{UAH} THE SIDE EFFECTS OF PHARMACEUTICAL DRUGS CAN CAUSE DRUG TOXICITY :-
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THE SIDE EFFECTS OF PHARMACEUTICAL DRUGS CAN CAUSE DRUG TOXICITY :-
Drug toxicity can affect any organ of the system such as :
Hematopoietic toxicity: adverse effects seen in the bone marrow
Hepatotoxicity: adverse effects seen in the liver
Nephrotoxicity/Renal toxicity: adverse effects seen in kidneys
Cardiotoxicity: adverse effects seen in the heart
Pulmonary toxicity: adverse effects seen in lungs
Skin toxicity: adverse effects seen primarily as a skin rash
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How Turmeric Saves You From Drug Induced Side Effects
Every year, numerous drugs are proposed by the pharma industry to treat a disease.
However a drug is prone to cause beneficial as well as toxic effects.
Companies spend a lot of time and money over clinical trials to determine the possible side effects a drug can cause.
FDA also invests a large amount of funds in ensuring that only those drugs that are safe for the system are marketed.
Despite of these measures, drug toxicity accounts for one-third of the cases of rejected novel drugs.
Every drug that is prescribed can be harmful to certain patients. This depends on the age, gender, genetic predisposition, drug allergy or inappropriate dosage or use of the drug.
According to Parascelsus, the father of toxicology, all compounds are toxic at high doses and all are safe at low doses.
It is important to accept that no drug is specific in its action and understanding a drug's adverse effects is as important as understanding its beneficial effects.
Mechanisms of Drug Toxicity
The adverse effects caused by a drug are mediated through the following mechanisms:
- On-target adverse effect: Drug binds to the desired target (enzyme, protein or any molecular component of the body to which the drug attaches and produces therapeutic effects) but at inappropriate concentrations or incorrect tissue producing an undesirable biological response.
- Off-target adverse effect: Drug binds to alternate target and produces side effects.
- Bioactivation: Drugs after ingestion or administration are converted into different compounds or metabolites which could possibly pose a risk to the system.
- Production of harmful immune responses: This accounts for the allergic responses elicited by a drug in certain individuals.
- Idiosyncratic responses: These include rare side effects in which the cause or mechanism is not clearly understood.
Drug toxicity can affect any organ of the system such as :
- Hematopoietic toxicity: adverse effects seen in the bone marrow
- Hepatotoxicity: adverse effects seen in the liver
- Nephrotoxicity/Renal toxicity: adverse effects seen in kidneys
- Cardiotoxicity: adverse effects seen in the heart
- Pulmonary toxicity: adverse effects seen in lungs
- Skin toxicity: adverse effects seen primarily as a skin rash
Turmeric or 'Gold Dust' of Ayurveda is a spice native to India and it is also used for curative and therapeutic purposes in traditional medicine.
Turmeric is reported to reduce the burden caused by drugs in the form of side effects or effects due to prolonged use or due to drug interactions and thus this herb can be visualized to have a positive role against drug induced toxicity.
Composition of Turmeric
Turmeric has proven anti-inflammatory, antioxidant, anti-microbial, anti-cancer and other pharmacological properties.
The bioactive properties of turmeric are attributed to various components isolated from its rhizome.
The important components are curcuminoids and the volatile oil.
Curcuminoids comprise of curcumin, monodemethoxycurcumin and bisdemethoxycurcumin.
They are natural antioxidants and impart the yellow color to the powder.
Volatile oil consists of aromatic (containing benzene ring) compounds out of which tumerone and ar-tumerone are considered medicinally quite important.
Curcumin accounts for 5-6.6% of turmeric while volatile oils make up less than 3.5% of the composition.
Sugars, proteins and resins are also isolated from the rhizome.
Role of Turmeric in Drug-induced Toxicity
Drug-induced oxidative stress is one of the mechanisms by which toxicity spreads to every organ in the system.
Commonly used drugs such as analgesics, antipsychotics, cancer therapies contribute to oxidative stress.
Reactive molecules that contain oxygen are known as reactive oxygen species (ROS).
They are normally formed in the body as a by-product of metabolic activity and are vital for cell-signaling pathways.
At high levels, ROS damage key cellular components like DNA, protein and lipid leading to cell death.
Antioxidant defenses in the body regulate the amount of ROS. Imbalance between ROS and antioxidant agents is known as oxidative stress.
Metabolism of a drug can produce a reactive intermediate which can be converted to a ROS and thus it can give rise to conditions of oxidative stress.
The immune system also contributes to drug-induced toxicity in organs like kidney and liver.
Tumor necrosis factor is a protein involved in inflammation that primarily regulates immune cells and in case of toxicity it worsens liver and kidney injuries.
Turmeric aids in controlling drug-induced organ toxicity by employing its anti-oxidant and anti-inflammatory properties.
As an anti-oxidant it scavenges ROS, inhibits lipid peroxidation (degradation of fats and related compounds by ROS in cell membrane leading to cell death) and by increasing the production of antioxidant enzymes.
Its antioxidant property is comparable to Vitamin C & E.
As anti-inflammatory agent, turmeric is known to inhibit the activity of TNF-alpha thereby regulating the activity of immune cells, release of pro-inflammatory mediators and spread of inflammation.
Scientific evidence regarding Turmeric's Detoxification activity
Research studies have proven that turmeric can protect against toxicity caused by analgesics like
- Paracetmol,
- Indometacin,
- Acetaminophen,
- Chemotherapeutic drugs like cisplastin, bleomycin, anticonvulsant and antideprassants like sodium valproate and fluoxetine etc.
Few of the drug-induced toxicities and the organs affected are mentioned below for a better understanding of turmeric's therapeutic effect.
Study 1
Paracetmol is a commonly available pain killer and also used to reduce fever.
Paracetmol overdose is known to cause fatal liver damage and it is the most common cause for acute liver failure in UK and USA.
A study investigated curcumin's protective action against liver damage caused by paracetmol overdose.
400mg/kg of curcumin and 500mg/kg of paracetmol were administered in different groups of rats.
Lowered antioxidant activities, infiltration of immune cells, increased levels of inflammatory mediators like IL-1, IL-8, TNF-alpha was seen in paracetmol treated groups while curcumin administration reduced all the paracetmol-induced alterations.
Results indicated that curcumin showed strong protective action against paracetmol induced damage by displaying its antioxidant and anti-inflammatory properties.
Study 2
Bleomycin is an anti-tumor antibiotic which is known to cause pulmonary fibrosis as a major side effect.
Pulmonary fibrosis is a condition in which scars develop in the lung tissue.
This is due to the accumulation of fibrous tissues in the lung, leading to thickening of the walls and troubled breathing.
Curcumin is proven to inhibit bleomycin-induced pulmonary fibrosis.
Bleomycin-induced pulmonary fibrosis is marked by infiltration of immune cells to lung tissues followed by production of toxic reactive oxygen species and inflammatory mediators such as TNF-alpha.
For experimental purposes, bleomycin was administered to rats to induce pulmonary fibrosis.
300mg/kg of curcumin was administered 10 days before the treatment and then continued throughout the duration of the treatment.
Elevated levels of TNF-alpha and reactive oxygen species were seen in bleomycin treated group while curcumin significantly reduced these levels.
Results suggested that curcumin works as a strong anti-inflammatory and anti-fibrotic agent against bleomycin induced pulmonary fibrosis.
Study 3
Indometacin is a non steroidal anti-inflammatory drug prescribed against fever, pain, stiffness and swelling.
As a part of its painkiller activity, indometacin inhibits enzymes like cyclooxygenases 1 and 2 which contribute to inflammation.
COX-1 and 2 are also responsible for production of prostaglandins which are compounds similar to hormones.
Prostaglandins primarily contribute to fever, pain and inflammation as well as are essential to maintain mucosal lining of the gastrointestinal tract.
Hence inhibition of COX-1, 2 leads to inhibition of prostaglandins and development of gastric ulcers.
Research has proven that curcumin exerts a gastroprotective effect against indometacin induced gastric ulcer.
Curcumin inhibits formation of indometacin induced gastric ulcers in a dose dependent manner offering 82% protection at 25mg/kg.
Indometacin causes oxidative damage by initiating lipid peroxidation and increased production of reactive oxygen species.
Curcumin protects against oxidative damage by scavenging ROS and increasing level of antioxidant enzymes. Curcumin also protects against gastric damage by indometacin by displaying its antioxidant property.
Study 4
Doxorubicin is a chemotherapeutic drug which is known to cause a number of adverse effects such as hair loss, nausea, vomiting, skin reactions, damage to heart and liver.
A study was conducted to observe turmeric's protective effects against DOX-induced cardiac, renal and hepatic toxicity in rats.
Various parameters which when altered are indicative of damage in particular organs were monitored.
Turmeric extract was found to attenuate DOX induced cardio and hepatic toxicity. It blocked DOX-induced nephrosis.
Turmeric was also successful in reducing increased cholesterol levels caused by DOX.
Results suggested that turmeric made use of a variety of its medicinal properties to ward off DOX-induced toxicity, the most important one being antioxidant property.
Study 5
Fluoxetine is a drug prescribed for depression that is known to cause side effects like insomnia, anxiety, dermatological reactions, nausea, sinusitis, sexual dysfunction etc.
Curcumin is known to attenuate fluoxetine induced reproductive toxicity in rats. Fluoxetine causes reproductive toxicity by creating conditions of oxidative stress.
Fluoxetine treatment in rats lead to degeneration of cells of the male reproductive system, inhibited spermatogenesis, brought about histological changes (change in tissues of the organ) and lowered the levels of testosterone and antioxidant enzymes.
Curcumin treatment brought about improvement in histological changes, increased testosterone levels and reduced oxidative stress by inhibiting lipid peroxidation.
Curcumin 's antioxidant property aided in reducing fluoxetine induced male reproductive toxicity.
Study 6
Gentamicin is an antibiotic that is used to treat bacterial infections.
It is administered intravenously, intramuscularly or topically to treat infections as oral dose is not absorbed appropriately by the intestine.
Gentamicin is a nephrotoxic agent that inhibits production of protein in kidney cells leading to cell death and kidney failure.
Dietary consumption of turmeric and ginger has proven to reduce gentamicin induced nephrotoxicity.
As a part of the experiment renal damage was induced in rats by administering 100mg/kg gentamicin for 3 days and pretreatment of turmeric and ginger in diet at 4% and 2% was provided.
Gentamicin caused significant renal damage and oxidative stress in kidneys.
Ginger and turmeric pretreatment protected the kidney and reduced oxidative stress by attenuating renal damage and improving antioxidant status in kidney.
Dosage
As such there is no prescribed dosage for drug induced toxicity.
Turmeric is best taken as part of diet.
Two great ways are by taking golden paste and golden milk. You can also look at some amazing turmeric recipes here>
You can easily take around 1 tsp of turmeric daily without any issues, though always start slow if you are new to it.
It is important to buy good quality turmeric, if you are confused about it, here are some recommended turmeric brands >
It is important to include fats and black pepper in your diet while taking turmeric as it helps in its absorption which otherwise is low.
Read detailed article on improving turmeric absorption here>
Precautions
Though turmeric is a herbal supplement it is prone to cause toxicity in certain individuals.
Caution is to be exercised while consuming turmeric supplements due to presence of substances which enhance its absorption in the body and one could be allergic to them.
Also drug interactions or overdose could cause harmful effects. Certain conditions in which turmeric supplements should be avoided or taken only as per prescription are:
- Pregnancy & Lactation
- Gall stones & bile passage obstructions
- Diabetes if already consuming blood thinning medications
- Prior to surgical procedures
- Consumption of blood thinning agents or antacids
Conclusion
The average cost to develop a safe and profitable drug is around US$ 1.7 billion.
Previously the metabolism and absorption of the drug in the body used to be major hurdle in drug development while today toxicity issues have increased.
Despite of toxicity and safety assessment performed at every stage of drug development, almost all drugs bring about side effects, someway or another.
Overdoses, inappropriate or prolonged use, drug interactions or individual's predisposition to allergy are few factors contributing to drug toxicity.
Turmeric is proven to ameliorate adverse effects caused by drugs and one can look forward to this herb as an adjuvant to standard therapy so as to overcome side effects.
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