PICOSWIFT

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Alcohol use disorder
• Acute alcohol intoxication
• Antiseptic for skin disinfection

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes, ion channels, enzymes, and receptors. Ethanol binds directly to the receptors for acetylcholine, serotonin, GABA, and NMDA receptors for glutamate. The sedative effects are mediated through binding to GABA receptors and glycine receptors, while also inhibiting NMDA receptor functioning. As an anti-infective, ethanol acts as an osmolyte, disrupting the osmotic balance across cell membranes. The acute effects result from competitive inhibition of glycine binding to NMDA receptors, leading to disrupted glutamatergic neurotransmission.

Pharmacodynamics

Ethanol produces cellular injury through dehydration and precipitation of cytoplasm, contributing to its bactericidal and antifungal actions. It can lead to neuritis and nerve degeneration when injected near nerve tissues. Up to 98% of ethanol in the body is oxidized, primarily by the hepatic enzyme alcohol dehydrogenase. Its modulation of neurotransmitter receptors, particularly GABA and NMDA, leads to its sedative properties and potential for developing tolerance with chronic use.

Pharmacokinetics

Ethanol is readily absorbed from the gastrointestinal tract and distributed throughout the body. It has a volume of distribution of approximately 0.5 to 0.6 L/kg. Ethanol is metabolized predominantly in the liver by alcohol dehydrogenase to acetaldehyde, which is further oxidized to acetic acid by aldehyde dehydrogenase. The elimination half-life of ethanol varies but is generally around 4 to 5 hours. Factors such as age, sex, body weight, and genetic variability can influence ethanol metabolism.

Contra-indications

• Hypersensitivity to ethanol
• Acute alcohol intoxication
• Severe liver disease
• Pregnancy (in non-medicinal use)
• Severe pancreatitis
• Severe head injury or intracranial bleeding

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Headache
• Sedation
• Cognitive impairment
• Respiratory depression
• Hypotension
• Gastrointestinal bleeding
• Alcohol withdrawal syndrome

Interactions

• CNS depressants (e.g., benzodiazepines, opioids) may enhance sedative effects
• Disulfiram may cause unpleasant reactions when taken with ethanol
• Acetaminophen may increase hepatic toxicity when used with ethanol
• Warfarin may have altered effects when used with ethanol

Precautions

• Caution in patients with a history of alcohol abuse
• Use with caution in patients with hepatic impairment
• Monitor for signs of respiratory depression
• Consider potential for addiction and withdrawal symptoms
• Use in moderation in older adults due to increased sensitivity

Pregnancy

Ethanol should be avoided during pregnancy due to the risk of fetal alcohol spectrum disorders.

Breast-feeding

Ethanol can pass into breast milk; breastfeeding should be avoided for a minimum of 2 hours after consumption.

Storage

Store in a cool, dry place away from light. Keep tightly closed and out of reach of children.

Formulations

• Oral solutions
• Topical antiseptics
• Intravenous formulations
• Medicinal tinctures

Indications

• Heavy metal poisoning
• Lead poisoning
• Mercury poisoning
• Cadmium exposure
• Arsenic toxicity
• Chronic exposure to heavy metals

Dosage

Children: Pediatric dosing should be carefully determined based on weight and specific clinical guidelines for the type of heavy metal exposure. Refer to the BNF for Children for detailed recommendations.

Adults: Dosage varies widely based on the specific heavy metal, exposure level, and treatment protocol. Refer to clinical guidelines for specific chelation therapy dosing or symptomatic management.

Mechanism of action

Heavy metals exert their toxic effects through various mechanisms, including the inhibition of enzymatic activity, disruption of cellular membranes, and generation of oxidative stress. They can bind to sulfhydryl groups in proteins, affecting their function. Additionally, heavy metals can interfere with the synthesis of hemoglobin and disrupt the transport of essential metals, leading to deficiencies and metabolic disturbances.

Pharmacodynamics

The pharmacodynamics of heavy metals are complex and depend on the specific metal in question. Heavy metals typically accumulate in the body, leading to chronic toxicity. The biological effects can manifest as organ-specific damage, such as neurotoxicity from lead exposure, nephrotoxicity from cadmium, and developmental toxicity from mercury. The effects can vary based on the duration and level of exposure.

Pharmacokinetics

The pharmacokinetics of heavy metals vary widely among different metals. They may be absorbed through the gastrointestinal tract, inhalation, or skin. Once in the body, heavy metals can be distributed to various tissues, including the liver, kidneys, and brain. They often bind to plasma proteins and can be stored in bones or fatty tissues. Excretion primarily occurs through urine and feces, although some metals may have prolonged half-lives in the body, leading to bioaccumulation.

Pregnancy

The safety of heavy metals during pregnancy is generally not established, and exposure should be minimized due to potential risks to fetal development.

Breast-feeding

Heavy metals can be excreted in breast milk, and exposure should be limited to avoid potential harm to the nursing infant.

Storage

Store in a cool, dry place away from direct sunlight. Specific storage conditions may vary based on the type of heavy metal.

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Powder
• Granules
• Tablets
• Syrup

Mechanism of action

Oxides do not have a single mechanism of action as they are a broad category of compounds. However, in general, metal oxides can exhibit catalytic properties, while non-metal oxides may participate in biochemical reactions by forming acids or bases upon dissolution in water.

Pharmacodynamics

The pharmacodynamics of oxides depend on the specific type of oxide and its interaction with biological systems. For instance, metal oxides may have antimicrobial properties, while certain non-metal oxides can influence metabolic pathways through their acid-base chemistry. The effects vary widely, necessitating specific studies for each oxide's role in therapeutic contexts.

Pharmacokinetics

The pharmacokinetics of oxides are also variable. Many metal oxides are poorly soluble and thus have limited absorption when ingested. Non-metal oxides, such as carbon dioxide, can be readily absorbed and utilized in metabolic processes. The distribution, metabolism, and excretion of oxides depend on their chemical form and the biological system in which they are involved.

Pregnancy

Not applicable as oxide is not a drug but a class of chemical compounds.

Breast-feeding

Not applicable as oxide is not a drug but a class of chemical compounds.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Bowel preparation prior to colonoscopy
• Preparation for other gastrointestinal diagnostic procedures

Dosage

Children: For children, the dosage must be determined according to age and weight. Refer to the BNF for Children for specific dosing guidelines.

Adults: For adults, the typical dosage for bowel preparation is 20 mg of sodium picosulfate (or as directed on the product label), usually taken in the evening before the procedure, often combined with magnesium citrate.

Mechanism of action

Sodium picosulfate is a contact laxative that inhibits the absorption of water and electrolytes while increasing their secretion into the intestinal lumen. It is converted by colonic bacterial enzyme sulfatase into an active metabolite, bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM), which acts directly on the colonic mucosa to stimulate colonic peristalsis.

Pharmacodynamics

Sodium picosulfate is classified as a stimulant laxative and has been shown to effectively produce a purgative effect in conjunction with magnesium citrate. In clinical studies, a significant majority of patients undergoing colonoscopy reported that sodium picosulfate-containing preparations provided effective bowel cleansing.

Pharmacokinetics

Sodium picosulfate is converted in the colon by bacterial enzymes into its active form, which exerts its effects locally in the colonic mucosa. The onset of action typically occurs within 6 to 12 hours after administration, depending on individual factors such as gastrointestinal motility.

Contra-indications

• Hypersensitivity to picosulfate or any of its components
• Severe dehydration
• Intestinal obstruction
• Appendicitis
• Acute abdominal pain of unknown origin
• Severe inflammatory bowel disease

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Electrolyte imbalance
• Dehydration

Interactions

• May interact with other laxatives, increasing the risk of dehydration and electrolyte imbalance
• Potentially alters the absorption of other medications taken simultaneously

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolytes in prolonged use
• Not recommended for use in children under 12 years unless advised by a healthcare professional

Pregnancy

There is limited data on the use of sodium picosulfate during pregnancy. It should only be used if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Sodium picosulfate is excreted in breast milk, but at therapeutic doses, it is not expected to adversely affect the nursing infant. Caution is advised.

Storage

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

Formulations

• Oral solution
• Tablets

Indications

• Used as an excipient in oral, topical, and parenteral formulations
• Stabilizer in emulsions and suspensions
• Thickening agent in gels and creams
• Binder in tablet formulations

Dosage

Children: Refer to specific product guidelines for dosage and formulation details, as PVP is typically used as an excipient rather than a primary therapeutic agent.

Adults: Refer to specific product guidelines for dosage and formulation details, as PVP is typically used as an excipient rather than a primary therapeutic agent.

Mechanism of action

Polyvinylpyrrolidone acts primarily as a solubilizing agent and excipient in drug formulations. It enhances the solubility and bioavailability of poorly soluble drugs by forming complexes that increase their dissolution rate. PVP can form hydrogen bonds with water, leading to improved hydration and dispersion of active pharmaceutical ingredients.

Pharmacodynamics

PVP exhibits properties that allow it to modify the viscosity and texture of formulations. It can increase the stability of active ingredients in a solution, thus prolonging their shelf life. The pharmacodynamic effects are largely dependent on its role as a vehicle rather than possessing intrinsic therapeutic activity. Its ability to form gels in the presence of water makes it useful in sustained-release formulations and controlled-release drug delivery systems.

Pharmacokinetics

PVP is not absorbed systemically when applied topically or when ingested in typical pharmaceutical doses. It is metabolized by hydrolysis into smaller molecules, which are then excreted in urine. Due to its high molecular weight, PVP is primarily eliminated through renal pathways. The pharmacokinetic profile indicates that it remains localized at the site of application, providing localized effects without significant systemic exposure.

Pregnancy

Polyvinylpyrrolidone (PVP) is generally considered safe for use during pregnancy when used in appropriate applications, but data on its safety is limited. Always consult a healthcare professional before use.

Breast-feeding

Polyvinylpyrrolidone is unlikely to pose a risk during breastfeeding, but consult a healthcare professional for advice on specific use.

Storage

Store at room temperature, away from moisture and heat. Keep in a tightly closed container.

Formulations

• Oral solution
• Topical gel
• Eye drops
• Injectable solution

Indications

• Hypokalemia
• Potassium depletion
• Electrolyte imbalance

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Potassium carbonate dissociates in the body to release potassium ions, which are essential for various physiological processes. These ions are critical for maintaining normal membrane potential, nerve impulse conduction, and muscle contraction. By increasing potassium levels in the blood, it helps to restore normal electrolyte balance.

Pharmacodynamics

Potassium is a vital electrolyte that plays a key role in maintaining fluid balance, acid-base balance, and muscle function. An adequate potassium level is crucial for cardiac function, as it helps regulate heart rhythm. Potassium carbonate acts to increase serum potassium levels, which can help prevent complications associated with potassium deficiency.

Pharmacokinetics

Potassium carbonate is rapidly absorbed in the gastrointestinal tract. The potassium ions are distributed throughout the body's fluids and tissues, primarily in intracellular compartments. Renal excretion is the primary route of elimination, with potassium being excreted through urine. The half-life of potassium in the body varies depending on the individual's renal function and dietary intake.

Contra-indications

• Hyperkalemia
• Severe renal impairment
• Adrenal insufficiency
• Untreated Addison's disease

Adverse effects

• Gastrointestinal irritation
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hyperkalemia
• Muscle weakness
• Cardiac arrhythmias

Interactions

• ACE inhibitors may increase the risk of hyperkalemia
• Potassium-sparing diuretics may lead to elevated potassium levels
• Non-steroidal anti-inflammatory drugs (NSAIDs) can impair renal function and increase potassium retention
• Digoxin levels may be affected by changes in potassium levels

Precautions

• Monitor serum potassium levels regularly, especially in patients with renal impairment or those on medications that affect potassium levels
• Use with caution in patients with cardiovascular disease
• Consider potential gastrointestinal side effects

Pregnancy

Potassium carbonate can be used during pregnancy if indicated, but caution is advised and serum potassium levels should be monitored.

Breast-feeding

Potassium carbonate is excreted in breast milk; however, it is generally considered safe when used as directed.

Storage

Store in a tightly closed container, in a cool, dry place, away from moisture and incompatible substances.

Formulations

• Oral tablets
• Oral powder
• Injection solution

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

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

Indications

• Caloric reduction in food and beverages
• Management of diabetes
• Weight management

Dosage

Children: Refer to the BNF for Children for specific guidelines on the use of sucralose in pediatric populations.

Adults: Sucralose is typically used in food and beverage products as a sweetener. There are no specific dosage recommendations for adults, as it is used according to taste preference and product formulation.

Mechanism of action

Sucralose acts as a positive allosteric modulator of the human sweet taste receptor. It interacts with the T1R taste receptor family, particularly enhancing the sweetness perception by binding to the hinge region of the receptor. This interaction induces a conformational change that stabilizes the active state of the receptor, increasing its responsiveness to sweet stimuli. This mechanism allows sucralose to mimic the taste of sugar without the associated caloric intake.

Pharmacodynamics

As a non-nutritive sweetener, sucralose does not undergo metabolic processing in the body, which means it does not contribute to energy intake. It provides intense sweetness at low concentrations, stimulating the sweetness receptors in the taste buds. The pharmacodynamic profile indicates minimal physiological effects beyond taste perception, making it suitable for dietary use without impacting blood glucose levels.

Pharmacokinetics

Sucralose is poorly absorbed in the gastrointestinal tract, with an estimated absorption rate of less than 15%. The majority of ingested sucralose is excreted unchanged in the urine. The elimination half-life is not well defined due to its minimal absorption, but it is generally considered to have a rapid clearance from the body. The pharmacokinetic properties support its use as a safe alternative to sugar for those managing caloric intake.

Pregnancy

Sucralose is generally considered safe during pregnancy, but it is recommended to consult a healthcare provider.

Breast-feeding

Sucralose is also considered safe during breastfeeding, although it is advisable to seek medical advice.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Granulated sucralose
• Liquid sucralose
• Tablets

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

Picosulfuric acid, as sodium picosulfate, is a contact laxative. Sodium picosulfate inhibits the absorption of water and electrolytes, and increases their secretion into the intestinal lumen. It is hydrolyzed by colonic bacterial enzyme, sulfatase, to form an active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM), which acts directly on the colonic mucosa to stimulate colonic peristalsis.

Pharmacodynamics

Sodium picosulfate is a stimulant laxative that in conjunction with magnesium citrate, produces a purgative effect on stools. In a multicentre, observational study comprising of patients undergoing colonoscopy, more than 93.0% of the patients receiving sodium picosulfate-containing preparations reported the colon cleansing effect to be effective.

Mechanism of action

Positive allosteric modulators of the human sweet taste receptor ...developed as a new way of reducing dietary sugar intake .../can be used as/ ...valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, .../the study/ reveal how ...sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.