FLUCOLD CAPSULES

Indications

• Pain and inflammation in musculoskeletal disorders
• Mild to moderate pain including dysmenorrhea
• Postoperative analgesia
• Dental pain
• Migraine
• Fever

Dosage

Adults: Initially 300–400 mg 3–4 times a day; increase if necessary up to 600 mg 4 times a day; maintenance 200–400 mg 3 times a day, may be adequate.

Mechanism of action

The exact mechanism of action of ibuprofen is unknown. However, it is considered a non-selective inhibitor of cyclooxygenase (COX), which is involved in the synthesis of prostaglandins and thromboxane. By inhibiting COX-1 and COX-2, ibuprofen decreases the production of prostaglandins that mediate inflammation, pain, and fever, while COX-1 inhibition may lead to gastrointestinal side effects.

Pharmacodynamics

Ibuprofen exerts its analgesic effects through multiple pathways involved in both acute and chronic inflammation. It reduces pain and inflammation by inhibiting the synthesis of prostanoids via COX-1 and COX-2. The pain relief is believed to be mediated through both peripheral effects at the site of injury and central effects within the nervous system, particularly affecting pain transmission pathways. Additionally, ibuprofen has antipyretic effects linked to its action on prostanoid synthesis in the hypothalamus.

Pharmacokinetics

Ibuprofen is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It is extensively metabolized in the liver, primarily by oxidation, and has an elimination half-life of approximately 2 to 4 hours. The drug is excreted mainly in the urine, with a small proportion eliminated unchanged. Renal impairment may affect ibuprofen clearance, necessitating caution in patients with compromised kidney function.

Contra-indications

• History of hypersensitivity to aspirin or any other NSAID
• Severe renal impairment
• Severe hepatic impairment
• Active peptic ulcer disease
• Caution in patients with asthma, angioedema, urticaria, or rhinitis precipitated by NSAIDs

Adverse effects

• Gastrointestinal ulceration
• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Rash
• Headache
• Tinnitus
• Visual impairment
• Fluid retention
• Increased blood pressure

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs or anticoagulants
• May reduce the antihypertensive effect of ACE inhibitors
• May increase serum levels of lithium
• May enhance the effects of other anticoagulants
• Caution with corticosteroids due to increased risk of gastrointestinal side effects

Precautions

• Use with caution in patients with mild to moderate hepatic impairment
• Use with caution in patients with mild to moderate renal impairment
• Monitor for signs of gastrointestinal bleeding
• Avoid use during the third trimester of pregnancy

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to the risk of closure of the fetal ductus arteriosus and possibly persistent pulmonary hypertension of the newborn.

Breast-feeding

Small amounts are present in milk. Manufacturer advises to avoid unless necessary.

Storage

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

Formulations

• Tablets (200 mg, 400 mg)
• Oral suspension (100 mg/5 mL)
• Gel (5%) for topical application
• Suppositories (various strengths)

Indications

• Nasal congestion
• Sinusitis affecting the maxillary antrum

Dosage

Children: For children aged 6-11 years, the recommended dose is 30 mg 3-4 times a day. For children aged 12-17 years, the dose is 60 mg 3-4 times a day. Caution is advised in children under 6 years.

Adults: The typical adult dose is 60 mg every 4-6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts primarily as a selective agonist of alpha-adrenergic receptors, which causes vasoconstriction of the nasal mucosa. This leads to a decrease in mucosal edema and congestion. It may also have some beta-adrenergic activity, contributing to bronchodilation.

Pharmacodynamics

The pharmacodynamic effects of pseudoephedrine include reduced nasal congestion and increased airflow through the nasal passages. Its action is dose-dependent, with higher doses leading to more pronounced effects. Side effects may include increased heart rate, hypertension, and CNS stimulation such as anxiety and insomnia.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is metabolized primarily in the liver and has a half-life of approximately 5-8 hours. The drug is excreted mainly in the urine, with a portion being unchanged.

Contra-indications

• Severe hypertension
• Severe renal impairment
• Severe hepatic impairment
• Hyperthyroidism
• Angle closure glaucoma
• Use in children under 6 years of age is not recommended due to safety concerns

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Dizziness
• Dry mouth
• Increased heart rate (tachycardia)
• Hypertension
• Palpitations
• Rebound congestion
• Irritability
• Tremors
• Hallucinations
• Dermatitis
• Muscle weakness
• Vomiting
• Piloerection

Interactions

• Monoamine oxidase inhibitors (MAOIs) may enhance the hypertensive effects
• Other sympathomimetics may increase the risk of cardiovascular effects
• Caution with antihypertensive medications as pseudoephedrine may counteract their effectiveness

Precautions

• Use with caution in individuals with cardiovascular disease
• Caution in patients with diabetes due to potential hyperglycemia
• Monitor patients with a history of psychiatric disorders as it may exacerbate symptoms
• Use with caution in patients with a history of seizures

Pregnancy

Manufacturer advises avoidance due to potential risks such as defective closure of the abdominal wall in newborns after first trimester exposure.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to the potential for irritability and disturbed sleep in infants.

Storage

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

Formulations

• Oral solution (e.g., Sudafed Decongestant 30mg/5ml liquid)
• Nasal drops (e.g., Galpseud 0.5% drops)

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

• Cough
• Pseudobulbar affect

Dosage

Children: Refer to the BNF for Children for specific dosing information tailored to paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the formulation and clinical context.

Mechanism of action

Dextromethorphan acts as a low-affinity uncompetitive antagonist of NMDA receptors and as an agonist at sigma-1 receptors. It also antagonizes α3/β4 nicotinic receptors. The clinical effects are thought to arise from NMDA receptor blockade and serotonin (5-HT) uptake inhibition, which may lead to increased serotonin receptor stimulation. However, the precise mechanisms by which these actions translate into therapeutic effects remain incompletely understood.

Pharmacodynamics

Dextromethorphan is considered an opioid-like molecule with a moderate therapeutic window, indicating that while it is effective at standard doses, higher doses can lead to intoxication. It has a moderate duration of action, making it suitable for use in cough management. Due to its potential for abuse and risk of intoxication, patients are advised to use it cautiously.

Pharmacokinetics

Dextromethorphan is metabolized primarily in the liver through the cytochrome P450 enzyme system, leading to the formation of its active metabolite, dextrorphan. The pharmacokinetics may be influenced by individual variations in metabolic pathways, which can affect the drug's efficacy and safety profile.

Contra-indications

• Hypersensitivity to dextromethorphan or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe respiratory insufficiency or asthma
• Persistent cough due to smoking, emphysema, or chronic bronchitis

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Drowsiness
• Confusion
• Constipation
• Abdominal discomfort
• Euphoria or dysphoria
• Serotonin syndrome (when used with serotonergic drugs)

Interactions

• May interact with MAOIs, leading to serious side effects
• Potential interactions with other CNS depressants, leading to increased sedation
• May enhance the effects of alcohol
• Can interact with medications that affect serotonin levels, increasing the risk of serotonin syndrome

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor use in patients with hepatic impairment
• Caution advised in patients with a history of seizures
• Should not be used in children under 2 years unless directed by a physician

Pregnancy

Dextromethorphan should be used during pregnancy only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Dextromethorphan is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral syrup
• Tablets
• Capsules
• Lozenges

Indications

• Nasal congestion due to cold
• Allergic rhinitis
• Sinusitis
• Eustachian tube dysfunction

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 30 mg every 6 hours, not exceeding 120 mg per day. For children aged 2 to 6 years

Adults: The typical adult dose is 60 mg every 4 to 6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. The agonism produces vasoconstriction in the mucosa of the respiratory tract, leading to decreased nasal congestion. It also inhibits norepinephrine, dopamine, and serotonin transporters, which may contribute to its sympathomimetic effects such as increased arterial pressure and heart rate. Additionally, pseudoephedrine has anti-inflammatory actions through the inhibition of NF-kappa-B and other transcription factors.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction resulting in a decongestant effect. Its sympathomimetic properties can lead to increased heart rate and blood pressure. The duration of action is typically short unless formulated as an extended-release product. Patients may experience central nervous system stimulation, which should be considered when prescribing.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. The drug is metabolized in the liver, primarily by the cytochrome P450 system, and has a half-life of about 6 hours. It is excreted mainly through the kidneys, with about 55-70% of the dose eliminated unchanged in the urine.

Adverse effects

• Increased blood pressure
• Centrally mediated side effects such as insomnia
• Nervousness
• Dizziness
• Headache
• Dry mouth

Interactions

• pseudoephedrine + linezolid: Severe (increases risk of elevated blood pressure)
• volatile halogenated anesthetics + pseudoephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with hypertension
• Use with caution in patients with cardiovascular disease
• May exacerbate conditions like hyperthyroidism or diabetes

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Use with caution; small amounts may pass into breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Extended-release oral tablets
• Liquid formulations

Indications

• Allergic rhinitis (hay fever)
• Allergic conjunctivitis
• Urticaria (hives)
• Other upper respiratory allergies

Dosage

Children: For children aged 2 to 6 years, the recommended dose is 1.25 mg to 2.5 mg taken

Adults: The usual adult dose for triprolidine is 2.5 mg to 5 mg taken orally, one to three times daily, as needed. Refer to the BNF for specific dosing recommendations.

Mechanism of action

Triprolidine binds to the histamine H1 receptor, inhibiting the action of endogenous histamine. By competing with histamine for H1-receptor sites on effector cells, it prevents the physiological responses mediated by histamine, such as pruritus, urticaria, and bronchoconstriction. The drug's anticholinergic effects also contribute to reduced secretion in the nasal mucosa.

Pharmacodynamics

In allergic reactions, allergens interact with surface IgE antibodies on mast cells, leading to degranulation and release of histamine. Histamine acts on H1-receptors to produce various effects, including itching, vasodilatation, and increased vascular permeability. Triprolidine, as an H1 antagonist, competes with histamine for receptor binding, effectively blocking these reactions and providing relief from allergy symptoms.

Pharmacokinetics

Triprolidine is absorbed well following oral administration, with peak plasma concentrations typically occurring within 2 to 4 hours. It has a relatively long half-life, allowing for sustained effects. The drug is metabolized in the liver and primarily excreted via urine. Due to its ability to cross the blood-brain barrier, triprolidine may also cause sedation as a side effect.

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation

Precautions

• Use with caution in patients with a history of glaucoma
• May exacerbate urinary retention in patients with prostatic hypertrophy
• Caution in driving or operating machinery due to sedative effects

Pregnancy

Triprolidine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

It is not known whether triprolidine is excreted in human 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

Mechanism of action

The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. IBUPROFEN AT 25 MG/KG IV INCREASED THE PRIMARY AND TOTAL HEMOSTATIC PLUG FORMATION TIME IN RABBIT EAR CHAMBERS WITH LASER-INDUCED INJURY. THE SAME DOSE INCREASED THE NUMBER OF CUMULATIVE EMBOLI OVER A 10 MINUTE PERIOD AFTER A LASER INJURY TO ARTERIOLES. IN DOGS, DOSES OF 10, 25, AND 50 MG/KG DID NOT ENHANCE THE RELEASE OF (125)I-LABELED FIBRIN DEGRADATION PRODUCTS FROM THE THROMBI AFTER INCUBATION IN PLASMIN, BUT THE LARGEST DOSE SIGNIFICANTLY DECREASED THE THROMBUS WEIGHT 90 AND 180 MINUTES AFTER DRUG ADMINISTRATION. THUS, IBUPROFEN HAD AN INHIBITORY EFFECT ON PLATELET FUNCTION IN VIVO AND IN LARGE DOSES DIMINISHED THE THROMBUS WEIGHT. L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response. We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open fie

Pharmacodynamics

Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials. The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region. The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system. In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.

Mechanism of action

Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood. Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor. Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT(1A) receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT(1A) agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT(1A) antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT(1A) agonism. Combined with previous work from our group, our results support the investigation of 5-HT(1A) agonists as pharmacotherapies for LID in PD patients. Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 hr after an injection of LPS/GalN (20 ug/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. /The

Pharmacodynamics

Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect. It has a moderate therapeutic window, as intoxication can occur at higher doses. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication.

Mechanism of action

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant and as a treatment of priapism. Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters. The sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria. Pseudoephedrine is also a partial agonist of the anococcygeal muscle. Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-1. THESE AGENTS /BRONCHODILATORS/ ACT ON BETA-2 RECEPTORS TO RELAX BRONCHIAL SMOOTH MUSCLE & PERIPHERAL VASCULATURE, APPARENTLY BY STIMULATING PRODN OF CYCLIC ADENOSINE-3.5-MONOPHOSPHATE (CAMP)... Pseudoephedrine acts on alpha-adrenergic receptors in the mucosa of the respiratory tract, producing vasoconstriction. The medication shrinks swollen nasal mucous membranes; reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. Also, drainage of sinus secretions may be increased and obstructed eustachian ostia may be opened. The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 hr after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction which leads to a decongestant effect. It has a short duration of action unless formulated as an extended release product. Patients should be counselled regarding the risk of central nervous system stimulation.

Mechanism of action

Triprolidine 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/ 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/ /SRP:/ The action of histamine results in increased permeability and formation of edema and wheal. H1 antagonists block that action. For more Mechanism of Action (Complete) data for TRIPROLIDINE (7 total), please visit the HSDB record page.

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. Triprolidine, is a histamine H1 antagonist that 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. Triprolidine has anticholinergic and sedative effects.