PRESERVATIVES, ANTI TB AGENTS, ANTI TB ANTIBIOTICS, ANTIFUNGAL AGENTS, TOP. AGENTS FOR DERMATOPHYTES, NUCLEOSIDE ANTIBIOTICS, ANTIFUNGAL ANTIBIOTICS;POLYENES & GRISEOFULVIN (Chapter 6)

Question 1

• used to prevent microbial contamination
• Ideal Characteristics: effective at low concentrations against all possible
microorganisms, nontoxic, compatible with other constituents used in the
preparation, stable for the shelf-life of the preparation

Answer 1

Preservative

Question 2

• p-hydroxybenzoic acid
• useful as preservative for liquid dosage forms
• have antifungal properties
• preservative effect tends to increase with molecular weight
• can cause irritation for sensitive skin

Answer 2

Parabens

Question 3

• more effective against molds

Answer 3

Methylparaben

Question 4

• more effective against yeasts
• more oil-soluble so it is preferred for oils and fats

Answer 4

Propylparaben

Question 5

10 Other Preservatives

Answer 5

1. Chlorobutanol
2. Benzyl Alcohol
3. Phenylethyl Alcohol
4. Benzoic Acid
5. Sodium Benzoate
6. Sodium Propionate
7. Sorbic Acid
8. Potassium Sorbate
9. Phenylmercuric Nitrate
10. Phenylmercuric Acetate

Question 6

• occurs naturally in rose oil and pine-needle oil
• used primarily in perfumery

Answer 6

Phenylethyl Alcohol

Question 7

• used externally as an antiseptic for lotions, ointments and mouthwashes; more
• effective as a preservative in foods and pharmaceutical products at low pH

Answer 7

Benzoic Acid

Question 8

• used as preservative in acidic liquid preparations in which benzoic acid is
releases

Answer 8

Sodium Benzoate

Question 9

• effective antifungal that is used as preservative

Answer 9

Sodium Propionate

Question 10

• an effective antifungal preservative
• used to preserve syrups, elixirs, ointments, and lotions containing components such as sugars that support mold growth

Answer 10

Sorbic Acid

Question 11

• used as the same way as sorbic acid

Answer 11

Potassium Sorbate

Question 12

• used to preserve injectable drugs but bacteriostatic efficacy is reduced in the presence of serum

Answer 12

Phenylmercuric Nitrate

Question 13

• used as preservative

Answer 13

Phenylmercuric Acetate

Question 14

• Acid fast bacteria
• Rod shaped, aerobic bacteria that does not form spores
• facultative intracellular, obligate aerobe
• causes Koch’s disease
• Lowenstein-Jensen medium (serpentine growth colonies)

Answer 14

Mycobacterium tuberculosis

Question 15

• Isonicotinic acid hydrazide
• Nydrazid®
• MOA: inhibits the synthesis of mycolic acid, an important component of the cell wall of mycobacteria
• Principal adverse effect: Peripheral neuritis due to the competition of INH with pyridoxal phosphate for the enzyme apotryptophanase
• co-administration of pyridoxine prevents peripheral neuritis

Answer 15

Isoniazid (INH or H)

Question 16

• Trecator SC®
• structural analogue of isoniazid
• used in the treatment of isoniazid-resistant tuberculosis
• S/E: GI irritation, hepatotoxicity, peripheral neuropathies, optic neuritis

Answer 16

Ethionamide

Question 17

• Pyrazinecarboxamide
• MOA: unknown
• used in combination with other agents because resistance develops rapidly
• S/E: hepatotoxicity (inc. ALT/AST)
• must be enzymatically hydrolyzed to pyrazinoic acid (active form)

Answer 17

Pyrazinamide (PZA or Z)

Question 18

• Myambutol®
• S/E: Optic neuritis
• loss of ability to discriminate between red and green
• MOA: inhibits the incorporation of mycolic acids in the cell walls of the bacteria

Answer 18

Ethambutol (EMB or E)

Question 19

• MOA: acts as a competitive inhibitor for p-aminobenzoic acid (PABA) in folate biosynthesis
• S/E: severe gastric irritation
• second-line treatment for TB

Answer 19

Para-Aminosalicylic Acid (PASA/PAS)

Question 20

• Lamprene®
• MOA: unkwown
• basic red-dye used in the treatment of leprosy, including dapsone-resistant forms
• S/E: Colored-maroon urine

Answer 20

Clofazimine

Question 21

• obtained from Streptomyces mediterranei
• includes Rifampin and Rifabutin

Answer 21

Rifamycin

Question 22

• Rifadin, Rimactane, Rifampicin
• the most active agent against TB
• enzyme INDUCER toxic effects are relatively infrequent
• when it is taken in combination with INH or ethambutol, incidence of HEPATOTOXICITY is significantly higher
• S/E: reddish color of body secretions, hepatotoxicity

Answer 22

Rifampin

Question 23

First Line Treatment for TB

Answer 23

• Rifampin
• Isoniazid
• Pyrazinamide
• Ethambutol
• Streptomycin

Question 24

PTB = 2 mos (RIPE w/ or w/o S)
4 mos - maintenance phase (R + I)

Answer 24

First Line Treatment for TB

Question 25

• Seromycin® • isolated from different species of Streptomyces: S. orchidaceus, S. garyphalus, S. lavendulus • MOA: prevents the synthesis of cross-linking peptide in the formation of bacterial cell walls

Answer 25

Cycloserine

Question 26

• isolated from Streptomyces capreolus

Answer 26

Capreomycin

Question 27

• only aminoglycosides used for tuberculosis • the first antibiotic effective in the treatment of TB (1944 by Waksman)

Answer 27

Streptomycin

Question 28

• study of fungi

Answer 28

Mycology

Question 29

• studied Trichophyton schoenleinii (1839)

Answer 29

Schonlein & Gruby

Question 30

• reported the yeast- like microorganism responsible for oral thrush (Candida albicans)

Answer 30

Langenbeck

Question 31

2 Groups of Fungal Infections

Answer 31

• Superficial mycoses • Deep-seated mycoses

Question 32

• most common • caused by dermatophytes • includes tinea or ringworm infections and Candida infections

Answer 32

Superficial Mycoses

Question 33

8 Causative agents of Ringworm Infections

Answer 33

1. Tinea capitis 2. Tinea barbae 3. Tinea faceie 4. Tinea cruris 5. Tinea pedis 6. Tinea manum 7. Tinea ungium (Onchomycosis) 8. Pityriasis versicolor

Question 34

8 Systemic Mycoses

Answer 34

1. Histoplasmosis 2. Sporotrichosis 3. Blastomycosis 4. Coccidioidomycosis 5. Cryptococcosis 6. Paracoccidioidomycosis

Question 36

Cutaneous Infections (Dermatophytoses)

Answer 36

1. Microsporum 2. Trichophyton 3. Epidermophyton 4. Malassezia furfur

Question 37

• refers to a group of fungal diseases in which both the skin and subcutaneous tissue are involved but typically no dissemination to the internal organ occurs

Answer 37

Subcutaneous Fungal Infections

Question 38

• tinea or ringworm

Answer 38

Dermatophytoses

Question 39

• acidic, fatty substance in and on the skin; functions as a natural antifungal agent and part of the innate immune system

Answer 39

Sebum

Question 40

• an antifungal agent that is non-irritating and nontoxic

Answer 40

Propionic Acid

Question 41

• unstable to moisture, forming zinc hydroxide and propionic acid • used as fungicide, particularly on adhesive tape

Answer 41

Zinc Propionate

Question 42

• used topically to treat superficial dermatomycoses caused by C. albicans and Trichophyton, Epidermophyton and Microsporum spp. • from caprylic acid found in coconut or palm oil

Answer 42

Sodium Caprylate

Question 43

• 10-Undecenoic acid • obtained from the destructive distillation of castor oil • can be used in concentrations up to 10% • traditionally used for athlete's foot

Answer 43

Undecylenic Acid

Question 44

• activity is due to acetic acid released by hydrolysis of the compound by esterases present in the skin

Answer 44

Triacetin

Question 45

• has both antiseptic and keratolytic properties • a poor antifungal agent

Answer 45

Salicylic Acid

Question 46

• contains 6% benzoic acid and 6% salicylic acid in a petrolatum base • benzoic acid cannot penetrate the outer layer of the skin in infected areas thus used with keratolytic agents

Answer 46

Whitfield's Ointment

Question 47

• used as a 1% cream for the treatment of superficial tinea infections • lesion typically worsens before it improves • iflammation and painful irritation are common

Answer 47

Haloprogin

Question 48

• Vioform® • 3% ointment or cream is used as a treatment for Trichomonas vaginalis (Vaginitis) • Vioform HC® - combination with hydrocortisone

Answer 48

Clioquinol

Question 49

• an agent of choice for cutaneous candidiasis, tinea corporis, tinea cruris, tinea pedis and tinea versicolor • second-line treatment for onychomycosis • MOA: at low concentrations, it blocks transport of amino acids into the cells; at high concentrations, membrane integrity is lost and cellular contents leak out

Answer 49

Ciclopirox Olamine

Question 50

• Ancobon® • used only in combination with Amphotericin B for the treatment of systemic mycoses and meningitis caused by Cryptococcus neoformans and Candida (Synergistic) • MOA: release 5-FU

Answer 50

Flucytosine

Question 51

3 Polyenes

Answer 51

1. Amphotericin B 2. Nystatin 3. Natamycin

Question 52

• Fungizone® • naturally occuring, produced by Streptomyces nodosus • MOA: binds to ERGOSTEROL present in the cell membrane disrupting membrane function, allowing electrolytes to leak out from the cell, resulting in cell death • drug choice for systemic mycoses (disseminated forms of coccidioidomycosis, North American blastomycosis, cryptococcosis, histoplasmosis, mucormycosis, aspergillosis and sporotrichosis) • S/E: Renal toxicity, acute febrile reaction, anemia, phlebitis

Answer 52

Amphotericin B

Question 53

• Mycostatin® • first isolated from a strain of Streptomyces noursei • used for the treatment of Candida (Monilial) infections • administered as an oral agent for the treatment of oral candidiasis • not absorbed systemically when administered orally • swish and swallow

Answer 53

Nystatin

Question 54

• Natacyn® • obtained from Streptomyces natalensis • fungicidal and fungistatic at the same concentration range • supplied as 5% ophthalmic suspension intended for the treatment of fungal conjunctivitis, blepharitis, and keratitis

Answer 54

Natamycin

Question 55

3 Other Antifungal Antibiotics

Answer 55

• Griseofulvin (Grifulvin® • Grisactin® • Gris-PEG®)

Question 56

• obtained from the mold Penicillium griseofulvum • absorption is increased by FATTY FOODS • compliance with the drug regimen is mandatory MOA: interacts with the microtubules within the fungus to disrupt the mitotic spindle and inhibit mitosis (arrests cell division in metaphase)

Answer 56

Griseofulvin

Question 59

4 Opportunistic Fungal Infections

Answer 59

1. Systemic candidiasis 2. Aspergillosis 3. Mucormycosis 4. Pneumocystis carinii