Fundamental of Pharmacology Flashcards
1
Q
What are the 5 ways a cell can communicate with other cells?
A
1 - endocrine (in the blood, long distance)
2 - paracrine (close cells)
3 - juxtacrine (cells touching or via membrane rceptors)
4 - autocrine (cells signals itself)
5 - neuronal
2
Q
In GPCRs, what determines its intracellular activity, for example, is the GPCR turned on or off?
A
- GTP = GPCR on
- GDP = GPCR off
3
Q
Of the four intracellular signalling below, which has the quickest reaction?
1 - GPCR
2 - Iontrophic receptors (ion or ligand gated)
3 - Kinase linked receptors
4 - cytoplasmic/nuclear receptor
A
- iontrophic receptors (ion or ligand gated)
- almost immediate
4
Q
In order rank the the four intracellular signalling below from quickest to slowest reaction?
1 - GPCR
2 - Iontrophic receptors (ion or ligand gated)
3 - Kinase linked receptors
4 - cytoplasmic/nuclear receptor
A
1 - Iontrophic receptors (ion or ligand gated)
2 - GPCRs
3 - kinase linked receptors
4 - cytoplasmic/nuclear receptor
5
Q
If a drug is being developed that will decrease cAMP levels, which GPCR will this be?
A
- Gai
6
Q
What is the definition of a side effect?
A
- undesirable secondary effect in addition to the desired therapeutic effect
- dose of drug is normal dose
7
Q
What is the definition of an adverse effect?
A
- harmful effect on a patient
- dose of drug is normal dose
8
Q
What is the definition of an adverse effect?
A
- deleterious, undesired effect
- dose of drug is higher than normal dose
9
Q
What is the difference between allosteric and orthosteric binding sites?
A
- orthosteric = active site
- allosteric = non active site, but binding changes conformation so orthosteric site can not be accessed
10
Q
When something binds to a receptor but the normal physiological or regulatory effect, what is this called?
A
- antagonist
11
Q
If something is able to bind to the allosteric site of a receoptor and does not have the same regulatory effect, what is this called in terms of pharmacodynamics?
A
- non competitive antagonist
12
Q
What is the difference between a competitive and non-competitive antagonist in terms of pharmacology?
A
- competitive antagonist = competes with agonist for orthosteric (active) binding site
- non-competitive antagonist = does no competes with agonist for orthosteric (active) binding site, rather it binds to allosteric binding site causing conformational changes in receptor
13
Q
Does the figure below show a competitive reversible or non-competitive reversible antagonist?
A
- competitive reversible
- a larger concentration (1000 vs 1) would be required to reduce effect of the agonist
14
Q
Does the figure below show a competitive reversible or non-competitive reversible antagonist?
A
- non-competitive reversible antagonist
- a larger concentration (10 vs 1) would significantly reduce the Cmax
15
Q
In terms of pharmacodynamics, what does affinity mean?
A
- the ability of a drug to bind with a receptor
16
Q
What is efficacy in relation to pharmacotherapy?
A
- the ability of an agonist to produce a biological effect
17
Q
What is Rmax in relation to efficacy in pharmacotherapy?
A
- efficacy determines how effect an agonist is at eliciting a biological effect
- Rmax = maximal response
18
Q
What is potency in relation to pharmacotherapy?
A
- which drug has the largest effect, i.e the most potent
19
Q
What is EC50 in relation to potency in pharmacotherapy?
A
- effective concentration to elicit a response in 50% of population taking the drug
20
Q
In the figure below which drug has the highest EC50, meaning it has the highest potency in pharmacotherapy, and why is this a good thing?
A
- drug A
- higher potentcy means lower EC50
- lower EC50 means lower drug dose required
21
Q
How do we calculate therapeutic index?
A
- TD50 / ED50
- TD50 = toxic dose in 50% of population using the drug
- ED50 = effetive dose in 50% of population using the drug
22
Q
What are the equilibrium potentials of Na+ and K+ in the cell?
A
- Na+ = +60mV
- K+ = -90mV
- helps maintain restint potential
23
Q
What does the resting membrane potential of a cell normally sit at?
A
- between -90 to -70mV
24
Q
Roughly what voltage needs to be reached for an action potential to occur?
A
- +20 - 40mV
25
In the image below of an action potential, which cation maintains the restin membrane?
- K+
26
Once a cell that is excitable and has recieved a stimulus, like a muscle cell, what cation is able to increase the resting membrane potential causing depolarisation?
- Na+
- positive charge increase the charge in the cell
27
In an action potential what is the threshold value?
- charge in cell increases about a certain value
- if this is reached the cell is commited to an action potential
28
In an action potential, once depolarisation has occured and Na+ channels begin to close, what cation is responsible for returning the membrane potential to resting or hyperrepolarisation?
- K+
- K+ channels open allowing positive charge to leave the cell
29
Once an action potential arrives the pre synapse and depolarises the pre synapse, what is released into the pre synapse and then what does this facilitate?
- Ca2+ channels open
- allows vesicles containing ACh to bind with pre synaptic membrane
30
In the autonomic system what is the neurotransmitter and receptor that is present between all pre and post ganglionic neurons?
- ACh
- all are nicotinic neurons (Nn) receptors
31
What is the definition of absorption in pharmacokinetics?
- transfer of a drug from the site of administration into the systematic circulation
- for example, a drug given orally then absorbed into the blood
32
What is the definition of distribution in pharmacokinetics?
- transfer of a drug from the genral circulation into other tissues around the body
33
What is the definition of metabolism in pharmacokinetics?
- process of a drug being altered
- alteration can enhance its action or enhance its elimination
34
What is the definition of excretion in pharmacokinetics?
- process where metabolites of a drug are removed from the body
35
The pH, enzymes, gut motility and first pass metabolism can all affect which of the A.D.M.E, which relates to pharmacokinetics?
- absorption
36
How do we calculate bioavailability in pharmacokinetics?
- area under the curve (AUC) for oral administration (OA) is divided by the AUC for IV administration
- AUC OA / AUC IV
37
If you are administering a drug at 25mg via IV, but the oral bioavailability is only 25%, what would you need to increase the dosage to, to ensure the same bioavailablity is provided?
- 25mg / 0.25% = 100mg
- 4 times more does needs to be given, but same bioavailability will be achieved
38
When considering bioavailability, what 2 factors from absorption, distribution, metabolism and excretion?
- absorption
- metabolism
39
Does a water or lipid soluble drug have a larger volume of distribution?
- lipid soluble
- able to cross membranes easier
40
When drugs are distributed they can be bound or unbound, which is able to have a therapeutic effect?
- unbound
41
Does the free or bound drug remain in the body for longer?
- bound drug
42
Bound drugs can remain in the body for longer, which 2 aspects from absorption, distribution, metabolism and excretion is bound drugs able to avoid once inside the body?
- metabolism (enzymes are unable to metabolise)
- excretion (too big to be filter in glomerulas)
43
Cytochrome P450 (CP450) is a superfamily of enzymes, responsible for the metabolism of most drugs. There are 2 phases of drug metabolism:
phase 1 = oxidation (gaining an oxygen and losing a electron ((H+) and reduction (gaining an electron (H+)
phase 2 = conjugation
Out of the 2 phases, which does CP450 work on?
- phase 1
44
Liver disease, other drugs, inducers or inhibitors are all able to influence one aspect of A.D.M.E?
- metabolism
45
If a patient is an ultrametaboliser of a drug, is this classed as an inducer or inhibitor?
- inducer
- drug is metabolised quickly and elimated from the body
46
If a patient is an poor metaboliser of a drug, is this classed as an inducer or inhibitor?
- inhibitor
- drug is metabolised slower and stay in the body for longer
47
If you are an ultra metaboliser, and you are given a pro-drug, would this increase or decrease:
- bioavailability
- therapeutic effect
- toxcitiy
- first pass metabolism
- metabolism rate
- bioavailability = increased (drug metabolised quickly and released into blood)
- therapeutic effect = increased (drug metabolised quickly and released into blood)
- toxcitiy = increased (drug metabolised quickly and released into blood)
- first pass metabolism = increased
- metabolism rate = increased
48
If you are an poor metaboliser, and you are given a pro-drug, would this increase or decrease:
- bioavailability
- therapeutic effect
- toxcitiy
- first pass metabolism
- metabolism rate
- bioavailability = decreased (drug metabolised slowly and released into blood)
- therapeutic effect = decreased (drug metabolised quickly and released into blood slowly reducing therapeutic effect)
- toxcitiy = decreased (drug metabolised quickly and released into blood slowly and reducing risk of toxicity)
- first pass metabolism = decreased
- metabolism rate = decreased
49
What is the mechanism of action of the antibiotic amoxicilin?
- able to pass through peptidoglycan layer of the bacteria
- can then bind and inhibit with transpeptidase
- reduces peptidoglycan production and bacterial cells lyse
50
What is the mechanism of action of vancomyosin?
- inhibits cell wall synthesis
- binds to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis meaning cell wall cannot form
52
What is the mechanism of action of clarithromycin?
- binds to 50S subunit of ribosome
- inhibits protein translation
53
What is the difference between bactercidal and bacteriostatic?
- bactercidal = kills bacteria
- bacteriostatic = inhibit the growth of bacteria
54
Tetracyclines, Aminoglycosides and Macrolids are classes of antibiotics, that share the method in how they are able to be effectibe at treating infections. What is the general mechanism of action of these classes of drugs?
- inhibit bacterial synthesis
- at ribosome
55
Ciprofloxacin is a a class of quinelone antibiotics, what is the mechanism of action?
- inhibit DNA synthesis
56
The Epstein-Barr ***virus*** (***EBV***), is a common viral infection, what type of virus is this?
* herpesvirus 4
* member of the herpes ***virus*** family
57
In drug treatment, empirical treatment describes what?
- antibiotic therapy commenced before the identification of the causative micro-organism is available
- local guidelines provide guide for this
58
Why does the gram negative staining not work on all bacteria?
- some strains posses special walls that staining cannot penetrate
- TB contains mycolic acid that Gram positive staining cannot penetrate
59
What is Ziehl–Neelsen staining?
- alternative staining used when gram positive staining cannot penetrate cell wall
- TB, which contains mycolic acid in its walls is an example
60
Acid fast staining, with the most common approach being the ziehl-neelsen stain, is an alternative staining used when gram positive staining cannot penetrate cell wall due to waxy surfaces such as mycolic acid on TB. What colour would TB and non TB stain when using the ziehl-neelsen stain?
- acid fast positive = pink/red such as TB
- non acid fast = blue/purple
61
Kirby Bauer Antibiotic Sensitivity Assay?
- antibiotic resistance to cultured bacteria can be tested
62
What is sensitivity and specificity?
- sensitivity = ability of a test to correctly identify patients with a disease
- specificity = the ability of a test to correctly identify people without the disease
63
What is the sellotape test?
- parasites can be seen visually generally
- sellotape on infected area will show eggs and potentially parasites under microscope
64
What does prophylactically mean in drug delivery?
- designed to prevent a disease
- vaccines
65
What is the mechanism of action of penicillin?
- penicillin specifically binds with a penicillin binding protein (PBB)
- PBB makes transpeptidoglycans for the bacterial cell wall
- penicillin inhibits transpeptidase and breaks transpeptidase bonds
- cell wall synthesis is stopped and cell lyses
66
What is the difference between vertical and horizontal gene transfer?
- vertical = genes are transferred down generations in offspring
- horizontal = genes are transferred across from an individual to others in the same generation, NOT inherited
67
If a gram + or gram - bacteria has been identified, which should recieve broad or narrow spectrum antibiotics?
- gram + bacteria = narrow spectrum
- gram - bacteria = broad spectrum
68
What is transpeptidase?
- bacterial enzyme responsible for cell wall synthesis
- needed to build bacterial cell walls
69
What are the 2 ways in which B-lactam antibiotics act on bacterial pathogens?
1 - breaking of transpeptide bonds in cell wall
2 - ⬇️ transpeptidase activity reducing cell wall turnover
70
β-lactamases are enzymes that are produced by bacteria. What do these enzymes do to antibiotics which contain B lactam rings?
- inhibit the B lactam antibiotics
- these bacteria are then resistant to B lactam antibiotics
71
Amoxicillin can sometimes be prescribed alongside clavulonic acid, why is this?
- clavulonic acid is able to inhibit B-lactamase
- Amoxicillin can function normally and inhibit transpeptidase
72
Vancomyosin can be used to treat bacterial infections. How are they able to break down bacterial cell walls?
- glycopeptide antibiotic
- means it targets the glycopeptide bonds in bacterial cell walls
73
What does ototoxic mean?
- toxicity of a drug to the ear lobe
74
Macrolids are a group of antibiotics, of which Clarithromycin is included. How do these drugs target bacteria?
- inhibit bacterial ribosome
- inhibit the synthesis of proteins
75
What are the 3 methods of horizontal antibiotic resistance amongst microorganisms?
1 - transduction
2 - transformation
3 - conjugation
76
What is a facultative anaerobe?
- an organism that makes ATP by aerobic respiration if oxygen is present
- is also capable of switching to fermentation if oxygen is not present
77
Lyme disease is a bacterial infection that can be spread to humans by infected ticks. What pathogen can cause this disease?
- bacteria shapped as spirochaete
- borrelia burgdorferi
78
What component of enveloped viruses aids viruses gain access to the host cells, allowing host cells to recognise the virion and gain entry?
- Spike proteins
79
What is the most common chromosome abnormality seen in first trimester spontaneous miscarriages?
- trisonomy
- 3 chromosomes
80
n meiosis, in which phase does recombination (sharing of genetic info) occur?
- prophase 1
81
Chiasmata due to recombination occur between which of the following?
- any two chromatids
- maternal chromatids
- non-sister chromatids
- sister chromatids
- non-sister chromatids
- they need to be different to encourage genetic variability
82
Father to son transmission is a key feature of which pattern of inheritance?
- Y linked recessive
83
In the cell where can gene expression be controlled in the cell?
- mRNA transcription
- RNA processing
- mRNA degradation
- mRNA translation
84
What is a transcription factor in RNA copying?
- protein
- required to recruit RNA polymerase to the promoter
85
Which of the following is one of the main driving forces of protein folding?
- chaperone proteins
- disulphide bonds
- entropic interactions
- hydrogen bonding
- hydrophobic interactions
- hydrophobic interactions
86
In a wound injury, what are the first 2 steps of the recovery process?
- 1st = dilation of blood vessels
- 2nd = infiltration of neutrophils
87
Although macrophages have a number of functions, what is their main function in the acute wound?
- removal of debris
88
When skin wounds initially heal, there is often evidence of a “puckering” distortion. Why?
- differentiation of muscle fibres in some fibroblasts, with contraction
89
In wound healing tissue can appear granular, feels friable to touch and bleeds easily? Why?
- low level of connective tissue
- no connective tissue means no support for cells
90
What does immune tolerance mean?
- organisms ability to be non-reactive to an antigen
- people who have allergies have lower immune tolerance
91
What is autoimmunity?
- a breakdown in immune tolerance
- immune system is unable to distinguish between dangerous and non dangerous antigens
92
What is the innate immune system?
- first line of defence (skin for example)
- respond quickly but cannot adapt
93
Adaptive immunity is normally slow to respond, however, when can it be fast to respond?
- during 2nd exposure to pathogen
- trained during first expsoure so quicker to respond
94
Where in the trilaminer disc would hematopoetic cells that form RBCs originate from?
- found in bone which is a connective tissue
- all connective tissue starts in mesoderm
95
What is clonal expanssion?
- the process where daughter cells originate from parent cells
- daughter cells can remain as daughter cell of differentiate further
- this is mitosis, and why the adaptive immune response is not fast initially
96
What are the 5 different isotypes of antibodies? (GAMED)
1 - IgG
2 - IgA
3 - IgM
4 - IgE
5 - IgD
97
What does valency mean in relation to antibodies?
- the ability of an antibody to bind with its antigen
- the more antigen binding sites the higher the valence
- IgM has the highest
98
What is affinity and avidity in relation to antibodies?
- affinity = strength of a single antibody-antigen interaction
- avidity = strength of all (\>1) antibody-antigen interactions
99
Why does IgM often have the largest concentration in the blood during the first time an antigen is exposed to the host?
- initial affinity for antigens can be poor
- IgM compensates for this with up to 10 antibody-antigen binding sites giving it a higher valence
100
Which antibody generally has the highest concentration in the body?
- IgG
101
102
What immune cells are involved in the innate immune system?
- neutrophils
- eosinophils
- basophils
- dendritic cells
- macrophages
103
What are pathogen associated molecular patterns (PAMPs)?
- specific parts of foreign bodies that the innate immune cells can recognise
104
What are pattern recognition receptors (PRR) and what is their role?
- receptors on innate immune cells that can detect antigens from foreign bodies
- able to detect pathogen associated molecular patterns
105
Pattern recognition receptors (PRR) are receptors on innate immune cells that can detect antigens from foreign bodies, including pathogen associated molecular patterns (PAMPs) There are 2 types of PRRs, the phagocytic and signalling PRR. What does each of these do when it comes into contact with PAMPs?
- phagocytic PRR = phagocytose what PAMPs are bound to and no need to release cytokines
- signalling PRR = release cytokines to recruit additional immune cells
106
What is the complement system in the innate immune system?
- a complex cascade of protein pathways
- each protein activates the next protein and induced inflammation
107
The Varicella-zoster virus (VZV) can cause what 2 common infections?
- chickenpox (children)
- shingles (adults)
108
c
- it is normally self limiting in children
- if a child has it they wont get it as an adult
109
Which MHC complex do T helper cells bind with and is this part of the endogenous or exogenous pathway?
- MHC-II
- CD4+ cells
- exogenous
110
Which MHC complex do T cytotoxic cells bind with and is this part of the endogenous or exogenous pathway?
- MHC-1 complex
- CD8+ cells
- exogenous pathway
111
Shingles can be caused by the varicella-zoster virus (VZV) a herpesviruses, can cause shingles in adults. Which group of adults is most at risk?
- immunocomprimised older adults
112
During immunisation or infection what are the first 2 immunoglobulin that B cells make?
- IgD = signal inflammation and immune response
- IgM = due to high avidity (multiple antigen binding sites)
113
When exposed to the same antigen again, which is the main antibody that is created by B cells?
- IgG
114
In antibodies what is class switching?
- switch from IgD or IgM to IgA, IgE or IgG
- switches to increase affinity
115
What is affinity maturation in active B cells?
- antibodies can change to increase affinity for an antigen
116
Why do B cells need to go through somatic hypermutation and clonal selection?
- progenitor B cell will have a specific sequence for antibodies
- with clonal expansion occurs there are somatic hypermutations
- this ensure the antibody of the daughter cell is specific to the antigen
117
What antigens can B and T cells bind with?
- B cells = any antigen (lipid, peptide or polysaccharide) as they are an antigen presenting cell
- T cells = peptide antigens on MHC-I and II comoplexes
118
How can the adaptive immune system make the innate immune system more specific to a particular antigen?
- Fab region of antibodies secreted by B cells bind to antigen
- Fc (constant) region of antibody binds to innate immune cells
- this cell is now specific to that antigen
119
What is opsonization in relation to how antibodies function?
- antibodies coat bacteria
- identifying bacteria for phagocytosis
- impairs virulence factors of pathogens
120
3 checks are required before a T cell becomes active to ensure it is not attack the host cells. What are these cells?
1 - T cell receptor binds to MHC-I or II
2 - MHC-I and II are checked by CD8 and CD4, respectively
3 - B7 on antigen presenting cell and CD28 on naive T cell bind
121
What does primordial prevention mean?
- avoiding the risk factors for a condition in the first place
122
What is the formula for sensitivity?
- proportion of people with condition with a positive test
- true positive / (true positive + false negative)
123
What is the formula for specificity?
- proportion of people without a condition with a negative test
- true negative / (true negative + false positive)
124
A positive predictive value (PPV) is the proportion of patients with a positive test that have the disease. How do we calculate the PPV?
- true positive / (true positive + false positive)
125
Negative predictive value (NVP) score is the proportion of patients with a negative test that do not have a disease. What is the formula to calculate negative predictive value?
- true negatives / (true negative + false negative)
126
If a test has a sensitivity of 80%, what does this mean?
- 80% or 8 in 10 patients with disease were correctly identified as having the condition/disease
- 20% or 2 in 10 patients with disease were incorrectly identified as not having condition/disease
127
If a test has a specificity of 80%, what does this mean?
- 80% chance or 8 in 10 patients without a condition/disease were correctly identified as not having the disease
- 20% chance or 2 in 10 patients were incorreclty identified as not having the disease
128
What is the Wilson-Jungner criteria used for clinically?
- assess the suitability of a national screening programme
129
In a diagnostic and screening test, when is sensitivity or specificity more important?
- screening = high sensitivity to rule out disease
- diagnosis = high specificity to rule out disease
130
What is health span?
- the amount of your life span spent in good health
- more important to focus on health span than life span
131
What is senescence?
- a cell DNA is damaged and leaves the cell cycle at G0 phase of interphase
- loss of a cell's power of division and growth, aimed at ensuring no tumours form
132
In senescence what does DNA methylation do to gene expression?
- methyl groups are added to DNA
- DNA sequence remains, but gene expression can be increased or decreased
- generally decreased as histones are packaged tighter
133
What is suspected to be the maximum number a cell can proliferate before it becomes undergoes, senescence or forms a tumour as defined as the Hayflic limit?
- 40-60 times times
134
What are quiscent cells?
- cells that stop proliferating
- BUT they maintain ability to proliferate
135
Do benign or malignant tumours have a faster groth rate and do either look like they tissue they have originated from?
- benign = slow growth and similiar appearance
- malignant = rapid and can be similiar, but normally very different
136
In malignant tumours, necrosis is common in the centre of the tumour, why?
- ischeamia
- lack of O2 and nutrients
137
What does adenoma and adenomatous mean?
- adenoma = cell growth of gland
- adenomatous = neoplasia cell growth of gland
138
In neoplasia, are cells and nucleous bigger or smaller?
- both are bigger
139
What does endophytic mean?
- to grow inwards
- malignant tumours grow inwards
140
What is ductal carcinoma in-situ?
- malignant neoplasia in ducts of lobules
- called in-situ because basement membrane remains intact
141
What are the 3 things included when grading a tumour?
1 - mitotic activity
2 - cellular factors (size and shape) (nucleus and cell size increases)
3 - similarities between tumour and original cell
142
Grading a malignant tumour from histolgy is really important and takes into account if mitosis can be see, cell size and shape and similarities between tumour and original cell. What does grading closely relate to?
- linear relationship between grading and clinical outcomes
- high grade = poorer clinical outcomes
143
How are tumours staged?
- TNM system
- T = tumour size
- N = nodal onvolvement
- M = metastasis
144
What is a commonly used approach to help staging of a malignant tumour using TNM?
- imaging
145
What is histone methylation and acetylation?
- histone tails are exposed (generally an N terminus)
- methyl or actyl group can be added to these tails
- methylation = histone pack tightly and genes not expressed
- acetylation = histone pack loosely and genes can be expressed
146
What are proto-oncogenes and oncogenes?
- proto-oncogene = genes involved in normal cell growth
- oncogene = mutations change proto-oncogenes into oncogenes, which are associated with tumour growth and development
147
What is the philadelphia chromosome?
- chromosome 9 and 22 share parts of chromosome called translocation
- causes chronic myelogenous leukaemia (CML)
148
What do tumour supressor and oncogene genes do to gene activity?
- tumour supressor = supress activity
- oncogene = increased activity
149
What are BReast CAncer genes?
- tumour supressor genes
- if mutated this can increase the risk of cancer
150
Where in the cell cycle do tumour supressor genes generally take place?
- G0
- following cytokinesis, cells are checked, if they are faulty they are removed prior to going through the cell cycle again
151
BReast CAncer genes 1 and 2 can increase the risk of cancer in males and females, which cancers specifically are increased in men and women due to BRCA genes 1 and 2?
- women = breast and ovarian cancer
- men = breast and pancreas cancer
152
What are the 2 main types of genes that cause cancer?
1 - oncogenes
2 - tumour supressor genes
153
What is TP53, that code for P53?
- tumour suppressor gene
- referred to an guardian of genome
154
What is the difference between fluid and crystallized intelligence?
- fluid intelligence = ability to reason and think flexibly
- crystallized intelligence refers to the accumulation of knowledge, facts, and skills that are acquired throughout life
155
Does fluid or crystallized intelligence decrease more rapidly with age?
- fluid intelligence = linear decline with age (faster)
- crystallized intelligence = slow decline with age
156
What is an example of an cohort effect?
- "young people do not realise how good they have it nowadays"
157
What is an example of an period effect?
- "a lot of people are losing their jobs at the moment due to covid-19"
158
What is an example of an age effect?
- "I cannot seem to shake of this cold, maybe its due to my age"
159
what does compression of morbidity mean?
- where the burden of lifetime illness can be compressed into a short period of time
- generally final 7-9 years of an older patients lifespan
160
What are the 3 most common national screening programmes for cancers?
1 - breast
2 - cervical
3 - colorectal
161
What is the difference between signs and symptoms?
- signs = quantifiable/objective evidence something is present (e.g. skin rash)
- symptoms = subjective presentation of a disease/condition
162
What does behavioural classification refer to with tumours, and what 2 things must be considered?
- how the tumour is behaving in the body
1 - is it benign or malignant
2 - grading and staging
163
What are the 3 ways metastasis can spread?
1 - haematogenous
2 - lymphatic
3 - transcoelomic (spread through tissue and cavities)
164
What is Predict Breast?
- online tool to predict breast cancer prognosis
- useful for patients post surgery
- can predict overall survival of patients from various treatments
165
What does adjuvant mean in curative therapy?
- generally given following primary treatment (surgery)
- used to reduce risk of micrometastases returning (radiotherapy or chemotherapy)
- aimed to boost immunity
166
What does neoadjuvant mean in curative therapy?
- treatment given prior to primary surgery
- aim is to reduce the tumour size
- aim is to reduce micrometastases
167
What are the 3 pillars of cancer treatment?
1 - surgery
2 - radiotherapy
3 - chemotherapy
168
Radiation is able to damage DNA and kill cancer cells. What is the direct action?
- radiation directly breaks up single and double stranded DNA
169
Radiation is able to damage DNA and kill cancer cells. What is the indirect action?
- ionisation of water produces free radicals such as hydroxyl group (OH)
- the OH group has an unpaired electron
- the OH can react and damage DNA
- this can cause double and single stranded breaks in DNA
170
What does fractionated treatment mean, and why is this approach used?
- application of a treatment separated with gaps
- allows healthy cells to recover
171
Why are small molecules used to treat cancer called small molecules?
- due to small size and molecular weight
- able to cross membrane and enter cells targeting cancers
172
Tamoxifan is a small molecule drug used as an endocrine therapy for breast and prostate cancer. What is the mechanim of action of Tamoxifan?
- small molecules of Tamoxifan are able to diffuse across membrane and bind to estrogen receptors
- inhibit estrogen binding and inhibt cellular proliferation and tumour development
173
Why is the identification of cell or tissue origin important when testing for oestrogen sensitive cells?
- if original tumour cell is breast tissue, then it may be over expressing oestrogen receptors
- therefore treatment can be directed more effectively
174
What is the small molecule Vemurafenib (sold under the name Zelboraf) used for generally?
- used to treat aprox 50% of patients with malignant melanoma and BRAF mutation
- BRAF causes a hyper-activation cell proliferation in melanocytes and tumour formation
175
What is the mechanims of action of the small molecule Vemurafenib (sold under the name Zelboraf)?
- diffuses into cell due to small size and molecular weight
- binds with BRAF gym and inhibits its action
176
The small molecule Vemurafenib (sold under the name Zelboraf) is generally used to treat melanom. Does everybody recieve this treatment for melanom?
- no, genetically tested for BRAF mutation
- if overexpression they will be prescribed
- example of personalised medicine
177
HER2 stands for human epidermal growth factor receptor 2, which binds with receptor tyrosine kinase on cell membranes and begins intracellular pathway activation through phosphorylation. These pathways are involved in DNA synthesis and cell proliferation. If there is a mutaiton in HER2 (20% of patients have this mutation) causing an overexpression of HER2 this can cause breast cancer. The immunotherapy drug Trastuzumab (Herceptin) can be used to treat patients who have this mutaiton, but what is the mechanism of action of Trastuzumab?
- antibody binds to HER2 receptor tyrosine kinase
- inhibits intracellular pathways stopping DNA synthesis and cell proliferation
- may signal cell for apoptosis as well
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How can you distinguish if a drug is an immunological drug?
- end in mab
- mab stands for monoclonal antibodies
- biologics work through antibodies
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When looking at a patients tumour, other cells can be seen. Specifically, immune cells. If a patient has immune cells present in or aorund the tumour, do they tend to have a better or worse prognosis?
- better
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Tumour cells are able to inhibit cytotoxic T cells. Normally, the T cell receptor binds with MHC-1 antigen recognising that the cell is sick. CD8+ confirms this by binding to MHC-1 and the cytotoxic T cell attempts to initiate apoptosis of cancer cell. However, what is the tumour cell able to do?
- cytotoxic T cells have a programmed cell death receptor 1 (PD-1)
- cancer cells have programmed cell death receptor ligand (PD-L1)
- binding of PD-L1 with PD-1 inactivates cytotoxic T cell apoptosis ability
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Tumour cells are able to inhibit cytotoxic T cells by binding their own programmed cell death receptor ligand (PD-L1) to the cytotoxic T cells programmed cell death receptor 1 (PD-1), thus inactivating cytotoxic T cell apoptosis ability, called an immune checkpoint. What is the mechanism of action of Nivolumab (Opdivo®) which is able to overcome this?
- Nivolumab is an antibody drug as it ends in mab
- the antibody binds to the programmed cell death receptor (PD-1) on cytotoxic T cell
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Can drugs can become resistant due to genetic differences within the tumour and other reasons. There is intrinsic and acquired drug resistance, what are these?
- acquired = - patients may have initiate response to drug, but then go into relapse
- intrinsic = - treatment naive patients, but no response following administration of drug
