Biochemicals principles of pharmacology Flashcards
1
Q
what does ACE inhibitors stand for
A
angiotensin converting enzyme inhibitors
2
Q
what are ACE inhibitors
A
enzyme inhibitors, drugs that target enzymes, protease
3
Q
targets of enzyme inhibitors include…
A
enzymes, ion channels, transport proteins, receptors
4
Q
examples of enzyme inhibitors used as an antibiotic
A
amoxicillin
5
Q
examples of enzyme inhibitors used for cardiovascular problems
A
ACE inhibitors, statins, aspirin
6
Q
examples of enzyme inhibitors used as an analgesic/pain
A
paracetamol, ibuprofen, rivaroxaban
7
Q
examples of enzyme inhibitors used as an anticoagulant/blood thinner
A
warfarin
8
Q
what are ACE inhibitors derived from
A
snake venom
9
Q
what do ACE inhibitors do
A
reduced blood pressure
10
Q
adverse effects of ACE inhibitors
A
coughs and dizziness
11
Q
what do the name of ACE inhibitors end in
A
-pril
captopril, lisinopril, ramipril
12
Q
what 2 things does ACE inhibitors reduce and what are the effects of it
A
- reduce formation of angiotensin II- reduces vasoconstriction and salt/water retention
- reduces breakdown of bradykinin (signalling peptides) into inactive peptides- increased bradykinin causes persistent coughing
13
Q
what causes a persistent cough
A
increased amount of bradykinin
14
Q
mechanism of action of a reversible inhibitor
A
non-covalent
15
Q
mechanism of action of a irreversible inhibitor
A
covalent
16
Q
example of a reversible inhibitor
A
captopril binding to ACE with hydrogen bonds
17
Q
example of a irreversible inhibitor
A
aspirin binding to cox enzymes
18
Q
what is enzyme kinetics
A
action of enzyme inhibitors can be determined using experiments that determine the rate of enzymatic reactions in response to changes like changing substrate concentration
19
Q
name the two types of plot/graphs used in enzyme kinetics
A
michaelis-menten
lineweaver-burk
20
Q
what does the michaelis-menten plot show
A
how rate changes as substrate concentration changes
21
Q
what is the michaelis-menten constant
A
Km, concentration of substrate at which the initial velocity of catalysis is half maximal
22
Q
what does the Km tell us
A
how well the enzyme binds to the substrate
23
Q
how to determine Km
A
doing experiments that vary substrate conc, enzyme conc constant, determine initial velocity (product formation over time)
24
Q
what is the problem with michaelis-menten plot and what is the solution
A
the hyperbola is difficult to fit accurately without a computer, solution is to us a double reciprocal plot (1/s and 1/v) which is the lineweaver-burk plot
25
what is the michaelis-menten equation
v=vmax[s]/Km+[s]
26
what is the lineweaver-burk equation
1/v=(Km/vmax)(1/[s]
)+1/vmax
27
how to transform a michaelis-menten graph into lineweaver-burk graph
do double reciprocals of the values in michaelis-menten (put the values 1/x)
28
why is lineweaver-burk plot better
allows more accurate estimation of Km and vmax
29
example of a calcium channel blocker
amlodipine
30
what do calcium ions do
trigger muscle contraction
31
calcium channel blockers such as amlodipine prevent the uptake of Ca2+ by what two structures
vascular smooth muscle and cardiomyocytes
32
what are the vascular effects of amlodipine
vasodilation (smooth muscle relaxation)
33
what are the cardiac effects of amlodipine
decreased contractility and decreased heart rate
34
what is amlodipine
calcium channel blocker
35
adverse effects of calcium channel blockers
arterial dilation, veins unaffected, excess fluid goes into surrounding tissue causing tissue to swell
36
what are ion channels
proteins that facilitate transport of molecules across the cell membrane
37
two types of ion channels and how they are controlled
1. voltage gated- controlled by potential differences
2. ligand gated- binding of a ligand will cause it to open
38
ion channels are multimeric proteins, what does multimeric mean
its a protein composed of several subunits
39
how does the calcium channel blocker amlodipine work
calcium channel has 4 aspartate residues, amlodipine binds and causes asymmetry in the selectivity filter which prevents calcium ions from passing through
40
what does potency mean
the amount of drug needed to produce an effect
41
how is the potency of a drug determined
by comparing the concentration at which 50% inhibition is achieved (IC50)
42
how is IC50 represented on a graph
10log
43
IC50 units of low, medium and high potency
low- mM
medium- μM
high- nM
44
two things that IC50 is used to measure for
ion channels and enzyme inhibitors
45
what characteristic of a drug is the most desired (potency and IC50)
high potency and low IC50
46
what are solute transporters
diverse proteins involved in transport of ions and organic compounds
47
what do thiazide diuretics do
inhibits action of specific transporters
48
effects of thiazide diuretics
reduce cardiac output, reduce blood volume, lowers blood pressure, increases water and salt excretion
49
where does energy for active transport come from
hydrolysis of ATP
50
what inhibits sodium potassium pump
cardiac glycosides
51
what do cardiac glycosides do
inhibit sodium potassium pump
51
what are the effects of inhibiting sodium potassium pump
reduces heart rate, increases the force of contraction of the heart muscle
51
what is used to treat heart failure
cardiac glycosides
51
example of a cardiac glycoside
digoxin
51
name 2 inhibitors used to treat hypotension
calcium channel blockers and thiazide diuretics
51
what are cardiac glycosides used for
treating heart failure
52
what is used to treat the stomach
proton pump inhibitor
52
what does the inhibition of sodium potassium ATPase lead to
increased intracellular sodium ion concentration which leads to increase of intracellular calcium ion concentration via the sodium calcium exchange system
53
name two parts of the nervous system
central and peripheral
54
name two parts of the peripheral nervous system
somatic and autonomic
55
difference between somatic and autonomic nervous system
somatic- voluntary control of skeletal muscles, sensory/motor control
autonomic- subconscious, organ function
56
types of autonomic nervous system
sympathetic and parasympathetic
57
difference between sympathetic and parasympathetic nervous system
sympathetic- prepares body, flight of fight, increases heart rate, vasoconstriction
parasympathetic- promotes restorative functions, rest or digest, slows heart rate
58
what is the anatomic difference between somatic and autonomic nervous system
somatic has a single axon extending from neurone in CNS to effector and autonomic is a two neurone system
59
what are the normal conditions in the heart in terms of signalling from the peripheral nervous system
balanced signals from sympathetic and parasympathetic
60
what does efferent mean
CNS to organ/muscle
61
what does afferent mean
organ to CNS
62
what is ganglion
cluster of peripheral autonomic neurones
63
anatomy of autonomic nervous system
-preganglionic neurone and post ganglionic neurone
sympathetic- short, long
parasympathetic- long, short
-two neurone chain
-CNS to ganglion to effector tissue
64
what is a synapse
structure/gap between 2 neurones that allow one neurone to transmit a signal to the second neurone
65
what does SNAP stand for
sympathetic noradrenaline, acetylcholine parasympathetic
66
what are beta blockers
competes with binding of noradrenaline/adrenaline to beta 1 adrenergic receptors to block sympathetic signalling to the heart
67
adverse effects of beta blockers
affinity for beta 2 adrenergic receptors so it can exacerbate asthma
68
short definition of beta blockers
antagonist of beta 1 adrenergic receptors
69
what are beta blockers used to treat
angina- chest pain from narrowing arteries supplying the heart
heart failure- not enough blood pumped to body
atrial fibrillation- irregular heartbeat
heart attack- blocked blood supply to heart
70
4 types of receptors
-ligand gated ion channels
-GPCR
-kinase linked receptors
-nuclear receptors
71
example of GPCR
adrenergic and cholinergic
72
example of ligand gated ion channel receptors
nicotinic acetylcholine
73
what does GPCR stand for
G protein coupled receptors
74
what do drugs do to receptors
drugs can stimulate or inhibit receptors, stimulators are agonists and drugs that inhibit are called antagonists
75
what are agonists
drugs that stimulate receptors
76
example of an agonist
adrenaline
77
what are antagonist
drugs that inhibit/block receptors
78
example of an antagonist
beta blockers
79
at effector organs what is the receptor for acetylcholine
muscarinic receptors
80
name the receptor adrenaline and noradrenaline binds to
adrenergic receptors
81
name of receptor acetylcholine binds to
cholinergic receptors
82
what is a ligand
chemical that can form a complex with a receptor
83
what is a receptor
protein that recognises a specific chemical signal from outside the cell
84
principles of signalling
specificity, amplification, modularity, desensitisation/adaptation, integration of signalling
85
what is specificity
receptor recognises a specific signal leading to a response
86
what is amplification
signal of a single ligand gives rise to many second messengers and modified molecules in the cell
87
describe the process of amplification
-ligand L binds to receptor R
-receptor R binds to intracellular G protein
-G protei activates enzyme (AC=adenylyl cyclase) that produces a second messenger cAMP
-signalling cascade
88
membrane proteins involved in gpcr signalling
integral, lipid modified, accessory
89
what is modularity
receptor signalling uses interchangeable parts
-both receptors use the same chemical to stimulate but different outcomes
90
what is desensitisation/adaptation
activation of a receptor triggers a feedback loop that inactivates the receptor
91
what is integration of signalling
activation of two or more receptors lead to a receptor that integrates both signals
92
describe scatchard analysis
93
what is B max in the scatchard analysis
total number of binding sites
94
what is the dissociation constnat in the scatchard analysis
1/2Bmax
95
autonomic nervous system anatomy
sympathetic- short, long
autonomic- long, short
96
what is potency
measure of drug activity expressed in terms of amount required to produce an effect
97
what is EC50
effective concentration at 50% of max response
98
what is receptor occypancy
fraction of receptors bound by ligand/drug
99
what is efficacy
ability of a drug to produce an effect
100
equation for response of drug
R=Rmax x conc of drug/(conc of drug+EC50)
101
what is a partial agonist
agonist that is unable to produce a full response even when all receptors are occupied
102
what is an agonist
stimulator
103
what is an antagonist
inhibitor
104
what does affinity of a ligand mean
ability of ligand to bind to a receptor
105
what is potency
concentration of an agonist required to reach half maximum effect
106
reversible antagonist and an example
non covalent ligand receptor interaction, competitive and uncompetitive
eg. propanolol to beta1 adrenergic receptors
107
irreversible antagonist and an example
covalent ligand and receptor interaction
eg. phenoxybenzamine binding to a1 and a2 adrenergic receptors
108
what is a pure antagonist
no effect on receptor activity
109
what is an inverse angonsist
inhibits constitutive activity
110
what are spare receptors
fraction of receptors not occupied at max response
111
what does unsurmountable mean
non competitive, irreversible, no amount of concentration can increase the response
112
what does parasympatholytic mean and example
substance that reduces the activity of the parasympathetic nervous system like atropine (antagonist)
113
what does sympathomimetic mean and example
substance increases sympathetic signals like adrenaline (agonist)
114
what is -mimetic and -olytic
sympathomimetic/parasympathomimetic= increases signals/activity
sympatholytic/parasympatholytic= reduces activity
115
what is therapeutic index and its equation
ratio of dose of drug that causes adverse effects to the dose that leads to desired pharmacological effect
Ti=TD50/ED50
TD50=toxic dose for 50% population
ED50=effective dose
116
