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MPharm > AA end lectures > Flashcards

AA end lectures Flashcards

1
Q

What are the aims for targeted therapy

A

limit side effects from infection and antibiotic
reduce development of antibiotic resistance

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2
Q

what is empirical therapy

A

Using antibiotics through statistical guessing
e.g. purulent tonsilitis - streptococcus pyogenes

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3
Q

how does age affect antibiotic use

A

Advanced age
- gastric acidity reduced
- Renal function deteriorating
o Toxicities of antibiotics increase  retained longer = hepatic and renal problems/ failure
- Allergic reaction increase

Children
- Underdeveloped liver function
- Renal function diminished = reduced antibiotic clearance
o Tetracycline = teeth staining
o Quinolones alter cartilage development
o Sulfonamides displace bilirubin = neurotoxic

Pregnancy
- Not safe – can pass across placenta and affect neonate
o Doxycycline, tetracycline
o Sulfonamide
o Aminoglycosides
- Penicillin, cephalosporins and clindamycin – safe

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4
Q

How does renal and liver function affect antimicrobial

A

Renal function
- Metabolised or excreted by kidneys
- Half life increases with impaired kidney function

Liver function
- Half life increase with impaired liver = toxicity

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5
Q

How does site of infection affect antimicrobial

A

Site accessibility may be affected by lipid solubility
- Metronidazole and rifampicin are lipid soluble drugs
o Better penetrate BBB

Abscesses
- Antibiotics cannot penetrate
- Purulent material may present – binds and inactivates aminoglycosides
- Low O2 concentration and low pH
o Aminoglycosides requires O2 for transport
o Reduce activity of erythromycin

Medicinal devices and biofilms

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6
Q

What are biofilms

A
  • Matrix provides physical barrier to diffusion of molecules
  • Deeper layers of biofilm are anaerobic and also organism have low metabolic activity there
    o Quinolones and aminoglycosides work poorly
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7
Q

What are some reasons for topical therapy

A
  • Targeted
    o Can achieve high concentration at the site
  • Less collateral damage
  • Enables the use of agents too toxic for systemic use
  • Avoids first pass metabolism
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8
Q

What are factors affecting effectiveness of topical antimicrobials

A

Some areas requiring treatment are inaccessible
Biological fluids may prevent agents from reaching site
Patient compliance
Topical agents may be more difficult to apply
Formulation may affect acceptability

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9
Q

What are antiseptics

A

Agents used for destruction or inhibition of microbes in or on living tissues

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10
Q

What medications can you use to treat MRSA

A

Clindamycin – 300-450mg tds
o 30% are resistant

Doxycycline 100mg bd
o 100% susceptibility

Trimethoprim/ sulfamethoxazole
o 95% susceptible

Rifampicin and fusidic acid

Quinolones – ciprofloxacin

Vancomycin
o 25 mg/kg loading dose to 15-20 mg/kg bd

Linezolid
o Oxazolidinone
 Inhibits protein synthesis

Daptomycin

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11
Q

What is melioidosis

A

Caused by Burkholderia pseudomallei

Transmission:
- Cutaneous, inhalation, aspiration and occasionally ingestion
- Can appear asymptomatic

Clinical presentations
- Most infections are subclinical
- Most common clinical manifestation is pneumonia then skin infections
- Bacteraemia and septic shock

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12
Q

What are antimicrobials that melioidosis are resistant to

A

Antimicrobial resistance
- Resistant penicillin, ampicillin, first and second generation cephalosporins, gentamicin, tobramycin and streptomycin

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13
Q

Exclusion from the cell melioidosis

A

Exclusion from the cell
o Reduced outer membrane permeability
o LPS contributes to intrinsic high-level polymyxin B resistance
o Lipid A modification by 4-amino-4-deoxy-L-arabinose
o LPS O-antigen and outer core components are important in resistance to cationic antimicrobial peptides

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14
Q

Efflux from the cell melioidosis

A
  • Efflux from the cell
    o AmrAB-OprB
     Aminoglycoside and macrolide resistance
    o BpeAB-OprB
     Macrolides, fluoroquinolones, tetracyclines
    o BpeEF-OprC
     Trimethoprim resistance
     Chloramphenicol, fluoroquinolones and tetracyclines
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15
Q

Enzymatic inactivation melioidosis

A
  • Enzymatic inactivation
    o Cleavage of B-lactam antibiotics by PenA
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16
Q

Altered target site melioidosis

A
  • Altered target sites
    o Target deletion
    o Ceftazidime resistance mechanism
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17
Q

Acquired antimicrobial resistance melioidosis

A
  • Mutations or horizontal gene transfer mediated by phages, plasmids or transposon elements
  • Ceftazidime
    o Loss of gene required for synthesis of a penicillin binding protein 3
    o Point mutation on PenA resulting in amino acid changes = increased ceftazimide hydrolysis
    o Upregulation of penA via SNP in promoter region
  • Clavulanic acid
    o Mutations in P167S
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18
Q

What are probiotic therapy

A

Live micro-organism that when administered in adequate amounts, confer health benefit on the host
Ideal characteristics of probiotic organisms
- Non-pathogenic
- Easily cultivated
- Adherent
- Able to form a stable population at site

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19
Q

What are uses of probiotics

A
  • Active treatment or as preventative
    o To restore, rebalance and support normal flora
  • Used for gastrointestinal and urogenital tract infections
  • Administered by
    o Ingesting capsules, drinks or applying pessaries to site
20
Q

Mechanism of action of probiotics

A

General mechanism
- Competitive inhibition for sites/ nutrients
- Antagonism through production of inhibitory substances
- Inhibition of toxin produced by pathogens
- Immunodomulation of the host

Lactobacilli
- Production of lactic acid
- Production of antimicrobial substances
- Production of hydrogen peroxide
- Formation of colonisation barrier

21
Q

What are bacteriocins

A
  • Antimicrobial peptides
  • Produced by wide range of organism

Mechanism of action
- Form pores in bacterial cell membrane
- Narrow spectrum activity

22
Q

What are probiotic yeast

A

Mechanism of action
- Secretes a protease that
o Digests toxin A and B molecules
o Digests toxin A and B receptors on brush border membrane

23
Q

Faecal microbiota transplantation

A

Transplanted into unhealthy recipient
- Recipient has reduced microbial diversity
- Transplanted via nasogastric tube or colonoscopy
Donors must be healthy
- Donor blood and stool are screened

Mechanism of action
- Transplant flora establishes in recipient
o Restore gut flora
- Increases microbial diversity in recipient compared to pre-transplant

24
Q

Bacteriophage therapy

A

Mechanism of action
- Phage lyses bacterial cells resulting in bacterial cell death

25
Q

Stages of bacteriophage

A
  • Phage infects bacteria
  • Phage replicates using bacterial cell machinery
  • Lyses bacteria and new phage released
  • New phage infect other bacteria
26
Q

advantages and disadvantages of bacteriophage

A

Advantages:
- Phages are highly specific
- Effective against MDR
- No overgrowth of bacteriophages
- No deleterious effects on host cell
- Relatively cheap

Disadvantages:
- Bioavailability
o Reduced with stomach acid
- Safety concern
o Development of phage antibody by host
o Bacterial toxin present in pahge preparation
o Lysogenic conversion
- Other
o Some MRSA less susceptible to phage
o Bacteria may develop phage resistance

27
Q

Garlic

A

Antimicrobial action from allicin
- Breaks down into sulfides = very potent against bacteria and fungi

Mechanism of action
- Allicin interferes with thiol containing enzymes
o Forms disulfide bonds with protonated sulfhydryl groups
o Inactivates protein in key microbial processes

28
Q

Cranberry

A
  • For urinary tract infections
  • Active components are proanthocyanidins

Mechanism of action
- Reduces E.coli expression of fimbriae
- Reduces E.coli adhesion and binding to epithelial cells

29
Q

Green tea

A
  • Traditional Chinese medicine used to treat a range of general ailments
  • Contains catechins
    o Phenolic compounds
    o Flavonoids
    o Anti-oxidant activity

Mechanism of action
- Antiviral
- Weak antibacterial
- Weak antifungal
- Immune-stimulatory

30
Q

Qinghaosu

A
  • Contains artemisinin

Mechanism of action
- Against plasmodium still investigated

31
Q

Honey

A
  • Mostly sugar

Mechanism of action
- Antibacterial activity against a range
- Due to
o High osmolarity/ low water availability
o Low pH
o Generation of hydrogen peroxide
o Other minor component

32
Q

Tea tree oil

A
  • Mostly terpenes

Mechanism of action
- Broad spectrum antimicrobial activity
- Loss of cell membrane polarity and integrity
- Loss of cell homeostasis
- Inhibition of respiration
- Anti-inflammatory activity

33
Q

Target selection

A

decision to focus on finding an agent with a particular biological action that is anticipated to have therapeutic utility

34
Q

Target identification

A

to identify molecular targets that are required for microbial growth or target a human gene

35
Q

Target validation

A

to prove that manipulating the molecular target can provide therapeutic benefit for patients

36
Q

Genomics

A

study of genes and their function

37
Q

Proteomics

A

study of proteome, the complete set of proteins produced by a species using technologies of large scale protein separation and identification

38
Q

Lead discovery

A

identification of small molecule modulators of protein function

39
Q

High throughput screening

A

screening of drug target against selection of chemicals

40
Q

Silico screening

A

computer simulated screening of chemicals

41
Q

Drug affinity

A

ability of drug to bind to its biological target

42
Q

Selectivity

A

drug should bind to specific receptor site on the cell

43
Q

Animal models of disease states

A

test conditions involving induced disease or injury similar to human conditions

44
Q

Behavioural studies

A

tools to investigate behavioural results of drugs

45
Q

Functional imaging

A

method of detecting or measuring changes in metabolism, blood flow, regional chemical composition and absorption

46
Q

Ex-vivo studies

A

experimentation on tissue in an artificial environment outside the organism with the minimum alteration of natural conditions

47
Q

Clinical trials

A

set of procedures in medicinal research and drug development to study the safety and efficacy of new drug

MPharm (20 decks)

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