Unit 13 week 2

Question 1

Amlodipine

Answer 1

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

Question 2

Aspirin

Answer 2

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

Question 3

Aspirin and hypertension

Answer 3

low-dose aspirin is frequently used to prevent cardiovascualr disease in high-risk patients (taken daily)

Question 4

Flucloxacillin

Answer 4

• 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

Question 5

Problematic bacteria in healthcare

Answer 5

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

Question 6

Strong risk factors for developing HAP

Answer 6

• 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

Question 7

Differences between cold and flu?/?

Answer 7

Question 8

Can influenza of lower respiratory tract lead to pneumonia?

Answer 8

yes

Question 9

Primary viral pneumonia

Answer 9

fatal

presents 2-3 days after influenza presentation

dyspnoea, cyanosis, proudctive haemoptysis, pulmonary oedema

elevated WBC

consilidation on CXR and percussion

Question 10

Secondary bacterial pneumonia

Answer 10

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

Question 11

British Thoracic Society (BTS) Community Acquired Pneumonia Care Bundle

Answer 11

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

Question 12

CURB-65 score

Answer 12

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

Question 13

What does pneumonia refer to?

Answer 13

any infectino of the lung parenchyma

Question 14

TYpical bacteria associated w pneunonia

Answer 14

streptococcus pneumoniae

hameohilus influenza

staph aureus

respond to beta lactam treatment

Question 15

Atypical bacteria associated with pneumonia

Answer 15

mycoplasma pneumoniae

Chlamydophila pneumoniae

legnionella pneumoniae

don’t respond to beta lactam treatment

Question 16

Other bacteria asscoaited with pneumonia

Answer 16

pseudomonas aeruginosa

enterobacteriae

group a streptococcus

Question 17

viruses associated with pneumonia

Answer 17

inflluenza type A and B

rhinovirus

coronavirus

Question 18

Definition of community acquired pneumonia

Answer 18

pneumonia that is thought to hav ebeen. acquired during the course of a hospital stay.

Question 19

community acquired pneumonia

Answer 19

acquired 48 hours of admission without being known to be present or incubating on admission

Question 20

pathophysiology of pneumonia

Answer 20

1. infectious agent is inhaled, aspirated from the stomach or arrives from elsewhere in the body
2. 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)
3. there is also activation of T cells that trigger cellular and humoral defence mechanisms
4. inflammatory reponse causes increased vascular permeabillity and therefore incresaed exudate
5. affected lobes of the lung begin to fill with inflammatory exudate from the surrounding tissue which leads to lung consolidation (solidifying)

Question 21

what is consolidation in pneumonia

Answer 21

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.

Question 22

Explain the lung sounds oresent in pneumonia

Answer 22

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

Question 23

Symtpoms of pneumonia

Answer 23

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

Question 24

risk factors

Answer 24

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

Question 25

how would pneumonia present under CXR

Answer 25

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

Question 26

how is ABG analysis used to identify pneumonia?

Answer 26

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.

Question 27

What would sputum and blood tests show that indicates pneumonia?

Answer 27

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.

Question 28

Common general blood tests in pneumonia

Answer 28

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

Question 29

tests specifically for bacterial pneumonia

Answer 29

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

Question 30

how to carry out sputum culture

Answer 30

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

Question 31

tests specifically for viral pneumonia

Answer 31

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

Question 32

hoWw is an antibiotic sensitivity test carried out? (3)

Answer 32

dilution method

disc diffusion method

e-TEST

Question 33

Dilution method of testing antibiotic sensitivity

Answer 33

1. Involves adding additional solvent to a solution to decrease its concentration.
2. The lowest concentration at which the isolate is completely inhibited is recorded as the minimal inhibitory concentration (MIC).
3. The MIC is the minimum concentration of the antibiotic that will inhibit this particular isolate.

Question 34

Disc method of evalutaing bacterial sensitivity to abs

Answer 34

1. A growth medium is evenly seeded throughout the plate with the isolate of interest that has been diluted at a standard concentration.
2. The test antibiotic immediately begins to diffuse outward from the discs.
3. After an overnight incubation (16-20h), the bacterial growth around each disc is observed.
4. Zones of inhibition are measured and if the measurements meet or exceed the standard then they are suitable for experiments.

Question 35

differences between viral and bacterial pneumonia

Answer 35

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

Question 36

antibioitc resistance of staph. aureus

Answer 36

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

Question 37

outcome of inaccurate prescribing

Answer 37

antibiotic resitance

increase in disease severity and length (creates less competition for pathogenic strain)

health complications

increase in healthcare costs as disease isnt resolved

Question 38

pathophysiology of s. aureus

Answer 38

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

Question 39

staph aureus profile

Answer 39

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.