debrisoquine

Action and Spectrum

Actions and Spectrum: 

Action: debrisoquine’s main mechanism of action is to inhibit the enzyme cytochrome P450 2D6 (CYP2D6), which plays a crucial role in the metabolism of various drugs. CYP2D6 is responsible for metabolizing a wide range of medications, including beta-blockers, antidepressants, and antipsychotics. Inhibition of CYP2D6 by debrisoquine can lead to altered metabolism and increased blood levels of drugs metabolized by this enzyme, potentially resulting in unexpected side effects or toxicities. 

Spectrum: debrisoquine has a limited therapeutic spectrum due to its adverse effects and interactions. It was mainly used for its antihypertensive and antiarrhythmic effects, although its use in these indications has decreased over time. 

Drug Interaction

Adverse Reaction

Frequency not defined  

failure of ejaculation 

drowsiness 

diarrhoea 

headache 

nasal decongestion 

fluid retention 

Postural hypotension 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Individuals with a known hypersensitivity or allergy to debrisoquine or any of its components should not use this medication. 

Arrhythmias: debrisoquine can affect heart rhythms and is generally contraindicated in individuals with certain arrhythmias (abnormal heart rhythms) such as ventricular arrhythmias. 

Heart Block: It should be used cautiously or avoided in patients with second- or third-degree heart block, as debrisoquine can further slowdown the heart’s electrical conduction. 

Heart Failure: debrisoquine may exacerbate heart failure symptoms in patients with severe heart failure. 

Cerebrovascular Disease: Individuals with a history of cerebrovascular disease, such as stroke or transient ischemic attacks, should avoid using debrisoquine due to potential effects on blood pressure and circulation. 

Renal Impairment: People with severe kidney dysfunction should use debrisoquine with caution, as the medication’s clearance may be affected. 

Hepatic Impairment: debrisoquine is metabolized by the liver, so individuals with severe liver impairment may experience altered metabolism and potential adverse effects. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

debrisoquine is a medication that was historically used as an antihypertensive and antiarrhythmic agent. 

Pharmacodynamics:  

debrisoquine acts primarily by blocking beta-adrenergic receptors, which are typically activated by the neurotransmitter norepinephrine (noradrenaline). By antagonizing these receptors, debrisoquine reduces the effects of norepinephrine, resulting in decreased heart rate and blood pressure.   

Pharmacokinetics: 

Absorption 

debrisoquine is administered orally, and its absorption from the gastrointestinal tract is relatively slow and incomplete. Its bioavailability is low, typically around 10-20%. It experiences substantial initial liver metabolism prior to entering the systemic circulation.  

Distribution 

Once absorbed, debrisoquine is distributed throughout the body. It has a relatively large volume of distribution, indicating that it distributes extensively into tissues. Plasma protein binding of debrisoquine is moderate, which means that a portion of the drug remains bound to proteins in the bloodstream. 

Metabolism 

debrisoquine is extensively metabolized in the liver primarily through the action of the cytochrome P450 2D6 enzyme (CYP2D6). This enzyme converts debrisoquine into its active metabolite, 4-hydroxydebrisoquine. However, some individuals have a genetic polymorphism that leads to reduced or absent CYP2D6 activity, resulting in poor metabolizers who experience significantly reduced metabolism of debrisoquine. 

Excretion and Elimination 

The active metabolite, 4-hydroxydebrisoquine, is further metabolized and then eliminated mainly through the kidneys in the form of glucuronide and sulfate conjugates. A small portion of unchanged Debrisoquine is also excreted in the urine. The elimination half-life of Debrisoquine and its metabolites can vary significantly between individuals, especially due to the influence of CYP2D6 genetic polymorphisms. 

Adminstartion

Administration:  

debrisoquine is usually administered orally in the form of tablets or capsules. It’s important to follow the instructions provided by the healthcare provider or the label on the medication packaging. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: debrisoquine 

Why do we use debrisoquine?  

Hypertension (High Blood Pressure): Originally, debrisoquine was employed to reduce hypertension in individuals with high blood pressure. Its mechanism involves disrupting the functioning of the sympathetic nervous system, which is responsible for blood pressure regulation. Nonetheless, contemporary antihypertensive drugs that are more efficient and better tolerated have superseded their use. 

Heart Conditions: debrisoquine might have been used to manage certain heart conditions, such as arrhythmias (irregular heartbeats) or angina (chest pain).