Antiparasitics and Antifungals

Question 0

What is the only helminth that causes opportunistic infections in aids patients?

Answer 0

Threadworms - can complete life cycle in human host

Question 1

What are three antihelminthic drugs?

Answer 1

Mebendazole
Ivermectin
Praziquantel

Question 2

Which helminths infect by skin penetration?

Answer 2

Hookworm
Threadworms
All others oral

Question 3

Which worms are treated with mebendazole?

Answer 3

Pinworms - intestine only
Whipworms - intestine only
Roundworm (ascaris) - intestine and lung
All infect orally with eggs
Hookworm - skin, lung, intestine - infects with larvae - suck blood leading to anemia
Trichinosis - from eating muscle of contaminated animals - disease proportional to number of larvae ingested

Question 4

What species is Ivermectin used for?

Answer 4

Drug of choice for threadworms
Few side effects and excellent cure rates
Single oral dose
Kills microfilariae but not adults
Primary control strategy for filariasis in endemic countries
Heartworm in dogs

Question 5

Mebendazole

Answer 5

Orally
Single dose often effective
Inhibit micro tubule assembly and block glucose uptake by nematodes
Drug resistance not a problem in humans

Question 6

Ivermectin

Answer 6

Contraindicated when impaired BBB

Agonist of glutamate gated chloride channels leading to paralysis of worm

Question 7

Praziquantel

Answer 7

Treatment of choice for tapeworms and fluke infections
Causes muscular paralysis and vacuolization in cells of infecting organism - May work by increasing calcium permeability
Oral dose well absorbed
Very low toxicity
Expensive

Question 8

What is the basic life cycle of malaria?

Answer 8

Mosquito bites and sporozoites invade bloodstream then implants in liver
Mature there and burst into bloodstream as invasive merozoites that infect RBCs repeatedly
Some stay in liver and lie dormant as hypnozoites

Question 9

What are the current recommendations for treatment of malaria?

Answer 9

Chloroquine unless resistant
If resistant -
Malarone - non pregnant adults or children
Artemether plus coartem - non pregnant adults or children
Quinine sulfate with something else
Mefloquine
All oral use

Question 10

Chloroquine

Answer 10

Inhibits polymerization of heme in food vacuole of parasite - toxic

Question 11

Quinine

Answer 11

Can be used for chloroquine resistant falciparum malaria

Typically in combo with doxycycline

Question 12

Atovaquone plus proguanil

Answer 12

Malerone
Broad spectrum activity against various parasitic infections
Inhibits ETC at cytochrome bc1 complex
Parasite mitochondria inhibited selectively over host
Proguanil metabolized to DHFR

Question 13

Artemisinins

Answer 13

Combo with coartem is recommended
Drug of first choice in resistant strains for the moment
Can cause neurotoxicity at high doses

Question 14

Mefloquine

Answer 14

Effective in chloroquine resistant strains
Mechanism of action unknown
Neurological and psychiatric side effects

Question 15

Doxycycline

Answer 15

Treatment and prophylaxis of chloroquine resistant

Don’t use in pregnant women

Question 16

What is recommended for malaria treatment in pregnant women?

Answer 16

If chloroquine resistant -

Mefloquine or combo of quinine sulfate and clindamycin

Question 17

What is recommended for treatment of severe malaria?

Answer 17

Parenteral admin
Only approved is quinidine gluconate
It is cardiotoxic

Question 18

What is the only drug active against the dormant liver forms of malaria?

Answer 18

Primaquine

Not in pregnant women or people with g6pd deficiency

Question 19

Iodoquinol

Answer 19

Antiamebic drug
Used for asymptomatic and mild intestinal inf
Can cause neurotoxicity in large doses

Question 20

Metronidazole

Answer 20

Active against anaerobic bacteria, Protozoa (inc giardia, trichomoniasis), and amebiasis
Very well absorbed in gut
Require co treatment with luminal drug
Enzymatic reduction and auto oxidation generates free radicals that degrade DNA and macromolecules
Mild GI, CNS effects and blood dyscriasis
Less activity against virulent intestinal forms than systemic inf

Question 21

What are the three classifications of chemotherapy against fungal infection?

Answer 21

Oral and parenteral drugs for systemic infections
Oral drugs for infections of skin and mucous membranes
Topical drugs for infections of skin and mucous membranes

Question 22

What are the three major classes of anti fungal drugs?

Answer 22

Polyenes (inc amphotericin b)
Azoles
Echinocandins

Question 23

Amphotericin b - mechanism of action

Answer 23

Used for deep systemic infections, esp in neutropenic patients
Fungicide
One side binds ergosterol and the other binds each other
Creates channel in membrane

Question 24

Amphotericin b - pharmacokinetics

Answer 24

IV admin Vd greater than total body water Doesn't cross BBB - intrathecally for brain Slow metabolism

Question 25

Amphotericin b - adverse effects

Answer 25

Most suffer immediate effects and slow toxicities Immediate - fever, chills, vomiting, headaches Nephrotoxicity Intrathecally can cause seizure Much of toxicity believed to be caused by detergent carrier - now available with lipids but expensive

Question 26

Amphotericin b - therapeutic uses

Answer 26

Drug of choice for most life threatening disseminated fungal inf Recently shifted to drug for induction of therapy

Question 27

Azoles - mechanism of action

Answer 27

Include topical imidazoles (ketoconazole) and more potent systemic triazoles (fluconazole, itraconazole) Inhibit p450 enzyme leading to depletion of ergosterol and altered membrane permeability Accumulation of precursor is toxic

Question 28

Azoles - pharmacokinetics

Answer 28

Oral admin Hydrophobic - prevent IV Absorption enhanced at low ph and by food Wide distribution but not to CSF except fluconazole Elim by hepatic metabolism

Question 29

Azoles - adverse effects

Answer 29

Inhibit p450 can lead to drug drug interactions Steroid hormones can drop Rifampin induces p450 and will lower concentrations

Question 30

Azoles - therapeutic uses

Answer 30

Ketoconazole for prostate cancer and Cushing's

Question 31

Fluconazole

Answer 31

High water solubility - oral or IV admin Low potential for inhibition of p450 enzymes High penetration into CNS - good for fungal meningitis Resistance in AIDs patients with thrush, otherwise uncommon

Question 32

Itraconazole

Answer 32

Most potent Preferred oral for inf from dermatohytes Less effect on p450 enzymes Insufficient penetration across BBB

Question 33

Flucytosine - mechanism of action

Answer 33

Prodrug used in combo with amphotericin b Metabolized to 5 FU by enzyme not in mammalian cells Further metabolized to 5 FdUMP which inhibits thymidine synthase needed for DNA replication

Question 34

Flucytosine - pharmacokinetics

Answer 34

Oral admin Wide distribution including CSF Glomerular filtration

Question 35

Flucytosine - adverse effects

Answer 35

High doses can cause bone marrow toxicity and blood dyscriasis Fungi become resistant rapidly when given alone

Question 36

Flucytosine - therapeutic uses

Answer 36

Amphotericin b used in combo is synergistic - makes membrane more permeable for flucytosine to enter more Particularly useful for c. Neoformans that causes cryptococcal meningitis

Question 37

Echinocandins - mechanism of action

Answer 37

Competitive inhibitors of beta 1,3 d glucan synthase | Inhibit cell wall synthesis

Question 38

Echinocandins - pharmacokinetics

Answer 38

IV admin Minimal distribution to CNS or ocular tissues Not metabolized by p450 so few drug interactions Excreted in kidneys

Question 39

Echinocandins - adverse effects

Answer 39

Less frequent or serious than other antifungals Infusion related hypersensitivity and histamine release Sometimes hepatotoxicity but asymptomatic

Question 40

Echinocandins - therapeutic uses

Answer 40

Active against yeast inf - first line for invasive candida in biofilms Against aspergillus Fungicidal in candida, otherwise fungistatic

Question 41

Caspofungin

Answer 41

Echinocandin Drug drug interactions Can be hepatotoxic