CORENZA-C COMBINATION PRODUCT EFFERVESCENT TABLET

Indications

• Nasal congestion
• Hypotension (particularly in acute settings)
• Vasopressor support during anesthesia

Dosage

Children: Refer to the BNF for Children for specific dosing information, as it varies based on age and indication.

Adults: For the treatment of hypotension, the recommended initial dose is 0.16–0.33 mL/minute as an intravenous infusion, adjusted according to blood pressure response. For nasal congestion, 0.25 to 0.5 mL of the 0.5% solution may be applied topically.

Mechanism of action

Phenylephrine primarily acts as a selective agonist for α1-adrenergic receptors. Activation of these receptors results in vasoconstriction of blood vessels, leading to increased systemic vascular resistance and blood pressure. It does not significantly stimulate β-adrenergic receptors, which makes it less effective at increasing heart rate compared to other sympathomimetics.

Pharmacodynamics

Phenylephrine's pharmacodynamic effects include increased peripheral vascular resistance and blood pressure due to its vasoconstrictive action. Its decongestant effects arise from vasoconstriction of nasal mucosal blood vessels, reducing swelling and congestion. The duration of action is dose-dependent and can vary based on the route of administration.

Pharmacokinetics

Phenylephrine is absorbed after oral administration but has a significant first-pass metabolism, which reduces its bioavailability. It is metabolized primarily in the liver and has a half-life of about 2.5 to 3 hours. The drug is excreted in urine, primarily as metabolites. The onset of action varies with the route of administration, with intravenous administration providing the most rapid effect.

Adverse effects

• Hypertension
• Reflex bradycardia
• Headache
• Nausea
• Vomiting
• Palpitations

Precautions

• Use with caution in patients with hypertension
• Monitor blood pressure frequently
• Use during pregnancy only if potential benefit outweighs risk

Pregnancy

Manufacturer advises use if potential benefit outweighs risk-may reduce placental perfusion and induce fetal bradycardia.

Storage

Store at room temperature, protect from light.

Formulations

• Phenylephrine hydrochloride 2.5mg tablets
• Phenylephrine hydrochloride 5mg tablets
• Phenylephrine hydrochloride 10mg tablets
• Phenylephrine hydrochloride solution for injection

Indications

• Vitamin C deficiency
• Scurvy
• Adjunct therapy in iron overload conditions

Dosage

Children: Child 1 month–3 years: 125–250 mg daily in 1–2 divided doses; Child 4–11 years: 250–500 mg daily in 1–2 divided doses; Child 12–17 years: 0.5–1 g daily in 1–2 divided doses.

Adults: 500 mg daily, taken in 1-2 divided doses, depending on the clinical condition and dietary needs.

Mechanism of action

Ascorbic acid functions primarily as a reducing agent, facilitating enzymatic reactions in the body, including the hydroxylation of proline and lysine in collagen synthesis. It also plays a role in the absorption of iron from the gastrointestinal tract and enhances the immune response.

Pharmacodynamics

Ascorbic acid is crucial for the maintenance of connective tissue and is involved in the metabolism of several amino acids. Its antioxidant properties help to mitigate oxidative stress and may play a role in reducing the risk of chronic diseases.

Pharmacokinetics

Ascorbic acid is absorbed in the intestines and is widely distributed throughout the body. The renal clearance of ascorbic acid is dose-dependent, with higher doses leading to increased excretion. The half-life varies but is generally around 15 to 30 minutes in healthy individuals, with tissue saturation levels influencing its retention.

Contra-indications

• Hypercalcaemia
• Hyperoxaluria
• Patients with cardiac dysfunction

Adverse effects

• Abdominal pain
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Weight loss
• Polyuria
• Sweating
• Thirst
• Vertigo

Interactions

• Increases risk of cardiovascular adverse effects with iron chelators
• Increases risk of cardiovascular adverse effects with deferiprone
• Increases risk of cardiovascular adverse effects with desferrioxamine

Precautions

• Use with caution in patients with iron overload
• Monitor for symptoms of overdose

Pregnancy

High doses teratogenic in animals but therapeutic doses unlikely to be harmful.

Storage

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

Formulations

• Ascorbic acid 50 mg tablets
• Ascorbic acid 100 mg tablets
• Ascorbic acid 200 mg tablets
• Ascorbic acid 250 mg tablets
• Ascorbic acid 500 mg capsules

Indications

• Mild to moderate pain relief
• Fever reduction
• Management of inflammatory conditions such as rheumatoid arthritis and osteoarthritis
• Prevention of cardiovascular events in patients with a history of myocardial infarction or stroke
• Management of acute coronary syndrome

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as this may differ significantly from adult dosing.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on the indication and patient factors.

Mechanism of action

Aspirin works primarily by irreversibly inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, leading to a decrease in the synthesis of prostaglandins and thromboxanes. This results in reduced inflammation, pain, and fever. The inhibition of COX-1 also reduces platelet aggregation by decreasing thromboxane A2 production, which is crucial for platelet activation and aggregation.

Pharmacodynamics

The analgesic effects of aspirin are attributed to its ability to inhibit the generation of prostaglandins, which mediate pain and inflammation. In addition to its pain-relieving and anti-inflammatory effects, aspirin's antiplatelet action is significant in the context of cardiovascular health, as it reduces the risk of thrombus formation in blood vessels.

Pharmacokinetics

Aspirin is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. It is extensively metabolized in the liver, primarily via hydrolysis to salicylic acid, which has its own therapeutic effects. The elimination half-life varies depending on the dose, ranging from 15 to 20 minutes for aspirin and several hours for salicylic acid. Aspirin and its metabolites are excreted primarily in the urine.

Contra-indications

• Active gastrointestinal bleeding
• History of peptic ulcer disease
• Severe renal impairment
• Severe hepatic impairment
• Hypersensitivity to acetylsalicylic acid or other NSAIDs
• Children and teenagers with viral infections (risk of Reye's syndrome)

Adverse effects

• Gastrointestinal irritation and bleeding
• Nausea and vomiting
• Dyspepsia
• Allergic reactions such as rash or asthma exacerbation
• Tinnitus (ringing in the ears)
• Renal impairment
• Hepatic dysfunction

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs or anticoagulants
• Enhanced effects of anticoagulants (e.g., warfarin, heparin)
• Reduced effectiveness of antihypertensive drugs (e.g., ACE inhibitors)
• Increased risk of renal impairment with diuretics
• Potential interaction with methotrexate, leading to increased toxicity

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in long-term use or in patients with renal impairment
• Assess the risk of bleeding before surgery or dental procedures
• Caution in patients with asthma or nasal polyps due to potential hypersensitivity reactions
• Consider the potential for Reye's syndrome in children and adolescents

Pregnancy

Use during pregnancy is generally not recommended, particularly in the third trimester, due to the risk of adverse effects on the fetus and complications during delivery.

Breast-feeding

Acetylsalicylic acid is excreted in breast milk; caution is advised if used while breastfeeding.

Storage

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

Formulations

• Tablets
• Enteric-coated tablets
• Effervescent tablets
• Suppositories
• Oral suspension

Indications

• Allergic rhinitis (hay fever)
• Allergic conjunctivitis
• Urticaria (hives)
• Other allergic conditions

Dosage

Children: For children aged 6 to 12 years, the usual dose is 2 mg every 4 to 6 hours as needed, not exceeding 12 mg per day. For children aged 2 to 6 years, consult the BNF for Children for appropriate dosing guidance.

Adults: The usual adult dose is 4 mg every 4 to 6 hours as needed, not exceeding 24 mg per day.

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor, preventing the action of endogenous histamine. This leads to temporary relief from symptoms like urticaria and pruritus. It also exhibits anticholinergic properties, which contribute to a drying effect on the nasal mucosa and inhibit smooth muscle responses mediated by histamine.

Pharmacodynamics

In allergic reactions, allergens interact with IgE antibodies on mast cells, leading to degranulation and histamine release. Histamine acts on H1 receptors, causing symptoms such as pruritus, vasodilation, and increased vascular permeability. Chlorpheniramine, as an H1 antagonist, competes with histamine for receptor binding, effectively mitigating these symptoms and providing symptomatic relief in conditions like hay fever and other upper respiratory allergies.

Pharmacokinetics

Chlorpheniramine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 2 to 6 hours. It is metabolized in the liver and has a half-life of approximately 12 to 15 hours. The drug is excreted primarily through urine, with both unchanged drug and metabolites being eliminated.

Contra-indications

• Hypersensitivity to chlorpheniramine or any component of the formulation
• Severe asthma or respiratory failure

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Confusion

Interactions

• Concurrent use with other central nervous system depressants may enhance sedation
• Increased anticholinergic effects when used with other anticholinergic drugs
• May interfere with the actions of certain medications used to treat Parkinson's disease

Precautions

• Use with caution in patients with glaucoma
• Caution in patients with prostate enlargement or bladder neck obstruction
• May impair the ability to drive or operate machinery due to sedation

Pregnancy

Chlorpheniramine is generally considered safe for use during pregnancy, but should be used only when clearly needed.

Breast-feeding

Chlorpheniramine is excreted in breast milk; caution is advised when used during breastfeeding.

Storage

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

Formulations

• Tablets
• Liquid syrup
• Injectable form

Indications

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the prescribing information for specific dosing guidelines based on the condition and patient characteristics.

Mechanism of action

Moroxide functions as a non-selective inhibitor of monoamine oxidase, leading to increased concentrations of monoamines in the synaptic cleft. This increase in neurotransmitter availability enhances mood and alleviates symptoms of depression and anxiety. The inhibition of MAO prevents the degradation of neurotransmitters, thus prolonging their action and enhancing neurotransmission.

Pharmacodynamics

The primary pharmacodynamic effect of moroxide is the elevation of mood and reduction of depressive symptoms through increased levels of serotonin, norepinephrine, and dopamine. It may also exert effects on other neurotransmitter systems, contributing to its overall antidepressant and anxiolytic properties. Therapeutic effects can take several weeks to become evident due to the complex adaptive changes in neurotransmitter systems.

Pharmacokinetics

Moroxide is absorbed well from the gastrointestinal tract and is subject to first-pass metabolism. It has a variable half-life, which may depend on the individual patient’s metabolism. The drug is primarily metabolized in the liver and is excreted through urine. Its pharmacokinetic profile suggests that regular monitoring may be necessary to optimize dosing and minimize side effects.

Pregnancy

The safety of moroxide during pregnancy has not been established. It should only be used if the potential benefits justify the potential risks to the fetus.

Breast-feeding

It is unknown whether moroxide is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

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

Indications

• Hypotension in surgical settings
• Nasal decongestion
• Mydriasis for ophthalmic procedures
• Management of shock states

Dosage

Adults: For intravenous administration, initial doses typically range from 100 to 500 micrograms, repeated as necessary, with careful monitoring of blood pressure. For nasal decongestion, phenylephrine is commonly administered as a 10 mg oral dose every

Mechanism of action

Phenylephrine exerts its effects primarily through agonism of alpha-1 adrenergic receptors, which results in vasoconstriction and mydriasis. The stimulation of these receptors inhibits the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibiting adenyl cyclase, leading to increased peripheral vascular resistance and elevated blood pressure. Additionally, phenylephrine indirectly promotes the release of norepinephrine from storage sites, further enhancing its vasoconstrictive effects.

Pharmacodynamics

Phenylephrine causes an increase in blood pressure and local vasoconstriction. Its ophthalmic formulations can induce mydriasis for 3-8 hours, while intravenous administration has a rapid onset with an effective half-life of about 5 minutes and an elimination half-life of approximately 2.5 hours. Caution is advised regarding potential side effects such as hypertension, arrhythmias, and rebound miosis with ophthalmic use, and bradycardia, allergic reactions, and tissue damage with intravenous use.

Pharmacokinetics

Phenylephrine is rapidly absorbed following intravenous administration, leading to a quick elevation in blood pressure. The drug undergoes metabolism primarily in the liver and is eliminated through urine. The pharmacokinetic profile indicates a short effective half-life which necessitates frequent dosing in continuous infusion settings for maintaining blood pressure levels.

Contra-indications

• Severe hypertension
• Hypersensitivity to phenylephrine
• Severe coronary artery disease
• Narrow-angle glaucoma

Adverse effects

• Hypertension
• Reflex bradycardia
• Arrhythmias
• Headache
• Dizziness
• Nausea
• Vomiting
• Local irritation (ophthalmic use)

Interactions

• MAO inhibitors may enhance the hypertensive effect
• Tricyclic antidepressants may increase the pressor response
• Concurrent use with oxytocic drugs may increase the risk of hypertension
• Can interact with other sympathomimetics

Precautions

• Use with caution in patients with hypertension, hyperthyroidism, or diabetes mellitus
• Monitor blood pressure regularly during treatment
• Caution in patients with cardiovascular disease
• Use with caution in elderly patients

Pregnancy

Phenylephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

It is not known whether phenylephrine is excreted in human milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Ophthalmic solution
• Injectable solution
• Oral tablet

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/ H1 antagonists inhibit most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/ H1 antagonists strongly block the action of histamine that results in increased permeability and formation of edema and wheal. /Histamine Antagonists: H1 Antagonists/ Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine induced changes in systemic blood pressure parallel these vascular effects. /Histamine Antagonists: H1 Antagonists/ Many of the H1 antagonists tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. These atropine like actions are sufficiently prominent in some of the drugs to be manifest during clinical usage ... . /Histamine Antagonists: H1 Antagonists/

Pharmacodynamics

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H₁-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

Mechanism of action

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia. Phenylephrine acts predominantly by a direct effect on alpha-adrenergic receptors. In therapeutic doses, the drug has no substantial stimulant effect on the beta-adrenergic receptors of the heart (beta1-adrenergic receptors) but substantial activation of these receptors may occur when larger doses are given. Phenylephrine does not stimulate beta-adrenergic receptors of the bronchi or peripheral blood vessels (beta2-adrenergic receptors). It is believed that alpha-adrenergic effects result from the inhibition of the production of cyclic adenosine-3',5'-monophosphate (cAMP) by inhibition of the enzyme adenyl cyclase, whereas beta-adrenergic effects result from stimulation of adenyl cyclase activity. Phenylephrine also has an indirect effect by releasing norepinephrine from its storage sites.

Pharmacodynamics

Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure, dilates the pupils, and causes local vasoconstriction. Ophthalmic formulations of phenylephrine act for 3-8 hours while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours. Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis. Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.