucocorticoid receptor
Keeps the receptor ligand friends. 2Hsp90 and 1 HSP 56 subunit
51
2 Examples of how glucocorticoids affect gene expression
Increase expression of lipocortin, downregulating PLA2 decreasing synthesis of PGs and lueoktrienes
inhibits production of IL-6 and IL-8
52
2 glucocorticoid drugs that are very specific for glucocorticoid effects
Dexamethasone and Betamethasone
53
Effect of prolonged steroids on hypothalmic pituitary axis
suppress the axis and supress endogenous cortisol production
54
Addisonian Crisis
acute adrenal insufficiency bc sudden withdrawal of therapeutic glucocorticoids
55
Which effector T cells can mediate steroid resistant rejection
Th17 producing IL 17,21,22
56
Th1 produces
IFN gamma, IL-2, TNFalpha - T cell Drive
57
Th2 produces
IL4,5,13 - B cell drive
58
T regulatory
IL10 - TGF beta
59
What downregulates Th2
INF-gamma
60
What downregulates Th1
IL-10
61
Basiliximab limitation
can be used to prevent induction but not to treat rejection because it is useless once the T cell has already received signal 3
62
Equine anti-thymphocyte globulin use
anplastic anemia
63
rabbit anti-thymocyte globulin
transplant
64
Important liitation of polyclonal antibodies
risk of antibody response, toxicity, immunosuppresion
65
Belatacet mechansim
Binds to CD80/86 better than CD28 and stops costimulation
66
Belatacept major risk
increased risk of post-transplant lyphoproliferative disorder.
only use when have some other viral infection?
67
High dose steroid effect
apoptosis of activated T and B cells
68
Calcineurin examples
tacrolimus and Cyclosporine binding to FK binding protein-12 and cyclophilin
69
Calcineurin mechanis
prevents calccineurin phosphatase. Inhibits IL-2 mediated response and transcription of IL-2, GM-CSF, TNFalpha and INF gamma
70
Calcineurin metabolized by
CYP3A4 means you have to monitor levels differently. If on it need to give higher levels.
71
Increased risk hyperglycemia/neurotoxicity (calcineurin)
tacrolimus
72
increased risk hypertension, hyperlipidemia, hyperuricemia
cyclosporine
73
Hirsutis/gingival hyperplasia
cyclosporine
74
mTOR inhibitors
Sirolimus and everolimus
75
mTOR inhibotor mechanism
inhibits protien kinase
76
mTOR effect
decrease cytokine dependent cellular proliferation, at G1 to S, induce T cell cycle arrest. Inhibit activation and proliferation
77
mTOR metabolized by
CYP3A, longer half-life than calcineurin so don't need to monitor as much
78
mTOR major toxicity
wound healing impairment
79
Azathioprine mechanism
blocks denotovo and salvage of purines. prevents DNA relplication
80
Mycophenolic acid products
block de novo purine synthesis, prevent DNA replication
81
Methotrexate
Folic acid antagonist. Arrest cells at S phase
82
Common drug interaction with azathioprine
Allopurinol inhibits xanthine oxidase which normally metabolizes azathioprine. So when both need to keep azathioprine levels lower
83
Monoclonal antibodies, IL2 receptor agonist
binds to alpha subunit of IL-2 receptor.
84
Basiliximab common use
used as an induction agent in organ transplant
85
basiliximab mechanism
anti CD-25 antbody that acts on activated T cells.
86
basilixmab cannot be used for
treating rejection
87
Induction therapies
basiliximab or rabbit antiglobulin
88
Maintinence therapies
calcineurin or mTOR w azathioprine or MPA w prednisone
89
3 types of Eicosanoids
Prostanoids, Leukotrienes, HETES and EETS
90
Eicosanoids derived from
arachidonic acid in cell membrane
91
Isoeicosanoids
products that do not depend on enzymes and are driven by free radicals
92
Phospholipase A2 function
catalyzes release of Arachidonic acid from embrane
93
COX function
AA to intermediary PGG2/PGH2
94
PGG2 platelet synthesize
TxA2
95
GI Endothelial cells PGG2 synthesize
PGE2
96
Vascular endothelial cels PGG2 synthesize
prostacyclin PGI2
97
Phospholipase A2 forms
cytosolic and inducible
98
Cox 1 function
constitutive activity
99
Cox 2 function
inducible and not in all cells
100
Platelet Cox form
Cox 1
101
Enthothelial cell Cox form
Cox 2
102
PGE2 ligand for
EP receptors (1-4)
103
PGI2 ligand for
IP receptor
104
TxA2 ligand for
TP receptor
105
PGF2alpha ligand for
FP receptor
106
TxA2 function
induce platelet aggregation, vasoconstriction, smooth muscle cell proliferation
107
PGI2 (prostacyclin I2)
inhibits platelet aggregation and smooth muscle cell proliferation, vasodilator and pro-inflammatory
108
Prostaglandin E1 and 2 function
cytoprotection in Gut w inhibition of gastric secretions
109
Which Cox for inhibition of gastric secretions
Cox 1
110
Prostaglandin E function on vessels
vasodilation (COX 1 and 2)
111
Prostaglandin E function on homeostasis
Regulate sodium and water with renin release (COX 1 and 2)
112
Prostaglandin E function, gastroutero muscles
contraction of smooth muscles COX1 and 2
113
Prostaglandin E inflammatory effects
Controls body temperature. Pro-inflammatory through COX 2
114
Prostaglandin F2 function
vascular smooth muscle and uterine contraction. Vasoconstrictor COX 1 and 2
115
Prostaglandin D2 effect vessels
cutaenous vasodilation. Inhibitino of aggregation
116
Prostaglandin D2 effect unusual
promotes sleep and changes hair follicle activity
117
Prostaglandin D2 immune effect
produced by mast cells->chemotaxis Th2 lymphocytes
118
Prostanoids in pain
PGE2, PGE1 PGI2
119
Prostanoids in heat
PGE2 and PGE1
120
Prostanoids in redness
PGE2, PGE1, PGI2
121
Prostanoids in swelling
PGI2, PGE2, PGD2
122
Reduces release of AA from membrane
steroids
123
reduce AA to PGG2/PGH2
attack COX, NSAIDS
124
Reduce production of prostanoids
target isomerases, Ridogrel
125
Ridogrel
Inhibits throboxane synthase
126
PGF2alpha medical function
causes luteal regression and induces smooth muscle contraction
127
carbaprost
PGF2 analogue for abortifacient and post partum bleeding
128
PGE2 PGE1 medical use
INduce uterine contraction
129
Misoprostol
PGE2 analogue used as abortifacient and gastric cytoprotection
130
Dinoprostone
PGE2 analogue for inducing labor
131
NSAID basics
weak acids that have sleectivity for both COX
132
Gold standard NSAID
Aspirin
133
Aspirin mechanism
inhibition of COX by competing for active site
134
Aspirin effect
acetylates SER-530 and causes irreversible inhibition
135
NSAID side effect
limit cytoprotection = gastropathy
136
Gastropathy mechanism
reduce PGE1,2 = reducegastric mucus and pH. Reduce TxA2 = inhibit clot = erosion, bleeding, ulcer
137
Which COX causes gastropathy
COX 1 inhibition
138
Coxib problem
inhibited only COX2 but had cardiovascular risks
139
Coxib problem mechanism
get an imbalance of the TxA2 and PGI2. Endothelial cells need COX 2 for antiplatelet effects.
140
NSAID renal adverse effects
renal disease need the vasodilation from prostaglandin. Inhibition leads to renal toxicities
141
NSAID renal effect mechanis
PGE induced renin secretio causes elevated blood pressure bc sodium reabsorption
142
Aspirin low dose
Inhibits platelet COX 1
143
High dose Aspirin
analgesic
144
Highest dose aspirin
anti-inflammatory
145
Reyes syndrome (aspirin)
hepatic toxicity, limits pediatric use
146
Salicylate toxicity (Aspriin
headache, tinnitus, dizziness. Ringing in ears most important
