COSAMIDE

Indications

• Epilepsy
• Generalized tonic-clonic seizures
• Partial-onset seizures
• Neuropathic pain (off-label use)

Dosage

Children: In pediatric patients aged 4 years and older, initial dosing typically starts at 2

Adults: For adult patients, the usual starting dose of lacosamide is 50 mg twice daily, which may be increased by 100 mg weekly based on clinical response, up to a maximum dose of 400 mg per day.

Mechanism of action

Lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels, shifting the slow inactivation curve to more hyperpolarized potentials. This increases the fraction of sodium channels in the slow inactivated state, resulting in stabilization of hyperexcitable neuronal membranes, and inhibition of repetitive neuronal firing. Unlike traditional sodium channel blockers, lacosamide does not affect the fast component of sodium currents.

Pharmacodynamics

Lacosamide is a highly potent antiepileptic with stereoselectivity and anticonvulsant properties. It also exhibits analgesic activity by blocking sensory neuronal voltage-gated sodium channels that mediate neuropathic pain responses. The drug is characterized as a chiral functionalized amino acid, where the S-stereoisomer does not have antiepileptic activity.

Pharmacokinetics

Lacosamide is well absorbed after oral administration with a bioavailability of approximately 100%. It is metabolized predominantly by hydrolysis and is not significantly affected by cytochrome P450 enzymes. The elimination half-life is approximately 13 hours, allowing for twice-daily dosing. The drug is primarily excreted in the urine, with less than 5% of the dose excreted unchanged. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to lacosamide or any of its excipients
• History of severe hypersensitivity reactions, including anaphylaxis
• Severe cardiac conduction disorders, including second or third degree atrioventricular block

Adverse effects

• Dizziness
• Fatigue
• Nausea
• Headache
• Diplopia
• Ataxia
• Somnolence
• Euphoria
• Palpitations
• Agranulocytosis
• Psychotic disorders
• Suicidal tendencies
• Angioedema
• Rhabdomyolysis

Interactions

• May enhance the effects of other CNS depressants
• Caution with concomitant use of drugs affecting cardiac conduction
• Potential for increased plasma levels when used with strong CYP3A4 inhibitors

Precautions

• Monitor for signs of hypersensitivity reactions
• Caution in patients with a history of drug abuse
• Use with caution in patients with cardiac conduction problems
• Assess renal function prior to use and adjust dose accordingly
• Gradual withdrawal is advised to prevent seizure exacerbation

Pregnancy

Limited data available; use only if the potential benefit justifies the potential risk to the fetus. Animal studies suggest potential risks.

Breast-feeding

Present in breast milk; use only if potential benefit outweighs risk.

Storage

Store at room temperature, protected from moisture and light. Keep out of reach of children.

Formulations

• Tablets (100 mg, 150 mg, 200 mg, 300 mg, 400 mg)
• Oral solution (10 mg/mL)
• Injection (20 mg/mL)

Indications

• Dose modification due to adverse drug reactions
• Therapeutic drug monitoring
• Management of drug interactions
• Adjustment for renal or hepatic impairment
• Pediatric dosing adjustments
• Geriatric dosing considerations

Dosage

Children: Refer to the BNF for Children for pediatric dosing adjustments, as they depend on various factors including age, weight, and specific clinical scenarios.

Adults: Refer to the specific drug monograph for detailed dosing information, as adjustments are highly individualized based on patient-specific factors.

Mechanism of action

The mechanism of action for adjustment is not applicable as it is not a specific drug but rather a clinical practice. However, the underlying principle involves tailoring pharmacotherapy to individual patient needs, which may include pharmacokinetic adjustments based on metabolism, clearance rates, and patient adherence.

Pharmacodynamics

Pharmacodynamics in the context of adjustment involves understanding how drugs affect the body and how different variables such as age, weight, kidney and liver function, and concomitant medications can influence the efficacy and safety of a drug regimen. Each adjustment is aimed at optimizing therapeutic outcomes while reducing toxicity.

Pharmacokinetics

Pharmacokinetics in the context of adjustment refers to the study of how the body absorbs, distributes, metabolizes, and excretes medications. Factors such as renal and hepatic function, body mass index, and age play critical roles in determining the appropriate adjustments needed in medication dosing. Understanding these parameters is essential for effective dose adjustment.

Pregnancy

Consult a healthcare professional before use, as the safety of adjustments during pregnancy may vary depending on the specific drug or treatment being adjusted.

Breast-feeding

Consult a healthcare professional before use, as the safety of adjustments during breastfeeding may depend on the specific drug or treatment being adjusted.

Storage

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

Indications

• Adjustment of pH in pharmaceutical formulations
• Facilitation of drug absorption
• Used in sterile preparations

Dosage

Children: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Adults: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Mechanism of action

Hydrochloric acid dissociates in aqueous solution to release hydrogen ions (H+), leading to a decrease in pH. This acidic environment promotes the activation of pepsinogen to pepsin, an enzyme essential for protein digestion. Additionally, the acidity aids in the absorption of certain minerals and drugs that require an acidic environment for optimal bioavailability.

Pharmacodynamics

The primary pharmacodynamic action of hydrochloric acid is the maintenance of gastric acidity, which is essential for normal digestive processes. The acidic environment helps in denaturing proteins, activating digestive enzymes, and providing a barrier against pathogenic microorganisms. Its effects can influence the absorption and efficacy of various medications, particularly those that are pH-dependent.

Pharmacokinetics

Hydrochloric acid does not undergo significant systemic absorption when used in its normal contexts, as it acts locally within the gastrointestinal tract. The amount of hydrochloric acid produced by the stomach varies with food intake and physiological needs. It is secreted by parietal cells in the gastric mucosa, and its secretion is regulated by neural, hormonal, and local factors. The half-life of hydrochloric acid is not applicable as it is continuously produced and neutralized within the gastrointestinal tract.

Contra-indications

• Hypersensitivity to hydrochloric acid or any of its components
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Esophageal irritation
• Gastric mucosal irritation
• Electrolyte imbalances

Interactions

• May interact with alkaline substances, potentially neutralizing hydrochloric acid
• Caution with antacids as they may affect the efficacy of hydrochloric acid

Precautions

• Use with caution in patients with a history of gastritis or gastric ulcers
• Monitor electrolytes in prolonged use
• Use cautiously in patients with respiratory conditions due to potential aspiration risks

Pregnancy

Hydrochloric acid is classified as a category C drug. Use during pregnancy only if clearly needed and the potential benefits justify the risks to the fetus.

Breast-feeding

There is limited data on the excretion of hydrochloric acid in human milk. Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and heat. Ensure the container is tightly closed.

Formulations

• Oral solutions
• Injectable forms
• Tablets

Indications

• Cryotherapy for the destruction of abnormal tissue
• Treatment of warts, moles, and other skin lesions
• Nitrogen narcosis in diving

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: For cryotherapy, the dosage and duration depend on the specific condition being treated and should be determined by the healthcare provider. Refer to specific guidelines for each condition.

Mechanism of action

In cryotherapy, the mechanism of action involves three stages: heat transfer, cell injury, and inflammation. The boiling point of liquid nitrogen is -196°C, which initiates heat transfer, leading to cell injury during the thawing process. The inflammation stage follows, characterized by edema and erythema, resulting from cellular death and contributing to local cell destruction. Additionally, nitrogen can cause direct toxic effects on brain functions, leading to nitrogen narcosis, which impairs cognitive abilities and motor functions due to its impact on nerve conduction.

Pharmacodynamics

Nitrogen's pharmacodynamics relate to its behavior in cryotherapy and asphyxiation. In cryotherapy, it induces tissue destruction through rapid cooling, leading to apoptosis of abnormal cells. In high-pressure environments, nitrogen narcosis affects the central nervous system, producing symptoms similar to alcohol intoxication, ultimately decreasing reasoning, decision-making abilities, and manual dexterity.

Pharmacokinetics

Nitrogen does not undergo metabolism in the traditional sense, as it is an inert gas at physiological conditions. Its pharmacokinetics involve physical principles of gas exchange and partial pressures. In the case of nitrogen narcosis, the effects are influenced by the partial pressure of nitrogen in the bloodstream, which increases with depth during diving. Nitrogen is primarily eliminated from the body through respiration.

Adverse effects

• Narcotic effect at high pressures
• Stupor or euphoria
• Decreased motor function and manual dexterity
• Asphyxiation due to oxygen displacement

Precautions

• Careful monitoring in environments with high nitrogen pressures
• Avoidance of rapid ascents in diving to prevent nitrogen narcosis
• Use in controlled settings to prevent asphyxiation risks

Pregnancy

Nitrogen is generally considered safe in terms of direct effects during pregnancy; however, the safety of exposure in high-pressure environments should be assessed.

Breast-feeding

Nitrogen is not known to affect breastfeeding; however, caution is recommended in environments where nitrogen levels may displace oxygen.

Storage

Store in a cool, dry place away from heat sources; liquid nitrogen should be handled with care due to extreme cold.

Formulations

• Liquid nitrogen
• Nitrogen gas (compressed)

Mechanism of action

Caused by neuronal hyperexcitability, seizures in epilepsy involve sustained firing of sodium-dependent action potentials. The slow inactivation process, intrinsic to voltage-gated sodium channel functioning, has been implicated in the paroxysmal depolarizing shifts associated with epileptic activity. The exact mechanism of action of lacosamide is not fully known; however, in vitro electrophysiological studies have shown that lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels, shifting the slow inactivation curve to more hyperpolarized potentials and augmenting the maximal fraction of channels in the slow inactivated state. This results in the stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing. Lacosamide does not affect the fast component of voltage-gated sodium currents, unlike traditional sodium channel blockers.

Pharmacodynamics

Lacosamide is an antiepileptic drug with high oral potency, stereoselectivity, and anticonvulsant effects. By blocking sensory neuronal voltage-gated sodium channels that mediate neuropathic pain responses, lacosamide was shown to possess analgesic activity. Lacosamide is a chiral functionalized amino acid. The S-stereoisomer does not exhibit antiepileptic activity.

Mechanism of action

In cryotherapy, mechanism of action could be classified into three stages: 1. heat transfer, 2. cell injury and 3. inflammation. Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. ... Nitrogen also has a direct toxic action of its own, affecting brain functions and inducing a stupor or euphoria. Nitrogen narcosis ("rapture of the deep" or "the martini effect") results from a direct toxic effect of high nitrogen pressure on nerve conduction and produces effects similar to alcohol intoxication. Complex reasoning, decision-making ability, motor function, and manual dexerity decrease. Individuals vary in this response widely, but it typically can be noticed among divers at depths exceeding 100 ft (30 m). For example, certain individuals experience no effect at depths of < or = 130 ft, whereas others feel some effect at around 80 ft. Nonetheless, the narcotic effect increases with increasing depth so that each additional 50 ft incrementally produces the effect of "another martini". A simple asphyxiant, nitrogen's main toxicty arises from its ability to displace O2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitrogen is an inert substance and does not exert a direct toxicological effect. Nitrogen acts by the physiological effect of simple asphyxia on the target species within a Controlled Atmosphere Treatment (CAT) bubble. The biocide action of nitrogen is due to its displacement of oxygen from an atmospheric oxygen level of 20.8% to levels < 0.2% v/v in the CAT bubble. The level of oxygen is the critical factor. Victims exposed to atmospheres deficient in oxygen, i.e. < 19%, will begin to display signs and symptoms of oxygen-deficient exposure of air due to an increase in nitrogen.