Ipravent Inhaler (CFC Free)

Indications

• Maintenance treatment of chronic obstructive pulmonary disease (COPD)
• Reversible airways obstruction in asthma
• Rhinorrhea associated with allergic and non-allergic rhinitis

Dosage

Children: For inhalation: Child 1 month

Adults: For inhalation: 20–40 micrograms 3–4 times a day. For intranasal administration: Apply 2–3 drops 2–3 times a day into each nostril.

Mechanism of action

Ipratropium bromide acts as a competitive antagonist of acetylcholine at muscarinic receptors. This inhibition prevents bronchoconstriction and promotes bronchodilation, thereby easing airflow in obstructive airway diseases. It primarily affects M1 and M3 muscarinic receptors in the airway smooth muscle and secretory glands, reducing mucus secretion and aiding ventilation.

Pharmacodynamics

The onset of action for ipratropium bromide typically occurs within 30 to 60 minutes after inhalation, with peak effects observed at this time. Its bronchodilatory effects can last for approximately 3 to 6 hours, making it suitable for multiple doses throughout the day. The drug is less effective than beta-agonists in producing bronchodilation but has a complementary role in therapy, especially for patients with chronic conditions requiring long-term management.

Pharmacokinetics

Ipratropium bromide is administered via inhalation, leading to localized action in the lungs with minimal systemic absorption. The systemic bioavailability is low, resulting in a reduced incidence of systemic side effects. It undergoes hepatic metabolism, with metabolites excreted primarily in the urine. The elimination half-life varies but is generally around 2 hours, allowing for flexible dosing intervals. The maximal effect is usually achieved within an hour post-administration.

Adverse effects

• dizziness
• epistaxis
• dry mouth
• nausea

Interactions

• beta2 agonists

Precautions

• Avoid spraying near eyes
• Patients with convulsive disorders should use with caution

Pregnancy

Ipratropium bromide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for individual assessment.

Breast-feeding

Ipratropium bromide is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Inhalation aerosol: 20-40 micrograms per actuation
• Nebulised solution: 250 micrograms per dose
• Nasal spray: 20 micrograms per actuation

Mechanism of action

Fluoropropane acts primarily as a refrigerant due to its low boiling point and favorable thermodynamic properties. Its mechanism of action in this context involves the absorption and release of heat as it transitions between liquid and gas phases. The presence of fluorine atoms enhances its stability and lowers its environmental impact compared to other halogenated compounds.

Pharmacodynamics

The pharmacodynamics of fluoropropane are not well established in clinical use, as it is primarily utilized for its physical properties rather than biological effects. Its efficacy is largely determined by its physical state changes and thermal properties, rather than receptor interactions or metabolic pathways commonly evaluated for pharmaceutical agents.

Pharmacokinetics

Detailed pharmacokinetic data for fluoropropane is limited due to its primary application as a refrigerant. However, it is anticipated that, like other halogenated hydrocarbons, it would exhibit low solubility in water and rapid phase changes. Inhalation exposure may lead to quick systemic distribution and potential metabolic pathways involving fluoride ion release, but specific studies are lacking.

Pregnancy

There is limited information on the use of fluoropropane during pregnancy. Use only if the benefits outweigh the risks.

Breast-feeding

It is unknown whether fluoropropane is excreted in human milk. Caution is advised.

Storage

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

Dosage

Children: Refer to BNF for Children for specific dosing guidance, as heptachlor usage is largely restricted.

Adults: Refer to BNF for specific dosing information, as heptachlor is not commonly used in clinical settings due to safety concerns.

Mechanism of action

Heptachlor mimics the action of picrotoxin, inhibiting gamma-aminobutyric acid (GABA)-stimulated chloride uptake, which leads to nerve excitation in insects. It competes for binding sites in the brain, causing central nervous system stimulation and resulting in increased transmitter release. This mechanism can lead to increased excitability and potentially toxic effects in target organisms.

Pharmacodynamics

As a neurotoxic agent, heptachlor causes hyperactivity and central nervous system stimulation in insects. Its effects on GABA receptors disrupt normal inhibitory neurotransmission, resulting in uncontrolled neuronal firing. While primarily studied in insects, similar mechanisms may be inferred in higher organisms, including potential neurotoxic effects in humans.

Pharmacokinetics

Heptachlor is lipophilic, leading to significant bioaccumulation in organisms and environmental persistence. It is metabolized in the liver to heptachlor epoxide, which is the more toxic form. The elimination half-life varies but can be prolonged due to its fat solubility and tendency to accumulate in fatty tissues.

Pregnancy

Heptachlor is classified as a category B drug. Animal studies have not shown any harm to the fetus, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

It is not known if heptachlor is excreted in human milk. Caution should be exercised when administering heptachlor to a nursing mother.

Storage

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

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Acute bronchospasm
• Bronchospasm associated with COPD

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 250 micrograms via inhalation, up to three times a day. For children under 6 years, dosing should be determined by a healthcare professional, and the use of ipratropium in this age group requires careful consideration.

Adults: The usual adult dose for ipratropium is 500 micrograms via inhalation, administered up to four times a day. The maximum dose should not exceed 2000 micrograms in 24 hours.

Mechanism of action

Ipratropium works by inhibiting the action of acetylcholine on muscarinic receptors in the bronchial smooth muscle, leading to bronchodilation. It prevents bronchoconstriction and reduces mucus secretion in the airways, thus improving airflow and decreasing respiratory distress.

Pharmacodynamics

The onset of action for ipratropium is typically within 15 minutes, with a peak effect occurring around 1 to 2 hours after administration. Its effect can last for approximately 4 to 6 hours. It is more effective in patients with COPD than in those with asthma, though it can be used in both conditions. The drug is sometimes used in conjunction with beta-agonists to enhance bronchodilation.

Pharmacokinetics

Ipratropium is poorly absorbed from the gastrointestinal tract and has minimal systemic bioavailability when inhaled. It has a half-life of approximately 1.5 hours. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile supports its use in inhaled formulations, as it provides localized effects with reduced systemic side effects.

Contra-indications

• Hypersensitivity to ipratropium or any component of the formulation
• Acute exacerbation of bronchospasm

Adverse effects

• Dry mouth
• Cough
• Headache
• Nausea
• Dizziness
• Pharyngeal irritation

Interactions

• Clozapine: Unknown (additive effect)
• Beta 2-agonists: Unknown (increases risk of glaucoma)
• Second-generation antipsychotics: Unknown (additive effect)

Precautions

• Use with caution in patients with glaucoma
• Patients with prostatic hyperplasia or bladder neck obstruction should be monitored closely
• Caution in patients with cardiovascular disorders

Pregnancy

Ipratropium is classified as category B. Limited data suggest it is not expected to cause harm to the fetus.

Breast-feeding

Ipratropium is excreted in breast milk but is not expected to harm a nursing infant. Consider benefits versus risks.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Inhalation solution
• Aerosol inhaler
• Nasal spray

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

EVIDENCE INDICATES THAT CYCLODIENE-TYPE-INSECTICIDES, EG, HEPTACHLOR EPOXIDE, MIMIC ACTION OF PICROTOXININ. THESE INSECTICIDES INHIBIT THE GAMMA-AMINOBUTYRIC ACID-STIMULATED CHLORIDE UPTAKE IN COXAL MUSCLE OF AMERICAN COCKROACH, & DIRECTLY COMPETE AGAINST LABELED DIHYDROPICROTOXININ FOR BINDING IN THE RAT BRAIN SYNAPTOSOMES. MOREOVER, SEVERAL CYCLODIENE RESISTANT INSECT STRAINS ARE RESISTANT TO PICROTOXININ. THIS CROSS-RESISTANCE IS SPECIFIC TO PICROTOXININ & DOES NOT EXTEND TO OTHER NEUROEXCITANTS. THESE INSECTICIDES, LIKE PICROTOXININ, CAUSE CENTRAL NERVOUS EXCITATION BY STIMULATING TRANSMITTER RELEASE. THESE RESULTS INDICATE THAT SOME OF THE NERVE EXCITATION SYMPTOMS THAT INSECTICIDES CAUSE ARE LIKELY DUE TO THEIR INTERACTION WITH PICROTOXININ RECEPTOR. HEPTACHLOR WAS EVALUATED FOR GENOTOXICITY & EPIGENETIC MEMBRANE EFFECTS. IT WAS NON-GENOTOXIC IN ARLHGPRT MUTAGENESIS ASSAY IN WHICH THE GENOTOXIC CARCINOGENS 7,12-DIMETHYLBENZ(A)ANTHRACENE & BENZO(A)PYRENE INDUCED SIGNIFICANT INCR IN MUTANT INCIDENCE. HEPTACHLOR INHIBITED INTERCELLULAR COMMUNICATION BETWEEN CULTURED LIVER CELLS, A PROPERTY DEMONSTRATED BY MANY TUMOR PROMOTING AGENTS, WHEREAS, BENZO(A)PYRENE DID NOT PRODUCE THIS EPIGENETIC EFFECT. The actions of the polychlorocycloalkane insecticide heptachlor, and its epoxide metabolite, were examined on GABA receptors in insects and vertebrates. Electrophysiological experiments on the cell body of the cockroach (Periplaneta americana) fast coxal depressor motor neuron (Df), and GABA-activated (36) Cl- uptake experiments on microsacs perpared from cockroach ventral nerve cords showed that both heptachlor and heptachlor epoxide blocked functional GABA receptors. The block appeared to be non-competitive and was voltage-independent over the membrane potential range -75 mV to -110 mV. There was no significant difference between the potencies of heptachlor and heptachlor epoxide in the functional assays for insect GABA receptors. Both compounds inhibited (35)S-t-butylbicyclophosphorothionate binding in insects and vertebrates. The findings provide further evidence for block of an insect GABA receptor/Cl- channel by the cyclodiene class of polychlorocycloalkanes, and reveal differences in the insecticide (35)S-t-butylbicyclophosphorothionate binding site interactions of insects and vertebrates. The effects of heptachlor on oxidative phosphorylation and electron transport in male Donryu rat liver mitochondria were investigated. The effects of 50 uM heptachlor on the respiratory activity of isolated liver mitochondria was tested in the presence of added succinate as a substrate. The effects of 100 uM heptachlor was tested in the presence of three kinds of substrates: succinate, beta-hydroxybutylate, and ascorbate plus N,N,N'N'-tetramethylphenylene-diamine. Heptachlor at 50 uM greatly inhibited the state 3 respiration, but inhibited the state 4 respiration hardly at all. The inhibition was released by 2,4-dinitrophenol. The higher dose suppressed state 3 and state 4 respiration almost completely with succinate as substrate. The findings suggest that the function of the electron transport system was also suppressed by the higher heptachlor dose even without oxidative phosphorylation.