Archive for May, 2016

Can Azithromycin be used in combination of Rifampin

May 31 2016 Published by under Drug Interactions

Azithromycin

Azithromycin is an antibiotic that is used for the treatment of variety of bacterial infections such as skin, ear, respiratory infections and sexually transmitted diseases (STDs).

The drug is available under generic name Azithromycin and marketed under the various brand names such as Zithromax, Azithrocin and Azyth. Pfizer is accountable for the manufacturing and marketing of Azithromycin.

Furthermore, Azithromycin is marketed as an ophthalmic solution under the brand name AzaSite by Inspire Pharmaceuticals. Azithromycin is a semi-synthetic, relatively broad spectrum, macrolide antibiotic.

Azithromycin plays a key role in the treatment of complication related to the bacterial infections such bronchitis, pneumonia, skin infections and infections of ear and throat.

It is also recommended to treat the sexually transmitted diseases and urinary tract infections. It is also used to prevent or treat the disseminated Mycobacterium avium complex (MAC) infection.

Azithromycin (in form of ophthalmic solution) is used to treat bacterial conjunctivitis (a bacterial eye infection).  The drug is also prescribed for the treatment of acute bacterial sinusitis caused by H. Influenza, M. Catarrhalis or S, pneumonia.

Sometime it is also used to treat the infection of H. pylori and Legionnaires’ disease (inflammatory lung infection caused by Legionella). It is also prescribed for the treatment of Whooping cough.

Azithromycin is a derivatives of erythromycin and available as a dihydrate salt. It is a semi-synthetic aliphatic heteromonocyclic antimicrobial agent with a molecular formula C38H72N2O12.

The drug is a dihydrate salt of (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-2-ethyl-3,4,10-trihydroxy-13-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one.

Azithromycin is available in tablet and oral suspension form for oral administration as well as in the form of ophthalmic solution. Azithromycin tablets are available in two different dosages of 250 mg and 500 mg, oral suspensions are available in two different dosages of 100 mg/5ml and 200 mg/5ml and both forms contain azithromycin dihydrate as active ingredient.

Azithromycin ophthalmic solution (AzaSite®) is available as 1% sterile solution which is an off-white viscous liquid. The dose of Azithromycin varies depending upon the age and diseased state of the patient.
Azithromycin 250 tablets

Rifampin

Rifampin belongs to the class of medications called antimycobacterials. It acts against a broad spectrum of bacteria including several forms of Mycobacterium. It is not effective against viral infections (e.g., common cold, flu).

Rifampin is a semisynthetic antibiotic that is produced from Streptomyces mediterranei. The drug is on the World Health Organization’s List of Essential Medicines, i.e., it is one of the most important medications needed in a basic health system.

The drug is available under generic name Rifampin and brand names Rifadin, Rimactane. Sanofi pharmaceutical company is responsible for its manufacture. Rifampin is a semisynthetic antibiotic derivative of rifamycin SV with a chemical formula C43H58N4O12.

The drug is chemically known as either 3-[[(4-Methyl-1-piperazinyl)imino]methyl]rifamycin or 5,6,9,17,19,21-hexahydroxy-23-methoxy-2,4,12,16,20,22–heptamethyl-8-[N-(4-methyl-1-piperazinyl)formimidoyl]-2,7-(epoxypentadeca[1,11,13]trienimino)naphtho[2,1-b]furan-1,11(2H)-dione 21-acetate.

Rifampin is recommended in combination with other antituberculosis medications for the treatment of all forms of tuberculosis, including tuberculous meningitis.

Rifampin is used for the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx but is not effective in cases where patients have developed the symptoms of meningitis.

Rifampin is used as a combination therapy for the treatment of leprosy (Hansen’s disease) and certain atypical (nontuberculous) mycobacterial infections, such as those caused by Mycobacterium avium complex (MAC).

Rifampin co-administered with other antistaphylococcal agents is also recommended in the treatment of serious infections brought about by Staphylococcus species (including methicillin- and multiresistant strains).

Rifampin is also indicated in the prophylactic treatment for intimate contacts of young children who develop infections with Haemophilus influenzae type b. the drug is a prescription drug and is to be taken on an empty stomach, either 1 hour before or 2 hours after food. It is taken orally with a glass of water. The drug is supplied as capsules or injections.
Rifampin uses

Rifampin capsules are available in two different dosage forms of 150 mg or 300 mg for oral administration and contain Rifampin as the active ingredient. Rifampin for injection is available in glass vials containing 600 mg Rifampin.

How Azithromycin and Rifampin work?

Azithromycin is effective against gram positive bacteria such as Staphylococcus aureus, S. agalactiae, S. pneumonia and pyogenes, gram-negative bacteria such as Haemophilus ducreyi, H. influenza, Moraxella catarrhalis and Neisseria gonorrhoeae and some other bacteria like Chlamydophila pneumonia, Chlamydia trachomatis and Mycoplasma pneumonia.

Azithromycin is a macrolides antibiotic (such as Erythromycin and Carbomycin) which acts by inhibiting the bacterial protein synthesis, quorum-sensing and formation of bacterial biofilm.

Macrolides primarily act through enhancing the dissociation of peptidyl-tRNA from ribosome, thus inhibiting transpeptidation and translocation step of protein synthesis (an intermediate steps of protein synthesis).

It has been observed that Azithromycin binds with the 50S subunit of ribosome and interferes with polypeptide synthesis. Therefore, it is predicted that stimulated dissociation of peptidyl-tRNA from ribosome is the major mechanism of action of Azithromycin.

Azithromycin competes for [14C] erythromycin ribosome binding site, suggesting that it binds to the same receptor as erythromycin. However, it does not affect the synthesis of nucleic acid.

The Azithromycin accumulates at very higher concentration in cells, predominantly in phagocytes and therefore delivered effectively in high concentrations to sites of infection.

Rifampin (a semisynthetic antibiotic) acts through inhibition of DNA-dependent RNA polymerase of mycobacteria and other microorganisms thereby forming a stable drug-enzyme complex.

The complex leads to suppression of initiation of chain formation in RNA synthesis but does not affect chain elongation. Although Rifampin binds to the holoenzyme but the site of action of the drug is the beta subunit of the enzyme.

Rifampin does not bind to the nuclear RNA polymerase from a variety of eukaryotic cells and hence, do not affect protein synthesis. Rifampin also inhibits RNA synthesis in mammalian mitochondria but at a considerable higher concentrations than that required for the inhibition of the bacterial enzyme.

High concentrations of the drug can also inhibit viral DNA-dependent RNA polymerases and reverse transcriptases. Rifampin is effective against both intracellular and extracellular microorganisms.

azithromycin dosage rifampin dosage

Can both Azithromycin and Rifampin be taken together in combination?

Yes, both the drugs can be taken together in combination. Clinical studies indicate the safety and efficacy of using the combination of the drugs in a variety of diseased states.

Azithromycin and Rifampin combination therapy is very effective for the treatment of chronic chlamydia-induced reactive arthritis, also known as Reiter’s syndrome (type of arthritis occurring due to a reaction to an infection elsewhere in the body) that is characterized by inflammation of the tendons, joints, urogenital tract, and eyes.

Azithromycin plus Rifampin drugs combination is beneficial and provides favorable effects in the chronic course of C. pneumoniae pneumonitis.

Animal studies indicate that the combination of Azithromycin and Rifampin produce higher rates of eradication of C. pneumoniae from lung tissues in comparison to Azithromycin alone.

Macrolides (Clarithromycin or Azithromycin), Ethambutol, and Rifamycins (rifampin, rifabutin) combination provide a therapeutic regime for the treatment of Mycobacterium avium complex (MAC) that is intrinsically resistant to many antibiotics and antituberculosis drugs.

Studies also indicate that Rifampin along with Azithromycin and Clarithromycin may play important role in the treatment of Staphylococcus aureus osteomyelitis in humans.

The recommended treatment of bartonella include the combination of  Azithromycin or Doxycycline with Rifampin, Clarithromycin or a Fluoroquinolone for at least 4-6 weeks.

Safety and precautions while taking Azithromycin: Rifampin combination

  • Azithromycin and Rifampin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
  • Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis) to Azithromycin or any other antibiotic such as Clarithromycin, Dirithromycin, Erythromycin and Rifamycins or any of the drug constituents.
  • Do not share the medications with other persons having the similar kind of problems. Consult your doctor for more details.
  • The drugs are generally not recommended to be taken in case of pregnancy and breastfeeding
  • Administration of the drugs (Azithromycin and Rifampin) is usually not recommended with alcohol.
  • Caution should be exercised with the use of Azithromycin oral solution in diabetic patients because it contains sucrose and in case of use of Rifampin, the management of diabetes becomes difficult.
  • Azithromycin should not be used along with antacids as they bind to the Azithromycin and prevent the absorption in intestine. Antacids should be used with caution in case of Rifampin and should be taken at least 1 hour after Rifampin uptake.
  • Rifampin should not be used along with birth control pills as the drug reduces the effectiveness of the pills.

Itraconazole oral and Simvastatin oral Drug Interactions
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Sporanox and Zocor

May 30 2016 Published by under Drug Interactions

What is Sporanox?

Sporanox is a Brand name for antifungal drug containing itraconazole as an active ingredient. Itraconazole is in a group of antifungals drugs called triazoles.

This drug fights infections that are caused by fungus, which can invade any part of the body including the mouth or throat, lungs, toenails, or fingernails.

It has a broader activity spectrum than fluconazole, but also less broad than voriconazole or posaconazole. Sporanox is active against Aspergillus, Blastomycosis, histoplasmosis, sporotrichosis, and onychomycosis.

Itraconazole has over 99% protein-bound and has virtually no penetration into cerebrospinal fluid thus it is not used to treat meningitis or other CNS infections.

However treatment with Sporanox has been successful for cryptococcal and coccidioidal meningitis. It is available in a form of a capsule and a solution (liquid) to be taken by mouth.

Other Brand names on a market containing itraconazole as an active ingredient are: Itrizol, Onmel, Oriconazol and Sporal.

What is the drug Sporanox used for?

Zocor medication

Zocor is a Brand name for a drug that contain simvastatin as an active ingredient which belongs to a group of drugs called HMG CoA reductase inhibitors, also known as “statins.”

Simvastatin works by reducing the levels of “bad” cholesterol – LDL (low-density lipoprotein), and triglycerides in the blood, while increasing levels of “good” cholesterol – HDL (high-density lipoprotein).

It is also used to reduce the risk of heart attack, stroke and other heart complications in people with diabetes, coronary heart disease, or other risk factors. Zocor is used in adults and children who are at least 10 years old.

Other Brand names for drugs containing simvastatin as an active ingredient are: Cholestat, Lipex, Sinvacor, Sivastin, Sorfox and Statex.

Zocor tablets

Zocor tablets

How does Sporanox and Zocor work in the body?

Itraconazole belong to imidazole/triazole group of antifungal agents. It works by inhibiting the enzyme cytochrome P450 14α-demethylase. This enzyme is important because it converts lanosterol to ergosterol, and is required in fungal cell wall synthesis.

The loss of normal sterols links with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of this drug. Mammalian cell demethylation is much less sensitive to fluconazole inhibition.

Itraconazole exhibits in vitro activity against Candida spp and Cryptococcus neoformans. Fungistatic activity has also been confirmed in normal and immunocompromised animal models for systemic and intracranial fungal infections caused by Cryptococcus neoformans and for systemic infections caused by Candida albicans.

Simvastatin is a lipid-lowering drug that is synthetically derived from the fermentation of fungi Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, rate-limiting enzyme in biosynthesis of cholesterol.

Interference with this enzyme activity reduces the quantity of mevalonic acid, a precursor of cholesterol. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.

Can patients take Sporanox and Zocor together?

Patients must avoid this combination because of high risk for dangerous interaction. Itraconazole oral can increase the blood level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism and increasing the risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

Rhabdomyolysis is a serious condition in which damaged skeletal striated muscle cells breaks down very fast. Breakdown products of damaged muscle cells are released into the bloodstream.

Some of these products, such as the protein myoglobin, can be very harmful to the kidneys and may lead to kidney failure, disseminated intravascular coagulation and death.

Also, simvastatin may increase the level or effect of itraconazole oral by affects how the drug is eliminated from the body through P-glycoprotein [MDR1] transporter.

The table below shows the incidence of side effects after Sporanox and Zocor administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Common side effects 1-10% Nausea (11%), Rash (9%), Abdominal pain (7%), Upper respiratory infection (9%), Headache (3-7%), Myalgia (5%), CPK elevation (>3x ULN) (5%) Eczema (5%), Vomiting (5%) Vertigo (5%), Edema (4%), Abnormal liver function test results (3%), Diarrhea (3%), Pruritus (3%), Fever (3%), Hypertension (3%), Fatigue (2-3%), Hypertriglyceridemia (2%), Hypokalemia (2%), Dizziness (2%), Constipation (2%), Flatulence (1-2%), Anorexia (1%), Decreased libido (1%), Hepatitis (1%), Albuminuria (1%), Malaise (1%), Transaminases increased (1%)

Special precautions and warnings during Sporanox and Zocor administration:

  • Patients should tell their doctor and pharmacist if they are allergic to Sporanox or Zocor, or any other medications, or any of the ingredients in these products.
  • Patients should tell their doctor and pharmacist what prescription and nonprescription medicines, nutritional supplements, vitamins and herbal preparations they are taking or plan to take.
  • In rare cases, simvastatin can cause a serious condition that result in skeletal muscle tissue breakdown, leading to kidney failure. Patients should call doctor immediately if they experience unexplained muscle pain, tenderness, or weakness especially if they also have unusual tiredness, fever and dark colored urine.
  • Before taking Zocor, patients should tell their doctor if they have ever had kidney or liver disease thyroid disorder or diabetes if they are Chinese descent, or if they drink more than 2 alcoholic beverages daily.
  • Grapefruit and grapefruit juice may interact with simvastatin leading to potentially dangerous effects. Patients should not consume grapefruit products while taking Zocor.
  • In rare cases Sporanox can cause heart failure. Patients should tell their doctor if they have or have ever had heart failure. Doctor may tell patients not to take Sporanox. Patients should also tell their doctor if they have or have ever had irregular heartbeat; heart attack; or any other type of lung, liver heart, or kidney disease. If patients experience any of the following symptoms such as: shortness of breath; weakness; excessive tiredness; coughing up white or pink phlegm; fast heartbeat; swelling of the ankles, or legs; feet, waking up at night; and sudden weight gain, they should stop taking Sporanox and call their doctor immediately.
  • Patients on Sporanox therapy should tell their doctor and pharmacist if they are taking following medicines or if they took them in the last 2 weeks before starting therapy with itraconazole: carbamazepine, efavirenz, isoniazid, rifabutin, rifampicin; nevirapine, phenobarbital; and phenytoin.
  • If patients are taking an antacid while they are on Sporanox therapy, take should take it 1 hour before or 2 hours after they take Sporanox.
  • Patients using Sporanox have to tell their doctor if they have or have ever had the conditions such as cystic fibrosis or any other condition that reduces the amount of acid in stomach, or HIV infection.
  • Women using Sporanox should tell their doctor if they are pregnant, plan to become pregnant, or are breastfeeding. Patients should not take this drug to treat nail fungus if you are pregnant or could become pregnant.
  • Sporanox can make patients dizzy or cause blurred or double vision. They should not drive a car or operate machinery until they know how this medication affects them.

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How long does nicotine (cotinine) stay in your system?

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How long does nicotine stay in your system

May 29 2016 Published by under Common Health Questions

What is Nicotine?

Nicotine structure and chemical information
Nicotine is a naturally occurring potent alkaloid found in the nightshade family of plants known as Solanaceae. It is synthesized in the roots and then gets accumulated in the leaves of the plants e.g., Nicotiana rustica, Nicotiana tabacum, Duboisia hopwoodii and Asclepias syriaca etc.  

Nicotine had been extensively used as an insecticide in the past and currently as a neonicotinoids (imidacloprid). The prime sources of Nicotine exposure include tobacco use, Nicotine gum and Nicotine replacement therapies.

Nicotine chemically is an amine and can easily breach the biological membranes as well as brain barriers. Nicotine is implicated in a diverse array of biological functions including gene expression, hormone secretion regulation and enzyme activities.

Nicotine acts as a cholinergic nicotinic agonist involved in stimulating neurons and blocking neurotransmission. It acts as a central nervous system (CNS) stimulant drug (in low amounts) and owes its stimulating effects to various neurotransmitters, including acetylcholine, dopamine, beta-endorphin, serotonin, norepinephrine.

However, higher amount of Nicotine is associated with harmful effects. Stimulation of the CNS may result in peripheral vasoconstriction, tachycardia (abnormally rapid heart rate), and increased blood pressure.

The stimulant effect of Nicotine further contributes to addictive properties of tobacco smoking. Addiction is characterized by physical dependence and tolerance, mood and perception altering effects, compulsive use, relapse after abstinence.

Nicotine also brings about stimulation of the chemoreceptor trigger zone which results in nausea and vomiting. Nicotine also has medical relevance due to its presence in tobacco smoke.

nicotine cycle of addiction

Nicotine withdrawal

Nicotine withdrawal is often associated with symptoms including irritability, sleep disturbances, intense desire, depression, anxiety, and increased appetite. The symptoms usually peak within the first few days after quitting smoking and then subside within a few weeks.

In some cases, the symptoms persist for a longer duration of time including months. Nicotine withdrawal is attributed to behavioral factors as well as the pharmacological effects of Nicotine and can lead to severe withdrawal symptoms.

Nicotine replacement therapies including gum, patches, and inhalers help to diminish the pharmacological aspects of withdrawal whereas behavioral therapies aid the smokers to employ strategies for prevention or evading these symptoms and urges.

Nicotine is used as a medicine to help quitting smoking but may also pose few health problems at even recommended doses during Nicotine replacement therapies.

Studies indicate the use of Nicotine to be associated with birth defects in fetus. The use of Nicotine during pregnancy may even pose a threat to child later in life for obesity, type 2 diabetes, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.

In vitro studies advocate the association of Nicotine with cancer. Consumption of Nicotine at high concentrations may be lethal. Nicotine overdose is not likely the result of smoking alone but mainly attributed to the use of electronic cigarettes which may cause the person to take Nicotine at more than the recommended dose.

Nicotine Mechanism of action

Nicotine acts as a stimulant drug in mammals that acts as an agonist and competitively binds at nicotinic acetylcholine receptors (ionotropic receptors consisting of five homomeric or heteromeric subunits) on dopaminergic neurons in cortico-limbic pathways.

The resultant binding initiates conformation change in the receptor architecture and opening of the ionic channel. The channel then leads to conductance of cations such as those of sodium, calcium, and potassium.

This leads to depolarization, activation of voltage-gated calcium channels and more influx of calcium in the axon terminal. Calcium causes a stimulation of vesicle trafficking towards the plasma membrane and dopamine release into the synapse.

Dopamine binding to its receptors contributes to addictive properties of Nicotine. Nicotine also binds to nicotinic acetylcholine receptors present on the chromaffin cells in the adrenal medulla.

Binding of Nicotine to the receptor opens the ion channel, causes influx of sodium and cell depolarization thereby activating voltage-gated calcium channels.

Calcium then leads to release of epinephrine from intracellular vesicles into the bloodstream resulting in vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar.

Chemical properties of Nicotine

  • Nicotine is a naturally occurring plant product and belongs to the class of organic compounds known as alkaloids and derivatives and contains mostly basic nitrogen atoms.
  • It also contains oxygen, sulfur and more rarely other elements including chlorine, bromine.
  • Nicotine is a bitter-tasting liquid which is strongly alkaline in nature and forms salts with acids
  • Pure Nicotine is a colorless, hygroscopic, oily liquid, miscible with water below 60 .
  • The average molecular weight of Nicotine is 162.2316 Dalton.
  • The melting point of Nicotine is -79 °C and boiling point 247 °C.
  • Nicotine is likely to be volatile owing to its unstable nature and soluble in organic solvents.
  • Nicotine turns brown and sticky in presence of light and air with odd smell and strong irritating odor.
  • Nicotine has a pKa of 8.5.
  • Nicotine easily penetrates the skin.
  • As free base Nicotine burn at a temperature below its boiling point, most of the Nicotine is burned when a cigarette is smoked; but, enough amount is inhaled to provide the desired effects.

Biological properties of Nicotine:

Tobacco plant Nicotiana tobacum

Therapeutic effects

The prime therapeutic use of Nicotine lies in the treatment of Nicotine dependence in order to eliminate smoking. Nicotine replacement therapy prescribes controlled levels of Nicotine to be prescribed to the patients in the form of gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays.

Electronic cigarettes are licensed as medical products for weaning the patients off their dependence on Nicotine. Studies indicate the chance of success of quitting by 50 to 70% by the use of these therapies.

Enhancing performance

Nicotine finds its implication as a performance-enhancing effector on cognition, alertness, and focus. Among the various nicotinic receptor subtypes, the α4β2 receptor is the subtype at which Nicotine exhibit highest binding affinity and also represents the biological target that mediates Nicotine’s addictive properties. Stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance.

Recreational

Nicotine is commonly used as a recreational drug owing to its stimulant effects. Recreational Nicotine products include chewing tobacco, cigarettes, cigars, e-cigarettes, snuff, and snus.

Tolerance and dependence of Nicotine:

Is Nicotine Addictive? For communication between nerve cells (neurons), brain uses certain substances or chemicals known as neurotransmitters. Neurotransmitters are produced by the brain and help to communicate signals and information between body and brain.

Neurotransmitters can also affect mood, sleep, concentration, weight, and can cause adverse symptoms when they are out of balance. Neurotransmitter levels can be depleted by several ways such as stress, neurotoxins, poor diet, drugs abuse (prescription and recreational), genetic predisposition, caffeine and alcohol use etc.

When Nicotine is consumed or inhaled it acts on nicotinic receptors and therefore keep them in highly activate condition. The excessive and chronic activation of nicotinic receptors is managed through masking or down regulation of active receptors.

This results in suppression of psychotropic effect of Nicotine. Within the brain, Nicotine targets dopamine system that is involved in pleasure response. Nicotine directly triggers off abnormal and therefore induces euphoria.

After smoking, the Nicotine ceases and the euphoria disappears. Consequently, more and more smoking attempt is required to recover the feel-good sensation. Hence, the need induces to smoke again.

Absorption of Nicotine:

Nicotine can be absorbed through the oral cavity, lung, skin, urinary bladder and gastrointestinal tract. The process and rate of absorption of Nicotine through biological membranes is dependent on pH. At acidic pH (pH>7) Nicotine is ionized and therefore unable to pass through biological membranes, whereas at higher pH or basic pH (pH<7), Nicotine is charged and not ionized, therefore, easily pass through the membranes.

At physiological pH (7.4) ~30% of Nicotine remain charged and therefore easily cross the membranes. Due to acidic pH of cigarette tobacco (~5.5), Nicotine is largely ionized (positively charged) and little absorbed via the buccal mucosa.

Inhalation of Nicotine is therefore necessary to allow its absorption via large area of alveolar epithelium. Once reached inside the lungs, Nicotine is rapidly reached to the systemic circulation through lung capillaries.

Following lung absorption, Nicotine is quickly distributed among all the body organs. As per the studies Nicotine takes ~10 seconds to reach the brain from the lungs.

Besides lungs, Nicotine is also absorbed through skin which mostly occurs during tobacco harvesting (handling) and Nicotine replacement therapies. Inside urinary bladder, Nicotine is reabsorbed through mucosa of bladder.

This process is pH dependent and reabsorption of the excreted urine occurs only when pH of urine is alkaline (between 8-9).The absorption of Nicotine through gastrointestinal tract is poor due to the acidic nature of this compartment.

Metabolism of Nicotine:

Studies with Nicotine have revealed a highly complicated pathway of metabolism, that primarily comprises cytochrome P-450 and FAD-containing monooxygenases.  Following absorption, Nicotine is extensively metabolized in the liver and produces a variety of metabolites.

The key metabolites of Nicotine metabolism are Nicotine N′-oxide and cotinine N′-oxide, which are produced as a result of mixed function oxidase system. Pathways of Nicotine metabolism are divided into the phases I and II metabolism.

The phase I metabolism involves the microsomal oxidation of Nicotine whereas phase II metabolism involves N- and O glucuronidation of Nicotine and its metabolites.

Excretion of Nicotine:

Before excretion, Nicotine undergoes extensive metabolization in the liver to form a wide variety of metabolites including Nicotine N-oxide and cotinine N-oxide.

Excretion studies with Nicotine have revealed that it can be excreted through various ways such as  urine, saliva, bile, feaces, sweat, gastric juice and breast fluid. It has been observed that about 55% (of total Nicotine consumed) of Nicotine is excreted through urine.

Studies have revealed that excretion of Nicotine through urine is affected by ascorbic acid, which increases the urinary excretion of cotinine and Nicotine. Urinary excretion of Nicotine is also affected by the pH of urine.

When pH is high or alkaline less Nicotine is excreted (due to reabsorption from urine), whereas at low pH or acidic condition high excretion of urine takes place (due to less reabsorption).

Studies also revealed that rate of Nicotine excretion affects the rate of Nicotine consumption that means higher excretion demands more consumption of Nicotine.  

How long does nicotine stay in your system

The duration of Nicotine stay in the body depends upon the amount and type of tobacco used. A reliable indicator of Nicotine use is cotinine that effectively detect the presence of Nicotine in the body.

Several tests have been used to detect the presence of Nicotine and can reliably   detect Nicotine as short as 2 days, or as long as 3 months. Nicotine testing is usually performed to detect use of tobacco products such as chewing tobacco, pipe tobacco, cigars, cigarettes and smokeless tobacco.

Following consumption, Nicotine is metabolized into cotinine by lungs and liver and subsequently excreted into the urine. Cotinine is a very reliable marker for Nicotine test and easily detectable in urine, blood as well as in saliva. A number of tests are available for quantitative as well as qualitative detection of Nicotine from blood, urine, and saliva.

How long does nicotine stay in blood

Nicotine blood test: Nicotine blood test can detect presence or absence as well as level of Nicotine. For this purpose, cotinine and anabasine (metabolic derivatives of Nicotine) are used as biomarkers.

Nicotine is metabolized into cotinine and anabasine, which are subsequently mixed into blood. Following metabolism, Nicotine is usually detected in blood from 1-3 days after last use of Nicotine products i.e. Nicotine patches or gum, cigarettes, smokeless tobacco etc.

However, cotinine stays for longer period and its levels can be detected in blood from 1 to 10 days after last use. The levels of both Nicotine and cotinine in blood may vary depending upon the amount of Nicotine consumed as well as health and age of the person.

Sometimes false positive results are also observed under certain circumstances such as thiocynate contamination. Therefore, results of Nicotine blood test may be false positive in person who are working at  metal refining areas where high levels of thiocyanate are present, or under consumption of almonds, cabbage, mustards, and broccoli (contains thiocyanate) and intake of medications such as amphetamines.

How long does nicotine stay in your urine

Nicotine urine test: The most common and readily available standard test for detecting Nicotine use is Nicotine urine test. The test detects presence of cotinine (Nicotine metabolites) in the urine, also used in blood tests.

The test is as simple as urine sugar test and comprises a strip that is dipped for 5 minutes in urine to detect the presence of cotinine. The overall result is read as either positive or negative that shows presence or absence of cotinine in the sample.

The test can easily detect the standard cutoff level of 200ng/ml of Nicotine in the urine. Cotinine level remains detectable in the urine for 3 to 4 days. However, in case of passive smokers, the level of cotinine can be detected as long as 15 to 20 days.

How long does nicotine stay in your saliva

Nicotine saliva test: Saliva test is the most recent, accurate and preferred method over the blood and urine tests, since it does not require tedious handling for urine or blood samples and provide accurate results with a superior sensitivity over urine test (0 to 2,000ng/ml of Nicotine).

In this test, a strip is soaked in saliva for a period of 20 minutes. Following incubation saliva is reacted with cotinine to compare different levels of cotinine to estimate the amount of Nicotine exposure.

How long does nicotine stay in your hair follicles

Hair follicle Nicotine test: The hair follicle test offers the longest detection window in all available Nicotine tests and can detect Nicotine for months after smoking cessation as Nicotine makes its way from blood stream that nourishes the hair follicle. However, the test is rarely employed due to its expensive nature.  

Does nicotine test detect the use of E-Cigarettes

does e cigarettes have nicotine

Is there nicotine in e cigarettes? The answer is yes. Nicotine test can also detect the use of E-Cigarettes. Since the tests are mainly rely on Nicotine and its metabolite and not on tobacco use. However, E-Cigarettes are delivered low amount of Nicotine then conventional cigarettes.

Nicotine Test Uses: Following are some common uses of Nicotine tests.

  1. Businesses: Nicotine tests are frequently used for various business purposes such as by employers to test employees for Nicotine use, life insurance companies to determine premiums and detect fraud.
  2. Parents: Parents frequently use Nicotine tests to check their children for Nicotine use.

How to flush nicotine out of your system

nicotine removal

Following consumption Nicotine can take 48-72h or more time to flush out completely from the system. It has been observed that Nicotine inhaled following cigarette smoking usually takes 6-8 hour to get rid from the body.

It means it stay in the body and bloodstream and cause cravings till you feed with more Nicotine. Therefore, it is essential to completely filter out the Nicotine from the body to avoid Nicotine withdrawal symptoms effectively.

The following are different ways that can be used to remove the Nicotine from the system effectively. Remove nicotine from body fast naturally.

  1. One of the most prevalent causes of Nicotine is the Cigarette smoking. The more you smoke the more Nicotine will be in your body. Therefore, it is advisable first to quit smoking and then switch to other ways that will help to filter Nicotine from your body.
  2. Next option is to drink lots of water so that hydrated body can easily remove or filter out all toxic materials including Nicotine.
  3. Eat green vegetables such as beans, eggplant, celery and cucumber. These vegetables help to increase removal of Nicotine from the body.
  4. Take lot of vitamin C and drink orange and carrot juice throughout the day. Besides this, infuse your diet with vitamins A, C, and E such as nettle, kiwi, pine needle tea, broccoli, oranges, strawberries, carrot etc. These vitamins help to improve immune system, metabolism and overall health.
  5. Deep breathing exercise improves circulation that infuse bloodstream with oxygen and enables the body to release toxins through sweat including Nicotine.
  6. Keep yourself away from coffee and alcohol since these substances usually triggers carving of Nicotine.
  7. To avoid smoking use oral substitute such as cinnamon stick, chewing gum or candy.
  8. Eat vegetables and food that can improve liver metabolism of toxins such as onions, garlic and egg yolks.

Can Wellbutrin help you quit smoking?
Meta-analysis of the acute effects of nicotine and smoking on human performance by Stephen J. Heishman,corresponding author Bethea A. Kleykamp, and Edward G. Singleton
How long does alcohol stay in your system

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Metformin and Zocor

May 28 2016 Published by under Drug Interactions

What type of drug is Metformin?

Metformin is a Generic name for a drug with antihyperglycemic properties that is used for treating non – insulin – dependent diabetes mellitus.

This drug can improve glucose levels in blood by decreasing the production of glucose in liver, decreasing intestinal absorption of glucose and increasing insulin-mediated glucose uptake.

Therapy with metformin may also decrease the risk of having a stroke, heart attack, or other diabetes-related complications. Metformin can induce weight loss and that’s why it is the drug of choice for obese patients with diabetes type two.

When it is used alone, this drug doesn’t cause hypoglycemia as side effect; but, it may potentiate the hypoglycemic effects of sulfonylureas drugs and insulin if they are used together. Metformin is available in the form of tablet in following dosage forms: 500, 750, 850 and 1000 mg. It is usually taken during meals.

Common Brand names on the market containing metformin as an active ingredient are: Glucophage, Glumetza, Glucophage XR, Fortamet, Metformin Sandoz, Diabex, Diaformin, Siofor, Metfogamma and Riomet.

Glucophage (metformin) tablets

Glucophage (metformin) tablets

What is Zocor used for

Zocor is a Brand name for a drug that contain simvastatin as an active ingredient which belongs to a group of drugs called HMG CoA reductase inhibitors, also known as “statins.”

Simvastatin works by reducing the levels of “bad” cholesterol – LDL (low-density lipoprotein), and triglycerides in the blood, while increasing levels of “good” cholesterol – HDL (high-density lipoprotein).

It is also used to reduce the risk of heart attack, stroke and other heart complications in people with diabetes, coronary heart disease, or other risk factors. Zocor is used in adults and children who are at least 10 years old.

Other Brand names for drugs containing simvastatin as an active ingredient are: Cholestat, Lipex, Sinvacor, Sivastin, Sorfox and Statex.

Zocor tablets

Zocor tablets

How does Metformin and Zocor work in the body?

Metformin reduces glucose levels in blood by decreasing the hepatic glucose production and intestinal glucose absorption, and by improving cell sensitivity to insulin by increasing peripheral uptake of glucose and utilization.

These effects are mediated by the initial activation of AMP-activated protein kinase which is a liver enzyme that plays a significant role in insulin signalization, energy balance, and the metabolism of glucose and lipids.

Activation of AMP- protein kinase is needed for inhibitory effect of metformin on liver cell production. Increased peripheral utilization of glucose is caused by improved insulin binding to its receptors.

Metformin administration also increases AMP- protein kinase in skeletal muscle cells. AMP- protein kinase is known to cause deployment of GLUT-4 to the cell plasma membrane, which results in insulin-independent glucose uptake.

The rare side effect called lactic acidosis can be caused by decreased liver uptake of lactate, which is one of the substrates of gluconeogenesis. Patients who have healthy renal function, the slight excess are simply cleared.

However, patients who have severe renal impairment the accumulation of lactic acid can be clinically significant. Conditions such as severe hepatic disease and acute/decompensated heart failure may precipitate lactic acidosis.

Simvastatin is a lipid-lowering drug that is synthetically derived from the fermentation of fungi Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, rate-limiting enzyme in biosynthesis of cholesterol.

Interference with this enzyme activity reduces the quantity of mevalonic acid, a precursor of cholesterol. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.

Can patients take Metformin and Zocor together?

Many doctors will prescribe this combination in diabetics with high cholesterol levels and increased risk of heart and coronary complications.

There are no direct interactions between Metformin and Zocor, and studies have showed that statin therapy significantly reduces cardiovascular events among individuals with and without a history of diabetes compared with placebo.

However, new findings suggest that higher doses of statins can induce diabetes in predisposed patients, by increasing glucose levels in blood. Women and elderly persons appear to be at increased risk.

Some experimental studies support the theory that statins may cause diabetes melitus by altering glucose homeostasis through both reduced insulin sensitivity and impaired insulin secretion.

Recent study reported that among patients treated with statins, the risk of developing diabetes was 9% higher over a 4-year period compared with patients randomized to placebo or standard care.

Studies have also found that hat those who were receiving the highest dose of statins developed greater insulin resistance, higher insulin levels, and higher hemoglobin A1c compared with those receiving the lowest statin dose or placebo, suggesting a potential dose effect.

Various aspects of statin’s side effect on glycemic control have to be explored. As further research continues, health professionals might still take some precautions to make risk benefit ratio more favorable for the patients.

The table below shows the incidence of side effects after Metformin and Zocor administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Asthenia, Diarrhea, Flatulence, Weakness, Myalgia, Upper respiratory tract infection, Hypoglycemia, GI complaints, Lactic acidosis (rare), Low serum vitamin B-12, Nausea/vomiting, Chest discomfort, Chills, Dizziness, Abdominal distention, Constipation, Heartburn, Dyspepsia, Nasopharyngitis, Headache, Peripheral edema, Pharyngitis, Osteoarthritis, CPK elevation, Transaminases increased, Upper respiratory infection, Constipation, Flatulence, Myalgia, Eczema, Abdominal pain, Vertigo

Special precautions and warnings during Metformin and Zocor administration:

  • Patients should tell their doctor and pharmacist if they are allergic to Metformin or Zocor, or any other medications, or any of the ingredients in these products.
  • Patients should tell their doctor and pharmacist what prescription and nonprescription medications, nutritional supplements, vitamins and herbal products they are taking or plan to take. Patients using Metformin should mention if they are using any of the following drugs: digoxin, insulin, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, tolazamide and tolbutamide. Doctor may need to change the doses of these medications or monitor carefully for side effects.
  • Before using Metformin, patients should tell their doctor or pharmacist their medical history, especially if they ever had or have: breathing problems such as obstructive lung disease and asthma, blood problems such as anemia or vitamin B12 deficiency, kidney or liver disease.
  • Patients should tell their doctor if they are pregnant, plan to become pregnant, or are breastfeeding. If they become pregnant while using Zocor or Metformin they should call a doctor. Pregnant patients should use Metformin only when it is clearly needed. Patients should discuss the risks and benefits with their doctor. Doctor may direct to use insulin instead of metformin during pregnancy.
  • Patients should tell their doctors that they are using metformin before having surgery or any X-ray scanning procedure that use injectable iodinated contrast material.
  • Patients may experience blurred vision, drowsiness or dizziness, or due to extremely low or high blood sugar levels. They should not drive, use machinery, or do any activity that requires alertness or clear vision until they are sure that they can perform such activities safely.
  • Patients should limit the usage of alcohol while using these medications because alcohol can increase the risk of lactic acidosis and low blood sugar can be developed.
  • High fever, diuretic such as hydrochlorothiazide, too much sweating, prolonged diarrhea, and vomiting may cause dehydration and increase the risk of lactic acidosis. Patients should stop taking metformin and tell their doctor if they have prolonged diarrhea or vomiting.
  • Geriatric patients may be at higher risk for side effects such as low blood sugar or lactic acidosis.
  • Metformin can make changes in the menstrual cycle, such as promote ovulation and this drug may also increase the risk of becoming pregnant.
  • Metformin can pass into breast milk, but only in small amounts. Patients should consult their doctor before breast-feeding.
  • Patients should talk with their doctor if they get hurt or develop a fever or infection. These conditions may affect blood sugar levels.
  • In rare cases, simvastatin can cause a serious condition that result in skeletal muscle tissue breakdown, leading to kidney failure. Patients should call doctor immediately if they experience unexplained muscle pain, tenderness, or weakness especially if they also have unusual tiredness, fever and dark colored urine.
  • Before taking Zocor, patients should tell their doctor if they have ever had kidney or liver disease thyroid disorder or diabetes if they are Chinese descent, or if they drink more than 2 alcoholic beverages daily.
  • Grapefruit and grapefruit juice may interact with simvastatin leading to potentially dangerous effects. Patients should not consume grapefruit products while taking Zocor.

Drug interaction between Heparin and Aspirin
Equagesic (Meprobamate and Aspirin) Drug Information

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Aspirin and Heparin interaction

May 27 2016 Published by under Drug Interactions

Why should you take aspirin every day?

Aspirin is an analgesic, non-steroidal anti-inflammatory drug which is used widely for the treatment of fever, inflammation and mild to moderate pain.

Aspirin also plays a key role in the treatment of inflammatory diseases such as rheumatoid arthritis (a progressive autoimmune disease primarily causes inflammation in joints), osteoarthritis (a disease of joint caused by breakdown of joint cartilage) and to reduce the risk of heart attack and deaths caused by heart attack.

Aspirin is usually recommended for the patients of ischemic stroke (blockage of blood flow to brain due to blood clot) or mini stroke (blockage of blood flow to brain for short time).

This drug is also used to treat the angina (sensation of chest pain occur when heart muscle does not get enough oxygen). The drug is available under generic name Acetylsalicylic acid (ASA) and brand name Aspirin.

The active component of the drug Aspirin is salicylic acid, which was initially isolated by Edward Stone from the bark of willow tree in 1763. The drug was first chemically synthesized by Felix Hoffmann at Bayer in 1897.

Aspirin is available as acetylsalicylic acid, which is a synthetic pharmaceutical aromatic homomonocyclic compound with a molecular formula C9H8O4. The drug Aspirin is chemically known as 2-(acetyloxy) benzoic acid.

It is available in the form of regular strength tablets and caplets, extra strength tablet, delayed-release tablet and quick chewable tablets for oral administration with food or without food.
how aspirin reduces fever

What is Heparin?

Heparin is a naturally occurring blood thinner also known as anticoagulant which is widely used to treat blood clotting during surgery. It is synthesized in the body by blood cells known as basophils and mast cells.

Heparin prevents the formation of blood clots as well as extension of existing clots within the blood. Besides this, Heparin works through induction of body natural clot lysis machinery that breakdowns the existing clots.

It is used to prevent deep vein thrombosis and pulmonary embolism (collectively known as venous thromboembolism). Heparin is widely used in the treatment of myocardial infarction, atrial fibrillation with embolization, unstable angina, acute and chronic consumption coagulopathies and as an anticoagulant therapy.

Chemically, Heparin belongs to glycosaminoglycan family of carbohydrates and made up of variably sulfated repeating disaccharide units which together form a polymer with a molecular weight ranging from 3 to 30 kDa.

The drug is available under generic name Heparin Sodium and brand names Hep-Lock, Hemochron, Hep-Lock U/P, HepFlush-10 and Heparin Lock Flush. The drug is commercially available as sodium salt known as Heparin sodium.

Heparin sodium is not taken by oral administration and should be given by intermittent intravenous injection or deeply under the skin and as a dilute (less concentrated) solution to be injected into intravenous catheters.

The drug is given as dilution in 50 or 100 mL of 5% dextrose injection, USP or 0.9% sodium chloride injection, USP, or by intravenous infusion.

The drug Heparin is enlisted in World Health Organization’s List of Essential Medicines, the most important medications needed in a basic health system.

The doses of the drug are adjusted as per the coagulation test performed approximately every 4 hours in the early stages of Heparin treatment.
What is Heparin?

How Aspirin and Heparin work?

Aspirin is a non-steroidal anti-inflammatory drug that inhibits cyclooxygenase (COX) enzyme and therefore known as COX inhibitor agent. The action of both acetyl and salicylate components of the acetylsalicylic acid (ASA or Aspirin) and its active metabolite salicylate are liable for the anti-inflammatory and analgesic properties through inhibition of cyclooxygenases.

ASA inhibits the COX (both COX-1 and COX-2) activity by binding to it irreversibly.  Inhibition of COX results in reduced formation of precursors of prostaglandins and thromboxane from arachidonic acid.

Antipyretic effect of ASA results from the intervention in production of Prostaglandin E1 which is a potent pyretic agent. ASA also inhibit the aggregation of platelets.

This inhibitory effect of ASA is resulted from the intervention in production of Thromboxane A2 which is accountable for the platelets aggregation.

Heparin and its derivatives (e.g., enoxaparin, dalteparin, tinzaparin) work through binding with the enzyme inhibitor antithrombin III (AT). Antithrombin acts as a cofactor of Heparin and its binding with Heparin results in conformational changes that result in its activation.

Once activated, AT inactivates thrombin, factor Xa and other proteases involved in clotting of the blood.  Inhibition factor Xa, thrombin and other proteases result in conversion of prothrombin to thrombin, and fibrinogen to fibrin. Beside this, Heparin also prevents formation of stable fibrin clot and prolongs the clotting time.

Heparin. Aspirin / phenyltoloxamine and Heparin Sodium Drug Interactions

Can both Aspirin and Heparin be taken together in combination?

Yes, Heparin in combination with Aspirin represents a valuable, safe, and effective therapeutic regimen for treatment of various conditions.

The combination therapy of Heparin and Aspirin is associated with a greater reduction in the risk of myocardial infarction or death in case of patients with unstable angina compared to those treated with Aspirin alone.

The use of Heparin [low molecular weight Heparin (LMWH) or unfractionated Heparin (UFH)] together with low-dose Aspirin (LDA) also leads to significant reduction in the rate of miscarriages and causes higher rate of live births in pregnant women with a history of recurrent miscarriages in contrast to LDA treatment alone.

However, the combination therapy has not been found to be effective in case of women with antiphospholipid antibody syndrome and/or in women with late pregnancy losses.

Studies also demonstrated a better antithrombotic effect at the site of carotid endothelial injury in case of combined therapy with Aspirin and Heparin than either drug used alone when given before the injury.

The combined treatment with Aspirin and Heparin may be clinically beneficial in acute carotid thrombosis secondary to carotid endarterectomy or carotid diseases.

Safety and precautions while taking Heparin: Aspirin combination

  • It is always recommended that analgesia should be dose–limited when used in combination due to their increased side effects. Caution should be taken before using Aspirin in combination with Heparin.
  • Do not use the medicine if you are hypersensitive or allergic to Heparin or nonsteroidal anti-inflammatory drugs (i.e. ibuprofen, naproxen, celecoxib) or salicylates, or to any ingredient of the drug formulation.
  • Heparin and Aspirin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
  • A close monitoring for the risk of bleeding is necessary in case of co-administration of Aspirin and Heparin.
  • The drugs are also not recommended if you have any blood clotting or bleeding disorder (i.e. haemophilia), asthma or breathing problem,  kidney disease, liver disease, vitamin K deficiency, low platelet count etc.
  • Do not stop taking low-dose Aspirin to prevent heart attack or stroke unless instructed by your doctor.
  • Cigarette smoking is usually not recommended during administration of Heparin as it decreases blood levels of Heparin and its efficacy.
  • Do not share the medications with other persons having the similar kind of problems. Consult your doctor for more details.
  • The drugs (Heparin and Aspirin) are generally not recommended to be taken in case of pregnancy and breastfeeding.

Can aspirin be taken with meprobamate?
Is it safe to take simvastatin with coumadin?

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Can Aspirin be used in combination of Meprobamate

May 26 2016 Published by under Drug Interactions

Is aspirin an organic compound?

Aspirin is an analgesic, non-steroidal anti-inflammatory drug which is used widely for the treatment of fever, inflammation and mild to moderate pain.

Aspirin also plays a key role in the treatment of inflammatory diseases such as rheumatoid arthritis (a progressive autoimmune disease primarily causes inflammation in joints), osteoarthritis (a disease of joint caused by breakdown of joint cartilage) and to reduce the risk of heart attack and deaths caused by heart attack.

Aspirin is usually recommended for the patients of ischemic stroke (blockage of blood flow to brain due to blood clot) or mini stroke (blockage of blood flow to brain for short time).

This drug is also used to treat the angina (sensation of chest pain occur when heart muscle does not get enough oxygen). The drug is available under generic name Acetylsalicylic acid (ASA) and brand name Aspirin.

The active component of the drug aspirin is salicylic acid, which was initially isolated by Edward Stone from the bark of willow tree in 1763. The drug was first chemically synthesized by Felix Hoffmann at Bayer in 1897.

Aspirin is available as acetylsalicylic acid, which is a synthetic pharmaceutical aromatic homomonocyclic compound with a molecular formula C9H8O4. The drug Aspirin is chemically known as 2-(acetyloxy) benzoic acid.

It is available in the form of regular strength tablets and caplets, extra strength tablet, delayed-release tablet and quick chewable tablets for oral administration with food or without food.
is aspirin an nsaid

What is Meprobamate?

Meprobamate belongs to the class of medications known as tranquilizers and is associated with sedative, hypnotic, anticonvulsant, anti-anxiety, and some indirect muscle relaxant properties.

The drug is marketed by Wallace Laboratories and Wyeth, among others. The drug is available under generic name Meprobamate and brand names such as Amepromat, Quivet, Miltown, Equanil, Meprospan, Zirponand etc.

Meprobamate is primarily used for the treatment of anxiety disorders. The drug is also indicated for the short-term management of insomnia, nervousness, tension and other conditions associated with anxiety.

Besides, Meprobamate is also recommended for the treatment of muscle spasm and immobility due to strains, sprains, and injuries of the back. Meprobamate is a carbamate derivate, synthetic in nature and belongs to the class of organic compounds known as organooxygen compounds.

The compound has a molecular formula C9H18N2O4. Meprobamate is chemically known as 2-Methyl-2- propyltrimethylene dicarbamate. The drug is supplied as tablets or capsules for oral administration by mouth with or without food.

The tablets are available in varying strength of 200 and 400 mg whereas the capsules are available in extended release forms. The drug is usually taken two to four times a day. Meprobamate is available as a combination product with Aspirin and also with conjugated estrogens.
What is Meprobamate?

How Aspirin and Meprobamate work?

Aspirin is a non-steroidal anti-inflammatory drug that inhibits cyclooxygenase (COX) enzyme therefore known as COX inhibitor agent.

The action of both acetyl and salicylate component of the acetylsalicylic acid (ASA or Aspirin) and its active metabolite salicylate are liable for the anti-inflammatory and analgesic properties through inhibition of cyclooxygenases.

ASA inhibits the COX (both COX-1 and COX-2) activity by binding to it irreversibly.  Inhibition of COX results in reduced formation of precursors of prostaglandins and thromboxane from arachidonic acid.

Antipyretic effect of ASA results from the intervention in production of Prostaglandin E1 which is a potent pyretic agent. ASA also inhibits the aggregation of platelets.

This inhibitory effect of ASA results from the intervention in production of Thromboxane A2 which is accountable for the platelets aggregation.

Meprobamate possesses central nervous system (CNS) depressing activity like other barbiturates. The mechanism of action of Meprobamate remains unexplored.

The drug potentiates the release of adenosine that is associated with its central effects. Animal studies indicate the action of the drug at multiple sites in the CNS that includes the hypothalamus, thalamus, limbic system, and spinal cord, excluding the medulla and the autonomic nervous system.

Meprobamate binds to GABAA receptors and brings about an interruption in the neuronal communication in the reticular formation and spinal cord thereby resulting in sedation and change in the perception of pain. The sedative effect of the drug also relaxes skeletal muscle tension.

Niacin tablets

meprobamate tabs

 

Can both Aspirin and Meprobamate be taken together in combination?

Yes, both the drugs can be taken together in combination. The drugs are available as a fixed dose combination pill in the market only as a prescription drug under the brand names Equagesic and Micrainin.

The combination medications consist of a non-steroidal anti-inflammatory drug (NSAID) and an anxiolytic agent. The drug is implicated in the short-term treatment of pain accompanied by tension and/or anxiety in patients with musculoskeletal disease.

Meprobamate acts by calming certain areas of the brain whereas Aspirin decreases the pain. Clinical studies indicate a greater degree of pain relief in case of combination pill as compared to Aspirin alone.

However, the combination pill is not recommended to be used longer than 10 days. Each tablet of Equagesic or Micrainin consists of 200 mg Meprobamate and 325 mg Aspirin.

The usual dosage of the combination pill is one or two tablets to be taken by mouth 3 to 4 times a day. The combination drug is not recommended for patients below the age of 12 years.

Safety and precautions while taking Aspirin: Meprobamate combination

  • Aspirin and Meprobamate may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
  • Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis) to Aspirin or Meprobamate or any of the constituents.
  • The combination drug is generally not recommended to be taken in case of pregnancy and breastfeeding.
  • Administration of the drug is usually not recommended with alcohol and other CNS depressants due to the additive effects. It is recommended to consult with your doctor before taking any of the above during drug administration.
  • Do not share the medications with other persons having the similar kind of problems. Consult your doctor for more details.
  • The drug should not be stopped abruptly before consulting the doctor if used for a longer time or taken in large doses.
  • In case of surgery including dental surgery, uptake of Aspirin in the combination medicine should be stopped 5 days before the surgery as it may cause bleeding problems.
  • Meprobamate (contained in this combination medicine) may bring about dryness of the mouth and long term drying may increase the chance of dental disease such as tooth decay, gum disease, and fungus infections.
  • The combination drug should be taken with caution in patients with history of diabetes, high blood pressure, gout, growth in the nose, bleeding/blood-clotting disorders, kidney or liver disease, brain problems, mental illness, stomach problems, difficulty in urinating.
  • It is recommended not to drive a car or operate machinery while taking the combination medication due to associated dizziness or drowsiness.
  • The drug is not recommended for patients 12 years of age and below.

Is it safe to take simvastatin with coumadin?
Is it safe to take aspirin and warfarin together?

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Coumadin and Zocor

May 25 2016 Published by under Drug Interactions

Is Coumadin the safest blood thinner?

Coumadin is a Brand name for an anticoagulant (or blood thinner) drug that contains warfarin as an active ingredient. Warfarin prevents the formation of blood clots as well as their migration by inhibiting vitamin K-dependent coagulation factors.

Coumadin is indicated for: treatment and prophylaxis of venous thrombosis and pulmonary embolism as its extension, treatment and prophylaxis of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement, reduction of recurrent myocardial infarction and thromboembolic events (such as stroke or systemic embolization) after myocardial infarction and therefore the reduction the risk of death.

Coumadin has no effects on an established thrombus, and can’t reverse ischemic tissue damage. The main targets of anticoagulant therapy are to prevent further extension of the formed blood clot and to prevent the risk of secondary thromboembolic complications that may result in serious and possibly fatal outcomes.

Despite its effectiveness, warfarin therapy has several issues. Many drugs interact with warfarin, as well as some foods (such as leaf vegetable foods because they typically contain large amounts of vitamin K1) and its activity has to be monitored by blood testing for parameter INR – International Normalized Ratio to be ensured that adequate safe dose is taken.

If INR value is high, patients are predisposed to an increased risk of bleeding, while low INR values indicates that the dose of warfarin is uneffective to protect against thromboembolic events.

Other Brand names for warfarin products on the market are: Jantoven, Marevan, Waran and Warfant.

Farin, Coumadin alternative

Farin, Coumadin alternative

What is Zocor?

Zocor is a Brand name for a drug that contain simvastatin as an active ingredient which belongs to a group of drugs called HMG CoA reductase inhibitors, also known as “statins.” Simvastatin works by reducing the levels of “bad” cholesterol – LDL (low-density lipoprotein), and triglycerides in the blood, while increasing levels of “good” cholesterol – HDL (high-density lipoprotein).

It is also used to reduce the risk of heart attack, stroke and other heart complications in people with diabetes, coronary heart disease, or other risk factors. Zocor is used in adults and children who are at least 10 years old.

Other Brand names for drugs containing simvastatin as an active ingredient are: Cholestat, Lipex, Sinvacor, Sivastin, Sorfox and Statex.

zoki

How does Coumadin and Zocor work in the body?

Warfarin works by inhibiting the enzyme activity of vitamin K reductase, which results in depletion of vitamin KH2 – the reduced form of vitamin K. Vitamin K is a cofactor for the carboxylation reactions of glutamate residues of vitamin K-dependent proteins, so this inhibition limits the gamma-carboxylation reactions and activation of the vitamin K-dependent coagulant proteins.

Therefore, the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins S and C is inhibited. Decreased levels of 3 of the 4 vitamin K-dependent coagulation factors (II, VII, and X) results in decreased prothrombin levels in blood and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Simvastatin is a lipid-lowering drug that is synthetically derived from the fermentation of fungi Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, rate-limiting enzyme in biosynthesis of cholesterol.

Interference with this enzyme activity reduces the quantity of mevalonic acid, a precursor of cholesterol. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.

Can patients take Coumadin and Zocor together?

Patients should never take Coumadin with Zocor without medical supervision. Warfarin is being co-prescribed increasingly with HMG-CoA inhibitors, such as simvastatin, for their benefits in reducing the risk of coronary events and stroke.

Many mechanisms for the interaction between Coumadin and Zocor have been postulated, including inhibition of warfarin metabolism, alteration in vitamin K availability, or protein binding displacement.

However, there are no relevant clinical data to confirm any of these. In conclusion, studies have found that concomitant simvastatin therapy results in alterations in warfarin pharmacokinetics, most likely through inhibition of the CYP450 enzymes: CYP2C9 and CYP3A4 which are responsible for the metabolism of warfarin rather than by modification of its pharmacodynamics.

Health professionals should be aware of the interaction between these commonly co-prescribed drugs and patients receiving warfarin should be monitored carefully when concurrent therapy with simvastatin is initiated to avoid over-anticoagulation and the high risk of bleeding.

The table below shows the incidence of side effects after Coumadin and Zocor administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Cholesterol embolus syndrome, Abdominal pain, Intraocular hemorrhage, Alopecia, Rash, Pruritus, Headache, Lethargy, Taste disturbance, Tissue necrosis, Hematuria, Anemia, Hepatitis, Respiratory tract bleeding, Hypersensitivity reaction, Hemorrhage, “Purple toe” syndrome, Increased fracture risk with long-term usage, Dizziness, CPK elevation, Transaminases increased, Upper respiratory infection, Constipation, Flatulence, Myalgia, Eczema, Abdominal pain, Vertigo

Special precautions and warnings during Coumadin and Zocor administration:

  • Patients should tell their doctor and pharmacist if they are allergic to Coumadin or Zocor, or any other medications, or any of the ingredients in these products.
  • Patients should tell their doctor and pharmacist what prescription and nonprescription medicines, nutritional supplements, vitamins and herbal preparations they are taking or plan to take. There are many drugs that have interactions with warfarin and those interactions can cause serious side effects.
  • Patients should tell their doctor and pharmacist if they have or have ever had diseases such as: atherosclerosis, diabetes, some liver or kidney disease, bleeding problems, porphyria, cardiovascular disease such as chest pain (angina), arrhythmias, high blood pressure or heart attack; an underactive adrenal or pituitary gland, or any condition that makes swallow difficult.
  • Patients using Coumadin should tell their doctor and pharmacist what herbal or botanical products they are taking, especially if they are using coenzyme Q10 prparation, Echinacea, Ginkgo biloba, garlic, goldenseal, ginseng, and St. John’s wort. There are also many other herbal or botanical products which might affect body’s response to Coumadin.
  • Patients should tell their doctor if they have or have ever had diabetes. Also they should tell their doctor if they have an infection, a gastrointestinal illness such as diarrhea, or sprue or an indwelling catheter.
  • Patients should also tell their doctor if they are pregnant or plan to become pregnant or if they are breast-feeding. If they become pregnant while using these drugs they should call their doctor immediately. Pregnant women should not take warfarin unless they have a mechanical heart valve, but only with medical supervision. Coumadin may harm the fetus.
  • If patients should have surgery, including dental surgery, they should tell their doctor or dentist that they are using these drugs. Doctor may tell to stop taking warfarin before the surgery or procedure or change your dosage of warfarin before the surgery or procedure.
  • Cigarette smoking may decrease the effectiveness of Coumadin.
  • In rare cases, simvastatin can cause a serious condition that result in skeletal muscle tissue breakdown, leading to kidney failure. Patients should call doctor immediately if they experience unexplained muscle pain, tenderness, or weakness especially if they also have unusual tiredness, fever and dark colored urine.
  • Before taking Zocor, patients should tell their doctor if they have ever had kidney or liver disease thyroid disorder or diabetes if they are Chinese descent, or if they drink more than 2 alcoholic beverages daily.
  • Grapefruit and grapefruit juice may interact with simvastatin leading to potentially dangerous effects. Patients should not consume grapefruit products while taking this medicine.

Coumadin and Aspirin for atrial fibrillation
Niacin and Aspirin interaction

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Coumadin and Aspirin

May 24 2016 Published by under Drug Interactions

What is Coumadin?

Coumadin is a Brand name for an anticoagulant (or blood thinner) drug that contains warfarin as an active ingredient. Warfarin prevents the formation of blood clots as well as their migration by inhibiting vitamin K-dependent coagulation factors.

Coumadin is indicated for: treatment and prophylaxis of venous thrombosis and pulmonary embolism as its extension, treatment and prophylaxis of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement, reduction of recurrent myocardial infarction and thromboembolic events (such as stroke or systemic embolization) after myocardial infarction and therefore the reduction the risk of death.

Coumadin has no effects on an established thrombus, and can’t reverse ischemic tissue damage. The main targets of anticoagulant therapy are to prevent further extension of the formed blood clot and to prevent the risk of secondary thromboembolic complications that may result in serious and possibly fatal outcomes.

Despite its effectiveness, warfarin therapy has several issues. Many drugs interact with warfarin, as well as some foods (such as leaf vegetable foods because they typically contain large amounts of vitamin K1) and its activity has to be monitored by blood testing for parameter INR – International Normalized Ratio to be ensured that adequate safe dose is taken.

If INR value is high, patients are predisposed to an increased risk of bleeding, while low INR values indicates that the dose of warfarin is uneffective to protect against thromboembolic events.

Other Brand names for warfarin products on the market are: Jantoven, Farin,  Marevan, Waran and Warfant.

Farin, Coumadin alternative

Farin, Coumadin alternative

Why should you take Aspirin every day?

Aspirin is a Brand name for a drug that contains acetylsalicylic acid as active ingredient. It works by lowering the substances in the body that can cause fever, pain and inflammation.

Aspirin is indicated to treat pain, and reduce inflammation and fever. Aspirin in lower dose (75-325mg) is sometimes used for a long-term treatment and prevention of heart attacks, strokes, and angina (chest pain) because it can prevent blood clothing.

Low doses of aspirin are usually given immediately after a heart attack to lower the risk of another heart attack or the death of heart tissue.

For cardiovascular conditions, Aspirin should be used only under the supervision of a doctor. Aspirin may be also effective in preventing certain types of cancer, such as colorectal cancer.

Other Brand names for acetylsalicylic acid on the market are: Ascriptin, Arthritis Pain, Aspir-Low, Aspir 81, Bufferin Low Dose, Bayer Childrens Aspirin, Durlaza, Ecpirin, Ecotrin, Fasprin, Miniprin and Halfprin.

benefits of aspirin a day

How does Coumadin and Asprin work in the body?

Warfarin works by inhibiting the enzyme activity of vitamin K reductase, which results in depletion of vitamin KH2 – the reduced form of vitamin K.

Vitamin K is a cofactor for the carboxylation reactions of glutamate residues of vitamin K-dependent proteins, so this inhibition limits the gamma-carboxylation reactions and activation of the vitamin K-dependent coagulant proteins.

Therefore, the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins S and C is inhibited. Decreased levels of 3 of the 4 vitamin K-dependent coagulation factors (II, VII, and X) results in decreased prothrombin levels in blood and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Aspirin manifest analgesic, anti-inflammatory and antipyretic poperties due to actions of both the acetyl and the salicylate portions of the molecule as well as by the active salicylate metabolite.

Aspirin irreversibly and directly inhibits the activity of both cyclooxygenase (COX-1 and COX-2) which results in decrease of the formation of precursors of thromboxanes and prostaglandins from arachidonic acid.

This makes acetylsalicylic acid different from other NSAIDS (such as ibuprofen, diclofenac or naproxen) which are reversible inhibitors. Aspirins antirheumatic actions are a result of its anti-inflammatory and analgesic.

The platelet aggregation-inhibiting actions of aspirin specifically include aspirins ability to act as an acetyl functional group donor to cyclooxygenase enzyme.

Irreversible acetylation renders cyclooxygenase enzyme inactive, thus preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack can’t synthesize new proteins, the effects persist during the life of the exposed platelets (7-10 days).

Acetylsalicylic acid may also inhibit production of prostaglandin I2 in blood vessel endothelial cells; however, inhibition of prostaglandin I2 is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.

Can patients take Coumadin and Aspirin together?

Patients on a Coumadin anticoagulant therapy should be very careful before taking any drugs for aches and pains. Taking NSAID (non-steroidal anti-inflammatory drugs) such as ibuprofen, naproxen, diclofenac, ketorolac, aspirin or any other NSAID for pain relief together with Coumadin can increase the risk of serious bleeding.

However, pain relievers that contain acetaminophen can be the best choice, and many doctors will recommend it. So, patients should never take Coumadin and Aspirin together without medical advice.

Aspirin will impair the function of platelets which are important for blood clotting, while Couamdin impairs blood clotting in a different way, by impacting the INR level.

If these are taken together at the same time, they will attack the body’s ability to do blood clotting in two separate ways. This could greatly increase the risk of having significant bleeding.

However, in some cases under doctor supervision these drugs combination can make sense. Coumadin takes care of cardioembolic “red clot” that occurs in blood low-flow states such as venous thromboembolism and atrial fibrillation, and the antiplatelet drug such as Aspirin treats the “white clot” associated with atherosclerosis.

Prothrombin time or INR should be monitored closely in patients on Coumadin therapy, and in many cases therapy need dose adjustment.

Patients should be advised to contact their doctor if they develop signs and symptoms of excessive anticoagulation, such as: bruising, vomiting, unusual or prolonged bleeding, headache, dizziness, change in stool or urine color, or weakness.

The table below shows the incidence of side effects after Coumadin and Aspirin administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Cholesterol embolus syndrome, Abdominal pain, Intraocular hemorrhage, Alopecia, Rash, Pruritus, Headache, Lethargy, Taste disturbance, Tissue necrosis, Hematuria, Anemia, Hepatitis, Respiratory tract bleeding, Hypersensitivity reaction, Hemorrhage, “Purple toe” syndrome, Increased fracture risk with long-term usage, Dizziness, Angioedema, Bronchospasm, GI pain, ulceration, bleeding, Dermatologic problems, Premature hemolysis, Platelet aggregation inhibition, Pulmonary edema (salicylate-induced, noncardiogenic), Renal damage, Rash, Urticaria, Tinnitus, Vomiting

Special precautions and warnings during Coumadin and Aspirin administration:

  • Patients should tell their doctor and pharmacist if they are allergic to Coumadin or Aspirin, or any other medications, or any of the ingredients in these products.
  • Patients should tell their doctor and pharmacist what prescription and nonprescription medicines, nutritional supplements, vitamins and herbal preparations they are taking or plan to take. There are many drugs that have interactions with warfarin and those interactions can cause serious side effects.
  • Patients should tell their doctor and pharmacist if they have or have ever had diseases such as: atherosclerosis, diabetes, some liver or kidney disease, bleeding problems, porphyria, cardiovascular disease such as chest pain (angina), arrhythmias, high blood pressure or heart attack; an underactive adrenal or pituitary gland, or any condition that makes swallow difficult.
  • Patients using Coumadin should tell their doctor and pharmacist what herbal or botanical products they are taking, especially if they are using coenzyme Q10 prparation, Echinacea, Ginkgo biloba, garlic, goldenseal, ginseng, and St. John’s wort. There are also many other herbal or botanical products which might affect body’s response to Coumadin.
  • Patients should tell their doctor if they have or have ever had diabetes. Also they should tell their doctor if they have an infection, a gastrointestinal illness such as diarrhea, or sprue or an indwelling catheter.
  • Patients should also tell their doctor if they are pregnant or plan to become pregnant or if they are breast-feeding. If they become pregnant while using these drugs they should call their doctor immediately. Pregnant women should not take warfarin unless they have a mechanical heart valve, but only with medical supervision. Coumadin may harm the fetus.
  • If patients should have surgery, including dental surgery, they should tell their doctor or dentist that they are using these drugs. Doctor may tell to stop taking warfarin before the surgery or procedure or change your dosage of warfarin before the surgery or procedure.
  • Cigarette smoking may decrease the effectiveness of Coumadin.
  • Patient using aspirin should tell their doctor if they have or have ever had asthma, frequent stuffed or runny nose, or nasal polyps. If they have these conditions, there is a high risk that they will have an allergic reaction to aspirin.
  • Patient using aspirin should also tell their doctor if they often have heartburn, stomach pain and if you have or have ever had ulcers, anemia, bleeding problems such as hemophilia, or liver or kidney disease.
  • Children and teenagers should not use Aspirin for flu or chicken pox symptoms before a doctor is consulted about Reye’s syndrome, a rare but very serious disease that is associated with Aspirin.

Can you take ibuprofen while on blood thinners?
Aspirin for Preventing Flushing From Niacin

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Can Aspirin be used in combination of Niacin

May 23 2016 Published by under Drug Interactions

Is Aspirin NSAID?

Aspirin is an analgesic, non-steroidal anti-inflammatory drug which is used widely for the treatment of fever, inflammation and mild to moderate pain.

Aspirin also plays a key role in the treatment of inflammatory diseases such as rheumatoid arthritis (a progressive autoimmune disease primarily causes inflammation in joints), osteoarthritis (a disease of joint caused by breakdown of joint cartilage) and to reduce the risk of heart attack and deaths caused by heart attack.

Aspirin is usually recommended for the patients of ischemic stroke (blockage of blood flow to brain due to blood clot) or mini stroke (blockage of blood flow to brain for short time).

This drug is also used to treat the angina (sensation of chest pain occur when heart muscle does not get enough oxygen). The drug is available under generic name Acetylsalicylic acid (ASA) and brand name Aspirin.

The active component of the drug aspirin is salicylic acid, which was initially isolated by Edward Stone from the bark of willow tree in 1763. The drug was first chemically synthesized by Felix Hoffmann at Bayer in 1897.

Aspirin is available as acetylsalicylic acid, which is a synthetic pharmaceutical aromatic homomonocyclic compound with a molecular formula C9H8O4.

The drug Aspirin is chemically known as 2-(acetyloxy) benzoic acid. It is available in the form of regular strength tablets and caplets, extra strength tablet, delayed-release tablet and quick chewable tablets for oral administration with food or without food.

aspirin nsaid

Aspirin tablets

What is Niacin?

Niacin is a water-soluble vitamin that belongs to the vitamin B family and occurs in many animal and plant tissues, with antihyperlipidemic activity.

The drug is available under generic names such as niacin, nicotinic acid, vitamin B3 and brand names Niacor, Niaspan, Slo-Niacin, Nicolar (discontinued).

Niacin, also known as nicotinic acid is a synthetic pharmaceutical organic compound with molecular formula C6H5NO2. The drug is supplied as tablets or capsules for oral administration by mouth.

The tablets are available in varying strength of 250, 500, 750, and 1000 mg whereas capsules in strength of 250 and 500 mg. It is available in different forms such as immediate release, extended or sustained release and no-flush Niacin. Niacin is an antihyperlipidemic agent that is primarily used to reduce the levels of cholesterol and triglyceride in the blood stream.

It is recommended for treatment of pellagra (arising due to Niacin deficiency). Niacin is also used for lowering the risk of osteoarthritis, Alzheimer’s disease, cataracts, and type 1 diabetes.

It is also implicated for treatment of schizophrenia, depression, hallucinations, and memory loss, migraines, chronic brain syndrome, motion sickness, alcohol dependence, and edema.

It is also recommended for treating acne, leprosy, attention deficit-hyperactivity disorder (ADHD), improving digestion, lowering blood pressure, improving circulation in some cases.

Niacin is indicated in lowering the risk of recurrent myocardial infarction in case of patients with a history of myocardial infarction and hyperlipidemia.

Besides, Niacin in combination therapy with a bile acid binding resin in patients with a history of coronary artery disease (CAD) and hyperlipidemia is recommended to treat atherosclerotic disease. Niacin is also prescribed as adjunctive therapy for treatment of severe hypertriglyceridemia.

What is Niacin

Niacin tablets.

How Aspirin and Niacin works?

Aspirin is a non-steroidal anti-inflammatory drug that inhibits cyclooxygenase (COX) enzyme therefore known as COX inhibitor agent. The action of both acetyl and salicylate component of the acetylsalicylic acid (ASA or Aspirin) and its active metabolite salicylate are liable for the anti-inflammatory and analgesic properties through inhibition of cyclooxygenases.

ASA inhibits the COX (both COX-1 and COX-2) activity by binding to it irreversibly.  Inhibition of COX results in reduced formation of precursors of prostaglandins and thromboxane from arachidonic acid.

Antipyretic effect of ASA results from the intervention in production of Prostaglandin E1 which is a potent pyretic agent. ASA also inhibits the aggregation of platelets.

This inhibitory effect of ASA is resulted from the intervention in production of Thromboxane A2 which is accountable for the platelets aggregation.

Niacin is a precursor molecule to cofactors such as nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) and also binds to a number of receptors including Nicotinic acid phosphoribosyltransferase, Nicotinate D-ribonucleotide phyrophsopate phosphoribosyltransferase, Niacin and the Nicotinate N-methyltransferase receptor.

However, the exact mechanism exerted by Niacin for altering lipid profiles is not well defined, but may involve many actions. These include lowering of hepatic triglycerides esterification, partial inhibition of release of free fatty acids from adipose tissue, and increase in the activity of enzyme lipoprotein lipase that may be responsible for increasing the rate of chylomicron triglyceride removal from plasma.

Besides, Niacin also causes a decrease in the levels of apolipoprotein B-100 (apo B) which is the major component of the VLDL (very low-density lipoprotein) and LDL fractions and thus a decrease in their synthesis. Niacin does not exert any effect on fecal excretion of fats, sterols, or bile acids.

niacin side effects

Niacin Tabs

aspirin before niacin

Aspirin Tabs

Can both Aspirin and Niacin be taken together in combination?

Aspirin Low Strength and niacin Drug Interactions:  Yes, both the drugs can be taken together in combination. Clinical studies indicate the safety and efficacy of using the combination of the drugs in reducing the severity and incidence of Niacin extended-release (NER) induced flushing.

Although associated with cardiovascular benefits, Niacin mainly causes adverse effects such as vasomotor side effects and increase in liver enzymes (flushing and hepatotoxicity).

This can be minimized with either small doses of Niacin or co-administration with Aspirin. It is generally recommended to take Aspirin 30 minutes prior to Niacin administration so as to inhibit COX1-dependent prostaglandin production in the skin that causes Niacin-induced flushing.

Data demonstrates that higher doses of Aspirin shows greater efficacy in decreasing intolerability to Niacin in contrast to lower doses (80 or 160 mg compared to 325 mg).

No combined formulation exists at present for Aspirin and Niacin, patents are being filed to develop fixed-dose combination product of sustained-release Aspirin (to maintain Aspirin at sufficient levels) and delayed and extended-release Niacin in order to increase patient compliance.

The combination of Aspirin and Niacin is usually very beneficial to minimize the risk of developing heart disease in patients with high cholesterol and showing a decreased response to Aspirin for the treatment of clogged arteries than patients with normal cholesterol levels.

Besides, clinical studies in healthy people and people with inflammation of the stomach caused by Helicobacter pylori infection (a bacterium causing ulcers) demonstrates the protective effect of Niacin/vitamin C on Aspirin side effects.

Safety and precautions while taking Aspirin: Niacin combination

  • Aspirin and Niacin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
  • Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis) to Aspirin or Niacin or any of the constituents.
  • Aspirin is generally not recommended to be taken in case of pregnancy and breastfeeding while only recommended amounts of Niacin should be taken during pregnancy which is 30 mg per day for women under 18 years of age, and 35 mg for women over 18.
  • Administration of the drugs (Aspirin and Niacin) is usually not recommended with alcohol because alcohol increases the level of acetylsalicylic acid about 50-100% in serum in case of Aspirin and causes worsening of flushing and itching in case of Niacin.
  • Do not share the medications with other persons having the similar kind of problems. Consult your doctor for more details.
  • Dosage adjustment of Aspirin is necessary during development of liver function abnormalities and Niacin is usually not recommended as it might increase liver damage.

Does Coumadin Interact with Tylenol?
Is it alright to take Ibuprofen while taking blood thinners?

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Coumadin and Ibuprofen

May 22 2016 Published by under Drug Interactions

Is Coumadin a blood thinner?

Coumadin is a Brand name for an anticoagulant (or blood thinner) drug that contains warfarin as an active ingredient. Warfarin prevents the formation of blood clots as well as their migration by inhibiting vitamin K-dependent coagulation factors.

Coumadin is indicated for: treatment and prophylaxis of venous thrombosis and pulmonary embolism as its extension, treatment and prophylaxis of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement, reduction of recurrent myocardial infarction and thromboembolic events (such as stroke or systemic embolization) after myocardial infarction and therefore the reduction the risk of death.

Coumadin has no effects on an established thrombus, and can’t reverse ischemic tissue damage. The main targets of anticoagulant therapy are to prevent further extension of the formed blood clot and to prevent the risk of secondary thromboembolic complications that may result in serious and possibly fatal outcomes.

Despite its effectiveness, warfarin therapy has several issues. Many drugs interact with warfarin, as well as some foods (such as leaf vegetable foods because they typically contain large amounts of vitamin K1) and its activity has to be monitored by blood testing for parameter INR – International Normalized Ratio to be ensured that adequate safe dose is taken.

If INR value is high, patients are predisposed to an increased risk of bleeding, while low INR values indicates that the dose of warfarin is uneffective to protect against thromboembolic events.

Other Brand names for warfarin products on the market are: Jantoven, Marevan, Farin, Waran and Warfant.

Coumadin blood thinner

Is Ibuprofen a blood thinner?

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Ibuprofen is a generic name for a drug containing the same name active ingredient.

It is used as a pain reliever for various conditions such as: headaches, dental pain, muscle pain, tendinitis (inflammation or irritation of a tendon, a thick cord that attaches bone to muscle), menstrual cramps, and for the treatment of pain, swelling and joint stiffness caused by arthritis, osteoarthritis, juvenile arthritis, bursitis, ankylosing spondylitis, psoriatic arthritis and gout.

It can also be used to temporarily reduce fever and for the treatment of common cold symptoms. Ibuprofen may be used intravascular with opiates for relieving moderate to severe pain. Ibuprofen lysine may be also used intravscular as a therapy for premature neonates with ductus arteriosus.

Ibuprofen is available in following dosage forms and strengths: capsule, capsule liquid filled, capsule coated (200, 220 and 400 mg), injection (100mg/ml), oral liquid (100 mg/5mL and 50 mg/1.25mL), solution (100 mg, 100 mg/5mL), suspension (100 mg, 200 mg/10mL, 100 mg/5mL) and tablet (200, 300, 400, 600 and 800 mg).

Common Brand names for ibuprofen are: Advil, Motrin, Brufen, Calprofen, Genpril, Ibu, Midol, Nuprin, Cuprofen, Nurofen, Ibuprofen 800 and PediaCare Children’s Pain Reliever/Fever Reducer IB.

is ibuprofen a blood thinner before surgery

How does Coumadin and Ibuprofen work in the body?

Warfarin works by inhibiting the enzyme activity of vitamin K reductase, which results in depletion of vitamin KH2 – the reduced form of vitamin K.

Vitamin K is a cofactor for the carboxylation reactions of glutamate residues of vitamin K-dependent proteins, so this inhibition limits the gamma-carboxylation reactions and activation of the vitamin K-dependent coagulant proteins.

Therefore, the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins S and C is inhibited. Decreased levels of 3 of the 4 vitamin K-dependent coagulation factors (II, VII, and X) results in decreased prothrombin levels in blood and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Ibuprofen inhibits synthesis of prostaglandins (substances in the body that play a key role in pain and inflammation processes in body tissues) by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2.

Inhibition of COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects while the inhibition of COX-1 may cause gastrointestinal bleeding and ulcers.

Ibuprofen has the lowest risk of causing gastrointestinal bleeding of all NSAID, producing balanced inhibitory effects on both COX-1 and COX-2 isoenzymes.

But, this advantage is lost at high doses. This drug may also inhibit chemotaxis, decrease proinflammatory cytokine activity, alter lymphocyte activity, and inhibit neutrophil aggregation – these effects may also contribute to anti-inflammatory activity.

Can patients take Coumadin and Ibuprofen together?

Patients on a Coumadin anticoagulant therapy should be very careful before taking any drugs for aches and pains. Taking NSAID (non-steroidal anti-inflammatory drugs) such as ibuprofen, naproxen, diclofenac, ketorolac, aspirin or other NSAID for pain relief together with Coumadin can increase the risk of serious bleeding.

However, pain relievers that contain acetaminophen can be the best choice, and many doctors will recommend it. So, patients should never take Coumadin and Ibuprofen together without medical advice.

Ibuprofen may impair the function of platelets which are important for blood clotting, while Couamdin impairs blood clotting in a different way, by impacting the INR level.

Although there is no direct interaction between the two medicines, if they are taken together at the same time, they will attack the body’s ability to do blood clotting in two separate ways. This could greatly increase the risk of having significant bleeding.

Prothrombin time or INR should be monitored closely in patients on Coumadin therapy. Patients should be advised to contact their doctor if they develop signs and symptoms of excessive anticoagulation, such as: bruising, vomiting, unusual or prolonged bleeding, headache, dizziness, change in stool or urine color, or weakness.

The table below shows the incidence of side effects after Coumadin and Ibuprofen administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Cholesterol embolus syndrome, Abdominal pain, Intraocular hemorrhage, Alopecia, Rash, Pruritus, Headache, Lethargy, Taste disturbance, Tissue necrosis, Hematuria, Anemia, Hepatitis, Respiratory tract bleeding, Hypersensitivity reaction, Hemorrhage, “Purple toe” syndrome, Increased fracture risk with long-term usage, Dizziness, Epigastric pain, Heartburn, Nausea, Tinnitus, Rash Vomiting , Edema, Fluid retention, Constipation

Coumadin and Ibuprofen side effects

Special precautions and warnings during Coumadin and Ibuprofen administration:

  • Patients should tell their doctor and pharmacist if they are allergic to Coumadin or Ibuprofen, or any other medications, or any of the ingredients in these products.
  • Patients should tell their doctor and pharmacist what prescription and nonprescription medicines, nutritional supplements, vitamins and herbal preparations they are taking or plan to take. There are many drugs that have interactions with warfarin and those interactions can cause serious side effects.
  • Patients should tell their doctor and pharmacist if they have or have ever had diseases such as: atherosclerosis, diabetes, some liver or kidney disease, bleeding problems, porphyria, cardiovascular disease such as chest pain (angina), arrhythmias, high blood pressure or heart attack; an underactive adrenal or pituitary gland, or any condition that makes swallow difficult.
  • Patients using Coumadin should tell their doctor and pharmacist what herbal or botanical products they are taking, especially if they are using coenzyme Q10 prparation, Echinacea, Ginkgo biloba, garlic, goldenseal, ginseng, and St. John’s wort. There are also many other herbal or botanical products which might affect body’s response to Coumadin.
  • Patients should tell their doctor if they have or have ever had diabetes. Also they should tell their doctor if they have an infection, a gastrointestinal illness such as diarrhea, or sprue or an indwelling catheter.
  • Patients should also tell their doctor if they are pregnant or plan to become pregnant or if they are breast-feeding. If they become pregnant while using these drugs they should call their doctor immediately. Pregnant women should not take warfarin unless they have a mechanical heart valve, but only with medical supervision. Coumadin may harm the fetus.
  • If patients should have surgery, including dental surgery, they should tell their doctor or dentist that they are using these drugs. Doctor may tell to stop taking warfarin before the surgery or procedure or change your dosage of warfarin before the surgery or procedure.
  • Cigarette smoking may decrease the effectiveness of Coumadin.
  • Patients should tell their doctor if they have or have ever had any of following conditions such as: asthma, frequent stuffed or runny nose or nasal polyps, swelling of the inside of the nose, swelling of the arms, feet, ankles, hands, or lower legs; lupus or liver or kidney disease.
  • Patients should mention to their doctor if they are using following drugs: ACE inhibitors such as: enalapril , fosinopril, lisinopril, benazepril, captopril, moexipril, diuretics lithium and methotrexate. Doctor may need to change the doses of these medications or monitor more carefully for side effects.
  • Patients should not take nonprescription ibuprofen with any other analgesic unless doctor tells that should.
  • If patients are giving ibuprofen to a child, it is important to tell the child’s doctor if the child has not been drinking fluids or has lost a large amount of fluid from repeated vomiting or diarrhea.

Coumadin and Tylenol Drug Interactions
Is it safe to take Cipro and Ibuprofen together?

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