IODOHYDROCORT-S OINTMENT

Indications

• Adrenocortical insufficiency
• Inflammatory bowel disease
• Severe acute asthma
• Acute hypersensitivity reactions
• Congenital adrenal hyperplasia
• Replacement therapy in adrenal insufficiency

Dosage

Children: For children aged 1-5 months: Initially 25 mg 3 times a day, adjusted according to response. For children aged 6 months-5 years: Initially 50 mg 3 times a day, adjusted according to response. For children aged 6-11 years: Initially 100 mg 3 times a day, adjusted

Adults: 100-500 mg 3-4 times a day or when required. For replacement in adrenocortical insufficiency, 20-30 mg once daily, adjusted according to response.

Mechanism of action

Hydrocortisone binds to the glucocorticoid receptor, leading to decreased vasodilation and permeability of capillaries, inhibition of leukocyte migration to inflammation sites, and changes in gene expression that promote anti-inflammatory pathways. It inhibits phospholipase A2, NF-kappa B, and other inflammatory transcription factors, stabilizing leukocyte lysosomal membranes and reducing the release of destructive enzymes. High doses can raise sodium levels and decrease potassium levels through mineralocorticoid receptor activity.

Pharmacodynamics

Hydrocortisone's pharmacodynamic profile includes the inhibition of various inflammatory mediators and the promotion of anti-inflammatory cytokines. Its effects are dose-dependent, with lower doses providing anti-inflammatory benefits, while higher doses exhibit immunosuppressive effects. It has a wide therapeutic index and moderate duration of action.

Pharmacokinetics

Hydrocortisone is metabolized primarily in the liver, with its effects lasting for several hours to days. The onset of action varies with the route of administration, being more rapid when given intravenously. Its half-life is influenced by factors such as dose and administration route, and it is excreted through urine as metabolites.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to hydrocortisone or any excipients

Adverse effects

• Increased risk of infections
• Hyperglycemia
• Hypertension
• Fluid retention and edema
• Gastrointestinal disturbances
• Mood changes
• Osteoporosis
• Peptic ulcer disease
• Cushing's syndrome with long-term use

Interactions

• Mitotane: Moderate decrease in hydrocortisone exposure
• Rifampicin: Moderate decrease in hydrocortisone exposure
• Cobicistat: Unknown effect, potential increase in hydrocortisone exposure
• Idelalisib: Unknown effect, potential increase in hydrocortisone exposure
• Clarithromycin: Unknown effect, potential increase in hydrocortisone exposure

Precautions

• Use with caution in patients with diabetes
• Monitor for signs of infection during therapy
• Consider dose adjustment in patients with hepatic impairment
• Gradual withdrawal is recommended to avoid adrenal insufficiency after prolonged therapy

Pregnancy

Hydrocortisone is categorized as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydrocortisone is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Injectable form (sodium succinate)
• Modified-release tablets
• Immediate-release tablets

Indications

• Herpes simplex virus infections
• Genital herpes
• Herpes zoster (shingles)
• Varicella (chickenpox)
• Prophylaxis in immunocompromised patients

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines based on the child's age, weight, and the condition being treated.

Adults: Refer to the BNF for specific dosing recommendations, as it may vary based on the condition being treated and the patient's renal function.

Mechanism of action

Acyclovir is converted to acyclovir monophosphate by the action of viral thymidine kinase. It is then phosphorylated to the diphosphate form by guanylate kinase and further to triphosphate by several cellular enzymes. Acyclovir triphosphate has a higher affinity for viral DNA polymerase than for cellular DNA polymerase, leading to DNA chain termination or inactivation of the viral enzyme, thus inhibiting viral DNA replication.

Pharmacodynamics

Acyclovir acts as a deoxynucleoside analog that selectively inhibits the action of viral DNA polymerase, preventing the replication of herpesviral DNA. It has a wide therapeutic window, and overdose is considered rare in otherwise healthy individuals.

Pharmacokinetics

Acyclovir is absorbed through the gastrointestinal tract and is widely distributed in body tissues and fluids. It undergoes renal excretion, primarily as unchanged drug, with a half-life of about 2.5 to 3 hours in patients with normal renal function. Its bioavailability is approximately 15-30%, and it is primarily eliminated via glomerular filtration and tubular secretion.

Interactions

• aciclovir+aminophylline: Moderate (increases exposure)
• aciclovir+theophylline: Moderate (increases exposure)
• aciclovir+livevaccines: Unknown (decreases efficacy)
• aciclovir+herpes-zostervaccine: Unknown (decreases efficacy)
• aciclovir+live: Unknown (decreases efficacy)
• mycophenolate+aciclovir: Unknown (increases risk of haematological toxicity)

Pregnancy

Acyclovir is classified as a category B drug for use during pregnancy. It should be used when the potential benefits outweigh the risks.

Breast-feeding

Acyclovir is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension
• Injection

Indications

• Bacterial skin infections
• Fungal skin infections
• Topical antiseptic for minor cuts and abrasions

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in paediatric patients.

Adults: For topical use, apply clioquinol to the affected area as directed by a healthcare professional. Refer to specific prescribing information for detailed dosage instructions.

Mechanism of action

Clioquinol is bacteriostatic, however, the precise mechanism of its action is unknown.

Pharmacodynamics

Clioquinol exhibits broad-spectrum antibacterial and antifungal properties. Its application to extensive or eroded areas of the skin can lead to increased protein-bound iodine (PBI) levels within 1 week. Continued treatment on smaller areas beyond 1 week may also result in elevated PBI levels.

Pharmacokinetics

The pharmacokinetics of clioquinol are not extensively characterized; however, it is generally absorbed through the skin when applied topically. Systemic absorption may lead to elevated iodine levels in the body, particularly with prolonged use.

Contra-indications

• Hypersensitivity to clioquinol or any of its components
• History of subacute myelo-optic neuropathy
• Thyroid disease or dysfunction

Adverse effects

• Skin irritation
• Allergic contact dermatitis
• Nausea
• Vomiting
• Diarrhea
• Thyroid dysfunction
• Peripheral neuropathy

Interactions

• May interact with medications affecting thyroid function
• Increased risk of adverse effects if used with other neurotoxic agents

Precautions

• Use with caution in patients with impaired thyroid function
• Monitor thyroid function during prolonged use
• Avoid application to large areas of broken skin

Pregnancy

Clioquinol should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus, as safety has not been established.

Breast-feeding

Clioquinol should be used with caution during breastfeeding, as it is unknown if it is excreted in human milk.

Storage

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

Formulations

• Topical ointment
• Topical cream

Indications

• Acne vulgaris
• Psoriasis
• Warts
• Seborrheic dermatitis
• Dandruff
• Hyperkeratosis

Dosage

Adults: For topical application, salicylic acid is typically applied once or twice daily, depending on the formulation and condition being treated. Specific dosing guidelines should be followed as per the BNF.

Mechanism of action

Salicylic acid exerts its effects by penetrating the skin and exfoliating the stratum corneum through keratolytic action, which helps in the dissolution of keratin and the removal of dead skin cells. This action facilitates the clearance of pores and can reduce acne lesions. Additionally, salicylic acid has anti-inflammatory properties that can help to decrease swelling and redness associated with various skin conditions. The compound is also known to inhibit the activity of enzymes involved in the synthesis of prostaglandins, which are mediators of inflammation.

Pharmacodynamics

The pharmacodynamics of salicylic acid involve its ability to enhance the turnover of skin cells and reduce the cohesiveness of keratinocytes in the stratum corneum. This leads to increased desquamation and a reduction in the formation of microcomedones in acne. Its anti-inflammatory effects are mediated through the inhibition of cyclooxygenase enzymes, leading to decreased production of pro-inflammatory mediators. This contributes to the reduction of inflammation and pain in affected areas.

Pharmacokinetics

Salicylic acid is absorbed percutaneously when applied topically, with systemic absorption increasing with higher concentrations and prolonged application. Once absorbed, it is metabolized predominantly in the liver to various conjugates, which are then excreted by the kidneys. The elimination half-life can vary based on the formulation and concentration used. For topical applications, significant first-pass metabolism may occur, limiting systemic exposure and reducing potential systemic side effects.

Pregnancy

Salicylic acid is classified as pregnancy category C. Its use should be avoided during pregnancy unless the potential benefits outweigh the risks.

Breast-feeding

Salicylic acid is excreted in breast milk, and caution is advised when using it during breastfeeding.

Storage

Store in a cool, dry place away from direct light.

Mechanism of action

The short-term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis. /Corticosteroids/ Reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. Plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels /were investigated/. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.

Pharmacodynamics

Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

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

Clioquinol is bacteriostatic, however, the precise mechanism of its action is unknown.

Pharmacodynamics

Clioquinol is a broad-spectrum antibacterial with antifungal properties. Application of clioquinol to extensive or eroded areas of the skin may lead to increased protein-bound iodine (PBI) levels within 1 week. In addition, elevated PBI levels may occur when relatively small areas of the skin are treated with clioquinol for more than 1 week.