Usage
Hydroxyquinolines are primarily used as antiparasitic and antifungal agents. Specifically, they are effective against various protozoal and fungal infections. Some hydroxyquinolines, such as hydroxychloroquine, are also used for the treatment of autoimmune diseases like lupus and rheumatoid arthritis.
Alternate Names
The class of drugs doesn’t have a single alternate name, but individual drugs within this class have various names:
- 8-Hydroxyquinoline: Quinolin-8-ol, oxine
- Hydroxychloroquine: Plaquenil, Quineprox
- Clioquinol: Vioform, Iodochlorhydroxyquin
- Broxyquinoline: Intestopan
How It Works
Mechanism of Action: Hydroxyquinolines exert their effects through various mechanisms depending upon the specific drug and target organism:
- Antiparasitic Action: Some hydroxyquinolines, like chloroquine and hydroxychloroquine, interfere with heme detoxification within the parasite, leading to its death. They also inhibit nucleic acid synthesis, hindering parasite growth and replication.
- Antifungal Action: 8-Hydroxyquinoline and its derivatives act as fungicides by chelating metal ions (such as copper and iron) essential for fungal growth. This disrupts fungal metabolism and leads to cell death.
- Anti-inflammatory Action (Hydroxychloroquine): Although the exact mechanism is not fully understood, hydroxychloroquine is thought to modulate immune responses by suppressing toll-like receptor signaling, cytokine production, and antigen presentation.
Pharmacokinetics: Pharmacokinetic parameters vary based on the specific hydroxyquinoline. Generally, these drugs are well-absorbed orally. Metabolism occurs primarily in the liver, and excretion is through renal and/or hepatic pathways. For example, hydroxychloroquine has a long half-life, requiring weekly dosing for malaria prophylaxis.
Dosage
Dosage guidelines are highly specific to individual hydroxyquinolines and the condition being treated. Consulting a drug formulary for specific drug information is crucial. Here’s an example for Hydroxychloroquine:
Standard Dosage
Adults:
- Malaria Prevention: 400 mg weekly, starting 2 weeks before travel and continuing for 4 weeks after returning.
- Lupus/Rheumatoid Arthritis: 400-600 mg daily initially, then adjusted to a maintenance dose of 200-400 mg daily.
Children:
Dosing is weight-based and should be determined by a physician. Use in young children is often restricted due to safety concerns.
Special Cases:
Dosage adjustments might be necessary in elderly patients and those with renal or hepatic impairment.
Clinical Use Cases
Hydroxyquinolines are not typically used in acute clinical settings like intubation, surgery, mechanical ventilation, or ICU care, except for the management of underlying autoimmune conditions.
Side Effects
Common Side Effects
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Headache
- Dizziness
Rare but Serious Side Effects
- Retinal toxicity (especially with long-term hydroxychloroquine use)
- Cardiomyopathy
- QT prolongation
- Neuropathy
- Myopathy
Contraindications
- Known hypersensitivity to the specific drug
- Pre-existing retinal disease (for hydroxychloroquine)
- Severe hepatic or renal impairment (for some hydroxyquinolines)
Drug Interactions
Hydroxyquinolines may interact with several drugs, including digoxin, antacids, and certain antibiotics. Co-administration with drugs that prolong the QT interval should be avoided.
Pregnancy and Breastfeeding
Hydroxychloroquine is considered relatively safe during pregnancy and breastfeeding. However, other hydroxyquinolines may pose risks and should be used with caution.
Drug Profile Summary
Information highly variable depending on the specific hydroxyquinoline.
Popular Combinations
Hydroxychloroquine is sometimes combined with other antimalarials or with methotrexate for rheumatoid arthritis.
Precautions
Pre-existing eye, liver, or kidney conditions should be carefully evaluated before prescribing hydroxyquinolines. Regular eye exams are recommended for patients on long-term hydroxychloroquine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydroxyquinolines?
A: Dosage varies greatly among individual hydroxyquinolines and depends on the indication. Always consult a reliable drug formulary for specific drug dosing recommendations.
Q2: What are the common side effects of Hydroxychloroquine?
A: Common side effects include nausea, vomiting, diarrhea, abdominal cramps, headache, and dizziness.
Q3: What is the mechanism of action of 8-Hydroxyquinoline as an antifungal agent?
A: It acts as a fungicide primarily by chelating metal ions essential for fungal growth.
Q4: Can Hydroxychloroquine be used during pregnancy?
A: Generally, yes, but consultation with a physician is crucial to assess benefits versus risks.
Q5: Are there any serious side effects associated with long-term Hydroxychloroquine use?
A: Yes, potential serious side effects include retinal toxicity, cardiomyopathy, and QT prolongation.
Q6: What are the contraindications for Broxyquinoline?
A: Contraindications include hypersensitivity to hydroxyquinolines, severe liver or kidney impairment.
Q7: How do Hydroxyquinolines work against parasites like malaria?
A: Some hydroxyquinolines, like chloroquine and hydroxychloroquine, interfere with heme detoxification and nucleic acid biosynthesis within the parasite.
Q8: What are the drug interactions to be aware of when prescribing Hydroxyquinolines?
A: Consult a comprehensive drug interaction database, as interactions can vary depending on the specific hydroxyquinoline. It’s important to note interactions with drugs that prolong the QT interval.
Q9: What precautions should be taken when prescribing hydroxyquinolines to elderly patients?
A: Due to potential age-related decline in organ function, dosage adjustments and close monitoring may be necessary. Consider potential drug interactions with other medications commonly used by elderly patients.
