Exam 4 - Chapters 20, 21, 22

Chermotherapy

The use of drugs to treat a disease

Antimicrobial drugs

Interfere with the growth of microorganisms within a host

Antibiotic

A substance produced by a microorganism that inhibits another microorganism

Selective toxicity

Specifically destroying microorganisms without damaging the host

Alexander Fleming

* 1st discovered Penicillin fungus (mold) in 1928
* This mold was inhibiting the growth of the bacteria
* 1940: first clinical trials of penicillin performed
* Inhibition: area where bacteria is gone or (killed)

Bactericidal

it will kill bacteria microorganisms directly 

Bacteriostatic

prevents microorganisms from growing

* So that hopefully then the immune system will take over

Inhibition of cell wall synthesis

* Penicillins
* Cephalosporins
* Bacitracin
* Vancomycin

Inhibition of protein synthesis

* Chloramphenicol
* Erythromycin
* Tetracyclines
* Streptomycin

\
Inhibition of nucleic acid replication and transcription

* Quinolones
* Rifampin

Injury to plasma membrane

* polymyxin B

Inhibition of essential metabolite synthesis

* Sulfanilamide
* Trimethoprim

B-Lactam Antibacterials

* inhibit formation of cross-linking peptides in peptidoglycan
* penicillins

Penicillins

* Natural penicillins
* Semisynthetic penicillins

Natural penicillins

Effective primarily against gram + bacteria

* Examples
* Penicillin G (requires injection)
* Penicillin V (taken orally)

Semisynthetic penicillins

Several are effective against both gram +/- bacteria

* Examples
* Oxacillin (narrow spectrum, only gram +, resistant to penicillinase)
* Ampicillin (broad spectrum, many gram -)

The effect of bacterial penicillinase on penicillin

penicillin —> penicillinase —> penicilloic acid

B-Lactam ring

CH-CH-C-N

B-Lactam Antibacterials

* Penicillins
* Cephalosporins
* Carbapenems

Cephalosporins

* derived from *Cephalosporium* fungi
* examples:
* cephalexin
* cephadrine
* Ceftriaxone
* Up to 15% of individuals who are allergic to penicillins are also allergic to cephalosporins

Carbapenems

* 2-part drugs: B-Lactam & a compound that prevents its degradation in the kidneys
* very broad spectrum (example: *Primaxin*)

Inhibitors of cell wall synthesis (prevents cell wall process)

* Polypeptide antibiotics
* Bacitracin
* Vancomycin
* Anti-*Mycobacterium* antiiotics
* Isoniazid
* Ethambutol

Polypeptide antibiotics

* Bacitracini
* Vancomycin

Bacitracin (Tracy who survived train hit: inhibitor of cell wall synthesis)

* tropical application for superficial infections
* targets great positives (streptococci & staphylococci)

Vancomycin (inhibitor of cell wall synthesis)

* derived from species of *Streptomyces* (bacterial species) found in the jungles of Borneo
* narrow spectrum use gains gram +
* One of out last defenses agains methicillin-resistant *S. aureus* (MRSA)
* Vancomycin-resistance in bacteria is considered a medical emergency since few alternatives exist

Anti-*Mycobacterium* antibiotics

* Isoniazid
* Ethambutol

Isoniazid (inhibitor of cell wall synthesis)

* Inhibits mycolic acid synthesis by mimicking 2 vitamins: niacin & pyridoxal

Ethambutol (inhibitor of cell wall synthesis)

* inhibits incorporation of mycolic acid into mycobacteria’s cell wall
* Given concurrently with isoniazid & is effective against slow-growing mycobacteria (such as *M. Leprae*)

Inhibitors of protein synthesis

* Chloramphenicol
* Aminoglycosides
* Tetracyclines
* Macrolides

Chloramphenicol (inhibitor of protein synthesis)

* broad spectrum
* Binds 50S subunit and inhibits peptide bond formation
* Usually not a 1st choice Antimicrobial drug due to its host toxicity (suppresses blood cell production in bone marrow)

Aminoglycosides (inhibitor of protein synthesis)

* broad spectrum
* Target the 30S subunit of the ribosome
* Examples:
* Streptomycin
* Neomycin
* Gentamicin
* Not widely used today unless other treatments fail because of host toxicity
* Can affect the auditory nerve and cause hearing damage (neurotoxicity)
* Can also damage kidneys (nephrotoxicity)

Tetracyclines (inhibitor of protein synthesis)

* broad spectrum
* Interfere with tRNA attachment on the 30S subunit of ribosome
* Not recommended for children because it forms complexes with calcium that may damage teeth & bones
* Together w/ B-lactams, comprise the 2 most important classes of antibiotics in clinical medicine

Macrolides (inhibitor of protein synthesis)

* target the 50S subunit of the ribosome (prevent translocation)
* Examples:
* Erythromycin
* Azithromycin
* Clarithromycin
* Often used in place of B-lactate for allergic patients

Injury to the plasma membrane

* polymyxin B

Polymyxin B (injury to the plasma membrane)

* topical application for gram - infections, especially those caused by species of *Pseudomonas*
* Combined with bacitracin & neomycin in an over-the-counter preparation (Neosporin)
* 1 of the few antibiotic preparations that does not require a prescription

Inhibitors of nucleic acid synthesis

* Rifampin
* Quinolones

Rifampin (inhibitors of nucleic acid synthesis)

* inhibits transcription (RNA synthesis)
* Used mainly to treat tuberculosis & leprosy
* A side-effect is the appearance of redish-orange urine, feces, saliva, sweat, and tears

Quinolones (inhibitors of nucleic acid synthesis)

* inhibit DNA replication by inactivating DNA gyrase
* Often used in treatment of urinary tract infections (UTI)
* Example: ciprofloxacin (cipro)

Competitive inhibitors

* inhibit folic acid synthesis
* Broad spectrum
* Most widely used example: Bactria
* Combination of *trimethoprim* and *sulfamethoxazole* (TMP-SMZ)

Antifungal drugs

* Echinocandins
* Polyenes
* Griseofulvin
* Tolnaftate (Tinactin) and Terbinafine (Lamisil)

Echinocandins (antifungal drug)

* inhibit cell wall synthesus
* Example: Cancidas is used against species of the yeast *Candida*

Polyenes (antifungal drugs)

* inhibit ergosterol synthesis in fungal cell membrane, causing membrane permeability & cell death
* Examples:
* Amphotericin B
* Nystatin

Griseofulvin (antifungal drug)

* inhibits fungal cell division
* Oral medication used for superficial fungal infections of the skin, hair, and nails

Tolnaftate (Tinactin) & Terbinafine (Lamisil)

* topical over-the-counter fungicides for athlete’s foot & jock itch

Antiviral drugs

Nucleoside analogs

* mimic structures of purines (A,G) & Pyrimidines (C,T)
* Acyclovir structurally resembles the nucleoside deoxyguanosine

\
Nucleoside Analogs B

The enzyme thymidine kinase combines phosphate with nucleosides to form nucleotides, which are then incorporated into DNA

Nucleoside Analogs C

Acyclovir has no effect on a cell not infected by a virus, that is, with normal a thymidine kinase. In a virally infected cell, the thymidine kinase is altered & converts the acyclovir (which resembles the nucleoside deoxyguanosin) to false nucleotide, which blocks DNA synthesis by DNA polymerase

Antiviral Drugs (2)

* Oseltamivir (Tamiflu) / Zanamivir (Relenza)
* Interferons

Oseltamivir (Tamiflu) / Zanamivir (Relenza): Antiviral drug

Block *neuraminidase* activity of influenza A and B viruses, inhibiting viral release from the host

Interferons: Antiviral drugs

* released by virus-infected cells & induce neighboring cells to synthesize antiviral proteins
* Imiquimod: drug that promotes interferon production

Testing drugs - the disk diffusion method

Testing Drugs - the E (epsilometer) test

Antibiotic resistance

* a variety of mutations can lead to antibiotic resistance in pathogens
* Mechanism of antibiotic resistance
* 1) enzymatic destruction of drug
* 2) blocking entry of drug
* 3) alteration of drug’s target site
* 4) rapid ejection (efflux) of the drug
* Resistance genes are often on *R plasmids* that can be transferred between bacteria

Antibiotic resistance

Resistance genes are often on *R plasmids* that can be transferred between bacteria

Resistance to antibiotics

* 1) blocking entry
* 2) inactivating enzymes
* 3) alteration of target molecule
* 4) efflux of antibiotic

Antibiotic resistance

* Misuse of antibiotics selects for resistance mutants. “Misuse” includes:
* Using outdated or weakened antibiotics
* Using antibiotics for the common cold and other inappropriate conditions
* Using antibiotics in animal feed
* Failing to complete the prescribed regimen
* Using someone else’s leftover prescription

\

Skin

*Staphylococcus aureus*

* Antibiotic resistance common
* Produces leukocidins
* Survives inside the phagolysosome
* Lysozyme resistant
* Forms biofilms

Folliculitis/Impetigo: Staphylococcal skin infection

Folliculitis: hair follicle infection

* sty: folliculitis of an eyelash
* furuncle: abscess, pus surrounded by inflamed tissue
* carbuncle: inflammation of skin tissue usually leading to fever

Impetigo: highly contagious, crusting sores that spread easily to surrounding areas, occurs mostly in children

Scalded skin syndrome: Staphylococcal skin infection

* Form of impetigo caused by exotoxin-producing staphylococci


* Most common in infants but can occur in adults, usually as toxic shock syndrome (tampons)

\

Streptococcal skin infection

* Caused by Group A, beta- M proteins hemolytic streptococci, especially *Streptococcus pyogenes*
* Secrete hemolysins that lyse RBCs
* Secrete hyaluronidase, which breaks down hyaluronic acid, the “cement” in connective tissue
* M proteins on some strains form a “fuzzy” outer layer and prevent activation of complement, allowing the pathogen to evade phagocytosis

\

Erysipelas: Streptococcal skin infection

* *S. Progenies* infection of dermis
* Spreads through lymphatic system and can lead to a variety of serious symptoms & death in untreated
* Cephalosporins are the antibiotics of choice

\
\
\
Scarlet fever: Streptococcal skin infections

* Caused by a strain of *Streptococcus pyogenes* that contains a lysogenic phage that enables the bacterium to produce *erythrogenic* toxin, a “superantigen”


* Symptoms are sore throat, fever, strawberry-like red tongue, and a rough-textured, red rash that blanches (press on red spot then turns white - if this doesn’t happen then it could be meningitis)

\

Invasive group A: Streptococcal infection

Necrotizing fasciitis (necro: death)

* caused by “flesh-eating” *S. Pyogenes*
* Secretes *exotoxin A*, a superantigen
* Tissue often erodes at the rate of 1 in per hour
* Often results in amputation of affected limbs

*Pseudomonas* Infections

Pseudomonas aeruginosa

* gram -, opportunistic, aerobic rod
* *Pseudomonas*-induced dermatitis
* Hair follicle infection (*folliculitis*) associated with public pools & hot tubs
* *Pseudomonas* infections in burn wounds
* *Pyocyanin* pigment produces a blue-green pus’
* Produce a grape-like, fruity odor

*Pseudomonas*-induced dermatitis 

Hair follicle infection (*folliculitis*) associated with public pools & hot tubs 

\
*Pseudomonas* infections in burn wounds 

* *Pyocyanin* pigment produces a blue-green pus’
* Produce a grape-like, fruity odor

Acne

Causative agent is Cutibacterium (Propionibacterium) acnes

* Gram-positive anaerobe
* Mild/moderate cases treated with topical salicylic acid or benzoyl peroxide
* Benzoyl peroxide is available combined with the antibiotics clindamycin (Benzaclin) or erythromycin (Benzamycin)
* Severe cases treated with isotretinoin (Accutane)
* Isotretinoin must not be given to pregnant women because it is a potent teratogen (causes birth defects in a developing fetus aka death of fetus)

Chickenpox: Viral skin lesions

* Varicella-zoster virus (HHV-3)
* Transmitted by the respiratory route
* Causes pus-filled vesicles
* Virus may remain latent in dorsal root ganglia
* Prevention: Live attenuated vaccine

\

Shingles: viral skin lesions

* A woman scratched through skin and skull to the brain
* Usually happens on one side of the body
* Reactivation of latent varicella-zoster virus releases virions that move along peripheral nerves to skin
* Results in “postherpetic neuralgia” if prolonged
* Prevention: Live attenuated zoster vaccine
* Acyclovir may lessen symptoms

\

Cold sores/Fever blisters: Viral skin lesions

* Human herpesvirus 1 (HSV-1) vesicles
* Up to 90% of the population is infected
* HSV-1 can remain latent in trigeminal nerve ganglia
* Treated with acyclovir

\

Warts: viral skin lesions

* Caused by human papillomavirus (HPV)
* May be dermal or genital
* Usually treated with salicylic acid or liquid nitrogen (cryotherapy), but extreme cases may require laser removal

\

Measles (Rubeola) virus: Viral skin lesions

* Transmitted by respiratory route
* Extremely contagious and can be life-threatening for infants and the elderly
* Causes macular rash of raised spots, as well as
* Koplik's spots opposite the molars in the oral cavity
* Prevented by MMR vaccination

\

Rubella virus: Viral skin lesions

* “German measles” Causes unraised macular rash and fever
* Symptoms generally mild, except in fetuses
* Congenital rubella syndrome causes severe fetal damage
* Prevented by MMR vaccination
* Measles
* Munks
* Rubella

\

Fungal skin infections

* Dermatomycoses (tineas)
* Candidiasis
* Madura foot

Dermatomycoses (tineas): Fungal skin infections

* occur on the head, groin, feet, or nails
* Fungus metabolizes keratin in epidermis
* Usually treated with topical antifungal drugs or griseofulvin (oral)

\

Candidiasis: Fungal skin infections

* Caused by Candida albicans (yeast)
* Often results from suppression of competing bacteria by antibiotics
* Occurs in skin and mucous membranes of urogenital tract (vaginitis) and mouth (thrush)
* Treated topically with miconazole or nystatin

\

\
Madura foot: fungal skin infection

* Caused by several tropical soil fungi
* Enters the dermis through small breaks in the skin, mainly in people who do not wear shoes
* May require amputation unless antifungal drugs are given early
* Treatment often sought late because the infection is generally painless
* Amputation is it gets extreme
* If caught early there are antibiotics but if already too advanced… no treatment

\

Parasitic infestations of the skin

* Scabies
* Pediculosis (Lice)

Scabies: (Parasitic infestations of the skin)

* *Sarcoptes scabiei* burrows into the skin to lay eggs
* Transmitted by direct contact
* Treated with topical insecticides

\

Pediculosis (Lice): (Parasitic infestations of the skin)

* Pediculus humanus capitis (head louse)
* Feed on blood
* Lay eggs (nits) on hair
* Treated with topical insecticides

Bacterial diseases of the eye

* Conjunctivitis (pinkeye)
* Ophthalmia neonatorum
* Trachoma

Conjunctivitis (pinkeye): (Bacterial diseases of the eye)

* An inflammation of the conjunctiva (inner eyelid and sclera) - sclera: white part of eyeball
* Usually viral, but may also be caused by *Haemophilus* *influenzae*, staphylococci, streptococci, and pseudomonads
* Associated with wearing unsanitary contact lenses

\

Ophthalmia neonatorum: (Bacterial diseases of the eye)

* Caused by *Neisseria gonorrhoeae*
* Transmitted to a newborn's eyes during passage through the birth canal
* Prevented by treating newborn's eyes with antibiotics, usually erythromycin ointment

\

Trachoma: (Bacterial diseases of the eye)

* Caused by *Chlamydia trachomatis*
* Infection causes inflammation and permanent scarring
* Scarring causes eyelashes to turn inward, leading to scratching of the cornea and blindness
* Leading cause of infectious blindness worldwide

The nervous system

The *meninges* are 3 layers of tissue that protect the central nervous system (CNS; the brain and spinal cord)

* 1) Dura mater: Outermost layer
* 2) Arachnoid mater: Middle layer
* Subarachnoid space contains *cerebrospinal fluid* (CSF)
* 3) Pia mater: Innermost layer

\

Dura mater: Meninges layer

* Outermost layer
* Really tough

Arachnoid mater: Meninges layer

* middle layer
* thinnest layer
* Subarachnoid space contains *cerebrospinal fluid* (CSF)

Pia mater: Meninges layer

* innermost layer

Bacterial Meningitis

* Meningitis
* Encephalitis
* Meningoencephalitis

Meningitis: bacterial meningitis

inflammation of meninges

* Initial symptoms of meningitis include fever, headache, and stiff neck followed by nausea and vomiting
* May progress to convulsions and coma
* Diagnosis is by Gram stain and/or serological testing of CSF (obtained by spinal tap)
* Treatment: Cephalosporins or vancomycin 

Encephalitis: bacterial meningitis

inflammation of the brain

* Initial symptoms of meningitis include fever, headache, and stiff neck followed by nausea and vomiting
* May progress to convulsions and coma
* Diagnosis is by Gram stain and/or serological testing of CSF (obtained by spinal tap)
* Treatment: Cephalosporins or vancomycin 

Meningoencephalitis: bacterial meningitis

Inflammation of both meninges and brain

* Initial symptoms of meningitis include fever, headache, and stiff neck followed by nausea and vomiting
* May progress to convulsions and coma
* Diagnosis is by Gram stain and/or serological testing of CSF (obtained by spinal tap)
* Treatment: Cephalosporins or vancomycin

\

Spinal Tap (Lumbar Puncture)

*Haemophulis influenzae* Meningitis

* Occurs mostly in children (6 months to 4 years)
* Gram-negative, aerobic bacterium that is part of the normal throat microbiota
* Pathogenic strains contain a type b capsule antigen
* These strains are often referred to simply as *Hib* (*Haemophilus influenzae* type b)
* Prevented by Hib vaccine

*Neisseria meningitidis* Meningitis

* Also called meningococcal meningitis
* Gram-negative, aerobic diplococci with a capsule
* 40% of people are healthy nasopharyngeal carriers
* Begins as throat infection and rash
* Six capsular serotypes are known:
* Protection from most serotypes is available in a vaccine that is recommended for college students

\

*Neisseria meningitidis*

Cerebrospinal fluid sample showing gram-negative diplococci

*Streptococcus pneumoniae* Meningitis

* Also called pneumococcal meningitis
* Caused by S. pneumoniae (a gram- positive coccus)
* 70% of people are healthy nasopharyngeal carriers
* Most common in children (1 month to 4 years)
* Prevented by vaccination

\

Listeriosis

* Caused by Listeria monocytogenes
* Gram-positive aerobic rod
* Usually foodborne; begins as fever and nausea, but can spread to CNS
* Can be transmitted across the placenta to a fetus and often causes abortions
* Reproduces inside phagocytes
* Treated with penicillin G

\

Tetanus

* Body injects endopores
* Caused by *Clostridium tetani*
* Gram-positive, endospore-forming anaerobe
* Grows in deep wounds, such as punctures
* Bacteria release tetanospasmin (eg. step on rusty nail) , a potent neurotoxin that blocks the relaxation pathway in muscles, causing *spastic paralysis* (muscles are always contracted, you loose the ability to relax muscles)
* Prevention by vaccination (DTaP)
* Tetanus immune globulin (TIG) is given to injured individuals whose vaccination history is unknown or out-of-date

\