Autonomic Nervous System ANS

There are two types of Nervous System
1. Central Nervous System CNS
2. Peripheral Nervous System PNS

PNS consists of neurons present out side brain and spinal cord

There are two types of neurons
1. Afferent neurons: Carry impulse from the periphery to CNS. (Towards CNS)
2. Efferent neurons: Carry impulse from CNS to Periphery. (Towards Periphery)

Efferent neurons are further divided into:
1. Somatic Nervous System
2. Autonomic Nervous System

The somatic nervous system controls voluntary movement of Body like skeletal muscle contraction and relaxation in locomotion.

The autonomic nervous system controls involuntary movement of the body.

There are three parts of efferent nerve fibers in ANS:
1. Pre Ganglionic Nerve fiber
2. Ganglia
3. Post Ganglionic fiber

There are two types of efferent nerve fibers
1. Sympathetic nerve fibers or Sympathetic neurons in the Sympathetic Nervous System
2. Parasympathetic nerve fibers or parasympathetic neurons in the Parasympathetic Nervous System

Effect of Autonomic Nervous System

                   Sympathetic Nervous System           Parasympathetic Nervous System

•                         Fight or Flight Response                                Rest and Digest
•                  Body Response to Stress Condition  
•              Adjust Individual in stressful Condition               Maintain essential body condition  
•              Physiological Effect not essential to life              Acts opposite to sympathetic nervous               Like                                                                       system  
•  Increase in Heart Rate, Blood Pressure
• Increase in blood flow to Skeletal Muscle 
•           and Cardiac Muscle 
• Divert blood flow from the skin to 
•           internal organs
• Dilation of Pupil
• Dilation of Bronchioles
• A mobilization of body energy

For a detailed explanation please visit the below link

https://www.youtube.com/edit?o=U&video_id=yqaY8gV3oPQ
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Neurotransmitter Acetylcholine. Cholinergic nerve fibres

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Runners High, Biology and Chemistry, Euphoria experienced due to anandamide.

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https://youtu.be/kmRK5hW5Mao

Antiamebic

CHEMOTHERAPY OF AMEBIASIS

Amebic infection is caused by Entamoeba histolytica. Amebic infection is called amebiasis or amebic dysentery. It is an infection of the intestine that may be acute or chronic in nature and either symptomatic or asymptomatic. Symptomatic amebiasis is characterized by mild diarrhea to fulminating dysentery. In severe condition or unattended amebiasis may also affect another physiological system of the body. Amebiasis in the liver is called hepatic amebiasis and amebiasis outside liver is called extrahepatic amebiasis.

Entamoeba histolytica is unicellular Protozoal Cells. Protozoal cells are eukaryotic cells. Their metabolic processes are very close to human cells metabolic processes. Thus antiprotozoal drugs are very toxic to human cells. E. histolytica exists in two forms i.e. trophozoites and cysts. Usually, patients suffering from symptomatic amebiasis carry trophozoites and asymptomatic patients carry cysts. Antiamebic drugs are effective against trophozoites.

Life cycle of Entameba histolytica

There are two stages of life cycle of Entameba histolytica

·         Trophozoites (Metabolically active stage)

·         Cysts (Metabolically inactive stage)

Cysts survive outside the human body in an inactive form for a longer duration. Trophozoites cannot survive outside the human body. Ameba cysts contaminate food through human feces. Cysts enter into human body through contaminated water and food. Cyst releases trophozoites inside human intestine. Trophozoites feed on intestinal flora, undergoes multiplication, invade intestinal mucosa, form ulcer on large intestinal mucosa wall and then invade physiological systems of human body. Inside rectum trophozoites form a cyst and excreted in feces.

Classification of antiamebic drugs:

Antiamebic drugs can be divided into following three classes, depending upon their site of action

· Luminal Antiamebic Drugs: (Luminal Amebicides): Diloxanide furoate, Diiodohydroxyquine, Iodoquinol, Clefamide, etc. They are effective against ameba in the intestinal lumen. They are amebicide do not effective against ameba present in intestinal mucosa wall or another physiological system. They are used to treat asymptomatic amebiasis or mild symptomatic amebiasis.

However, they are also used in combination with systemic amebicides or mixed amebicides to eradicate the infection

· Systemic amebicides or Tissue amebicides: Emetine, Dihydroemetine, Chloroquine. They act as amebicide in the intestinal wall, liver, and other extrahepatic tissues. But they are not effective against ameba present in intestinal lumen However, they are not a drug of choice to treat amebiasis due to their toxic effect.

·    Mixed Amebicides: Metronidazole, Tinidazole, Secnidazole, Ornidazole etc. They are effective against both luminal amoeba and tissue ameba. Luminal amebicides are used with mixed amebicides to eradicate the amebic infection.

Diloxanide furoate: It is dichloroacetamide derivatives. It is administered by oral route. 90% of diloxanide is absorbed. It is hydrolyzed inside mucosal cells. 10 % unabsorbed diloxanide furoate present in lumen produce the amebicidal effect. Absorbed hydrolyzed diloxanide is distributed in tissue vert poorly. Thus they cannot produce a therapeutic effect in tissues. Metabolised diloxanide furoate is excreted in urine.

It produces mild adverse effects like flatulence, dryness of mouth, pruritis, and urticaria. It is contraindicated in pregnant women and children below two years.

Emetine and dehydroemetine: They are Ipecac alkaloid and highly toxic. Thus, they have been replaced by other more effective and safer amebicides like nitroimidazole derivatives. Emetine and dehydroemetine are used in nitroimidazole failure. However, dehydroemetine is less toxic than emetine.

They are administered by the intramuscular or subcutaneous route to avoid GIT disturbance. They concentrate in liver, lungs, and kidney. They are also slowly metabolized and slowly excreted in urine. Thus they produce a cumulative effect. Their half-life is about 5 days. The patient should be under close supervision of medical practitioner during drug administration and treatment.

They are effective against trophozoites in tissues not in the intestinal lumen. They are effective against trophozoites in tissues not in the intestinal lumen. They block polypeptide chain elongation thus they block protein synthesis to produce amebicide effect.

Adverse Effects: Nausea, Cardiotoxicity, Neuromuscular weakness, dizziness, and rashes.

Chloroquine: It is systemic amebicide (Tissue Amebicide). It is rapidly absorbed from GIT and distributed throughout the body but maximum concentration is found in liver. Thus it is not effective against E. histolytica trophozoites in the intestine and very effective against E. histolytica trophozoites in the liver.

Therapeutic Uses: It is used in metronidazole failure in the treatment of amebiasis. It is used in combination with metronidazole and diloxanide furoate to treat amebiasis and hepatic abscess. It is also useful in invasive intestinal amebiasis.

Metronidazole: It is 5 nitroimidazole derivative. It is rapidly and completely absorbed from GIT. Food decreases the rate of metronidazole absorption but it does not affect the extent of its absorption. Metronidazole is completely absorbed even in presence of food in GIT. It is well distributed throughout the body but its concentration in the liver is much more than any other tissues. It is metabolized in the liver by oxidation followed by glucuronidation. Metabolites are excreted in urine.

Mechanism of action: It kills E. histolytica trophozoites and also anaerobic organism including anaerobic bacteria. It also produces a toxic effect to anoxic and hypoxic cells. (Cells not oxygenated is called anoxic cell and Cells not adequately oxygenated is called hypoxic cells)

Its penetration into bacterial cells and protozoal cells is faster than mammalian cells/ It freely penetrates into bacterial cells and protozoal cells. Inside cells, 5-nitro group of metronidazole acts as electron receptor and metronidazole undergo reduction reaction. Reduced form is a cytotoxic compound that binds to protein and DNA of cells. It produces breakage of DNA strands and death of cells. It has also the radisensitization effect on hypoxic tumor cells.

It does not penetrate freely into mammalian cells thus its toxic effect on mammalian cells is less than on microbial or protozoal cells.

Antibacterial Spectrum: It acts against parasites like E. histolytica, Trichomonas vaginitis, Giardia lamblia, Balantidium collie. It is also effective against anaerobic bacteria both gram –ve and gram +ve.

Adverse effects:

GIT: Nausea, vomiting, epigastric distress, abdominal cramp, metallic taste, yeast infection in the mouth (Oral moniliasis)

CNS: Seizure and peripheral neuropathy associated with numbness in extremity. These are most serious side effects.

Hematological: Reversible leukopenia.

Genito Urinary: Deep red-brown urine color. Dysuria (Pain, discomfort, burning during urination), cystitis, polyurea(Abnormally large volume of urine) etc.

Drug Interaction: It should not be consumed with alcoholic products. It produces the disulfiram-like effect with alcohol (Antabuse like reaction), abdominal cramp, nausea, vomiting headache, flushing, etc. (Antabuse is the brand name of disulfiram that is used to treat alcoholism by producing nausea and unpleasant effects). If it is administered with disulfiram, it produces an acute psychotic reaction (Confusional state)

Cimetidine blocks metronidazole metabolism. Thus cimetidine precipitate metronidazole side effects,

It is also contraindicated during pregnancy, especially in the first trimester.

Tinidazole: It has a longer duration of action than metronidazole due to the slow rate of metabolism.

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Antivirus

Antivirus

Viruses are smallest microorganism consist of nucleic acid enclosed in a protein coat (Capsid). They do not have a cell wall and cell membrane. They do not carry out metabolic processes. They depend upon host metabolic processes. It is very difficult to treat virus infection. Antivirus drugs are used to treat viral infection. 

There are two types of viruses:

• DNA Viruses: Smallpox virus, Herpes virus
• RNA Viruses: Influenza virus (Orthomyxovirus)                                                                                                    Measles and mumps virus (Paramixo virus)

Classification: Antiviral drugs are classified depending upon their therapeutic uses.

·         

•        Respiratory tract viral infection treatment

o   Amantadine

o   Ribavirin

o   Rimantadine

• ·         Herpes and Cytomegalovirus infection

o   Acyclovir

o   Cidofovir

o   Famcicloviro   Penciclovir

o   Ganciclovir

o   Trifluridine

• ·         Hepatitis and leukemia due to viral infection

o   Interferon

•          HIV infection treatment

RESPIRATORY TRACT VIRAL INFECTION TREATMENT

Respiratory tract viral infections are caused by Influenza A virus, Influenza B virus and syncytial virus (RSV: Respiratory syncytial virus).Vaccines are available to prevent influenza A virus infection. Immunisation should be preferred. Antiviral drugs are used to prevent and control respiratory tract infections in non-immunized patients. Clinical symptoms of viral infections appear at a later stage of infection. Thus antiviral drugs the inhibit virus replication (virus growth) have very low efficacy. They are mostly used as prophylactic agents.

Amantadine: It is a water-soluble compound that inhibits virus matrix protein M_2. M₂ acts as an ion channel in the virus. Ion channels are used in acid-mediated dissociation of Ribonucleoprotein complex.  This helps fusion of virus in host cell membrane as endosomes. Endosomes have an acidic environment that causes un-coating of the virus and intracellular transport of virus. Amantadine blocks M₂ proteins that inhibit virus multiplication.

Pharmacokinetics: It is well absorbed from GIT, well distributed throughout the body including CSF. It can cross the blood-brain barrier. The unchanged active drug is excreted in urine. Thus it accumulates in a patient body suffering from renal dysfunction.

Adverse Reactions: Nervousness, Confusion, Hallucination, Seizure, and Coma, Loss of appetite, Nausea. It is contraindicated in lactating and pregnant women because it easily crosses the placental barrier and excreted unchanged in lactating mother milk.

Uses: Amantadine is only effective against influenza A virus infection. It is more useful as a prophylactic agent than therapeutic agent. It is used in the epidemic to prevent influenza A virus infection. It is also used as a supplement in vaccination to prevent influenza A virus infection.

As a therapeutic agent, it is particularly useful to treat influenza A virus infection in a nonimmunized patient.

   

Rimantadine: It is analog to amantadine. Its rate absorption from GIT is slower than amantadine but has a high volume of distribution and low CNS toxicity. It is extensively metabolized in the liver and excreted in urine. About 15% unchanged drug is also excreted in urine.

Ribavirin: It is broad-spectrum antiviral agent effective against both RNA and DNA viruse. Ribavirin acts at the various site to block virus replication. Enzyme adenosine kinase converts ribavirin to ribavirin 5 monophosphate (RMP). RMP is phosphorylated to ribavirin triphosphate (RTP). RTP compete with GTP and ATP to block GTP dependent enzymes necessary for mRNA synthesis.

 It is administered by an oral route and intravenous route. It is also used as an aerosol in respiratory tract viral infection. Unchanged drug and its metabolites are excreted in urine.

 Anemia, Increase in bilirubin and uric acid level in blood.

HERPES VIRUS INFECTION TREATMENT

Herpes virus produces various diseases like cold sores, viral encephalitis, genital infection etc.

Acyclovir: It is synthetic purine nucleoside analog. It is highly effective against the herpes virus. Herpes virus enzyme thymidine kinase converts acyclovir to acyclovir monophosphate. Host cells convert acyclovir monophosphate to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate blocks DNA polymerase enzyme to act on Deoxyguanosine triphosphate. Acyclovir triphosphate incorporates itself to virus DNA. This causes premature DNA chain termination.

Acyclovir triphosphate is more sensitive to viral DNA polymerase enzyme than host cells polymerase enzyme. Virus cells activate acyclovir to acyclovir monophosphate. In absence of virus, acyclovir monophosphate will not be synthesized. Thus acyclovir will not produce its action. Due to these two factors, acyclovir is selective to infected host cells not healthy host cells.

Some viruses do not have enzyme thymidine kinase or polymerase. These viruses are resistant to acyclovir.

Pharmacokinetics: It is administered by intravenous route, oral route, and topical route. It is well distributed throughout the body including CSF. Metabolites are excreted in urine.

Adverse Effects: the Topical application may produce local irritation. Oral administration may develop nausea, vomiting, diarrhea, and headache. High dose of intravenous route develops renal dysfunction.

Therapeutic Uses: It is used in herpes simplex virus type I and II infection. It is more effective in the initial stage of infection. It is the drug of choice to treat herpes simplex encephalitis, genital herpes infection. It is also used as the prophylactic agent.

Famciclovir and Penciclovir: Famciclovir is a prodrug. It is metabolized to active penciclovir. It is used to treat acute herpes zoster. It is administered orally.

Ganciclovir: It is similar to acyclovir. Ganciclovir is more 
than acyclovir. It has very low oral bioavailability thus it is administered by intravenous route. It is well distributed throughout the body and excreted unchanged in urine. Its half-life is about 3-4 hours. Ganciclovir is carcinogenic, embryotoxic and teratogenic.

Foscarnet: It has broad antiviral activity. It inhibits herpes virus DNA polymerase and HIV reverse transcriptase. It is poorly absorbed by oral route thus it is administered by intravenous route. It is well distributed throughout the body. The highest concentration is found in the bone matrix. Unchanged drug is excreted in urine by glomerular filtration.

Adverse Effect: Nephrotoxicity, anemia, nausea, and fever.

Uses: It is used to treat rhinitis in HIV patient. It is also useful in acyclovir-resistant herpes simplex virus.

Vidarabine (Adenine Arabinose): It is adenine nucleoside analog. It has the least toxicity. However, acyclovir is preferred than vidarabine. It is phosphorylated in cells to form vidarabine 5 triphosphate that inhibits viral DNA polymerase i.e. inhibition of viral DNA synthesis. It acts on both host cells and viral DNA polymerase. But it has more affinity for virus DNA polymerase.

Vidarabine is administered by intravenous route. It is quickly metabolized by adenine diamine to hypoxanthine arabinoside. It produces a synergistic effect with vidarabine. It is slightly soluble in water thus it is administered with a large volume of water by the intravenous route. It penetrates into CNS thus it is used to treat encephalitis due to the herpes virus. Vidarabine ointment is used to treat hepatic and vaccinial keratitis. Vidarabine with acyclovir is used in life-threatening virus infection. 

HUMAN DEFICIENCY VIRUS (HIV) INFECTION TREATMENT

Purine and pyrimidine nucleoside forms are used against HIV as an antiretroviral agent. HIV protease inhibitors are also used against HIV.

Zidovudine: It is thymidine analog referred as AZT (Azidothymidine). It is used in HIV 1 virus infection to improve immunity. It also helps to prevent and cure the related infection.

Enzyme thymidine kinase phosphorylates zidovudine to zidovudine triphosphate that competitively inhibits DNA polymerase enzyme (i.e. a reverse transcriptase). Zidovudine has higher affinity with virus DNA polymerase than human DNA polymerase. Zidovudine also terminate chain formation during DNA synthesis. Thymidine and ribavirin antagonize action zidovudine.

Pharmacokinetics: It is well absorbed by the oral route. Food contents slow down the rate of drug absorption but do not affect total absorption of the drug. Drugs are completely absorbed from GIT even in presence of food. It is well distributed in the body including CNS. It is metabolized by glucuronidation into inactive metabolites. It has 1 hr of half-life. Glucoronide metabolites are excreted in urine.

Adverse Effect: Anemia, granulocytopenia, severe headache, seizure.

Didanosine: It belongs to the dideoxynucleoside. It is used to treat Zidovudine resistant HIV infection. It is not used in the initial stage of resistant. It acts as zidovudine. It is metabolized to didanosine adenosine triphosphate (ddATP) by various phosphorylation reaction. ddATP incorporate into DNA to terminate DNA chain elongation (just like zidovudine).

Pharmacokinetics: It is rapidly absorbed from GIT. Alkaline media favor its absorption. Thus it is administered with an antacid or chewable buffered tablet or in a buffered solution. Food in GIT reduces the rate of absorption. Thus it is advisable to administer drug under fasting condition. It is well distributed in the body including CNS. But CNS penetration is less than zidovudine. It is rapidly excreted in urine.  55% of the unchanged drug is also excreted in urine.

Zalcitabine: It is analog of deoxycytidine. Its mechanism of action is similar to Zidovudine. Zalcitabine is well absorbed from GIT, food reduces the rate of absorption. It is well distributed in the body including CNS. But its penetration into CNS is less than Zidovudine. It is metabolized into inactive deoxyuridine. It is excreted in fecal matter. Unchanged zalcitabine is excreted in urine also. Both active and metabolites are excreted in fecal matter.

Adverse Effects: Rash stomatitis peripheral neuropathy, headache mouth ulcer and edema.

Stavdine:

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Antiseptics Disinfectants

Antiseptics and Disinfectants

Antiseptics are antimicrobial agents to apply on the living surface to kill or prevent the growth of microorganism to reduce or prevent microbial infection or sepsis. Disinfectants are antimicrobial agents to apply on the nonliving surface (inanimate surface) to kill or prevent microorganism growth to reduce their number to prevent infection. They do not kill spores. Antibiotics are the metabolic product of bacteria that kill or prevent the growth of the selective microorganism. Antibiotics are usually used to control systemic microorganism infections. Antiseptics are not used for systemic microorganism infections. They are used for topical infections. They are not selective and harm almost all microorganisms. They are used to clean the wound and do not support wound healing. In fact, they impair wound healing.

Word germicide includes both antiseptic and disinfectant. They are widely used with household products soap, toothpaste, after saving lotion etc.

Mechanism of action: Antiseptics and disinfectants produce their action by any one or combination of following mechanisms:

·         Microorganism protoplasm oxidation

·         Microorganism protein denaturation

·         Microorganism cell metabolism impairment

·         Surfactant like action

Ideal antiseptic and disinfectant: Ideal antiseptics and disinfectants should of following characteristics:

·         It should not be absorbed from skin or mucous membrane into systemic circulation

·         It should be chemically stable

·         It should have a broad antimicrobial spectrum

·         It should have rapid action

·         It should be nonirritating to tissues

·         It should not impair wound healing

·         It should be effective even in presence of pus, exudates, and tissue degradation products

·         It should not have an offensive odor, color and staining properties.

·         It should not produce hypersensitivity reaction

Classification

·         Acids: Ethanol, Isopropyl Alcohol

·         Aldehydes: Formaldehyde, Glutaraldehyde,

·         Phenol Derivatives: Phenol, Cresol, Paraben, Thymol, Resorcinol, Chlorhexidine, Chlorhexidine Gluconate, Chloroxylenol, Hexachlorophene

·          Halogens: Chlorine, Iodine, Iodophores, Chloramine

·         Oxidising Agents: Hydrogen peroxide, Potassium permanganate, Benzoyl peroxide

·         Dyes: Gentian Violet, Methylene Blue, Brilliant Green

·         Heavy Metals: Mercury Compounds, Silver Compounds, Zinc Compounds

ACIDS: Acids are bactericidal at pH less than 3 and bacteriostatic at pH between 3 and 6. They are used as antiseptic, fungicide and to preserve food.

·         Acetic Acid: 5% concentration of acetic acid is used as bacteriostatic. Less than 5% concentration acts as bacteriostatic. 1% acetic acid solution is used in surgical dressings as antimicrobial agents. 0.25% to 2% acetic acid solution is used as an antimicrobial agent in external ear infection and lower urinary tract infection as an irrigation solution. It is very effective against aerobic gram –ve bacteria. 5% acetic acid solution is used to suppress the growth of microorganism on the extensively burning skin.

·         Benzoic Acid: 0.1% benzoic acid prevents the growth of bacteria and fungus in acidic media. It is tasteless and nontoxic. Thus it is also used as a preservative.

·         Boric Acid: Aqueous solution of boric acid is used to irrigate eye, vagina, large wound, and bladder. It is less volatile than acetic acid, thus, it remains on the surface for longer duration upon topical application. 16.7% boric acid combine with salicylic acid is used to remove worts.

·         Salicylic acid: It is bacteriostatic, fungicidal and keratolytic. It is for external use to treat chronic leg ulcer, eczema, psoriasis, and seborrheic dermatitis. It is an ingredient of Whitefield’s ointment that contains benzoic acid and salicylic acid to treat tinea pedis infection.

ALCOHOL

·         Ethyl alcohol (Ethanol): It is an antimicrobial agent with low potency and moderate efficacy. Ethanol 60% v/v to 90%v/v is used as antiseptic. Its antiseptic property decreases above 80% v/v strength. It acts as bacteriostatic by denaturing bacterial proteins. Alcohol is an antimicrobial agent that has following properties:

o   Bacteriostatic and fungicidal

o   Ethanol 40% to 60% is most effective against staphylococci

o   Ethanol 70% control 90% of bacteria within 2c minutes on moist skin

o   Ethanol 80% or above has low antiseptic property

o   Ethanol increases the germicidal effect of chlorhexidine, iodine, iodophors, and hexachlorophene

o   Ethanol alone has not much effect on an open wound. It forms coagulum on an open wound. Bacteria may grow below coagulum

o   Ethanol produces irritation and burning on an open wound.

o   Ethanol is not much effective against spores

o   It is inflammable. Thus lesser surgery should be applied after complete evaporation of ethanol

o   Isopropyl Alcohol: It is more potent and less toxic than ethanol. 68% to 72% of isopropyl alcohol is used as a skin antiseptic.

ALDEHYDE: Aldehydes are effective against bacteria, spores, fungi, and viruses. Mainly formaldehyde and glutaraldehyde are used as a disinfectant.

·         Formaldehyde: 2% to 8% aqueous solution of formaldehyde is used as a germicide. It is used to disinfect inanimate (non-living) objects like surgical instruments. It should not be used as antiseptic to the mucous membrane. However, methenamine is urinary antiseptic that produces an antimicrobial effect in urinary tract by releasing formaldehyde in the urinary tract.

Formaldehyde solution polymerizes to form a white deposit in concentrated stock solution 

·         Glutaraldehyde: It polymerizes slowly than formaldehyde. 2%w/v solution is used as a broad-spectrum disinfectant. It is effective in alkaline pH not in acidic pH.

Formaldehyde and glutaraldehyde vapor are carcinogenic. They irritate the eye and mucous membrane of the respiratory tract. Both cause dermatitis. They are used to clean, disinfect, and sterilize heat-sensitive surgical instruments. They are also used to maintain an aseptic condition in the aseptic room, injectable manufacturing room etc by fumigation. They are used to disinfect incubators, cold rooms, benches,

· Chlorhexidine: It is most commonly used a surgical antiseptic. It is colorless, odorless with bitter and unpleasant taste. It is effective against bacteria but bacterial spores and acid-fast bacteria are resistant to chlorhexidine. It has a longer duration of action with higher therapeutic index. It is effective in presence of blood, pus, and soap. It is most effectve at pH 5.5 and 8

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