Infection Flashcards
(232 cards)
1
Q
what is infection prevention?
A
Infection prevention and control (IPC) prevents patients and health workers from being harmed by avoidable infection and as a result of antimicrobial resistance.
Infection prevention also includes vaccination against preventable diseases and antibiotic prophylaxis for surgical procedures and recurrent infections
2
Q
what are the 3 things neccessary for infections to spread?
A
Source: Places where micro-organisms live (e.g., sinks, surfaces, human skin)
Susceptible Person with a way for micro-organisms to enter the body
Transmission: a way microorganism are moved to the susceptible person
3
Q
what are the 2 tiers of reccommended precautions to prevent the spread of infections in healthcare settings?
A
Standard Precautions are used for all patient care. They protect healthcare providers from infection and prevent the spread of infection from patient to patient
Transmission-Based Precautions are the second tier of basic infection control and are to be used in addition to Standard Precautions for patients who may be infected or colonized with certain infectious agents. The Personal Protective Equipment (PPE) recommended will be dependent on the mode of transmission
4
Q
healthcare associated infections?
A
Healthcare associated infection (HCAI) is defined as any infection acquired in relation to the delivery of healthcare in its widest sense. This includes care in hospitals and in the community via General Practitioners and health centres
5
Q
clostridium difficile
A
Bacteria that causes infection when the guts normal flora is disrupted or if immunocompromised
Prior treatment with antibiotics (especially broad-spectrum) is one of the main risk factors for C.difficile infection
Produce toxins that damage the lining of the colon
Symptoms range from mild, self‑limiting diarrhoea to perforation of the colon, sepsis and death
Infection can commonly reoccur in patients
Can be spread between patients on hospital wards via contact transmission from infected faeces
Spores survive in the environment for a long time
Spores are not killed by alcohol gel, hands must be washed with soap and water
6
Q
screening for resistant organisms?
A
High-risk patients are screened for resistant organisms when they are admitted into hospital or before any operation
This is to ensure that any patient colonised with a resistant organism is managed with appropriate infection control measures to avoid passing the resistant organisms to other patients
Antibiotic therapy may also need to be adjusted to ensure that treatment given cover this additional resistance
Patients can be screened for:
MRSA (Methicillin Resistant Staphylococcus aureus infections)
Nose, throat, groin + any wounds
GRE (Glycopeptide resistant enterococci)
Rectal swab
CPO (Carbapenemase-producing organisms)
Rectal swab
7
Q
pneumococcal vaccinations?
A
Pneumococcal vaccines protect against Streptococcus pneumoniae a
pathogen which can cause severe infections like meningitis, sepsis and
pneumonia
* The vaccine is now given as part of routine childhood immunisations
* Additional doses are recommended for all patients over the age of 65 and in
the “at risk groups” detailed in the green book
* The vaccination programme has been highly successful in reducing the
frequency of invasive pneumococcal infections caused by strains covered by
the vaccine including near elimination of some strains
8
Q
causes of resisitance?
A
over prescribing of antibiotics
patient non compliance
poor quality of antibiotics
use of antibiotics in domestic animals
poor hygeine and sanitation
lack of new antibiotics being developed
9
Q
consequences of antimicrobial resistance at patient level
A
delay in appropriate antibiotic therapy
increased hospital length of stay
alternative antibiotics need to be used
10
Q
what is antimicrobial stewardiship?
A
An organisational or
healthcare-system-wide
approach to promoting and
monitoring judicious use of
antimicrobials to preserve
their future effectiveness
11
Q
what is prudent prescribing?
A
Prudent prescribing is not to
prescribe as few antibiotics as
possible but to identify that small
group of patients who really need
antibiotic treatment and then
explain, reassure and educate the
large group of patients who don’t
12
Q
evedience gathering of bacterial infection
A
- drug allergy history
antibiotic treatment
local antimicrobial prescribing guidance
clinical indication
cultures
13
Q
empirical antibiotics
A
When is empirical treatment indicated?
* When pathogen and/or antibiotic sensitivities are uncertain (best guess)
* What two main factors determine how effective empirical treatment will be?
* Local pathogen epidemiology data
* Local antibiotic sensitivity data
* How should empirical therapy evolve when following best practice?
* Streamline to narrow-spectrum antibiotic when sensitivities are available
14
Q
narrow spectrum antibiotics
A
more specific and are only active against certain groups or strains of bacteria
15
Q
broad spectrum antibiotics
A
inhibit a wider
range of bacteria and are
more likely to drive
resistance and have
increased likely hood of
causing C.difficile infection
16
Q
antibiotic classes
A
access, Watch and Reserve,
taking into account the impact of different antibiotics and antibiotic classes
on antimicrobial resistance, to emphasize the importance of their
appropriate use.
17
Q
access antibiotics
A
First or second choice
antibiotics
offer the best
therapeutic value, while
minimizing the
potential for resistance
18
Q
watch antibiotics
A
First or second choice
antibiotics only
indicated for specific,
limited number of
infective syndromes
More prone to be a
target of antibiotic
resistance and therefore
prioritised as targets of
stewardship programs
and monitoring
19
Q
reserve antibiotics
A
Highly selected patients
(life-threatening
infections due to multi-
drug resistant bacteria)
Closely monitored and
prioritised as targets of
stewardship programs
to ensure their
continued effectiveness
20
Q
infection
A
Invasion of the body or a body part by a pathogenic organism, which multiplies and
produces harmful effects on the body’s tissues
21
Q
colonisation
A
the presence and multiplication of microorganisms without tissue invasion or damage
22
Q
carriage
A
the condition of harbouring a pathogen within the body e.g. nasal carriage of MRSA
23
Q
benefits of iv to Po switch
A
Remove lines quicker – reduce risk of line related infections and phlebitis /
thrombophlebitis
* Reduced nursing work load
* increased patient satisfaction and comfort
* Facilitate earlier discharge
* Decreased costs
* Most sustainable – less plastic needed
* Narrow spectrum agents – reduce AMR and other consequence of broad
spectrum agents such as C.difficile
24
Q
Why is there so much inappropriate prescribing of antibiotics?
A
lack of awareness
time constraints
decision fatigue
uncertain diagnosis
assuming that other prescribers are the problem
patient satisfaction and pressure
25
agent
A substance, living or non-living, or a force, the excessive
presence or relative lack of which may initiate a disease process
26
infection
Entry and development or multiplication of an infectious
agent in the body of human or animals
27
transmission of infection
Spread of infectious agent through the
environment to another person from the reservoir and source
28
3 major ways pathogens can be transported
1. Transmission between humans
2. Via environmental factors (such as soil or water)
3. Between humans and animals (via vectors)
29
zoonoses
Zoonoses are infectious diseases where
the pathogen is transmitted from an
infected animal to a human (in these
cases the animals are the reservoirs)
30
vector borne trnsmission
where part of
the life cycle of the pathogen takes places
in the human host, however, part of the life
cycle must take place in another species
which is known as the vector
31
broad spectrum antibiotics
target both gram positive and negative
32
infection pathogenesis : listeria monocytogenes
1. colonisation
2. invasion
3. proliferation
4. dissemination
33
pathophysiology
study of the underlying mechanisms by which diseases occur and develop
34
3 systemic effects of infection
fever
sepsis
organ dysfunction
35
host defense against infections
innate immune responses
adaptive immune responses
36
primary function of lymphocytes
b= generates diverse activity
t= secretes chemical messengers
plasma cell= secretes antibodies
nk= destroys virally infected cells
37
pneumonia
Inflammation of the lungs caused by a bacterial or viral infection, in which the air sacs fill with pus and can become solid
1) Community acquired pneumonia (CAP)
2) Hospital acquired pneumonia (HAP)
3) Aspiration pneumonia
oral antibiotics (amoxicillin)
Rescue packs are often made up of:
* Antibiotic: Doxycycline 200mg stat, then 100mg OD (5 – 7 days)
* Oral steroid: Prednisolone 30mg OD (5 – 7 days)
38
prophylactic antibiotics
Before offering prophylactic antibiotics;
* Ensure patients have had sputum cultures and sensitives completed rule out other causes (E.g. TB)
* Ensure patients have had training in airway clearance to ensure sputum is being adequately cleared
* Ensure patient have CT scan to rule out other pathologies (e.g. lung cancer)
* Consider getting advise from respiratory specialists
39
selective toxicity
ability of drug to kill or inhibit pathogen while damaging host as little as possible
40
broad spectrum drugs
target and inhibit many kinds of bacteria
41
narrow sectrum drugs
effective only against a limited variety of bacteria
42
bacteriostatic
Prevent bacterial
growth (no killing)
* Reversible effect
* Bacterial clearance
depends on the
immune system
>4
43
bactericidal
kill the target bacteria
irreversible effect
appropriate in poor immunity
<4
44
minimal inhibitory concentration
lowest concentration of drug that
prevents the visible growth of the pathogen
* It varies against different bacterial species (spectrum of activity)
* Indicator for assessing bacterial drug resistance
45
minimal bacterial concentration
lowest concentration of drug that kills the patogen
46
antimicrobial activity can be measured by...
dilution susceptibility
disk diffusion
the Etest
47
dilution susceptibility tests
Used to determine MIC and MBC values.
* Inoculating media with different concentrations
of a drug and fixed number of bacteria.
* Broth or agar with lowest concentration
showing no growth is MIC.
* Liquid media from tubes that showed no
growth are then cultured into agar plates
* The lowest antibiotic concentration from the
tubes that fails to support the microbe’s
growth is the MBC
48
disk diffusion test
used to determine susceptibility or resistance
* Measurement of the clear zones diameter
(no growth) around disks compared to a
standardized chart, determining
susceptibility or resistance
* Diameter correlates with MIC (empirically)
Wider clear zone indicates that a microbe
is more susceptible to that antibiotic.
Narrower clear zone indicates drug
resistance
49
the Etest
* Bacterial is inoculated on agar,
then Etest® strips are placed on
the surface.
* Etest® strips contain a gradient of
an antibiotic.
* Intersection of elliptical zone of
inhibition with strip indicates MIC
17
* Sirirat/Shutterstock
50
most common causative organisms
streptococcous pneumoniae
influenza viruses
51
CURB-65
confusion
urea over 7
respiratory rate over 30
blood pressure less than 90/60
age more than 65
0-1 is low= amoxicillin 500mg TDS (5 days)
2 is moderate= amoxicillin + clarithromycin
3= high= co-amoxiclav
52
hap
hospital cquired pneumonia
non-severe= co-amoxiclav 625mg TDS
severe= tazocin 4.5g TDS
53
sepsis
syndrome defined as life threatening organ dysfunction due to dyregulared host response
54
coagulopathy
DIC formation of microemboli and haemorrhage= loss of peripheral digits or limbs
55
sepsis treatment
give high flow oxygen
take blood cultures
give iv antibiotics
give iv fluids
measure lactate
meaure urine output
WITHIN FIRST HOUR
56
start smart then focus
give broad antibiotic--> give narrow agent
48-72 hours of iv antibiotic--> review
57
antibiotic choice
source of infection
patient characteristics
antimicrobial resistance
immunisation status
local guidlines
58
sepsis unkown source
>20 no penicillin allergy= amoxixillin and gentamycin
>20 penicillin allergy= levofloxacin and gentamycin
<20 no peniccilin allergy= tazocin and clarithromycin
<20 peniccilin allergy= meropenem
<20 severe penicillin allergy= vancomycin
59
gentamycin
dependant on weight
ototoxicity
nephrotoxicity
narrow therapeutic index
dangerous side effect profile
check renal function twice a day (<20-30ml= change)
short course
report any hearing problems
60
metronidazole
peripheral neuropathy
blood dyscrasis
avoid sun (topical)
avoid alc (oral/iv) (OSCE)
61
vancomycin
loading dose--> body weight
mainatnenece ose--> renal function
ototoxicity
nephrocity
infusion related reactions
narrow therapeutic index
must be given slowly over hours
monitor twice weekly
62
sepsis chest source
<48 hours = community acquired pneumonia
non pen = co amoxiclav and clarithrimycin
pen all= levofloxacin
> 48 hours= hospital acquired pneumonia
non pen=tazocin
pen all= meropenem
severe pen all= levoflaxin
63
sepsis abdominal
> 20 no pen = amoxicillin
> 20 pen all= gentamycin
<20 no pen= tazocin
<20 pen all= meropenem
<20 severe pen=teiclopleinin
64
teicoplanin
loading= weight
maintan= weight+ renal function
blood dyscraesias
nephrocitoxicity
therapeutic drug leves
65
sepsis urine
>20 = gentamycin
<20 no pen= tazocin
<20 pen all= meropenem
<20 sev pen all+ ciproflaxacin
66
bacterial meningitis
an infection of the surface of the brain by bacteria leading to inflammation. the infecting bacteria have usually travelled there from anither mucosal surface via the oatients blood stream
67
meningitis risk factors
chemo therapy
winter months
incomplete vaccines
smokers
chronic patients
infection
living in crownde hoiseholds
age
68
complications of meningitis
death
stroke
neurologiccal complications
physical complications
69
meningitis symptoms
fever
nausea
lethargy
irritability
refuse food/ drink
headache
muscle pain
chills shivering
no blanching rash
stiff nec
cold hands
unusual skin colour
hyptension
back rigidity
70
meningistis diagnosis
drug history
patient history
physical exam
lumbar punture
CT scan of head
blood tests
identify risk factors
71
meningitis treatment
over 60
no pen= ceftrixaone
pen all= chlorampheicol
pen resistance= vancomycin
viral = aciclovir
under 60
no pen= ceftrixone
pen all= chloramphenicol
pen resis= vancomycin
viral = aciclovir
72
bacteria are .. cells
prokaryotic
without a nucleus
without membrane bound organelles
73
antimicrobial chemotherapy
drugs to treat infectious diseases, having selctive toxicity against the pathogens involved, while damaf]ging the host as little as possible
74
selective toxicity
ability to kill or inhibit pathogen while damaging host as little as possible
75
bacteriostatic
inhibit growth
76
bactericidal
kill the bacteria
77
measuring effectiveness of antimicrobial drugs
minimal inhibitory concentration (lowest concentration of drug that prevents the visible growth of the pathogen)
minimal bactericidal concentration (lowest concentration of drug that kills the pathogen)
78
MBC/MIC >4
bacteriostatic
79
MBC/MIC <4
bacteriocidal
80
antimicrobial activity tests
dilution suceptibility test
disk diffusion tests
the etest
81
gram positive
thick peptidoglycan
82
gram negative
thin peptidoglycan
83
peptidoglycan formation
bacterial transpeptidase form peptide cross-link bridges between tetrapeptide of NAMs of peptidoglycan strands
beta lactam bind to and block transpeptidases which block new cell wall formation and bacterial lysis
84
inhibitors of cell wall synthesis
b lactam antibiotics
cephalosporins
glycopeptide
carbapenems and monobactams
85
b lactam antibiotics
block formation of peptide bridges
bactericidal effect and high therapeutic index
subclasses= penicillins, cephalosporins, carbapenams, monobactams
86
natural penicillins
penicillin G and V
narrow spectrum
very low resistance to b lactamase
87
semisynthetic penicillins
antistaphyloccocal pen (narrow,flucloxallin)
aminopenicillins (broad ,ampicillin, amoxicillin(gram neg)(co-administered))
antipseudomonal pen (extended broad, piperacillin, combination)
88
penicillin adverse effects
rash
anaphylaxis
death
croos reactivity (avoid beta lacatams)
GI distress
CNS toxicty
contraindications= hypersensitivity
penicillin resistance
89
cephalosporins
structurally and functionally similar to penicillins
beta lactam ring
bactericidal
early(cefalexin) = gram +
late (cefotaxime)= gram -
5th gen (ceftaroline)= both
90
cepholasporin side effects
all to pen
react with alcohol
nephrotoxicity
disturb gut flora
91
carbapenems and monobactams
beta lacatms
same mechanisms of penicillin
broad spectrum
92
glycopeptide
not beta lactam antibiotics
vancmycin is a glycopeptide
inhibit cell wall synthesis
binds to terminal amino acids linked to NAM of peptidoglycan
prevents the transpeptdation without targeting the enzyme
only effective against gram +
93
glycopeptide side effects
ototoxicity
nephrotoxicty
red man syndrome
agranulocytis
94
antibiotics for inhibition of protein synthesis
aminoglycosides (mRNA misreading)
tetracyclines (block attachement of tRNA site A)
macrolides (prevent translocation step)
lincosamines( prevent translocation step)
oxazolidines (interfere with the translation initiation)
chloramphenicol (block the attachement of tRNA)
95
translation in bacteria
initiation= ribosome assemle with the mRNA and the first tRNA
elongation= amino acids are brought to the ribosome by tRNAs and linked together to form a chain
termination= the finished polypeptide is released and the ribosome is dissassembled
96
aminoglycosides
a cyclohexane ring and amino sugars
distrupt protein elongation
bactericidal effect
irreversible binding to 30s
mainly used for aerobic gram -
IV infused or appled locally
narrow therapeutuc range
ototoxicity
nephrotoxicty
neuromuscular toxicity
97
tetracyclines
4 cyclohexane core structure
bacteriostatic
inhibition of protein synthesis elongation
broad spectrum
GI distress
photosensitivity
staining of teeth
hepatotoxicity
headache and visual disturbances
contraindicated in children and pregnant
interact with many things
do not give to children under 12
98
macrolides
inhibition of protein elongation
' thromycin'
bacteriostatic effect
block translocation step
broad spectrum
can use in pen all
GI disit
hepatoxicoty
dry mouth
interact with a lot of things (OSCE, PAPE)
99
lincosamines
'damycin'
inhibition of protein elongation
bacteriostatic
Gram +
broad spectrum
GI distress
cross resistance with macrolites
100
oxazolidines
inhibition of protein elongation
against gram +
bacteriostatic effect
thrombocytopeinia
severe optic neuropathy
101
chloramphenicol
inhibition of protein elongation
bacteriostati
broad
apkastic anaemia
blood disorder
hypersensitivity
102
antibiotics acting as antimetabolites
sulfonamides
103
antimetabolites
block functioning bacterial metabolic pathways
stop progression of the metabolic pathway
bacteriostatic
broad
selective toxicity
104
sulfonamides
folic acid is essentia to produce purines (DNA)
act by competing with PABA as a substrate for the enzyme synthesis
bacteriostatic effect
higjly selective
105
trimethoprim
DHFR targeted by trimethoprim
bacteriostatic effect
106
sulphonamides SAR
free para amino group
para substituted phenyl ring
sulphonamide
sulph and amino group directly attached to the aromatic ring
R2
107
penicillins SAR
strained b lactam ring
COO-
bicyclic ring
acylamino side chains
sulphur is usual but not essential
Cis stereochemistry of the bicyclic ring
108
acid resistant penicillins
issue 1= sensitive to acidic pH
Issue 2= limited breadth of activity
109
broad spectrum penicillins
hydrophobic group (the more hydrophobic --> the less active on gram negative)
hydrophillic groups = better activity on gram negative, less on gram positive
110
b lactamse inhibitors SAR
strained beta lactam ring
enol ether group
no substitution at C-6
R stereochemistry
COOH group in C2 and OH in C-9
111
cephalosporins SAR
variations of the 7-acylamino side chain
variations of the 3-acetoxymethyl side chain
extra substitution at carbon 7
112
antibiotics that inhibit nucleic acid syntheis
fluoroquinolones (topoisomerases)
rifamycines (RNA polymerase)
113
fluoroquinolones
'floxacin'
broad
bactericidal effect
Gram - and +
inhibit DNA replucation by interfering with the bacteria topoisomerases leading to cell deeath
DNA gyrase (gram -)(coils)
Topoisomerase IV (gram +) (unraveles)
GI distress
tendonitis
prolongs QT interval
seizures
risk of aortic aneurysm
114
rifamycins
inhibition of the inatioation of bacterial DNA transcriptio by blocking activity of the beta subunit of the bacterial RNA
broad
GI distres
minor hepatotoxicity
discolouration of body fluids
many interactions
rapid development of resistance
115
antibiotics that have alternative mechanisms
nitroimidazoles (metronidazole)
nitrofurantoin
116
nitromidazoles
metronidazole
generating free radicals in bacteria
bactericidal effect
leads to DNA fragmentation
only aerobes
low redox potential
treat infection of anaerobic bacteria
GI distress
skin reaction
taste disturbances
peripheral neuropathy
avoid sulight when topical
117
nitrofurantoin
generating reactive free radicals in bacteria
generate instable metabolites
bactericidal effect
discoloration of body fluids
pulmonary toxicit
peripheral neuropathy
blood disordes
118
treatment for tuberculsis
newly diagnosed= (RIPE) Rifampicin + isoniazid + pyrazinamide+ ethambutol (2 months)
continuation phase= (RI) rifampicin= isoniazid (4 months)
re treatment (7 months) = RIPE+ strepomycin
119
innate antibiotic resistance
bacteria are naturally resistant to an antibiotic
120
accquired antibiotic resisitance
when there is a change in the genome of a bacterium acquring the ability in the presence of a drug by mutations, vertical transfer, horizontal transfer
121
persistant bacteria (drug tolerant bacteria)
bacteria in biofilms produce a polysacharide matrix, representing a physocal barrier that antibiotics and immunity struggle to penetrate effectively
dormant and slowly-dividing cells--> slow metabolism --> difficult to be inhibited
122
drug resistance acquisition
transmission of DNA from parent to offspring
bacterial chromosomes and plasmids
through asexual reproduction
cell division
plasmid DNA replication
conjugation
transduction
transformation
123
conjugation
horizontal transfer
transfer from a donor cell to a recipient cell genetic variation
124
transduction
horizonatl transfer
no direct contact
transfer gentc material between bacterial cells by viruses
125
transformation
bacterial cell taking up DNA from the environment
donor cell could release DNA, when they are killed
126
mechanism of drug resistance
alteration of the drug target site
drug inactivation
reduced drug intake into the cell
drug efflux
127
alteration of the drug target site
mutations in specific genes that encode an altered drug target
usually occuring at the chromosomal level
altered target site--> decreased drug-target binding affinity
128
drug inactivation
producing enzymes that break down antibiotics
acquisition of genes that produce a new enzyme that tramsfers of an unusual chemical group to the drug, making it ineffective
129
limiting drug uptake
physical barrier to void/ reduce the cell entry of antibiotics
130
drug efflux
bacteria expressing efflux pumps --> pumping kees the concentration of antibiotic below therapeutic levels
131
antimicrobials
include antibiotics , anti virals and antibacterials
132
clostridium difficile
gram + anaerobe
minor part of gut flora
risk factors: exposure to broad spectrum antibiotics
multiple antibiotic exposures
proton pum inhibitors
co morbidities
133
pseudomonas aeruginosa
gram - bacillus
not a part of natural flora
opportunistic pathogen
immunocompromised hosts are susceptible
134
infection markers
fever
rigor
chills
myalagia
malaise
headache
anorexia
delirium
erythema
pain
heat
swelling
pus
change in body temo
tachycardia
hypotension
tachypnoea
135
infection markers
increased white blood cells
changes to neutrophils
increased platelets
increased C reactive protein
increased erythrocyte sedimentation rate
increased serum creatinine
increased liver function test
change to procalcitonin level
presence of organism
microscopy
culture
serology
polymerase chain reaction
136
what do you want an antibiotic to do
bond to target
occupy an adequate number of binding site
remain at binding site for sufficient time period
137
dose optimisation
time and concentration should be above the MIC
138
machanism of resistant
penetration resistance
efflux pump
hydrolysis
mutation of the binding site
139
principes of therapy
antibacterial drug choice
antibacterial, considerations before starting therapy
advice to be given to patients anf their family
antibacterials considerations during therpay
superinfection
notifiable diseases
sepsis and arly management
140
blind antibacterial pescribing
give broad then narrow when you know what is the infection
141
symptoms of HIV
stage 1 flu like symptoms
stage 2 majority are asymptomatic
stage 3- AIDS CD4 level<200 cells/mm3
142
HIV treatment effectiveness tests
when patients are taking HIV treatment, the viral load is a more important indicator of their jealth and of the effectiveness of the treatment than the CD4 cell count
143
principle of combination therapy
cobining different antiviral drugs with distinct mechanisms of action having a probed synergistic activity against HIV and HCV
144
the goals of HAART in patients with HIV infections
reduce plasma viral RNA to an undetectable level
improve the immune system functions
prevent or reduce drug resistance
reduce morbididty and mortality
improve life quality
prevent HIV transmission
145
initial HIV regimen
3 or mpre HIV drugs
three times daily
with food
146
simplified HIV regimen
1 combination HIV drug
once daily
no food neccessary
147
goals of DAAs combinational therapy
eradivate virus
prevent the mergence of drug resistance
reduce risk of all caise mortality
broaden the spectrum of antiviral voverage
shorten the treatment, improving adherance
improve life quality
prevent HCV transmission
148
azole antifungals
triazoles
imidazoles
149
triazoles
flucanazole
itranconazole
150
imidazoles
clotrimazole
miconazole
151
polyene antufungals
amphoterin B (need to test first)
nystatin
152
echinocandin antifungals
andilafugin, casofungin and micafungin
153
types of antifungals
flucytosine
echinocandin
polyene
azole
griseofulvin
terbinafine
154
aspergillosis
caused by aspergillus species in soil
aerolised spores
immunocompromised patients
fever,cough, pleuritic pain
voriconazole 200mg bd--> amphotericin b 3mg/kg
155
candidiasis
miconazole
clotrimazole
vaginal
oral
156
systemic candidiasis
infection of blood or other normally sterile sites
fever, tachy
casofungin
fluconazole
157
cryptococcosis
found in bird excrements
lungs are effected
pyexia, cough, dyspnoea, chest pain, weight loss, fatigue
fluconazole or amphotericin b
158
cryptococcal meningittis
progressive, life threataning, chronic or subacute meningitis
headache, meningismus
amphoyerin b and flucytosine followed by fluconazole after 2 weeks for 8 weeks
159
histoplasmosis
from soil/ bird droppings
asymptomatic
can spread to eye (blindness)
fever, headache mor dyspnoea
itraconazole or amphoterin b (severe)
160
skin and nail infections
treated otc
azole
161
GI infections
diverticulitis
gastroenteritis
parasites
162
diverticulitis
small bulges or pockets that can develop in the lining of the intestine as people age
If the diverticula become inflamed or infected, causing more severe symptoms, it's called acute diverticulitis
treament usually involes dietary manipulation
constant, more severe abdominal pain
* pyrexia
* diarrhoea or constipation
* mucus or blood in the stools, or sometimes rectal bleeding
when to refer= uncontrollable abdominal pain, dehydration, unalble to tolerate antibiotics, over 65
treatment= co-amoxiclav 500/125mg tds 5days
163
gastroenteritis
enteric infection with viruses, bacteria and parasites
sudden onset diarrhoea, faecal urgency, bloods/mucois in stools
Transmission of gastrointestinal infection from person-to-person may occur
through one or more of a variety of different pathways, including faecal-
oral, foodborne, environmental, and airborne routes
164
GI parasites
cryptosporidiosis
=transmitted by animal-to-human or human-to-human contact, by occupational or
recreational exposure to contaminated land or water, or by consuming contaminated water
or food
* usually lasts for 1–2 weeks, and recurrence of symptoms is reported in around one-third of
cases
giardiasis
=can be transmitted by person-to-person spread by the faecal-oral route; by contact with the
faeces of infected animals; by consumption of contaminated food or drink; waterborne
including swimming in contaminated water; or by sexual transmission, particularly among
men who have sex with men
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GI treatments
oral rehydration
antimobility
antibiotics
DAMN (if diarrhoea/ vomiting) (Diuretics, ACEi, metformin, NSAIDs)
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eye infections
conjunctivitus
styes
blepharitis
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conjunctivitis
red eye with discharge
without visual disturbances
cloramphenicol eye drops
self limiting
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styes
acute onset painful, localised swelling near the eye margin
usually unilateral
antibiotic treatment not indicated unless accompying conjunctavitis, l
large stye not clearing
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blepharytis
burning, itching and or crusting of the eyelids
symptoms are worse in the morning
both eyes
recurrent hordeolum
contact lens intolerance
cure not henerally possible
symp treat= gently wash twice daily
antibiotic for anterior blepharitis
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dental abscess
pain
unpleasant taste
fever and malaise
trismus in severe cases
emergency if airway compromised, spreading infection
refer to dentist
analgesia
amoxicillin
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malaria
potentially serious plasmodia sp, parasitic infection tansmitted by bie of infected mosquito
fever
sweats
malaise
diarrhoea
cough
impaired conciousness
severe anaemia (severe malaria)
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travellers to malarious regions ABCD
awareness of risk
bite avoidance
chemoprophylaxis
diagnosis
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malaria drugs
* Chloroquine (weekly), proguanil (daily): start one week before travel, for duration of travel AND for four weeks after return
* Doxycycline (daily): start 1-2 days before travel, for duration of travel AND for four weeks after return
* Mefloquine (weekly): start 2-3 weeks before travel, for duration of travel AND for four weeks after return
* Atovaquone/proguanil (daily): start one week before travel, for duration of travel AND for seven days after return
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UTIs
cuystitis
complec UTI
pyelonephritis
urosepsis
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cystitis
pain when urinating
frequency and urgancey of urinating
infection/ inflammation of blader
Occurs when bacteria pass up along urethra and enter and multiply within the bladder, causing inflammation
Normal Symptoms
* Signs of impending attack: itching or pricking sensation in urethra
* More frequent desire to pass urine
* Urgent need to pass urine throughout day and night
* Can only pass few burning, painful drops of urine (dysuria)
* Bladder may not feel completely empty after urinating
* Cloudy and strong-smelling urine: sign of bacterial infection
Symptoms Needing Referral
* Haematuria (blood in urine)- may just be severe UTI, but could be kidney stone (blood with pain) or
potentially bladder/kidney cancer (blood but no pain)
* Symptoms suggestive of upper UTI- pain in lower back, loin pain and tenderness, systemic
symptoms such as fever, nausea and vomiting
* Abnormal vaginal discharge- local fungal or bacterial infection
* Cystitis symptoms & alteration in vaginal discharge & lower abdo pain= ? chlamydia
treat= sef-limiting, antibiotics , siple analgesia, alkalysing agents
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complicated lower UTIs
POM treat= nitrofurantoin or trimethoprim, pivmecilliam
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pyelonephritis
infection/ inflammation of kidneys
Happens when the bacteria that cause cystitis travels from the bladder up to one or both kidneys
fever, shivers, nausea, pain in lower back
must treat with antibiotics, mkigyt need analgesia too
severe=
If CrCL over 30mL/min
* Gentamicin OD IV for max of 5 days
If CrCL under 30mL/min
* Piperacillin-tazobactam (Tazocin®) 4.5g IV TDS
* OR Meropenem IV (for non-severe penicillin allergy)
* OR drug as per micro advice in severe penicillin allergy
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urosepsis
bacteria from uti move into bloodstream
As person’s body tries to fight the infection, it can cause heart rate, fever, chills and confusion, which can lead to organ failure and death
o heart rate and respiratory rate
o Fever and chills
o Little to no urine output (oliguria or anuria)
o Anxiety, impending sense of doom/death
o Dizziness, inability to focus, loss of consciousness
o Organ failure and septic shock (low BP, cyanosis, pale extremities)
o UTI symptoms
treat=
If CrCL over 30mL/min
* Gentamicin OD IV for max of 5 days
If CrCL under 30mL/min
* Piperacillin-tazobactam (Tazocin®) 4.5g IV TDS
* OR Meropenem IV (for non-severe penicillin allergy)
* OR drug as per micro advice in severe penicillin allergy
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barriers of managing UTIs
* Resistance
o High rates of UTI resistance due to mismanagement in past
o Push to have urine MSU to ensure appropriate, targeted treatment
* Prophylaxis
o Not a common practice anymore
o Increases risks of resistance
o Is common in children, try to avoid in elderly
* Commissioning of services
o UTI service not available in all community pharmacies
o No equity in service provision across Wales
* Misdiagnosis (e.g. confusion and falls)
o Treating UTI may resolve these issues
o Quick and easy to rule out UTI
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pathogen
A pathogen is defined as an organism causing disease to its host (human).
Pathogens are taxonomically widely diverse (appearance, size).
Acellular pathogens (non-living): viruses
Cellular (living) pathogens: bacteria, fungi, protozoa and parasites
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protozoan causing malaria
from the genus plasmodium
4 species affect humans: plamodium falciparum, plasmodium vivax, plasmodium malariae and plasmodium ovale
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life cycle of malarial protozoa
1-Bite of an infected female mosquito
2-Sporozoite stage enters the circulatory system and reaches the liver in 1 hour
3-Grow and multiply by asexual division within liver cells in 5-7 days
4-As merozoites, leave the liver to re-enter the
bloodstream and invade the erythrocytes →continue to grow and multiply further for 1-3 days 5-Infected erythrocytes break, releasing parasite in intervals of approximately 48 hours. Chemicals released by the ruptured cells → related to patient’s symptoms
6-Some parasites develop into male and female
gametocytes
7- Humans transmit the parasite to the female
mosquito during a blood meal
8-In the mosquito’s stomach
9-The zygotes in turn become motile and invade the midgut wall of the mosquito
10- Parasites make their way to the mosquito’s
salivary glands
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antimalarial chemotherapy
* Quinoline ->Mefloquine
* Tetracycline -> Doxycycline
* Diaminopyrimidine -> Trimethoprim, Pyrimethamine
* 4-Aminoquinolines -> Chloroquine
* Biguanide -> Proguanil
* Naphthoquinone -> Atovaquone
* Sulphonamides -> Sulphadoxine
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substituted quinolines MoA
Quinoline act rapidly on the erythrocytic stage of the parasite
The parasite digests the host cell’s haemoglobin which is transported into the of the plasmodium food vacuoles→ digestion supplies the organism with a source of amino acid
MoA: aromatic quinoline ring binds via π-stacking to the porphyrin nucleus of haematin → Drug-heme complex blocks further conversion to haemozoin. Free toxic hematin is now present, which leads to the death of the plasmodium
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fungi
Fungi: eukaryotic organisms and possess a cell wall.
Most fungi are saprophytes → live on dead organic matter in the soil or on decaying leaves or wood The fungal kingdom includes yeasts, moulds, rusts, and mushrooms Some fungi are defined parasites as they live off of living matter and cause disease
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fungal infection
fungal infection is called a mycosis (topical infections,
systemic, or both)
Some can cause opportunistic infections if introduced into
a human through wounds or by inhalation (fatal)
All fungi produce spores → transported by direct contact or through the air
The fungal kingdom includes yeasts, moulds, rusts, and mushrooms
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biochemical targets of antifungal chemotherapy
Difference in sterol components provides the biochemical basis of selective
toxicity for most of the currently available antifungal drugs
(cholestrol in human and ergosterol in fungi)
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ergosterol biosynthesis inhibitors
steryl-14a-demethlase (3 successive hydroxylations of the 14a-methyl grouo --> from hydrocarbon to alcohol --> aldehyde --> carboxcylic acid
the methyl group is eliminated as formic acid)
this enzyme is the primary target for the azole antifungal agents
drugs=
azoles
allyl amines
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amorolfine
inhibition of ergosterol biosynthesis
through inhibition of Δ14-reductase and Δ8,Δ7-
isomerase →incorporation into fungal cell
membranes of sterols retaining a Δ14 double
bond, a Δ8 double bond, or both. None of
these will have the same overall shape and
physicochemical properties as ergosterol→
membranes with altered properties and
malfunctioning of membrane-embedded
proteins
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polyene membrane disruptors
High Affinity for sterol-containing
membranes over membranes containing
cholesterol → basis for their greater
toxicity to fungal cells
Lipophilic portion crosses the cell lipid
bilayer forming a pore in the cell
membrane → become leaky, and the cells
die because of the loss of essential cell
constituents (ions and small organic
molecules)
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responsibilities of the developed nhs authorities
* organisational control and funding of the NHS systems
* family planning
* provision of health services
* prevention, treatment and alleviation of disease, illness, injury, disability and mental disorder.
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structural similarities in antifungal, viral and biotic
heterocycles
amide bond
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heterocyclic compounds
Cyclic compounds that have one or more atoms different than C (N, O, or S)
Heterocyclic compounds
Aromatics (special type of unsaturated with conjugated double bonds - 4, 6,
or 10 pi electrons) and non-aromatics (do not have pi electrons or they are not
conjugated)
Non-carbon atoms are referred to as heteroatoms.
Saturated = containing single bonds or unsaturated = containing double or
triple carbon to carbon bonds
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C.diff
C.Diff is a bacteria that causes infection when the guts normal flora is distrupted or immunocompromised (prior treatment of antibiotics is one of the main risk factors for c.diff)
it produces toxins that damage the lining of the colon
can be spread between oatinets on hospital wards via contact transmission (spored survie for a long time, not killed by alcohol gel, hands must be washed by soap and water)
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MRSA
methicilin resistant staphylococcus aureus infection
highly resistant in the gut
decolonisation therapy for 5 days
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prudent prescribing
not prescribe to patinets unless they are very vulnerable nad it is the last option
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epidemiology
epidemiology is the study of how often diseases occur in different groups of people and why. epidemiological information is used to plan and evaluate strategies to prevent illness and as a guide to the management of patinets in whom disease has already developed
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zoonoses
vector borne transmission
(between human and animal)
example. malaria
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HIV
caused by a retrivirus that infects and replicates primarly in human CD4+ T cells and macrophages
risk: current or former partner with HIV, sex with someone that is positive, needle stick injury
symp:stage-1= flu-like symp. stage-2=(longstanding HIV) asymptomatic. symp 3= AIDS (CD4level <200 cells/mm3)
diagnosis: thorough history: weight loss, fever, sweats, rash, immunocompromised, opportinistic infection
initial diagnosis: antibodies, nucleic acid test (NAT) and blood or saliva sample,CD4 lymphocyte count (healthy person= more than 500 cells/microlitre)(HIV= CD4 are below200) and viral load
viral load is more important than CD4 count as it measures their progress and how well the treatment is working
treatment aim for undetecatable viral load, preserve immune function, reduce mortality and morbidity, reduce transmission, minimise drug toxicity
treat with combination of ART aims to improve physical and physiological well being of infected people
initiate treatment without CD4 count being important
treat with NRTI and NNRTIs and boosted protease inhibitors
backbone are two drugs from the NRTI class, this is normally in combination with an integrase inhibitor
pre exposure prophylaxis is a combination of two antiretroviral drugs that are taken before and after sex to reduce the risk of HIV
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mechanisms of pathogen-host interaction
the machanisms of pathogen-host interaction is adherance, immune evasion and tissue damage
colonisation-pathogen establishes resisdence at the site of infection
invasion- pathogens breach host barriers and gain access to deeper tissues
proliferation- pathigens multiply and spread within the host
dissemination- pathogens spread to other sites within the host or to new hosts
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etiology
idiopathic, nosocomal , iatrogenic, multifactoral
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flu symptoms
high temp
tiredness
headache
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e.coli symptoms
diarrhoea
stomach
cramps
occ.fever
blood in stool
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signs and symps of a staphylococcus aureus infection
painful red lump or bump on the skin, hot red and swollen skin
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causes of fever
caused by the release of pyrogens that increase prostoglandins that stimulate endogenous pyrogens to alter hypothalmic setpoint and trigger immune and inflammatory response
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causes of sepsis
infection triggers a dysregulated immune response leading to inflammatory response, release of pro-inflammatory cytokines which causes endothelial dysfunction, coagulation abnormalities and organ dysfunction
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causes of organ dysfunction
prevent by mainatining adequate oxygen delivery to cells
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immune response
leukocytosis, t cell activation, B cell proliferation, NK cell killing and increased WBC adhesion
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SIRS
describes the inflammation process
SIRS includes 2 of the following: temp more than 38 or less than 36, HR more than 90BPM, greater than 20 breaths per minute, CO2 conc less than 32mmHg, WBC more than 12,000 or fewer than 4000
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pathogenesis of UTIs
colonization (urethra)--> uroepithelium penetration (bladder) --> ascension (ureters)--> pyelonephriis (kidneys)--> acute kidney injury (kidneys)
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4 clinica prevention stages
primordial prevention (societal structures), primary prevention (immunisations), secondary prevention (early detection, screening), tertiary prevention (prevent relaps)
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cells of the immune response
B lymphocytes generates diverse antibodies
T lymphocytes secretes chemical messengers
plasma cells secrete antibodies
NK cells destroy virally infected cells
T cells directly destroy pathogens, but they regulate nearly all other types of the adaptive immune
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3 biological systems of the complement systems
optimisation of micro-organisms (covalent bonding of complement proteins to surface of microbes which will promote phagocytosis), activation and attraction of the leucocytes in immune defense(act upom leucocytes C3/C5), lysis of target cells (membrane attack complex bind to microbial membrane to increase permiability to cause cell lysis, C5/C9)
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adaptive immunity
when B cells produce antibodies, primary response to antigen causes plasma cells (generate antibodies) and memory cells, secondary response is memory cells form plasma cells more quickly. also, much of response controlled by T lymphocytes to generate secondary response, secrete cytokines to enhance immune responses, Th1 cells secrete cytokines to regulate immunological actvity and develop macrophages and other types of T cells. Th2 cells act on B cells to go to plasma to make antibodies. cytotoxic T cels kill target cells that are virus-infected by inducing apoptosis
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minimal inhibitory conc
lowest conc of drug that prevents growth of the pathogen
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minimal bactericidal conc
lowes conc of drug that kills the pathogen
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MBC/MIC ratio
bacteriostatic is MBC/MIC ratio is greater than 4
bacteriocidal is MBC/MIC ratio is less than 4
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antimicrobial activity measurement
measured by diltion susceptability test (put differnet drug conc in the tibes with the bacteria and see where the turbidity stops(bacterioscidal) to see the effectiveness of the drug), disk diffusion tests (disks impregnated with diff antibiotics and a microbe, antibiotic diffises from disk inti agar, establoshing agar gradient, higher conc near the disk, smaller disk shows reistant) and the Etest (bacterial is inoculates on agar then etest strips are placed on the surface which contain a gradient of antibiotic, intersection of eliptical zone of inhibtion indicates MIC)
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inhibition of cell wall
B lactams- penicillins, cephalosporins, monobactams, carbapenams
glycopeptides- vancomycin
peptidoglycan formation is by NAG and NAM units joined by bacterial transpeptidases by beta lactam units
B lactam antibiotics bind and block transpeptidases, and block the transpeptidation of peptidoglycan strands to prevent the synthesis of complete cell walls, leading to lysis of bacteria. also activates enzymes to break down peptidoglycan
B lactams antibiotics need to contain Beta lactam ring
natural penicillinsare penicillin G and V, both are most effective for gram +, have very low resistance to beta lactamase
three major groups of semisynthetic penicillins: antistaphylococcal penicillins (penicillinase-resistant penicillin (flucloxacillin, only gram +)), aminopenicillins (broad spec, ampicillin, amoxicillin), antipseudomonal penicillins (extended broad spec(gram - and anaerobes), piperacillin, only available in comb with beta lactamase inhibitors)
cephalosporins have same mechanisms as all the b lactams antibiotics
penicillin alls could also be all to cephalosporins
carbopenams and monobactams have same mechanisms as all b lacatams, only in IV form to treat complex infections resistant to bacteria
contraidications in patients with severe pen all
glycopeptide (not b lactam antibiotic)- vancomycin is a glucopeptide produced by streptomyces spp. , inhibit cell wall synthesis, binds to teminal amino acids linked to NAM of peptidoglycan and prevents the transpeptidation, without tarheting the enzyme, excusove against gram + , treat C.diff and MRSA and enterococcal infections, IV (reduced intestinal absorption), ototoxocity, nephrotoxicity, red man syndrome, neutropenia
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inhibition of protein synthesis
30S subunit- aminoglycosides, tetracycline
50S subunit- macroglides, lincosamides, chloramphenicol, oxazolidinones
ribosomes are machinery to synthesise proteins,inhibition of protein synthesis leads to cessation of bacterial growth or cell death
bacterial 70s allow for selective toxicity, they consist of small 30c and a large 50s subunit
aminoglycosides cause mRNA misreading
tetracyclines block the attachement of tRNA to the ribosome site A
macroglides prevent the translocation step
lincosamines prevent the translocation step
oxazolidinones interfere with the translation initiation
chloramphenicol block the attache=ment of tRNA o the ribosomal site A
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acting as a metabolite
folic acid synthesis- sulfonamides, trimethoprim
mycolic acid synthesis- izoniazid
block functioning of bacterial metabolic pathways (selective toxicity)
folic acid is essential to produce purines, bacteria synthesise folic acid, starting from a precursor p-aminobenzoic acid (PABA)
sulfonamides act by competing with PABA as a substrate for the enzyme dihydropteroate synthase
DHFRis used as folic acid needs to be reduced to be active
trimethoprim is targeting DHFR to stop the synthesis of folic acid
sulfonamides and trimethoprim can be administered together (co-trimoxazole) as they have a sequential blocking mechanism (block folic acid synthesis at two different steps--> potential synergistic effect)
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inhibition of nucleic acid synthesis
DNA synthesis- ciprofloxacin, levofloxacin, moxifloxacin (floroquinilones)
RNA synthesis- rifamycins, rifampin
inhibit topoisomerases (DNA gyrase (gram -)and topoisomerase IV(gram +))esential for DNA relication
DNA gyrase unravels supercoiles DNA (required for bacterial DNA replication)
floroquinolones are broad spec, inhibit DNA gyrase and topoisomerases IV--> making DNA inaccessible --> blocking bacterial DNA replication--> cell death
inhibit RNA polymerase catalysing the step of DNA transcription into mRNA
rifampicin inhibit the initiation of bacterial DNA transcription by blocking the activity of the beta subunit of the bacterial RNA polymerase, broad spec, treat tuberculosis and some meninigits (enter cerebrispinal fluid)
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alternative mechanisms
nitroimidazoles- metronidazole
nitrofurantoin
metrindazole generates free radicals in bacteria genarating an instable nitroso radical meatbolites (ROS)--> leads to DNA fragmentation. only covers anaerobes
nitrofurantoin genrates free radicals in bacteria--< instable metabolites--> interfere with RNA, DNA and other componenets synthesis, coverage against gram + cocc and some gram -, used to treat UTIs
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4 main mechanisms of drug resistance
alteration of the drug target site(mutations in specific genes that encode an altered drug),
drug inactivation(producing enzymes that breakdown antibiotics OR acquisition of genes that produce a new enzyme that transfers of an unusual chemical group to the drug making it ineffective), reduced drug intake into the cell(physical barrier to avoid the cell entry of antibiotics), drug efflux( bacteria expressing efflux pumps--> active transpirt across the plasma membrane to dispose of toxic substances--> not specific)
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virus life cycle and their antiviral agents
attachement (entry inhibitor)- a generic virus becomes attached to a target epithelial cell
penetration (fusion inhibitor)- the cell engulfs the virus by endocytosis
uncoating (M2 blockers)- viral contants are released
biosynthesis (NRTI or NNRTI)(integrase inhibitors for HIV)- viral RNA enters the nucleus where it is replicated by the virl RNA polymerase
protein synthesis, protein maturation and virion assembly (viral protease inhibitors)
release (neuraminidase inhibitors)- new viral particles are made and are released into the extracellular fluid
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virus attachement inhibitors
HIV gp120 proteins bind to CD4 receptor on T-immune cells. CD4 binding enables gp120 to interact with a coreceptor proetin (CCR5 or CXCR4) of the host cell
viral attachment inhibitors (virus target) targets the HIV gp120 preventing its binding to CD4 which means gp120 cannot interact with a corecptor protein of the host cell
viral attachment inhibitors (cell-host targets) are CCR5 antagonists which prevents the HIV-1 gp120/CCR5 interaction
227
viral penetration inhibitors
corecptor binding induces insetion of the gp41 fusion petide into the cell membrane, this promotes fusion between the viral envelope and host membranes
the drug type enfuvirtide (fuzeon) is a peptide derived from pg41, to mimic components of the HIV-1 fusion mchinery as it binds to gp41, preventing HIV envelope fusion with the cell membrane
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viral uncoating inhibitors
the influenza virus M2 protein is a proton channel embedded in the viral envelope, influenza virus entry activates the M2--> protons enter the viral core--> acidification--> viralgenome is released into the cell
M2 blockers bind and block the M2 channel lumen preventing virus uncoating
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viral genome replication
HIV reverse transcriptidase preforms reverse transcription--> using single-stranded RNA genome to generate complementary DNA (cDNA), HIC cDNA can be intergrated into the human DNA and is used by the cellular enzymes to transcribe RNA to produce viral proteins and replicate genome
NRTI(nucleostide analogues) mimic and compete with the natural nucleotides to bind the enzyme active site, once incorporataed they terminate polymerase elongation
NNRTI (non-nucleoside) bind to viral polymerases at allosteric sites (allosteric inhibition) causing an enzyme structure rearrangments and indirectly inhibit its function
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viral protease inhibitors
viral proteases cleave viral polyprotein precursors to form individual functional mature proteins
protease inhibitors selectivly bind to viral proteases stronger than natural substarte, inhibiting proteolytic cleavage of polyprotein precursors into key proteins
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HIV
HIV is seperated into HIV-1 and HIV 2
HIV 1 is more virulent and more infective
HIV result in high mutation rate result in large gentic variabiloty
treatment is HAART
goals of HAART is reduce plasma viral RNA to an undetectabke level, improve the immune system functions, prevent or reduce drug resistance, reduce morbidity or mortality improve life quality, prevent transmisson
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