GALANTIC 8

Indications

• Mild to moderately severe dementia in Alzheimer's disease

Dosage

Adults: Initially, 8 mg once daily for 4 weeks, increased to 16 mg once daily for at least 4 weeks, with a maintenance dose of 16-24 mg daily.

Mechanism of action

Galantamine competitively and reversibly inhibits the acetylcholinesterase enzyme in the central nervous system, particularly in the frontal cortex and hippocampal regions. By blocking the breakdown of acetylcholine (ACh), it enhances ACh levels in the synaptic cleft, which is critical for cognitive functions such as memory and learning. Additionally, galantamine is a positive allosteric modulator of nicotinic acetylcholine receptors, further promoting cholinergic signaling.

Pharmacodynamics

Galantamine increases acetylcholine levels by inhibiting acetylcholinesterase, which enhances cholinergic tone both centrally and peripherally. While it does not modify the underlying neurodegenerative process of dementia, clinical studies indicate that galantamine can improve cognitive function, global function, activities of daily living, and behavioral symptoms in patients with Alzheimer's disease and vascular dementia.

Pharmacokinetics

Galantamine is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is metabolized primarily in the liver via cytochrome P450 enzymes (especially CYP2D6 and CYP3A4) and has an elimination half-life of approximately 7 to 8 hours. The drug is excreted mainly through the urine, and dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Severe asthma
• History of seizures
• Severe pulmonary disease
• Congestive heart failure
• Unstable angina
• Peptic ulcers
• History of significant bradycardia
• Sick sinus syndrome
• Supraventricular conduction abnormalities

Adverse effects

• Decreased appetite
• Arrhythmias
• Dizziness
• Drowsiness
• Gastrointestinal discomfort
• Hallucinations
• Headache
• Hypertension
• Malaise
• Muscle spasms
• Nausea
• Skin reactions
• Syncope
• Tremor
• Vomiting
• Weight loss

Interactions

• Bupropion (moderate - increases exposure)
• Cinacalcet (moderate - increases exposure)
• Cobicistat (moderate - increases exposure)
• Idelalisib (moderate - increases exposure)
• Terbinafine (moderate - increases exposure)
• Clarithromycin (moderate - increases exposure)

Precautions

• Use with caution in elderly patients
• Monitor for signs of bradycardia
• Potentially inappropriate for patients with persistent bradycardia
• Caution with concurrent use of drugs that affect heart rate

Pregnancy

Use in pregnancy only if clearly needed. Safety has not been established.

Breast-feeding

Use with caution as galantamine is excreted in breast milk.

Storage

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

Formulations

• Galantamine hydrobromide 4 mg/ml oral solution (sugar-free)
• Galantamine hydrobromide 8 mg modified-release capsules
• Galantamine hydrobromide 16 mg modified-release capsules
• Galantamine hydrobromide 24 mg modified-release capsules
• Galantamine hydrobromide 20 mg/5 ml oral solution (sugar-free)

Indications

• Respiratory conditions (e.g., asthma, chronic obstructive pulmonary disease)
• Cough (e.g., as an antitussive)
• Anxiety and sleep disorders (when associated with specific formulations)

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as it is determined based on weight and age for the specific formulation.

Adults: Refer to the specific product monograph for dosing information, as it varies based on the drug formulation and indication.

Mechanism of action

Hydrobromides often act as competitive antagonists or agonists at specific receptor sites, depending on the drug involved. The exact mechanism can vary widely, but many hydrobromide-containing drugs modulate neurotransmitter activity, impacting various pathways in the body such as those involved in the central nervous system or respiratory function. The metabolic pathways include Phase I reactions primarily mediated by cytochrome P450 enzymes, which facilitate the functionalization and clearance of these compounds.

Pharmacodynamics

The pharmacodynamics of hydrobromide salts are largely determined by the specific drug they are associated with. Generally, hydrobromides may exhibit effects such as sedation, bronchodilation, or antitussive actions. The efficacy and adverse effects are influenced by the drug's receptor selectivity, affinity, and the pharmacological properties inherent to the parent compound.

Pharmacokinetics

Hydrobromides typically exhibit variable pharmacokinetic profiles depending on the specific drug formulation. They are generally absorbed rapidly following oral administration, with peak plasma concentrations occurring within a few hours. Metabolism primarily occurs in the liver through cytochrome P450 enzymes, particularly CYP2E1, among others. The elimination half-life varies but is often in the range of several hours, allowing for once or twice-daily dosing in many formulations. Excretion is usually via the kidneys, with metabolites being eliminated in urine.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

Caution is advised; consider the importance of the drug to the mother against potential risks to the breastfeeding infant.

Storage

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

Mechanism of action

Alzheimer’s disease is characterized by progressive, irreversible degeneration of acetylcholine-producing neurons, cognitive impairment, and the accumulation of neurofibrillary tangles and amyloid plaques. The cholinergic system plays a critical role in memory, alongside other important neural functions such as attention, learning, stress response, wakefulness and sleep, and sensory information. Studies show that acetylcholine (ACh) is involved in the modulation of acquisition, encoding, consolidation, reconsolidation, extinction, and retrieval of memory. The gradual loss of cholinergic neurons in Alzheimer’s disease (AD) may, therefore, contribute to the memory loss exhibited by AD patients. Acetylcholinesterase is secreted by cholinergic neurons to rapidly hydrolyze ACh at the synaptic cleft to release acetate and choline. Choline is later recycled back into the presynaptic cholinergic neuron via reuptake by the high-affinity choline transporter. There is some evidence demonstrating the potential involvement of the acetylcholinesterase enzyme in the formation of amyloid fibrils. Galantamine competitively and reversibly inhibits the anticholinesterase enzyme in the CNS (namely in the frontal cortex and hippocampal regions) by binding to the choline-binding site and acyl-binding pocket of the enzyme active site. By blocking the breakdown of ACh, galantamine enhances ACh levels in the synaptic cleft. Nicotinic acetylcholine receptors (nAChR) in the CNS are mostly expressed at the presynaptic neuronal membrane to control the release of multiple neurotransmitters, such as ACh, glutamate, GABA, dopamine, serotonin, norepinephrine. Agonists of nAChRs improve performance in cognitive tasks, while antagonists of nAChR impair cognitive processes. Some studies show a decrease in the expression and activity of nAChRs in patients with AD, which may explain the reduction in central cholinergic neurotransmission in these patients. Galantamine binds to nAChRs at the allosteric site, leading to a conformational change of the receptor, increased ACh release, and increased activity of neighbouring glutaminergic and serotoninergic neurons. The modulation of nAChRs facilitates both excitatory and inhibitory cholinergic transmissions in brain tissues and increases receptor sensitivity. The modulated release of other neurotransmitters by galantamine may also contribute to the upregulation of nAChRs and amelioration of behavioural symptoms in AD. Galantamine, a tertiary alkaloid, is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this mechanism is correct, galantamine's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine alters the course of the underlying dementing process. The cause of cognitive impairment in Alzheimer's Disease is not fully understood, it has been shown that acetylcholine producing neurons degenerate. The cholinergic loss has been correlated with cognitive impairment and a density of amyloid plaques. Galantamine is a tertiary alkaloid and it competes with and is a reversible inhibitor of acetylcholinesterase. The exact mechanism of galantamine is not known, but it is believed to enhance cholinergic function.

Pharmacodynamics

Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels. Galantamine acts both centrally and peripherally to inhibit both muscle and brain acetylcholinesterase, thereby increasing cholinergic tone. Galantamine is also a positive allosteric modulator of neuronal nicotinic acetylcholine receptors. As dementia is a progressive neurodegenerative disease, galatamine has a negligible effect in altering the course of the underlying process of dementia and may exert its therapeutic effectiveness for a short period of time. However, galantamine promoted improvements in cognition, global function, activities of daily living, and behavioural symptoms in clinical studies of Alzheimer’s disease. Galantamine exhibited therapeutic efficacy in studies of vascular dementia and Alzheimer’s disease with cerebrovascular disease. In one study, galantamine reversed scopolamine-induced acute anticholinergic syndrome that was characterized by drowsiness, disorientation, and delirium.