Unit 13 week 2 Flashcards
Amlodipine
CHEMISTRY: calcium channel blocker
PHARMACOLOGY: primary target: L-type voltage gated calcium channels
Activity: antagonist
PHYSIOLOGY:
L-type calcium channels found in all excitable cells, but amlodipine has a higher affinity for smooth muscle > cardiac muscle.
Binds to calcium channel decreasing Ca2+ influx which is needed for smooth muscle contraction = vasodilation
CLINICAL: essential hypertension, angina
Aspirin
Primary target: cyclooxygenase 1 and 2 (non-selective) Activity: inhibitor
PHYSIOLOGY: acetyl group of acetylsalicylic acid (aspirin) irreversibly binds with a serine residue on the COX-1 enzyme
Inhibition of COX-1 prevents production of prostaglandins released during inflammation. PGL increase sensitivity of pain receptor neurones.
Inhibition of cox-1 also inhibits platelet aggregation- stopping the conversion of arachidonic acid to thromboxane A2
Indicated use- pain, fever, inflammation
-reducing risk of cardiovascular death in suspected MI
prevention of cardiovascular disease
Aspirin and hypertension
low-dose aspirin is frequently used to prevent cardiovascualr disease in high-risk patients (taken daily)
Flucloxacillin
- penicillin derivative beta lactam class antibiotic
- narrow spectrum used in treating gram positive bacterial infections
- MOA: binds to penicillin-binding proteins located inside the bacterial cell wall with its B-lactam ring.
- This inhibits the final stage of bacterial cell wall synthesis- the cross linking of peptidoglycans
- this affects the cells ability to cope with the osmotic gradient across its cell wall
- the bacteria undergo cell lysis mediated by bacterial wall autolytic enzymes - such as autolysins
Problematic bacteria in healthcare
MRSA- methicillin resistant staphyloccocus aureus
Part of normal skin commensal
can cause severe skin infections and bacteraemia
C.diff- Clostridium difficile
Gut commensal
Antibiotics cause disruption of normal gut flora allowing an increase in C. Diff
Toxin producing C. Diff causes severe diarrhoea and can cause colitis
C.diff spores can live in the environment
Strong risk factors for developing HAP
- Poor infection control/ hand hygiene
- Intubation and mechanical ventilation
- Presence of MDR bacteria- think immunodeficiency
- Aspiration
WEAK risk factors:
Acid suppression drugs
Depressed consciousness
Chest or upper abdomonal surgery
Differences between cold and flu?/?
Can influenza of lower respiratory tract lead to pneumonia?
yes
Primary viral pneumonia
fatal
presents 2-3 days after influenza presentation
dyspnoea, cyanosis, proudctive haemoptysis, pulmonary oedema
elevated WBC
consilidation on CXR and percussion
Secondary bacterial pneumonia
initial improvement of symptoms followed by recurrence of fever and cough with productive sputum
requires more aggressive therapy than viral as it is more severe
British Thoracic Society (BTS) Community Acquired Pneumonia Care Bundle
Its aim is to ensure patient safety with timely prescribing and administration of oxygen followed by timely antibiotics administered after assessment of a CXR and risk score. Success is measured using length of stay and mortality for patients admitted.
1) Perform CXR within 4hrs of admission
2) Assess Oxygen Saturation and prescribe oxygen according to appropriate target range
3) Calculate CURB 65 in all patients where CXR demonstrates pneumonia
4) Administer antibiotics within 4hrs of diagnosis appropriate to CURB 65 score
CURB-65 score
Adults diagnosed with community‑acquired pneumonia in hospital have an assessment to find out how serious the pneumonia is (it is a mortality risk assessment). This includes a CURB65 score, which uses the person’s age, symptoms, blood pressure and a blood test to help decide how serious the risks are for that person, whether they need to stay in hospital and what treatment they should have.
Higher the score the worse off
categories
- Confusion (abbreviated mental test score of <8/10)
- Urea (>7 mmol/L)
- RR >/= 30 bpm
- BP (SB <90 DBP <60)
- Age > 65 years
What does pneumonia refer to?
any infectino of the lung parenchyma
TYpical bacteria associated w pneunonia
streptococcus pneumoniae
hameohilus influenza
staph aureus
respond to beta lactam treatment
Atypical bacteria associated with pneumonia
mycoplasma pneumoniae
Chlamydophila pneumoniae
legnionella pneumoniae
don’t respond to beta lactam treatment
Other bacteria asscoaited with pneumonia
pseudomonas aeruginosa
enterobacteriae
group a streptococcus
viruses associated with pneumonia
inflluenza type A and B
rhinovirus
coronavirus
Definition of community acquired pneumonia
pneumonia that is thought to hav ebeen. acquired during the course of a hospital stay.
community acquired pneumonia
acquired 48 hours of admission without being known to be present or incubating on admission
pathophysiology of pneumonia
- infectious agent is inhaled, aspirated from the stomach or arrives from elsewhere in the body
- infectious agent invades the parenchyma which causes an inflammatory response (macrophage engulfs pathogen, releases pro inflam cytokines e.g., TNFa, IL-8, Il-1, attracting neutrophils to site)
- there is also activation of T cells that trigger cellular and humoral defence mechanisms
- inflammatory reponse causes increased vascular permeabillity and therefore incresaed exudate
- affected lobes of the lung begin to fill with inflammatory exudate from the surrounding tissue which leads to lung consolidation (solidifying)
what is consolidation in pneumonia
Consolidation of the lung occurs when the air within the small airways of the lung is replaced with something else, this can be fluid such as blood or pus or a solid such as contents from the stomach. In pneumonia, the cause of consolidation is dead cells and debris from the immune system battling the infection cause a build up of pus which fills the small airways.
Explain the lung sounds oresent in pneumonia
Crepitations
- crackles (crepitations) or bubbling noises made by movement of fluid in tiny air sacs of thre lungs. coarse crackles are associated with bronchiectasis or resolving pneumonia
- fine crackles are associated with pulomary oedema or interstitial fibrosis
- dull thuds when percussed indicate fluid in lung or collapse of part of a lung
- sounds can be made by pleural layers rubbing together
- lack of breathing sounds in some areas suggests that air is not entering that part of the lung
Symtpoms of pneumonia
develop suddenly if typical bacterial cause, gradually if atypical (check this)
cough, may be unproductive or productive with haemotysis
dyspnoea
chest pain which gets worse with breathing or coughing
tachycardia
fever
malaise
fatiguie
risk factors
Age ≥65 years – incidence of CAP increases significantly with age
Smoking
Environmental exposures
Poor nutritional status
Functional impairment
COPD, asthma and bronchitis – associated with 2-fold to 4-fold increased risk of CAP
Poor oral hygiene
Immunosuppressive therapy
Oral steroids
Treatment with proton pump inhibitors or H2 antagonists
Previous CAP (in last 1-2 years)
Residence in nursing home – residents have an increased risk of aspiration pneumonia
Alcohol misuse
how would pneumonia present under CXR
pneumonia is usually due to purulent material (consolidation) filling the alveoli
this is denser than the air that usually fills it so absorbs more x rays, less fall on the film behind, the denser areas appear white
how is ABG analysis used to identify pneumonia?
expect to see:
hypoxaemia (lower O2) due to purulent debris blocking gas transfer
low to normal level of C02
lactate level check for sepsis
respiratory alkalosis and metabolic acidosis?
Physiological shunting has taken place – ventilation is not able to occur at all alveoli due to presence of purulent material, despite them being adequately perfused. As a result, blood flowing through these dysfunctional alveoli is not oxygenated, and enters circulation once more.
What would sputum and blood tests show that indicates pneumonia?
The goal with these tests is to find out what the organism is that is causing the pneumonia, therefore in an attempt to reduce its spread to other people, determine the severity of the infection and to guide any treatment such as antibiotics sensitivity.
Common general blood tests in pneumonia
Full blood count – determines the number and the type of white blood cells present, an increase in WBC e.g neutrophil or monocyte percentage would suggest inflammation/infection, there may also be a rise in platelet count
o Urea and electrolytes – blood tests for sodium, potassium and other ions in order to determine how severe the illness is
o Arterial blood gases – assesses the oxygen, carbon dioxide levels and pH of the blood
o CRP – indicates inflammation
tests specifically for bacterial pneumonia
Sputum culture and gram staining – this identifies the cause of bacterial pneumonia
o AFB smear and culture – requested when tuberculosis or a non tuberculous mycobacteria infection is suspected
o Blood culture – used to detect septicaemia when it is suspected that infection has spread from the lungs to the blood or from the blood to the lungs
how to carry out sputum culture
fresh sputum sample is usually collected first thing in the morning, it is then broken up with a substance called mucolyse which ensures that the bacteria in the sample is evenly distributed, once homogenized, it is placed on appropriate nutrient media and incubated under conditions which simulate body temperature. This encourages bacteria to grow. Once the organism has been detected, follow up testing is usually antimicrobial susceptibility testing which helps to determine the best treatment
tests specifically for viral pneumonia
Polymerase chain reaction to detect a broad range of viral pathogens in respiratory secretions or a nose or throat swab
Extra;
- Pleural fluid analysis – if any fluid has accumulated in the pleural space it can also be tested for the organism
- Fungal culture – sometimes used but usually not the leading cause of pneumonia
- Mycoplasma and legionella testing
hoWw is an antibiotic sensitivity test carried out? (3)
dilution method
disc diffusion method
e-TEST
Dilution method of testing antibiotic sensitivity
- Involves adding additional solvent to a solution to decrease its concentration.
- The lowest concentration at which the isolate is completely inhibited is recorded as the minimal inhibitory concentration (MIC).
- The MIC is the minimum concentration of the antibiotic that will inhibit this particular isolate.
Disc method of evalutaing bacterial sensitivity to abs
- A growth medium is evenly seeded throughout the plate with the isolate of interest that has been diluted at a standard concentration.
- The test antibiotic immediately begins to diffuse outward from the discs.
- After an overnight incubation (16-20h), the bacterial growth around each disc is observed.
- Zones of inhibition are measured and if the measurements meet or exceed the standard then they are suitable for experiments.
differences between viral and bacterial pneumonia
Viral Bacterial
Symptoms Less severe More severe
Breathing sounds. similar both sides different on one side
side of lung both only one side or lobe
X-ray more diffuse one particulalry dense area
antibioitc resistance of staph. aureus
MRSA resistant phenotype was brought about by selection of the gene mecA
mecA codes for penicillin binding protein 2a which is a transpeptidase that catalyses cell wall crosslinking even when B-lactam antibiotics are being used
outcome of inaccurate prescribing
antibiotic resitance
increase in disease severity and length (creates less competition for pathogenic strain)
health complications
increase in healthcare costs as disease isnt resolved
pathophysiology of s. aureus
adhesins- bind to cell surface receptors on host tissues, host cells and soluble factors in blood. Binds to complement factors, preventing complement cascase
Superantigens- potent immunostimulators
Proteases- target host immune factors and tissues
capsule
staph aureus profile
pyogenic gram positive coccus (ball)
virulence factors:
Adherence and evasion of the host immune response.
· Secreted enzymes that degrade host structures
· Secreted toxins that damage host cells
· Proteins that cause antibiotic resistance
Staphylococcus aureus produces a polysaccharide capsule, enabling attachment to artificial materials and resulting in significant prosthetic valve and catheter associated infection and a resistance to host cell phagocytes.
Staphylococcus aureus also expresses surface protein A, which binds the Fc portion of immunoglobulins, allowing the organism to escape antibody-mediated killing.
