This document discusses drugs used to treat gastrointestinal infections. It covers anti-protozoal drugs like metronidazole and diloxanide furoate that act against protozoa. It also discusses anthelminthic drugs like albendazole and pyrantel pamoate that act against helminths. Finally, it discusses anti-spasmodic drugs like dicyclomine and drotaverine that are used to relieve gastrointestinal spasms. Metronidazole acts by becoming an electron sink within protozoa cells. Albendazole acts by inhibiting microtubule polymerization in helminths. Drotaverine acts as a phosphodiesterase-4 inhibitor to

1. Miscellaneous drugs:
Gastrointestinal infections
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajgunj Medical Campus, Kathmandu
12 July 2020 (28 Asar 2077), Sunday

2. By the end of this discussion, BSc Nursing
1st year students will be able to:
List the drugs used for the treatment of gastro-intestinal protozoal and
helminthic infections
Explain the mechanism of action and adverse effects of anti-protozoal
and anthelminthic agents
List the drugs used to relieve gastro-intestinal spasm
Explain the mechanism of action of drotaverine

3. Anti-protozoal drugs
These agents are active against protozoa
Unicellular
Eukaryotic
Belongs to the phylum Protozoa
Acts by killing the organism
Classified according to the organism susceptible and site of action

4. Anti-protozoal drugs: Classification
Anti-amoebic drugs
Tissue amoebicides
Luminal amoebicides
Drugs for giardiasis
Metronidazole, Nitazoxanide, Quiniodochlor, Furazolidine

5. Anti-amoebic drugs: Classification
Tissue amoebicides:
For intestinal + extraintestinal amoebiasis
Nitroimidazoles (-dazole)
• Metronidazole,Tinidazole, Secnidazole, Ornidazole, Satranidazole
Alkaloids:
• Emetine, Dihydroemetine
For intestinal amoebiasis only
• Chloroquine

6. Anti-amoebic drugs: Classification
Luminal amoebicides:
Amides
• Diloxanide furoate, Nitazoxanide
8-hydroxyquinolines
• Quinidochlor, Iodoquinol
Antibiotics
• Tetracyclines, Paromomycin

7. Metronidazole
Broad spectrum amoebicidal drug
Not effective in aerobic bacteria and aerobic environment
Mechanism of action:
Enters into protozoal cells by diffusion
Gets reduced to highly reactive nitro radical
Competes with biological electron acceptors for electrons generated
by pyruvate oxidation (PFOR pathway)
Cells become energy deficient and dies

8. Metronidazole: Uses
Amoebiasis (Entamoeba histolytica)
Giardiasis (Giardia lambia)
Trichomonas (Trichomonas vaginalis)
Anaerobic bacterial infection
Pseudomembranous enterocolitis
Acute necrotizing ulcerative gingivitis (Trench mouth)
H. pylori gastritis

9. Metronidazole: Adverse effects
Frequent and unpleasant, but not serious:
Anorexia, nausea, metallic taste, abdominal cramps
Thrombophlebitis of injected vein
Dilute solution properly
Allergic reactions: STOP the drug, not to be used in future as well!
Less frequent side effects:
Headache, glossitis, dryness of mouth and impairment of
concentration
Peripheral neuropathy and CNS effects on prolonged administration
Seizures in high dose
Leukopenia on repeated doses

10. Emetine
Alkaloid from Cephaelis ipecacuanha
Potent and directly acting amebicide
Kills trophozoites
Administered by s.c. or i.m. injection: 60
mg OD

11. Mechanism of action:
Arrests intra-ribosomal
translocation of tRNA amino
acid complex
Inhibits protein synthesis in
amoebae
Emetine: Mechanism of action

12. Emetine
Local irritant and has high systemic toxicity
Nausea, vomiting (due to CTZ stimulation and gastric irritation),
abdominal cramps, diarrhoea, weakness, stiffness of muscles,
myositis, hypotension, ECG changes and myocarditis.
Uses
Acute amoebic dysentery
Amoebic liver abscess
Liver fluke infestation
In patients not tolerating metronidazole

13. Diloxanide furoate
Highly effective luminal amoebicide
Directly kills trophozoites responsible for production of cysts
Uses:
Intestinal amoebiasis
Asymptomatic cyst passers
Side effects:
Very well tolerated
Flatulence, occasional nausea, itching and rarely urticaria

14. Nitazoxanide
Acts by
Inhibiting pyruvate:ferredoxin oxidoreductase (PFOR) enzyme
Protozoa becomes energy deficient
Uses:
Cryptosporidium parvum infection
Amoebic dysentery
Giardiasis
Side effects:
Mild and infrequent: Abdominal pain, vomiting and headache

15. Anthelminthic drugs
These drugs are active against helminths (worms)
Acts by:
Kills the worm (Vermicidal)
Expels the worm (Vermifuge)
Classified on the basis of organism susceptible

16. Anthelminthic drugs: classification
For roundworm, hookworm, pinworm
Albendazole, mebendazole, pyrantel pamoate, piperazine, levamisole
For threadworm
Ivermectin, albendazole
For whipworm, Trichinella spiralis
Albendazole, Mebendazole

17. Anthelminthic drugs: classification
For Filariasis
Diethylcarbamazine, Ivermectin, Albendazole
ForTapeworm
Praziquantel, Niclosamide, Albendazole
For Hydatid disease
Albendazole, Mebendazole

18. Albendazole
Broad spectrum anthelmintic
Acts by:
Binds to microtubular protein β-tubulin of
the parasite
Inhibits polymerization of microtubules
Microtubules gradually lost and paralysed
Additional actions:
Blocks glucose uptake by parasite
Depletes glycogen stores by inhibiting mitochondrial
enzymes

19. Albendazole: Uses
Drug of choice:
Roundworm (Ascaris lumbricoides)
Hookworm (Ancyclostoma duodenale)
Tapeworm (Neurocysticercosis)
Pinworm (Enterobius vermicularis)
Hydatid disease (Echinococcous sps.)
Cutaneous larva migrans (Ancyclostoma caninum)
Trichinella spiralis

20. Albendazole: Side effects
Excellent tolerability
Gastrointestinal side effects:
Nausea, diarrhoea, abdominal pain
Dizziness
On prolonged use:
Headache, fever, alopecia, jaundice, neutropenia

21. Pyrantel pamoate
Mechanism of action:
Activation of nicotinic cholinergic receptors in the worms
Leads to Persistent depolarization
Slowly developing contracture and spastic paralysis
Worms are then expelled
Uses:
Pinworm infection (Enterobiasis)
Roundworm, Hookworm, Strongyloides
Adverse effects:
Occasional GI symptoms, headache and dizziness

22. Niclosamide
Mechanism of action:
Inhibits oxidative phosphorylation in mitochondria and interfering
with anaerobic generation of ATP by the tapeworm
Injured worms are partly digested in the intestine
Use:
Tapeworm (Taenia, H. nana)
Adverse effects:
Occasional: minor abdominal symptoms
Rare: malaise, pruritus and light headedness

23. Praziquantel
Mechanism of action:
At lower concentration,
Rapidly taken up by susceptible worms
Causes leakage of intracellular calcium from the membranes
Contracture and paralysis
Worms lose grip and get expelled
At relatively higher concentrations,
Vacuolization of the tegument and release of the contents of worms
Followed by their destruction by immune mechanisms

24. Praziquantel
Uses:
Tapeworms
Neurocysticercosis
Schistosomes
Adverse effects:
Bitter taste: nausea
Abdominal pain
Headache, dizziness and sedation.
Reaction to the destroyed parasites:
Itching, urticaria, rashes, fever and bodyache
Neurological complications (see below).

25. Anti-spasmodic agents
Relieves painful contraction in gastro-intestinal tract
Anti-cholinergics are used
Hyoscine butyl bromide
Atropine methonitrate
Clidinium
Pipenzolate methyl bromide
Dicyclomine
Acts by blocking M3 receptors present in smooth muscles of intestines
Dicyclomine also has direct muscle relaxant actions

26. Drotaverine as Anti-spasmodics
Mechanism of action:
Inhibits phosphodiesterase-4 (PDE-4)
Elevation of intracellular cAMP/cGMP
Smooth muscle relaxation
Use
Intestinal, biliary and renal colics, irritable bowel syndrome, uterine
spasms, etc
Adverse effects:
Headache, dizziness, constipation and flushing
Fall in BP on i.v. injection

27. Conclusion: Classwork!
GI antiprotozoal: metronidazole, diloxanide furoate
GI anthelminthics: mebendazole, albendazole, pyrantel pamoate
Metronidazole
M/A: acting as an electron sink
S/E: metallic taste, anorexia
Albendazole:
M/A: microtubule destruction ( beta tubulin polymerization affected)
S/E: nausea/voimitting, cramps, dizziness,
GI spasm: dicyclomine, drotaverine
Drotaverine M/A: PDE4 inhibitor

28. Questions??
Thank you!