SYNFLEX M TABLETS 85MG + 500MG

Indications

• Pain and inflammation in osteoarthritis
• Pain and inflammation in rheumatoid arthritis
• Management of acute pain
• Musculoskeletal disorders

Dosage

Adults: 1 g once daily, taken at night, or 0.5–1 g daily, taken in the morning and 1 g at night depending on severity.

Mechanism of action

Naproxen exerts its clinical effects by blocking both COX-1 and COX-2 enzymes, which decreases prostaglandin synthesis. COX-1 is constitutively active and found in normal tissues, while COX-2 is inducible and primarily associated with pain, fever, and inflammation. The inhibition of COX-2 mediates the desired antipyretic, analgesic, and anti-inflammatory effects, while COX-1 inhibition is linked to gastrointestinal and renal side effects.

Pharmacodynamics

Naproxen displays anti-inflammatory, analgesic, and antipyretic activity. Its pharmacological effects stem from the inhibition of cyclooxygenase, which reduces prostaglandin synthesis in various tissues, including synovial fluid and gastric mucosa. While effective for pain relief, naproxen can raise blood pressure and increase the risk of gastrointestinal bleeding, especially when combined with other risk factors such as corticosteroids or anticoagulants.

Pharmacokinetics

Naproxen is absorbed after oral administration, with peak plasma concentrations typically occurring within 2 to 4 hours. It has a half-life of approximately 12 to 17 hours, allowing for twice-daily dosing in many cases. The drug is extensively metabolized in the liver, primarily via oxidation and glucuronidation, and is excreted mainly via the urine. Renal impairment can affect its clearance, necessitating caution in patients with existing kidney issues.

Contra-indications

• History of hypersensitivity to aspirin or any other NSAID
• Severe hepatic impairment
• Severe renal impairment
• Active gastrointestinal bleeding or peptic ulcer disease

Adverse effects

• Gastrointestinal upset
• Nausea
• Dizziness
• Headache
• Drowsiness
• Rash
• Renal toxicity
• Increased blood pressure
• Gastrointestinal bleeding
• Hypersensitivity reactions (e.g., angioedema, urticaria)

Interactions

• Increased risk of gastrointestinal bleeding with anticoagulants or corticosteroids
• May reduce the antihypertensive effect of certain antihypertensives
• Increased risk of nephrotoxicity when used with other nephrotoxic agents

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in patients with renal impairment
• Caution in patients with cardiovascular disease due to potential increase in blood pressure
• Use lowest effective dose for the shortest duration necessary

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risk of fetal ductus arteriosus closure.

Breast-feeding

Use with caution during breast-feeding as it is present in milk; manufacturer advises avoiding if possible.

Storage

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

Formulations

• Oral tablet
• Orodispersible tablet
• Oral suspension

Indications

• Acute migraine attacks
• Cluster headaches

Dosage

Children: For children aged 5–17 years, the initial dose is 500 micrograms once daily, taken at night, with potential increases up to 1.5 mg daily in divided doses. The maximum single dose (at night) is 1 mg.

Adults: Initially 50–100 mg, taken as soon as possible after the onset of a migraine attack. A second dose of 50–100 mg may be taken after at least 2 hours if required, but not exceeding a maximum of 300 mg per day.

Mechanism of action

Sumatriptan acts as an agonist at the 5-HT1B and 5-HT1D serotonin receptors. This activation leads to vasoconstriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. It decreases carotid arterial blood flow while increasing blood flow velocity in the internal carotid artery and middle cerebral artery, effectively reducing migraine symptoms. Sumatriptan does not cross the blood-brain barrier.

Pharmacodynamics

Sumatriptan effectively constricts cranial blood vessels and prevents the release of vasoactive neuropeptides. Its pharmacodynamics are characterized by a rapid onset of action, particularly via subcutaneous injection, and a potential for medication-overuse headaches in patients using it frequently. The drug's effects are dose-dependent and vary based on the route of administration.

Pharmacokinetics

Sumatriptan is rapidly absorbed following subcutaneous injection, with peak plasma concentrations occurring within 12-15 minutes. Oral bioavailability is approximately 14%, with a half-life of about 2.5 hours. It undergoes extensive first-pass metabolism in the liver, primarily by monoamine oxidase A, leading to its metabolites which have minimal activity. The drug is primarily excreted in the urine.

Contra-indications

• Severe hypertension
• Uncontrolled hypertension
• Acute porphyrias
• History of ischemic heart disease
• Peripheral vascular disease
• Severe hepatic impairment

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Dry mouth
• Diarrhea
• Fatigue
• Musculoskeletal stiffness
• Abnormal sensations (paresthesia)
• Palpitations
• Chest discomfort
• Vision changes (blurred vision)
• Serotonin syndrome
• Myocardial ischemia
• Hypersensitivity reactions

Interactions

• MAO inhibitors (e.g., moclobemide) may increase exposure to sumatriptan
• Concomitant use with other triptans or ergotamine derivatives is contraindicated due to increased risk of vasospastic reactions
• Propranolol may increase sumatriptan plasma levels

Precautions

• Monitor for signs of serotonin syndrome
• Use with caution in patients with a history of seizures
• Consider cardiovascular evaluation in patients with risk factors for coronary artery disease
• Not recommended for use in the elderly due to lack of safety data

Pregnancy

Sumatriptan should only be used in pregnancy if the benefit outweighs the risk, as safety in pregnancy has not been established.

Breast-feeding

Sumatriptan is excreted in breast milk. Caution is advised when administering to breastfeeding mothers, and it is recommended to wait at least 12 hours after administration before breastfeeding.

Storage

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

Formulations

• Sumatriptan 50 mg tablets
• Sumatriptan 100 mg tablets
• Sumatriptan 3 mg/0.5 ml injection
• Sumatriptan nasal spray 20 mg
• Sumatriptan orodispersible tablets 10 mg

Mechanism of action

As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme. Naproxen has pharmacologic actions similar to those of other prototypical nonsteroidal anti-inflammatory agents (NSAIAs). The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis. Naproxen inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2) (also referred to as prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2), respectively), have been identified that catalyze the formation of prostaglandins in the arachidonic acid pathway. Naproxen, like other prototypical NSAIAs, inhibits both COX-1 and COX-2. Although the exact mechanisms have not been clearly established, NSAIAs appear to exert anti-inflammatory, analgesic, and antipyretic activity principally through inhibition of the COX-2 isoenzyme; COX-1 inhibition presumably is responsible for the drugs' unwanted effects on GI mucosa and platelet aggregation. The anti-inflammatory, analgesic, and antipyretic effects of naproxen and other nonsteroidal anti-inflammatory agents (NSAIAs), including selective inhibitors of COX-2 (e.g., celecoxib, rofecoxib), appear to result from inhibition of prostaglandin synthesis. While the precise mechanism of the anti-inflammatory and analgesic effects of NSAIAs continues to be investigated, these effects appear to be mediated principally through inhibition of the COX-2 isoenzyme at sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Naproxen stabilizes lysosomal membranes and inhibits the response of neutrophils to chemotactic stimuli. The drug does not possess glucocorticoid or adrenocorticoid-stimulating properties. Naproxen lowers body temperature in patients with fever. Although the mechanism of the antipyretic effect of nonsteroidal anti-inflammatory agents is not known, it has been suggested that suppression of prostaglandin synthesis in the CNS (probably in the hypothalamus) may be involved. Naproxen-induced inhibition of prostaglandin synthesis may result in decreased frequency and intensity of uterine contractility. Prostaglandins E2 and F2alpha increase the amplitude and frequency of uterine contractions in pregnant women; current evidence suggests that primary dysmenorrhea is also mediated by these prostaglandins. Whether the increased production of prostaglandins associated with primary dysmenorrhea is mediated by COX-1 or COX-2 remains to be determined. Blood concentrations of a metabolite of prostaglandin F2alpha have been found to decrease in women with dysmenorrhea who were receiving naproxen. Therapy with naproxen has been effective in relieving menstrual pain and has reduced blood loss in women with menorrhagia, probably by inhibiting the formation of these prostaglandins. Administration of naproxen during late pregnancy may prolong gestation by inhibiting uterine contractions.

Pharmacodynamics

Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use. Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers.

Mechanism of action

Sumatriptan is an agonist of 5-HT_1B and 5-HT_1D. This agonism leads to constriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. Sumatriptan decreases carotid arterial blood flow, but increases blood flow velocity in the internal carotid artery and middle cerebral artery.[A179734 Agonism of the 5-HT_1B and 5-HT_1D receptors also inhibits sensory neurons, preventing the release of vasoactive peptides.[A179734 Sumatriptan does not cross the blood brain barrier. Sumatriptan and other currently available drugs that are effective for acute migraine, including dihydroergotamine and ergotamine, have binding affinity for serotonin type 1 (5-HT1) receptors, particularly the 5-HT1D (also called 5-HT1Dalpha) and 5-HT1B (also called 5-HT1Dbeta) subtypes located on trigeminal sensory neurons innervating dural blood vessels. The 5-HT1B and 5-HT1D receptors function as autoreceptors, activation of which leads to inhibition of firing of serotonin neurons and a reduction in the synthesis and release of serotonin. Upon binding to these 5-HT1 receptor subtypes, sumatriptan inhibits adenylate cyclase activity via regulatory G proteins, increases intracellular calcium, and affects other intracellular events that lead to vasoconstriction and inhibition of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release. Sumatriptan has the highest affinity for the 5-HT1D receptor, the most common serotonin receptor subtype in the brain, and a 2- to 17-fold lower affinity for 5-HT1A receptors; agonist activity at 5-HT1A and other serotonin receptors may be responsible for some of the adverse effects noted with administration of serotonin or serotonergic antimigraine drugs (eg, ergotamine, dihydroergotamine). Sumatriptan has essentially no affinity for (based on standard radioligand binding assays) nor pharmacologic activity at other serotonin receptors (eg, 5-HT2, 5-HT3) or at receptors of the dopamine1, dopamine2, muscarinic, histamine, benzodiazepine, or alpha1-, alpha2-, or beta-adrenergic type. Sumatriptan is a selective agonist of vascular serotonin (5-hydroxytryptamine; 5-HT) type 1-like receptors, probably the 5-HT1D and 5-HT1B subtypes. The mechanisms involved in the pathogenesis of migraine and cluster headache are not clearly understood; consequently, the precise mechanism of action of sumatriptan in the management of these disorders has not been established. However, current data suggest that sumatriptan may ameliorate migraine and cluster headache through selective constriction of certain large cranial blood vessels and/or inhibition of neurogenic inflammatory processes in the CNS. While some features of migraine clearly reflect effects on cerebral blood vessels, neurogenic mechanisms involving activation of the trigeminovascular system also have been implicated; current evidence suggests that both mechanisms may be involved. The vascular 5-HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may also contribute to the antimigrainous effect of sumatriptan in humans. Sumatriptan selectively reduces carotid arterial blood flow and/or constricts carotid arteriovenous anastomoses in anesthetized animals without appreciable effects on arterial blood pressure or total peripheral resistance. The drug produces contraction of vascular smooth muscle in vitro in saphenous veins in dogs and humans, but such contractions are weaker than those produced by serotonin or ergot alkaloids (eg, methysergide). For m

Pharmacodynamics

Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides. The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily. Medication overuse headaches may occur in patients who use sumatriptan frequently.