WEEK 4: ANTI-FUNGAL AND ANTI-PARASITIC DRUGS Flashcards

1
Q

State the 2 main classes of drugs used as anti-fungal treatment and examples under each class.

A
  1. POLYENES: MOA of polyenes is the formation of pores in the fungal cell membrane, which allows leakage of cellular contents, ultimately leading to cell lysis.

*Amphotericin B
*Nystatin

  1. MACROLIDES: Macrolides are a class of antibiotics that are primarily used to treat bacterial infections. They work by inhibiting protein synthesis in bacteria.

*Macrolides, such as erythromycin, clarithromycin, and azithromycin

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2
Q

Outline diseases which can be treated using amphotericin B.

A

Aspergillus
Blastomyces
Cryptococcus
Candida
Coccidioides
Histoplasma
Leishmania
Trypanosome

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3
Q

Describe the MOA of amphotericin B.

How do fungi develop resistance against it?

A

Work by binding to ergosterol in the fungal cell membrane, causing the cell membrane to become permeable and allowing essential cellular components to leak out.

Resistance
 ↓ ergosterol content of the fungal membrane.

Efflux Pumps: Fungi can develop efflux pumps that actively pump out Amphotericin B from the fungal cell, preventing it from reaching effective concentrations within the cell.

Cell Wall Modifications: Some fungi may develop changes in their cell wall structure, which can reduce the drug’s ability to access the cell membrane.

Biofilm Formation: In some cases, fungi can form biofilms that act as protective barriers, making it difficult for the drug to penetrate and reach the fungal cells.

Reduction in Uptake: Fungi can downregulate or reduce the expression of proteins responsible for Amphotericin B uptake.

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4
Q

Outline characteristics of amphotericin B.

A

*Poorly absorbed across the gut
* Oral drug good only for infection within the gut
*Injectable preparations require addition of sodium deoxycholate
soluble colloidal dispersion
Insoluble in water
High Intravenous doses
Poorly crosses the BBB

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5
Q

State the infusion related toxicity of amphotericin B symptoms.

What is infusion rate?

What premedication can be given to prevent the toxic reaction?

A

Fever, chills, headache, and hypotension.

Infusion rate refers to the rate at which a fluid, medication, or solution is administered intravenously (through an IV or intravenous line) into a patient’s bloodstream.

It is typically measured in units of volume per unit of time, such as milliliters per hour (mL/hr) or drops per minute (gtts/min).

Administer a small test dose to gauge the severity of the reaction.
Slowing the infusion rate

Premedication with antihistamines and steroids

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6
Q

Amphotericin B results in nephrotoxicity.

Outline 3 signs which are related to this.

A

CUMULATIVE TOXICITY (NEPHROTOXITY)
Azotemia
Azotemia is a medical term that refers to an elevated level of nitrogen-containing compounds, particularly urea and creatinine, in the blood. These compounds are waste products that are normally excreted by the kidneys.

RTA
Renal Tubular Acidosis (RTA): Renal tubular acidosis is a medical condition that involves the kidney’s inability to effectively remove excess acid from the bloodstream and excrete it in the urine.

Potassium & Magnesium wasting.

Potassium wasting, also known as hypokalemia, refers to a condition in which there is a significant depletion of potassium in the body.

Magnesium wasting, also called hypomagnesemia, is a condition characterized by abnormally low levels of magnesium in the blood.

Salt loading may prevent and even reverse amphotericin B-induced azotemia by an unknown
mechanism.

Overall Toxicity:

Liposomal amphotericin B is often considered a less toxic alternative to conventional amphotericin B and is preferred when the risk of kidney toxicity needs to be minimized, especially in patients with underlying kidney disease.

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7
Q

State other polyene macrolides

A

OTHER POLYENE MACROLIDES

  1. AMPHOTERICIN A
    Not used clinically.
    Experimental drug
  2. NYSTATIN
    Poorly absorbed across the membranes.
     Its mainly used for local candida infection.
    Vomiting and local irritation
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8
Q

What are azoles?

State the 2 types of azoles and their examples.

A

They work by inhibiting the synthesis of ergosterol, a crucial component of the fungal cell membrane. Azoles are fungistatic, meaning they inhibit the growth and reproduction of fungi rather than killing them directly

Imidazoles
 Ketoconazole
 Miconazole
 Clotrimazole

Triazoles
 Itraconazole
 Voriconazole
 Fluconazole

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9
Q

Describe characteristics of KETOCONAZOLE

A

 Unlike AmphoB: Not active against Aspergillus
Oral & topical formulation
Oral ketoconazole has largely been replaced by triazoles
 Topical drug: Dermatophytes
Mucocutaneous candidiasis
Seborrheic dermatitis

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10
Q

Outline side effects of ketoconazole.

A

 Nausea, anorexia, and vomiting
 Hepatotoxicity
 CP450 Inhibitor
 Antiandrogen effects
 Teratogenic

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11
Q

Describe characteristics of MICONAZOLE & CLOTRIMAZOLE.

A

Topical Imidazoles
Poorly absorbed orally
Widely used topically in the treatment of dermatophyte and
Candida infections.
Local irritation (i.e., stinging & burning sensation)

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12
Q

State the 3 triazoles.
Describe them

A

ITRACONAZOLE
 Itraconazole is the drug of choice for the treatment of dimorphic fungi.
 Rarely used for treatment of infections due to Candida and Aspergillus species because of the availability of newer and more effective agents.
 Poor permeability of the blood–brain
barrier (BBB)

FLUCONAZOLE
 High oral bioavailability (nearly 100%)
 Very good CSF penetration
 Azole of choice for systemic candidiasis & cryptococcal meningitis
 No Activity against aspergillus
 Nausea, vomiting, and rashes

VORICONAZOLE
* Candida
* Aspergillus
* Crosses the BBB

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13
Q

State 4 examples of dimorphic fungi.

A

Dimorphic fungi
Blastomycosis, Sporotrichosis, Paracoccidioidomycosis, and Histoplasmosis.

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13
Q

State the 4 other fungal drugs.

A

Flucytosine
Caspofungin
Griseofulvin
Terbinafine

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14
Q

Pyrimidine antimetabolite
Resistance due to decreased levels of any
of the enzymes
It is effective in combination with
amphotericin B for treating candidiasis or
cryptococcosis.
Bone marrow suppression

What drug is described above?

A

Flucytosine

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15
Q

β-glucan synthase inhibitor
 Poor oral bioavailability (Available only in parenteral form).
Penetrates poorly into CSF
 Txcandida and aspergilusinfections
 Extremely well tolerated (minor GIT upset)

What drug is described above?

A

CASPOFUNGIN

16
Q

Oral formulation
Gets concentrated in keratinized
tissues
 Interact with microtubules/ disrupt
mitotic spindles/ Arrest fungal mitosis
 Tx of dermatophytes
AE (Headache, GIT upset), CP450
inducer, Teratogenic

What drug is described above?

A

GRISEOFULVIN

17
Q

 Squalene epoxidase inhibitor
 Fungicidal
Oral/ topical
Onychomycosis (fungal infections of
nails or nail beds)
GIT disturbances, rash, headache

What drug is described above?

A

TERBINAFINE

18
Q

State the 3 forms of malaria and their causative agents.

A

FORMS OF MALARIA
1. Benign tertian malaria
 Plasmodium vivax
 Plasmodium ovale

  1. Malignant tertian malaria
     Plasmodium falciparum
     P. falciparum, which constitutes up to 98% of all
    malaria cases in Botswana!!!
  2. Quartan malaria
     Plasmodium malariae
19
Q

Which 2 species of malaria can become dormant in the liver (Hypnozoites)?

A

P. Vivax and P. Ovale can become dormant in the liver (Hypnozoites).

20
Q

Outline drugs used to treat acute malaria attack.

A

DRUGS USED TO TREAT THE ACUTE ATTACK
*Quinoline methanol’s
*Artemisinin
*Folate antagonists

21
Q

State the symptoms of acute malaria attack.

A

An attack usually starts with shivering and chills,
followed by a high fever, followed by sweating and
a return to normal temperature.

22
Q

Describe the MOA of chloroquine.

State some of the side effects of chloroquine.

A

Chloroquine binds to heme, preventing its polymerization to hemozoin.

Unwanted effects include nausea, vomiting, urticaria, headaches, blurring of vision.

Plasmodium falciparum is now resistant to chloroquine in most parts of the world

23
Q

Describe the following other quinoline methanol’s.
1. Quinine
2. Mefloquine

A

OTHER QUINOLINE METHANOLS

QUININE
 Bitter taste
 Hypoglycemia
 Cinchonism: Tinnitus, Hearing Impairment, Headache, Nausea and Vomiting, Visual Disturbances, Confusion or Delirium, Cardiac Arrhythmias
 Blackwater fever

MEFLOQUINE
 Gastrointestinal Upset

 Teratogenic: ability of a substance, agent, or factor to cause congenital malformations or birth defects in a developing fetus.

 Plasma half-life of up to 30 days

24
Q

Artemether. Artesunate. Dihydroartemesinin.
 Interact with heme in the parasitic food vacuole and generates cytotoxic
radical species
 First choice for chloroquine resistant malaria in most countries
 Often combined with longer acting agents. COARTEM = Artemether +
lumefantrine
 Commonly reported adverse effects are gastrointestinal.

Name the type of anti-malarial drug described above.

A

ARTEMESININS

25
Q

Describe MOA of anti-folate drugs.

A

 Sulfadoxine: dihydropteroate synthase inhibitor

Pyrimethamine: dihydrofolate reductase inhibitor

 FANSIDAR = Pyrimethamine sulfadoxine effective against chloroquine resistant malaria
 Folic acid deficiency (Megaloblastic
anemia)

26
Q

What is radical cure?

A

Radical cure means complete elimination of malaria parasite from the body.

27
Q

Name the drug administered as radical cure.

A

Primaquine

28
Q

Name the drug that is combined with primaquine to achieve radical cure.

A

 To achieve the radical cure primaquine is combined with a blood schizonticide.

29
Q

The first line antimalarial drug for the treatment of uncomplicated Falciparum malaria is ____________with a single dose of primaquine.

A

The first line antimalarial drug for the treatment of
uncomplicated Falciparum malaria is Artemether
Lumefantrine (AL) with a single dose of primaquine.

30
Q

What is the function of schizonticide?

State the contraindication for primaquine.

A

 Tissue schizonticide (Eradicates the hypnozoites
 Gametocidal (Interrupting the transmission of the disease)
 Metabolites of primaquine are believed to act as oxidants.
 Contraindicated in G6PD deficiency and pregnancy.

31
Q

OUTLINE DRUGS FOR CHEMO-PROPHYLAXIS OF MALARIA.

A

Chloroquine
Mefloquine
Doxycycline, Tafenoquine, Atovaquone
proguanil

32
Q

Describe characteristics of drugs used for chemoprophylaxis of malaria.

A

 Block the link between the exoerythrocytic
stage and the erythrocytic stage and prevents clinical attacks
 They are given to individuals who intend
travelling to an area where malaria is
endemic
Most are started a week before entering the
area and should be continued throughout
the stay and for up to a month afterwards
Different agents may be required for different
travel destinations

33
Q

Albendazoleand mebendazole.
 Active against nematodes(roundworms) and cestodes(tapeworms)
 Bind to beta tubulin and interferes with microtubule dependent function
(motility and DNA replication)
 Irreversibly inhibit glucose uptake leading to glycogen depletion
 Contraindicated in pregnancy.

What class of anti-helminthic drugs is described above?

A

Benzimidazoles

34
Q

 Increases the parasite’s permeability to calcium ions
DOC for all forms of schistosomiasis
 It is also used in conjunction with niclosamide for tapeworms.
Common AEs are abdominal pains and cramps.

What class of anti-helminthic drugs is described above?

A

PRAZIQUANTEL

35
Q

 DOC for onchocerciasis and strongyloidiasis
 Activates the glutamate gated chloride ion
channels
 Headache, ataxia, seizures

What anti-helminthic drug is described above?

A

IVERMECTIN

36
Q

 Used for txof filarial infections
 Inhibits arachidonic acid metabolisms
 Commonly reported AE are headache and
GIT upset.
 Mazzotti reaction:

What anti-helminthic drug is described above?

A

DIETHYLCARBAMAZINE

37
Q

Name the drug associated with Mazzotti reaction.

Outline symptoms associated with this reaction.

A

The Mazzotti reaction is characterized by the following symptoms and effects, which typically occur within a few hours to a couple of days after taking ivermectin:

Itching and Rash: Individuals may experience intense itching, which can be accompanied by the development of a rash, typically consisting of papules (small, raised bumps) and sometimes hives.

Fever: A mild to moderate fever is a common symptom of the Mazzotti reaction.

Lymph Node Swelling: Enlargement and tenderness of lymph nodes, particularly in the neck and inguinal (groin) regions, can occur.

Joint Pain and Muscle Aches: Many people report experiencing joint pain and muscle aches during the Mazzotti reaction.

General Malaise: A general feeling of illness, malaise, and discomfort is also common.