Medovir

Indications

• Chronic constipation
• Portal-systemic encephalopathy

Dosage

Children: Child 1-11 months: 2.5 mL twice daily, adjusted according to response. Child 1-4 years: 5 mL twice daily, adjusted according to response. Child 5-10 years: 10 mL twice daily, adjusted according to response. Child 5-17 years: 5-20 mL twice daily, adjusted according

Adults: Initially 15 mL twice daily, adjusted according to response. For hepatic encephalopathy, doses can be 30-50 mL three times a day, adjusted to produce 2-3 soft stools per day.

Mechanism of action

Lactulose is broken down by saccharolytic bacteria in the large intestine into organic acids, such as lactic acid, which increases intraluminal gas formation and enhances peristaltic gut motility. This osmotic effect increases water content in stool, facilitating bowel movements. Additionally, it acidifies the colonic contents, helping to treat portal-systemic encephalopathy by promoting the conversion of ammonia to ammonium ions, which are less absorbable.

Pharmacodynamics

Lactulose has minimal systemic absorption, exerting its effects predominantly within the gastrointestinal tract. It enhances stool volume and softens stool, which may lead to increased bowel sounds, feelings of bloating, belching, flatus, and diarrhea. These effects contribute to its laxative properties and its role in treating hepatic encephalopathy.

Pharmacokinetics

Lactulose is poorly absorbed from the gastrointestinal tract and exerts its action locally. It typically takes 24 to 48 hours to manifest its laxative effect. The substance is not metabolized before reaching the colon, where it is fermented by gut bacteria, resulting in the production of short-chain fatty acids and gases.

Contra-indications

• Galactosaemia
• Gastrointestinal obstruction
• Gastrointestinal perforation
• Risk of gastrointestinal perforation
• Lactose intolerance

Adverse effects

• Diarrhoea
• Gastrointestinal discomfort
• Nausea
• Abdominal pain
• Flatulence
• Vomiting
• Electrolyte imbalance

Precautions

• Caution in patients with a history of gastrointestinal disorders
• Monitor for electrolyte imbalance in prolonged use

Pregnancy

Not known to be harmful, but manufacturer advises to avoid.

Breast-feeding

Manufacturer advises to avoid.

Storage

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

Formulations

• Lactulose 10g/15ml oral solution
• Lactulose 680 mg per 1 ml
• Lactulose granules

Indications

• Herpes simplex virus infections (HSV-1 and HSV-2)
• Varicella-zoster virus infections (shingles and chickenpox)
• Prevention of herpes virus infections in immunocompromised patients

Dosage

Children: Refer to BNF for Children for appropriate dosing information, as paediatric doses vary based on age, weight, and specific indication.

Adults: For the treatment of herpes simplex infections, the typical adult dose may be 200 mg taken five times daily for 5 days. In cases of severe infections, intravenous acyclovir may be administered at a dose of 5-10 mg/kg every 8 hours, adjusted based on renal function.

Mechanism of action

Acyclovir is phosphorylated by viral thymidine kinase to form acyclovir monophosphate, which is then converted to acyclovir diphosphate and subsequently to acyclovir triphosphate by various cellular enzymes. Acyclovir triphosphate exhibits a higher affinity for viral DNA polymerase than for cellular DNA polymerase, allowing it to incorporate into viral DNA and cause chain termination or competitive inhibition of the enzyme, thus halting viral replication.

Pharmacodynamics

As a deoxynucleoside analog, acyclovir inhibits viral DNA polymerase, preventing the replication of herpesviruses. Its selectivity for viral over cellular enzymes contributes to its therapeutic efficacy and safety profile, offering a wide therapeutic window with a lower risk of overdose in healthy individuals.

Pharmacokinetics

Acyclovir is absorbed orally with variable bioavailability. It is widely distributed in body tissues and fluids, including the central nervous system. The drug is primarily eliminated by renal excretion, with a half-life of approximately 2.5 to 3 hours in patients with normal renal function. Dosage adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to acyclovir or any component of the formulation

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Fatigue
• Renal toxicity
• Neurotoxicity (e.g., tremors, confusion)

Interactions

• Probenecid may decrease renal clearance of acyclovir, increasing its plasma concentration
• Zidovudine may increase the risk of hematologic toxicity when used with acyclovir

Precautions

• Renal impairment may require dosage adjustment
• Caution in patients with dehydration or renal dysfunction to prevent nephrotoxicity
• Monitor for neurological side effects, particularly in cases of rapid infusion

Pregnancy

Acyclovir is classified as a category B drug. Animal studies have not shown any harm to the fetus, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Acyclovir is excreted in breast milk, but the amounts are generally considered to be low. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Acyclovir 200 mg tablets
• Acyclovir 400 mg tablets
• Acyclovir 800 mg tablets
• Acyclovir 5 mg/ml powder for injection
• Acyclovir 5% cream for topical use

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Powder
• Granules

Indications

• Used as a binder in tablet formulations
• Serves as a disintegrant to improve drug release
• Acts as a thickening agent in liquid formulations
• Enhances bioavailability of poorly soluble drugs

Dosage

Children: Dosage is dependent on the specific formulation and intended use. Refer to formulation guidelines for appropriate concentrations.

Adults: Dosage is dependent on the specific formulation and intended use. Refer to formulation guidelines for appropriate concentrations.

Mechanism of action

Pregelatinised starch acts primarily as a thickening agent and binder in pharmaceutical formulations. When mixed with water, it swells and forms a gel-like consistency, which helps in the uniform distribution of active ingredients and enhances their release and absorption in the gastrointestinal tract. Its ability to gel enables better disintegration of tablets upon administration, facilitating the dissolution of the drug.

Pharmacodynamics

The pharmacodynamics of pregelatinised starch is closely related to its physical properties as a polymer. Upon contact with water, it hydrates and expands, creating a viscous solution that can improve the release profile of drugs. This can lead to enhanced dissolution rates of poorly soluble compounds, improving their bioavailability. Additionally, it can impact the stability and shelf-life of formulations by providing a protective matrix for active ingredients.

Pharmacokinetics

Pregelatinised starch is not absorbed systemically as it primarily acts as an excipient. It undergoes gastrointestinal transit without significant degradation. Its function is to facilitate the release and absorption of the active pharmaceutical ingredients in the formulation rather than exhibiting pharmacokinetic properties of its own.

Pregnancy

Pregelatinised starch is generally considered safe for use during pregnancy, but it is recommended to consult a healthcare provider before use.

Breast-feeding

Pregelatinised starch is considered safe during breastfeeding, but it is advisable to seek medical advice.

Storage

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

Formulations

• Powder
• Capsules
• Tablets

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

Mechanism of action

Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate has higher affinity for viral DNA polymerase than cellular DNA polymerase and incorporates into the DNA where the missing 2' and 3' carbons causes DNA chain termination. In other cases acyclovir triphosphate competes so strongly for viral DNA polymerase that other bases cannot associate with the enzyme, inactivating it. Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of acyclovir is highly selective due to is affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase adn into triphosphate by a number of cellualr enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. Acyclovir inhibits viral DNA synthesis ... . Its selectivity of action depends on interaction with two distinct viral proteins. Cellular uptake and initial phosphorylation are facilitated by HSV thymidine kinase. The affinity of acyclovir for HSV thymidine kinase is about 200-fold greater than for the mammalian enzyme. Cellular enzymes convert the monophosphate to acyclovir triphosphate, which is present in 40- to 100-fold higher concentrations in HSV-infected than in uninfected cells, and competes for endogenous deoxyguanosine triphosphate (dGTP). The immunosuppressive agent mycophenolate mofetil potentiates the antiherpes activity of acyclovir and related agents by depleting intracellular dGTP pools. Acyclovir triphosphate competitively inhibits viral DNA polymerases and, to a much smaller extent, cellular DNA polymerases. Acyclovir triphosphate also is incorporated into viral DNA, where it acts as a chain terminator because of the lack of 3'-hydroxyl group. By a mechanism termed suicide inactivation, the terminated DNA template containing acyclovir binds the enzyme and leads to irreversible inactivation of the DNA polymerase. The concentration of the endogenous neurotoxin quinolinic acid (QA) is increased in the central nervous system of mice with herpes simplex encephalitis. /The authors/ have previously shown that the antiherpetic agent acyclovir (AC) has the ability to reduce QA-induced neuronal damage in rat brain, by attenuating lipid peroxidation. The mechanism by which QA induces lipid peroxidation includes the enhancement of the iron (Fe)-mediated Fenton reaction and the generation of free radicals, such as the superoxide anion (O(2)(-)). Thus, the present study determined whether AC has the ability to reduce Fe(2+)-induced lipid peroxidation, O(2)(-) generation and QA-induced superoxide anion generation, and to bind free Fe. O(2)(-) and Fe(2+) are also cofactors of the enzymes, indoleamine-2,3-dioxygenase (IDO) and 3-hydroxyanthranilate-3,4-dioxygenase (3-HAO) respectively. These enzymes catalyse steps in the biosynthesis of QA; thus, the effect of AC on their activity was also investigated. AC significantly attenuates Fe(2+)-induced lipid peroxidation and O(2)(-) generation. AC reduces O(2)(-) generation in the presence of QA and strongly binds Fe(2+) and Fe(3+). It also reduces the activity of both IDO and 3-HAO, which could be attributed to the superoxide anion scavenging and iron binding properties, respectively, of this drug.

Pharmacodynamics

Acyclovir is a deoxynucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpesvirus. Acyclovir has a wide therapeutic window as overdose is rare in otherwise healthy patients.

Mechanism of action

Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose. Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids. Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening. All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take 24 to 48 hours after using the medication for this laxative effect to become evident. At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE). As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood. These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia. And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.

Pharmacodynamics

Lactulose formulations are most commonly administered via the oral route or the rectal route. Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut. In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.