Antifungal and Antihelminthic Drugs

1. Antifungal Drugs &
Anthelminthic Drugs
Presenter-
Dr Arun Singh
Resident
Doctor
Department of
Pharmacology
SMS Medical
College,Jaipur

2. Antifungal
Drugs

3. Learning Objectives
oIntroduction to fungi
oStructure of fungi
oTypes of fungi
oTypes of fungal infection
oClassification of antifungal drugs
oDrugs for systemic fungal infections
oSystemic drugs for superficial fungal infections
oTopical drugs for superficial fungal infections

4. Introduction to fungi
• Fungi are Eukaryotic cells.
• They possess mitochondria, nuclei & cell membranes.
• While bacterial cells are prokaryotic. So, anti-bacterial
agents can exhibit Selective toxicity.
• In contrast, similarity between fungal & mammalian
cells makes Antifungal drugs nonselective.
• Thus, Antifungal drugs are in general more toxic than
antibacterial agents.

5. Structure of fungi
• A fungus is a two layered structure made up of a cell
wall and a cell membrane.
• The cell wall is made up of chitins, proteins and beta
glucans.
• The cell membrane is made up of lipids called as
ergosterol and contains an enzymes called as beta
glucan synthase that synthesizes beta glucans for the
cell wall.
• Ergosterol is synthesizes from squalene which get
converted into squalene epoxide to lanosterol.
• Lanosterol in multiple steps get converted into
ergosterol with the help of enzyme 14-α sterol
demethylase.

6. • Fungi can be divided into
four classes –
1. Yeasts
2. Yeast-like fungi
3. Dimorphic fungi
4. Moulds

7. Types of fungi
Type Characteristics Causative Fungi Cause
1.Yeasts Reproduce by
budding
Cryptococcus
neoformans
meningitis
2.Yeast-like fungi Which partly
grows like yeast
and partly as
filaments called
hyphae
Candida albicans oral/ vaginal
thrush and
systemic
candidiasis.
3.Dimorphic fungi Which can grow as
filaments or as
yeast
Histoplasma
capsulatum
systemic infections
4.Moulds
(Dermatophytes)
Filamentous fungi
which reproduce
by forming spores
Trichophyton sp.
Microsporum sp.
Epidermophyton
sp.
skin or nail
infections called
tines or `ringworm'

8. Factors aiding the spread of fungal disease:-
Action of immunosuppressant drugs
Acquired immunodeficiency syndrome (AIDS)
Broad-spectrum antibiotics
Chemotherapy agents

9. Overview of fungal infections
• Fungi that can cause infections live
-In association with humans commensally,
-In Environment
• Fungal infections are termed as MYCOSES.
• In the UK, the commonest fungal disease is systemic
Candidiasis.

10. Classification of fungal infections
• Mycoses are classified according to the tissue levels initially
colonized:-
1. Superficial mycosis :
Superficial mycoses are limited to the outermost layers of the skin and hair.
An example of such a fungal infection is Tinea versicolor, a fungus
infection that commonly affects the skin of young people, especially the
chest, back, and upper arms and legs.
Tinea versicolor is caused by a fungus that lives in the skin of some adults.
It does not usually affect the face.

11. 2. Cutaneous mycoses
Cutaneous mycoses extend deeper into the epidermis, and also include
invasive hair and nail diseases.
These diseases are restricted to the keratinized layers of the skin, hair,
and nails.
Unlike the superficial mycoses, host immune responses may be evoked
resulting in pathologic changes expressed in the deeper layers of the skin.
The organisms that cause these diseases are called dermatophytes, the
resulting diseases are often called ringworm, dermatophytosis or tinea.
Dermatophytes only cause infections of the skin, hair, and nails, and are
unable to induce systemic, generalized mycoses, even in
immunocompromised hosts.

12. 3. Subcutaneous mycoses
Subcutaneous mycoses involve the dermis, subcutaneous tissues, muscle and
fascia.
These infections are chronic and can be initiated by piercing trauma to the
skin which allows the fungi to enter.
These infections are difficult to treat and may require surgical interventions
such as debridement.
4. Systemic mycoses due to primary pathogens
Systemic mycoses due to primary pathogens originate primarily in
the lungs and may spread to many organ systems.
Organisms that cause systemic mycoses are inherently virulent.
In general, primary pathogens that cause systemic mycoses are dimorphic.

13. 5. Systemic mycoses due to opportunistic pathogens
Systemic mycoses due to opportunistic pathogens are infections of
patients with immune deficiencies who would otherwise not be infected.
Examples of immunocompromised conditions include AIDS, alteration
of normal flora by antibiotics, immunosuppressive therapy,
and metastatic cancer. Examples of opportunistic mycoses
include Candidiasis, Cryptococcosis and Aspergillosis.

14. Classification of antifungal drugs
• Antifungals can be grouped into three classes based on their site of action.
1- Antifungal Antibiotics :
(a)Polyene macrolide-Which interact with fungal membrane sterols
physicochemically. e.q. Amphotericin- B & Nystatin.
(b)Heterocyclic benzofurans-Disruption of mitotic spindle and inhibition of fungal
mitosis. e.q. Griseofulvin.
2- Synthetic :
(a)Azoles : Which inhibit the synthesis of ergosterol (the main fungal
sterol)
i)Imidazoles :Econazole, Ketoconazole , Miconazole, Clotrimazole
ii)Triazoles : Fluconazole , Itraconazole, Voriconazole

15. (b)Antimetabolite: Inhibition of nucleic acid synthesis e.q. Fluocytosine
(5-FC)
(c)Allylamine: Squalene epoxidase inhibitors : e.g. Terbinafine &
Naftifine
3-Other topical agents:
e.q. Tolnaftate, Undecylenic acids, Benzoic acid, Quiniodochlor,
Ciclopirox olamine, Butenafine, Sod.thiosulfate.

16. Classification of antifungal drugs
• Based on treatment given according route of administration:-
(A)Drugs used to treat systemic fungal infection:
1.Triazoles 2.Amphotericin-B 3.Ketoconazole(Imidazole) 4.Echinocandis
5.Flucytosine(5-FC)
(B)Drugs given systemically for treating Superficial infections:
1.Griseofulvin 2.Terbinafine
(C)Topically used Antifungal drugs:
1.Nystatin 2.Clotrimazole 3.Miconazole 4.Butaconazole 5.Sertaconazole
6.Oxiconazole 7.Ciclopirox 8.Benzoic acid & Sodium Thiosulphate

17. DRUGS FOR
SYSTEMIC
FUNGAL
INFECTIONS

18. Amphotericin-B
1.Classification and pharmacokinetics:-
Amphotericin B is a polyene antibiotic related to nystatin.
Amphotericin is poorly absorbed from the gastrointestinal tract and is
usually administered intravenously as a nonlipid colloidal suspension, as a
lipid complex, or in a liposomal formulation.
The drug is widely distributed to all tissues except the central nervous
system (CNS).
Elimination is mainly via slow hepatic metabolism; the half-life is
approximately 2 wk.

19.  A small fraction of the drug is excreted in the urine; dosage modification is
necessary only in extreme renal dysfunction.
Amphotericin B is not dialyzable.
2. Mechanism of action:-
The fungicidal action of amphotericin B is due to its effects on the
permeability and transport properties of fungal membranes.
Polyenes are molecules with both hydrophilic and lipophilic characteristics
(i.e. they are amphipathic).
They bind to ergosterol, a sterol specific to fungal cell membranes, and cause
the formation of artificial pores .
Resistance, though uncommon, can occur via a decreased level of or a
structural change in membrane ergosterol.

20. 3. Clinical uses:-
Amphotericin B is one of the most important drugs available for the
treatment of systemic mycoses and is often used for initial induction
regimens before follow-up treatment with an azole.
It has the widest antifungal spectrum of any agent and remains the drug
of choice, or codrug of choice, for most systemic infections caused by
Aspergillus, Blastomyces, Candida albicans, Cryptococcus, Histoplasma,
and Mucor.
Amphotericin B is usually given by slow intravenous infusion, but in
fungal meningitis intrathecal administration, though dangerous, has been
used.

22. Local administration of the drug, with minimal toxicity, has been used in
treatment of mycotic corneal ulcers and keratitis.
4. Toxicity:-
a. Infusion related—Adverse effects related to intravenous infusion commonly
include fever, chills, muscle spasms, vomiting, and a shock-like fall in blood
pressure.
These effects may be attenuated by a slow infusion rate and by premedication
with antihistamines, antipyretics, meperidine, or glucocorticoids.
b. Dose limiting—Amphotericin B decreases the glomerular filtration rate and
causes renal tubular acidosis with magnesium and potassium wasting.
Anemia may result from decreases in the renal formation of erythropoietin.

23. Although concomitant saline infusion may reduce renal damage, the
nephrotoxic effects of the drug are dose-limiting.
Dose reduction (with lowered toxicity) is possible in some infections when
amphotericin B is used with flucytosine.
Liposomal formulations of amphotericin B have reduced nephrotoxic
effects, possibly because of decreased binding of the drug to renal cells.
c. Neurotoxicity—Intrathecal administration of amphotericin B may cause
seizures and neurologic damage.

24. B. Flucytosine (5-Fluorocytosine [5-FC])
1. Classification and pharmacokinetics:-
5-FC is a pyrimidine antimetabolite related to the anticancer drug 5-
fluorouracil (5-FU).
It is effective orally and is distributed to most body tissues, including the CNS.
The drug is eliminated intact in the urine, and the dose must be reduced in
patients with renal impairment.
2. Mechanism of action:-
Flucytosine is accumulated in fungal cells by the action of a membrane
permease and converted by cytosine deaminase to 5-FU, an inhibitor of
thymidylate synthase.
Selective toxicity occurs because mammalian cells have low levels of
permease and deaminase.

25. Resistance can occur rapidly if flucytosine is used alone and involves
decreased activity of the fungal permeases or deaminases.
When 5-FC is given with amphotericin B, or triazoles such as
itraconazole, emergence of resistance is decreased and synergistic
antifungal effects may occur.
3. Clinical uses:-
The antifungal spectrum of 5-FC is narrow; its clinical use is limited
to the treatment, in combination with amphotericin B or a triazole, of
infections resulting from Cryptococcus neoformans, possibly systemic
candidal infections and chromoblastomycosis caused by molds.

26. 4. Toxicity:-
Prolonged high plasma levels of flucytosine cause reversible
bone marrow depression, alopecia, and liver dysfunction

27. Azole Antifungal Agents
1.Classification and pharmacokinetics:-
The azoles used for systemic mycoses include ketoconazole, an
imidazole, and the triazoles fluconazole, itraconazole, posaconazole, and
voriconazole.
Oral bioavailability is variable (normal gastric acidity is required).
Fluconazole, posaconazole, and voriconazole are more reliably absorbed
via the oral route than the other azoles.
Most triazoles are available in both oral and intravenous formulations.
The drugs are distributed to most body tissues, but with the exception of
fluconazole, drug levels achieved in the CNS are very low.

28. Liver metabolism is responsible for the elimination of
ketoconazole, itraconazole, and voriconazole.
Inducers of drug metabolizing enzymes (e.g. rifampin) decrease
the bioavailability of itraconazole.
Fluconazole is eliminated by the kidneys, largely in unchanged
form.
2. Mechanism of action:-
The azoles interfere with fungal cell membrane permeability by
inhibiting the synthesis of ergosterol.
These drugs act at the step of 14α-demethylation of lanosterol,
which is catalyzed by a fungal cytochrome P450 isozyme.

29. With increasing use of azole antifungals, especially for long-term prophylaxis
in immunocompromised and neutropenic patients, resistance is occurring,
possibly via changes in the sensitivity of the target enzymes.
3. Clinical uses :-
a. Ketoconazole—
Because it has a narrow antifungal spectrum and causes more adverse effects than
other azoles, ketoconazole is now rarely used for systemic mycoses.
The drug is not available in parenteral form.
However, ketoconazole continues to be used for chronic mucocutaneous candidiasis
and is also effective against dermatophytes.
b. Fluconazole—
Fluconazole is a drug of choice in esophageal and oropharyngeal candidiasis and for
most infections caused by Coccidioides.

30. A single oral dose usually eradicates vaginal candidiasis.
Fluconazole is the drug of choice for treatment and secondary prophylaxis
against cryptococcal meningitis and is an alternative drug of choice (with
amphotericin B) in treatment of active disease due to Cryptococcus
neoformans.
The drug is also equivalent to amphotericin B in candidemia.
c. Itraconazole—
This azole is currently the drug of choice for systemic infections caused by
Blastomyces and Sporothrix and for subcutaneous chromoblastomycosis.
Itraconazole is an alternative agent in the treatment of infections caused by
Aspergillus, Coccidioides, Cryptococcus, and Histoplasma.

31. In esophageal candidiasis, the drug is active against some strains resistant
to fluconazole.
Itraconazole is also used extensively in the treatment of dermatophytoses,
especially onychomycosis.
d. Voriconazole—
Voriconazole has an even wider spectrum of fungal activity than
itraconazole.
It is a codrug of choice for treatment of invasive aspergillosis; some
studies report greater efficacy than amphotericin B.
Voriconazole is an alternative drug in candidemia with activity against
some fluconazole-resistant organisms and in AIDS patients has been used
in the treatment of candidial esophagitis and stomatitis.

32. e. Posaconazole—
The broadest-spectrum triazole, posaconazole has activity against most
species of Candida and Aspergillus.
It is the only azole with activity against Rhizopus, one of the agents of
mucormycosis and is used for prophylaxis of fungal infections during
cancer chemotherapy and in salvage therapy in invasive aspergillosis.
4. Toxicity:-
Adverse effects of the azoles include vomiting, diarrhea, rash, and
sometimes hepatotoxicity, especially in patients with preexisting liver
dysfunction.
Ketoconazole is a notorious inhibitor of hepatic cytochrome P450
isozymes and may increase the plasma levels of many other drugs,
including cyclosporine, oral hypoglycemics, phenytoin, and warfarin.

33. Inhibition of cytochrome P450 isoforms by ketoconazole interferes
with the synthesis of adrenal and gonadal steroids and may lead to
gynecomastia, menstrual irregularities, and infertility
The other azoles are more selective inhibitors of fungal cytochrome
P450.
Although they are less likely than ketoconazole to cause endocrine
dysfunction, their inhibitory effects on liver drug-metabolizing enzymes
have resulted in drug interactions.
Voriconazole causes immediate but transient visual disturbances
including blurring of vision of unknown cause in more than 30% of
patients.

34. Based on animal studies voriconazole is a class D drug in terms of pregnancy
risk.
Visual dysfunction has not been reported with posaconazole, but the drug is an
inhibitor of CYP3A4, increasing the levels of cyclosporine and tacrolimus.
Recent advances:-
Isavuconazole is recent azole approved for treatment of mucormycosis and
aspergillosis.
Effinaconazole is a recent drug approved for treatment of fungal toe nail
infections.

35. Echinocandins
1.Classification and pharmacokinetics:-
Caspofungin is an echinocandin, the first of a novel class of antifungal
agents.
Other echinocandins include anidulafungin and micafungin.
Used intravenously, the drugs distribute widely to the tissues and are
eliminated largely via hepatic metabolism.
Caspofungin has a half-life of 9–12 h.
The half-life of micafungin is slightly longer, and that of anidulafungin
is 24–48 h.
2. Mechanism of action:-
The echinocandins have a unique fungicidal action, inhibiting the
synthesis of β(1-3)glucan, a critical component of fungal cell walls.

36. 3. Clinical uses:-
Caspofungin is used for disseminated and mucocutaneous Candida
infections in patients who fail to respond to amphotericin B and in the
treatment of mucormycosis.
Anidulafungin is used for esophageal and invasive candidiasis.
Micofungin is used for mucocutaneous candidiasis and for prophylaxis
of Candida infections in bone marrow transplant patients.
4. Toxicity:-
Infusion-related effects of caspofungin include headache,
gastrointestinal distress, fever, rash, and flushing (histamine release).

37. Micafungin also causes histamine release and elevates blood levels of
the immunosuppressant drugs cyclosporine and sirolimus.
Combined use of echinocandins with cyclosporine may elevate liver
transaminases.

38. SYSTEMIC
DRUGS FOR
SUPERFICIAL
FUNGAL
INFECTIONS

39. Griseofulvin
1.Pharmacokinetics:-
Oral absorption of griseofulvin depends on the physical state of the drug—
ultra-micro-size formulations, which have finer crystals or particles, are more
effectively absorbed—and is aided by high-fat foods.
The drug is distributed to the stratum corneum, where it binds to keratin.
Biliary excretion is responsible for its elimination.
2.Mechanism of action:-
Griseofulvin interferes with microtubule function in dermatophytes and may
also inhibit the synthesis and polymerization of nucleic acids.
Sensitive dermatophytes take up the drug by an energy-dependent
mechanism, and resistance can occur via decrease in this transport.
Griseofulvin is fungistatic.

40. 3.Clinical uses and toxicity:-
Griseofulvin is not active topically.
The oral formulation of the drug is indicated for dermatophytoses of
the skin and hair, but has been largely replaced by terbinafine and the
azoles.
Adverse effects include headaches, mental confusion, gastrointestinal
irritation, photosensitivity, and changes in liver function.
Griseofulvin should not be used in patients with porphyria.
Griseofulvin decreases the bioavailability of warfarin, resulting in
decreased anticoagulant effect, and it also causes disulfiram-like
reactions with ethanol.

41. Terbinafine
1.Mechanism of action:-
Terbinafine inhibits a fungal enzyme, squalene epoxidase.
It causes accumulation of toxic levels of squalene, which can interfere
with ergosterol synthesis.
Terbinafine is fungicidal.
2.Clinical uses and toxicity:-
Terbinafine is available in both oral and topical forms.
Like griseofulvin, terbinafine accumulates in keratin, but it is much more
effective than griseofulvin in onychomycosis.
Adverse effects include gastrointestinal upsets, rash, headache, and taste
disturbances.
Terbinafine does not inhibit cytochrome P450.

42. Azoles
 The azoles other than voriconazole and posaconazole are commonly
used orally for the treatment of dermatophytoses.
Pulse or intermittent dosing with itraconazole is as effective in
onychomycoses as continuous dosing because the drug persists in the
nails for several months.
Typically, treatment for 1 wk is followed by 3 wk without drug.
Advantages of pulse dosing include a lower incidence of adverse
effects and major cost savings.
 Topical forms of various azoles are also available for use in
dermatophytoses.

43. TOPICAL DRUGS
FOR
SUPERFICIAL
FUNGAL
INFECTIONS

44. A number of antifungal drugs are used topically for superficial
infections caused by C albicans and dermatophytes.
Nystatin is a polyene antibiotic (toxicity precludes systemic use) that
disrupts fungal membranes by binding to ergosterol.
Nystatin is commonly used topically to suppress local Candida
infections and has been used orally to eradicate gastrointestinal fungi in
patients with impaired defense mechanisms.
Other topical antifungal agents that are widely used include the azole
compounds miconazole, clotrimazole, and several others.

45. Antihelminth
ic Drugs

46. Learning Objectives
Introduction
Types of helminths
Drugs for treatment of helminthic infections
Goal of drug therapy
Individual drugs
Mechanism of action
Therapeutic Uses
Adverse Effects

47. Introduction
 Helminthiasis is infestation with one or more intestinal
parasitic worms(helminth).
 Infected people excrete helminth eggs in their faeces,
which then contaminate the soil in areas with inadequate
sanitation.
 Other people can then be infected by ingesting eggs or
larvae in contaminated food, or through penetration of
the skin by infective larvae in the soil.
Lead to chronic illness, malnutrition, anemia.

48. Types of Helminths
Nematodes Trematodes Cestodes

49. Types of helminths Micro-organism Responsible
1.Cestodes(Tapeworm) Taenia saginata (beef tapeworm)
Taenia solium (pork tapeworm)
Diphyllobothrium latum (fish tapeworm)
Echinococcus granulosus (dog tapeworm)
2.Trematodes(Flukes) Schistosoma species (blood flukes)
Clonorchis sinensis (liver fluke)
Paragonimus westermani (lung fluke)
3.Nematodes(Roundworm) Enterobius vermicularis (pinworm)
Trichuris trichiura (whipworm)
Ascaris lumbricoides (roundworm)
Ancyclostoma and Necator species (hookworms)
Strongyloides stercoralis (threadworm).

56. Goal of Drug
Therapy
1.To control infections
2.To eliminate the
parasites
3.To reduce
transmission of infection

57. Types of antihelminthic drugs
• Classification of anti-helminthic drugs based on chemical structure:-
1.Piperazines:Diethylcarbamazine citrate (DEC), Piperazine citrate.
2.Benzimidazoles: Albendazole, Mebendazole, Thiabendazole
3.Heterocyclins:Oxamniquine, Praziquantel.
4.Natural products: Ivermectin, Avermectin
5.Vinyl pyrimidines: Pyrantel, Oxantel
6.Amide: Niclosamide
7.Nitro derivative: Niridazole
8.Imidazothiazole: Levamisole

58. DRUGS THAT
ACT AGAINST
NEMATODES

59. A. Albendazole
1.Mechanisms:-
The action of albendazole is thought to involve inhibition of microtubule
assembly.
The drug is larvicidal in ascariasis, cystercercosis, hookworm, and hydatid
disease and is ovicidal in ascariasis, ancyclostomiasis, and trichuriasis.
2.Clinical use:-
Albendazole has a wide antihelminthic spectrum.
It is a primary drug for ascariasis, hookworm, pinworm, and whipworm
infections and an alternative drug for treatment of threadworm infections,
filariasis, and both visceral and cutaneous larva migrans.
Albendazole is also used in hydatid disease and is active against the pork
tapeworm in the larval stage (cysticercosis).

60. 3. Toxicity:-
Albendazole has few toxic effects during short courses of therapy (1–
3 d).
However, a reversible leukopenia, alopecia and elevation of liver
function enzymes can occur with more prolonged use.
Long-term animal toxicity studies have described bone marrow
suppression and fetal toxicity.
The safety of the drug in pregnancy and young children has not been
established.

61. B. Diethylcarbamazine
1.Mechanisms:-
Diethylcarbamazine immobilizes microfilariae by an unknown mechanism, increasing their
susceptibility to host defense mechanisms
2. Clinical use:-
Diethylcarbamazine is the drug of choice for several filarial infections including those caused by
Wucheria bancrofti and Brugia malayi and for eye worm disease (Loa Loa).
The drug undergoes renal elimination, and its half-life is increased significantly by urinary
alkalinization.
3. Toxicity:-
Adverse effects include headache, malaise, weakness, and anorexia.
Reactions to proteins released by dying filariae include fever, rashes, ocular damage, joint and
muscle pain, and lymphangitis.
In onchocerciasis, the reactions are more intense and include most of the symptoms described as
well as hypotension, pyrexia, respiratory distress, and prostration.

62. C. Ivermectin
1.Mechanisms:-
Ivermectin intensifies γ-aminobutyric acid (GABA)-mediated neurotransmission in
nematodes and causes immobilization of parasites, facilitating their removal by the
reticuloendothelial system.
Selective toxicity results because in humans GABA is a neurotransmitter only in the CNS,
and ivermectin does not cross the blood-brain barrier.
2. Clinical use:-
Ivermectin is the drug of choice for onchocerciasis, cutaneous larva migrans,
strongyloidiasis, and some forms of filariasis.
3. Toxicity:-
Single-dose oral treatment in onchocerciasis results in reactions to the dying worms,
including fever, headache, dizziness, rashes, pruritus, tachycardia, hypotension, and pain in
joints, muscles, and lymph glands.

63. These symptoms are usually of short duration, and most can be
controlled with antihistamines and nonsteroidal anti-inflammatory
drugs.
Avoid other drugs that enhance GABA activity.
Ivermectin should not be used in pregnancy.
Recent advance:-Moxidectin is a new antihelminthic drugs approved for
treatment of O. volvulus. It acts by stimulating glutamate sensitive
chloride channels, which leads to flaccid paralysis.

64. D. Mebendazole
1.Mechanism:-
Mebendazole acts by selectively inhibiting microtubule synthesis and glucose
uptake in nematodes.
2. Clinical use:-
Mebendazole is a primary drug for treatment of ascariasis and for pinworm
and whipworm infections.
Mebendazole has also been used as a backup drug in visceral larval migrans.
Less than 10% of the drug is absorbed systemically after oral use, and this
portion is metabolized rapidly by hepatic enzymes.
Plasma levels may be decreased by carbamazepine or phenytoin and increased
by cimetidine.

65. 3. Toxicity:-
Mebendazole toxicity is usually limited to gastrointestinal irritation,
but at high doses granulocytopenia and alopecia have occurred.
The drug is teratogenic in animals and therefore contraindicated in
pregnancy.

66. E. Piperazine
1.Mechanism:-
Piperazine paralyzes ascaris by acting as an agonist at GABA receptors.
The paralyzed roundworms are expelled live by normal peristalsis.
2. Clinical use:-
Piperazine is an alternative drug for ascariasis.
3. Toxicity:-
Mild gastrointestinal irritation is the most common side effect.
Piperazine should not be used in pregnant patients or those with hepatic
or renal dysfunction or seizure disorders.

67. F. Pyrantel Pamoate
1.Mechanism:-
Pyrantel pamoate stimulates nicotinic receptors present at neuromuscular junctions of nematodes.
Contraction of muscles occurs, followed by a depolarization-induced paralysis.
The drug has no actions on flukes or tapeworms.
2. Clinical use:-
Pyrantel pamoate has wide activity against nematodes killing adult worms in the colon but not the
eggs.
It is a drug of choice for hookworm and roundworm infections and an alternative drug for
pinworms.
The drug is poorly absorbed when given orally.
3. Toxicity:-
Adverse effects are minor but include gastrointestinal distress, headache, and weakness. Use with
caution in patients with hepatic dysfunction.

68. G. Thiabendazole
1.Mechanism:-
Thiabendazole is a structural congener of mebendazole and has a similar action
on microtubules.
2.Clinical use:-
Because of its adverse effects, thiabendazole is an alternative drug in
strongyloidiasis and trichinosis (adult worms).
Thiabendazole is rapidly absorbed from the gut and is metabolized by liver
enzymes.
The drug has anti-inflammatory and immunorestorative actions in the host.
3. Toxicity:-
Thiabendazole is much more toxic than other benzimidazoles or ivermectin, so
these other drugs are preferred.

69. Its toxic effects include gastrointestinal irritation, headache, dizziness,
drowsiness, leukopenia, hematuria, and allergic reactions, including
intrahepatic cholestasis.
Reactions caused by dying parasites include fever, chills,
lymphadenopathy, and skin rash.
Irreversible liver failure and fatal Stevens-Johnson syndrome have also
been reported.
Avoid in pregnant patients or those with hepatic or renal disease.

70. DRUGS THAT
ACT AGAINST
TREMATODE
S

71. A. Praziquantel
1.Mechanism:-
Praziquantel increases membrane permeability to calcium, causing marked
contraction initially and then paralysis of trematode and cestode muscles; this
is followed by vacuolization and parasite death.
2. Clinical use:-
Praziquantel has a wide antihelminthic spectrum that includes activity in both
trematode and cestode infections.
 It is the drug of choice in schistosomiasis (all species), clonorchiasis, and
paragonimiasis and for infections caused by small and large intestinal flukes.
The drug is active against immature and adult schistosomal forms.
 Praziquantel is also 1 of 2 drugs of choice (with niclosamide) for infections
caused by cestodes (all common tapeworms) and an alternative agent (to
albendazole) in the treatment of cysticercosis.

72. 3. Pharmacokinetics:-
Absorption from the gut is rapid, and the drug is metabolized by the
liver to inactive products.
4. Toxicity:-
Common adverse effects include headache, dizziness and drowsiness,
malaise, and, less frequently, gastrointestinal irritation, skin rash, and
fever.
Neurologic effects can hypertension and seizures.
Corticosteroid therapy reduces the risk of the more serious reactions.
Praziquantel is contraindicated in ocular cysticercosis.
In animal studies, the drug increased abortion rate.

73. B. Bithionol
1.Clinical use:-
Bithionol is a codrug of choice (with triclabendazole) for treatment of
fascioliasis (sheep liver fluke) and an alternative agent in paragonimiasis.
The mechanism of action of the drug is unknown.
Bithionol is orally effective and is eliminated in the urine.
2. Toxicity:-
Common adverse effects of bithionol include nausea and vomiting,
diarrhea and abdominal cramps, dizziness, headache, skin rash (possibly
a reaction to dying worms), and phototoxicity.
Less frequently, pyrexia, tinnitus, proteinuria, and leukopenia may occur.

74. C. Metrifonate Metrifonate
It is an organophosphate prodrug that is converted in the
body to the cholinesterase inhibitor dichlorvos.
The active metabolite acts solely against Schistosoma
haematobium (the cause of bilharziasis).
Toxic effects occur from excess cholinergic stimulation.
The drug is contraindicated in pregnancy.

75. D. Oxamniquine
Oxamniquine is effective solely in Schistosoma mansoni infections
(intestinal bilharziasis), acting on male immature forms and adult
schistosomal forms.
The drug causes paralysis of the worms, but its precise mechanism is
unknown.
Dizziness is a common adverse effect (no driving for 24 h); headache,
gastrointestinal irritation, and pruritus may also occur.
Reactions to dying parasites include eosinophilia, urticaria, and pulmonary
infiltrates.
It is not advisable to use the drug in pregnancy or in patients with a history
of seizure disorders.

76. DRUGS THAT
ACT AGAINST
CESTODES

77. A. Niclosamide
1.Mechanism:-
Niclosamide may act by uncoupling oxidative phosphorylation or
by activating ATPases.
2. Clinical use:-
Niclosamide is an alternative drug to praziquantel for infections
caused by beef, pork and fish tapeworm.
It is not effective in cysticercosis (for which albendazole or
praziquantel is used) or hydatid disease caused by Echinococcus
granulosus (for which albendazole is used).
Scoleces and cestode segments are killed, but ova are not.

78. Niclosamide is effective in the treatment of infections from small and
large intestinal flukes.
3. Toxicity:-
Toxic effects are usually mild but include gastrointestinal distress,
headache, rash, and fever.
Some of these effects may result from systemic absorption of antigens
from disintegrating parasites.
Ethanol consumption should be avoided for 24–48 h.