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Pharmacology > Basics of Pharmacology > Flashcards

Basics of Pharmacology Flashcards

Includes information about pharmacokinetics, drug development and the autonomic nervous system

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

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2
Q

What is medical pharmacology?

A

Concerned with the use of chemicals in the prevention, diagnosis and treatment of disease

Especially in humans

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3
Q

What is toxicology?

A

Area of pharmacology concerned with the undesirable effects of chemicals on biological systems

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4
Q

What is the most widely consumed psychoactive drug?

A

Caffeine

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5
Q

What are the main two branches of pharmacology?

A

Toxicology

Medical pharmacology

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6
Q

Where is caffeine found?

A

Coffee

Cocoa

Tea

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7
Q

What class of drug is caffeine?

A

Methylxantheine

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8
Q

What is another name for caffeine?

A

Xantheine

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9
Q

What are the two ways in which caffeine works?

A

Inhibits PDE

Blocks the adenosine receptor

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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

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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

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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

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13
Q

What are the effects of cAMP?

A

Increased heart rate

Bronchodilation

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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

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15
Q

What biological chemical is structurally similar to caffeine?

A

ATP

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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

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17
Q

What is the toxic dose (TD50)?

A

The dose at which a drug is toxic for 50% of the population

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18
Q

What is the lethal dose (LD50)?

A

The dose at which the drug is lethal for 50% of the population

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19
Q

What is the therapeutic index?

A

Indicates the toxicity of a drug

TD50/ED50

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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

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21
Q

Examples of drugs with low therapeutic indeces

A

Foxgloves = digoxin

Chemotherapy

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22
Q

Definition of pharmacology

A

Study of how drugs affect the function of host tissues or combat infectious organisms

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23
Q

What are most drug targets?

A

Receptors

Enzymes

Ion channels

Transporters

DNA

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24
Q

What is a desirable aspect in drugs?

A

Higher affinity for target than other bonding sites

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25
Q

What benefits are there to drugs having a higher affinity for target than other bonding sites?

A

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

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26
Q

What are receptors?

A

Protein macromoleules on or in cells that act as recognition sites for endogenous ligands

Initiate cellular responses in a coordinated manner

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27
Q

What is an agonist?

A

A drug that binds to a receptor and activates a cell’s response similar to an endogenous/exogneous ligand

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28
Q

What is an antagonist?

A

A drug that reduces or inhibits the action of an agonist

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29
Q

What are the two aspects of the action of agonists when they bind to their receptor?

A

Agonist -receptor interaction - affinity and occupancy

Agonist-induced response - efficacy

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30
Q

What is the Law of Mass action?

A

The rate of reaction is equal to the product of the concentrations of the reactants

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31
Q

What is Ka?

A

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

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32
Q

What is the Hill-Langmuir equation?

A

Relationship at equilibrium between Ka, [agonist drug] and the proportion of receptor occupied

What percentage of binding sites is occupied by ligands

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33
Q

Why is it not possible to know with certainty the concentration of drugs at the receptors?

A

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
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34
Q

What is a full agonist?

A

Maximum response produced by a drug correpsonds to the maximum response that the tissue can give

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35
Q

What is a partial agonist?

A

They do not give the maximum tissue response in any concentration

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36
Q

Why do partial agonists not evoke the full response?

A

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

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37
Q

What is efficacy?

A

Ability of a drug, after binding to its receptor, to activate the transduction mechanisms that lead to a response

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38
Q

What is an inverse agonist?

A

Blocks the endogenous activity of a constitutively active receptor

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39
Q

What are the types of antagonism?

A

Competitive antagonism

Irreversible antagonism

Physiological antagonism

Non-competitive antagonism

Pharmacokinetic antagonism

Chemical antagonism

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40
Q

What is competitive antagonism?

A

Binds to a receptor, preventing the binding of an agonist

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41
Q

How can we overcome the effect of a competitive antagonist?

A

The binding is reversible

Overcome by raising the concentration of the agonist

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42
Q

What is the Kb?

A

Reciprocal for the affinity of the antagonist for its receptor

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43
Q

What is irreversible competitive antagonism?

A

The antagonist binds irreversibly

Usually because of the formation of covalent bonds

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44
Q

What is physiological antagonism?

A

Antagonist has the opposite biological action of agonist

Antagonist reduces the effect of an agonist, but through working on different receptors

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45
Q

What is Non-competitive antagonism?

A

Antagonist does not block the receptor itself, but the signal transfuction process initiated by receptor activation

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46
Q

What is pharmacokinetic antagonism?

A

Reduces the free concentration of a drug at its target by

  • reducing drug absorption
  • accelerating renal or hepatic elimination
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47
Q

What is chemical antagonism?

A

Combines with the drug to produce an insoluble and inactive complex

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48
Q

How do drugs affect the body?

A

Acting on receptors
Inhibiting carriers
Modulating or blocking ion channels
Inhibiting enzymes

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49
Q

What are the four types of receptor?

A

G-protein coupled

Ionotropic

Receptors that affect gene transcription

Receptors linked to enzymes

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50
Q

What is the structure of G-protein coupled receptors?

A

Polypeptide chain

Seven transmembrane helices

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51
Q

What is the response time of G-protein coupled receptors?

A

Seconds

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52
Q

How do G-protein coupled receptors carry out their function in the cell?

A

Signal transduction occurs by activation of particular proteins that modulate enzyme activity/ion channel function

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53
Q

What is another name for G-protein coupled receptors?

A

Metabotropic receptors

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54
Q

What are the 3 types of G-proteins in the human body?

A

Gq
Gs
Gi

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55
Q

What is the target activated by Gq?

What is the consequence of this activation?

A

Phospholipase C

PIP2 activation
IP3 activation, leading to the release of Ca2+ from intracellular stores
DAG activation, which activates protein kinase C

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56
Q

What is the target activated by Gs?

What is the consequence of this activation?

A

Adenylate cyclase

Converts ATP to cAMP
Activates protein kinase A

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57
Q

What is the target activated by Gi?

What is inhibited by Gi activation?

What is the consequence of this target activation?

A

K+ channels in the membrane

Adenylate cyclase

Increased opening of the K+ channels leads to hyperpolarization

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58
Q

What are the 3 subunits of G-proteins?

A

Alpha

Beta

Gamma

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59
Q

Describe the activation of G-protein

A

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

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60
Q

What are ionotropic receptors?

A

They are receptors linked to ion channels

Channel is a part of the receptor

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61
Q

What is the response time of ionotropic receptors?

A

Milliseconds

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62
Q

How do ionotropic receptors work?

A

Agonist binds

Channel opens

Lets ions through

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63
Q

What is an example of an ion channel?

A

Nicotinic receptor

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64
Q

What are nuclear receptors?

A

Receptors linked to gene transcription

Regulate gene transcription

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65
Q

Where are nuclear receptors found?

A

Some are found in the cytosol and migrate to the nucleus after binding to a ligand

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66
Q

Describe how nuclear receptors work

A

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

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67
Q

How do receptors linked to enzymes work?

A

Activation initiates an intracellular pathway involving cytosolic and nuclear transducers and eventually gene transcriptors

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68
Q

Describe the structure of receptors linked to enzymes

A

Contain large extracellular portion that contains the binding sites for ligands

Contain intracellular portion that has integral enzyme activity

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69
Q

What are the target proteins of the cascades stimulates in receptors linked to enzymes?

A

Ion channels

Transporters

Contractile proteins

Secretory mechanisms

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70
Q

Describe how tyrosine kinases become activated

A

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

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71
Q

What are the two main types of membrane transport proteins?

A

ATP-powered ion pumps

Transporters

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72
Q

What are the three principal ion pumps?

A

Sodium pump

Calcium pump

Na+/H+ pump

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73
Q

What is the importance of sodium pumps?

A

Maintain osmotic balance, cell volume and membrane potential

In many cells, it is the primary mechanism for transporting Na+ outside the cell

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74
Q

What are the two main transporters involved in drug action?

A

Symptorters

Antiporters

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75
Q

How do drugs target different channels or receptors?

A

Some drugs interact directly with ion channels

Some drugs produce effects on enzyme reactions by substrate competition or modifying the enzyme

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76
Q

What do bioassays do?

A

Measures the action of drugs

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77
Q

Why do we need to measure the action of drugs?

A

Investigating a new/chemically unknown substance in drug development

Investigating endogenous mediators

Measuring unwanted actions of drugs

78
Q

What are the two types of responses a drug can have?

A

Graded

All or none (quantal)

79
Q

How does a graded response appear on a bioassay?

A

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
Q

What does the distance between two lines in a bioassay for two graded response drugs relate to?

A

The relative potency of each

81
Q

How is an all-or-none response shown in a bioassay?

A

Expressed as the percentage of individuals giving the all-or-none response

82
Q

What are comparative bioassays?

A

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
Q

What are the 5 stages of drug development?

A

Preclinical

Phase I

Phase II

Phase III

Phase IV

84
Q

Potency always relates directly to therapeutic usefulness

TRUE or FALSE

A

FALSE

85
Q

What are the objectives of clinical trials?

A

Determine the maximum achievable response

Determine the incidence of unwanted effects

Objective assessment of two or more methods of treatment

86
Q

Do clinical trials provide information on the comparative efficacy or potency of two drugs?

A

Efficacy

Because it is difficult to compare the log dose-response curves for test and control drugs

87
Q

What are two important principles of conducting clinical trials?

A

Random allocation of test and control groups

Double-blind design

88
Q

What is the placebo effect?

A

An inert preparation may be found to have demonstrable effect if the patient believes it to be pharmacologically effective

89
Q

What is meta-analysis?

A

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
Q

What determines the number of subjects required for clinical trials?

A

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
Q

Why is the LD50 a poor measure of human toxicity?

A

Measures only death, not other sublethal effects

Almost certainly be different in humans

Neglects adverse long-term effects

No account of idiosynchratic responses

92
Q

What is pharmacokinetics?

A

Explores the changes in drug concentration in the body with time

93
Q

Why is pharmacokinetics important?

A

Allows us to understand the time course of drug effects

94
Q

What have autoradiographs and chemical analysis shows about drug distribution?

A

Drugs do not penetrate uniformly throughout the body

95
Q

How do we split the body into compartments?

A

Depending on how tissues behave.

Tissues that behave similarly are thought to be in the same compartment.

96
Q

What is the use of compartments?

A

Describe the time course for drug disposition and predict the changes in concentration that occur following administration

97
Q

What are the two models of drug-distribution?

A

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
Q

Examples of rapidly equilibrating tissues

A

Lung

Kidneys

99
Q

Compare the pharmacokinetic profile of one and two-compartment models

A

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
Q

What is the plasma half-life?

A

Time taken for any given plasma concentration to decrease by 50%

101
Q

We can determine the plasma half-life of a zero order drug

TRUE or FALSE

A

FALSE

102
Q

Why can we not determine the plasma half-life of a zero-order drug?

A

Unstable

The half-life changes with the dosage

103
Q

What is zero-order kinetics?

A

The rate of the process is independent of the drug’s concentration

104
Q

An important aspect of carrier-mediated transport

A

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
Q

What does the volume of distribution tell us?

A

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
Q

What is the volume of distribution of albumin?

A

Low

5 litres

Large protein, so does not pass through into the interstitial environment and stays in the blood

107
Q

What is the volume of distribution of glucose?

A

High

50 litres

Can pass through into all body compartments, including the blood, interstitial fluid and intracellular environment

108
Q

What is the volume of distribution of sodium chloride?

A

Medium

20 litres

Passes into the interstitial fluid but can not efficiently enter the intracellular environment

109
Q

What is the definition of clearance?

A

The volume of plasma cleared of drug per unit time

Elimination rate/concentration

110
Q

What is the total body clearance?

A

Sum of all the clearances occurring by whatever routes are applicable to the drug in question

111
Q

What, in terms of clearance, is favourable for zero-order drugs?

A

The drug is completely cleared from the system following elimination

First-order drugs are never fully cleared from the system

112
Q

Why are patients taking contraceptive pills whilst on short course of broad-spectrum antibiotics advised to take other contraceptive precautions?

A

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
Q

Describe the cumulative effect some drugs have during their clearance

A

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
Q

Describe the plateu phase for drug clearance

A

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
Q

What is the equation for drug plasma concentration

A

Dose rate/clearance

Can be used to calculate the dose rate, if you know the clearance and drug dose required

116
Q

What is the steady state for drug elimination?

A

The rate of drug administration equals the elimination rate

117
Q

What are two approaches to treating drug overdoses in children?

A

Kinetics - stop absorption to prevent distribution to other organs

Dynamic - give proper antidote

118
Q

Describe the use of ferrous sulphate

A

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
Q

Describe aspirin absorption

A

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
Q

How can doctors manipulate the absorption of aspirin clinically?

A

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
Q

What is aspirin?

A

A weak acid

122
Q

What is paracetamol?

A

A weak base

123
Q

How is the absorption of aspirin and paracetamol different?

A

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
Q

What does A- in aspirin dissociation represent?

A

The ionised form

125
Q

What does AH in aspirin dissociation represent?

A

The protonated form

Passes through lipid membranes easily

126
Q

What does BH+ in paracetamol dissociation represent?

A

Both the protonated and ionised forms

127
Q

What does B in paracetamol dissociation represent?

A

The form that is highly absorptive

128
Q

What causes anaphylaxis?

A

Bronchoconstriction and systemic vasodilation caused by the release of histamines and leukotrienes

129
Q

What are two ways two treat anaphylaxis?

A

Block the inflammatory mediators released

Treat the symptoms

130
Q

Why is it not easy to treat anaphylaxis by blocking the release of inflammatory mediators?

A

We don’t know all the inflammatory mediators released

131
Q

What is the standard of care of treating anaphylaxis?

A

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
Q

Describe a clinical use of competitve antagonists

A

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
Q

Describe a clinical use of a chemical antagonist

A

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
Q

Describe the history of pharmacological antagonism

A

Paul Ehrlich discovered the first true antibiotic which was aimed at a specific pathogen

This was termed drug 606

135
Q

What are the first two things you want to find out about a drug?

A

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
Q

What are the two ways in which pharmacological agonists differ?

A

Potency

Efficacy

137
Q

What does potency refer to?

A

The amount of drug necessary to produce an effect

Determined normally by the EC50

The lower the EC50, the more potent the drug

138
Q

What does efficacy refer to?

A

The maximum response a drug can cause

The Emax determines the efficacy

The larger the Emax, the more efficient the drug is

139
Q

Show how two drugs can differ in their potency

A

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
Q

Clinical examples of full and partial agonists

A

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
Q

Why is it important to distinguish between full and partial agonists?

A

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
Q

What are pure antagonists?

A

Do not elicit a response unless the agonist has bound to the receptor

143
Q

Example of a reversible antagonist

A

Propanolol

144
Q

Example of an irreversible antagonist

A

Aspirin - forms double bonds

145
Q

What happens to the dose response curves when administering a reversible antagonist?

A

The Emax stays the same (efficacy)

The EC50 increases (potency decreases)

146
Q

What happens to the dose response curves when administering an irreversible antagonist?

A

The Emax decreases

Some receptors are lost through irreversible binding

147
Q

How long does the effect of an irreversible antagonist last?

A

Until the receptor becomes degraded and a new one is formed

148
Q

Example of a irreversible antagonist

A

Aspirin

Inhibitor of cyclooxygenase

Acetylates the enzyme until it becomes proteolysed

149
Q

How can the effect of an inverse agonist be investigated?

A

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
Q

Describe the special measures that need to be taken when resecting a pheochromocytoma

A

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
Q

Why does withdrawal happen?

A

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
Q

What are the two drugs used to tackle withdrawal of opioids?

A

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
Q

Why are partial agonists better than full agonists in treating withdrawal?

A

Full agonists act like the drug itself

Partial agonists inhibit the effect of the drug whilst reducing the withdrawal symptoms

154
Q

Where is acetylcholine found in the body?

A

Neuromuscular junction

Autonomic ganglia

Postganglionic parasympathetic nerve endings

Synapses in the CNS

155
Q

What are the two types of receptor that bind to acetylcholine?

A

Nicotinic

Muscarinic

156
Q

Describe the synthesis of acetylcholine

A

Synthesised by choline acetyltransferase

Combines choline and acetic acid

157
Q

What type of molecule is acetylcholine?

A

Ester

158
Q

How is acetylcholine released from neurons?

A

Ca2+ mediated exocytosis

Triggered by a nerve action potential

159
Q

What process in acetylcholine action is an important target for pharmacology?

A

Modulation of Ach release by presynaptic receptors

160
Q

Inhibition of choline uptake is clinically useful

TRUE or FALSE

A

FALSE

161
Q

Inhibition of ACh release is not clinically useful

TRUE or FALSE

A

TRUE

162
Q

Which presynaptic receptors inhibit the release of acetylcholine in postganglionic nerve endings?

A

A2-adrenoceptors

Muscarinic receptors

Opioid receptors

163
Q

Which presynaptic receptors facilitate the release of Ach?

A

B-adrenoceptors (parasympathetic nerve endings)

Nicotinic receptors (NMJ)

164
Q

Example of a drug/toxin that inhibits Ach release

A

Botulinum toxin

Inhibits the fusion of Ach vesicles with the cell membrane

165
Q

What type of molecule is Ach?

A

Ester

166
Q

Where are muscarinic receptors found?

A

Smooth muscle

Cardiac muscle

Glands

CNS neurons

167
Q

Where are nicotinic receptors found?

A

Neuromuscular junction

Autonomic ganglia

Adrenal medulla

CNS neurons

168
Q

Which 5 classes of drugs affect the action of cholinergic receptors?

A

Non-depolarising agents (neuromuscular blockers)

Depolarising agents (neuromuscular blockers)

Anticholinesterases

Agonists

Antagonists

169
Q

Where are nicotinic receptors mostly found?

A

Postsynaptic neuron

170
Q

Describe the structure of nicotinic receptors

A

Cation channel

5 subunits
In the NMJ - 2a, b, d, e
In the neurons - 2a, 3b

171
Q

What is the consequence of nicotinic channel opening?

A

Na+ influx

Membrane depolarisation

Action potential initiation

172
Q

Describe the function of non-depolarising blocking agents

A

Competitive antagonists

Effect is reversed by anticholinesterases

173
Q

Describe the function of depolarising blocking agents

A

Activates the receptor

Causes maintained depolarisation

Prevents the end-plate potential from producing a propagated action potential

174
Q

What are the unwanted effects of neuromuscular blockers (depolarising and non-depolarising agents)?

A

Hypertension

Bradycardia

Cardiac dysrhythmias caused by increased K+ release

175
Q

What are the clinical uses of neuromuscular blockers?

A

Muscle relaxation in anaesthetised patients during surgery

Prevents injuries during electroconvulsive therapy

176
Q

What are the effects of ganglion-blocking agents?

A

Block sympathetic and parasympathetic transmission

Caused by receptor antagonism or direct channel block

177
Q

What is the clinical use of ganglion-blocking agents?

A

Lower blood pressure during surgery

178
Q

Describe the structure of muscarinic receptors

A

G-protein coupled receptor

7 transmembrane proteins in their amino acid sequence

179
Q

What are the 5 muscarinic subtypes?

A

M1 (neural) - Gq

M2 (cardiac) - Gi

M3 (glandular) - Gq

180
Q

What are the actions of M1 muscarinic agonists ?

A

Gastric acid secretion

181
Q

What are the actions of M2 muscarinic agonists?

A

Decreased rate and force of heartbeat

182
Q

What are the actions of M3 muscarinic agonists?

A

Smooth muscle contraction

Glandular secretion

Vasodilation via release of endothelial NO

183
Q

What is the effect of muscarinic antagonists?

A

Inhibition of secretions

Tachycardia

Relaxation of smooth muscle

Antiemetic action

Antiparkinsonian action

184
Q

Clinical use for muscarinic agonists

A

Sinus bradycardia

Bronchospasm reduction in asthma

Reduce acid secretions in ulcers

185
Q

Clinical use of muscarinic antagonists

A

Lower intraocular pressure in glaucoma

Increases motility in GI

186
Q

What are the two forms of cholinersterases?

A

Acetylcholinesterase

Butyrylcholinesterase

187
Q

Describe the process of ACh hydrolysis

A

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
Q

What is the action of anticholinesterases?

A

Inhibit cholinesterase, leading to the enhancement of cholinergic transmission

189
Q

What types of anticholinesterases can be found in the body?

A

Short acting

Medium duration of action

Irreversible -organophosphates

190
Q

What are the effects of anticholinesterases?

A

Autonomic effects - bradycardia, hypotension

Action on NMJ - muscle fasciculation, increased twitch tension

Action at CNS - respiratory failure, loss of consciousness

191
Q

What are the clinical uses of anticholinesterases?

A

Eyedrops to treat glaucoma

Myasthenia gravis

Alzheimer’s disease

192
Q

What does the pKa of aspirin (3.4) mean?

A

At a pH of 3.4, half of asipirin is protonated and half is ionised

Pharmacology (13 decks)

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