PHARMACOLOGICAL EFFECTS OF COMMON MEDICATIONS WITH GRAPEFRUIT JUICE

PHARMACOLOGICAL EFFECTS OF COMMON MEDICATIONS WITH GRAPEFRUIT JUICE
Grapefruit is a healthy addition to a well-balanced diet. However, the fruit or juice has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse events. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 (CYP3A4) system, low bioavailability, and a narrow therapeutic index. Grapefruit juice interacts through the intestinal CYP3A4 system and can inhibit the concentration for 24–72 hours.1 This list is based on manufacturer's prescribing information and is not a complete list of medications that may interact with grapefruit. Caution should be taken by both patient and physician and monitor adverse reactions when taking medications that may interact with grapefruit or juice.
Brand	Generic	Clinical Implications of Co-administration with Grapefruit or Grapefruit Juice
ANTIARRHYTHMICS
Cordarone	amiodarone	Inhibits CYP3A4-mediated metabolism of oral amiodarone resulting in increase plasma levels of amiodarone. Avoid co-administration.
Multaq	dronedarone	Moderate inhibitor of CYP3A, results in a 3-fold increase in dronedarone exposure and a 2.5-fold increase in Cmax. Avoid co-administration.
Ranexa	ranolazine	Moderate CYP3A inhibitor. Limit dose of Ranexa to 500mg twice daily.
Tikosyn	dofetilide	Inhibitor of the CYP3A4 isoenzyme, thus could increase systemic dofetilide exposure. If co-administration is necessary, use with caution.
ANTIMALARIAL
Coartem	artemether/lumefantrine	May increase concentrations of artemether and/or lumefantrine and potentiate QT prolongation.
ANTIPSYCHOTIC
Orap	pimozide	Inhibits CYP3A4-mediated metabolism of pimozide. Avoid co-administration.
CALCIUM CHANNEL BLOCKERS
Nimotop	nimodipine	Elevates plasma concentrations and prolongs action of nimodipine due to a decreased first pass metabolism or reduced clearance. Avoid co-administration.
Plendil	felodipine	2-fold increase in felodipine AUC and Cmax. Avoid co-administration prior to and during treatment.
Procardia	nifedipine	2-fold increase in nifedipine AUC and Cmax with no change in half-life. Avoid co-administration.
Sular	nisoldipine	3-fold increase in nisoldipine Cmax and 2-fold increase in nisoldipine AUC. Avoid co-administration before and after dosing.
CHOLESTEROL-LOWERING MEDICATIONS
Lipitor	atorvastatin	Inhibits CYP3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2 liters per day).
Mevacor	lovastatin	Inhibits CYP3A4 and can increase plasma concentrations of lovastatin. Avoid large quantities of grapefruit juice (>1 quart daily).
Zocor	simvastatin	Inhibits CYP3A4 and can increase plasma concentrations of simvastatin and may increase risk of myopathy. Avoid large quantities of grapefruit juice (>1 quart daily).
H1-RECEPTOR ANTAGONIST
Allegra	fexofenadine	May reduce bioavailability and exposure of fexofenadine. In a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Take with water.
IMMUNOSUPPRESSANTS
Neoral	cyclosporine	Affects metabolism and increases blood concentrations of cyclosporine. Avoid co-administration.
Prograf	tacrolimus	Affects CYP3A-mediated metabolism and should be avoided.
Torisel	temsirolimus	May increase plasma concentrations of sirolimus, a major metabolite of temsirolimus, and should be avoided.
INTERMITTENT CLAUDICATION THERAPY
Pletal	cilostazol	Increase in the Cmax of cilostazol by ∼50%, but has no effect on AUC.
KINASE INHIBITORS
Gleevec	imatinib	May increase plasma concentrations of imatinib and should be avoided.
Sprycel	dasatinib	May increase plasma concentrations of dasatinib and should be avoided.
Sutent	sunitinib	May increase plasma concentrations of sunitinib and should be avoided.
Tarceva	erlotinib	Dose reduction in 50mg decrements should be considered if severe adverse reactions occur. Use with caution.
Tasigna	nilotinib	May increase plasma concentrations of nilotinib and should be avoided.
PSYCHOTROPIC AGENTS
BuSpar	buspirone	4.3 fold increase in Cmax; 9.2 fold increase in AUC. Avoid drinking large amounts (200mL double-strength three times daily) of grapefruit juice.
Halcion	triazolam	Increases the Cmax of triazolam by 25%, increases AUC by 48%, and increases half-life by 18%. Use with caution.
Tegretol	carbamazepine	Inhibits carbamazepine metabolism and may increase plasma carbamazepine levels. Use with caution.
Versed	midazolam	Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system

PREVENTION OF DENTAL CARIES

Dental caries, also known as tooth decay or a cavity, is a disease where bacterial processes change carbohydrate like sugar in food left on teeth to acid that demineralises hard tooth structure (enamel, dentin, and cementum). If demineralisation exceeds saliva and other remineralisation like from calcium, these tissues progressively break down, producing dental caries (cavities, holes in the teeth). Two groups of bacteria are responsible for initiating caries:Streptococcus mutans and Lactobacillus. If left untreated, the disease can lead to pain, tooth loss and infection.Today, caries remains one of the most common diseases throughout the world. Cariology is the study of dental caries.

Dosing and Titration of Commonly Used Antipsychotics

An antipsychotic (or neuroleptic) is a tranquilizing psychiatric medication primarily used to manage psychosis (including delusions or hallucinations, as well as disordered thought), particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics.


Most of the drugs in the second generation, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine. Both generations of medication tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets.
                                                              (or)

Antipsychotics are mainly used to treat the symptoms of schizophrenia and bipolar disorder, but can also be used to treat major depression, dementia, and some specific childhood disorders.

Restless legs syndrome (RLS)

Restless legs syndrome (RLS) or Wittmaack–Ekbom syndrome is a neurological disordercharacterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs. Moving the affected body part modulates the sensations, providing temporary relief.
                                                                  (or)

Restless leg syndrome is a disorder in which there is an urge or need to move the legs to stop unpleasant sensations.

Causes, incidence, and risk factors

Restless leg syndrome (RLS) occurs most often in middle-aged and older adults. Stress makes it worse. The cause is not known in most patients.

Narcolepsy/ADHD

Narcolepsy:

Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by an excessive urge to sleep in inappropriate times, such as while at work or at school. Narcoleptics usually experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which is often confused with insomnia. When a narcoleptic falls asleep they generally experience the REM stage of sleep within 10 minutes; whereas most people do not experience REM sleep until after 90 minutes.
                                                      ( or)
Narcolepsy is a sleep disorder that causes excessive sleepiness and frequent daytime sleep attacks.

Causes, incidence, and risk factors

Narcolepsy is a nervous system disorder, not a mental illness. Anxiety does not cause narcolepsy.

Multiple sclerosis

Multiple sclerosis ( MS), also known as disseminated sclerosis or encephalomyelitis disseminata is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. Disease onset usually occurs in young adults, and it is more common in women.
(or)
Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord (central nervous system).


An autoimmune disorder is a condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue. There are more than 80 different types of autoimmune disorders.

ISCHEMIC HEART DISEASE

INTRODUCTION:

Ischemic Heart Disease, also known as Coronary Artery Disease, is a condition that affects the supply of blood to the heart. The blood vessels are narrowed or blocked due to the deposition of cholesterol on their walls. This reduces the supply of oxygen and nutrients to the heart muscles, which is essential for proper functioning of the heart. This may eventually result in a portion of the heart being suddenly deprived of its blood supply leading to the death of that area of heart tissue, resulting in a heart attack. 

As the heart is the pump that supplies oxygenated blood to the various organs, any defect in the heart immediately affects the supply of oxygen to the vital organs like the brain, kidneys, liver, etc. This leads to the death of tissue within these organs and their eventual failure. Ischemic Heart Disease is the most common cause of death in many countries around the world. 

CAUSES OF ISCHEMIC HEART DISEASE

ALZHEIMER'S DEMENTIA

Dementia is a loss of brain function that occurs with certain diseases. Alzheimer's disease (AD), is one form of dementia that gradually gets worse over time. It affects memory, thinking, and behavior.

Memory impairment, as well as problems with language, decision-making ability, judgment, and personality, are necessary features for the diagnosis.

Causes, incidence, and risk factors:

Age and family history are risk factors for AD.

• As you get older, yoru risk of developing AD goes up. However, developing Alzheimer's disease is not a part of normal aging.
• Having a close blood relative, such as a brother, sister, or parent who developed AD increases your risk.
• Having certain combination of genes for proteins that appear to be abnormal in Alzheimer's disease also increases your risk.

Other risk factors that are not as well proven include:

• Longstanding high blood pressure
• History of head trauma
• Female gender

There are two types of AD -- early onset and late onset.

• In early onset AD, symptoms first appear before age 60. Early onset AD is much less common than late onset. However, it tends to progress rapidly. Early onset disease can run in families. Several genes have been identified.
• Late onset AD, the most common form of the disease, develops in people age 60 and older. Late onset AD may run in some families, but the role of genes is less clear.

The cause of AD is not entirely known, but is thought to include both genetic and environmental factors. A diagnosis of AD is made when certain symptoms are present, and by making sure other causes of dementia are not present.

The only way to know for certain that someone has AD is to examine a sample of their brain tissue after death. The following changes are more common in the brain tissue of people with AD:

• "Neurofibrillary tangles" (twisted fragments of protein within nerve cells that clog up the cell)
• "Neuritic plaques" (abnormal clusters of dead and dying nerve cells, other brain cells, and protein)
• "Senile plaques" (areas where products of dying nerve cells have accumulated around protein).

Alzheimer's disease

When nerve cells (neurons) are destroyed, there is a decrease in the chemicals that help nerve cells send messages to one another (called neurotransmitters). As a result, areas of the brain that normally work together become disconnected.

The buildup of aluminum, lead, mercury, and other substances in the brain is no longer believed to be a cause of AD.

treatment:

 None of the available treatments for Alzheimer's dementia are curative or are known to reverse or halt the process of the disease. The primary goal of treatment is to maintain cognitive function and to improve quality of life for the patient. A thorough baseline assessment using rating scales (eg, mini-mental status exam, global deterioration scale) should be performed before starting drug therapy. Dose titration should be done slowly in order to assess the tolerability of the regimen and to minimize the incidence of severe adverse drug reactions.
Cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine, tacrine):                                 

Although the etiology of cognitive impairment in Alzheimer's disease is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer's disease. It is believed that AChE inhibitors exert their effects by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. These agents can be classified as non-selective (eg, tacrine) or selective (eg, donepezil) reversible inhibitors of AChE. Tacrine is a potent centrally-acting inhibitor of AChE. However, it is used infrequently in clinical practice due to side effects that are often significant and dose-limiting (eg, hepatotoxicity, GI upset). Selective inhibitors of AChE in the CNS have improved safety profiles since they have little effect on AChE in the peripheral tissues; these agents are not associated with hepatotoxicity. 

These drugs may be used to aid in improving cognitive functioning or to slow disease progression in mild-moderate Alzheimer's dementia. A decrease in the frequency of behavioral and neuropsychiatric symptoms may be another benefit. An observation period of 6 to 12 months is necessary to assess the efficacy of the therapeutic regimen. Therapy should be discontinued when continued or accelerated deterioration is seen after 6 months' therapy. Switching to an alternative cholinesterase inhibitor is recommended if the MMSE score is greater than 2 to 4 points after a year of treatment.
N-methyl-D-aspartate receptor antagonists (eg, memantine):                                                        

Persistent activation of N-methyl-D-aspartate (NMDA) receptors in the CNS by the excitatory amino acid glutamate is believed to contribute to the symptoms of Alzheimer’s disease. Memantine is believed to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels.

Memantine is indicated for moderate to severe Alzheimer's dementia, either as monotherapy or in combination with cholinesterase inhibitors; it has not been shown to prevent or slow neurodegeneration.

BREAST CANCER

INTRODUCTION:

Cancers are a group of diseases that cause cells in the body to change and grow out of control. Most types of cancer cells form a lump or mass called a tumor, and are named after the part of the body where the tumor first starts.

A tumor is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic).Tumor is not synonymous with cancer. A tumor can be benign, pre-malignant or malignant, whereas cancer is by definition malignant.

Breast cancer begins in breast tissue, which is made up of glands for milk production, called lobules, and the ducts that connect lobules to the nipple. The remainder of the breast is made up of fatty, connective, and lymphatic tissue. 


CAUSES OF BREAST CANCER:

The exact cause of breast cancer is unknown and there are no fixed causes for breast cancer. Myths in identifying the causes of breast cancer are more prevalent than the real cause. 

Some of the causes that have been collectively associated with breast cancer are:

CHEMOTHERAPY DRUGS ACTING AGAINST BREAST CANCER

Chemotherapy (sometimes cancer chemotherapy) is the treatment of cancer with anantineoplastic drug or with a combination of such drugs into a standardized treatment regimen.

Most commonly, chemotherapy acts by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that it also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract and hair follicles; this results in the most common side effects of chemotherapy: myelosuppression (decreased production of blood cells, hence also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss).

Breast cancer (malignant breast neoplasm) is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas.


CHEMOTHERAPY DRUGS: