Hyoscine Butylbromide

Indications

• Nausea and vomiting due to motion sickness
• Palliative care for excessive respiratory secretions
• Premedication prior to surgery
• Management of bowel colic

Dosage

Children: Refer to the BNF for Children for specific dosing information; dosage

Adults: For motion sickness, the recommended dosage is 150–300 micrograms taken 30 minutes before travel, followed by 150–300 micrograms every 6 hours as needed, with a maximum of 900 micrograms per day. For palliative care and other indications, doses may vary; refer to BNF for specific guidance.

Mechanism of action

Hyoscine hydrobromide exerts its effects by antagonizing muscarinic receptors, particularly M1 receptors located in the vestibular system and the vomiting center of the brain. This action reduces the excitatory input from the vestibular system, which is responsible for motion sickness. Additionally, it diminishes gastrointestinal motility and secretions, effectively alleviating symptoms of nausea and vomiting.

Pharmacodynamics

As an anticholinergic agent, hyoscine hydrobromide decreases the activity of the parasympathetic nervous system. Its sedative effects can also lead to drowsiness and sedation, which may be beneficial in some patients but could impair the ability to perform skilled tasks. Its antimuscarinic properties can result in side effects like dry mouth, urinary retention, and blurred vision due to reduced secretions and muscle relaxation.

Pharmacokinetics

Hyoscine hydrobromide is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 hour. It has a half-life of approximately 3 to 6 hours. The drug is extensively metabolized in the liver, and its metabolites are excreted primarily through the kidneys. Its effects can vary based on the route of administration, with transdermal patches providing prolonged action.

Contra-indications

• Asthma
• Bronchiectasis
• Bronchitis
• Epilepsy
• Severe coronary artery disease
• Pyloroduodenal obstruction
• Susceptibility to angle-closure glaucoma
• Urinary retention

Adverse effects

• Anticholinergic syndrome
• Anxiety
• Decreased appetite
• Arrhythmia
• Blood disorders
• Increased bronchial secretion viscosity
• Confusion
• Dizziness
• Drowsiness
• Dry mouth
• Epigastric discomfort
• Fatigue
• Haemolytic anaemia
• Headache
• Hypotension
• Jaundice
• Movement disorders
• Muscle spasms
• Nightmares
• Palpitations
• Photosensitivity reaction
• Urinary retention
• Blurred vision

Interactions

• Antihistamines
• Sedatives
• Clozapine therapy

Precautions

• Caution in elderly patients due to increased susceptibility to anticholinergic side effects
• Use with caution in hepatic impairment
• Use with caution in renal impairment
• May impair performance of skilled tasks (e.g. driving or cycling) due to drowsiness

Pregnancy

Most manufacturers advise avoiding use during pregnancy; however, there is no evidence of teratogenicity. Use in the latter part of the third trimester may cause adverse effects in neonates such as irritability, paradoxical excitability, and tremor.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Sublingual tablets
• Transdermal patches
• Subcutaneous injection
• Intramuscular injection
• Continuous subcutaneous infusion

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Mechanism of action

Butyl compounds act by interacting with various biological pathways depending on their specific structure. For example, in the context of pharmaceutical use, they may function as solvents for drugs, enhancing solubility and bioavailability, or may have specific receptor interactions based on their functional groups. The precise mechanism of action would vary with the specific butyl derivative.

Pharmacodynamics

The pharmacodynamics of butyl compounds can vary widely. Generally, they may affect various physiological processes depending on their chemical nature. For example, butyl derivatives may exhibit anti-inflammatory, analgesic, or even anesthetic properties in certain contexts. The pharmacodynamic profile is largely dependent on the specific butyl compound and its interactions with cellular receptors and enzymes.

Pharmacokinetics

The pharmacokinetics of butyl compounds vary significantly among different derivatives. Commonly, these compounds are absorbed through various routes, depending on their formulation. They may undergo metabolic processes in the liver before being excreted primarily via urine. The exact absorption rates, half-lives, and clearance rates would depend on the specific butyl derivative and its formulation.

Pregnancy

There are no specific studies regarding the use of butyl compounds in pregnancy. Caution should be exercised.

Breast-feeding

There is limited information on the excretion of butyl compounds in human breast milk. Caution is advised.

Storage

Store in a well-closed container, protected from light and moisture.

Indications

• Irritable bowel syndrome
• Other gastrointestinal disorders associated with smooth muscle spasms

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Butylbromide acts as a competitive antagonist of muscarinic acetylcholine receptors. This inhibition decreases the contractility of smooth muscle in the gastrointestinal tract, leading to reduced spasms and discomfort. It predominantly affects the parasympathetic nervous system, which regulates involuntary bodily functions.

Pharmacodynamics

The pharmacodynamic effects of butylbromide include relaxation of smooth muscle and reduction of secretions in the gastrointestinal tract. This results in decreased gastrointestinal motility and relief from cramping and pain associated with smooth muscle contractions. The onset of action is typically rapid, making it effective for acute symptoms.

Pharmacokinetics

Butylbromide is absorbed from the gastrointestinal tract following oral administration. It is distributed throughout the body, with a preference for tissues with high cholinergic activity. The drug undergoes hepatic metabolism, and its metabolites are excreted primarily through the urine. The half-life and exact pharmacokinetic parameters can vary depending on individual patient factors.

Pregnancy

Butylbromide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether butylbromide is excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

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

Indications

• Motion sickness
• Nausea and vomiting
• Pre-operative sedation
• Spasmodic disorders of the gastrointestinal tract

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Hyoscine exerts its effects primarily by antagonizing muscarinic acetylcholine receptors, which inhibits cholinergic transmission in the central nervous system and peripheral tissues. This results in decreased gastrointestinal motility, reduced salivation, and diminished vestibular sensitivity, which are beneficial in preventing nausea and vomiting associated with motion sickness.

Pharmacodynamics

The pharmacodynamic effects of hyoscine include sedation, amnesia, reduction of motion sickness symptoms, and relaxation of smooth muscles in the gastrointestinal tract. These actions are dose-dependent, and the drug may also exhibit peripheral anticholinergic effects such as decreased secretions in the respiratory tract.

Pharmacokinetics

Hyoscine is well absorbed from the gastrointestinal tract and can also be administered transdermally or via injection. It has a bioavailability of approximately 90% when taken orally. The drug undergoes extensive hepatic metabolism, and its elimination half-life is about 3 to 6 hours. It is primarily excreted in the urine as metabolites, and the onset of action varies based on the route of administration.

Contra-indications

• Hypersensitivity to hyoscine or any of its excipients
• Myasthenia gravis
• Severe glaucoma
• Prostatic hypertrophy
• Obstructive gastrointestinal disease

Adverse effects

• Drowsiness
• Confusion
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Tachycardia

Interactions

• clozapine+hyoscine: Unknown (additive effect)
• antipsychotics, second generation+hyoscine: Unknown (additive effect)

Precautions

• Use with caution in patients with cardiovascular disease
• May impair the ability to drive or operate machinery
• Caution in patients with a history of seizures

Pregnancy

Hyoscine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines.

Breast-feeding

Hyoscine is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Injectable solution
• Transdermal patch

Indications

• Antiseptic for skin disinfection
• Solvent in pharmaceutical formulations
• Cleaning agent in laboratories and healthcare settings

Dosage

Children: For pediatric use, consult specific guidelines in the BNF for Children, as dosing may vary based on age, weight, and clinical circumstances.

Adults: For skin antisepsis, apply isopropyl alcohol topically in a concentration of 70% to the affected area. Dosage may vary based on clinical indication and setting.

Mechanism of action

Isopropyl alcohol works primarily as an antiseptic by denaturing proteins and disrupting cell membranes of bacteria, viruses, and fungi, leading to cell lysis and death. Its efficacy is enhanced by the presence of water, which facilitates the penetration of the alcohol into microbial cells.

Pharmacodynamics

Isopropyl alcohol exhibits a rapid onset of action against a variety of pathogens, including gram-positive and gram-negative bacteria, fungi, and some viruses. Its antimicrobial activity is concentration-dependent, with higher concentrations generally providing a broader spectrum of activity. It is commonly used in concentrations ranging from 60% to 90%, with 70% being optimal for disinfection due to its ability to penetrate the cell wall effectively.

Pharmacokinetics

Isopropyl alcohol is readily absorbed through the skin and mucous membranes. After absorption, it is metabolized primarily in the liver to acetone, which is then further metabolized and excreted, mostly via urine. The elimination half-life of isopropyl alcohol varies but is typically around 2 to 3 hours. Its effects can be influenced by factors such as dosage, route of exposure, and individual metabolic differences.

Pregnancy

Isopropyl alcohol should be used with caution during pregnancy. It is a category C drug, indicating that risk cannot be ruled out.

Breast-feeding

Caution is advised when using isopropyl alcohol during breastfeeding, as it is not known if it is excreted in human milk.

Storage

Isopropyl alcohol should be stored at room temperature, away from heat and flame. Keep the container tightly closed and in a well-ventilated area.

Formulations

• Isopropyl alcohol 70% solution
• Isopropyl alcohol 99% solution

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.