BONSITY

Indications

• Cerebral edema
• Elevated intracranial pressure
• Acute kidney injury
• Oliguria
• Glaucoma
• Renal function diagnostic aid

Dosage

Adults: For cerebral edema, administer 0

Mechanism of action

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. This action reduces cerebral edema and intracranial pressure. As a diuretic, it increases the osmolality of glomerular filtrate, leading to increased urinary excretion of water and preventing sodium and chloride reabsorption in the renal tubules. Mannitol also facilitates the urinary excretion of toxic substances and can help in assessing renal function by measuring glomerular filtration rate (GFR).

Pharmacodynamics

Mannitol is classified as an osmotic diuretic. It is chemically similar to other sugar alcohols but has a unique ability to promote diuresis by remaining unabsorbed in the renal tubules. Its use is indicated for conditions associated with increased body fluids, such as cerebral edema and glaucoma. Mannitol may be combined with other diuretics to enhance diuretic efficacy. Inhaled formulations are used in cystic fibrosis, though they may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption, which allows for its urinary excretion rate to serve as a measurement of GFR. It does not undergo significant metabolism and is eliminated primarily through the kidneys. The onset of action occurs within 30 to 60 minutes after intravenous administration, with effects lasting for several hours. Administration may require monitoring of renal function and fluid balance.

Contra-indications

• Anuria
• Severe dehydration
• Severe renal impairment
• Intracranial bleeding

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Dry mouth
• Confusion
• Visual impairment
• Hypotension
• Electrolyte imbalances
• Pulmonary edema
• Hemoptysis (with inhalation use)
• Bronchospasm (with inhalation use)

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Other diuretics may have additive effects
• Caution with nephrotoxic agents

Precautions

• Caution in patients with diabetes mellitus
• Caution in the elderly
• Caution in patients with gout
• Caution in patients with hepatic impairment
• Monitor renal function and electrolytes regularly
• May cause blue fluorescence of urine

Pregnancy

Manufacturer advises avoid due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoid due to lack of information available.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Solution for injection
• Inhalation powder
• Oral solution

Indications

• Osteoporosis in postmenopausal women
• Osteoporosis in men at high risk of fracture
• Glucocorticoid-induced osteoporosis

Dosage

Children: Not established; refer to the BNF for Children for specific guidance

Adults: The recommended dosage for adults is 20 micrograms administered subcutaneously once daily.

Mechanism of action

Teriparatide acts by binding to the PTH type 1 receptors (PTH1R) on osteoblasts, which are bone-forming cells. This interaction activates downstream signaling pathways (PKA and PKC) that promote osteoblastic activity, leading to increased new bone formation. Unlike continuous exposure to PTH, which can lead to bone resorption, the intermittent dosing of teriparatide promotes net bone gain, enhancing both trabecular and cortical bone through stimulation of osteoblastic activity over osteoclastic activity.

Pharmacodynamics

As a PTH analog, teriparatide stimulates bone formation and increases markers of bone turnover. It has been shown to increase bone mineral density (BMD) and reduce the risk of vertebral and non-vertebral fractures. Teriparatide also influences calcium and phosphate metabolism, causing transient increases in serum calcium and urinary calcium excretion, as well as mild reductions in serum phosphorus levels. Its anabolic effects on bone contribute significantly to improved skeletal strength.

Pharmacokinetics

Teriparatide is administered via subcutaneous injection, with peak plasma concentrations typically occurring within 30 minutes post-injection. The elimination half-life is approximately 1 hour, and it is primarily metabolized by the liver. Teriparatide's pharmacokinetic profile allows for once-daily dosing, which is essential for its efficacy in stimulating bone formation. Renal function can impact teriparatide clearance, and caution is advised in patients with significant renal impairment.

Contra-indications

• Hypersensitivity to teriparatide or any of its excipients
• Uncontrolled hypercalcemia
• Pregnancy
• Severe renal impairment (creatinine clearance less than 30 mL/min)
• History of osteosarcoma or other skeletal malignancies

Adverse effects

• Nausea
• Dizziness
• Headache
• Muscle cramps
• Arthralgia
• Palpitations
• Fatigue
• Hypercalcemia
• Peripheral edema
• Constipation
• Diarrhea
• Vomiting
• Insomnia
• Anxiety
• Rare allergic reactions such as angioedema and urticaria

Interactions

• Strontium ranelate - avoid concurrent use
• Diuretics - may increase the risk of hypercalcemia
• Thiazide diuretics - may increase calcium levels
• Other medications affecting calcium metabolism

Precautions

• Caution in patients with cardiovascular disease, cerebrovascular disease or peripheral arterial disease
• Monitor for signs of hypercalcemia
• Caution in patients with renal impairment
• Consider monitoring for osteosarcoma in patients with Paget's disease or prior radiation therapy

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential toxicity as indicated by animal studies.

Breast-feeding

Manufacturer advises to avoid use during breastfeeding due to the presence of teriparatide in human milk.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light. After first use, the solution can be stored at room temperature for up to 28 days.

Formulations

• Teriparatide 250 micrograms per 1 mL solution for injection in a pre-filled disposable pen
• Teriparatide 20 micrograms/80 microlitres solution for injection in a pre-filled cartridge

Indications

• Infections (topical treatment)
• Wound care (as an antiseptic)
• Ear infections (as an ear drop solution)
• Acid-base balance in metabolic acidosis

Dosage

Children: Refer to established guidelines as dosage may vary based on the formulation and indication.

Adults: Refer to established guidelines as dosage may vary based on the formulation and indication.

Mechanism of action

Acetic acid exerts its effects primarily through its ability to lower pH levels, creating an acidic environment which is inhospitable to many pathogens. It can disrupt the integrity of microbial cell membranes, leading to cell lysis and death. Additionally, acetic acid can promote the healing of wounds and enhance the absorption of certain medications when used as a solvent.

Pharmacodynamics

The pharmacodynamics of acetic acid involve its interaction with biological systems, leading to changes in cellular functions. Its acidic nature helps in the denaturation of proteins and disruption of microbial metabolism. This contributes to its antibacterial and antifungal activities, making it effective against a range of pathogens.

Pharmacokinetics

Acetic acid is rapidly absorbed in the gastrointestinal tract when ingested. It is metabolized primarily in the liver, converting to acetyl CoA and subsequently entering various metabolic pathways including the citric acid cycle. The elimination half-life varies but is generally short, with excretion occurring mainly via urine. When applied topically, absorption is minimal, and local effects are predominant.

Pregnancy

The safety of acetic acid during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is no specific information available regarding the use of acetic acid during breastfeeding. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Keep tightly closed in a well-ventilated area.

Indications

• Topical treatment of localized infections
• Antiseptic for skin and mucous membrane applications
• Astringent in certain dermatological conditions

Dosage

Children: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Adults: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Mechanism of action

Glacial acetic acid exerts its effects primarily through its acidic properties, leading to protein denaturation and cell lysis in microbial cells. This action disrupts cellular integrity, promoting the death of bacteria and fungi. Additionally, it can alter the pH of tissues, which may contribute to its antiseptic effects.

Pharmacodynamics

The pharmacodynamic effects of glacial acetic acid are largely attributed to its ability to lower the pH in the local environment, which can inhibit the growth of certain pathogens. Its astringent properties help to reduce secretions and promote tissue contraction, which can be beneficial in managing conditions that involve inflammation or excessive exudation.

Pharmacokinetics

Glacial acetic acid is absorbed through the skin and mucous membranes when applied topically. Once absorbed, it can be metabolized by the liver, with elimination primarily occurring through urine. The exact pharmacokinetic parameters can vary based on the route of administration and the formulation used, but detailed data on half-life and volume of distribution are not well-characterized in standard references.

Pregnancy

Glacial acetic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as a category C drug.

Breast-feeding

It is not known whether glacial acetic acid is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a tightly closed container, in a cool, dry place away from incompatible substances.

Indications

• Adjustment of pH in pharmaceutical formulations
• Facilitation of drug absorption
• Used in sterile preparations

Dosage

Children: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Adults: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Mechanism of action

Hydrochloric acid dissociates in aqueous solution to release hydrogen ions (H+), leading to a decrease in pH. This acidic environment promotes the activation of pepsinogen to pepsin, an enzyme essential for protein digestion. Additionally, the acidity aids in the absorption of certain minerals and drugs that require an acidic environment for optimal bioavailability.

Pharmacodynamics

The primary pharmacodynamic action of hydrochloric acid is the maintenance of gastric acidity, which is essential for normal digestive processes. The acidic environment helps in denaturing proteins, activating digestive enzymes, and providing a barrier against pathogenic microorganisms. Its effects can influence the absorption and efficacy of various medications, particularly those that are pH-dependent.

Pharmacokinetics

Hydrochloric acid does not undergo significant systemic absorption when used in its normal contexts, as it acts locally within the gastrointestinal tract. The amount of hydrochloric acid produced by the stomach varies with food intake and physiological needs. It is secreted by parietal cells in the gastric mucosa, and its secretion is regulated by neural, hormonal, and local factors. The half-life of hydrochloric acid is not applicable as it is continuously produced and neutralized within the gastrointestinal tract.

Contra-indications

• Hypersensitivity to hydrochloric acid or any of its components
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Esophageal irritation
• Gastric mucosal irritation
• Electrolyte imbalances

Interactions

• May interact with alkaline substances, potentially neutralizing hydrochloric acid
• Caution with antacids as they may affect the efficacy of hydrochloric acid

Precautions

• Use with caution in patients with a history of gastritis or gastric ulcers
• Monitor electrolytes in prolonged use
• Use cautiously in patients with respiratory conditions due to potential aspiration risks

Pregnancy

Hydrochloric acid is classified as a category C drug. Use during pregnancy only if clearly needed and the potential benefits justify the risks to the fetus.

Breast-feeding

There is limited data on the excretion of hydrochloric acid in human milk. Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and heat. Ensure the container is tightly closed.

Formulations

• Oral solutions
• Injectable forms
• Tablets

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Disinfection of skin and mucous membranes
• Preservative in pharmaceutical formulations
• Antiseptic in medical and veterinary applications

Dosage

Children: Refer to BNF for Children for specific dosing recommendations tailored to paediatric patients.

Adults: Refer to BNF for specific dosing guidelines based on the formulation and condition being treated.

Mechanism of action

Metacresol exhibits antimicrobial activity by disrupting the cell membrane of bacteria, leading to cell lysis and death. Its effectiveness is attributed to its ability to denature proteins and dissolve lipid membranes, which is critical for maintaining the integrity of bacterial cells.

Pharmacodynamics

The pharmacodynamic effects of metacresol are primarily related to its antiseptic and disinfectant properties. It is effective against a wide range of pathogens, including bacteria, fungi, and some viruses. The concentration and exposure time are key factors that influence its efficacy, with higher concentrations generally leading to increased antimicrobial activity.

Pharmacokinetics

Metacresol is absorbed through the skin and mucous membranes, and its systemic absorption can vary based on the route of administration. It is metabolized primarily in the liver and excreted in the urine. The half-life and excretion rates can vary significantly based on individual factors such as age and liver function. Precautions should be taken to minimize exposure due to its potential toxicity.

Pregnancy

There is limited data on the use of metacresol in pregnancy. It is advisable to avoid use unless the potential benefits outweigh the risks.

Breast-feeding

Caution is advised when using metacresol during breastfeeding, as the effects on the nursing infant are not well studied.

Storage

Store in a tightly sealed container at room temperature, away from light and moisture.

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Mechanism of action

Parathyroid hormone (PTH) is an endogenous hormone that regulates calcium and phosphate metabolism in bone and kidney. It regulates bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. It mediates its physiological actions by binding to the PTH receptors. Excess PTH - such as in certain disease states like hyperparathyroidism - can cause increased osteoclast activity and accelerated bone resorption. Interestingly, the effects of PTH depend on the dose and pattern of exposure of PTH to the bone. Continuous exposure to PTH promotes bone resorption, whereas intermittent exposure to low-dose PTH can induce bone formation more favourably than bone resorption. Similarly, teriparatide's skeletal effects depend upon the systemic exposure pattern. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. Teriparatide mediates its osteoanabolic actions by binding to the N-terminal moiety to PTH type 1 receptors (PTH type 1R), which are G-protein coupled receptors expressed on various cells, including osteoblasts, osteocytes, and renal tubular cells. Binding of teriparatide to PTH receptors on osteoblasts activates the downstream PKA- and PKC-dependent signaling pathways that promotes anabolic effects on bone. For example, teriparatide increases expression of pro-osteoclastogenic cytokines like receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. It also upregulates transcriptional expression of pro-osteoblastogenic growth factors like insulin-like growth factor 1 (IGF1) and fibroblast growth factor 2 (FGF2). Teriparatide also downregulates the synthesis of sclerostin, which is a negative regulator of bone formation. It also promotes the differentiation of osteoblasts. The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide are manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation. Endogenous 84-amino-acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

Pharmacodynamics

Teriparatide is a PTH analog that works to stimulate bone formation in both men and women. It increases skeletal mass, increases markers of bone formation such as bone-specific alkaline phosphatase (BSAP) and procollagen I carboxy-terminal propeptide (PICP), and increases bone strength. Like endogenous PTH, teriparatide affects calcium and phosphate homeostasis. It causes a transient increase in serum calcium levels and increases urinary calcium excretion. In clinical trials, it also produced transient phosphaturia and mild transient reductions in serum phosphorus concentration.