RCM Week 3 (pneumonia)

Question 1

What is the volume of distribution and how do you calculate it

Answer 1

It is the apparent volume in which a drug is dissolved in the body

Vd = amount in body / conc
= dose / conc at t=0

Question 2

What is clearance of a drug and how do you calculate it

Answer 2

The volume of plasma cleared of a drug in unit time

(Ml / min) , (L/h)

Clearance = renal clearance + hepatic clearance

Question 3

What is first order kinetics

Answer 3

Rate of elimination is proportional to concentration of drug

Ct = C0e-kt

Where Ct = conc at t=t
C0 = conc at t=0
K = rate constant (per min or per hour)
T= time

Question 4

How do you calculate half life

Answer 4

T1/2 = 0.693/ k

Question 5

What is the steady state

Answer 5

The level that is the aim for the patients plasma concentration to be
Where
Administration rate = elimination rate

Question 6

How do you calculate infusion rate

Answer 6

Clearance x Css (concentration steady state)

Question 7

What is aminophylline

Answer 7

Used sometimes in severe asthmatic attacks
Is a bronchodilator
Given by IV infusion
(Is the salt of theophylline 80%)

Question 8

How to calculate an oral dose

Answer 8

Dose - CL x CSS x tau / F

Tau is the dosage interval

• double the dose = double the conc
• F stands for bioavailability (fraction of the drug that is absorbed)

Question 9

Describe the design of dosage regimens

Answer 9

1) the therapeutic window
- large TW ‘ maximal dose’ strategy
- small TW ‘target level’ strategy

Question 10

What is the maximal dose strategy for dosage regimens

Answer 10

Give a large dose and give it frequently as you have a wide safety margin

Question 11

What is the target level strategy for dosage regimens

Answer 11

Used for drugs with a small therapeutic window

IV infusion usually used so concentration is constant and avoids fluctuations

Question 12

What is a strategy for reaching the plasma concentration more rapidly in the case of urgent medications

Answer 12

Loading dose = target Css x Vd / F

Then, maintenance dose = target Css x CL x tau / F

Question 13

What is anti microbial chemotherapy

Answer 13

Using chemicals (antibacterials and antibiotics / anti microbials) drugs to selectively kill bacteria, viruses and fungi without affecting the host

Question 14

What does antimicrobial chemotherapy target

Answer 14

• bacterial cell wall
• bacterial ribosomes
• bacterial folate metabolism
• bacterial DNA gyrase

Question 15

What do all penicillins have in common

Answer 15

The beta lactam ring that can be broken down by bacteria

Question 16

Describe the mode of action of penicillin

Answer 16

They target bacterial cell wall synthesis by binding irreversibly to a transpeptidase, which cross links peptidoglycan chains in the bacterial cell wall

• only effective against dividing organisms as division requires cells wall synthesis, leading to lysis
• penicillins are bactericidal : cause lysis of bacteria

Question 17

What are beta-lactamases

Answer 17

Beta lactamases are secreted by resistant bacteria and can inactivate penicillin

To overcome this, clavulanic acid is included with some agents eg amoxicillin to inhibit the B-lactamases
And other penicillins eg flucloxacillin are resistant to B-lactamases

Question 18

Advantages and disadvantages of clarithromycin

Answer 18

Advantages: very effective
Disadvantages: has lots of drug interactions.

Question 19

Describe the action of tetracyclines

Answer 19

They inhibit protein synthesis by binding to the 30S subunit of the bacterial ribosome and prevent tRNA from binding at the acceptor (A) site

They actively accumulate in bacterial cells

They are bacteriostatic

Their use has decreased due to resistance

Question 20

Describe how macrolides work eg clarithromycin, erythromycin

Answer 20

They prevent the translocation of the 50S subunit of the bacterial ribosome along the mRNA

• prevent protein synthesis
• bacteriostatic

Question 21

Pros and cons of using macrolides (clarithromycin, erythromycin)

Answer 21

Pros: often used as an alternative to penicillin in patients with an allergy

Cons: macrolides are cytochrome P450 (liver- responsible for drug metabolism) inhibitors and associated with a range of drug interactions (increase concentrations of interacting drugs as they cant be broken down)

Question 22

How do aminoglycosides work eg gentamicin, neomycin, tobramycin

Answer 22

Aminoglycosides bind irreversibly to the 30S subunit of bacterial ribosomes, leading to misreading of mRNA and interfere with protein synthesis

They are bactericidal and used to manage gram negative bacteria

Synergy with penicillins: breakdown of cell wall increases uptake of aminoglycosides

Question 23

Describe how quinolones work eg ciprofloxacin, norfloxacin

Answer 23

These are inhibitors of bacterial DNA gyrase topoisomerase II and topoisomerase IV

Gram negative bacteria: dna gyrase is inhibited and quinolones inhibit the supercoiling of the bacterial DNA which is essential for DNA repair and replication

Gram positive bacteria: topoisomerase IV is the target and quinolones interfere with the separation of DNA strands on replication

Bactericidal

Question 24

What is trimethoprim

Answer 24

A safe antibacterial used in UTIs

• structurally related to folate
• folate antagonist and inhibiting the bacterial dihydrofolate reductase, which converts folate to tetrahydrofolate

-trimethoprim is less potent against the human form of the enzyme

Bacteriostatic

Question 25

What are sulphonamides

Answer 25

Analogues of p-aminobenzoic acid and inhibit the growth of bacteria by competitively inhibiting the enzyme dihydropteroate synthase, involved in the synthesis of folate from PABA The availability of DNA and RNA precursors is therefore reduced

Question 26

What is metronidazole

Answer 26

A pro drug which is activated by anaerobic bacteria to cytotoxic products which damages the helical structure of DNA, protein and the cell membrane - it is used against anaerobic bacteria and Protozoa - one of the only antibiotics that interferes with alcohol

Question 27

What is croup

Answer 27

Inflammation around the epiglottis in young children | - inspiratory strider due to narrowed airways

Question 28

Describe the influenza virus

Answer 28

Segmented negative ssRNA genome 8 segments encode 11 proteins

Question 29

What are the high risk groups that would receive the flu vaccine

Answer 29

``` Lung disease Cardiac disease Renal disease Endocrine disease Immunodeficiency Liver disease Anyone >65 Pregnancy Young child ```

Question 30

What are the bacterium’s that cause tuberculosis

Answer 30

Mycobacterium tuberculosis mainly | Less commonly: M. Bovis (in cattle) M.africanum, M.microti

Question 31

Clinical features of TB

Answer 31

Non specific: fever, weight loss, night sweats Respiratory symptoms: Cough, shortness of breath, haemoptasis, chest pain

Question 32

What are the layers of blood vessels

Answer 32

Lumen Tunica intima (internal elastic lamina) Tunica media (external elastic lamina) Tunica adventitia

Question 33

What type of cells line the lumen of blood vessels

Answer 33

Simple squamous endothelial

Question 34

Structure related to function of arteries and veins

Answer 34

Large T media in arteries for strength Diameter of lumen is relatively smaller Veins have thin walls and large lumen

Question 35

How are vessels adapted to allow blood flow

Answer 35

Endothelium is a smooth non stick surface which facilitates laminar flow

Question 36

When does turbulent flow in blood vessels occur

Answer 36

Turbulent flow occurs where vessels branch and when blood pressure is raised This can eventually damage the endothelium which exposes the blood to collagen and other factors that cause the blood to clot

Question 37

What is a thrombus

Answer 37

Solid mass of blood constituents formed within the vascular system in life

Question 38

What is atherosclerosis

Answer 38

Fatty deposits in the Tunica intima harden the walls and narrow the lumen- this reduced blood flow to the tissues: ischaemia

Question 39

What causes varicose veins

Answer 39

Incorrect functioning of valves

Question 40

What are arterioles and venules

Answer 40

Arterioles are small vessels with muscular walls Venules are the smallest vessels in the venous circulation

Question 41

What is the role of arterioles in resistance and blood pressure

Answer 41

Reduced blood flow leads to improper perfusion of tissues and lack of nutrients (ischaemia) which can lead to cell death Too much flow damages delicate tissue structure Arterioles control this by varying their diameter

Question 42

What are capillaries

Answer 42

Thin walled vessels to facilitate exchange of nutrients with the tissue: - endothelial cells ( 1 cell thick) + BM + collagen fibrils - occasional pericyte + BM - approx 5-8 microns in diameter - endothelial cells are joined by tight junctions and contain many vesicles

Question 43

What is the endothelial cell function

Answer 43

Permeability barrier - produces extracellular matrix - produces factors that modulate blood flow - produces anticoagulants and prothrombotics - regulates inflammation - cell growth

Question 44

3 types of capillaries

Answer 44

Continuous : found in nervous system, fat and muscle tissue Fenestrated : have pores / holes (leaky capillaries) found in the glomerulus Sinusoidal: much bigger holes to allow cells to move in and out found in liver, and bone marrow

Question 45

What is pneumonia

Answer 45

Infection and inflammation of the lung parenchyma

Question 46

How does pneumonia cause breathlessness

Answer 46

Fluid accumulates in the alveoli and impairs gaseous exchange

Question 47

How is the PCR test carried out for COVID 19

Answer 47

A nasal and throat swab done at the same time Aim is to see if there’s any DNA and a machine then amplifies the DNA so even if there are only small amounts it can still be detected

Question 48

Difference between community and hospital acquired pneumonia

Answer 48

Any pneumonia (bacteria or viruses) acquired before being admitted to hospital is community acquired Any pneumonia you get more than 48 hours after coming into hospital is hospital acquired Important to classify properly as the pathogens involved are different and antibiotic treatment is different

Question 49

What is community acquired pneumonia

Answer 49

Acquired before or within the first 48 hours of coming into hospital Acute illness with : Cough And - new focal chest signs, or fever or dyspnoea/ tachypnoea And Radio graphic evidence of new lung infiltrates (X-ray)

Question 50

How does one get pneumonia

Answer 50

Failure of body’s own defence mechanisms against infectious agents: - cough - mucociliary escalator - macrophages Could be due to virulent organism or immune dysfunction / dysregulation

Question 51

Clinical presentation of pneumonia

Answer 51

Chest infection often complicates a ‘cold’ especially in more elderly patients - green sputum - consistent with infection - crackles heard on chest - indicating fluid - resp rate 30 breaths per min normally 13-15 per min Body’s response to poor O2 saturation: - chest pains on breathing - pleuritic pain? - pyrexia at 39c - infection - patient very confused due to hypoxia and / or systemic infection

Question 52

Summary of the clinical respiratory and non respiratory features of pneumonia

Answer 52

Respiratory: cough, breathlessness, chest pain Non respiratory: fever, confusion, drowsiness, lethargy / tiredness

Question 53

Clinical signs of pneumonia

Answer 53

General examination: - temperature - high respiratory rate - low O2 levels - low BP Auscultation of the chest - decreased air entry - crackles

Question 54

Investigations to test for pneumonia

Answer 54

1) blood tests : - markers of infection - markers of dehydration 2) microbiology: to identify causative organisms - blood cultures - sputum cultures - urine samples 3) other tests: not always required unless diagnostic uncertainty or failure to respond to treatment - CT scan of chest - bronchoscopy

Question 55

How is arterial O2 levels linked to pneumonia

Answer 55

Arterial O2 levels should be >95% <92% patient is likely to have symptoms of hypoxia It is measured by pulse oximetry with a non invasive device on the finger

Question 56

What is the CURB 65 severity assessment

Answer 56

- confusion - urea >7mmol/l - resp rate >30/min - blood pressure, SBP <90 or DBP <60 mmHg Age >65 0-1 points = 1.5% mortality 2 points = 9.2% mortality 3-5 points = 22% mortality

Question 57

What is enoxaparin.

Answer 57

An injectable anticoagulant to prevent thrombosis - patients who are immobile in hospital are at risk of DVT due to poor venous return and the blood stagnates - DVT poses a risk for a life threatening pulmonary embolism

Question 58

How can pneumonia be treated with antibiotics

Answer 58

Co-amoxiclav and clarithromycin Blind: the best guess: the concept of using broad spectrum agents in the absence of microbiological evidence

Question 59

3 different types of treatment for pneumonia

Answer 59

1) antimicrobial therapy: - broad spectrum antibiotics initially narrow spectrum antibiotics antivirals 2) supportive measures - oxygen - IV fluids 3) symptomatic treatment - paracetamol - painkillers

Question 60

What is co-amoxiclav

Answer 60

Amoxicillin and clavulanic acid | - clavulanic acid is a beta lactamase inhibitor to prevent bacterial beta-lactamases degrading the beta-lactam ring

Question 61

Why are antibiotics administered intravenously

Answer 61

The patient is severely unwell and a rapid response is needed Swallowing may also be different - once afebrile for 24 hours then aim to switch to oral (easier and not complicated by a risk of line infection)

Question 62

Explain the 4 stages of pneumonia : consolidation, red hepatization, grey hepatization, resolution

Answer 62

1) consolidation: - 1st 24 hours - cellular exudate comprising neutrophils, lymphocytes etc replace alveolar air - congestion of surrounding capillaries 2) red hepatization - occurs within 1st 3 days - hyperaemic lung with engorged capillaries - fibrinous exudates fill alveoli along with RBCs 3) grey hepatization - occurs after the above - lung appears ‘grey’ because of disintegration of red cells; persistence of fibrin exudate 4) resolution - phagocytosis / enzymatic digestion of bacteria / exudates by leucocytes - restoration of lung architecture

Question 63

What is treatment failure

Answer 63

Clinical deterioration: * persistence or reappearance of fever * respiratory failure (increasing oxygen requirement) * radiographic progression * need for mechanical ventilation * shock * death

Question 64

What are cephalosporins

Answer 64

Eg cefaclor, cefalexin, cefotaxime, cefuroxime - B-lactam antibiotics Act in a similar way to penicillins - they show cross reactivity with penicillins and approximately 0.5-6.5% of penicillin-allergic patients will also be allergic to cephalosporins

Question 65

What are glycopeptides

Answer 65

Eg teicoplanin, vancomycin - these also inhibit bacterial cell wall synthesis by inhibiting the growth of the peptidoglycan chain - they are often used to manage severe infections due to ‘superbugs’ such as methicillin-resistance staphylococcus aureus (MRSA) - largely bactericidal

Question 66

What are aminoglycosides eg gentamicin, neomycin, tobramycin

Answer 66

Aminoglycosides bind irreversibly to the 30S subunit of bacterial ribosomes leading to misreading of mRNA and interfere with protein synthesis They are bactericidal and used to manage gram-negative bacteria Synergy with penicillins: breakdown of cell wall, increases uptake of aminoglycosides