COLDRID SYRUP

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

• Mild to moderate pain
• Fever
• Headaches
• Muscle aches
• Arthritis
• Backaches
• Toothaches
• Colds

Dosage

Adults: For adults, the typical dosage is 500 mg to 1 g every 4 to 6 hours, with a maximum daily limit of 4 g. In cases of intravenous administration, the dosage is 15 mg/kg every

Mechanism of action

Paracetamol is thought to exert its analgesic effects by inhibiting cyclo-oxygenase (COX) enzymes, specifically COX-1 and COX-2, which are involved in the synthesis of prostaglandins responsible for pain sensation. Unlike most NSAIDs, paracetamol does not exhibit peripheral anti-inflammatory effects. Its antipyretic action is believed to result from direct action on heat-regulating centers in the brain, leading to peripheral vasodilation and sweating.

Pharmacodynamics

Paracetamol has been shown to have both antipyretic and analgesic effects, lacking any significant anti-inflammatory activity. It does not interfere with platelet aggregation or disrupt hemostasis, making it a safer option for individuals at risk of bleeding. Allergic reactions to paracetamol are rare. The drug does not affect uric acid secretion or acid-base balance when used at recommended doses.

Pharmacokinetics

Paracetamol is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 30 to 60 minutes after oral administration. It is primarily metabolized in the liver via conjugation with glucuronide and sulfate, with a minor pathway involving cytochrome P450 enzymes. The elimination half-life ranges from 1 to 4 hours, with renal excretion of metabolites as the primary route of elimination.

Adverse effects

• Nausea and vomiting
• Liver injury
• Renal damage
• Hypersensitivity reactions
• Flushing
• Hypotension
• Anorectal erythema
• Angioedema
• Agranulocytosis
• Thrombocytopenia
• Leukopenia
• Severe cutaneous adverse reactions (SCARs)

Interactions

• Increased risk of methaemoglobinaemia with topical prilocaine
• Increased risk of methaemoglobinaemia with topical anaesthetics
• Increased anticoagulant effect with coumarins
• Increased risk of hepatotoxicity with imatinib
• Decreased exposure with rifampicin
• Decreased exposure with pitolisant

Precautions

• Monitor patients with liver disease or heavy alcohol use for increased risk of hepatotoxicity
• Adjust doses in patients taking enzyme-inducing antiepileptic medications
• Use caution in patients with renal impairment
• Clinical judgement is required for dose adjustment in weight-based dosing

Pregnancy

Paracetamol is generally considered safe to use during pregnancy for pain and fever relief, but should be used at the lowest effective dose for the shortest duration necessary.

Breast-feeding

Paracetamol is excreted in breast milk in small amounts and is considered safe for use while breastfeeding.

Storage

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

Formulations

• Oral tablets (500 mg)
• Oral suspension (120 mg/5 mL, 500 mg/5 mL)
• Rectal suppositories (various strengths)
• Intravenous infusion (various strengths)

Indications

• Chronic idiopathic urticaria
• Perennial allergic rhinitis
• Seasonal allergic rhinitis
• Allergic asthma
• Physical urticaria
• Atopic dermatitis

Dosage

Children: For children aged 6 to 12 years, the dosage is typically 5 mg to 10 mg once daily depending on the severity of symptoms. For children aged 2 to 6 years, the usual dose is 2.5 mg to 5 mg once daily. Specific dosing should refer to the BNF for Children.

Adults: The typical adult dose is 10 mg once daily, which can be adjusted based on the severity of symptoms and patient response.

Mechanism of action

Cetirizine selectively inhibits peripheral H1 receptors, effectively blocking the action of histamine, which is responsible for allergic symptoms. It has demonstrated negligible anticholinergic and antiserotonergic effects, and studies indicate minimal penetration into the central nervous system, reducing the likelihood of sedation.

Pharmacodynamics

Cetirizine exhibits antihistaminic activity that effectively minimizes or eliminates symptoms of various allergic conditions such as chronic idiopathic urticaria and allergic rhinitis. It has anti-inflammatory properties that may assist in asthma management and can significantly reduce the duration and dosage of topical anti-inflammatory treatments for conditions like atopic dermatitis. Its effects can be observed within 20 minutes of administration, lasting up to 24 hours.

Pharmacokinetics

Cetirizine is well absorbed orally with peak plasma concentrations occurring approximately 1 hour after dosing. It has a half-life of about 8 hours, allowing for once-daily dosing in most cases. The drug is primarily excreted in the urine, with minimal hepatic metabolism, making it suitable for patients with liver impairment.

Adverse effects

• dry mouth
• drowsiness
• fatigue
• headache
• nausea

Precautions

• Use with caution in patients with renal impairment
• Caution advised in individuals with a history of seizures

Pregnancy

Cetirizine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Cetirizine is excreted in breast milk; caution is advised when administered to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• tablets
• oral solution
• syrup

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

According to its FDA labeling, acetaminophen's exact mechanism of action has not been fully established - despite this, it is often categorized alongside NSAIDs (non-steroidal anti-inflammatory drugs) due to its ability to inhibit the cyclo-oxygenase (COX) pathways. It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms. One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclo-oxygenase, COX-1 and COX-2, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly. Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme that is unique from the known variants COX-1 and COX-2. This enzyme has been referred to as _COX-3_. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat. The exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge. Although further investigation is warranted, the active metabolite of acetaminophen (AM404) was shown to interact with several molecular targets, including the Ca_v3.2 calcium channel, the cannabinoid CB1 receptors, TRPV1 receptors, and Na_v1.8 and Na_v1.7 channels. Acetaminophen produces analgesia and antipyresis by a mechanism similar to that of salicylates. Unlike salicylates, however, acetaminophen does not have uricosuric activity. There is some evidence that acetaminophen has weak anti-inflammatory activity in some nonrheumatoid conditions (e.g., in patients who have had oral surgery). ... Acetaminophen lowers body temperature in patients with fever but rarely lowers normal body temperature. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. The effects of acetaminophen on cyclooxygenase activity have not been fully determined. Acetaminophen is a weak, reversible, isoform-nonspecific cyclooxygenase inhibitor at dosages of 1 g daily. The inhibitory effect of acetaminophen on cyclooxygenase-1 is limited, and the drug does not inhibit platelet function. Therapeutic doses of acetaminophen appear to have little effect on cardiovascular and respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing. Acetaminophen (N-acetyl-p-aminophenol (APAP)) is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associated previous use of therapeutic APAP doses with the risk of chronic obstructive pulmonary disease (COPD) and asthma. The transient receptor potential ankyrin-1 (TRPA1) channel is expressed by peptidergic primary sensory neurons. Because NAPQI, like other TRPA1 activators, is an electrophilic molecule, /the researchers/ hypothesized that APAP, via NAPQI, stimulates TRPA1, thus causing airway neurogenic inflammation. NAPQI selectively excites human recombinant and native (neuroblastoma cells) TRPA1. TRPA1 activation by NAPQI releases proinflammatory neuropeptides (substance P and calcitonin gene-related peptide) from sensory nerve terminals in rodent airways, thereby causing neurogenic edema and neutrophilia. Single or repeated administration of therapeutic (15-60 mg/kg) APAP doses to mice produces detectable levels of NAPQI in the lung, and increases neutrophil numbers, myeloperoxidase

Pharmacodynamics

Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation. Allergic reactions are rare occurrences following acetaminophen use.

Mechanism of action

Cetirizine, a metabolite of _hydroxyzine_, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. _In vivo_ and _ex vivo_ animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. _Ex vivo_ studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly. Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H1 receptors.

Pharmacodynamics

**General effects and respiratory effects** Cetirizine, the active metabolite of the piperazine H₁-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis. The clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trials. **Effects on urticaria/anti-inflammatory effects** It has anti-inflammatory properties that may play a role in asthma management. There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h. Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis.

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.