GOLDGESTANT COMBINATION PRODUCT ELIXIR

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

• Allergic rhinitis (hay fever)
• Urticaria (hives)
• Allergic conjunctivitis
• Common cold symptoms

Dosage

Children: For children aged 6-12 years, the dose is typically 2 mg every 4 to 6 hours, not exceeding 12 mg per day. For children under

Adults: The usual adult dose for chlorpheniramine is 4 mg every 4 to 6 hours, not to exceed 24 mg per day.

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor, preventing endogenous histamine from exerting its effects. This leads to temporary relief from symptoms such as sneezing, pruritus, and increased vascular permeability associated with allergic reactions. The drug competes with histamine for H1-receptor sites on effector cells, thus antagonizing most of the pharmacological effects of histamine, including its actions on smooth muscle and vascular permeability.

Pharmacodynamics

In allergic reactions, allergens trigger the degranulation of mast cells and basophils, leading to the release of histamine. Chlorpheniramine, as an H1 antagonist, competes for receptor binding, effectively blocking histamine-induced effects, such as itching, vasodilation, and bronchoconstriction. This results in relief from symptoms like sneezing, watery eyes, and nasal discharge.

Pharmacokinetics

Chlorpheniramine is well absorbed from the gastrointestinal tract. It undergoes hepatic metabolism and its effects can last for several hours. The onset of action is typically observed within 1 to 2 hours following oral administration, with peak effects occurring around 2 to 6 hours. The drug is eliminated primarily through urine, with a half-life ranging from 12 to 15 hours, though this can vary based on individual factors.

Contra-indications

• Hypersensitivity to chlorpheniramine or any component of the formulation
• Acute asthma attacks
• Severe hypertension
• Narrow-angle glaucoma
• Prostatic hypertrophy

Adverse effects

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

Interactions

• Alcohol
• CNS depressants
• MAO inhibitors
• Anticholinergic agents
• Beta-blockers

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with liver or kidney impairment
• Avoid in elderly patients due to increased risk of sedation and anticholinergic effects
• May impair the ability to drive or operate machinery

Pregnancy

Chlorpheniramine should be used in pregnancy only if clearly needed. Consult medical professionals for guidance.

Breast-feeding

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

Storage

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

Formulations

• Tablets
• Syrup
• Oral suspension

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

Indications

• Nasal congestion
• Cough-cold formulations
• Appetite suppression

Dosage

Adults: Refer to the BNF for

Mechanism of action

Phenylpropanolamine acts directly on alpha- and, to a lesser extent, beta-adrenergic receptors in the respiratory tract mucosa. Activation of alpha-adrenergic receptors induces vasoconstriction, which decreases tissue hyperemia, edema, and nasal congestion, thereby improving nasal airway patency. PPA may also stimulate beta-receptors, resulting in tachycardia and a positive inotropic effect. The drug likely functions by releasing norepinephrine from its storage sites, with alpha-adrenergic effects emerging from inhibition of adenyl cyclase activity and beta-adrenergic effects from cyclic adenosine 3',5'-monophosphate (AMP) production via adenyl cyclase activation. Repeated use can lead to norepinephrine depletion, resulting in tachyphylaxis.

Pharmacodynamics

Phenylpropanolamine, classified as a sympathomimetic, primarily serves as a decongestant. Its usage has declined due to safety concerns, particularly the risk of hemorrhagic stroke in female patients. Despite its decongestant properties, the FDA has advised against its use in over-the-counter products since 2000, reflecting its potential adverse effects.

Pharmacokinetics

The pharmacokinetics of phenylpropanolamine include its absorption, distribution, metabolism, and excretion characteristics, though specific data on half-life and bioavailability are not detailed in the provided information. Its sympathomimetic effects are mediated through adrenergic receptor stimulation, and prolonged use may lead to decreased efficacy due to tachyphylaxis.

Contra-indications

• Hypersensitivity to phenylpropanolamine or any component of the formulation
• Severe hypertension
• Severe coronary artery disease
• Hyperthyroidism
• Glaucoma
• Concurrent use of monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Hypertension
• Tachycardia
• Nervousness
• Dizziness
• Insomnia
• Headache
• Dry mouth
• Nausea
• Vomiting
• Constipation

Interactions

• MAO inhibitors - may cause hypertensive crisis
• Tricyclic antidepressants - may enhance hypertensive effect
• Beta-blockers - may diminish the effectiveness of phenylpropanolamine
• Other sympathomimetics - increased risk of cardiovascular side effects

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor blood pressure regularly during treatment
• Caution in patients with diabetes, prostate enlargement, or urinary retention
• Not recommended for use in children under 12 years of age

Pregnancy

Phenylpropanolamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Safety in pregnancy has not been established.

Breast-feeding

It is not known whether phenylpropanolamine is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

Formulations

• Phenylpropanolamine hydrochloride tablet
• Phenylpropanolamine syrup

Indications

• Nasal congestion due to allergies
• Common cold
• Sinusitis
• Appetite suppression

Dosage

Children: Refer to specific product guidelines for dosing information, as it can vary by formulation and indication.

Adults: Refer to specific product guidelines for dosing information, as it can vary by formulation and indication.

Mechanism of action

Phenylpropanolamine acts primarily as an adrenergic agonist, stimulating alpha-1 adrenergic receptors. This stimulation results in vasoconstriction of blood vessels in the nasal mucosa, leading to decreased edema and congestion. Additionally, it may have effects on the central nervous system, contributing to appetite suppression.

Pharmacodynamics

The pharmacodynamics of phenylpropanolamine involves its action on adrenergic receptors, particularly alpha-1 receptors, which mediate smooth muscle contraction and vasoconstriction. This leads to increased blood pressure and decreased blood flow to the nasal mucosa, ameliorating symptoms of nasal congestion. Its central effects may also include increased alertness and decreased appetite, although these effects vary among individuals.

Pharmacokinetics

Phenylpropanolamine is absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 1 to 3 hours after oral administration. It is metabolized by monoamine oxidase and other pathways in the liver, with a half-life ranging from 2 to 4 hours. The drug is primarily excreted in the urine, both as unchanged drug and metabolites. Factors such as age, liver function, and other medications can influence its pharmacokinetics.

Contra-indications

• Hypersensitivity to phenylpropanolamine or any component of the formulation
• Severe hypertension
• Severe cardiovascular disorders
• Hyperthyroidism
• Glaucoma
• Use in patients taking monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Insomnia
• Nervousness
• Dizziness
• Headache
• Tachycardia
• Palpitations
• Hypertension
• Dry mouth
• Nausea

Interactions

• Increased risk of hypertension when used with other sympathomimetics
• Potentially increased effects with MAOIs leading to hypertensive crises
• May decrease effectiveness of antihypertensive medications

Precautions

• Use with caution in patients with a history of hypertension
• Monitor blood pressure regularly during treatment
• Caution in patients with diabetes mellitus or prostate enlargement
• Avoid use in pregnant or breastfeeding women unless clearly necessary

Pregnancy

Phenylpropanolamine is not recommended during pregnancy due to potential risks. Consult a healthcare provider for alternative treatments.

Breast-feeding

It is advisable to avoid phenylpropanolamine while breastfeeding due to potential effects on the infant. Consult a healthcare provider for safer alternatives.

Storage

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

Formulations

• Tablets
• Capsules
• Syrup

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.

Mechanism of action

Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors, producing tachycardia and a positive inotropic effect. The mechanism of action of phenylpropanolamine has not been conclusively determined. The drug may directly stimulate adrenergic receptors but probably indirectly stimulates both A- and B-adrenergic receptors by releasing norepinephrine from its storage sites. It is believed that B-adrenergic effects result from stimulation of cyclic adenosine 3',5'-monophosphate (AMP) production by activation of the enzyme adenyl cyclase, whereas A-adrenergic effects result from inhibition of adenyl cyclase activity. With prolonged use or too frequent administration, indirectly acting sympathomimetics may deplete norepinephrine in sympathetic nerve endings and tachyphylaxis may develop. Tachyphylaxis induced by one indirectly acting sympathomimetic may result in refractoriness to other drugs of the same class. /Phenylpropanolamine hydrochloride/ Whether the alpha1- and alpha2-adrenoceptor mediated increases in diastolic blood pressure effected by phenylpropanolamine and its enantiomers are altered by, or independent of beta2-mediated vasodilation, or beta2-adrenoceptor blockade were studied in pithed rats. The pressor responses were enhanced in the presence of the antagonist ICI-118551 and diminished in the presence of albuterol. It was concluded that each form of phenylpropanolamine possesses the intrinsic ability to interact with all of the adrenoceptors in the system used and that the interaction with those adrenoceptors determines the net increase in diastolic blood pressure that follows the intravenous administration of the compounds. These findings have a bearing on the recent controversy regarding the use of beta-blocking agents in the treatment of overdosage of phenylpropanolamine.

Pharmacodynamics

Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine.