Session 9 Flashcards
Some differences between antibiotics (anti-bacterials, anti-fungals) and antivirals:
- Generally fewer viruses have specific antiviral drugs
- Antivirals are virostatic rather than virucidal, i.e. they do not ‘kill’ existing viruses, they just stop the replication of new viruses – the host immune response is required to clear existing virus
- Much less rarely given empirically – you normally confirm the presence of the virus before starting treatment - though now acyclovir (for treating HSV, VZV meningitis/encephalitis) and oseltamivir (for treating influenza) are being used more empirically, like antibiotics
• Much less broad-spectrum, i.e. antivirals are designed for a specific virus usually (exceptions, interferon, ribavirin), though some drugs can cover different viruses with the
same replication step/ virus family, e.g. tenofovir (HIV, HBV), acyclovir (HSV, VZV), ganciclovir (HSV, VZV, CMV, HHV6, HHV7, HHV8)
What are the ways Non-antiretroviral drugs work?
- Agents that directly inactivate viruses (virucides)
- Agents that inhibit viral replication
- Immunomodulators (of host response to viral infection)
- Immunoglobulins - Pooled human sera from blood donors, containing preformed antibodies (IM/ SC/ IV injection)
- Agents that directly inactivate viruses (virucides):
- Can they be systemically used?
- Mainly used for the?
- Non-organic (detergents, chlorine-based agents)
- Organic solvents (e.g. ether, alcohol,chloroform)
- Radiation (e.g. UV light, laser therapy for warts)
- Cryotherapy (e.g. for warts – removes lesions, may not inactivate virus itself)
- Non-organic (detergents, chlorine-based agents)
- However, these cannot be used systemically, and only in specific situations topically.
- cleansing of fomites
- Where are the targets for agents that inhibit viral replication:
- Disadvantages
- Give general examples of drugs which inhibit viral replication
- Attachment
- Uncoating
- RNA/DNA replication
- Protein synthesis
- Assembly
- Release
- Attachment
- Interference with host-cell metabolism can result in adverse effects
- Ineffective against non-replicating or latent viral infections.
- May exhibit rebound effects when drug is stopped
- Development of drug resistance is possible and common in some cases (e.g. HIV drugs)
- Non- or poorly standardised sensitivity/ resistance assays
- Interference with host-cell metabolism can result in adverse effects
Immunomodulators (of host response to viral infection):
- How do they work and which viruses do they target?
- Give examples of drugs which act as immunomodulators
- Replace deficient host immunity (e.g. immunoglobulins for HBV, VZV, HAV, rabies, vaccinia; HNIG/ IVIG; adaptive T cell immunotherapy)
- Enhance host immunity (e.g. interferons, Imiquimod)
What is this image showing?
Oral herpes (HSV 1) in a PWH ICU patient
What is this image showing?
Buttock herpes (HSV 2) in a PWH postnatal patient
How can we test for HSV
Detect virus in vesicle fluid
type specific serology
in the image -> Immunofluorescent (IF) confirmation of HSV1 or HSV 2 after positive CPE in viral culture
Anti-herpes virus drugs
- Give examples
- These drugs are mainly active against which viruses
- Resistance arises via?
- ADRs
- Aciclovir (oral, IV)/ valaciclovir (oral, prodrug);
Penciclovir (topical, IV)/ Famciclovir (oral, prodrug) - guanosine nucleoside analogues:
- Mainly active against HSV 1/2, VZV
Resistance arises via absent/ reduced TK enzyme, or altered TK substrate target, or
altered DNA polymerase
Well tolerated, but some nephrotoxicity. 1- 4% of patients may show
CNS symptoms:
lethargy, confusion, tremor, myclonus, hallucinations, delirium, seizures, extrapyramidal signs, autonomic symptoms, coma
Mechanism of Action of Acyclovir
- HSV-infected human cell
- acyclovir enters the cell and are converted to acyclovir monophosphate by the herpes simplex virus enzyme thymidine kinase (TK)
- Enzymes in the human cell add two more phosphates -> active drug acyclovir triphosphate
- The acyclovir triphosphate competes with 2 - deoxyguanosine triphosphate (dGTP) as a substrate for viral DNA polymerase as well as acting as a chain terminator.
- In actual infection, the herpes simplex virus releases its naked capsid that delivers DNA to the human nucleus; the active drug acyclovir triphosphate exerts its action on the viral DNA located in the nucleus.
- What is this image showing?
- How do we treat this?
- State the route of administration for the treatment
- CMV retinitis
- Ganciclovir or foscarnet initially.
Cidofovir can be used for resistant cases
- Ganciclovir (IV, intravitreal)/ valganciclovir (oral, prodrug)
Anti-herpes virus drugs (2)
Ganciclovir (IV, intravitreal)/ valganciclovir (oral, prodrug) – guanosine nucleoside analogues:
- Mechanism of action?
- Resistance arises due to ?
- Adverse effects: ?
- Inhibits viral DNA polymerase, slowing and terminating viral DNA elongation
- UL97 gene mutations or DNA polymerase (UL54) gene mutations
- nephrotoxic, myelosuppressive, neurotoxic. 5-15% patients
may show CNS symptoms: headache, behavioural changes, confusion, psychosis,
convulsions, coma
Give an example of an anti-herpes drug which is a cytidine nucleotide analogue and how it is administered
Cidofovir (IV, topical)
Anti-herpes virus drugs (3)
Cidofovir (IV, topical) - cytidine nucleotide analogue:
- Mainly active against?
- Mechanism of action?
- Resistance arises only via ?
- Adverse effects:
- Active against dsDNA viruses including possibly all human herpes viruses (HHV 1-8),
polyomaviruses, poxviruses, adenoviruses. - Inhibits viral DNA polymerase and DNA chain elongation
- mutations in the viral DNA polymerase (e.g. mutations in the CMV UL54 gene)
- nephrotoxic, myelosuppressive. Neutropenia (~24%) may be show as: fever,
nausea, vomiting, diarrhoea, headache, rash, lethargy, iritis, uveitis
Give an example of a herpes drug which is a pyrophosphate analogue & route of administration
Foscarnet (IV, intravitreal)
Anti-herpes virus drugs (4)
Foscarnet (IV, intravitreal) - pyrophosphate analogue:
- Active against ?
- Resistance arises via
- ADRs and why
- ganciclovir (GCV)-resistant CMV, aciclovir (ACV)-resistant HSV, e.g. for CMV retinitis
- mutations in the viral DNA polymerase or RT, but these do not usually cause resistance to GCV or cidofovir
- Narrow therapeutic index, with mainly nephrotoxicity. CNS adverse effects: headache,
seizures, tremor, irritability, hallucinations, fever, rash, diarrhoea, nausea, vomiting, anxiety,
fatigue, genital, ulcerations
What is the information in the table telling us?
State the Anti-hepatitis drugs that can be used for Hepatitis B and their routes of administration
- Lamivudine (3TC, oral) - cytidine nucleoside analogue
- Adefovir (oral) - adenosine nucleotide analogue
- Emtricitabine – a 5’ fluorinated nucleoside analogue derivative of lamivudine
- Entecavir – a guanosine nucleoside analogue:
Tenofovir
Anti-hepatitis drugs: Hepatitis B
Lamivudine (3TC, oral) - cytidine nucleoside analogue:
- Mechanism of action
- Resistance arises by?
- ADRs?
- Acts as false substrate and chain terminator of reverse transcriptase (RT) enzyme in HIV and HBV replication
- point mutations: M550I/V+others in YMDD motif of HBV DNA polymerase-RT with: 14-32%, 38%, 53% and 67% after 1, 2, 3 and 4 years of treatment, respectively
- Usually well-tolerated, though a rise in liver enzymes is one of the most common adverse effects
Anti-hepatitis drugs: Hepatitis B
Adefovir (oral) - adenosine nucleotide analogue
- Mechanism of action?
- ADRs?
- Acts as competitive false substrate and chain terminator of reverse transcriptase (RT) enzyme in HIV and HBV replication (including HBV DNA polymerase)
- Usually well-tolerated at the lower doses used to treat HBV (occasional headache, abdominal discomfort, diarrhoea). The main problem when using higher doses initially for HIV treatment was nephrotoxicity, hence it is no longer used for HIV treatment.
Anti-hepatitis drugs: Hepatitis B
Emtricitabine – a 5’ fluorinated nucleoside analogue derivative of lamivudine:
- Mechanism of action?
- Resistance develops within?
- ADRs
- Inhibitor of viral DNA polymerase, as per lamivudine
- 2 years of therapy against HBV
- Well-tolerated, with reports of nausea, headache, hyper-pigmentation of palms and soles. Other adverse effects difficult to distinguish from those of other drugs in HIV combination therapy
Anti-hepatitis drugs: Hepatitis B
Entecavir – a guanosine nucleoside analogue:
- Mechanism of action?
- Resistance?
- Adverse effects: ?
- Selectively inhibits hepadnaviruses (HBV), anything between 30-1000-fold more active
than lamivudine against HBV, in vitro - No reported viral resistance to this drug during these trials
- headache dizziness, lethargy, GI upset (abdominal discomfort, nausea, diarrhoea), photosensitivity
Give examples of Anti-hepatitis drugs for Hepatitis C & their route of administration
- Ribavirin (oral, IV, inhaled) - guanosine analogue
Anti-hepatitis drugs: Hepatitis C
Ribavirin (oral, IV, inhaled) - guanosine analogue:
- Mechanism of action?
- Resistance?
- Adverse effects:
- Inhibits both RNA/ DNA viruses, probably by different mechanisms in different viruses
- Reversibly alters cellular nucleotide stores, viral RNA/mRNA synthesis, lethal mutagenesis of some viral RNA genomes
- Inhibits both RNA/ DNA viruses, probably by different mechanisms in different viruses
- is rare, only documented in Sindbis virus and HCV (with the HCV RNA polymerase mutation F415Y) to date
- systemic dosing causes reversible anaemia (extravascular haemolysis) with bone-marrow suppression at higher doses. Other reported adverse effects include: pruritus, myalgia, rash, nausea, depression, anxiety, cough
Interferons are produced by?
Naturally produced by the body’s non-specific, innate immune response (IM injection):
Interferons (IFNs)
Naturally produced by the body’s non-specific, innate immune response (IM injection):
- Potent cytokines:
- Three major classes in clinical use:
- Used mainly in treating?
- Mechanism of action?
- Adverse effects?
- immunomodulating, antiproliferative
- IFN-a and IFN-b (30% aa similarity) produced by almost all cells: response to viral infection, ds RNA, bacteria, protozoa, mycoplasma, IL-1, IL-2, TNF
- IFN-g restricted to T-lymphocytes, NK cells in response to IL-2, antigens, mitogens
- IFN-a and IFN-b (30% aa similarity) produced by almost all cells: response to viral infection, ds RNA, bacteria, protozoa, mycoplasma, IL-1, IL-2, TNF
- HBV and HCV (PEG-IFNs – longer half-life)
- Not directly antiviral but stimulate proteins to enhance cellular resistance to viral infection
- In the first hours to days : flu-like illness, fever, chills, headache, malaise, myalgia, arthralgia, nausea, vomiting, diarrhoea
Give examples of protease inhibitors, NS5A inhibitors & polymerase inhibitors
Give an example of Anti-influenza drugs & route of administration
Neuraminidase inhibitors (NAIs) - oseltamivir (oral)/ zanamivir (inhaled)
Anti-influenza drugs
Neuraminidase inhibitors (NAIs) - oseltamivir (oral)/ zanamivir (inhaled):
- Mechanism of action?
- Effective against?
- Resistance arises due to?
- Adverse effects (oseltamivir): ?
- Adverse effects (zanamivir): ?
- Reversible inhibitors of NA enzyme that cleaves the sialic-acid receptor-HA bond between host-cell and virus
- Inf A and B and amantadine/ rimantidine resistant strains
- mutations in NA gene (H274Y/ H275Y), producing a less fit virus. It is relatively infrequent, at present
- generally well-tolerated, some nausea, vomiting, abdominal discomfort (10-15% of patients), also rashes (rarely SJS), headaches
- again well-tolerated, though reported bronchospasm, pulmonary oedema, respiratory arrest (rarely), exacerbation of underlying airways disease in some patients
Antiretroviral (HIV) drugs
What is the life cycle of HIV showing stages for possible drug interventions
Give the categories for anti-retroviral (HIV) drugs
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Protease Inhibitors (PIs)
- Fusion Inhibitors (FIs)
- Integrase inhibitors (INIs)
- Receptor inhibitors (R5 inhibitors)
- Others (continually in development)
Give examples of drugs which fall under these categories
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Protease Inhibitors (PIs)
Drugs for treating HIV (antiretrovirals): trade and generic names, and abbreviations.
NRTIs
- Give examples of NRTIs
- Mechanism of action
- Active against?
- Specific adverse effects:
- Nucleoside RT inhibitors: zidovudine (AZT), didanosine (ddI), stavudine (d4T), lamivudine (3TC), abacavir (ABC), emtricitabine, tenofovir (a nucleo tide RTI), etc.
- Act by inhibiting the DNA polymerase function of the HIV RT enzyme. The NRTIs act as false substrates and lack the 3’-OH group for DNA elongation, so when incorporated, will terminate production of the HIV DNA provirus
- HIV-1 and HIV-2
- hyperlactataemia, lactic acidosis, hepatomegaly+steatosis (possibly fatal).
- Resistance is common, and arises readily with poor adherence, with many primary resistance mutations: M41L, E44D, K65R, D67N, K70R, L74V, V118I, M184V, L210W, T215Y, K219Q, Q151M – some may sensitise to NNRTIs
- hyperlactataemia, lactic acidosis, hepatomegaly+steatosis (possibly fatal).
NNRTIs
- Give example of NNRTIs
- Mechanism of action?
- Active against HIV-1 but NOT HIV-2
- Specific adverse effects:
- Non-nucleoside RT inhibitors: nevirapine, delavirdine, efavirenz, etravirine, rilpivirine, etc.
- Non-competitive inhibitors of HIV RT by allosteric inhibition of enzyme function, binding at different sites from the NRTI sites – therefore synergism possible with combination therapy
- erythematous maculopapular rash, raised LFTs both of which can be serious, occasionally fatal (nevirapine);
- light-headedness, dizziness, sleep disturbance, headache, mania, psychosis, rash and raised LFTs and cholesterol (efavirenz)
- Resistance mutations arise readily, especially with poor adherence and monotherapy and can be long-lasting and class-specific, including: K103N, V106M, V108I, Y181C, Y188L, G190A/S
- erythematous maculopapular rash, raised LFTs both of which can be serious, occasionally fatal (nevirapine);
PIs
- Give examples of protease inhibitors:
- Mechanism of action?
- Active against both?
- Specific adverse effects:
- saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, tipranavir, darunavir, etc.
- Block the cleavage of viral polyproteins by HIV protease enzyme, preventing the production of viral proteins for the formation of final mature, complete virions
- HIV-1 and HIV-2
- may induce or inhibit cytP450 and alter the hepatic metabolism of other drugs
- chronic use increases cholesterol, TAGs; hyperglycaemia, hyperlipidaemia, new onset DM - resulting increased risk of MIs; may alter body fat distribution (lipodystrophy)
- Resistance tends to increase with the cumulative number of mutations present and tend to be drug-specific, including: D30N, L33I, M46L, I50V, V82A, I84V, L90M
- may induce or inhibit cytP450 and alter the hepatic metabolism of other drugs
FIs
- Give an example ofa fusion inhibitors:
- Mechanism of action
- Administration
- Active against ?
- Specific adverse effects:
- enfuvirtide (T-20)
- Interfere with attachment/ fusion process between HIV gp120/ gp41 and cellular CD4/ CCR5/ CXCR4 receptors
- The only HIV drug that must be given by injection (s/c) – as part of salvage combination Rx
- HIV-1 only, NOT HIV-2
- Injection site pain, induration, erythema, nodules, cysts, pruritis, ecchymoses
- Hypersensitivity reactions, rash, fever, nausea, vomiting, chills, hypotension, raised LFTs
- Resistance has been documented in vitro in the gp41 coding region of HIV (codons 36-45)
- Injection site pain, induration, erythema, nodules, cysts, pruritis, ecchymoses
Newer antiretroviral (HIV) drugs (2)
Entry inhibitors: CD4/ gp120/ CCR5 inhibitors: Maraviroc, etc.
- Integrase inhibitors prevent integration of HIV DNA provirus into host cell genome: Raltegravir, etc.
Antiviral drug resistance testing so far…
- HIV
- HBV (for antivirals with specific viral targets – not interferon) CMV
- Others: Influenza, HSV, VZV
- Future: HCV? Already available and in guidelines – application still controversial
Why is antiviral drug resistance testing needed?
Some obvious reasons:
- To optimise the clinical outcomes, quality of life, longevity of the patient
- To save costs and adverse effects of ineffective therapy
- To reduce the pool of drug resistant viruses in the population that may transmit between individuals, reducing the effectiveness of standard therapy
- CMV causes problems in
- Can cause
- babies and transplant patients
- Blindness, transplant rejection, encephalitis
When is it performed?
When there is evidence of therapeutic failure:
- Because the virus has become resistant, despite good compliance/adherence to therapy (i.e. a rising viral load, on Rx and/or continuing clinical disease)
- Because there is suspicion that the patient is not taking the drug (poor compliance/ adherence) (i.e. a rising viral load, continuing clinical disease)
- Because the patient cannot tolerate the adverse effects of the drug and an alternative regimen is required
- At baseline to check if the newly diagnosed patient is carrying any resistant viruses so the ineffective drugs can be avoided immediately
How is it performed?
- Phenotypic characterisation linked to genetic mutations:
- Thereafter, a sequencing/ genotyping approach may be sufficient for most of the drug resistant mutations commonly seen
- Incubate suspected drug resistant virus with varying concentrations of the drug of interest in a culture system
- Look for graded response compared to a wild-type virus, e.g. enzyme-activity changes, PRNT
- Incubate suspected drug resistant virus with varying concentrations of the drug of interest in a culture system
- Sequencing/ inspection
- Specific oligonucleotide capture/ binding
- Sequencing/ inspection
What is this drug used for
Hep C
- Defining antibacterials and their mechanisms of action
- Indications for antibacterials
- Making empirical antibacterial choices
- Antibacterial susceptibility testing
- MICs, breakpoints
- Pharmacokinetics and pharmacodynamics
- Resistance
- Antimicrobial stewardship
What is an antibacterial drug
- Chemical substance that ?
- Generally limited range of activity related to ?
- Selective toxicity
- Antibiotic = ?
No such thing as a “powerful” antibiotic
- kills or inhibits the growth of bacteria at a. discrete target site
- presence or absence of target site & ability of drug to reach target
3.
- antibacterial drug of microbial origin e.g. penicillin from Penicillium mold
Antibiotic targets
DNA synthesis:
Quinolones e.g. ciprofloxacin
Folic acid antagonists e.g.trimethoprim sulphonamides
Protein synthesis:
Aminoglycosides e.g. gentamicin
Macrolides e.g. erythromicin
Tetracyclines
Cell wall synthesis
Beta-lactams e.g. penicillins cephalosporins carbapenems
Glycopeptides e.g. vancomycin
The two reasons for antibiotics
- Prevention of infections
- Therapy of significant bacterial infections
Prophylaxis of bacterial infections
Which patients require prophylaxis, give e.g.
People at increased risk of infection
- Peri-operative (Prevention of surgical site infections)
- Short term (Meningitis contacts)
- Long term ( Asplenia & Immunodeficiency)
Therapy of a clinically significant bacterial infections
Clinically significant means?
An infection that left untreated will cause death, permanent harm or medium to long term disability
- Treatment of culture proven infection
- Empirical treatment of suspected infection
What is the likely cause of infection?
What information can allow you to determine the causative organism
What f@ctots must you consider when determining - Which antibiotics are likely to be effective?
What’s factors allow you to determine - Which antibiotic is the best choice?
Antibiotic adverse events (4)
- Toxicities
- Allergic reactions
- Idiosyncratic reactions (perculiar)
- Ecological effects (• Clostridium difficile • Selection of resistance)
- Drug interactions
What is this image showing
What are the ideals of an antibiotic?
Specific
non toxic
long half life
(one more)
Measuring susceptibility of bacteria to antibacterials:
- Disc sensitivity testing
- E-test method for minimal inhibitory concentration (MIC) measurement
What is this showing?
E-test method for minimal inhibitory concentration (MIC) measurement
What is this showing
Disc sensitivity testing
- Minimum Inhibitory Concentration (MIC): (define)
- Units are ?
- Antibiotic and isolate specific
- MIC measurement for many different isolates of the same species of bacteria (e.g. E coli) and the same antibiotic (e.g. co-amoxiclav) will give a population MIC distribution
- Minimum concentration of antibiotic required to inhibit growth of a bacterium in vitro
- mg/l (or equivalently μg/ml)
When doing MIC need to state organism and antibiotic being used
Breakpoints
- Considers the
- Predicts likely response
- • MIC
• Antibiotic pharmacokinetics
- • Susceptible
- Intermediate
- Resistant
just becomes mic works in vitro will it work in a person?
Baby affect microbiotia of the gut maybe effect the immunological development directly or indirectly through breast milk
Idiosyncratic reaction (lecture)
Just comes out of the blue, do not know the cause
Give IV enter hepatocytes bilary
go Opin to bowel and can cause effects
Pharmacokinetics
- Determinants of blood and tissue antibiotic concentrations
- Chemical attributes, e.g hydrophobicity, protein binding
- Bioavailability- impact if you can give a drug orally
- Many antibacterials are only available parenterally which means ?
- Physio-anatomical barriers, e.g.
• Body size and composition can influence PK
- (Intravenous injection or infusion)
- blood - brain barrier, blood-retina barrier, prostate, bone
Therapeutic drug monitoring why?
• To ensure ( - adequate dose - non-toxic dose)
E.g. • Aminoglycosides • glycopeptides
Normally safe to overdose on antibiotics
Gentamicin, narrow window
Give enough but not too much
What is this graph showing?
Cmax:MIC ratio
Greater ratio more likely killing effect
For getamycin lower doses but continuously /throughout the day
Pharmacodynamics
- Time dependent killing
- Concentration dependent killing
- • Succesful treatment requires prolonged antibiotic presence at site of infection
• But not high concentration
• Percentage of time free drugmconcentration exceeds MIC
%fT>MIC
- • Succesful treatment requires high antibiotic concentration at site of infection
• But not for long
• Ratio of maximum drug concentration to MIC
Cmax/MIC
Define:
MDR (multi-drug resistant
PDR (pan-drug resistant)
XDR (extensively drug resistant)
Carbapenem resistance
- Reduced bacterial intracellular concentration
- Decreased permeability (porin loss)
- Efflux pump mutations - Carbapenemase production
- Serine β-lactamase (1. KPC 2. OXA-48j
- Metallo-β-lactamase (1. NDM 2. IMP 3. VIM)
Antimicrobial Stewardship - intervention types
• Persuasive
Education
Consensus
Opinion leaders
Reminders
Audit
Feedback
• Restrictive
Restricted susceptibility reporting
Formulary restriction
Prior authorisation
Automatic stop orders
• Structural
Computerised records
Rapid lab tests
Expert systems
Quality monitoring
What is the impact of immunosuppression on antiviral therapy?
- Virus will stay for longer
- Effects seen for longer
What is the role of viral load testing in antiviral therapy? How is it used in defining treatment endpoints? Give examples for 2 viruses.
What is meant by a low genetic barrier to resistance?
What is meant by an ‘unfit’ virus? Give an example of this and how this
may impact on clinical practice and patient outcomes.
Mutation creates a virus that can not replicate efficiently , so continuing the treatment for the unmutated virus
Mutated might be resisted to the drug meant it will replicate more slowly or not at all so may be benefit to continuing treatment
Antimicrobial Agents Case History: 62-year-old man presented to A&E with acute shortness of breath. He gave a 7-day history of cough with yellow-green sputum and increasing wheeze. He had a history of smoking unfiltered cigarettes since the age of 13 years. His usual exercise tolerance of 400 yards, limited by breathlessness, was now only a few yards. He had not sought the advice of his GP prior to admission and as a consequence takes no medication. He had an anaphylactic reaction to penicillin 50 years ago. Full blood count reveals a high neutrophil count of 20. His admission CXR revealed hyper-inflated lung fields with right basal collapse.
1. What are the probable diagnoses?
Right basal Pneumonia
COPD - emphysema, bronchitis
Tumour blocks bronchus
Repeat Chest x Ray after 6 weeks to make sure there is no cancer
Smoking COPD and cancer
Right basal collapse cancer or consolidation
What percentage oxygen therapy should be administered?
Confirmed COPD with CO2 retention give a lower
Acutely unwell sack on 15l titratable with serum blood gasses
Give 100% oxygen
Do blood gas if retaining CO2 want to titrate oxygen down
Start of 15l oxygen about as coose to 100%
Then titrate down if CO2 high once done blood das via century mask ventury have different diameters through the flow rate
If they are retaining BYPAP and CPAP
Are antibiotics indicated? If so, which class and what is the mechanism of action?
Yes
Use CURB-65
Tetracycline
Doesn’t give info but because he is penicillin allergic -> doxycycline
What is the relevance of his allergic reaction?
Determines the drug administered - cannot give penicillin
Case History: A 30-year-old lady presented with a six-week history of worsening cough, fever, and weight loss, which had not responded to two successive courses of antibiotics. A sputum smear is positive for Acid-fast bacilli (AFB).
- What is her diagnosis?
- Which drugs would you use and for how long?
- Pulmonary TB
- All four for two months
Then I and R for four months
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
O for orange
H for
J joint pain
V for vision
All hepatotoxic apart for ethambutol
What baseline tests would you do prior to starting drug therapy?
Interferon gamma releasing assay (IGRAs)
TST - tuberculin sensitivity test
Tuberculin skin test
U and Es
LFTs
And visual acuity snellen Test
What monitoring of the drugs is required?
By a specialist:
• Adherece
• Side effects (blurred vision, orange) -> Change or retire are up if ADRs
- Why Get Tested?
- When To Get Tested?
- Sample Required?
- To help detect and identify infections caused by Mycobacterium tuberculosis, the cause of tuberculosis (TB), and other Mycobacterium species, which are known as acid-fast bacilli (AFB); to monitor the effectiveness of treatment
- When you have signs and symptoms of a lung infection, such as a chronic cough, weight loss, fever, chills, and weakness, that may be due to TB or a nontuberculous mycobacterial (NTM) infection; when you have a positive TB screening test and you are in a high-risk group for progressing to active disease; when you have a skin or other body site infection that may be due to mycobacteria; when you are undergoing treatment for TB
- For suspected cases of tuberculosis lung infections, usually three sputum samples are collected early in the morning on different days. If the affected person is unable to produce sputum, a bronchoscope may be used to collect fluid during a procedure called a bronchoscopy. In children, gastric washings/aspirates may be collected. Depending on symptoms, urine, an aspirate from the site of suspected infection, cerebrospinal fluid (CSF), other body fluids, or biopsied tissue samples may be submitted for AFB smear and culture.
What advice would you give to the patient after starting
treatment?
ADRs
The patient is taking the combined oral contraceptive pill (COCP), but wishes to start a family soon.
- What should she be advised? Does the COCP affect her treatment?
- What will happen to the immediate family contacts?
- Use extra contraception
No TB antibiotics decreases the effectiveness of COCP
Change contraceptive method
Induces cytochrome P450 so it is metabolised faster (rifampicin)
- Risk of family members /close contacts being infected
Active latent or if you have the vaccine mons two tuberculin test
Interferon gamma test (blood test) active and latent Tb will be positive
Main thing is symptoms to detect against active and latent (CXR)
Family members chemoprophylaxis
If active full wack of 6 months course
After 3 weeks on treatment the patient notices that she has become jaundiced.
12. What should be done?
Pyrazinamide - hepatotoxicity - intra hepatic jaundice
Stop RIP
Stop meds
Do blood tests
Monitor for resolution
Reintroduce drugs or titrate them (lower dose)
Or second line drugs into place streptomycin
