Pholtex Plus

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

• Dry cough
• Cough caused by respiratory infections

Dosage

Children: For children aged 6-11 years, the recommended dose is 2-5 mg taken 3-4 times a day. For children aged 12-17 years, the dosage is 5-10 mg taken 3-4 times a day. Pholcodine should be avoided in children under 6 years.

Adults: For adults, the typical dosage is 5-10 mg taken 3-4 times a day.

Mechanism of action

Pholcodine exerts its effects directly on the cough center in the medulla oblongata, acting on peripheral reflexogenic receptors to suppress the cough reflex. This mechanism allows pholcodine to alleviate coughing without significantly impacting respiratory function.

Pharmacodynamics

Therapeutic doses of pholcodine do not typically cause respiratory depression, CNS excitation, or other side effects commonly associated with narcotics. It selectively targets the cough center while preserving respiratory activity, thus reducing the risk of addiction and psychological dependence. However, it is noted to have a stronger respiratory depression effect compared to codeine and can induce hypotension similar to codeine. Additional pharmacological effects include histamine release induction, anti-histaminic activity, anti-acetylcholinic action, anti-convulsant properties, and mild tranquilizing effects.

Pharmacokinetics

Pholcodine is absorbed well when taken orally and is metabolized in the liver. Its pharmacokinetic profile indicates it is distributed widely throughout the body. The elimination half-life and specific metabolic pathways are not detailed in the provided sources, but it is important to consider hepatic and renal function when prescribing.

Contra-indications

• Known hypersensitivity to pholcodine or any of its components
• Severe hepatic impairment
• Severe renal impairment
• Children under 6 years of age

Adverse effects

• Drowsiness
• Nausea
• Constipation
• Dry mouth
• Dizziness
• Hypotension

Interactions

• Caution with other cough and cold preparations that may contain similar active ingredients
• May interact with central nervous system depressants, enhancing sedative effects
• Caution is advised when combined with antihistamines

Precautions

• Use with caution in patients with respiratory conditions
• Care should be taken to administer the correct dose, especially in children
• Avoid use in patients with a history of substance abuse

Pregnancy

Pholcodine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pholcodine is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Pholcodine 5 mg/5 mL linctus
• Pholcodine 10 mg/5 mL linctus strong
• Pholcodine 2 mg/mL oral solution
• Pholcodine sugar-free linctus

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

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

The mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the "cough center."

Pharmacodynamics

The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine. It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action.