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Chemotherapeutics Pharmacology - Coggle Diagram
Chemotherapeutics Pharmacology
Bacteriostatic
Do not kill
Bacteria remain visible
Arrest replication
Limit spread
Arrest growth
Require immune system t clear pathogens
Bactericidal
Seriously ill
Immunocompromised
Aggressive
Reduces viable bacteria
Kill bacteria
Selection of antimicrobial therapy
Susceptibility of infective organisms to different agents when cultured
Bacteriostatic vs bactericidal?
Timing- after identification? Critically ill?
Site of infection- BBB, etc.
Identification of the infecting organism- gram stain, morphology, antigens, RNA sequencing, host responses
Patient factors
Patient factors
Hepatic function- concentrated or eliminated by liver
Perfusion- decreased circulation reduces drug delivery
Renal function- accumulation of certain Abs
Age- renal/hepatic function low in neonates & elderly
Pregnancy/lactation- foetal & neonatal effects
Immune function- bactericidal vs bacertiostatic
Chemotherapeutic Spectra
Narrow-Spectrum Antibiotics: acting only on a single or limited group, isoniazid acts on mycobacteria
Extended-Spectrum Antibiotics: modified act against gram + & some gram -, Ampicillin
Groups of clinically important bacteria
Broad-Spectrum Antibiotics: act on a wide variety of microorganisms, can alter normal bacterial communities, can lead to superinfections like C. Diff, tetracycline, fluoroquinolones
Antibiotic Resistance
Bacteria are considered resistant to an antibiotic if the max. level of the antibiotic that can be tolerated by the host doesn't halt the growth
A bunch of bacteria including a resistant variety.
Get bathed in antibiotics. Most of the normal bacteria die.
The resistant bacteria multiply & become more common.
Eventually, the entire infection evolves into a resistant strain.
Viral Particles- Virions
Membranous envelope of lipids- only some have this
NO metabolic machinery
Protein coat- capsid
Very different to eukaryotes, prokaryotes
Genetic Material- RNA DNA
Antiviral Therapeutics
Strategies
PREVENT viral infections through vaccination
TREAT active infections by interrupting lifecycle
3.BOOST immune system of pt.- latent virus (A latent viral infection usually doesn't cause any noticeable symptoms & can last a long period of time before becoming active & causing symptoms
Challenges
Some treatments are prophylactic-PrEP Pre Exposure Prophylaxis
Clinical symptoms appear late in infection:
most particles have already replicated.
drugs targeting replication limited effect
Rapid Mutation rate of viruses leads to drug resistance
HIV
5 classes of antiretroviral drugs:
NRTI- nucleoside reverse transcriptase inhibitor
NNRTI- non-nucleoside reverse transcriptase inhibitor
PI- protease inhibitor
Entry inhibitor
Integrase inhibitor
Each target a diff. process in the lifecycle:
Fusion of virus to cell membrane
Reverse transcription of viral RNA to DNA
Integration of viral DNA to host genome
Proteasomal digestion of viral proteins into functional proteins
Combo. to treatments:
2 NRTIs + PI or NNRTI or Integrase Inhibitor
Avoid overlapping toxicities + resistances
Drug interactions
Goals of HIV therapy
Restore & preserve immune function
Reduce related morbidity & mortality
Maximally & durably suppress HIV replication
Improve quality of life
HPV
Viral DNA insert itself into the host genome
HPV oncoproteins E6 & E7. E6 inactivates a host cell tumour suppressor p53.
E6 & E7 target diverse cellular pathways involved in the regulation of cell cycle control & cell death
an oncogenic virus
HPV9 protects against 9 strains, licensed in 2014
Can lead to: genital warts, cervical cancer
HPV vaccine estimated to protect against 7 out of 10 cervical cancers
Cancer
Cancer arise due to a series of genetic & epigenetic changes: loss of tumour suppressor genes, activation of proto-oncogenes to oncogenes
Cancers- diseases of altered gene expression/ function/ regulation
200 diff. types of cancer
Uncontrolled proliferation of cells
Uncontrolled cell growth & spread from genomic dysregulation & loss of cell signalling control
A disease of genome damage & loss of growth control
Antimetabolites
Some of these agents like methotrexate BLOCK DHFR
Needed in production of folates for DNA synthesis
Antimetabolites are purine or pyrimidine analogues that interfere with metabolic processes such as DNA & RNA synthesis
Aromatase inhibitors
MOA: inhibits conversion of androgens to oestrogen in the adrenal cortex (main source of oestrogens in post-menopausal women)
Clinical use: tx of breast cancer in post-menopausal women (advanced prostate carcinoma)
Anastrozole, letrozole, exemestane
Adverse effects on bone
Trastuzumab
Humanised murine monoclonal antibody
Clinical use: 25-30% breast cancers overexpress HER2, constitutively ON growth factor signalling, >> cancer proliferates rapidly
Binds to oncogenic protein: HER2/ERBB2: member of the wider family of receptors with tyrosine kinase activity