The Public Flashcards
1
Q
What is inflammation?
A
A critical innate defence between microbial invaders and their hosts
Body’s primary method of defence against infection
2
Q
What characterises inflammation
A
Increase vascular permeability which:
allows diffusible components to enter the site of infection
Cellular infiltration by chemotaxis
Movement if inflammatory cells to site of injury
3
Q
Which types of cells are involved in acute inflammation?
A
neutrophils, Allergy, eosinophils, mast cells
4
Q
Whuch types of cells are involved in chronic inflammation?
A
Macrophages, lymphocytes
5
Q
What is the difference in chemical mediators in acute and chronic inflammation?
A
Acute - complement, kinins, prostaglandins, leukotrienes, cytokines (IL-1 IL-6), interferon
Chronic - cytokines but different
6
Q
Describe a acute inflammation visible lesion
A
Rash, pus, absess
7
Q
Describe a chronic inflammation visible legion
A
Rash, fibrosis, granuloma
8
Q
Give 2 examples of acute inflammation clinical examples
A
Abscesses
Allergic reaction
9
Q
Give 2 examples of chronic inflammation clinical examples
A
Autoimmune conditions
Cystic fibrosis
10
Q
6 types of inflammatory diseases
A
IBD COPD Heart disease/atherosclerosis Alzheimers Disease Rheumatoid arthritis Cancer
11
Q
What are monokines
A
Cytokines secreted by mononucclear phagocytes
12
Q
What are lymphokines
A
Cytokines secreted by activated T cells (especially T helper)
13
Q
What are interleukins
A
Cytokines mediating signalling between white blood cells
14
Q
What are four functions or cytokines
A
Development of cellular and humoral immune responses
Induction of inflammatory response
Regulation of haematopoiesis
Wound healing
15
Q
What do the cytokines secreted during acute inflammation do?
A
Activate NK and CTL cells
Supress tumour
16
Q
What do the cytokines secreted during chronic inflammation do?
A
Tumour cells escape immine response so tumour progression
17
Q
What is stress?
A
A specific response by the body to a stimulus that disturbs or interferes with normal physiological equilibrium/homeostasis
18
Q
What does stress affect?
A
Affects the hypothalamus - high levels of glucocorticoids so more supression of pro inflam cytokines and chemokines
19
Q
What happens to the glucocorticoids during chronic stress?
A
The levels dont matter anymore because the signals are not taken notice of by the body
Reactive oxygen species produced which can oxidise to cause mutations
20
Q
How does cortisol impair immune function?
A
Changes cytokine secretion - decreases levels of tumor necrosis factor
Decreases IL-2
Induces WBC death
Decreases inflammatory response
21
Q
What changes in the adipose tissue when obese?
A
More leptin, less adiponectin
22
Q
What does leptin do?
A
When levels increase, it signals us to stop taking any more food for energy as we don’t need it
23
Q
Which types of macrophages are found in lean people vs obese people?
A
M2 - lean
M1 - obese and produce inflammatory cytokines
24
Q
In what ways does obesity facilitate the development of autoimmune diseases?
A
Cause chronic inflammation
Upregulate T helper 17 cells – produce pro inflame cytokines
Down reg of deregulatory cells
Development of antibodies that lead to autoimmune complications
Macrophages that do not support cells death (inhibit it) – leads to lipolysis leading to aggregates, recognised by immune system as foreign – autoimmune
Some autoantibodies produced – recognise some of our cells as foreign
Alterations in gut - Accumulations of strains of bacteria that are not helpful
Vitamin B not enough levels- can lead to cells which loose myelin which protects neurones from microenvironmental stresses – multiple sclerosis can occur
25
Outcomes of dysregulation (inflammation not terminated properly)
```
Allergy/asthma
Type 1 diabetes
MS
IBD
Psoriasis
Obesity
Arterioscleosis
```
26
Outcomes of homeostasis (inflammation maintained)
Immunity
Health
Well-being
Prolonged living
27
What do antibodies do as drugs?
Attach to non-physiological cells and attract NK cells
| The mechanism of attack involves the release of cytoplasmic granules containing perforin and granzymes
28
Internal factors affecting immune responses to therapeutic proteins
```
Genetic factors - modulating the immune response and related to gene defect
Age related
Disease related
Concomitant treatment
Treatment related
```
29
External factors affecting immune responses to therapeutic proteins
Protein structire
Formulation and packaging
Aggregation and adduct formation
Impurities
30
Ways to reduce immunogenicity
Change AA sequence of glycosylation patterns
Link proteins to polymers
Use humanized versions of the proteins
Reduce the immunogenic response by immunosuppresive treatments
Use another route of admin
31
What is antisense therapy?
Designing an antisense molecule against the mutated part of DNA
Blocks that bit from being read and copied
32
Advantages of antisense therapy
Same effect as enzyme inhibitor or receptor antagonist
Highly specific where the oligonucleotide is 17 nucelotides or more
Smaller dose levels required
Potentially less side effects
33
Disadvantages of antisense therapy
Must target exposed sections of mMRNA
Instability and polarity of oligonucleotides
Short lifetime of oligonucleotides and poor absorption across cell membranes
34
What is micro-RNA (miRNA) and how does it work?
Short segments of double stranded RNA
RISC makes it single stranded (siRNA)
siRNA binds to complementary mRNA region
mRNA is cleaved by enzyme complex- degregated so no gene product sythesised
35
What are the hallmarks of cancer?
```
An inflammatory environment
Insensitivity to growth inhibitors
Limitless replicative potential
Sustained angiogenesis
Self-sufficiency in growth signals
Evasion of apoptosis
Tissue invasion and metastasis
```
36
What drives the hallmarks of cancer processes?
Signal transduction and the activity of tyrosine kinases
37
What is the signal transduction process?
Signal, reception, amplification, transduction, response
38
What converts an external signal to intra-cellular signals?
Conformational changes in the structure of the receptor
39
What are Tyrosine Kinase Receptors?
Receptors with an extra-cellular and intra-cellular domain
40
What does the intracellular domain in RTK's do?
Phosphorylates tyrosine residues in target proteins which can initiate signal cascades and cause changes in expression of genes
41
What are the 3 essential RTK components?
```
Ligand binding site (extracellular domain)
Transmembrane domain (α helix)
Domain with tyrosine kinase activity (cytosolic)
```
42
In what two ways can you modulate kinase activity?
Disruption of ligand-receptor interactions
| Inhibition of kinases
43
Give two drugs the disrupt ligand receptor interactions and explain how they work
Bevacizumab - binds to growth factor and prevents it binding so tumour blood vessel development disrupted (colorectal cancers)
Trastuzumab(herceptin) prevents binding of EGF to HER2 receptor so no signal transduction - onlt if this gene overexpressed
44
Give two drugs that inhibit kinase activity and explain how they work
Imatinib mesylate - inhibits ATP binding to the bcr/abl fusion protein
Gefitinib prevents ATP binding to EGFR - so no dimerisation
45
Give examples of targeted cancer therapies
Disruption of oestrogen and receptor interaction
Inhibiting MAPK signalling (Dabrafenib and vemurafenib)
Inhibit pro-tumour inflammation
Promote anti-tumour inflammation
46
Summarise anti-tumour immune activation
Endogenous tumour antigens released during tumour lysis (by chemo or local radiation)
These are captured by dendritic cells, activated by GLAAS technology t generate an anti tumour immune respone
Immune system attacks the primary tumour and distal metastases
47
Summarise promoting anti tumour inflammation
T cell responses controlled by immune checkpoints to protect the body from damaging immune responses
Develop drugs to target these checkpoints which stops anti tumour T cell mediated responses
48
What is anti-CTLA4 therapy?
monoclonal antibody (ipilimumab) binds to CTLA4 checkpoint blocking signalling and allowing activation of anti tumour T cell response
49
What is PD-1/PD-L1 therapy?
Monoclonal antibodies (Nivolumab) block signal so enables T cell response, T cell proliferation and therefore anti-tumour activity
50
Explain the dental caries process
Sugar meets plaque, acid is release
Acid causes minerals (calcium phosphate) to be lost from the tooth surface into saliva (demineralisation)
Saliva bicarbonate neutralises the acid so minerals go back into the tooth and remineralise it
51
Give 3 predisposing and 3 protective factors of caries
1. Frequent sugar intakes
2. Acid producing bacteria
3. Reduced saliva flow
1. Fluoride
2. Saliva
3. Time
52
What are the risk factors for General and Oral Health?
```
Diet
Stress
Control
Hygiene Smoking
Alcohol
Exercise
Injuries
Obesity
Diabetes
Cancers
Cardiovascular Disease
Respiratory Disease
Mental Illness
Dental Caries
Periodontal Disease
Skin Disease
Trauma-Teeth and Bones
```
53
How many baby teeth do we have and how are they split up?
20
| Into 4 quadrants - A,B,C,D,E
54
How are permanent teeth identified?
1-7
55
Which numbers correlate to which teeth?
1, 2 - incisors
3 - canine
4, 5 - premolar
6,7 - molar
Potentially another 4 wisdom teeth which are molars too
Potentially 32 permanent teeth altogether
56
What bacteria is found in plaque?
Streptococcus mutans
57
What will be affected if you floss incorrectly?
Periodontitis membrane
58
How does fluoride reduce caries?
Held in the enamel and plaque. When the pH drops during an acid attack, the reservoir acts as a source of free fluoride ions.
Calcium fluoride is incorporated into the enamel as hydroxyfluorapatite of fluorapatite as part of remineralisation
59
How old do you have to be to be prescribed Fluoride toothpaste?
2,800 ppm - over 10
| 5,000 - over 16
60
What is plaque called above and below the gumline?
Above - supragingival
| Below - subgingival
61
What is the aquired pellicle of dental plaque?
A conditioning film of saliva on the teeth in the polymicrobial biofilm, which is removed when brushing
62
What is the initial phase of human caries and is it reversible?
'White spot' and it IS reversible at this stage
63
Why do we get human caries? What is the cause?
Eating sugar
Low salivary flow
Low exposure to fluoride
Bacteria involved in the formation of lesions on the basis of their function
64
Which bacteria are best at being acidoduric and acidogenic and what do these terms mean?
Mutans streptococci
Lactobacilli
Acidogenic - ferment sugar to produce acid
Acidoduric - survive acidic conditions
65
Which pH puts you at risk of caries?
A pH lower than 5.5
66
How can we break the caries cycle?
```
Eat less sugar
Good oral hygiene
Antimicrobial agents
Raise Ph of mouth
Oral probiotics
Increase salivary flow
Increase fluoride exposure
Repair enamel
```
67
What is periodontal disease?
Disease of the supporting tissues of the tooth
68
Describe the environment of the gingival crevice
```
Anaerobic
Abundance of protein in the environment
Sometimes a hostil inflammatory response
Further down has less oxygen
Have to be able to cope with inflammation
```
69
What are the four main types of periodontal disease?
Gingival disease
Chronic periodontis
Necrotising periodontal disease
Aggressive periodontitis
70
What is gingivitis and what causes it?
Reversible inflammation of the gums due to poor oral hygiene, hormonal disturbances, drug therapy or smoking
(pre-cursor for periodontal disease)
71
What is chronic periodontis?
Untreated
Cause of teeth loss
Loss of attachment - irreversible
Alveolar bone loss = increased depth and BOP
72
How deep is the periodontal pocket normally?
2mm
73
What are the 'RED' pathogens for periodontal disease?
Porphyromanas gingivalis
Treponema denticola
Tannerella forsythia
74
Where do periodontopathogens come from?
Some can attach to the mucosa and have been isolated from the tounge biofilm
75
What is necrotizing periodontal disease and what symptoms does it have?
An underlying systemic infection
Painful and bad breath
Grey pseudo-membrane on the gingivae
76
What is responsible for aggressive periodontitis?
Aggregatibacter actinomycetemcomitans (AA) leukotoxin
77
What is the treatment for aggressive periodontitis?
Tetracycline
Metronidazole - preffered as targets anaerobes
Amoxicillin
78
What other types of periodontal disease are that occur in certain groups?
Pregnancy gingivitis
Group A streptococcal gingivitis
Diabetes Gingivitis
HIV periodontal disease
79
What is the process that causes periodontal disease?
Plaque accumulates
Host inflammatory response
Flow of GCF increases
Delivery of nutrients and fluid available
Proteolytic bacteria proliferate
Local pH increases (alkaline products from metabolism) - redox reduces
Up regulation of bacteria virulence factors
A change in the resident microflora
80
Which other health factors are people with periodontal disease more likely to have?
```
CVD
Respiratory diease
Diabetes
Risk of premature labour
Risk of low birth weight (then leads to more risks in life)
```
81
Oral bacteria can enter the bloodstream, give 3 examples of what this can cause
Streptococci and endocarditis
Infectious atherosclerosis
Aspiration pneumonia
82
Which surfactant causes toothpaste to foam?
Sodium Lauryl Sulphate
83
What is the role of fluoride and what is the optimum ppm?
Influences remineralisation of enamel
| Inhibits metabolism of some plaque bacteria
84
What is substantivity of antimicrobials?
How long an antimicrobial can maintain its activity for
85
Wht might an antimicrobial be used?
if people cannot maintain oral health using mechanical methods
86
What is chlorhexadine, what is it for and what is it found in?
A broad spectrum anitmicrobial (antiseptic) that reduces plaque, caries and gingivitis
In mouthwash, gel, varnish only
87
What is triclosan and how does it work?
A broad spec bisphenol
Selectively inhibits obligately anaerobic gram negative bacteria
Inhibits acid production, reduces inflammation, inhibits bacterial fatty acid metabolism
Need fatty acids to make membrane so membrane indirectly disrupted
Can be enhanced by formulation with a co-polymer or zinc citrate
NOT FOR MOUTHWASHES (but can be)
88
Give examples of enzymes in dental care and their role
Dextranases and glucanases - modify plaque matrix
Glucose oxidase and amyloglucosidase - boost salivary peroxidase system
Menthol, thymol and eucalyptol can penetrate plaque
Oils - disrupt cell membranes and inhibit enzymes
Plant extracts
89
What are QAC's and how do they work?
Quaternary Ammonium Compounds
e.g. Cetyl-pyridium chloride
Broad spec, substantive
Binds to bacterial cell membranes and disrupts integrity
Inhibits glucan synthesis and co-aggregation
MOUTHWASH ONLY
90
Are metal salts more potent that triclosan, CPC ect?
No, not as potentally antimicrobial
91
What do zinc salts in dental formulations do?
Inhibit bacterial glycolysis so reduce acid production in the mouth
92
What does zinc lactate in dental formulations do?
Inhibits VSC production so reduce smell
93
What do stannous fluorides in dental formulations do?
Inhibit caries formation
| Reduce dental hypersensitivity
94
What properties does Sodium Lauryl Sulphate have?
Detergent - disrupts lipids
| Bactericidal - inactivates bacterial enzymes
95
What is the role of arginine in dental products?
Arginine salts used
Arginine metabolised to ammonia by oral bacteria
Raises pH in mouth, keeping it above the critical caries level
Also a sensitivity agent so blocks dental tubules
96
Why is sugar free gum beneficial?
increase salivation, no sugar so no acid, shear force on oral cavity
97
Give examples of sugar substitutes.
Aspartame
| Saccharin
98
Which sugar substitutes are found in sugar free gum?
Sorbitol, mannitolm lactitol
99
What are probiotics and why might they be used? Give an example
beneficial bacteria that you put on or in you in the hope of having a beneficial affect
Potential life long protection
E.g. - non pathogenic mutans streptococci
100
Which pathogen most commonly causes UTI's and in what % of cases?
E.coli
| 85% cases
101
Which other bacteria can cause UTI's in more vulnerable/immunocompromised people?
```
Staphylococci spp (UT surgery, catheter)
Proteus spp (GIT)
Klebsiella spp (GIT)
Pseudomonas spp (Hospital acquired)
```
102
Why do women get UTI's more often?
Shorter urethra so bacteria have less distance to travel
| Predisposed to ascending infection with Grm –ve bacteria from the GI tract
103
What are the symptoms of a UTI?
Frequency
Dysuria
Urgency
Haematuria
104
How are UTI's managed?
OTC potassium and sodium citrate (alkaline)
OTC analgesia
Public health role (differential diagnosis, pregnancy)
105
When should you refer someone with a suspected UTI?
Pregnancy
Recurrent or non-resolving/worsening cystitis
Children and men
Symptoms suggestive of ascending infection (pyelonephritis)
Diabetes
106
What are the features of pyelonephritis and how do they differ from a normal UTI?
Ioin pain
Fever
Malaise (no temp with regular UTI)
107
Does the bladder naturally have bacteria in?
NO, completely sterile
108
What should stop urine flow back up to the kidney?
Sphincter
109
In which groups doe pyelonephritis need hospital referral?
Pregnant women
Dehydration/unable to keep fluids down
Recurrent pyelonephritis
Men (in whom there is no obvious cause)
110
When might further investigation into pyelonephritis be needed?
Recurrent UTI
>45 with haematuria (blood in urine) that persists after UTI treated
>60 with unexplained non-visible haematuria and raised WCC on dipstick
111
How is a UTI diagnosed?
Symptoms
Urine dipstick for nitrites, leukocytes, protein and blood
Mid Stream Sample of Urine (MSSU)
Treat when symptomatic and urine dipstick is positive (except pregnancy)
112
Why are recurrent UTI's a risk?
They carry an increased risk of renal damage
113
How many episodes of UTI's per year can you have before investigation is requires?
3
114
Why might UTI's be recurring?
Kidney stones
Local obstruction - benign growth, enlarged prostate, congenital
Restricting urine flow
115
What is classified as an uncomplicated UTI?
Women (inc pregnancy)
| Single episode in children
116
What is classified as a complicated UTI?
Men
Structural abnormality - - indwelling catheter, stent, nephrostomy tube, vesicouteric reflux, prostatic hypertrophy, ect ect
117
What is Vesicouteric reflux? What may be the cause in children?
Faulty sphincter
Urine back up ureter taking bacteria with it
May just not be fully developed in children yet
118
What advice on UTI prevention and symptom control should be given?
```
Fluids to pas through and clear bladder
Avoid caffeine and alcohol
Empty bladder often and ensure full emptying
Wipe front to back
Empty bladder after sex
Analgesia
```
119
Why are UTI's a risk in pregnant women?
Very common and often asymptomatic
| Risk of progression to pyelonephritis
120
When are pregnant women screened for UTI's?
At their first midwife appointment (bacteruria screening)
121
If a woman is found to have a UTI during pregnancy, what happens?
Treated with antibiotics even if no symptoms
Urine culture 7 days after antibiotic
Monthly urine cultures after this
122
When should a UTI for children be treated?
When a dipstick is positive
123
How long is treatment for a child with a UTI?
if cystitis/lower UTI treat for 3 days
| if at risk of pyelonephritis or upper UTI treat for 10 days
124
How long is treatment given for a UTI in adults?
3 days treatment
125
If an antibiotic is given for a UTI, what influence the choice of which one to use?
```
Local resistance patterns and formularies
Previous exposure
Culture results
Allergy status/intolerances
Renal function
Likelihood of interactions
```
126
Why does renal function affect the use of antibiotics for a UTI?
Antibiotics are having a local effect
Need to get large concs of antibiotics in the bladder
They wont reach the bladder in large concs if not producing enough urine
127
Which antibiotics are given for a regular UTI?
```
Trimethoprim
Nitrofurantoin
Cephalosporins
Co-amoxiclav
Quinolones
Gentamicin – IV ONLY
```
128
How long are antibiotics given for a complicated and uncomplicated UTI?
3-5 days
(uncomplicated)
7 -10 days
(complicated)
129
Which antibiotics are given for a recurrent UTI?
```
Treat as UTI,
Trimethoprim
Nitrofurantoin
Cephalosporins
Co-amoxiclav
Quinolones
Gentamicin – IV ONLY
BUT consider prophylaxis with Trimethoprim
```
130
How long are antibiotics given as prophylaxis for a recurrent UTI?
3-6 months
131
Which antibiotics are given to treat acute pyelonephritis?
2nd-generation cephalosporin – BROAD SPEC
Quinolone
Gentamicin
132
Give examples of 2nd gen cephlosporins used in pyelonephritis?
Ceflacor (oral)
| Cefuroxime (IV)
133
Which antibiotics are used to treat asymptomatic bacteruria?
Pregnancy
1st line: nitrofurantoin (avoid at term)
2nd line: cefalexin
134
How long are antibiotics given to treat asymptomatic bacteruria?
7 days
135
How long are antibiotics given to treat acute pyelonephritis?
14 days
136
Why is Trimethoprim contraindicated in the first trimester of pregnancy?
It is a folate antagonist
137
What are the side effects of Trimethoprim?
Blood disorders long term
| Bone marrow suppression
138
What are the side effects of Nitrofuratoin?
Nausea, GI disturbance
Many people vomit
Rarely, pulmonary reactions, peripheral neuropathy- stop immediately
Contraindicated in renal impairment
139
What are the side effects of Cephalosporins/penicillins?
GI disturbances
| C diff risk
140
What are the side effects of 4-quinolones?
Rarely arthralgia, tendon damage
Caution in epilepsy
broad spectrum so C diff risk
141
What are the side effects of Gentamicin?
Nephrotoxic, ototoxic
142
What is the Pharmacists role regarding UTI's?
```
Differential diagnosis and referral
OTC treatments (analgesia, alkanising agents)
Lifestyle advice
Advice on use of antibiotics
Monitoring for side effects
```
143
Which antibiotics target Cell wall synthesis?
```
Cycloserine
Vancomycin
Bacitracin
Penicillins
Cephalosporins
Monobactams
Carbapenems
```
144
Which antibiotics target Folic acid metabolism?
Trimethoprim
| Sulfonamides
145
Which antibiotics target DNA gyrase?
The Quinolones Nalidixix acid and Ciprofloxacin
| Novobiocin
146
Which antibiotics target RNA elongation
Actinomycin
147
Which antibiotics target Cytoplasmic membrane structure and function?
Polymyxins
| Daptomycin
148
Which antibiotics target DNA directed RNA polymerase?
Rifampin
| Streptovaricins
149
Which antibiotics target Protein synthesis 50s?
Erythromycin (macrolides)
Chloramphenicol
Clindamycin
Lincomycin
150
Which antibiotics target Protein Synthesis 30s?
```
Tetracyclines
Spectinomycin
Streptomycin
Gentamycin
Kanamycin
Amikacin
Nitrofurans
```
151
Which antibiotics target lipid biosynthesis?
Platensimycin
152
Which antibiotics target protein synthesis (tRNA)?
Mupirocin
| Puromycin
153
What is Isoniazid used to treat?
TB
154
What is antibiotic resistance?
The acquired ability of a microorganism to resist the effects of a chemotherapeutic agent to which it is normally sensitive (some are naturally resistant before exposure)
155
What is the difference in generation time of human vs human-associated bacteria?
Human: 10-15 million minutes
| Human-associated bacteria: 20-100 minutes
156
What is the difference in abundance of human vs human-associated bacteria?
Human: 6.070,000,000
| Human-associated bacteria: 697,000,000,000,000,000,000,000
157
What are 5 biochemical mechanisms of antibiotic resistance
```
Overproduction/alteration of target
Alternative pathway (bypass)
Decreased influx/increased efflux
Drug modification
Drug destruction
```
158
How do bacteria get antibiotic resistance genes?
Mutation - spontaneous
| Horizontal gene transfer
159
Summarize the three types of horizontal gene transfer
Transformation - free DNA into bacterial cell (can be plasmids)
Conjugation - plasmid transfer cell to cell
Transduction - involves bacteriophages
160
Are plasmids independent of chromosomal DNA?
Yes
161
Can plasmid replication occur independently?
Yes
162
Do plasmids only carry genes for normal growth? Which types of genes do they carry?
No
| Normal, extra, genes for
163
How does conjugation occur?
Ferility factor - transfer pilius connects 2 organisms together and DNA can transfer down the tube
164
What issue do microbial biofilms have?
The organism is susceptible when screened but when embedded in a biofilm it is not susceptible to antimicrobials
165
Antibiotic resistance increases with:
Use and time
166
What are the next steps against antibiotic resistance?
Antimicrobial stewardship
Combination therapy
Develop new antibiotics
