A Review on Management of Psychosis using Pharmacological Strategies

Amrish Kumar1*, Asso.Prof.(Dr.) Vrish Dhwaj Ashwlayan2, Assts.Prof.(Mrs.) Mansi Verma3, Prof.(Dr.) Vipin Kumar Garg4, Assts.Prof.(Mr.) Avnesh Kumar5, Prof. (Dr.) Satish Kumar Gupta6, Asso.Prof(Dr.) Sameksha Koul7, Assts.Prof. (Dr.) Anjana Sharma8, Asso.Prof(Dr.) Anurag Chaudhary9, Prof(Dr.) Anoop Kumar10, Asso.Prof. (Dr.) Sachin Kumar11, Mr. Firoj Khan12, Asso.Prof.(Dr.) Lubhan Singh13, Dr. Nitin Sharma14, Prof. Mr. Abhinav Agrawal15 and Prof.(Dr.) Neeraj Kant Sharma16


Anxiolytics
The most widely used are benzodiacepines, which act upon a specific GABA receptor. This family of drugs has a very quick effect, but they aren't recommended for a long time use because they can produce dependence and their effects are limited. They are also used like anticonvulsants.

Antiepileptics
This group of drugs is used in psychiatry for the maintenance and control of bipolar disorders, and they are useful too like anti aggressive drugs. The therapeutic drug monitoring is necessary when some of these substances are administrated because of their potential toxicity and the pharmacological interactions with other treatments.

Lithium
It is a salt used for control of manic symptoms and maintenance of bipolar disorders. Its action mechanism is unknown, despite its usefulness and generalized utilization. It's necessary to control its plasmatic level into a tight range to avoid toxicity and to achieve its function.
Other drugs widely used in psychiatric disorders: methadone, anticholinesterases, stimulants, alcohol aversive are also important due to their side effects and their pharmacologic interactions [1].

Antidepressants
First antidepressant drugs were a casual finding and they affect to various neurotransmitters systems. Usually these old drugs produce many secondary effects. Afterwards, some hypotheses have emerged about the neurotransmission implicated in depression (monoamines: serotonin, noradrenalin and dopamine).
Drug development progresses in parallel to this investigation so more selective drugs appeared as Selective Serotonin Reuptake Inhibitors, (from now on SSRIs), ameliorating secondary effects.
Antidepressant classification depends on the assumption of their action mechanism. Following that schema, there are eight different pharmacological mechanisms at least. Most of the antidepressants block monoamine reuptake, but others block alpha-2 receptors or monoaminoxidase enzyme [2].

Monoamine reuptake inhibitors Tricyclic and tetracyclic antidepressants (TCA)
The tricyclic and tetracyclic branch of antidepressants has a demonstrated and high efficacy, only limited by their sedative and anticholinergic effects. They act on a huge number of receptors, and

Abstract
Psychosis are very common in medical problem about Forty percent of the people that, have anxiety or depression which are associated to physical illness. By which, psychiatric problem is an important part of medical attention and many people usually have psychiatric drugs associated to other treatments. In reality, research which is to be done in Nineteen Seventy-Four demonstrated that integrated therapy (i.e. combined use of medication and psychotherapy) is not harmful to the patient, but is actually useful. However, the conflict between pharmacotherapy and psychotherapy had already made a great disservice to patients, sometimes delaying the required drug treatment (e.g. the importance of duration of untreated psychosis for the prognosis of schizophrenia) or other avoiding effective psychological interventions that could lead to a better quality of life and reduce the risk of suicide. This may be the case when considering dialectical behaviour therapy or exposure and response prevention techniques in cognitive behavioural therapy for borderline personality disorder and obsessive compulsive disorder, respectively. Unfortunately, today, despite a muchvaunted integration of treatments, on the one hand we often deal with reductionist attitudes that judge psychotherapy as irrelevant and consider drug therapy alone sufficient for treatment.  i.
None of the others seems so effective.

iv.
Others: Alimentary conduct disorder and pain disorder.

Noradrenalin selective reuptake inhibitors
It selectively inhibits the reuptake of norepinephrine, but it has little effect on the reuptake of serotonin or dopamine.
It is structurally related to fluoxetine. It has little affinity for

Inhibitors of the reuptake of serotonin and norepinephrine Venlafaxine
It is a potent inhibitor of the reuptake of serotonin, at higher doses inhibits the reuptake of noradrenaline and slightly inhibits the reuptake of dopamine. The absorption is good at digestive level and suffer important hepatic metabolism, by CYP 2D6 isoenzyme, so some SSRIs isozyme inhibitor drugs may increase plasma levels of venlafaxine, giving effects at low doses which are resolved once the inhibitor drug is withdrawn.

Duloxetine
Like venlafaxine, it inhibits the reuptake of both serotonin and norepinephrine, Duloxetine has a minimal affinity for dopamine and histamine receptors. It has significant hepatic metabolism, with many metabolites. It's a moderate inhibitor of CYP 2D6. Its excretion is renal [4].

Inhibitors of the reuptake of norepinephrine and dopamine (bupropion)
It is usually more effective on symptoms of depression than anxiety and quite useful in combination with SSRIs. It has some dopaminergic effects and therefore can induce mild psychostimulant effects. The mechanism of action is not known with accuracy. It seems that weakly inhibits the reuptake of dopamine, raising levels of it in the nucleus accumbens. This increase in dopamine levels in the "area of reward" of the brain may be responsible for the use of bupropion in the cessation. Some data indicate that it exerts its antidepressant effects increasing the functional efficiency of the noradrenergic systems. Apparently, it has no effect on the serotonin system, so it is not effective to block panic attacks.

Serotoninergic modulators: Trazodone
Its mechanism of action is the modulation of serotonergic neurotransmission; it is a relatively specific inhibitor of the reuptake of serotonin. It does not cause any anticholinergic effects. It has Alfa1 adrenergic antagonism and antihistaminergic activity, so

Monoamine Oxidase Inhibitors (MAOIs)
They inhibit the enzyme MAO, who is responsible for the oxidative deamination of neurotransmitters such as serotonin, However, it should be noted that this risk is low, less than 1%.
Other adverse effects are orthostatic hypotension and tachycardia,

Risperidone
Its mechanism of action is mediated by its high affinity for 112 the prevention of recurrences. It has been used in child psychiatry in the treatment of aggressive and serious behavior disorders.
There is an increase in brain-vascular accidents in connection with the use of risperidone and olanzapine in elderly patients with dementia, a complication which advised the prescription of this drug with much caution in such patients. There is a long-acting form of risperidone that can be used twice a month in injection for maintenance treatment.

Olanzapine
Its main indication has been the treatment of schizophrenia, acute episodes of mania and maintenance of bipolar affective disorder. Its structure is similar to clozapine and its mechanism of action is unknown, although it has a stronger affinity for the receptor 5HT 2 A than by the dopamine receptor D 2 . Olanzapine also acts at various levels, interacting with D 1 and D 2 dopaminergic, 5HT 2 A serotoninergic, H1 histaminergic, and muscarinic receptors. Olanzapine carries a lower risk of episodes of Parkinsonism, dystonia and tardive dyskinesia.

Quetiapine
It has clozapine similar profile, with a moderate affinity to D2 receptors and moderate-intense to 5HT2 serotoninergic receptors.
It is a partial agonist of 5HT 1

Ziprasidone
It has high antagonism of 5HT 2 A, 5HT 1 D, 5HT 2 C serotoninergic and D 2 dopaminergic receptors. It has a low tendency to cause extrapyramidal effects because them high ratio 5HT 2 A / D 2 and its low affinity for adrenergic, muscarinic and histaminergic receptors.
Ziprasidone is metabolized in the liver by isoenzymes 3A4 of the P450, through a process of reduction effect of aldehyde oxidase. Its The fact that ethanol, barbiturates, and BZD have similar actions on the same receptor explains their drug synergy (and therefore the danger of the combined overdose) and its cross tolerance. This last property is used in the detoxification of alcoholics with BZD [6].

Drugs used in opioid addiction: Methadone
Methadone is an opioid analgesic with an outstanding action on the mu receptor. In cases of opioid dependence methadone is useful for treatment of detoxification, maintenance, and harm reduction.

Special situations
Opioid analgesics are generally contraindicated in acute respiratory depression, obstructive respiratory processes and patients in treatment with opioid antagonists (naltrexone

Renal failure and psychoactive drugs
If the drug is dialyzable, such as lithium, it will experience a sharp decline in its blood levels after dialysis, so post-dialytic of such drugs levels should be obtained to determine what amount is provided after the process. Certain drugs that are metabolized / eliminated by the kidney will accumulate, with the risk of toxicity, despite not using high doses of these, so that such drugs should be avoided or give at lower doses. In general, the doses to be used will be two-thirds of the usual doses of the drug, except drugs with primarily renal elimination, in which will have to evaluate the clearance of creatinine (ClCr) as an indicator of renal function and the dose to use of the drug. Plasma levels of the drug in question must be controlled, at least once a month, and immediately after the initial dose of medication must provide wherever possible. In renal failure protein binding is lower than in healthy individuals, so usually there is a greater amount of free drug in plasma, with higher therapeutic and side effects. The higher protein binding, the lesser dialyzable is the drug, what it's important to prescribe lower doses.
In general, most of the psychotropic substances aren't dialyzable, except lithium, gabapentine, pregabaline and others [7]. them. Adhering to medication dosages and schedules is important.

Conclusion
If you wish to adjust the medication routine, please consult your doctor as abruptly stopping some of these medicines may cause a Discontinuation Syndrome, with either a worsening of earlier symptoms or the appearance of other physical or psychological symptoms.