Antifungals

Question 1

What is Liposomal AMB?

Answer 1

10% AMB incorporated in uniform sized unilamellar liposomes. Liposomes are made of lecithins and other biodegradable phospholipids.

Question 2

Adverse effects of amphotericin B (AMB)?

Answer 2

1) Acute reaction - Fever, chills, aches and pain all over the body, vomiting, dyspnea. It lasts fir 2-5 hours and is due to release of cytokines (eg. TNF alpha). Hydroxortisone 0.6mg/kg may be infused along with AMB infusion to reduce severity of this reaction

2) Long term toxicity
- Nephrotoxicity. (Reduced GFR, Azotemia, Hypokalemia, Hypomagnesemia)
- Anemia
- CNS toxicity (only on intrathecal injection)

Question 3

Uses of AMB.

Answer 3

1. Systemic mycoses - DOC
   
   • For severe infection we can give induction therapy with AMB and later replace it with a safer alternative antifungal drug like Azoles for continuation of therapy
2. Febrile neutropenia
3. Kala azar - Resistant cases of Kala azar and Cutaneous Leishmaniasis

Question 4

Ketokonazole— Classification, Uses, Side effects, Interactions.

Answer 4

Classification: It is the first orally active, broad spectrum antifungal drug. It is an Imidazole drug under the Azole group.

Uses:

1) Orally
a) Dermatophytosis as it is highly concentrated in stratum corneum
b) Monilial vaginitis- Reserved for recurrent or resistant cases

2) Topically:
a) Seborrhea and dandruff
b) Tinea versicolor involving limited area of skin

3) Due to inhibition of steroid synthesis, it has been used for Cushings syndrome.

S/E:

1) GI upset : Nausea, vomiting - m/c side effects
2) Inhubition of androgen synthesis and displacement from protein binding site: Gynecomastia and infertility in males (After few weeks of use)
3) Menstrual irregularities in females
4) Decreases plasma hydrocortisones levels

Interactions:

• H2 blockers, PPIs which reduce gastric acidity decrease the absorption of KTZ
• Enzyme imducers decrease efficacy of KTZ
• KTZ inhibits metabolism and increases blood levels of drugs like Warfarin, Phenytoin, Carbamazepine, Omeprazole, HIV protease inhibitors etc

Question 5

Name the azoles effective in Mucor mycosis.

Answer 5

Posaconazole and Isavuconazole

Question 6

Which azole has minimum hepatic metabolism?

Answer 6

Posaconazole.

It is mostly excreted unchanged in urine.

Question 7

MOA of Terbinafine.

Answer 7

Inhibits Squalene epoxidase which converts squalene to squalene epoxide.
Squalene epoxide is converted to lanosterol and then ergosterol.

Accumulation of squalene leads to FUNGICIDAL EFFECT.

Question 8

What is whitfield ointment?

Answer 8

Benzoic acid (5 or 6%) + Salicylic acid (3%)

Question 9

Griseofulvin: Mechanism of action, Uses, S/E, Interactions.

Answer 9

MOA: It binds and inhibit polymerised microtubules. Thus it interferes with mitosis and produces stunted fungal hyphae.

Pharmacokinetic: Better absorbed with fatty meal.

Uses:

1. Dermatophytosis (highly concentrated in hair, nail, skin)
2. Drug of choice for Tinea capitis

S/E: Low toxicity drug

1. Headache
2. GI disturbance
3. Hepatotoxicty (should be discontinued)
4. Peripheral neuritis
5. Neutropenia

Interactions:

1. It is an enzyme inducer- can decrease efficacy of other drugs
2. OCP failure may occur

Question 10

Drug of choice for Fungal corneal ulcers.

Answer 10

Natamycin.

Question 11

MOA of Azoles.

Answer 11

Inhibits the enzyme Lanosterol 14-alpha-demethylase, this prevents synthesis of Ergosterol.
It is a CYP450 enzyme of the fungi.

Imidazoles have low specificity for fungal CYP450 and have relatively higher systemic toxicity than Triazoles.