Pharmacology Flashcards
1
Q
What is the function of receptors?
A
They are the sensing elements of the cell
They respond to chemical messengers e.g. hormones, transmitters
They induce a specific response within cells
- induce the release of or synthesis of hormones/transmitters
- Turn on/off a cell
- Increase/decrease gene expression
2
Q
What does an agonist do?
A
Activates a receptor
3
Q
What does an antagonist do?
A
Prevents a receptor from activating
4
Q
Draw what happens when an antagonist is present
Draw what happens when an agonist is present
A
Agonist
Directly leads to ion channel opening and closing
Transduction mechanisms lead to enzyme activation/inhibition, ion channel ovulation and DNA transcription
Antagonist
Leads to no effect because endogenous mediators are blocked
5
Q
What are ion channels? And how can drugs interact with ion channels?
A
Ion channels are channels in/on a cell that open to allow ions across.
An increase or decrease in ion concentrations can activate/inhibit specific cell functions e.g.
hormone/ transmitter release and gene transcription.
Drugs can interact with ion channels:
- At the site of the ion channel
- Via intermediate stages involved in channel opening
6
Q
What does an ion channel blocker do?
A
Blocks the ion channel so nothing can pass through it.
7
Q
What does an ion channel modulator do?
A
Increases or decreases ion channel opening probability
8
Q
What is the function of enzymes?
A
Increase the rate of a specific reaction
They act to speed up the formation or breakdown of specific hormones and neurotransmitters e.g. serotonin, dopamine and acetylcholine
9
Q
What is a enzyme inhibitor?
A
To stop the action of the enzyme. No reaction occurs.
10
Q
What is an enzyme false substrate?
A
To slow an enzyme down a false substrate is introduced. Introduces inert molecules so that it takes longer to break down the active molecules.
For example 10 molecules of serotonin is broken down in 1 minute. But if 10 molecules of inert substances are added to the 10 serotonin molecules, it will take longer to break it down.
11
Q
What is an enzyme pro-drug?
A
A Pro-drug is an inactive drug before it reaches the enzyme. The enzyme works on the pro-drug, activates it and then the active drug is produced.
12
Q
What are the drug actions of enzymes?
A
Drugs can act to inhibit enzyme function e.g. monoamine oxidase inhibitors increase serotonin
Enzymes can be used as drug activators. This allows a drug to be designed so that it is active only in the regions where a specific enzyme is found.
13
Q
What is the function of carrier molecules?
A
Provide transport of small organic molecules across cell membranes.
Facilitate the transport of lipid insoluble molecules e.g. transport of glucose and amino acids into cells and the reuptake of neurotransmitters e.g. noradrenalin and serotonin
14
Q
How do normal transporters work?
A
Molecule passes through the cell membrane as normal
15
Q
How do transport inhibitors work?
A
Can either block the entrance of the cell so nothing can enter it or it can remain inside the cell membrane so no molecules can pass through.
16
Q
How do false substrates work for transporters?
A
A false substrate means that something can be placed in the cell that isn’t usually found in there. Can ‘trick’ the transporter into thinking that the molecule usually lives in the cell.
Can be used in cancer treatment to introduce drugs that kill the cells.
17
Q
What is the purpose of a receptor?
Explain the two types of response given:
What does the rate of response depend on?
A
The purpose of a receptor is to elicit a cellular response.
The responses can be:
Rapid e.g. synaptic transmission occurring within milliseconds
Slow: e.g. thyroid hormones induced response occurring over hours and days
The rate of receptor responses depends on the molecular structure and nature of the transduction mechanism.
18
Q
What is a ligand-gated ion channel? And what do they typically respond to?
A
Also known as ionotropic receptors or transmitter gated ion channels.
They are similar to ion channels but incorporate a ligand- binding (receptor)
They typically respond to fast acting neurotransmitters e.g. nicotinic acetylcholine receptors, GABA A receptors and NMDA receptors
19
Q
What are G-protein coupled receptors? What is the response rate?
A
Also known as metabotropic receptors
They mediate their response via intracellular (located on the cells membrane within the cell) proteins called G-Protein activation
Responses tend to be slower than those observed with ligand-gated ion channels e.g muscarinic acetylcholine receptors and adrenoreceptors
20
Q
What are kinase-linked receptors?
A
They are membrane receptors responding to protein meditators.
Linked to an intracellular domain by a single transmembrane helix.
In many cases the intracellular domain is enzymatic in nature e.g. receptors for insulin, cytokines, growth factors
21
Q
What are nuclear receptors?
A
They regulate gene transcription
Located in the cytosol
Migrate to the nuclear compartment when a ligand is present e.g. steroid hormones and thyroid hormones
22
Q
What is the timescales of;
A - ligand-gated ion channels
B- G-protein coupled receptors
C- kinase-linked receptors
D: nuclear receptors
A
A milliseconds
B seconds
C hours
D days
23
Q
Draw out the summary of receptor types:
A
See summary of receptor types in lecture 1
24
Q
Draw the structure of the 4 receptor families:
A
See diagram in lecture 1
25
What is the molecular structure of ligand-gated ion channels?
The best studied is the nicotinic acetylcholine receptor: consists of five subunits, 2 alpha, beta, gamma and delta each of 40-58 kDa
These subunits all show sequence homology
The structure requires two alpha subunits which bind acetylcholine (Ach). For activation two Ach molecules need to bind to the receptor.
26
Draw out the structure of a nicotine Ach Receptor
See lecture 1 notes
27
How do Ligand-gated ion channels work?
They control the fastest synaptic events in the nervous system e.g. postsynaptic transmission
They mediate action potentials, indicating that the speed of events is rapid (milliseconds)
E.g. Ach at a neurotransmitter junction or glutamate in the CNS increases Na+ and K+ permeability within cells
A conformational change in the ion channel results in ions being allowed to flow through it
28
Describe the molecular structure of G- protein coupled receptors
Basic structure comprises of seven transmembrane domains with an extracellular N-terminus and intracellular C-terminus
29
What is the mechanism of activation of G-protein coupled receptors? Draw the diagram to show this mechanism
Activation occurs via agonist binding, this results in conformational change of the membrane bound receptor.
Refer to diagram in lecture 1
30
What is the G-protein made up of?
Consists of 3 subunits, alpha, beta and gamma
Guanine nucleotides are bound to the alpha subunit of the g-protein
In the inactivation state, the alpha subunit binds GDP and the beta + gamma subunits remain together as a complex.
All three subunits remain membrane bound next to each other
31
Draw the mechanism of action of the G-protein
Refer to lecture 1 slides
32
How are G-proteins activated?
Binding of an agonist to the receptor results in a confirmations change that attracts the receptor to the alpha subunit
The GDP bound to the alpha subunit is replaced by GTP (GTP has a higher energy state than GDP due to an extra phosphate group)
The GDP/GTP exchange causes the alpha subunit to dissociate from the beta/gamma complex
33
What happens after a G-protein is activated?
The GTP bound alpha subunit can then move and associate itself with a target protein such as; enzymes, ion channels or intracellular messengers
This would either activate or inactivate the target protein
34
How are g-proteins inactivated?
Inactivation occurs by the hydrolysis of GTP to GDP through activity of the GTPase enzyme located within the alpha subunit.
The GDP bound alpha subunit then dissociates from the target protein and reunites with the beta/gamma subunit
35
How is the G-protein target regulated?
The target molecule regulates the activity of the GTPase enzyme
This means that the extent to which a response is required is under control of the target molecule as opposed to the G- protein
This mechanism results in the amplification of the initial receptor/agonist binding response
36
What are the three main targets for G-proteins?
- Adenylate cyclase: enzyme responsible for cAMP formation
- Phospholipase C: Enzyme responsible for inositol phosphate and diacylglycerol formation
- ion channels: in particular Ca2+ and K+ channels
37
Discuss the adenylate cyclase/ cAMP system
Cyclic 3’, 5’ adenosine monophosphate (cAMP) is a second messenger within a signal transduction cascade.
cAMP is synthesised from ATP within a cell by action of a membrane bound enzyme called adenylate cyclase
cAMP is inactivated by a family of enzymes known as phosphodiesterases
Agonist of particular G-protein receptors induce their effects by increasing /decreasing the concentration of cAMP
cAMP is hydrolysed by phosphodiesterases
38
What is the targets of cAMP?
cAMP is involved in the following cellular responses:
- regulating enzymes involved in energy metabolism, cell division and cell differentiation
- ion transport
- ion channels
- contractile proteins in smooth muscles
These responses are brought about by the activation of protein kinases by cAMP
39
Draw the example of cAMP targeting
Refer to lecture 1 notes
40
Describe the phospholipase C/ inositol phosphate system
Phospholipase C activation occurs via G-protein ligand binding
Phospholipase C (PLC) is a membrane bound enzyme responsible for forming the second messengers diacylglycerol (DAG) and 1,4,5-trisphosphate (IP3) from the substrate phosphatidylinositol 4,5-bisphosphate (PIP2)
41
Draw the IP3 second messenger pathway
Refer to lecture 2
42
Draw the PLC/PIP2 cycle
Refer to lecture 2 slides
43
What are the functions of IP3 targets?
Induces the release of Ca2+ ions from intracellular stores, such as the endoplasmic reticulum and mitochondria
Both the endoplasmic reticulum and mitochondria have IP3 receptors located on their cellular membranes
44
What are the functions of DAG targets?
Activates the membrane bound protein kinase, protein kinase C
Act to increase intracellular Ca2+ concentrations
45
Draw the summary of G-protein signalling
Refer to lecture 2 slides
46
What are kinase-linked and related receptors?
These proteins form receptors for various hormones and growth factors
Intracellular signalling involves tyrosine kinase activity
Agonist binding induces the dimerisation and conformational change that leads to tyrosine autophosphorylation
Through further numerous phosphorylation events, gene transcription can be regulated
47
Draw a diagram to show the transduction in kinase-linked receptors
See lecture 2 slides
48
What are nuclear receptors?
Receptor mediated DNA transcription
These receptors are located in the cytosol and move into the nucleus once ligand binding has occurred
Agonists pass through the cell membrane (lipophilic e.g. steroids) and bind to these nuclear receptors
Agonist/receptor binding results in specific gene transcription
Response an take a few minutes to a few days
49
How are ion channels used as drug targets?
Ions cannot penetrate the cell membrane e.g. k+, Na+ and Ca2+
The only way they canoe in/out of the cell is through protein channels
Ion channel are made from proteins that span the width of the membrane
They are characterised by:
- selectivity
- gating properties
- molecular architecture
50
Discuss the selectivity of ion channels
Cation selective: Na+, K+, Ca2+ or permeable to all three
Anions selective: Cl-
51
What are voltage gated ion channels?
Open when membrane is depolarised
Selective K+, Na+ and Ca2+ channels
Short lasting responses (milliseconds)
52
What are ligand gated ion channels?
Activated by agonist binding e.g. GABA, glutamate
Ca2+ activated potassium channels, open when Ca2+ increases
53
What are calcium release channels?
Ca2+ release from intracellular stores e.g. endoplasmic reticulum and mitochondria
54
What are store-operated calcium release ion channels?
Calcium induced calcium release via channels located on the cellular membrane.
Mechanism, at present, is poorly understood
55
How is receptor expression controlled?
Receptor expression can vary within cells
Expression can depend on a number of factors:
- cell cycle
- cell function
- time of day
Regulation is poorly understood
56
How can disease target receptors?
Disease can target receptors in mainly two ways:
- Auto-antibodies directed against receptor proteins
- Mutations in genes encoding for specific receptors involved in signal transduction
E.g. myasthenia graves is a neuromuscular junction disorder, where auto-antibodies target Ach receptors
57
Draw a diagram to show how drugs can bind to receptors
See lecture 2 slides
58
What are bioassays?
Methods for comparing the properties of different substances or the same substance under different conditions
A estimate of the concentration or potency of a substance by measurement of the biological response produced on administration/application
59
What are the aims of bioassay?
To provide information that will predict the effect of a particular drug within a clinical situation
The overall aim is to improve patients suffering due to disorders/diseases
60
What are the models of bioassays?
Current models used in the assay of novel drugs/compounds:
- cell lines
Express human receptors
Engineered to express protein of interest
- Animal organs
- Animals (system approach)
Transgenic models; mimic various disease states
61
What are the uses of bioassays?
Measures the pharmacological activity of new or chemically undefined substances
Investigate the function of endogenous mediators
Measure drug toxicity and unwanted effects
Bioassays play a vital role in the development of new drugs
62
What are the two general principles of bioassays?
The use of standards:
Comparing the response of an unknown compound against a known compound. The use of controls
The design of bioassays:
A bioassay must provide an estimation of an effective dose/concentration of a compound or drug when compared to a known drug induced response
63
What does dose response in bioassays mean?
Assess the potency of drugs
Curves must be parallel for a valid comparison I.e. general sensitivity patterns should be similar
64
What are the two distinct categories of bioassays in humans?
Humans and clinical pharmacology:
Assess mechanisms of drug action in humans
Clinical trials:
Assess the effectiveness of a drug on treatment of a particular condition in human subjects
Provide a measure of therapeutic effectiveness of a drug
65
What is an example of a bioassay in humans?
Codeine and morphine.
Four subjects each given 2 doses of drug prior to assessing pain relief
Smaller doses of morphine were effective at achieving similar or better pain relief
66
How are animal models used in bioassay?
Drugs can be tested by inducing disease states in animals e.g. inducing vomiting by motion sickness and then providing an antidote
Complex disorders can be defined by observing physiological and behaviour responses in animals e.g. epilepsy. Induce an epileptic seizure and provide an antidote via drug intervention
67
What are the limitations of using animal models in bioassays?
They are not always the right way forward.
If it very difficult to model many human disorders in animals e.g. Alzheimer’s disease, depression, psychosis, Parkinson’s diseases
Some compounds can be species specific e.g. a drug may have a remedial effect in a mouse but may show no effect on humans as seen in some stroke drugs
68
How are genetic approaches used in animal models?
Using genetic tools it has been possible to generate animals that lack or over express particular genes
This can mimic many human disease/ disorder states e.g. obese mice, retinal degenerate mice, hypertensive rats
Transgenic animals:
The animal of choice tends to be a mouse due to complete genome identification.
Germ line mutation
‘Knock out mice’ a gene has been taken out, so the animals will lack a particular protein e.g. a specific receptor
‘Knock in mice’ a gene has been added to the genome, sighs animals will explores an extra protein e.g. a human specific receptor
69
What are the disadvantages of transgenic animals?
Manipulation of the genome can lead to adverse effects e.g.death during development
Transgenic adults may present with abnormal behaviour patterns compared with wild type mice (controls I.e. normal not transgenic)
Adding or taking out a gene could influence normal physiological function
Every cell in a transgenic animal is influence by the genetic manipulation. Therefore, systemic effects can be adverse due to lack of global gene function
70
What are clinical trials?
Critical phase of drug development
To observe the effects of new drugs on human subjects in comparison to a existing drug already in use
Novel compounds/drugs can also be compared to placebo effects
Trials are always randomised to minimise biasing the results/outcomes
Clinical trials can provide information on drug induced side effects in humans
71
How is bias avoided in clinical trials?
Randomisation:
Variables include ages, sex, disease severity
Difficult in small groups
Double blind technique:
Investigator or subject are unaware of the line of treatment
Can prevent investigator/subject biasing results knowing which drugs have been administered
72
What is the right sample size for clinical trials?
Ethical councils prevent samples sizes form being too large.
However smaller sample sizes can result in errors:
Type 1 error - false positive, there is a difference in using the novel drug but it is not true
Type II error - false negative, no difference is found using the novel drug, but there is a actually a difference
73
How are errors minimised in clinical trials?
Errors are minimised by using statistical tests
74
What are the measures of a clinical trial?
Ethics of a clinical trial, is it right?
Clinical trial results are valued by an overall measure of therapeutic efficacy,quality adjusted life-years. (QALYs)
Does the Novel drug increase life expectancy?
Does the novel drug increase the quality of life, improve health?
Both life expectancy and the quality of life need to be assessed together
75
How is benefit and risk balanced in clinical trial?
Therapeutic index
Individual variability not considered
Effective dose may vary considerably Within individuals due to size,sex, age etc
Very little value in measuring the clinical usefulness of a drug
76
How do you calculate therapeutic index?
Max non toxic dose divided by max effective dose
77
What is thalidomide?
Sedative developed in the late 1950’a and used as a sleeping pill.
Following use, it was quickly discovered as having antiemetic properties this given to pregnant woman for morning sickness
Severe side effects resulted in significant defects in children (phocomelia) Approximately 20,000 children affected
78
How does a drug exert its therapeutic class?
A drug binds to a particular site in the body, which then causes a cascade of effects, leading to a measurable therapeutic response
Or
A drug binds to a particular site in the body which prevents a cascade of effects. Leading to a measurable therapeutic response.
79
At what site do drugs act?
Receptors:
- ligand-gated ion channels, g-coupled receptors, enzyme linked (kinase) receptors (all in the outer membrane of the cell) and intracellular receptors
- will have an endogenous (natural) ligand
- involved in the maintenance of homeostasis (normal function)
Targets:
- Enzymes, carriers/transports, ion channels
80
How do drug-receptor interactions occur?
A drug first needs to bind to a receptor in order to have an effect (or the prevent an effect from occurring)
Receptors and drugs both have ‘shapes’ I.e 3D conformations based on their chemical structures
The shape of the drug and receptor have to match for an effect to occur. If the shape does not match, no effect occurs
Binding between a drug and a receptor is usually reversible due to non-covalent chemical bonds (H- bonds, van deer waals)
Binding between a drug (D) and a receptor (R) can be written mathematically
81
What is the mathematical equation of drug and receptor binding?
k on
| D+R ———> DR
82
Why do we need two rate constants to explain binding and non binding?
As binding is reversible, two rate constants are needed to explain binding (k on) and unbinding (k off)
83
What does affinity mean
Affinity measures the overall extent of binding between a drug and a receptor, taking into account binding and unbinding
84
What does Ka mean?
Ka = equilibrium affinity constant = k on / k off
Ka is expressed in inverse units of concentration eg M-1
85
What does Kd mean?
Kd = equilibrium dissociation constant = 1/ Ka = k off / k on
Describes the same idea as Ka but in reverse
Kd is expressed in units of concentration (eg M)
86
What does high affinity mean?
High affinity = a larger value of Ka = a smaller value of Kd
Means the drug binds more to the receptor
87
Describe the volume of binding at high and low concentrations
At high concentrations, not all the drug binds to the receptors
At low concentrations, most of the drug binds to the receptor
88
What conformational states can the drug-receptor complex exist as?
And what equation joins this information together?
Inactive denoted by DR
Active denoted by DR*
The effects comes after activation to DR * m
k on Ka
D+R ——-> DR ———> DR*
89
What does efficacy of a drug mean?
The efficacy of a drug is the ability to produce the activated for of the drug-receptor complex (and by extension the expected effect)
Efficacy is proportional to Ka/ k (Greek b with tail)
90
What two things are required for the expected effect of a drug to be obtained?
Affinity (binding) and efficacy (activation)
91
What does potency mean?
Potency is used to describe the overall activity of the drug, taking into account both affinity and efficacy
92
What is an agonist?
An agonist is a drug that mimics the effect of the endogenous (natural) ligand
Agonists will show affinity for the receptor I.e. they will bind to the receptor
Agonists will show efficacy at the receptor I.e. they will activate the receptor to the DR* state
The biological response to an agonist drug is usually shown with a dose response curve (see notes)
Usually the concentration is shown on the log10 scale
The maximum response to an agonist is known as the Emax
The agonist concentration of producing 59% of the maximum response is known as EC50
93
What does Emax mean?
An indirect measure of receptor occupancy
The maximum response
94
What does EC50 mean?
It is an indirect measure of affinity and shows the agonist concentration producing 50% of the maximum response
95
What is Emax and EC50 used for?
Can be used to compare between drugs
96
If drug A’s effect (Emax and EC50) is obtained at a lower concentration, what can the drug be described as?
Potent
97
Draw a drug dose response curve of 3 drugs and detail the most and least potent
See lecture notes
98
What is an antagonist?
An antagonist is a drug that prevents the effect of the endogenous (natural) ligand
Antagonists will show affinity at the receptor I.e. they will bind to the receptor
Antagonists do not show efficacy at the receptor I.e they will prevent activation of the receptor to the DR* state
Antagonists will prevent the natural ligand from binding to the receptor
The biological response to an antagonist drug is also shown with a dose response curve
99
Draw a dose response curve with parts labelled A,B,C and D
See lecture notes
Curve a is the normal endogenous ligand and is given alone
Curves B,C and D are where the same concentration of normal endogenous ligand is given in the presence of an antagonist at increasing concentrations
100
What happens to the EC50 and Emax of an antagonist?
The Emax remains the same as the normal endogenous ligand and antagonist compete for the receptor
The EC50 will increase depending on the effectiveness of the strength of the antagonist
101
What neurotransmitter acts on a lot of receptors around the body?
Adrenaline (epinephrine)
102
What does agonism (stimulation) of beta 1 receptors in the heart lead to?
Increased blood pressure
103
A receptor that is stimulated can cause increased blood pressure. What is this receptor and where is it found?
Beta 1 receptors in the heart
104
What does antagonism of beta 1 receptors lead to? And what condition can these be used to treat?
Reduced blood pressure and can be used in the treatment of hypertension
105
What do we need to give to reduce blood pressure?
Beta 1 antagonists
106
What are beta 1 receptors known as and give some examples of these:
Beta blockers
Propranolol
Atenolol
Metoprolol
107
What effect does agonism of beta 2 receptors have on the lungs?
Bronchial relaxation
108
To cause bronchial relaxation, what type of drug would be given and what receptors will these target?
Agonism of beta 2 receptors in the lungs
109
What do beta 2 receptors do and what condition are they used to treat?
They increase breathing capacity and are used in the treatment of asthma
110
Salbutamol, salmetarol and albuterol are examples of what drugs?
Beta 2 agonists
111
Give 3 examples of beta 2 agonists
Salbutamol, salmetarol and albuterol
112
Draw the two state model of receptor behaviour and state two assumptions
Ka K*(a)
| D+R —-> DR —-> DR* ——> biological effect
113
Draw the more complicated, reversible two-state model of receptor behaviour
See lecture notes
114
What does the reversible two state model of receptor behaviour show?
There will be an equilibrium between R and R* (no drug)
The ratio of R*/R is important
Some constitutive activity I.e. there will be a response even in the absence of antagonist or endogenous ligand
There will be an equilibrium between DR and DR* (with drug)
The ratio of DR*/DR is important
The difference in R*/R and Dr*/DR will determine how the drug behaves at the receptor and what the biological effect will be
115
What happens if DR*/DR >>> R*/R
Most, if not all, receptors become activated in the presence of the drug
The drug has much higher affinity for the R* state than the R state
Response is similar to that of the endogenous ligand
The drug is described as a full agonist
116
What happens if DR*/ DR > R*/R
Some receptors become activated in the presence of the drug
The drug has higher affinity for the R* state than the R state, but not as much as for the full agonist
Response is less than that of the endogenous ligand
Response is proportional to the % of activated receptors
The drug is described as a partial agonist
117
What happens if DR*/DR = R*/R
The presence of the drug has no effect on the number of receptors activated
There is no response to the endogenous ligand
Only constitutive activity occurs
The drug is described as a neutral antagonist
118
What happens if DR*/DR < R*/R
Some receptors become de-activated in the presence of the drug
Response is opposite to that of the endogenous ligand
Response is proportional to the % of unactivated receptors
The drug is described as a inverse agonist
119
Draw the summary graph of the reversible two state model of receptor behaviour
See lecture notes
120
What does intrinsic activity mean?
Efficacy. Given as a % relative to the effect of the endogenous ligand or full agonist
121
What does Emax mean?
Maximum biological response to an agonist
122
What does EC50 mean?
The agonist concentration producing 50% of Emax
123
What does EC50 and Emax not tell us about a drug?
About the efficacy
124
Draw the graph showing a comparison of agonist efficacy
See lecture notes
125
Draw the graph showing agonist potency
See lecture notes
126
Antagonists can either be ________ or __________
Competitive or non-competitive
127
What does a competitive antagonist mean?
Competitive antagonists compete with the natural ligand and agonists, so their effects can be overcome by increasing ligand or agonist concentration
= surmountable = reversible
Non competitive antagonists do not compete with the natural ligand or agonists I.e, they act at a slightly different site, so their effects can not be overcome by increasing ligand or agonist concentration
= non-surmountable = irreversible
128
Draw the graphs showing drug receptor activity in competitive and non-competitive antagonists and give details of what is shown
See lecture notes
129
What does IC50 mean?
The antagonist concentration required to reduce the effect of the natural ligand by 50%
130
What does IC stand for?
Inhibitory concentration
131
What does a smaller IC50 mean?
Implies a more effective antagonist
132
What does pA2 mean?
pA2= the negative log10 of the molar concentration of antagonist that makes it necessary to double the concentration of the agonist needed to elicit the original response obtained in the absence of antagonist
133
What does a larger pA2 mean?
A larger pA2, implies a more effective antagonist
134
What does pA2 and IC50 show?
They give similar information about how effective an antagonist is
135
Why is it important for a pharmacist to understand how drugs act in the body?
Prediction of the desired clinical effect
- action of the drug on the target receptor
Prediction of undesired clinical effects i.e side effects
- action of the drug on the other (off-target) receptors
Prediction of clinical doses
- dependant on Emax and EC50 (agonist) or IC50 (antagonist)
Prediction of interactions when two drugs are given together
Two drugs which have similar actions e.g. two agonists or two antagonists
Two drugs which have opposite actions e.g one agonist and one antagonist
Prediction of contraindications of drugs, this is dependant on the biology of the system being treated
136
What is hypertension commonly treated with?
Beta antagonists
137
What receptors does propranolol work on?
Propranolol is non-selective, I.e. it acts on both beta 1 and beta 2 receptors, so will have off target effects ( side effects) as well as an anti-hypertensive effect
138
What receptors does atenolol work on?
Atenolol is relatively beta 1 selective I.e. it acts much more specifically on beta 1 receptors, so has a more specific anti-hypertensive effect with fewer side effects
139
Is atenolol or propranolol more commonly prescribed for the treatment of hypertension ? Explain why
Atenolol is more commonly supplied because it is selective on b1 receptors so has less side effects that propranolol which is non-selective
140
What causes tremors (shaking)?
Stimulation of beta 2 receptors in skeletal muscle
141
What medication is given to reduce tremors?
Beta 2 antagonist
142
Which medication is more effective at treating tremors? Atenolol or propranolol?
Propranolol because it is non-selective so will help treat tremors.
Atenolol is beta 1 selective so will not help tremors which are caused by the stimulation of beta 2 receptors
143
What is asthma commonly treated with?
Beta 2 agonist e.g. salbutamol
144
Where are beta 1 receptors found?
The heart
145
Where are beta 2 receptors found?
In the lungs
146
What drugs are contraindicated in asthma patients?
Beta 2 antagonists because they cause broncho constriction
147
What is an undesired effect of salbutamol?
Tremor if given systematically due to its beta 2 agonist activity on skeletal muscle
