Doxycycline Action, History, Uses, Side effects, Dosage and Brands in Pakistan

May 25, 2024
0 Likes
110 Views
0 Comments

Introduction to Doxycycline

Doxycycline is a synthetic antibiotic derived from oxytetracycline. It is known for its effectiveness against a wide range of gram-positive and gram-negative bacteria. Additionally, it has applications beyond bacterial infections, including treatment for acne, malaria prophylaxis, and certain inflammatory conditions.

Doxycycline is available in different forms, including tablets, capsules, and liquid suspensions. There are two different salt forms of doxycycline available: doxycycline hyclate and doxycycline monohydrate. One difference between the two is that doxycycline hyclate is soluble in water, while doxycycline monohydrate is very slightly soluble in water.

Historical Background

Doxycycline was first synthesized in the early 1960s by Pfizer, to create a tetracycline antibiotic with improved pharmacokinetic properties. It was introduced to the market in 1967 under the brand name Vibramycin. Since then, it has become one of the most frequently prescribed antibiotics globally.

Mechanism of Action

Doxycycline works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of bacteria, preventing the addition of amino acids to the growing peptide chain. This action effectively halts bacterial growth and replication, making this drug a bacteriostatic antibiotic.

Inclusion in WHO’s List of Essential Medicines

Doxycycline holds a significant position on the World Health Organization’s List of Essential Medicines, reflecting its vital role in addressing priority healthcare needs on a global scale.

Availability as a Generic Medicine

Doxycycline is readily available as a generic medicine, ensuring its widespread accessibility and affordability, thereby contributing to its extensive usage.

Prescription Statistics

In 2021, doxycycline ranked as the 82nd most commonly prescribed medication in the United States, with more than 8 million prescriptions, highlighting its widespread usage and importance in medical practice.

Clinical Uses

Doxycycline is prescribed for a wide array of conditions, including bacterial infections, non-bacterial infections, and inflammatory conditions. Some of these include:

Bacterial Infections

Doxycycline is used to treat a variety of bacterial infections, including:

Respiratory Infections: Such as bronchitis (inflammation of the bronchial tubes), pneumonia (an infection of the lungs caused by bacteria, viruses, or fungi.), and sinusitis (inflammation or swelling of the sinuses, which are air-filled spaces in the forehead, cheeks, and around the eyes.).
Urinary Tract Infections: Doxycycline is Effective against certain pathogens causing urinaary tract infections (UTIs).
Sexually Transmitted Infections: Including chlamydia (a common sexually transmitted infection caused by the bacterium Chlamydia trachomatis.) and gonorrhea (sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. It infects the genital tract, rectum, and throat. ).
Skin Infections: Such as cellulitis (skin infection that affects the deeper layers of the skin and the underlying tissue. It is usually caused by bacteria such as Staphylococcus and Streptococcus) and infected wounds.
Tick-Borne Diseases: Including Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis.

Non-Bacterial Infections

Doxycycline also has efficacy against non-bacterial pathogens:

Malaria: Used as a prophylactic treatment for travelers to malaria-endemic regions.
Rickettsial Infections: Effective against rickettsia, which causes diseases like typhus.
Certain Parasitic Infections: Such as filariasis (a parasitic disease caused by infection with filarial worms transmitted through mosquito bites. ).

Anti-Inflammatory Effects

Apart from its antimicrobial properties, doxycycline exhibits anti-inflammatory effects. It is commonly used in the treatment of:

Acne: It Reduces inflammation and bacterial load in acne vulgaris.
Rosacea: Doxycycline helps manage the inflammatory component of this chronic skin condition.
Periodontal Disease: Used as an adjunctive therapy to control periodontitis.

Doxycycline Uses in Urdu

ڈوکسی سائیکلائن مختلف بیماریوں کے علاج کے لیے مقرر کیا جاتا ہے، جن میں بیکٹیریا کی سانچے، غیر بیکٹیریا کی سانچے، اور انفلیمیٹری شرائط شامل ہیں۔ کچھ مثالیں شامل ہیں

بیکٹیریا کی سانچے

تنفسی انفیکشن: جیسے کہ برونکائٹس (برانکائیل ٹیوبوں کی سوزش)، نیومونیا (پھیپھڑوں کی ایک انفیکشن جو بیکٹیریا، وائرس، یا قففنی کیشمیر کی وجہ سے ہوتا ہے)، اور سائنوسائٹس (سائنوسز کی سوزش یا سوجن، جو ماتھے، گالوں، اور آنکھوں کے ارد گرد ہوتی ہیں۔)

مثانے کی انفیکشن: ڈوکسی سائیکلائن مخصوص پیتھوں کے خلاف کام کرتا ہے.

جنسی طریقے سے پھیلنے والی انفیکشنز: یہ چلمیڈیا (ایک عام جنسی طریقے سے پھیلنے والی انفیکشن جو بیکٹیریم کلمیڈیا ٹراکوماٹس کی وجہ سے ہوتی ہے) اور گونوریہ (جنسی طریقے سے پھیلنے والی انفیکشن جو بیکٹیریم نیسیرو گونوری ہے۔ یہ جنسی عضو، ریکٹم، اور گلے کو متاثر کرتی ہے۔) شامل ہیں۔

جلدی انفیکشن: جیسے کہ سیلولائٹس (جلد کی گہرائی کی سطح اور اس کی اندرونی تشکیل پر اثر انداز ہونے والی انفیکشن، جو اسٹافیلوکاکسس اور اسٹریپٹوکوکس کی بناوٹ سے ہوتی ہے) اور متاثرہ زخمات۔

ٹک بارن امراض: لائم بیماری، راکی ماؤنٹن سپوٹڈ فیور، اور اہرلی کیوسس کے معالجے میں موثر ہے۔

غیر بیکٹیریا کی سانچے

میلیریا: سفر کرنے والوں کے لیے میلیریا آخری معالجے کے طور پر استعمال ہوتا ہے۔

ریکٹسیل انفیکشنز: ریکٹسیا کے خلاف موثر ہوتا ہے، جو ٹائیفوئیڈ جیسی بیماریوں کا سبب بناتی ہے۔

کچھ پیراسیٹک انفیکشنز: جیسے فلیریاسس (ایک پیراسیٹک بیماری جس کی وجہ سے مچھر کا کاٹنا فلیریل ورمز کی وائرل انفیکشن ہوتی ہے۔)۔

انفلیمیٹری شرائط کی ضدی اثرات

کیل: یہ اکنے کی ایک غیر متوقع صورت ہے۔ یہ اکنوں میں دورانیہ اور بیکٹیریائی بوجھ کو کم کرتا ہے۔

رُوسیشے: ڈوکسی سائیکلائن اس دائمی جلدی حالت کے انفرادی عنصر کو موڑتا ہے۔

پریڈونٹل بیماری: دندانہ کی حالت کو کنٹرول کرنے کے لیے استعمال ہوتا ہے۔

Dosage and Administration

Doxycycline is available in various forms:

Oral Tablets and Capsules: Commonly available in 50 mg, 100 mg, and 200 mg strengths.
Oral Suspension: Suitable for patients who have difficulty swallowing pills.
Intravenous (IV) Formulation: Used in hospital settings for severe infections.

Administration Guidelines

Adults: Typically, the dosage ranges from 100 mg to 200 mg per day, depending on the severity and type of infection.
Children over 8 Years: Dosage is generally calculated based on body weight.
Administration: Should be taken with a full glass of water to prevent esophageal irritation, and preferably not lying down immediately after ingestion.

Side Effects and Adverse Reaction

Some reported side effects of doxycycline are categorized as common and serious which are mentioned below:

Common Side Effects

Gastrointestinal Disturbances: Nausea, vomiting, diarrhea, and loss of appetite.
Photosensitivity: Increased sensitivity to sunlight, leading to sunburns.
Esophageal Irritation: If not taken with adequate water or lying down.

Serious Adverse Reactions

Allergic Reactions: Including rash, itching, and in rare cases, anaphylaxis.
Intracranial Hypertension: Symptoms include headache and blurred vision.
Hepatotoxicity: Liver damage, especially with prolonged use.

Contraindications and Precautions

Before starting this medication, ensure you do not have any allergies to doxycycline or other tetracycline antibiotics like demeclocycline, minocycline, tetracycline, or tigecycline.

To confirm the safety of this medication for you, inform your doctor if you have a history of:

Liver disease
Kidney disease
Asthma or sulfite allergy
Increased pressure inside your skull
Concurrent use of isotretinoin, seizure medicine, or blood thinners like warfarin (Coumadin).

Interactions with Other Drugs

Certain medications interact with doxycycline, potentially affecting its effectiveness or causing adverse effects. Before taking this medication, inform your doctor if you are already taking any of the following medicines:

Indigestion Remedies (Antacids): These can interfere with the absorption of doxycycline, so it’s advisable to avoid taking them simultaneously.
Stomach Ulcer Medicines Containing Bismuth (e.g., Pepto-Bismol): Bismuth-containing medications may reduce the effectiveness of doxycycline or cause interactions, so it’s essential to discuss alternatives with your doctor.
Other Antibiotics (e.g., Rifampicin): Combining doxycycline with other antibiotics like rifampicin may lead to decreased effectiveness or increased risk of side effects. Your doctor will advise on the appropriate timing and dosage.
Acne Medicines Containing Vitamin A (e.g., Isotretinoin): Concurrent use of this antibiotic with vitamin A-containing acne medications may increase the risk of intracranial hypertension. Close monitoring is necessary.
Warfarin: Doxycycline may potentiate the effects of warfarin, increasing the risk of bleeding. Your doctor will monitor your international normalized ratio (INR) closely and adjust the warfarin dosage accordingly.
Medicines for Epilepsy (e.g., Phenytoin or Carbamazepine): It may reduce the effectiveness of epilepsy medications, necessitating adjustments in dosage. Regular monitoring is essential.
Ciclosporin: Concurrent use of this drug with ciclosporin, an immunosuppressant, may lead to increased ciclosporin levels in the blood, potentially causing toxicity. Your doctor will monitor ciclosporin levels and adjust the dosage as needed.
Typhoid Vaccine (Oral): The oral typhoid vaccine may not be as effective if taken concurrently with this antibiotic. It is recommended to discuss alternative vaccination options with your healthcare provider.

Mixing Doxycycline with Herbal Remedies and Supplements

In addition to medications, certain herbal remedies and supplements may interact with this antibiotic. Inform your doctor if you are taking any of the following supplements:

Supplements Containing Aluminium, Bismuth, Calcium, Magnesium, or Zinc: These minerals can interfere with the absorption of this drug, so it’s best to avoid taking them simultaneously.
Iron Supplements: Concurrent use of iron supplements with this antibiotic may reduce the absorption of both medications. It’s advisable to take them at least two hours apart.

Resistance and Antibiotic Stewardship

Antibiotic resistance is a significant concern with the use of doxycycline. Overuse and misuse of antibiotics contribute to the development of resistant strains. Strategies to combat resistance include:

Appropriate Prescribing: Only prescribing this antibiotic when necessary.
Patient Education: Informing patients about the importance of completing the prescribed course.
Infection Control Measures: Preventing the spread of resistant bacteria in healthcare settings.

Pharmacokinetics of Doxycycline

Absorption

Doxycycline is efficiently absorbed from the upper part of the small intestine. After oral administration, it reaches peak concentrations in the blood plasma within one to two hours. The substance’s absorption is almost complete, making it highly effective for treating various infections.

Distribution

Once absorbed, doxycycline has a high plasma protein binding rate of approximately 80-90%. This high binding rate facilitates its extensive distribution throughout the body. Doxycycline penetrates almost all tissues and body fluids. It achieves particularly high concentrations in the following areas:

Gallbladder
Liver
Kidneys
Lungs
Breast Milk
Bones
Genitals

Conversely, doxycycline reaches lower concentrations in:

Saliva
Aqueous Humor (eye fluid)
Cerebrospinal Fluid (CSF)
Inflamed Meninges

In comparison, the tetracycline antibiotic minocycline shows significantly better penetration into the CSF and meninges.

Metabolism and Excretion

Doxycycline undergoes negligible metabolism, meaning that most of the drug remains unchanged in the body. It is actively excreted into the gut through two pathways:

Via the Gallbladder
Directly from Blood Vessels

In the gut, some doxycycline forms inactive chelates. The drug is eliminated primarily through the following routes:

Renal Excretion: About 40% is eliminated via the kidneys, though this percentage is much lower in individuals with end-stage kidney disease.
Biliary and Fecal Excretion: A significant portion is excreted into the intestines and expelled in feces.

Pregnancy and Lactation

FDA Classification and Risks

Doxycycline is categorized by the FDA as a class D drug in pregnancy. This classification indicates that there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks. This antibiotic crosses the placenta and can affect the developing fetus.

Breastfeeding

This medication crosses into breast milk. Although doxycycline’s specific risk of causing dental staining in primary teeth is undetermined, other tetracycline antibiotics are known to disrupt bone and tooth development. These antibiotics carry a class warning about the risk of staining teeth and reducing the development of dental enamel in children exposed in utero, during breastfeeding, or in young childhood.

Tetracycline Class Warnings

Tetracyclines, including doxycycline, traditionally carry warnings regarding their use during pregnancy and in children up to eight years of age. The primary concerns are:

Bone and Tooth Development: Potential disruption, leading to inhibited bone growth and permanent staining of teeth.
Dental Enamel Hypoplasia: Reduced development of dental enamel, which can lead to tooth discoloration and increased susceptibility to cavities.

Specific Considerations

Despite the general warnings associated with tetracyclines, the FDA has acknowledged that the actual risk of dental staining from doxycycline is undetermined. Current evidence suggests that this drug has little or no effect on the hypoplasia of dental enamel or the staining of teeth.

Recommendations and Guidelines

Q Fever and Tick-Borne Diseases: The CDC recommends the use of doxycycline for the treatment of Q fever and tick-borne rickettsial diseases in young children, despite the potential risks, due to its effectiveness and the severity of these infections.
Malaria: It is also advocated for use in malaria treatment and prophylaxis, recognizing its benefits in preventing and treating this serious disease.

Chemistry of Doxycycline

Expired tetracyclines or those exposed to acidic conditions (pH less than 2) can lead to nephrotoxicity. This toxicity is attributed to the formation of a degradation product called anhydro-4-epitetracycline, which can cause Fanconi syndrome. However, in the case of doxycycline, the absence of a hydroxyl group in the C-6 position prevents the formation of this nephrotoxic compound. Despite this, caution is still advised when administering tetracyclines, including doxycycline, to patients with kidney injury, as they can exacerbate azotemia due to their catabolic effects.

Chemical Properties

Doxycycline, doxycycline monohydrate, and doxycycline hyclate are yellow, crystalline powders known for their bitter taste. Among them, doxycycline hyclate exhibits a faint smell of ethanol. When dissolved in water, a 1% aqueous solution of doxycycline hyclate has a pH ranging from 2 to 3.

Brands in Pakistan

In Pakistan, doxycycline is readily accessible and marketed under diverse brand labels, including:

ADOXA by PHARMA HEALTH PAKISTAN (PVT) LTD.
ARBEV by PEARL PHARMACEUTICALS.
ARDOX by ENGLISH PHARMACEUTICALS INDUSTRIES.
CORODOX by PEARL PHARMACEUTICALS.
DOXCID by MEDERA PHARMACEUTICALS (PVT) LTD.
DOXYBACT by SEATLE PHARMA PAKISTAN (PVT) LTD.
DOXYMED by MEDICEENA PHARMA (PVT) LTD.
DOXYTAB by NEUTRO PHARMA (PVT) LTD.
Nordox is manufactured by Platinum Pharmaceuticals.
KORCIN by VENTURE CHEMICAL & PHARMACEUTICALS (PVT) LTD.
PANDOX by PAKHEIM INTERNANATIONAL PHARMA.
REMYCIN by HIGH – Q INTERNATIONAL.
U-SODOX by USAWA PHARMACEUTICALS.
VIBRAMYCIN by PFIZER LABORATORIES LTD.
VOXIN by REMINGTON PHARMACEUTICAL INDUSTRIES (PVT) LTD.

Conclusion

Doxycycline remains a versatile and valuable antibiotic with a broad range of applications. While it is generally well-tolerated, awareness of its potential side effects, contraindications, and interactions is crucial for safe and effective use. Healthcare providers play a key role in ensuring it is prescribed appropriately, thereby minimizing the risk of resistance and ensuring optimal patient outcomes.

FAQs

1. What infections does doxycycline treat?

Doxycycline is effective against a variety of infections, including respiratory tract infections, urinary tract infections, skin infections, sexually transmitted infections, and tick-borne diseases.

2. Can doxycycline be used for acne?

Yes, it is commonly prescribed for moderate to severe acne due to its antibacterial and anti-inflammatory properties.

3. Is it safe to take doxycycline during pregnancy?

Doxycycline is generally not recommended during pregnancy due to the risk of harm to the developing fetus, especially during the second and third trimesters.

4. How should doxycycline be taken?

Doxycycline should be taken with a full glass of water, and it is advisable not to lie down immediately after taking the medication to prevent esophageal irritation.

6. Can children take doxycycline?

Doxycycline is not recommended for children under 8 years old due to the risk of tooth discoloration and inhibition of bone growth. For older children, the dosage is typically adjusted based on body weight.

7. What should I avoid while taking doxycycline?

While taking doxycycline, avoid excessive sun exposure due to the increased risk of photosensitivity. Also, avoid taking antacids, iron supplements, and certain other medications that can interfere with its absorption.