Pharmacodynamics Flashcards
(99 cards)
1
Q
4 types of targets
A
- receptors
- ion channels
- enzymes
- carrier molecules/transporters
2
Q
Specificity
A
specific for that receptor (will key fit into lock)
3
Q
Affinity
A
how well drug binds to receptor (will key turn)
4
Q
intrinsic activity
A
magnitude of effect of drug once it is bound
5
Q
competitive vs noncompetitive binding
A
reversible vs irreversible
6
Q
Agonist
A
significant receptor affinity and full intrinsic activity- enhances physiological process
7
Q
Full agonist
A
generates maximal response
8
Q
Inverse agonist
A
generates response opposite of endogenous substance (stimulates receptor but gives opposite response)
9
Q
Partial agonist
A
significant receptor affinity but only fractional intrinsic activity
10
Q
agonist-antagonist
A
partial agonists that also have antagonist activity (when given with full agonist, it may decrease effect of full agonist)
11
Q
Antagonist
A
significant receptor affinity but no intrinsic activity
12
Q
potency and drug response curve
A
increased affinity of drug for receptor shifts curve to the left
13
Q
slope of drug response curve
A
of receptors occupied for effect- steep slope= majority of receptors
14
Q
efficacy and dose response curve
A
intrinsic ability to produce effect- higher plateau=greater efficacy
15
Q
Drug response Equation
A
Drug + receptor = drug receptor complex = tissue response
DRC is usually constant but TR varies from person to person
16
Q
C50
A
concentration associated with 50% of response
17
Q
Timing and Potency
A
relative potency varies on time course of drug (peak effect fentanyl vs morphine)
18
Q
ED50
A
effective dose in 50% of population (we use ED99)
19
Q
TD50
A
toxic dose in 50% of population
20
Q
LD50
A
lethal dose in 50% of population
21
Q
Therapeutic Index
A
LD50/ED50
better TI for anesthesia is LD1/ED99
22
Q
synergy
A
summing of simultaneous effects of 2+ drugs where combined effect is greater than effect of either drug when given alone (target different receptors)
23
Q
additive
A
effect in which 2 substances/actions used in combination produce total effect same as sum of individual effects (target same receptors)
24
Q
tachyphylaxis
A
rapid decrease in response to repeated doses over short period of time (ex- ephedrine)
25
desensitization
chronic loss of response over longer period of time or absolute loss of receptors (ex- beta adrenergic receptors)
26
tolerance
larger and larger doses required to produce same effect; altered sensitivity of receptors (ex- chronic opiate use)
27
Down regulation
continued stim. of cells; desensitize; receptors go down in number
28
up regulation
chronic administration of antagonist; make more receptors (beta blockers)
29
Sodium Ion Channels
activation of Na channels allows influx of Na into cell (positive/depolarization)
30
Local anesthetics
bind to Na channels in closed state (prevent Na influx)
| Class 1 antiarrhythmics
31
CCBs
bind to receptors on voltage gated Ca ion channels- keeps them inactive/closed, prevents influx of Ca- slows down HR
Class IV antiarrhythmics
32
Class III antiarrhythmics
amiodarone, bretylium
block K ion channels- prolong depolarization
decrease portion of cardiac cycle where myocardial cells are excitable
33
Ligand Gated Ion channels
undergo conformational change after ligand binds to it extracellularly- opens pore in which ions travel down concentration gradient
34
GABA receptors in brain
ligand gated channel
inhibitory; anion (Cl) (GABAa)
when activated, neuron transmission is inhibited
35
Nicotinic receptors in brain
ligand gated channel
| excitatory; cation (Na)
36
serotonin receptors in brain (5HT3)
ligand gated channel
| excitatory, cation
37
glycine receptors in brain
ligand gated channel
| inhibitory; anion
38
glutamate receptors in brain
ligand gated channel
| excitatory
39
Anesthetic drugs that are agonist for GABA
benzos, barbituates, propofol, etomidate
40
How many subunits of 5 must ACh be bound to in nicotinic receptors to open?
2
41
Opening of Nicotinic ACh receptor
allows Na and Ca to move in, K to move out
| allows current flow to depolarize endplate
42
Alpha 1 receptors
activation increases intracellular Ca, leading to muscle contraction
also inhibits insulin secretion and lipolysis
43
Beta 1 receptors
located on postsynaptic membranes of heart
stimulation initiates kinase phosphorylation cascade through 2nd messenger system- increases intracellular Ca and increases troponin binding to Ca- +chorono, dromo, and inotropic effects
44
Alpha 2 receptors
presynaptic nerve terminal
activation inhibits adenylate cyclase-decreasing entry of Ca
decreases release of NE, stimulation of postsynaptic receptors in CNS produces sedation and decreases SNS outflow
45
Beta 2 receptors
postsynaptic on smooth muscle/glands
activates adenylate cyclase and 2nd messenger system- smooth muscle relaxation (bronchodilation, vasodilation, relaxation of uterus, bladder, gut; glycogenolysis, lipolysis, gluconeogenesis, insulin release)
46
Muscarinic receptors
activates cholinergic receptors at postganglionic PNS junction of cardiac/smooth muscle
G protein coupled- 2nd messenger system
47
nicotinic receptors
found at synaptic junctions of SNS and PNS ganglia
| Ionotropic- affects Na flow
48
M1 receptors
CNS, salivary glands, parietal cells
| increases IP3/DAG -> CNS excitation, increased memory, locomotor activity, gastric acid secretion
49
M2 receptors
heart
| decreases cAMP -> decreased rate, force, AV conduction
50
M3 receptors
smooth muscle, exocrine glands
| increased IP3/DAG-> all smooth muscle contraction except: vasodilation, glandular secretion
51
Non-depolarizers
antagonist to nicotinic receptors
| channel remains closed, no ion flow
52
Succinylcholine
agonist to nicotinic receptors
only 2 alpha subunit needed- opens channel
depolarizes but stays attached longer than ACh
53
Zofran
5HT3 antagonist
54
cyclic AMP
```
intracellular 2nd messenger system
mobilizes stored energy
increased HR and force of contraction
relaxation of SMOOTH muscle
involved in nitric oxide pathway
```
55
cyclic AMP effects
bronchodilation, prevents platelet aggregation, positive inotropic action in heart, antiglaucoma, reduces BP, reduces inflammation
56
IP3
triggers release of Ca from storage vesicles
57
Cardiac Signal Transduction- G protein
drugs stimulate Gs (increases cAMP) or Gi (inhibits cAMP) signals
affects influx of Ca and release from SR
58
Cardiac Signal Transduction- IP3
increasing IP3 stimulates release of Ca from SR
59
Vascular Signal Transduction- Gs proteins
increase in cAMP causes relaxation
60
Vascular Signal Transduction- IP3
vascular smooth muscle contraction via protein phosphorylation
61
Nitric Oxide
produced from amino acid L-arginine by enzymatic action of NOS
diffuses into vascular smooth muscle and binds to activate guanylyl cyclase (catalyzes dephosphorylation of GTP to cGMP)
62
How does cGMP induce smooth muscle relaxation?
- inhibits Ca entry into cell
- activates K channels- hyperpolarization/relaxation
- stimulates cGMP dependent protein kinase- activates myosin light chain phosphatase- leads to smooth muscle relaxation
63
Vascular Effects of NO
vasodilation, antithrombotic effect, anti inflammatory effect, antiproliferative effect
64
H1 receptors
stimulation causes hives, bronchoconstriction, motion sickness, separation of cell lining of vessels, and smooth muscle relaxation
65
H2 receptors
found on parietal cells in stomach- mainly responsible for gastric acid levels
66
Opioid Receptors (G protein)
inhibit adenyl cyclase, decrease conductance of Ca channels, open K channels, hyperpolarizes cells, decreases neuronal activity, suppress release of substance P
67
Anticholinesterase Drugs
inhibit acetylcholinesterase- prevents breakdown of ACh (more ACH at NMJ)
edrophonium, neostigmine
68
PDE inhibitors
- milrinone, amrinone
- competitive inhibitory action on PDE III isoenzyme
- increased intracellular cAMP and cGMP, inward flow of Ca
- positive inotropic and bronchial smooth muscle relaxation effect
69
COX inhibitors
inhibit prostaglandin synthesis- NSAIDs, ASA, toradol
| bad for renal insufficiency, asthma
70
ACE inhibitors
prevents conversion of angiotensin I to II
| captopril, enalapril
71
lb to kg
1 kg = 2.2 lbs
72
Calculating BMI
mass/height^2
73
IBW
Female 105 lbs + 5 lbs(every in over 5')
| Male 106 lbs + 6 lbs (every in over 5')
74
Percentage of solution
move decimal place 1 to the right- how many mg/ml
75
1:1000 and 1:200,000
1 mg/ml and 5 mcg/ml
76
strongest to weakest bonds
covalent, ionic, hydrogen, van der waals
77
isomers
same chemical formula but different structures
78
stereoisomers
differ in spatial arrangements
| enantiomeres- mirror images
79
racemic mixtures
50/50 enantiomeres
each may have different effect, excretion, etc
thiopental, ketamine, bupivicaine, atracurium, etc
80
hydrocarbons
all carbon atoms with H attached
81
saturated hydrocarbons
all single bonded H
| alkanes, hexanes
82
unsaturated hydrocarbons
one or more double/triple bonds
| alkenes (2), alkynes (3), benzene ring
83
Amines
NH3
when 3 H ions, it is ammonia
metabolized by oxidation
rocuronium
84
Alcohols
ROH
85
Phenols
ROH where R is benzene ring
86
Ethers
ROR
alkyl groups attached by oxygen
metabolized by hydroxylation
thioether, enflurane, isoflurane
87
Carbonyl
C=O
88
aldehydes
RCHO
89
ketones
RCOR
90
Carboxylic acids
RCOOH
91
Esters
RCOOR
carbonyl attached to alkoxy
metabolized by hydrolysis
esmolol
92
Amides
RCONH2
metabolism by hydrolysis and N oxidation
lidocaine
93
Alkanes
usually contain only C/H
hydrophobic, lipophilic
metabolism usually by P450
halothane
94
Alkenes
C/H atoms
contain at least 1 double bond (fixed)
metabolized by epoxide
95
Alkyne
triple bond between 2 carbon atoms
| metabolism not extensive (hard to break down)
96
Aromatics
benzenes, phenyls, heterocyclics
metabolism similar to alkenes
double bond oxidized to epoxide
propofol
97
Alcohols
contain hydroxyl group -OH
metabolized either by oxidation/conjugation
phenol- alcohol attached to benzene ring
albuterol
98
Conjugate base
after acid donates proton
99
conjugate acid
after base accepts proton
