Drug interaction When a substance affects the activity of a drug this situation called drug interaction , for example

: the effects are increased or decreased, or they give a new effect that neither produces on its own. usually, interaction between drugs come to mind (drugdrug interaction). but, interactions might also exist between drugs & foods (drug-food interactions), in addition to drugs & herbs (drug-herb interactions). These may occur out of accidental misuse or due to rare of information about the active ingredients involved in the relevant substances. Generally , the possibility of poor or unexpected outcomes, so drug interaction should be avoided . but, drug interactions have been deliberately used, like coadministering probenecid with penicillin prior to mass production of penicillin. Due to penicillin was difficult to manufacture, it was useful to find a way to reduce the amount required. A dose of penicillin persists longer when taken with it, and it should the patients to take less penicillin over a course of therapy because probenecid retards the excretion of penicillin.. The co-administration of carbidopa with levodopa which is a current example of a drug interaction used for advantages . Using of Levodopa in the management

of Parkinson's disease and must reach the brain in an un-metabolized state to be useful. The effect of the levodopa is decreased and the risk of side effect will increase when given by itself because It is metabolized in the peripheral tissues outside the brain. So the co-administration of carbidopa with levodopa allows more levodopa to reach the brain un-metabolized and also decrease the risk of side effects because the carbidopa reduces the peripheral metabolism of levodopa . Many processes may lead to drug interactions. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the Absorption, Distribution, Metabolism, and Excretion (ADME) of a drug. also, pharmacodynamic properties of the drug lead to drug interactions , e.g. the co-administration of areceptor antagonist and an agonist for the same receptor Metabolic drug interactions

Many drug interactions are because of alterations in drug metabolism Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptors. One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. This system may be affected by both enzyme induction or enzyme inhibition, as show in the examples.

Enzyme induction : drug A induces the body to produce more of an enzyme which metabolises drug B. The effective concentration of drug B will reduced , the effectiveness of drug B will be loss . Effectiveness of drug A will not altered.

Enzyme inhibition - drug A reduce the production of the enzyme metabolising drug B, therefore an elevation of drug B occurs possibly cause overdose.

Bioavailability - drug A influences the absorption of drug B.

The examples described above may have different outcomes according to the nature of the drugs. For example, if Drug B is a prodrug, then the drug need to enzyme activation to provide the active form of drug . thus, enzyme induction by Drug A would raise the effectiveness of the drug B by increasing its metabolism to its active form. Enzyme inhibition by Drug A would reduce the effectiveness of Drug B. In addition, Drug A and Drug B may affect each other's metabolism. Antidepressants

A class of drugs that reduce symptoms of depressive disorders by correcting chemical imbalances of neurotransmitters in the brain which called antidepressant. Chemical imbalances may be responsible for changes in mood and behavior. The communication link between nerve cells in the brain called neurotransmitters which are very important. Neurotransmitters reside within vesicles found in nerve cells, which are released by one nerve and taken up by other nerves. Neurotransmitters are taken up by the same nerves that released them not taken up by others nerves. This process is called "reuptake."serotonin, dopamine and norepinephrine (noradrenaline) which are the specific neurotransmitters in brain to depression. Generally, antidepressants work by inhibit the reuptake of specific neurotransmitters, therefore increasing their levels around the nerves inside the brain, such as selective serotonin reuptake inhibitors (SSRIs), that will affect serotonin levels in the brain will affect by the antidepressant. Conditions are antidepressants used? Several conditions will treated . They include, but are not limited to: depression, generalized anxiety disorder, agitation, obsessive compulsive disorders(OCD), manicdepressive disorders, bedwetting, major depressive disorder, diabetic peripheral neuropathic pain, neuropathic pain, social anxiety disorder, posttraumatic stress disorder (PTSD) etc. Some of label uses of antidepressants urticaria (hives), include, hot but are not limited

to: fibromyalgia,chronic

flashes, hyperhidrosis

, pruritus itching,premenstrual symptoms, bulimia nervosa, Tourette syndrome, binge eating disorder, etc. differences among antidepressants Antidepressants differ in their effects on neurotransmitters, recognized uses, adverse effects and drug interactions. All antidepressants that are used for depression are effective, there is no evidence that one antidepressant is more effective than another. but, patients may respond to one antidepressant, and not respond to another antidepressant.

Side effects of antidepressants?

Antidepressants Withdrawal may cause withdrawal symptoms if suddenly discontinued.

symptoms

include

nausea,

vomiting,

dizziness, headache,

irritability, sleep disturbance, nightmares, psychosis, and seizures. All antidepressants should have advice about use in children and adolescents. Antidepressants raise the risk of suicidal thinking and behavior in short-term studies in children and adolescents with depression and other psychiatric disorders. Should balance this risk of suicide with the clinical need for the drug for anyone will use of this drugs for child or teenager . Patients who are on therapy should be observed for clinical worsening, unusual

changes in behavior.

Classes of antidepreesents and their drug interaction

Tricyclic antidepressants (TCAs) Tricyclic antidepressants (TCAs) are a class of antidepressant associated with sedation,dry mouth, blurred vision, constipation, urinary retention, and increased pressure in the eye. They are also associated withhypertension, abnormal heart rhythms, anxiety, insomnia, seizures, headache,rash, nausea, and vomiting, abdominal cramps, weight loss, and sexual dysfunction. Tricyclic antidepressants rarely cause liver failure. Drug interaction: Combining tricyclic antidepressants (TCAs) with clonidine (Catapres) may lead to dangerous elevations in blood pressure because TCA may inhibit the antihypertensive effect of clonidine. Combining TCAs with carbamazepine(Tegretol) may result in lower TCA blood levels and higher carbamazepine levels, leading to decreased TCA efficacy or increased carbamazepine toxicity. TCAs may increase the effects of epinephrine, norepinephrine and dopamine. Dangerous increases in blood pressure and abnormal heartbeats may occur. Cimetidine(Tagamet) may reduce the breakdown of some TCAs [for example, amitriptyline(Elavil)] and potentially lead to increased side effects.

Selective serotonin reuptake inhibitors (SSRIs) Selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) are two classes of antidepressants associated with abnormal thinking, agitation, anxiety, dizziness, headache, insomnia, sexual dysfunction, sedation, tremor, sweating, weight loss, diarrhea, constipation, dry mouth, rash, and nausea. Rarely, SSRIs have been associated with hyponatremia (low

sodium), hypoglycemia (low blood glucose), and seizures. Drug interaction: Selective serotonin reuptake inhibitors (SSRIs) should not be combined with other drugs that increase brain serotonin levels [for example, Wort, MAOIs,

TCAs, sumatriptan(Imitrex), linezolid (Zyvox), St

John's

amphetamines]

because there is a risk of dangerous adverse effects. The risk of gastrointestinal bleeding may be increased when SSRIs are combined with nonsteroidal antiinflammatory drugs (NSAIDs).

Monoamine oxidase inhibitors (MAOIs) Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant associated with postural hypotension (feeling faint upon standing due to decreased blood flow to the brain), high blood pressure, fainting, abnormal heart rhythm, dizziness, headache, drowsiness, insomnia, anxiety, constipation, nausea, diarrhea, sexual dysfunction, weight gain or weight loss, andedema. Seizures, rash, blurred vision, and hepatitis are infrequently associated with MAOIs. Drug interaction: Monoamine oxidase inhibitors (MAOIs) should not be combined with other antidepressants or other drugs that increase serotonin levels [for example, amphetamines, linezolid (Zyvox), St. Johns Wort, sumatriptan (Imitrex)]. Such combinations cause excessive serotonin levels in the brain, which may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death.

Administration of MAOIs and other antidepressants or drugs that elevate serotonin should be separated by 14 days. Administration of MAOIs with epinephrine,
5

norepinephrine, phenylephrine, pseudoephedrine, and dopamine may lead to hypertensive crisis. MAOIs interact with tyramine containing foods, resulting in a hypertensive crisis.

Examples of Antidepressants Tricyclic antidepressants (TCA)

amitriptyline (Elavil) amoxapine clomipramine (Anafranil) desipramine (Norpramin) doxepin (Sinequan) imipramine (Tofranil) nortriptyline (Pamelor) protriptyline (Vivactil) trimipramine (Surmontil)

Selective Serotonin Reuptake Inhibitors

citalopram (Celexa) escitalopram (Lexapro) fluoxetine (Prozac, Sarafem) fluvoxamine (Luvox) paroxetine (Paxil) sertraline (Zoloft)

erotonin Norepinephrine Reuptake Inhibitors

duloxetine (Cymbalta) venlafaxine (Effexor) desvenlafaxine (Pristiq)

Monoamine Oxidase Inhibitors

phenelzine (Nardil) tranylcypromine (Parnate) isocarboxazid (Marplan) selegiline (EMSAM, Eldepryl)

Others

maprotiline Mirtazapine (Remeron) trazodone Bupropion (Wellbutrin) nefazodone (Serzone)