Module 11 - Antimicrobials Continued Flashcards
(41 cards)
Antifungal Agents:
-few in number
-selective toxicity is difficult (fungi are eukaryotes, like human cells)
-have ergosterol - a lipid in fungal membranes (humans have cholesterol)
-some times no single antifungal is ideal (ringworm infection of the nails or recurrent vaginal candidiasis are frequently intractable)
-resistance occurs
Azoles or Imidazoles:
-Inhibits cell membrane synthesis (ergosterol)
-Small molecule, easily absorbed
-Clotrimazole (Lotrimin) and miconazole (Monistat) are useful topical preparations
-Fluconazole used increasingly to treat Candida (avoid in 1st trimester especially)*
-Ketoconazole (Nizoral) is the agent of choice for serious infections*
-issues in pregnancy
Ketoconazole:
-Effective orally but can be used topically
-3-20% report nausea when given orally
-Hepatic toxicity can be a problem
-Teratogenic
(can cause congenital defects)
-Syndactyly and polydactyly
-CONTRAINDICATED during pregnancy (unless no choice)
-At high doses may block steroid levels:
Oestrogen and progesterone: may affect contraceptive function
Testosterone: may lead to gynecomastia
Fluconazole- another family member also has evidence of teratogenicity at high dose (Category D at high doses)- low dose less evidence of an issue
Polyenes:
-amphotericin B and nystatin (mycostatin)
-inhibit cell membrane function:
-bind to cell membrane and cause leakage of cell products and cell death (breaks ergosterol and not cholesterol)
-selective toxicity because humans do not have the binding site
-used to treat serious systemic fungal infections
-Amphotericin B given IV, orally, or topically
Used to treat serious infections
Side effects: fever, nausea, malaise, chills
*Safe during pregnancy (category B)
-Nystatin topical only (category A)
Used to treat Candida in mouth, mucous membranes (vaginal)
Athlete’s foot (cutaneous mycosis)
Minimal side effects
Antivirals:
-During the last 20 years a range of new antivirals for HIV, Hepatitis B and C and influenza have been discovered
-All are virustatic not virucidal→ they suppress replication, not kill viruses
-Difficulty with antivirals is how to interfere with viral activity in the cell and not harm the host
-We know viruses depend on host’s protein synthesis machinery
Antiviral Site of Action:
- Absorption (T-20- binds HIV gp41 site to stop attachment)
- Penetration and uncoating (amantadine)
- Viral DNA/RNA synthesis (aciclovir,
nevirapine) - Viral protein synthesis (interferons)
- Assembly (protease inhibitors)
- Release (no therapy available)
Anti Herpesvirus Agents: Nucleoside Inhibitors:
-Aciclovir, ganciclovir, valaciclovir
-Inhibits DNA polymerase of one or more members of the herpesvirus family
Acyclovir is used in the treatment of HSV and VZV infections
Ganciclovir is used in CMV as well HSV/VZV
Valacyclovir (a derivative of acyclovir) is used for genital herpes
-Minimal toxic-side effects for it is active only in infected cells
Antivirals for HSV and pregnancy:
-people with known recurrent genital HSV infection should be offered aciclovir or valaciclovir suppression at 36 weeks’ gestation to decrease the risk of clinical lesions and viral shedding at the time of delivery and therefore decrease the need for Caesarean section
Nucleoside Inhibitors: Mechanism of Action
slide 12
Antiretroviral Therapy:
-Aim is to keep plasma HIV-1 load low to maintain the CD4 count
-Many different types of agents used to achieve this including nucleoside and nucleotide reverse transcriptase inhibitors(RTI), non-nucleoside RTI, Protease/fusion/integrase inhibitors, Chemokine receptor antagonists
-Therapy with combinations of antiretroviral drugs is referred to as antiretroviral therapy (ART)
Anti-influenza Agents:
-Can target Influenza A alone or both A and B viruses
-Amantadine (A only):
Inhibits an early step in viral replication, probably viral uncoating
For some strains, they also alter hemagglutinin processing
Can be given prophylactically during outbreaks
Can also use as treatment: if given within 48 hrs of symptoms it reduces disease severity
May cause minor neurological disturbances, insomnia
Zanamivir/Oseltamivir
-Neuraminidase Inhibitors
-Targets the surface glycoprotein neuraminidase
-Acts against strains A and B
-Same usage as amantadine
slide 15
Antihepatitis Agents:
-the aim of of treatment is to reduce risk of liver cirrhosis and carcinoma by keeping BHV/HCV levels low
-Hepatitis B-IFN or nucleoside and nucleotide analogues (lamivudine)
-hepatitis C
-Direct acting antivirals have recently become approved to treat chronic HCV – prevents virus replication and can “cure” in 90% of cases
*currently not approved in pregnancy, but may become of use in the future
Resistance:
In comparison to antibiotics, resistance to antiviral agents is uncommon
Vaccines: General Concepts:
-Vaccines provide active immunisation, because the adaptive immune system responds to antigens in the vaccine a produces memory B and T cells. These cells are then available to respond quickly (memory) if an infection with that pathogen occurs after immunisation.
Antibodies generated by vaccination (or repeated vaccination) are directly available to fight the pathogen when an infection occurs
-Passive immunisation is provided by antiserum or other immunoglobulin (what B cells would normally make) based treatments that provide antibodies to protect from (or treat) infection, but do not induce memory response, and provide only temporary immunity
What is a Vaccine:
-a biological preparation that is designed to induce an adaptive immune response to a pathogen so that upon subsequent exposure to that pathogen the individual will be protected
Edward Jenner
- 1796: cowpox to immunise against smallpox
- now there is a worldwide eradication of smallpox
Aims of Vaccination:
For individuals:
Reduce or prevent symptoms of infectious disease
For society as a whole:
Prevent transmission of infectious disease (avoid epidemics or pandemics)
Eradicate disease from humans (long-term lofty goal)
Basic Types of Approved Vaccines (6 total types- 8 with new COVID Vaccines):
1.Live attenuated
2.Inactivated (primarily good at inducing antibodies)
A) Whole
B) Fractional:
1. Subunit
2. Toxoid
3. Polysaccharide based- Whole/conjugate
3.mRNA *
4.Viral-vectored*
-* New classes that have been approved with COVID
- Live Attenuated Type Vaccines
-Attenuated virus still infects humans and replicates
-Usually it has reduced replication, assembly or release
-They generally stay within the local injection site
-This allows an immune response to occur to clear the virus without a large spread or load of infection
How are attenuated viruses produced? Slide 31
Live Attenuated Type Vaccines:
BENEFITS:
-Works well for viruses (harder for bacteria)
-Because it mimics infection, it develops a full immune response against the pathogen
-Both antibody mediated and cellular mediated
-Most potent vaccine type so it doesn’t usually require adjuvants
RISKS/NEGATIVES:
-Risk of reversion to wild type virulent strain
-Can’t be given to everyone- dangerous for immunocompromised and not recommended for pregnant women
-Needs to be kept cold to maintain activity
SLIDE 33
Live Attenuated Vaccine Use in Pregnancy:
-pregnancy is reduced cellular immunity
-Nearly all live attenuated vaccines pose risk to the foetus and sometimes the mother.
-Most are contraindicated.
MMR
Varicella
Smallpox
Typhoid
Yellow Fever
Nasal influenza (should not use)
