PET D WORM TABLETS

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

Store in a cool, dry place away from heat and direct sunlight.

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Roundworm infections
• Hookworm infections
• Whipworm infections
• Pinworm infections
• Other helminth infections

Dosage

Children: Child 1 month–9 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to 3 mg/kg daily in divided doses, dose to be increased gradually over 3 days. Child 10–17 years: Initially 1 mg/kg daily in divided doses on the first day, then increased to

Adults: 100 mg for 1 dose, if reinfection occurs, a second dose may be needed after 2 weeks.

Mechanism of action

Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization into microtubules. This leads to impaired glucose uptake and depletion of glycogen stores in the parasites, resulting in decreased ATP production, immobilization, and eventual death of the helminths.

Pharmacodynamics

Mebendazole is a synthetic broad-spectrum anthelmintic. Its principal mode of action is through the inhibition of tubulin polymerization, which results in the loss of cytoplasmic microtubules. This action disrupts organelle movement and interferes with the normal physiological processes of helminths, effectively leading to their death.

Pharmacokinetics

Mebendazole is poorly absorbed from the gastrointestinal tract, which contributes to its effectiveness as an anthelmintic. After oral administration, the drug is primarily metabolized in the liver. Its low solubility limits absorption, but it can still exert its effects on the intestinal parasites present in the gastrointestinal tract. The drug's elimination half-life is variable, and it is not significantly distributed in body tissues.

Contra-indications

• Blood disorders

Adverse effects

• Abnormal sensation in eye
• Anaemia
• Appetite decreased
• Asthenia
• Asthma exacerbated
• Chest discomfort
• Coma
• Confusion
• Conjunctival haemorrhage
• Constipation
• Diarrhoea
• Difficulty standing
• Difficulty swallowing
• Dizziness
• Fever
• Gastrointestinal discomfort
• Headache
• Hepatitis
• Hypotension
• Joint disorders
• Leucopenia
• Lymphatic abnormalities
• Myalgia
• Nausea
• Oedema
• Pain
• Psychiatric disorder
• Seizure
• Severe cutaneous adverse reactions (SCARs)
• Stupor
• Tachycardia
• Tremor
• Urinary incontinence
• Vertigo
• Vomiting

Interactions

• Cimetidine (increases concentration of mebendazole)

Precautions

• Use with caution in patients with epilepsy
• Use with caution in patients with Sjögren’s syndrome

Pregnancy

Embryotoxic in animal studies, avoid if possible.

Breast-feeding

No information available.

Storage

Store in a cool, dry place away from light.

Formulations

• Chewable tablet 100 mg

Indications

• Schistosomiasis caused by Schistosoma mansoni
• Schistosomiasis caused by Schistosoma japonicum
• Tapeworm infections, including Taenia solium and Hymenolepis nana

Mechanism of action

Praziquantel is hypothesized to target the β subunits of voltage-gated Ca2+ channels in parasites such as Schistosoma mansoni and Schistosoma japonicum. This action leads to increased calcium influx, causing rapid contraction and paralysis of the worms. The drug also induces tegumental disintegration and vacuolization in schistosomes, significantly affecting adult worms more than juveniles. Secondary effects include inhibition of glucose uptake and depletion of glycogen levels.

Pharmacodynamics

Praziquantel exhibits a rapid onset of action against trematodes and cestodes, causing significant changes in the permeability of the cell membrane of the parasites. This results in muscle contraction, tegumental damage, and eventual death of the worms. It selectively targets schistosomes and is ineffective against nematodes. The drug's efficacy is notably reduced against juvenile schistosomes and may diminish after a few weeks of treatment.

Pharmacokinetics

Praziquantel is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours post-administration. It undergoes extensive hepatic metabolism, primarily by CYP450 enzymes, and has a half-life of approximately 1-3 hours. The drug is excreted mainly in urine as metabolites, with a small fraction excreted unchanged. The pharmacokinetics can be affected by co-administration with certain other drugs that alter its metabolism.

Adverse effects

• dizziness
• hepatitis
• neutropenia
• seizure
• severe cutaneous adverse reactions

Interactions

• mitotane+praziquantel: Severe (decreases exposure)
• rifampicin+praziquantel: Severe (decreases exposure)
• chloroquine+praziquantel: Moderate (decreases exposure)
• cobicistat+praziquantel: Unknown (increases exposure)
• dexamethasone+praziquantel: Unknown (decreases exposure)
• grapefruit juice+praziquantel: Unknown (increases exposure)
• cimetidine+praziquantel: Unknown (increases exposure)
• idelalisib+praziquantel: Unknown (increases exposure)

Pregnancy

Manufacturer advises avoiding use due to toxicity observed in animal studies.

Breast-feeding

Amount present in milk is too small to be harmful; however, the manufacturer advises avoiding use.

Storage

Store in a cool, dry place away from light.

Formulations

• tablets
• oral suspension

Indications

• Thickening agent in topical formulations
• Anti-caking agent in powders
• Carrier for active pharmaceutical ingredients

Dosage

Children: Refer to specific formulation guidelines in the BNF for Children.

Adults: Refer to specific formulation guidelines in the BNF.

Mechanism of action

Aerosil exerts its effects primarily through its surface characteristics. The interaction of silica particles with biological systems can lead to cytotoxicity and cellular transformation, which are influenced by the distribution of silanol groups and the presence of trace metals such as iron. The cytotoxic effects are related to the ability of silica to generate reactive oxygen species, leading to oxidative stress in cells. The biological response to aerosil is sensitive to the composition and structural features of the silica surface, indicating that its activity is a surface-originated phenomenon.

Pharmacodynamics

The pharmacodynamic properties of aerosil are related to its ability to modify the rheological properties of formulations, improve flowability, and prevent clumping. Its cytotoxic effects at high concentrations can lead to cellular stress and transformation, although these effects are primarily of concern in occupational exposure rather than therapeutic use. The dose-response relationship can vary based on the specific type of silica and its surface modifications.

Pharmacokinetics

Aerosil is not absorbed systemically when used in pharmaceutical formulations due to its high molecular weight and physical properties. Inhalation of silica dust can lead to pulmonary exposure, where it may elicit inflammatory responses and potentially lead to silicosis over prolonged exposure. Its elimination from the body does not occur via typical metabolic pathways; instead, silica particles may be cleared from the lungs by macrophage action and mucociliary clearance mechanisms.

Indications

• Irritable bowel syndrome
• Abdominal pain
• Gastrointestinal spasm
• Functional gastrointestinal disorders

Dosage

Children: Refer to specific guidelines or consult a healthcare professional for appropriate paediatric dosing.

Adults: Refer to specific guidelines or consult a healthcare professional for appropriate adult dosing.

Mechanism of action

Glicolate works by inhibiting the action of acetylcholine on muscarinic receptors in the smooth muscle of the gastrointestinal tract. This inhibition reduces the contractions of the smooth muscle, leading to decreased motility and spasm in the intestines. It may also have some central nervous system effects, contributing to its overall antispasmodic properties.

Pharmacodynamics

The pharmacodynamics of glicolate involve its ability to modulate the autonomic nervous system, specifically through anticholinergic activity. This results in reduced peristalsis and a decrease in the frequency of contractions in the gastrointestinal tract. The drug may also reduce secretions in the digestive system, contributing to its therapeutic effects.

Pharmacokinetics

Glicolate is absorbed through the gastrointestinal tract, with peak plasma concentrations occurring within a few hours after administration. It undergoes hepatic metabolism, and its metabolites are excreted primarily via the kidneys. The half-life of glicolate can vary, but it generally suggests a dosing regimen that accommodates its duration of action.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Diarrhea
• Abdominal pain
• Headache
• Dizziness

Precautions

• Use with caution in patients with renal impairment
• Monitor liver function during treatment
• Consider potential for allergic reactions

Pregnancy

Limited data on safety in pregnancy, use only if clearly needed.

Breast-feeding

Not known if excreted in breast milk; exercise caution.

Storage

Store at room temperature, away from moisture and heat.

Indications

• Antiseptic for skin disinfection
• Solvent in pharmaceutical formulations
• Cleaning agent in laboratories and healthcare settings

Dosage

Children: For pediatric use, consult specific guidelines in the BNF for Children, as dosing may vary based on age, weight, and clinical circumstances.

Adults: For skin antisepsis, apply isopropyl alcohol topically in a concentration of 70% to the affected area. Dosage may vary based on clinical indication and setting.

Mechanism of action

Isopropyl alcohol works primarily as an antiseptic by denaturing proteins and disrupting cell membranes of bacteria, viruses, and fungi, leading to cell lysis and death. Its efficacy is enhanced by the presence of water, which facilitates the penetration of the alcohol into microbial cells.

Pharmacodynamics

Isopropyl alcohol exhibits a rapid onset of action against a variety of pathogens, including gram-positive and gram-negative bacteria, fungi, and some viruses. Its antimicrobial activity is concentration-dependent, with higher concentrations generally providing a broader spectrum of activity. It is commonly used in concentrations ranging from 60% to 90%, with 70% being optimal for disinfection due to its ability to penetrate the cell wall effectively.

Pharmacokinetics

Isopropyl alcohol is readily absorbed through the skin and mucous membranes. After absorption, it is metabolized primarily in the liver to acetone, which is then further metabolized and excreted, mostly via urine. The elimination half-life of isopropyl alcohol varies but is typically around 2 to 3 hours. Its effects can be influenced by factors such as dosage, route of exposure, and individual metabolic differences.

Pregnancy

Isopropyl alcohol should be used with caution during pregnancy. It is a category C drug, indicating that risk cannot be ruled out.

Breast-feeding

Caution is advised when using isopropyl alcohol during breastfeeding, as it is not known if it is excreted in human milk.

Storage

Isopropyl alcohol should be stored at room temperature, away from heat and flame. Keep the container tightly closed and in a well-ventilated area.

Formulations

• Isopropyl alcohol 70% solution
• Isopropyl alcohol 99% solution

Indications

• Nutritional support
• Source of carbohydrates
• Dietary fiber source
• Animal feed

Dosage

Children: As with adults, there are no specific dosing recommendations for maize for children. It can be introduced into the diet in age-appropriate forms and quantities, keeping in mind the overall dietary balance.

Adults: There are no specific dosing recommendations for maize as it is typically consumed as part of a balanced diet. It can be included in daily meals in various forms such as whole kernels, flour, or as part of dishes.

Mechanism of action

Maize primarily acts as a source of energy due to its high carbohydrate content. The complex carbohydrates in maize are broken down into glucose, which is then utilized by the body for energy production. It also contributes to dietary fiber intake, which can aid in digestive health and regulation of blood sugar levels.

Pharmacodynamics

The consumption of maize influences blood glucose and insulin levels due to its carbohydrate content. It has a relatively low glycemic index when consumed in whole form, which can help in managing blood sugar levels. The dietary fiber present in maize can also promote satiety and aid in weight management.

Pharmacokinetics

The digestion of maize begins in the mouth with salivary amylase breaking down starches into simpler sugars. In the stomach and small intestine, enzymes further break down these carbohydrates. The resultant glucose is absorbed into the bloodstream, where it is transported to cells for energy production. The absorption rate can vary based on the form of maize consumed (e.g., whole kernels versus processed forms).

Pregnancy

Maize is generally considered safe for consumption during pregnancy as it is a staple food and provides essential nutrients.

Breast-feeding

Maize is safe to consume while breastfeeding and can provide important nutrients to both the mother and the infant.

Storage

Store in a cool, dry place, away from moisture and pests. Properly sealed containers can help prolong shelf life.

Formulations

• Whole maize grains
• Maize flour (cornmeal)
• Maize starch
• Maize oil

Indications

• Ascariasis
• Partial intestinal obstruction due to Ascaris lumbricoides

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Piperazine functions as a GABA receptor agonist, selectively binding to muscle membrane GABA receptors in nematodes. This binding induces hyperpolarization of nerve endings, leading to flaccid paralysis of the worms. By blocking the response of worm muscle to acetylcholine, piperazine alters cell membrane permeability to ions, resulting in hyperpolarization and suppression of spontaneous spike potentials, thereby facilitating the expulsion of the worm through normal intestinal peristalsis.

Pharmacodynamics

Piperazine is effective as an anthelminthic, particularly for treating infections from Ascaris lumbricoides. It induces reversible muscle paralysis in nematode parasites by hyperpolarizing their cell membranes. The primary clinical use is in addressing complications such as partial intestinal obstruction caused by these worms, a condition more frequently encountered in children.

Pharmacokinetics

The pharmacokinetics of piperazine, including absorption, distribution, metabolism, and excretion, have not been well-characterized in the available literature. However, it is generally understood that piperazine is absorbed from the gastrointestinal tract and is metabolized in the liver. Further detailed studies may be required to elucidate its complete pharmacokinetic profile.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Headache
• Dizziness

Precautions

• Use with caution in patients with renal impairment
• Consider potential interactions with other central nervous system depressants

Pregnancy

Limited data are available on the safety of piperazine during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Piperazine is excreted in breast milk; use with caution and consider the need for monitoring the infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Piperazine citrate
• Piperazine hydrate

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Nutritional supplementation
• Energy source in enteral nutrition
• Excipient in pharmaceutical formulations

Dosage

Children: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Adults: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Mechanism of action

Starch is broken down into glucose units by enzymes such as amylase during digestion. The glucose is then absorbed in the intestines and utilized for energy production in the body's cells. This pathway involves hydrolysis of the glycosidic bonds, converting starch into simpler sugars.

Pharmacodynamics

Starch primarily serves as an energy source. Its digestion and absorption lead to an increase in blood glucose levels, which provides energy for metabolic processes. In this context, it plays a crucial role in maintaining energy homeostasis in the body.

Pharmacokinetics

Starch is not absorbed in its polymeric form; it must first be enzymatically hydrolyzed into simpler sugars such as maltose and glucose. The digestion and absorption of starch occur predominantly in the small intestine, with glucose being readily absorbed into the bloodstream. The rate of absorption can vary depending on the type of starch and its physical form.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

• Use with caution in individuals with known allergies to starch or starch derivatives
• Monitor for gastrointestinal symptoms in patients with a history of digestive disorders

Pregnancy

Starch is generally considered safe for use during pregnancy. However, it should be consumed in moderation as part of a balanced diet.

Breast-feeding

Starch is deemed safe for nursing mothers when used in moderation as part of a balanced diet.

Storage

Store in a cool, dry place away from moisture and direct sunlight.

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Indications

• Skin irritation prevention
• Moisture absorption
• Prevention of friction-related skin conditions
• Use in cosmetic formulations

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as talcum powder should be used cautiously in children.

Adults: Apply talcum powder as needed to the affected area, ensuring it is applied to clean, dry skin.

Mechanism of action

Talcum works primarily as an absorbent, reducing moisture and friction on the skin. Its fine particle size allows it to coat surfaces effectively, providing a smooth application that helps to prevent irritation and chafing. It does not have a pharmacological mechanism of action like traditional medications but serves a physical purpose in topical formulations.

Pharmacodynamics

Talcum's pharmacodynamics are largely related to its physical properties rather than biochemical effects. By absorbing moisture and reducing friction, talcum helps to maintain skin integrity and prevents conditions such as rashes and irritation. Its inert nature ensures that it does not provoke significant biological responses when applied topically in appropriate amounts.

Pharmacokinetics

Talcum is not absorbed systemically when applied topically. Its pharmacokinetic profile is characterized by local effects at the site of application. When used as a powder, it remains on the skin surface and acts as a barrier without entering the bloodstream. However, inhalation of talcum powder can lead to respiratory issues, as it may cause irritation in the lungs.

Pregnancy

Talcum powder should generally be avoided during pregnancy due to potential risks of inhalation and respiratory complications.

Breast-feeding

Use with caution, as talcum powder may be inhaled by the infant, posing a risk of respiratory issues.

Storage

Store in a cool, dry place, away from moisture and direct sunlight.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies. Although the exact mechanism of anthelmintic activity of mebendazole has not been fully elucidated, the drug appears to cause selective and irreversible inhibition of the uptake of glucose and other low molecular weight nutrients in susceptible helminths; inhibition of glucose uptake appears to result in endogenous depletion of glycogen stores in the helminth. Mebendazole does not inhibit glucose uptake in mammals. Mebendazole appears to cause degenerative changes in the intestine of nematodes and in the absorptive cells of cestodes. The principal anthelmintic effect of the drug appears to be degeneration of cytoplasmic microtubules within these intestinal and absorptive cells. Microtubular deterioration results in inhibition of organelle movement and interferes with the absorptive and secretory function. As a result of excessive accumulation of intracellular transport secretory granules, hydrolytic and proteolytic enzymes are released and cause cellular autolysis. This irreversible damage leads to death of the parasite. Vermicidal; may also be ovicidal for ova or most helminths; mebendazole causes degeneration of parasite's cytoplasmic microtubules and thereby selectively and irreversibly blocks glucose uptake in susceptible adult intestine-dwelling helminths and their tissue-dwelling larvae; inhibition of glucose uptake apparently results in depletion of the parasite's glycogen stores; this, in turn, results in reduced formation of adenosine triphosphate (ATP) required for survival and reproduction of the helminth; corresponding energy levels are gradually reduced until death of the parasite ensues; mebendazole does not appear to affect serum glucose concentrations in humans, however. Benzimidazoles produce many biochemical changes in susceptible nematodes, eg, inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation ... /but/ the primary action ... /should be/ to inhibit microtubule polymerization by binding to beta-tubulin. The selective toxicity of these agents derives from the fact that specific, high-affinity binding to parasite beta-tubulin occurs at much lower concn than does binding to the mammalian protein ... Benzimidazole-resistant Haemonchus contortus display reduced high-affinity drug binding to beta-tubulin and alterations in beta-tubulin isotype gene expression that correlate with drug resistance ... Two identified mechanisms of drug resistance in nematodes involve both a progressive loss of "susceptible" beta-tubulin gene isotypes together with emergence of a "resistant" isotype with a conserved point mutation that encodes a tyrosine instead of phenylalanine at position 200 of beta-tubulin. While this mutation may not be required for benzimidazole resistance in all parasites, eg, Giardia lamblia, benzimidazole resistance in parasitic nematodes is unlikely to be overcome by novel benzimidazole analogs, because tyrosine also is present at position 200 of human beta-tubulin. /Benzimidazoles/

Pharmacodynamics

Mebendazole is a (synthetic) broad-spectrum anthelmintic. The principal mode of action for Mebendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.

Mechanism of action

Although the exact mechanism of action is unknown, praziquantel was hypothesized to target the β subunits of voltage-gated Ca₂₊ channels, particularly in Schistosoma mansoni and Schistosoma japonicum, due to the lack of two conserved serine residues in these subunits. This is supported by the finding that co-administration of calcium channel blockers like nicarpidine and nifedipine renders 50% of Schistosoma mansoni resistant to praziquantel. Increased exposure of antigens on the worm surface was also observed, but little research has been done to elucidate on the mechanism of action.

Pharmacodynamics

In vitro studies on trematodes and cestodes have shown that praziquantel induces a rapid contraction of schistosomas by a specific effect on the permeability of the cell membrane. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased Ca2⁺-influx may play an important role. Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is specific to trematodes and cestodes; nematodes (including filariae) are not affected. Praziquantel is active against schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini. Published in vitro data have shown a potential lack of efficacy of praziquantel against migrating schistosomulae. An interesting quirk of praziquantel is that it is relatively ineffective against juvenile schistosomes. While initially effective, effectiveness against schistosomes decreases until it reaches a minimum at 3-4 weeks. Effectiveness then increases again until it is once again fully effective at 6-7 weeks.

Mechanism of action

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and

Mechanism of action

Piperazine is a GABA receptor agonist. Piperzine binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis. Piperazine blocks the response of the /target species/ worm muscle (best studied in Ascaris), causing flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis. The predominant effect of piperazine on /the target species/ Ascaris is to cause a flaccid paralysis that results in expulsion of the worm by peristalsis. ... Piperazine blocks the response of Ascaris muscle to acetylcholine, apparently by altering the permeability of the cell membrane to ions that are responsible for the maintenance of the resting potential. The drug causes hyperpolarization and suppression of spontaneous spike potentials with accompanying paralysis. Piperazine citrate causes reversible muscle paralysis in intestinal nematodes, presumably by causing hyperpolarization of nerve endings /in this target species/. /Piperazine citrate/ Piperazine and its salts, as a gamma-aminobutyric acid (GABA)-like substance, induce a reversible flaccid paralysis in the /target/ nematode parasites. This is provoked by a hyperpolarization of the cell membrane followed by suppression of spontaneous spike potentials. THe paralyzed nematodes are expelled from the gut lumen by normal peristaltic actions. In mammals, motorcortical GABAa inhibition is important for initiation of smooth flexion and/or extension movements of the extremities affecting motor and postural control. When injected into the hand motor cortical area of three infant macaque monkeys, the GABA agonist muscimol disrupted forelimb movement showing a posture of dropped wrist and fingers as if the radial nerve were paralysed. Interestingly, the three investigated animals exhibited large inter-individual differences in sensitivity to the action of the same dose of muscimol, being low in one, moderate in the second and substantial in the third. Injection into the medial segment of globus pallidus elicited choreiform movements and injections into substantia nigra pars reticulata provoked severe axial posture anomalies with rotational behaviour as well as contralateral hypotonia. Although the symptoms induced by piperazine in sensitive species exhibits some of these features, it is possible that its effects in mammals also involve other modes of action as well, in as much as a nicotinic action on rat sympathetic ganglia in vitro was reported in one series of experiments.

Pharmacodynamics

Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.