Pharmacology Flashcards
1
Q
what is a drug?
A
chemical substance of known structure which, when administered to a living organism, produces a biological effect
2
Q
what is pharmacology?
A
branch of medicine concerned with uses, effects and modes of action of drugs
3
Q
what is pharmacodynamic?
A
how the drug affects the body
4
Q
what is druggability/ligandability?
A
the ability of a protein target to bind to a small molecule with high affinity.
5
Q
what is the estimated number of human genes that are druggable?
A
10-15%
6
Q
what are four types of drug targets?
A
receptors
enzymes
transporters
ion channels
7
Q
what is a receptor?
A
component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligand’s observed effects which could be an intracellular response
8
Q
what kind of susbtance can ligands be? (2) give examples
A
exogenous (e.g. drug)
endogenous (e.g. hormones, neurotransmitter)
9
Q
what is a ligand?
A
a molecule that binds to another (usually larger) molecule
10
Q
what is an agonist?
A
compound that binds to a receptor and activates it
11
Q
what is an antagonist?
A
a compound that reduces the effect of an agonist, do not activate receptors
12
Q
what are the two types of antagonists?
A
competitive antagonist
non-competitive antagonist
13
Q
what is another name of competitive antagonist?
A
selective antagonist
14
Q
what is another name of non-competitive antagonist?
A
allosteric antagonist
15
Q
where do competitive antagonists bind?
A
same site as agonist (orthosteric site)
16
Q
where do non-competitive antagonists bind?
A
other site to agonist binding site (called allosteric site)
17
Q
what can a competitive antagonist do?
A
reverse effects of agonist
18
Q
what does a non-competitive antagonist do to the site of an agonist?
A
conformation changes so agonist can’t bind to it
19
Q
what are the three types of chemicals that communicate with receptors? give examples
A
- neurotransmitters (acetylcholine, serotonin)
- autacoids (cytokines, histamine)
- hormones (testosterone, oestrogen)
20
Q
what are the four types of receptors?
A
- ligand-gated ion channels
- G protein coupled receptors
- Kinase-linked receptors
- cytosolic/nuclear receptors
21
Q
typically, what type of chemical work on ligand-gated ion channels? give an example
A
neurotransmitters e.g. nicotinic acetylcholine
22
Q
how fast do ligand-gated ion channels work?
A
milliseconds
23
Q
how does the effects of the receptor initiate an effect?
A
ligand binds to receptor -> receptor channel opens (coupling between receptor and ion channel so ion channel opens)
24
Q
give two examples of G protein coupled receptors
A
beta-adrenoceptors
muscarinic ACh receptors
25
how fast do G protein coupled receptors work?
within seconds
26
what are G protein coupled receptors?
membrane receptor coupled to intracellular effector system via G protein
27
how do the G protein coupled receptors lead to a change in the cell?
ligand binds to receptor causing changes in receptor causing changes with G protein which lead to activation of intracellular signalling pathway
28
how does a G protein shape change with the receptor?
GTPase is part of receptor, changes to receptor lead to GTPase changing G protein. G protein in GTP format will keep signalling off, and in GDP format will make signalling on. GTPase causes changes from GTP to GDP etc.
29
give three examples of uses of kinase-linked receptors
1. cytokine receptors
2. for insulin
3. for growth factors
30
how fast do kinase receptors work?
hours
31
describe the structure of kinase-linked receptors
extracellular binding domain linked to intracellular domain by single transmembrane helix
32
what molecules are the most common ligands for kinase-linked receptors?
peptide molecules
33
how do kinase-linked receptors lead to changes in the cell?
ligand binds to receptor leading to phosphorylation of intracellular domain of receptor leading to cellular signalling cascade usually leading to gene transcription
34
what is common about ligand-gated receptors, G protein coupled receptors, kinase-linked receptors that is not common to cytosolic/nuclear receptors?
the first three work by transducing a signal from outside of cell leading to changes in receptor which initiates signalling cascade
35
give 3 example of cytosolic/nuclear receptors
steroid hormone, thyroid hormone, oestrogen hormone receptors
36
how fast do cytosolic/nuclear receptors work?
hours
37
where are cytosolic/nuclear receptors found?
soluble phase of cell
some in cytosol then move to nucleus when ligand activated
others already in nucleus
38
what do cytosolic/nuclear receptors do?
transcription regulators (activators usually)
39
what is the structure of cytosolic/nuclear receptors?
DNA binding domain and Ligand binding domain:
DNA binding domain made of two zinc fingers which can interact directly with DNA and recognise different parts of DNA
Ligand binding domain can directly interact with ligand protein, leading to changes in receptor which changes zinc fingers so that they can access DNA.
(zinc fingers can't interact or recognise DNA without ligand)
40
describe the zinc fingers in DNA binding domain
two cysteine rich loops in amino acid change held together in formation by zinc ions
41
how do cytosol/nuclear receptors lead to changes in cell?
ligand bound to receptor -> receptor bound to DNA -> transcription occurs
42
give an example of a receptor that has subtypes? give the subtypes and their jobs
```
histamine receptors
H1: allergic responses
H2: gastric acid secretion and contraction of ileum
H3: CNS disorders e.g Alzheimer's
H4: immunity and inflammatory
```
43
what is potency?
can be measure of effective concentration at 50% (EC50) which is the concentration of agonist needed to reach half the maximum response. having a lower concentration to reach a higher response means higher potency
44
what is efficacy?
maximum response achievable from a dose, can be referred to as Intrinsic Activity referring to ability of drug-receptor complex to produce maximum functional response
45
what is a partial agonist?
those that can never get a total full response from a receptor. their efficacy is lower than that of the ability of the receptor. a full agonist has more efficacy than a partial agonist
46
give an example of a non-selective agonist
isopernaline non-selective to beta-adrenoceptor because can bind to beta1 and beta2 receptors
47
what is isopernaline used for?
bradycardia (to slow heart rate) and heart block
48
give an example of a selective agonst
salbutamol selective to beta2-adrenoceptor
49
what is salbutamol used for?
open medium and large airways for COPD and asthma
50
what are the four factors that govern drug action with receptors?
affinity
efficacy
receptor number
signal amplification
51
what is affinity
how well a ligand binds to the receptor
52
what is efficacy
how well a ligand activates the receptor
53
which out of affinity and efficacy is shown by both antagonists and agonists
affinity
54
how does receptor number effect drug interaction with a receptor
number of receptors present on cell surface varies. cells have receptor reserves but the reserves are not for partial agonists
55
what is meant by signal amplification in the context of drugs interacting with receptors
some tissues are better at signal amplification than others, two tissues may have same receptor and same agonist but one tissue will have a larger response because it has more signal amplification ability
56
what is tolerance?
reduction in the drug/agonist effects over time, occurring due to continuously, repeated, high concentrations of agonist
57
what is desensitisation?
occurs if uncoupling, internalisation, degradation of receptor occurs
58
what is an enzyme inhibitor?
molecule that binds to an enzyme and decreases (normally) its activity. prevents the substrate from entering the enzyme's active site thus preventing the enzyme from catalysing the reaction
59
what are the two types of enzyme inhibitors?
irreversible and reversible inhibitors
60
how do irreversible inhibitors work?
react with enzyme and change it chemically e.g. via covalent bonds
61
what is a reversible inhibitor?
those that bind non-covalently to enzyme
62
give two examples of drugs that are enzyme inhibitors
statins
| angiotensin converting enzyme inhibitors
63
what enzyme do statins inhibit?
HMG-CoA reductase in cholesterol production pathway
64
what do statins reduce and why are they taken?
they reduce bad cholesterol and they reduce the risk of cardiovascular disease and mortality in those with high risk
65
what enzyme do ACE inhibitors work on?
angiotensin converting enzyme
66
what is the renin-angiotensin-aldosterone system for?
blood pressure regulator, increases blood pressure by increasing salt and water retention
67
what do ACE inhibitors reduce and why do people take them?
reduce angiotensin 2 (because ACE inhibited so less angiotensin 1 -> 2) reduce blood pressure
68
what is wrong in Parkinson's disease?
abnormal low dopamine in brain.
69
how is LDOPA linked to dopamine?
LDOPA is a precursor to dopamine but has to cross the blood brain barrier to become dopamine
70
name four inhibitors used to treat parkinson's disease
1. peripheral DDC inhibitor
2. peripheral COMT inhibitor
3. central COMT inhibitor
4. Monoamine oxidase B inhibitor
71
what does peripheral DDC inhibtor do?
inhibits DDC enzyme outside of brain from converting LDOPA to dopamine outside of brain so more LDOPA enters brain to make dopamine in brain
72
what does peripheral COMT inhibitor do?
inhibits COMT enzyme in periphery so prevents breakdown of LDOPA so more LDOPA enters brain
73
what does central COMT inhibitors do?
block central COMT which convert dopamine to another substance, therefore the inhibition means that there is more dopamine to activate D1 and D2 receptors
74
what do monoamine oxidase B inhibitors do?
prevent dopamine breakdown in brain
75
what do we mean by transport when referring to cells?
transport: molecules moving across cell membrane allowing cells to get what they need e.g. ions, glucose
76
give three examples of channels that use passive transport
- ENaC (epithelium sodium channels)
- voltage gated channels
- receptor activated channels
77
describe ENaC
selectively permeable to Na ions and cause absorption of Na ions in some areas.
78
where are ENaC found?
kindey- collecting ducts
colon
lungs
sweat glands
79
what endogenous substance blocks ENaC
atrial natriuretic peptide
80
what exogenous substance blocks ENaC
amiloride
| thaizide
81
where are voltage gated channels found?
excitable cells membrane e.g. muscle, neurons
82
when are voltage gated channels closed and open?
resting membrane potential- closed
| depolarised membrane potential- activated and opened
83
give four ions that can use voltage gated channels to pass
calcium
sodium
potassium
84
what does activation of voltage gated calcium channels lead to?
calcium enters cell and activated calcium-sensitive potassium channels leading to muscle contraction/ excitation of neurons etc.
85
what is a drug that blocks calcium channels?
amlodipine
86
what does amlodipine do to calcium channels?
stops calcium ions entering vascular smooth and cardiac muscle
87
what is amlodipine used for?
reduce blood pressure because causes vasodilation and less peripheral vascular resistance
88
what does lidocaine do in relation to voltage gated channels?
blocks transmission of action potential so does not allow voltage gated channels to open
89
what is lidocaine used for?
anaesthetic
90
how does increased glucose affect potassium channels?
increased glucose leads to voltage gated potassium channels being locked in pancreas beta cells so lots of repetitive firing of of action potential leading to lots of calcium entry triggering insulin release
91
name a drug that lowers blood glucose by blocking voltage gated K channels?
nateglinide
92
give a example of receptor activated channel
receptor activated chloride channels
93
what is another two names for receptor activated channels
ligand gated ion channel
| ionotropic channel
94
what opens receptor activated channels
ligand binding to receptor
95
describe GABA-A receptors and how they are involved to receptor activated chloride channels
chloride channel attached that opens when GABA (ligand) (inhibitory neurotransmitter) binds to GABA-A receptor on post-synaptic membrane
96
what does the opening of GABA-A receptor activated chloride channels do
lots of Cl- enter cell so hyperpolarisation occurs
97
give a drug that can enhance the GABA-A receptor activated chloride channel and how it does so
phenobarbitone by increasing permeability of channel to chloride
98
what are the names of the three main protein ports in the cell membrane?
uniporters
symporters
antiporters
99
what are uniporters?
use energy to pull molecules into cell
100
what is a symporter
co-transporter
use movement into cell of one molecule to pull in another molecule against its concentration gradient (molecule so not always ions)
101
give an example of a symporter
Na-K-Cl cotransporter (NKCC) moves those ions into cell in same direction. found in organs that secrete fluids
102
give a drug that inhibits NKCC
furosemide
| binds to NKCC so Na, Cl, K lost in urine (inhibits NKCC at thick ascending limb of loop of henle)
103
what is an antiporter
cotransporter
uses energy from one substance moving down its gradient (mostly Na/K/H) to move another substance against its concentration gradient
104
give two examples of antiporters
na/k ATPase
| k/H ATPase
105
what does Na/K ATPase do
pumps 3Na out and 2K into cell against their concentration gradient using ATP
106
give a drug that inhibits Na/K ATPase and why it is used
Digoxin
| atrial fibrillation, atrial flutter, heart failure
107
how does digoxin reduce heart rate
inhibits Na/K ATPase so more intracellular Na so less activity from Na-Ca exchanger so more Ca intracellular which lengthens cardiac action potential leading to a decreased heart rate
108
where is K/H ATPase used and what does it do
in stomach
proton pump
exchanges K from intestinal lumen with cytoplasmic H so acidifies stomach and activates pepsin enzymes
109
what blocks K/H ATPase
proton pump inhibitors
| inhibit acid secretion
110
give an example of a drug that use irreversible inhibition
Omeprazole
