RCM Week 3 (pneumonia) Flashcards
What is the volume of distribution and how do you calculate it
It is the apparent volume in which a drug is dissolved in the body
Vd = amount in body / conc
= dose / conc at t=0
What is clearance of a drug and how do you calculate it
The volume of plasma cleared of a drug in unit time
(Ml / min) , (L/h)
Clearance = renal clearance + hepatic clearance
What is first order kinetics
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
How do you calculate half life
T1/2 = 0.693/ k
What is the steady state
The level that is the aim for the patients plasma concentration to be
Where
Administration rate = elimination rate
How do you calculate infusion rate
Clearance x Css (concentration steady state)
What is aminophylline
Used sometimes in severe asthmatic attacks
Is a bronchodilator
Given by IV infusion
(Is the salt of theophylline 80%)
How to calculate an oral dose
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)
Describe the design of dosage regimens
1) the therapeutic window
- large TW ‘ maximal dose’ strategy
- small TW ‘target level’ strategy
What is the maximal dose strategy for dosage regimens
Give a large dose and give it frequently as you have a wide safety margin
What is the target level strategy for dosage regimens
Used for drugs with a small therapeutic window
IV infusion usually used so concentration is constant and avoids fluctuations
What is a strategy for reaching the plasma concentration more rapidly in the case of urgent medications
Loading dose = target Css x Vd / F
Then, maintenance dose = target Css x CL x tau / F
What is anti microbial chemotherapy
Using chemicals (antibacterials and antibiotics / anti microbials) drugs to selectively kill bacteria, viruses and fungi without affecting the host
What does antimicrobial chemotherapy target
- bacterial cell wall
- bacterial ribosomes
- bacterial folate metabolism
- bacterial DNA gyrase
What do all penicillins have in common
The beta lactam ring that can be broken down by bacteria
Describe the mode of action of penicillin
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
What are beta-lactamases
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
Advantages and disadvantages of clarithromycin
Advantages: very effective
Disadvantages: has lots of drug interactions.
Describe the action of tetracyclines
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
Describe how macrolides work eg clarithromycin, erythromycin
They prevent the translocation of the 50S subunit of the bacterial ribosome along the mRNA
- prevent protein synthesis
- bacteriostatic
Pros and cons of using macrolides (clarithromycin, erythromycin)
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)
How do aminoglycosides work eg gentamicin, neomycin, tobramycin
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
Describe how quinolones work eg ciprofloxacin, norfloxacin
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
What is trimethoprim
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
What are sulphonamides
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
What is metronidazole
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
What is croup
Inflammation around the epiglottis in young children
- inspiratory strider due to narrowed airways
Describe the influenza virus
Segmented negative ssRNA genome
8 segments encode 11 proteins
What are the high risk groups that would receive the flu vaccine
Lung disease Cardiac disease Renal disease Endocrine disease Immunodeficiency Liver disease Anyone >65 Pregnancy Young child
What are the bacterium’s that cause tuberculosis
Mycobacterium tuberculosis mainly
Less commonly: M. Bovis (in cattle) M.africanum, M.microti
Clinical features of TB
Non specific: fever, weight loss, night sweats
Respiratory symptoms:
Cough, shortness of breath, haemoptasis, chest pain
What are the layers of blood vessels
Lumen
Tunica intima (internal elastic lamina)
Tunica media (external elastic lamina)
Tunica adventitia
What type of cells line the lumen of blood vessels
Simple squamous endothelial
Structure related to function of arteries and veins
Large T media in arteries for strength
Diameter of lumen is relatively smaller
Veins have thin walls and large lumen
How are vessels adapted to allow blood flow
Endothelium is a smooth non stick surface which facilitates laminar flow
When does turbulent flow in blood vessels occur
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
What is a thrombus
Solid mass of blood constituents formed within the vascular system in life
What is atherosclerosis
Fatty deposits in the Tunica intima harden the walls and narrow the lumen- this reduced blood flow to the tissues: ischaemia
What causes varicose veins
Incorrect functioning of valves
What are arterioles and venules
Arterioles are small vessels with muscular walls
Venules are the smallest vessels in the venous circulation
What is the role of arterioles in resistance and blood pressure
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
What are capillaries
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
What is the endothelial cell function
Permeability barrier
- produces extracellular matrix
- produces factors that modulate blood flow
- produces anticoagulants and prothrombotics
- regulates inflammation
- cell growth
3 types of capillaries
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
What is pneumonia
Infection and inflammation of the lung parenchyma
How does pneumonia cause breathlessness
Fluid accumulates in the alveoli and impairs gaseous exchange
How is the PCR test carried out for COVID 19
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
Difference between community and hospital acquired pneumonia
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
What is community acquired pneumonia
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)
How does one get pneumonia
Failure of body’s own defence mechanisms against infectious agents:
- cough
- mucociliary escalator
- macrophages
Could be due to virulent organism or immune dysfunction / dysregulation
Clinical presentation of pneumonia
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
Summary of the clinical respiratory and non respiratory features of pneumonia
Respiratory: cough, breathlessness, chest pain
Non respiratory: fever, confusion, drowsiness, lethargy / tiredness
Clinical signs of pneumonia
General examination:
- temperature
- high respiratory rate
- low O2 levels
- low BP
Auscultation of the chest
- decreased air entry
- crackles
Investigations to test for pneumonia
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
How is arterial O2 levels linked to pneumonia
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
What is the CURB 65 severity assessment
- 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
What is enoxaparin.
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
How can pneumonia be treated with antibiotics
Co-amoxiclav and clarithromycin
Blind: the best guess: the concept of using broad spectrum agents in the absence of microbiological evidence
3 different types of treatment for pneumonia
1) antimicrobial therapy:
- broad spectrum antibiotics initially narrow spectrum antibiotics antivirals
2) supportive measures
- oxygen
- IV fluids
3) symptomatic treatment
- paracetamol
- painkillers
What is co-amoxiclav
Amoxicillin and clavulanic acid
- clavulanic acid is a beta lactamase inhibitor to prevent bacterial beta-lactamases degrading the beta-lactam ring
Why are antibiotics administered intravenously
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)
Explain the 4 stages of pneumonia : consolidation, red hepatization, grey hepatization, resolution
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
What is treatment failure
Clinical deterioration:
- persistence or reappearance of fever
- respiratory failure (increasing oxygen requirement)
- radiographic progression
- need for mechanical ventilation
- shock
- death
What are cephalosporins
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
What are glycopeptides
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
What are aminoglycosides eg gentamicin, neomycin, tobramycin
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
