Basics of Pharmacology Flashcards
Includes information about pharmacokinetics, drug development and the autonomic nervous system (192 cards)
1
Q
What two main aspects of a drug does pharmacology study?
A
How the drug interacts with the body
How the body interacts with drugs
2
Q
What is medical pharmacology?
A
Concerned with the use of chemicals in the prevention, diagnosis and treatment of disease
Especially in humans
3
Q
What is toxicology?
A
Area of pharmacology concerned with the undesirable effects of chemicals on biological systems
4
Q
What is the most widely consumed psychoactive drug?
A
Caffeine
5
Q
What are the main two branches of pharmacology?
A
Toxicology
Medical pharmacology
6
Q
Where is caffeine found?
A
Coffee
Cocoa
Tea
7
Q
What class of drug is caffeine?
A
Methylxantheine
8
Q
What is another name for caffeine?
A
Xantheine
9
Q
What are the two ways in which caffeine works?
A
Inhibits PDE
Blocks the adenosine receptor
10
Q
What was the original way the effects of caffeine were identified?
A
Chromatography to extract
Determine the chemical structure through mass spectrometry, UV, IR and NMR
11
Q
What do caffeine’s effect tell us about its targets in the body?
A
Since the effects are instant, the target cannot be nucleic acids since this would take too long
12
Q
How does caffeine inhibt PDE?
A
Neurons that synapse on heart cells and lungs release NT which cause the release of adenynyl cyclase when bound to their receptors.
Adenynyl cyclase converts ATP to cAMP
cAMP is degraded into AMP by PDE, making its effect short-lived
Caffeine inhbits the effect of PDE, causing the accumulation of cAMP
13
Q
What are the effects of cAMP?
A
Increased heart rate
Bronchodilation
14
Q
How does caffeine affect the adenosine receptor?
A
Blocks it
Adenosine is a neuromodulator that leads sleepiness
Caffeine competes with adenosine and its receptor, causing the subject to feel less sleepy
15
Q
What biological chemical is structurally similar to caffeine?
A
ATP
16
Q
What is the effective dose (ED50)?
A
Dose at which a drug is effective for 50% of the population
Concentration of drug against effectiveness can be plotted on quantal dose response curves
17
Q
What is the toxic dose (TD50)?
A
The dose at which a drug is toxic for 50% of the population
18
Q
What is the lethal dose (LD50)?
A
The dose at which the drug is lethal for 50% of the population
19
Q
What is the therapeutic index?
A
Indicates the toxicity of a drug
TD50/ED50
20
Q
The higher the TI, the more safe the drug is
TRUE or FALSE?
A
TRUE
TD50 is the numerator, so the higher the TI, the higher the dose required for the drug to be toxic
21
Q
Examples of drugs with low therapeutic indeces
A
Foxgloves = digoxin
Chemotherapy
22
Q
Definition of pharmacology
A
Study of how drugs affect the function of host tissues or combat infectious organisms
23
Q
What are most drug targets?
A
Receptors
Enzymes
Ion channels
Transporters
DNA
24
Q
What is a desirable aspect in drugs?
A
Higher affinity for target than other bonding sites
25
What benefits are there to drugs having a higher affinity for target than other bonding sites?
Ensures the drug's free concentration is not reduced by non-productive binding
Allows lower doses to be used, reducing the risk of unwanted actions at other binding sites
26
What are receptors?
Protein macromoleules on or in cells that act as recognition sites for endogenous ligands
Initiate cellular responses in a coordinated manner
27
What is an agonist?
A drug that binds to a receptor and activates a cell's response similar to an endogenous/exogneous ligand
28
What is an antagonist?
A drug that reduces or inhibits the action of an agonist
29
What are the two aspects of the action of agonists when they bind to their receptor?
Agonist -receptor interaction - affinity and occupancy
Agonist-induced response - efficacy
30
What is the Law of Mass action?
The rate of reaction is equal to the product of the concentrations of the reactants
31
What is Ka?
Dissociation equilibrium for the binding of the drugs at the receptors
The reciprocal of the affinity constant
Value of Ka is equal to the concentration of agonist drug that results in occupancy of 50% of the receptors
pKa = pH at which 50% of receptors are occupied by the drug
32
What is the Hill-Langmuir equation?
Relationship at equilibrium between Ka, [agonist drug] and the proportion of receptor occupied
What percentage of binding sites is occupied by ligands
33
Why is it not possible to know with certainty the concentration of drugs at the receptors?
Because of factors that complicate the picture, including:
1. Enzymatic degradation
2. Binding to tissue components
3. Problems related to diffusion of drug to site of action
34
What is a full agonist?
Maximum response produced by a drug correpsonds to the maximum response that the tissue can give
35
What is a partial agonist?
They do not give the maximum tissue response in any concentration
36
Why do partial agonists not evoke the full response?
They bind to the same number of receptors as the full agonists = not to do with affinity
But they are less able to elicit a response from the receptors to which they bind
37
What is efficacy?
Ability of a drug, after binding to its receptor, to activate the transduction mechanisms that lead to a response
38
What is an inverse agonist?
Blocks the endogenous activity of a constitutively active receptor
39
What are the types of antagonism?
Competitive antagonism
Irreversible antagonism
Physiological antagonism
Non-competitive antagonism
Pharmacokinetic antagonism
Chemical antagonism
40
What is competitive antagonism?
Binds to a receptor, preventing the binding of an agonist
41
How can we overcome the effect of a competitive antagonist?
The binding is reversible
Overcome by raising the concentration of the agonist
42
What is the Kb?
Reciprocal for the affinity of the antagonist for its receptor
43
What is irreversible competitive antagonism?
The antagonist binds irreversibly
Usually because of the formation of covalent bonds
44
What is physiological antagonism?
Antagonist has the opposite biological action of agonist
Antagonist reduces the effect of an agonist, but through working on different receptors
45
What is Non-competitive antagonism?
Antagonist does not block the receptor itself, but the signal transfuction process initiated by receptor activation
46
What is pharmacokinetic antagonism?
Reduces the free concentration of a drug at its target by
- reducing drug absorption
- accelerating renal or hepatic elimination
47
What is chemical antagonism?
Combines with the drug to produce an insoluble and inactive complex
48
How do drugs affect the body?
Acting on receptors
Inhibiting carriers
Modulating or blocking ion channels
Inhibiting enzymes
49
What are the four types of receptor?
G-protein coupled
Ionotropic
Receptors that affect gene transcription
Receptors linked to enzymes
50
What is the structure of G-protein coupled receptors?
Polypeptide chain
Seven transmembrane helices
51
What is the response time of G-protein coupled receptors?
Seconds
52
How do G-protein coupled receptors carry out their function in the cell?
Signal transduction occurs by activation of particular proteins that modulate enzyme activity/ion channel function
53
What is another name for G-protein coupled receptors?
Metabotropic receptors
54
What are the 3 types of G-proteins in the human body?
Gq
Gs
Gi
55
What is the target activated by Gq?
What is the consequence of this activation?
Phospholipase C
PIP2 activation
IP3 activation, leading to the release of Ca2+ from intracellular stores
DAG activation, which activates protein kinase C
56
What is the target activated by Gs?
What is the consequence of this activation?
Adenylate cyclase
Converts ATP to cAMP
Activates protein kinase A
57
What is the target activated by Gi?
What is inhibited by Gi activation?
What is the consequence of this target activation?
K+ channels in the membrane
Adenylate cyclase
Increased opening of the K+ channels leads to hyperpolarization
58
What are the 3 subunits of G-proteins?
Alpha
Beta
Gamma
59
Describe the activation of G-protein
Before agonists bind, the G protein is bound to the transmembrane glycoprotein receptor
GDP occupies the binding site on the a-subunit
When the agonist binds to the receptor, the alpha subunit separates from the closely associated beta and gamma subunits
GDP is replaced by GTP
Both the alpha and beta/gamma subunits can interact with their target enzymes
60
What are ionotropic receptors?
They are receptors linked to ion channels
Channel is a part of the receptor
61
What is the response time of ionotropic receptors?
Milliseconds
62
How do ionotropic receptors work?
Agonist binds
Channel opens
Lets ions through
63
What is an example of an ion channel?
Nicotinic receptor
64
What are nuclear receptors?
Receptors linked to gene transcription
Regulate gene transcription
65
Where are nuclear receptors found?
Some are found in the cytosol and migrate to the nucleus after binding to a ligand
66
Describe how nuclear receptors work
Cytoplasmic receptor binds to its agonist
The receptor changes conformation and enters the nucleus
The complex interacts with DNA and alters gene expression
The transcribed genes induce sysnthesis of some mediator proteins and inhibit the synthesis of others
67
How do receptors linked to enzymes work?
Activation initiates an intracellular pathway involving cytosolic and nuclear transducers and eventually gene transcriptors
68
Describe the structure of receptors linked to enzymes
Contain large extracellular portion that contains the binding sites for ligands
Contain intracellular portion that has integral enzyme activity
69
What are the target proteins of the cascades stimulates in receptors linked to enzymes?
Ion channels
Transporters
Contractile proteins
Secretory mechanisms
70
Describe how tyrosine kinases become activated
Unbound receptors contain tyrosine subunits bound to their structure
Agonist binds to the 2 receptor sites
Leads to dimerisation of these 2 receptors
The tyrosine kinases in each receptor phosphorylate using phosphate from ATP
SH2-containing proteins bind to phosphate residues on tyrosine of the dimers and activate intracellular pathways
Depending on the kinases they phosphorylate, the cell will respond differently
71
What are the two main types of membrane transport proteins?
ATP-powered ion pumps
Transporters
72
What are the three principal ion pumps?
Sodium pump
Calcium pump
Na+/H+ pump
73
What is the importance of sodium pumps?
Maintain osmotic balance, cell volume and membrane potential
In many cells, it is the primary mechanism for transporting Na+ outside the cell
74
What are the two main transporters involved in drug action?
Symptorters
Antiporters
75
How do drugs target different channels or receptors?
Some drugs interact directly with ion channels
Some drugs produce effects on enzyme reactions by substrate competition or modifying the enzyme
76
What do bioassays do?
Measures the action of drugs
77
Why do we need to measure the action of drugs?
Investigating a new/chemically unknown substance in drug development
Investigating endogenous mediators
Measuring unwanted actions of drugs
78
What are the two types of responses a drug can have?
Graded
All or none (quantal)
79
How does a graded response appear on a bioassay?
Expressed as the relative efficiency of each drug carrying out a graded response
One of the drugs act as a standard to compare the effect of the new drug
The distance between them reveals their relative potency
80
What does the distance between two lines in a bioassay for two graded response drugs relate to?
The relative potency of each
81
How is an all-or-none response shown in a bioassay?
Expressed as the percentage of individuals giving the all-or-none response
82
What are comparative bioassays?
Compare the biological activity of different drugs
Comparison of ED50 for each drug can be used to get a rough estimation of their relative potencies
83
What are the 5 stages of drug development?
Preclinical
Phase I
Phase II
Phase III
Phase IV
84
Potency always relates directly to therapeutic usefulness
TRUE or FALSE
FALSE
85
What are the objectives of clinical trials?
Determine the maximum achievable response
Determine the incidence of unwanted effects
Objective assessment of two or more methods of treatment
86
Do clinical trials provide information on the comparative efficacy or potency of two drugs?
Efficacy
Because it is difficult to compare the log dose-response curves for test and control drugs
87
What are two important principles of conducting clinical trials?
Random allocation of test and control groups
Double-blind design
88
What is the placebo effect?
An inert preparation may be found to have demonstrable effect if the patient believes it to be pharmacologically effective
89
What is meta-analysis?
Combines the results of several independent trials with the hope of achieving significant result
This is useful because it is often difficult to recruit many subjects
90
What determines the number of subjects required for clinical trials?
The significance level sought after and the power of the trial
Influenced by type I (proposing a difference when none exists) errors and type II (failure to detect a real difference) errors
91
Why is the LD50 a poor measure of human toxicity?
Measures only death, not other sublethal effects
Almost certainly be different in humans
Neglects adverse long-term effects
No account of idiosynchratic responses
92
What is pharmacokinetics?
Explores the changes in drug concentration in the body with time
93
Why is pharmacokinetics important?
Allows us to understand the time course of drug effects
94
What have autoradiographs and chemical analysis shows about drug distribution?
Drugs do not penetrate uniformly throughout the body
95
How do we split the body into compartments?
Depending on how tissues behave.
Tissues that behave similarly are thought to be in the same compartment.
96
What is the use of compartments?
Describe the time course for drug disposition and predict the changes in concentration that occur following administration
97
What are the two models of drug-distribution?
One-compartment - drug distributes throughout the body at the same rate
Two-compartment - drug equilibrate in different tissues at different rates. Well perfused organs first, then poorly perfused organs.
Two compartments are: well perfused vs poorly perfused organs
98
Examples of rapidly equilibrating tissues
Lung
Kidneys
99
Compare the pharmacokinetic profile of one and two-compartment models
In one-compartment models, the plasma concentration declines exponentially with time at the same rate = zero-order
In two-compartment models, the graph shows two sections: an initial steep decline as the drug enters the highly perfused organs, and then a plateu phase as the drug is distributing to the poorly perfused organs
100
What is the plasma half-life?
Time taken for any given plasma concentration to decrease by 50%
101
We can determine the plasma half-life of a zero order drug
TRUE or FALSE
FALSE
102
Why can we not determine the plasma half-life of a zero-order drug?
Unstable
The half-life changes with the dosage
103
What is zero-order kinetics?
The rate of the process is independent of the drug's concentration
104
An important aspect of carrier-mediated transport
Drugs and biotransformations are saturable phenomena that in the steady state follow Michaelis-Menten kinetics
Steady state = the rate of complex formation (decreases) is equal to the rate of product formation (increases)
105
What does the volume of distribution tell us?
How extensively the drug has distributed in the body
The higher the volume of distribution, the more the drug has become distributed
The lower the volume of distribution, the more likely the drug is confined to the bloodstream
106
What is the volume of distribution of albumin?
Low
5 litres
Large protein, so does not pass through into the interstitial environment and stays in the blood
107
What is the volume of distribution of glucose?
High
50 litres
Can pass through into all body compartments, including the blood, interstitial fluid and intracellular environment
108
What is the volume of distribution of sodium chloride?
Medium
20 litres
Passes into the interstitial fluid but can not efficiently enter the intracellular environment
109
What is the definition of clearance?
The volume of plasma cleared of drug per unit time
Elimination rate/concentration
110
What is the total body clearance?
Sum of all the clearances occurring by whatever routes are applicable to the drug in question
111
What, in terms of clearance, is favourable for zero-order drugs?
The drug is completely cleared from the system following elimination
First-order drugs are never fully cleared from the system
112
Why are patients taking contraceptive pills whilst on short course of broad-spectrum antibiotics advised to take other contraceptive precautions?
When oestrogen enters the blood, it passes through the liver where it is metabolised by the P450 system
This conjugates the oestrogen, rendering it inactive.
Conjugated form passes through the hepatic portal vein where the microbiome deconjugates it, making it active again and therefore increasing its half-life
113
Describe the cumulative effect some drugs have during their clearance
Since most drugs are eliminated exponentially, whenever a second dose is administered, some of the preceeding dose will still be in the body and the new peak concentration will exceed the original dose
114
Describe the plateu phase for drug clearance
Elimination of drug increases until a plateu is reached where the whole of the dose is eliminated during the dosing interval
The rate of approach to plateau is determined by the elimination rate constant
115
What is the equation for drug plasma concentration
Dose rate/clearance
Can be used to calculate the dose rate, if you know the clearance and drug dose required
116
What is the steady state for drug elimination?
The rate of drug administration equals the elimination rate
117
What are two approaches to treating drug overdoses in children?
Kinetics - stop absorption to prevent distribution to other organs
Dynamic - give proper antidote
118
Describe the use of ferrous sulphate
Ferrous sulphate absorbs through kinase-mediated absorption
Vitamin C is needed to transform Fe3+ into Fe2+ to be absorbed
Since iron is something humans need, we have developed efficient systems to transport the compound into our system through evolution
119
Describe aspirin absorption
Aspirin is absorbed passively through lipids
There are two forms of aspirin: protonated (AH) or ionised (A-)
AH-> A- + H+
The protonated form of aspirin can pass through lipids
In an acidic environment like the stomach, the equilibrium favours the protonated form, so there will be more absorption
120
How can doctors manipulate the absorption of aspirin clinically?
To minimise the reabsorption in the kidney, favouring the equilibrium towards the ionised form will be effective
Increasing the pH of the urine and making it more alkaline will reduce the reabsorption of the protonated form
121
What is aspirin?
A weak acid
122
What is paracetamol?
A weak base
123
How is the absorption of aspirin and paracetamol different?
It all boils down to the behaviour of the two
Aspirin is a weak acid, and dissociates in the body from the protonated to the ionised form
AH -> A- + H+
Absorption therefore prefers acidic conditions
Paracetamol is a weak base, and dissociates in the body to form both the protonated an ionised form
B + H+ -> BH+
Absorption therefore prefers alkaline environments
124
What does A- in aspirin dissociation represent?
The ionised form
125
What does AH in aspirin dissociation represent?
The protonated form
Passes through lipid membranes easily
126
What does BH+ in paracetamol dissociation represent?
Both the protonated and ionised forms
127
What does B in paracetamol dissociation represent?
The form that is highly absorptive
128
What causes anaphylaxis?
Bronchoconstriction and systemic vasodilation caused by the release of histamines and leukotrienes
129
What are two ways two treat anaphylaxis?
Block the inflammatory mediators released
Treat the symptoms
130
Why is it not easy to treat anaphylaxis by blocking the release of inflammatory mediators?
We don't know all the inflammatory mediators released
131
What is the standard of care of treating anaphylaxis?
Treating the symptoms
Adrenaline
Acts on bronchi and vasculature to counteract the effect of allergic reactions
Adrenaline is a physiological antagonist of histamine and leukotriene
132
Describe a clinical use of competitve antagonists
Opioid overdose
Causes death through binding to receptors on the brain leading to decreased respiratory rate
Naloxone has a similar structure to opioid acts on the opioid receptor
133
Describe a clinical use of a chemical antagonist
Wilson's disease
Genetic disorder characterised by copper poisoning in the body due to an inability to regulate the metal
Penicillamide, a chelator that binds to copper ions, removes the free circulating copper and allows it to be removed by the kidneys
134
Describe the history of pharmacological antagonism
Paul Ehrlich discovered the first true antibiotic which was aimed at a specific pathogen
This was termed drug 606
135
What are the first two things you want to find out about a drug?
If it binds to a wanted receptor
Use a concentration occupancy graph
What the effect of a drug is
This is calculated through the EC50
136
What are the two ways in which pharmacological agonists differ?
Potency
Efficacy
137
What does potency refer to?
The amount of drug necessary to produce an effect
Determined normally by the EC50
The lower the EC50, the more potent the drug
138
What does efficacy refer to?
The maximum response a drug can cause
The Emax determines the efficacy
The larger the Emax, the more efficient the drug is
139
Show how two drugs can differ in their potency
Loop diuretics and thiazide diuretics are both used to treat hypertension
Loop diuretics are very potent and only used in times of emergency
Thiazide diuretics are used to treat chronic hypertension
140
Clinical examples of full and partial agonists
Morphine and buprenorphine are both used for pain treatment
Buprenorphine does not cause full response on the cell it binds to, since it does not activate the intracellular transduction mechanisms fully = partial agonist
141
Why is it important to distinguish between full and partial agonists?
If you use a full agonist to treat pain and then change to a partial agonist, the pain for the patient will increase
Buprenorphine administered with morphine will outcompete morphine through competitive binding to the opioid receptors and cause the pain to increase
paracetamol -> buprenorphine -> morphine
142
What are pure antagonists?
Do not elicit a response unless the agonist has bound to the receptor
143
Example of a reversible antagonist
Propanolol
144
Example of an irreversible antagonist
Aspirin - forms double bonds
145
What happens to the dose response curves when administering a reversible antagonist?
The Emax stays the same (efficacy)
The EC50 increases (potency decreases)
146
What happens to the dose response curves when administering an irreversible antagonist?
The Emax decreases
Some receptors are lost through irreversible binding
147
How long does the effect of an irreversible antagonist last?
Until the receptor becomes degraded and a new one is formed
148
Example of a irreversible antagonist
Aspirin
Inhibitor of cyclooxygenase
Acetylates the enzyme until it becomes proteolysed
149
How can the effect of an inverse agonist be investigated?
Through isolating heart cells and washing away the epinephrine present
Binding adrenaline through chemical antagonists prevents it from having any action on the heart
150
Describe the special measures that need to be taken when resecting a pheochromocytoma
The benign tumour makes adrenaline, so touching the tumour during surgery leads to a hypertensive crisis
To prevent this we need to use adrenaline antagonists that bind to the adrenoreceptors
These have to be irreversible, because the amount of adrenaline released during surgery will counteract the action of the antagonists
151
Why does withdrawal happen?
Cells exposed to opioids have hypertrophied adenylyl cyclase since the adenylate cyclase has become inhibited by morphine
The molecule becomes overly active to compensate for the inhibitory activity of the opioid, producing more cAMP
When the patient stops taking morphine, the adenylyl cyclase activity remains high and so a lot of cAMP is produced, which causes withdrawal symptoms
152
What are the two drugs used to tackle withdrawal of opioids?
Methadone - full agonist, long half-life
Buprenorphone - partial agonist, stops craving, competitive antagonist for opioid receptors with heroin
Long half-life means that the effect of the treatments are more drawn out and more time is needed before the patient suffers from withdrawal symptoms
153
Why are partial agonists better than full agonists in treating withdrawal?
Full agonists act like the drug itself
Partial agonists inhibit the effect of the drug whilst reducing the withdrawal symptoms
154
Where is acetylcholine found in the body?
Neuromuscular junction
Autonomic ganglia
Postganglionic parasympathetic nerve endings
Synapses in the CNS
155
What are the two types of receptor that bind to acetylcholine?
Nicotinic
Muscarinic
156
Describe the synthesis of acetylcholine
Synthesised by choline acetyltransferase
Combines choline and acetic acid
157
What type of molecule is acetylcholine?
Ester
158
How is acetylcholine released from neurons?
Ca2+ mediated exocytosis
Triggered by a nerve action potential
159
What process in acetylcholine action is an important target for pharmacology?
Modulation of Ach release by presynaptic receptors
160
Inhibition of choline uptake is clinically useful
TRUE or FALSE
FALSE
161
Inhibition of ACh release is not clinically useful
TRUE or FALSE
TRUE
162
Which presynaptic receptors inhibit the release of acetylcholine in postganglionic nerve endings?
A2-adrenoceptors
Muscarinic receptors
Opioid receptors
163
Which presynaptic receptors facilitate the release of Ach?
B-adrenoceptors (parasympathetic nerve endings)
Nicotinic receptors (NMJ)
164
Example of a drug/toxin that inhibits Ach release
Botulinum toxin
Inhibits the fusion of Ach vesicles with the cell membrane
165
What type of molecule is Ach?
Ester
166
Where are muscarinic receptors found?
Smooth muscle
Cardiac muscle
Glands
CNS neurons
167
Where are nicotinic receptors found?
Neuromuscular junction
Autonomic ganglia
Adrenal medulla
CNS neurons
168
Which 5 classes of drugs affect the action of cholinergic receptors?
Non-depolarising agents (neuromuscular blockers)
Depolarising agents (neuromuscular blockers)
Anticholinesterases
Agonists
Antagonists
169
Where are nicotinic receptors mostly found?
Postsynaptic neuron
170
Describe the structure of nicotinic receptors
Cation channel
5 subunits
In the NMJ - 2a, b, d, e
In the neurons - 2a, 3b
171
What is the consequence of nicotinic channel opening?
Na+ influx
Membrane depolarisation
Action potential initiation
172
Describe the function of non-depolarising blocking agents
Competitive antagonists
Effect is reversed by anticholinesterases
173
Describe the function of depolarising blocking agents
Activates the receptor
Causes maintained depolarisation
Prevents the end-plate potential from producing a propagated action potential
174
What are the unwanted effects of neuromuscular blockers (depolarising and non-depolarising agents)?
Hypertension
Bradycardia
Cardiac dysrhythmias caused by increased K+ release
175
What are the clinical uses of neuromuscular blockers?
Muscle relaxation in anaesthetised patients during surgery
Prevents injuries during electroconvulsive therapy
176
What are the effects of ganglion-blocking agents?
Block sympathetic and parasympathetic transmission
Caused by receptor antagonism or direct channel block
177
What is the clinical use of ganglion-blocking agents?
Lower blood pressure during surgery
178
Describe the structure of muscarinic receptors
G-protein coupled receptor
7 transmembrane proteins in their amino acid sequence
179
What are the 5 muscarinic subtypes?
M1 (neural) - Gq
M2 (cardiac) - Gi
M3 (glandular) - Gq
180
What are the actions of M1 muscarinic agonists ?
Gastric acid secretion
181
What are the actions of M2 muscarinic agonists?
Decreased rate and force of heartbeat
182
What are the actions of M3 muscarinic agonists?
Smooth muscle contraction
Glandular secretion
Vasodilation via release of endothelial NO
183
What is the effect of muscarinic antagonists?
Inhibition of secretions
Tachycardia
Relaxation of smooth muscle
Antiemetic action
Antiparkinsonian action
184
Clinical use for muscarinic agonists
Sinus bradycardia
Bronchospasm reduction in asthma
Reduce acid secretions in ulcers
185
Clinical use of muscarinic antagonists
Lower intraocular pressure in glaucoma
Increases motility in GI
186
What are the two forms of cholinersterases?
Acetylcholinesterase
Butyrylcholinesterase
187
Describe the process of ACh hydrolysis
Ach binds to enzyme
Acetyl group is transferred to a serine OH on the enzyme, resulting in transiently acetylated enzyme + free choline
Hydrolytic cleavage of the serine-acetyl bond releases acetyl group
188
What is the action of anticholinesterases?
Inhibit cholinesterase, leading to the enhancement of cholinergic transmission
189
What types of anticholinesterases can be found in the body?
Short acting
Medium duration of action
Irreversible -organophosphates
190
What are the effects of anticholinesterases?
Autonomic effects - bradycardia, hypotension
Action on NMJ - muscle fasciculation, increased twitch tension
Action at CNS - respiratory failure, loss of consciousness
191
What are the clinical uses of anticholinesterases?
Eyedrops to treat glaucoma
Myasthenia gravis
Alzheimer's disease
192
What does the pKa of aspirin (3.4) mean?
At a pH of 3.4, half of asipirin is protonated and half is ionised
