Anti-Infectives Animal cells: Cholesterol

Fungal cells: Ergosterol

Coronavirus (Corona viridae)
*This difference is enough so that amphotericity can choose to
– part of RNA viruses
destroy fungi, but not human cells
Viruses
*Antifungal agents want to bind more in ergosterol than
- contain protein, RNA/ DNA cholesterol
- Not living organism because they can’t catalyze their
own/ not self sufficient
- Infect to multiply Heavy metals that were used for anti-infectives before which
- Basic requirement: are toxic:
• Protein: There could be presence of
capsules, which makes the virus resistant • Mercury
• Nucleic Acid: Could be a group of DNA/ • Antimony
RNA) • Arsenic
*African Sleeping Sickness- agent still use arsenic
(Suramin)
Chemotherapy/ Chemotherapeutic agents
*Arsenic and Antimony were somehow still used up to this date
- Not just about anticancer agents for protozoans
- Not just anti-infective Protozoans: single-celled eukaryotes
- Agents that kill other cells e.g. Amoebiasis (Entamoeba hisolytica)
Plasmodium falciparum – malaria
Introduction: Giardia lamblia
• Joseph Lister
- Carbolic acid
What type of Carbolic acid? Phenol Philippines: Triple burden due to:
1. Spraying apparatus 1. Communicable Diseases (Infectious Diseases)
2. Lessens post-operative infection 2. Non-communicable (e.g. Diabetes)
- Saw the need to perform antisepsis prior to surgery 3. Diseases of rapid urbanization (e.g. Depression)
- Hand washing: Limit surgical infection

Antibiotics (1950s)
• Paul Erlich
- Compound 606/ Magic Bullet/ Problem: Emerging resistance of antibacterials
Arsphenamine (Brand Name: Salvarsan) –
*Antifungals also create resistance
Selectively toxic to Syphilis
(Causative agent: Treponema pallidum)
Problem with Arsphenamine?
Contains Arsenic which makes it toxic to the body Germicide
- Selective toxicity: Kill one type of organism without - Local anti-infective
harming the other / Aim not to harm the other cells - Classified into 2:
In case of anti-infectives: Kill pathogens 1. Antiseptic
Common between Fungal cells and Human cells? – intended to be applied on living tissues
– in contact with bodily fluids
• Eukaryotes – Main concern:
• Being both eukaryotic makes it hard to make 1. Low toxicity on living tissues,
antifungal agents 2. But still have to be effective on
• Only difference is their sterols microbes
 3. Stable Sanitization
4. Active
- Concern of Public health
5. Low surface tension > Spread
- Reduce the amount of microbes to an acceptable
easily
level only
6. Non-irritating
- Doesn’t have the need to remove everything
7. Non-allergenic
*If anti-infectives doesn’t work, antisepsis should be done
*Topical solutions should spread, and not be absorbed in the
systemic circulation
*The ideal antiseptic does not exist, but compounds that will
come close to it are: Bacitracin & Silver Sulfadiazine (burns)
Alcohols
ROH

2. Disinfectant – intended to be applied on inanimate
surface, but usually cannot handle spores
- Can be lethal to living tissues, since
needed for inanimate objects
- Problem: Comes into contact with organic
matter
- Should not be inactivated in the presence
of other components
- Main Concern: Non-corrosive
Pleasing
Non-Staining
Odorless
• Phenol Coefficient
Turbid = Growth
No turbidity = No growth
Lower turbidity = Possibly inhibit
Higher Phenol Coefficient = More potent
Phenol served as a standard for qualifying
anti-infectives, but not reliable
Sterilization
- Eliminate spores
• Dry heat sterilization
• Moist Heat
• Filtration
• Ionizing Radiation
• Gas Sterilization: Use of Ethylene Oxide
Autoclave: 121 C 15 psi 15 seconds
Pasteurization: Milder; won’t last long
MOA: Denaturation – disrupt protein and cell membranes
so alcohol can slip up; happens due to Van der Waals
forces: depends R- group
Solubility: comes from the - OH group: Hydrogen bonds
*The longer the alkyl group = More Van der Waals forces
= More Non-polar = More disruption in the cell membrane
= More carbon groups = Becoming Insoluble = increase
MW = Increase potency = But only till it reaches up to
Carbon 8
Beyond carbon 8 (Octanol): Not soluble = Not effective
More branched: Lesser van der Waals = Less potent =
Cannot disrupt cell membrane
2 Common Examples
• Ethanol
• Isopropanol
In 40% of Isopropanol = 60% Ethanol
*More branched = Less potent, except for
Isopropanol
*In anti-infective agents: It is important to consider the contact
time
For Ethanol: 60% is as effective as 95% ; Below 60% = Still
effective, if increased contact time
Alcohol derivatives
• Ethylene oxide – cyclic ether

Decontamination
- Marked reduction
Only
- Very unstable
 - Highly reactive: Can explode when exposed to
Oxygen: Prepared as Carboxide (10% Ethylene
oxide, 90% Carbon dioxide)
- Reacts through alkylation
- Needs to react to remove strain in Carbon
- Used for gas sterilization only
- Used because it does not involve heat, but has high
toxicity, which can cause cancer through alkylation
• Aldehydes
- Reactive due to the carbonyl carbon
e.g.
- Formaldehyde: Antiseptic – has an ability to cause
Alkylation > has Adverse Effects: Mucosal Irritation
Formaline – Solution of Formaldehyde in water
- Glutaraldehyde (Cidex): Used to rapidly sterilize
operating equipments
+Activated glutaraldehyde if there is an alkaline buffer
If too acidic: Stable, but not sporicidal (does not work
on spores)
If too basic: Tend to be inactive
Can be reused
Phenols
Phenols
MOA: Denaturation
- Can have mild local anaesthetic effect
- More active when you substitute alkyl, alyl, halogens
with nonpolar constituents, especially in the para
position
- Cause keratolysis (break skin)
- Cause dermatitis
- Use in high conc.: Can cause Phenol burn
*Phenols are diluted
* For certain compounds, you want them to be keratolytic
e.g. Phenols as antifungals
e.g. Salicylic acid, Resorcinol, Hexyl Resorcinol
-used as keratolytic phenol agents
Keratolytic + Antiseptic = can be used as topical antifungal
= for fungal infections of the skin
Levels of fungal infection
1. Superficial
2. Cutaneous (e.g. Athlete’s foot, caused by tinea
fungus)
3. Subcutaneous
4. Deep
*Derivatized phenols are more effective (Substitution: Often
less toxic)
Para-Chlorophenol: Addition of Chlorine
- More potent
- Retains its anti-irritant effect
- Relative derivative: Dichlorobenzyl alcohol –
Antiseptic, also used in lozenges because of its anti-
irritant effect, also has local anaesthetic effect
Cresol
- Hydroxytoluene
- Possesses creosote odor
Creosote oil – came from Juniperus oxycedrus
-contains related compound: creosole
* Cresole and Creosole have the same odor
- Due to the addition of nonpolar groups: Have
decreased solubility in water
Thymol
- Used as antiseptic
Eugenol
- Has a local anaesthetic effect
Hexylresorcinol
- Advantage: Has local anaesthetic effect = less
irritation in the throat
- Surfactant effect enables it to spread
- Related Compound: Amylmetacresol (present in
Strepsils)
Essential oils: phenolic class – have relaxing property on the
throat
*Principle: Since they can disrupt cell membranes through Van
der Waals force
*Presence of Hydrocarbon group: can disrupt cell membrane
Problem:
If Hydrocarbon groups become larger: become water insoluble
Oxidizing Agents
MOA: Upon oxidation > Release Oxygen
- Not as effective as they could be
- Have poor penetrability in the lipid bilayer
- Oxygen cannot spread
- Have short period of activity
- NO oxygen – Not active
Release Other Reactive Oxygen Species (e.g. Hydroxyl
radical, Oxygen radical, Peroxides) > Cause indirect oxidative
effect to the bacteria
Potassium Permanganate – once used on humans to cause
direct oxidation
1. Carbamide Peroxide: Mixture of urea and Peroxide
- Just releases peroxide (activity will cause oxidation of
the bacteria
- Effective for anaerobic microorganisms
- Effect/ Use: Cosmetic (Whitening): involves releasing
of reactive oxygen species, Remove earwax
2. Benzoyl Peroxide
- Has an additional property of being both keratolytic
and keratogenic > skin will be in confusion > Leads to
epithelial proliferation (Dead skin eventually get
replaced due to the fast turnover of the skin)
- Induce the repair
Halogen-Containing Compounds
1. Iodine
MOA: Protein inactivation, usually binds to aromatic
groups
- More of an Antiseptic
- Has the ability to cause sulfhydryl oxidation
- One of the oldest germicides still used
- One of the most effective
- Problem: has a staining effect
: In very high concentrations, can be irritating
- To manage the irritating effect, Iodophors where
invented:
Iodophors – complexes of Iodine, and an organic
material, able to reduce volatility, increase water
solubility, more effective,
*slow release of Iodine solves the irritating effect
No Iodine = No effect
- Polyvinylpyrrolidone
2. Chlorine
- E.g. Sodium hypochlorite – used to disinfect water
- More of a disinfectant
- Usually causes chlorination of amide hydrogen
- Causes sulfhydryl oxidation similar to Iodine
- Halazone – organic compound which slowly releases
the chlorine in water, and sustains disinfectant effect;
Chlorine is bound to Nitrogen
Cationic Surfactants
- Can be used as disinfectants
- Perform surfactant action on cell membranes (destroy
cell membranes)
- Very active against a wide range of microorganisms
(bacteria, fungi, protozoans)
- Disadvantage: Not active against spores and easily
inactivated
- Used for soap solutions that has quaternary
ammonium compounds
- Keratolytic: Allows it to have penetration
- Soap contains Sodium Lauryl Sulfate > sulfate:
- Cationic surfactant + Anionic surfactant = No activity
- Cationic surfactants are inactivated by soaps, talc
- Slow effect unlike other anti-infectives which are fast
- Should not be reused, because they can harbor
microbes
- Effective at first
Quaternary Ammonium Compounds
• Benzalkonium Chloride
• Cetylpyridinium Chloride
• Chlorhexidine gluconate – Contains guanidino group
- Does not have quaternary ammonium, but acts
similarly to other cationic surfactants