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Amebicides

Amebicides

Amebicides are drugs toxic to amoebas such as Entamoeba Entamoeba A genus of ameboid protozoa characterized by the presence of beaded chromatin on the inner surface of the nuclear membrane. Its organisms are parasitic in invertebrates and vertebrates, including humans. Nitroimidazoles histolytica (the causative organism of amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis). Parasites enter the GI tract where trophozoites can penetrate the intestinal wall and cause an invasive infection. Amebicides are classified based on where the drug is most effective: intestinal lumen or tissues. Intestinal-lumen amebicides include iodoquinol and paromomycin. Tissue amebicides include the nitroimidazole drug class (e.g., metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess, tinidazole Tinidazole A nitroimidazole alkylating agent that is used as an antitrichomonal agent against trichomonas vaginalis; entamoeba histolytica; and giardia lamblia infections. It also acts as an antibacterial agent for the treatment of bacterial vaginosis and anaerobic bacterial infections. Nitroimidazoles). Treatment of symptomatic disease usually requires a combination of both classes.

Last updated: 16 Sep, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis

  • Also known as amoebic dysentery Dysentery Acute inflammation of the intestine associated with infectious diarrhea of various etiologies, generally acquired by eating contaminated food containing toxins, biological derived from bacteria or other microorganisms. Dysentery is characterized initially by watery feces then by bloody mucoid stools. It is often associated with abdominal pain; fever; and dehydration. Gastroenteritis
  • Infection caused by the parasite Entamoeba Entamoeba A genus of ameboid protozoa characterized by the presence of beaded chromatin on the inner surface of the nuclear membrane. Its organisms are parasitic in invertebrates and vertebrates, including humans. Nitroimidazoles histolytica
  • Transmission:
    • Fecal-to-oral route
    • Consumption of contaminated food and water
  • Invasive infection is characterized by:
  • Serious complications:
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
    • Intestinal fistulas
    • Fulminant colitis Fulminant colitis Pseudomembranous Colitis
Pathogenesis of entamoeba histolytica

The pathogenesis of invasive Entamoeba Entamoeba A genus of ameboid protozoa characterized by the presence of beaded chromatin on the inner surface of the nuclear membrane. Its organisms are parasitic in invertebrates and vertebrates, including humans. Nitroimidazoles histolytica infection:
In 10% of cases, E. histolytica colonizes the large intestine Large intestine The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy mucosa and invades via secretion Secretion Coagulation Studies of proteinases and lytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes. This causes cellular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and lysis of the membranes, respectively. This chain of events induces mucosal cell apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage and disrupts tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions between cells, allowing for flask-shaped ulcers Flask-Shaped Ulcers Entamoeba spp./Amebiasis, abscesses, and fistulas to form. Invasion may reach the portal venous system, through which E. histolytica can spread to other organs.

Image by Lecturio. License: CC BY-NC-SA 4.0

Classification of amebicides

A combination of tissue and luminal amebicides are prescribed to treat amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis.

Luminal amebicides:

  • Destroy cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change and trophozoites in the intestinal lumen
  • Usually poorly absorbed (drug remains in the intestinal lumen)
  • Includes:
    • Iodoquinol
    • Paromomycin

Tissue amebicides:

  • Destroy trophozoites invading the tissues
  • Usually well absorbed (very little remains in the intestine)
  • Includes the nitroimidazoles Nitroimidazoles Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Nitroimidazoles:
    • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
    • Tinidazole Tinidazole A nitroimidazole alkylating agent that is used as an antitrichomonal agent against trichomonas vaginalis; entamoeba histolytica; and giardia lamblia infections. It also acts as an antibacterial agent for the treatment of bacterial vaginosis and anaerobic bacterial infections. Nitroimidazoles

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Iodoquinol

Mechanism of action

  • Luminal amebicide
  • The mechanism of action is not fully understood.

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

  • Poorly absorbed (approximately 90% remains in the intestine)
  • Excreted in the feces

Indications

Iodoquinol is used to treat amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis (limited availability in the United States): 

  • Action against cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change and trophozoites in the intestinal lumen 
  • Usually used in combination with a tissue amebicide for symptomatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Can be used alone for asymptomatic infection

Adverse effects

  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Abdominal pain Abdominal Pain Acute Abdomen
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Rash Rash Rocky Mountain Spotted Fever and pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Peripheral neuropathy Neuropathy Leprosy
  • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies or atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

Iodoquinol is contraindicated in individuals with an allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction or intolerance to iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones.

Paromomycin

Mechanism of action

Site of action for aminoglycosides amebicides

The site of action for aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides, which target the 30S ribosomal subunit
tRNA tRNA The small RNA molecules, 73-80 nucleotides long, that function during translation (translation, genetic) to align amino acids at the ribosomes in a sequence determined by the mRNA (RNA, messenger). There are about 30 different transfer rnas. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl trnas (RNA, transfer, amino Acyl), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure: transfer RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure: messenger RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure

Image by Lecturio. License: CC BY-NC-SA 4.0

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
    • Poor orally (most remains in the intestinal lumen)
    • A small amount is absorbed.
  • Excretion:
    • Mostly in feces
    • The absorbed drug is excreted in urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat (unchanged).

Indications

  • Amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis: 
    • Action against cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change and trophozoites in the intestinal lumen 
    • Usually used in combination with a tissue amebicide for symptomatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Can be used alone for asymptomatic infection
  • Giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis
  • Leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis

Adverse effects

  • Abdominal cramps Cramps Ion Channel Myopathy
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Ototoxicity Ototoxicity Damage to the ear or its function secondary to exposure to toxic substances such as drugs used in chemotherapy; immunotherapy; or radiation. Glycopeptides

Precautions

Caution should be used in individuals with:

  • Renal impairment → ↑ accumulation and toxicity Toxicity Dosage Calculation
  • Bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis or ulcerative/inflammatory bowel disease → ↑ absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption

Nitroimidazoles

Members of the drug class

  • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
  • Tinidazole Tinidazole A nitroimidazole alkylating agent that is used as an antitrichomonal agent against trichomonas vaginalis; entamoeba histolytica; and giardia lamblia infections. It also acts as an antibacterial agent for the treatment of bacterial vaginosis and anaerobic bacterial infections. Nitroimidazoles

Mechanism of action

  • Tissue amebicide
  • Nitroimidazoles Nitroimidazoles Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Nitroimidazoles passively diffuse into the microbial cell. 
  • Nitroreductases Nitroreductases Enzymes which reduce nitro groups (nitro compounds) and other nitrogenous compounds. Nitroimidazoles (produced by susceptible organisms) → reduce the nitro group Nitro Group Nitroimidazoles on the molecule
  • Results in the production of:
    • Free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
    • Cytotoxic Cytotoxic Parvovirus B19 metabolites → interact with host DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure → strand breakage and destabilization of the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure helix
  • Cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
  • Effect:

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
  • Distribution:
    • Distributed widely in tissues
    • Low protein binding (< 20%)
    • Crosses the blood- brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification barrier
  • Metabolism and excretion:
    • Extensively metabolized in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
    • Excreted mainly through the urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat

Indications

In addition to anaerobic bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, nitroimidazoles Nitroimidazoles Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Nitroimidazoles can be used for:

  • Amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis:
    • Effective for intestinal wall and extraluminal trophozoites
    • Does not kill cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
    • Usually used in combination with a luminal amebicide
  • Giardiasis Giardiasis An infection of the small intestine caused by the flagellated protozoan giardia. It is spread via contaminated food and water and by direct person-to-person contact. Giardia/Giardiasis
  • Trichomoniasis

Adverse effects

  • GI upset
  • Disulfiram-like reaction with alcohol (due to inhibition of aldehyde dehydrogenase)
  • Dysgeusia Dysgeusia A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality. Nitroimidazoles (metallic taste) 
  • Peripheral neuropathy Neuropathy Leprosy 
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome) 
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat discoloration (red/brown color)

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (1st trimester)
  • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding 
  • Severe hepatic impairment

Drug interactions

  • Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism-containing elixirs:
    • Cough syrups
    • IV trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim– sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim
  • Disulfiram (can cause acute psychosis)
  • ↓ Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of:
    • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
    • Ergot
  • ↓ Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metabolism of:
    • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
    • Warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants
    • Carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs

References

  1. Rosenthal, P.J. (2012). Antiprotozoal drugs. In Katzung, B.G., Masters, S.B., and Trevor, A.J. (Eds.), Basic & Clinical Pharmacology (12th edition, pp. 915–936). https://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf
  2. Weller, P.F. (2021). Antiprotozoal therapies. In Bogorodskaya, M. (Ed.), UpToDate. Retrieved September 4, 2021, from https://www.uptodate.com/contents/antiprotozoal-therapies
  3. Uptodate Lexicomp. Retrieved September 4, 2021, from:
  4. Campbell, S., and Soman-Faulkner, K. (2020). Antiparasitic drugs. StatPearls. Retrieved September 4, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK544251/
  5. Dhawan, V.K., Cleveland, K.O., and Cantey, J.R. (2019). Amebiasis medication. In Bronze, M.S. (Ed.), Medscape. Retrieved September 4, 2021, from https://emedicine.medscape.com/article/212029-medication
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