Pharmacology of
Antiparasit Drugs
Common Drugs
Used in Parasitic Diseases
I. A. Intestinal Anthelminthics
II. B. Extra Intestinal Anthelminthics
III. C. Amoebicides
IV. D. Anti Toxoplasmosis
V. E. Anti Malaria
A. Intestinal Anthelminthics
For:
-Nematode Infections
Pyrantel pamoate
Piperazine
Levamizole
Mebendazole
Thiabendazole
-Cestode infections
Niclosamide
Praziquantel
Albendazole
Pyrantel pamoate (Combantrin)
Slightly absorbed (70% feces, 15% urine) less systemic side
effects
Inhibits Cholinesterase (responsible for hydrolyzing acetylcholine to
choline) excess acetylcholine at nerve synapse increasing
impulse frequency the worms are spastic
Dose: 10 mg/kg
Ascaris, Ancylostoma & Enterobius single dose
Necator 3 days
Preparation
Tablets, 125 mg, 250 mg
Syrup 25 mg/ml
Piperazine (Vermago)
Well absorbed from GIT
Binds GABA receptor in muscle membrane hyperpolarization &
impulse suppression flaccid paralysis
Dose for:
Ascariasis: 3-6 mg daily for 1-2 days
Enterobiasis: 2 mg daily for 7 days
Preparation: tablets, syrups
Levamizole
Rapidly absorbed from GIT
Interferes carbohydrate metabolism inhibits production of succinate
dehydrogenase muscular paralysis
Side effect with single anthelminthic dose are unusual
Dose for Ascariasis 2.5 mg/kg in single dose
Preparation: tablets 40 or 50 mg.
Mebendazole (Vermox)
Poorly absorbed needs higher dosages
Damage structure and block glucosa uptake Worms are slowly
death, eggs can not grow to be larvae
Side effects: teratogenic
Dose:
Enterobiasis, 100 mg as single use
Ascaris, Hookworms, Trichuris : 100 mg once or twice for 3-4 days
Preparation : Tablets 100 mg
Thiabendazole (Mintezole)
Broad spectrum
Rapidly absorbed
Has immuno-modulating effects
Binds tubulin beta inhibit microtubule polymerization
Dose 25 mg/kg 7 days for:
Strongyloides stercoralis
Cutaneus larva migrans/creeping eruption
Ascaris, Trichuris, Enterobius
Trichinosis
Preparation: Chewable tablets 500 mg
Niclosamid (Yomesan)
Not absorbed and does not appear to irritate the gastrointestinal
tract side effects are minimal
Blocks phosphorilation of ADP structural damage the worms
being excreted in a partially digest
Dose for Taeniasis: 1 g chewed, followed by 1 g one hour later
Preparation: chewable tablet, 0.5 g
Praziquantel
Broad spectrum
Well absorbed
Increases permeability of membrane parasite for Ca-ion spastic
paralysis
Dose for:
Schistosomiasis, cysticercosis, echinococciasis 20-40 mg/kg single
dose
Taeniasis : 10 mg/kg
Preparation : tablets 600 mg
Albendazole
Broad spectrum
Absorbed immediately
Blocks glucose intake of larvae and adult worms ATP decreases die
Teratogenic
Dose for:
Ascaris, Trichuris, Hookworms: 400 mg single dose
Enterobius : 400 mg single dose, repeat 1 week later
Cysticercosis : 15 mg/kg for 1 month
Hydatid disease : 800 mg/day for 30 days
Preparation : tablets 200 mg
B. Extra intestinal Anthelminthics
Diethyl carbamazine (Hetrazan)
Rapidly absorbed
Used for treating Blood Nematode, Ascariasis and Cutaneus Larva
Migrans
Dosage: 5-6 mg/kg 1 day each week or month for 6 – 12 doses.
Preparation: tablet 50 mg or syrup 24 mg/ml
C. Amoebicides
Metronidazole (Flagyl)
First choice for treating amoebiasis
Broad spectrum (both intestinal or extra intestinal amoebiasis)
Rapidly absorbed
Disrupting the DNA helical structure inhibiting nucleic acid
synthesis
It has also valuable action against anaerobic bacteria
Preparation: tablets 500 mg, infusion 5 mg/ml
D. Anti Toxoplasmosis
Spiramycine
A macrolide antibiotic
Inhibit protein synthesis
Dose: 6-9 juta U, 2-3 x/day
E. Antimalarial drugs
Choloroquine
Acts mainly on the large ring-form and mature trophozoite
Well absorbed
inhibits peroxidative activity of hem and interferes with non-enzymatic
polymerization -> dead parasites
Dose: 25 mg base/kg spread over three days
Preparation: tablet and injection (s.c, i.m and i.v)
Quinine
Acts principally on the mature trophozoite
Well absorbed
Side effect: tinnitus, nausea, vomiting, orthostatic hypotension,
hyperinsulinaemic hypoglycaemia
Dose:
Oral dose: 10 mg salt/kg three times daily for 7 days.
Severe malaria: given by rate-controlled intravenous infusion in
either 0,9% saline, 5% or 10% dextrose or by i.m injection.
Sulfadoxine-pyrimethamine
Sulfadoxine Inhibit plasmodial folate synthesis
Pyrimethamine inhibit development of the mature trophozoite and hang
pre-erythrocytic and sporontocidal activities.
Dose: 1,25 mg/kg single oral
Mefloquine
Used for treatment of MDR falciparum malaria
Moderately well absorbed, extensively distributed and slowly
eliminated.
Dose: 15 mg/kg followed by 10 mg/kg 8-24 hours later
Preparation: tablets
Given in combination with arthemisin results in a more rapid
recovery & enhanced oral bioavailability
Tetracycline/Doxycycline
Broad spectrum antibiotics which have potent but slow action
against asexual blood stages of all species of malaria; also active
against primary intrahepatic stages of P. falciparum
Doxycyclin is the most widely used both for prophylaxis and
treatment.
The antibacterial drug act on protein or nucleic acid synthesis.
Used as standard therapy of uncomplicated falciparum malaria,
combined with QUININE 10 mg salt/kg three times daily,
+ Tetracycline 4 X 250 mg /day for 7 days.
or doxycycline 2 X 100 mg per day for 7 days
Arthemisinin and Artesunate
Very effective against all stages of malaria parasite.
Monotherapy is not recommended. Therefore use in combination with
longer acting agents i.e Mefloquine (50mg/120mg)
Preparation : PO, IV, IM Dosage for 3 days
Primaquine
Againts hypnozoites of P.vivax and the gametocyte of P.falciparum.
Contraindicated in pregnancy
Preparation/use:
For P. vivax & P.ovale : 0.25 to 0.5 mg/kg (adult dose 15 to 30 mg)
together with food for 14 days
For P.falciparum: of 0.5 mg/kg (30 mg) single dose
PHARMACOLOGY OF
ANTIVIRAL DRUGS
Viral Infections
A virus cannot replicate on its own, It must attach to and enter
a host cell then uses the host cell’s energy to synthesize
protein, DNA, and RNA
Viruses are difficult to kill because they live inside the cells
Any drug that kills a virus may also kill cells
A well-functioning immune system will eliminate or effectively
destroy virus replication
Immunocompromised patients have frequent viral infections
Cancer patients, especially leukemia or lymphoma
Transplant patients, due to pharmacologic therapy
AIDS patients, disease attacks immune system
ANTIVIRAL DRUGS
- Many antiviral drugs are purine or pyrimidine analogs.
- Many antiviral drugs are prodrugs must be phosphorylated by viral
or cellular enzymes in order to become active.
- Antiviral drugs typically have a restricted spectrum of antiviral
activity and inhibit a specific viral protein, most often an enzyme
involved in viral nucleic acid synthesis.
- Single nucleotide changes leading to amino acid substitutions in a target
protein often are sufficient to cause antiviral drug resistance.
- Effective host immune response remain essential for recovery from
infection.
The major sites of antiviral drug action
Replicative cycles of herpes simplex virus, an example of a DNA virus,
and the probable sites of action of antiviral agents.
Replicative cycles of influenza, an example of an RNA virus, and
the loci for effects of antiviral agents.
ACYCLOVIR
Derivate: Acyclovir, gancyclovir, famcyclovir, pemcyclovir
Mechanism of action
• Inhibits viral DNA-polymerase inhibit DNA syntesis
• Only actively replicating viruses are inhibited
Antiviral spectrum and resistance
• Acyclovir: HSV-1, HSV-2, VZV.
• Gancyclovir: HSV-1, HSV-2, VZV, EBV, CMV.
• Viral resistance may occur due to decreased production of thymidine kinase
and altered viral DNA polymerase
Administration: topical, oral (acyclovir), IV (acyclovir, gancyclovir)
Adverse effects
• Nausea and vomiting,diarrhea (acyclovir PO)
• Neurotoxicity (1-5% of patients) (headache, tremor, behavioral changes,
delirium, seizures, coma) (acylovir and gancyclovir, high doses IV)
• Nephrotoxicity (crystalluria, hematuria, renal insufficiency (acyclovir, high
doses IV)
• Mielosuppression (neutropenia, thrombocytopenia) (gancyclovir)
• Teratogenic effects in animals
IDOXURIDINE AND TRIFLURIDINE
Mechanism of action
The drugs are converted by cellular enzymes to their triphosphate analogs
which inhibits viral DNA synthesis.
Antiviral spectrum and resistance
Antiviral spectrum includes HSV-1, HSV-2 and VZV.
Administration
topically administered (eye, oral, genital mucosae)
Adverse effects
• Pain, pruritus, edema involving the eye or lids.
• Allergic reactions (rare)
Therapeutic uses
-Ocular, oral, genital HSV infections
FOSCARNET
Mechanism of action
The drug directly inhibits viral DNA-polymerase and viral inverse
transcriptase (it does not require phosphorylation for antiviral activity)
Antiviral spectrum and resistance
Antiviral spectrum includes HSV-1, HSV-2, VZV, CMV and HIV.
Administration: IV
Adverse effects
• Hypocalcemia and hypomagnesemia (due to chelation of the drug with
divalent cations) are common.
• Neurotoxicity (headache, tremor, irritability, hallucinations, seizures)
• Nephrotoxicity (acute tubular nephrosis, interstitial nephritis)
Therapeutic uses alternative drug for:
• HSV infections (due to thymidine kinase deficient strains which are
acyclovir resistant)
• HSV infections in immunocompromised patient
• CMV retinitis (gancyclovir resistant)
• CMV infections in immunocompromised patient
AMANTADINE
Mechanism of action: Inhibition of viral uncoating by:
• Blockade of the viral membrane matrix protein M2, an ion channel required
for the fusion of the viral membrane with the cell membrane.
• Rising the pH of the endosome (an acidic pH inside the endosome is required
for viral uncoating)
Antiviral spectrum and resistance
• Influenza A virus (not B and C virus)
• Resistant variants are selected rapidly during treatment (approximately in 30%
of treated patients)
Adverse effects
• Anorexia, nausea and vomiting, urinary retention, Nervousness,insomnia,
difficulty concentrating, ataxia
• Delirium, hallucinations, seizures (in high doses)
• Teratogenic
Therapeutic uses: Treatment and Prevention influenza A
Administration: oral
RIBAVIRIN
Mechanism of action
• Inhibition of synthesis of guanosine-triphosphate which leads to
inhibition of nucleic acid synthesis in general
• Specific inhibition of viral mRNA synthesis
Antiviral spectrum and resistance
Wide range of DNA and RNA viruses are susceptible, including influenza
A, B and C viruses, parainfluenza viruses, measles virus, HSV-1, HSV-2,
CMV, RSV
Administration: oral, IV, inhalatory
Adverse effects
• Inhalatory: Conjunctival irritation, transient wheezing, reversible
deterioration in pulmonary function.
• Oral and IV: hemolytic anemia and bone marrow suppression,
Headache, insomnia, mood alteration, Teratogenic
Therapeutic uses
• Drug of choice for: RSV bronchiolitis and pneumonia in hospitalized
children
• Alternative drug for Influenza, parainfluenza, measles virus infection in
immunocompromised patients
VIDARABINE
Mechanism of action
The drug is converted by cellular enzymes to its triphosphate analog which
inhibits viral DNA-polymerase.
Antiviral spectrum and resistance
• Antiviral spectrum of vidarabine includes HSV-1, HSV-2 and VZV.
• Resistant due to mutation in DNA-polymerase have been detected.
Administration: topical or IV.
Adverse effects
Dose-dependent toxicity (after IV administration):
• Neurotoxicity (headache, tremor, confusion, seizures)
• Anemia, leukopenia, thrombocytopenia.
• Syndrome of inappropriate secretion of ADH.
• The drug is mutagenic and teratogenic in animals.
Therapeutic uses: alternative drug for
• HSV keratoconjunctivitis (topical).
• Neonatal herpes.
• VZV infections in immunocompromised patient.
INTERFERONS
Three major classes of human interferons (IFN): alpha, beta, gamma
Mechanism of antiviral action
Binding to specific receptors of the host cells and Induction of enzymes (protein
kinase, oligoadenylate synthase, phosphodiesterase) inhibition of translation
(late viral RNA and protein synthesis)
Antiviral spectrum
Antiviral spectrum includes HBV, HCV, HDV, HSV, VZV, CMV and human
papillomavirus (HPV).
Adverse effects
Acute flu-like syndrome (fever, headache, myalgia, arthralgia, nausea and
vomiting)
Therapeutic uses
• Chronic hepatitis B and C
• HZV infection in cancer patients
• CMV infections in renal transplant patients
• Refractory condylomata acuminata
• AIDS related Kaposi’s sarcoma
Replicative cycle of HIV-1, an example of a retrovirus, showing the sites
of action of antiviral agents.
ZIDOVUDINE
Mechanism of action
• Phosphorylated by cellular thymidine kinase to the corresponding
nucleotide analog inhibits the RNA dependent DNA-polymerase
blocking DNA synthesis
Antiviral spectrum and resistance
• Antiviral spectrum includes HIV-1, HIV-2, HTLV-1 and other retroviruses.
• Highly resistant mutants have been recovered from many AIDS patients
treated for more than 6 months.
Adverse effects
Severe anemia and leukopenia, Malaise, fever, fatigue, headache, nausea and
vomiting, diarrhea, insomnia, agitation (mainly during first few weeks)
Therapeutic uses
• Initial drug of choice in AIDS patients with CD4 counts less than 500/mm3.
(the drug initially reduces morbidity and mortality, but the effect is
transient)
• In asymptomatic HIV-infected individuals the drug slow the rate of
progression of AIDS.
Didanosine, Zalcitabine and stavudine
Mechanism of action
Phosphorylated by cellular thymidine kinase to the corresponding nucleotide
analog inhibits the RNA dependent DNA-polymerase blocking DNA
synthesis
Antiviral spectrum and resistance
The drugs are active against HIV-1 and HIV-2, including most zidovudine
resistant strains
Adverse effects
• Painful peripheral neuropathy (up to 30% of patients)
• Pancreatitis (can be fatal)
• Headache, insomnia, agitation, seizures (didanosine)
• Arthralgia, fever, rash
• Stomatitis, esophageal ulceration (zalcitabine)
• Hepatic steatosis, lactic acidosis (can be fatal)
Therapeutic uses
Advanced HIV infection in patients who are intolerant of or deteriorating on
zidovudine.
PROTEASE INHIBITORS
Derivat
Atazanavir, Darunavir, Fosamprenavir, Lopinavir, Nelfinavir, Tipranavir,
Saquinavir, Ritonavir and Indinavir
Mechanism of action
inhibiting HIV protease the drugs block the maturation of the virus and
therefore are active in both acutely and chronically infected cells
Antiviral spectrum and resistance
The drugs are active against HIV-1 and HIV-2, including most strains resistant
to nucleoside analogs
Adverse effects
• Nausea and vomiting, diarrhea, abdominal pain
• Skin rashes, urticarial
Drug interactions
Drugs which inhibit the hepatic mixed function oxidase system may increase
plasma concentrations of HIV protease inhibitors.
Therapeutic uses
Advanced HIV infection (in combination with deoxynucleoside antiretroviral
drugs)
Entry Inhibitors (Efuvirtide)
Resistance can occur but there is no
cross resistance
Drug administration subcutaneously in
combination with other antiretroviral
drugs
Side effects: Local injection site
reaction, hypersensitivity reaction,
Eosinophilia
