1. Antipsychotic drugs (neuroleptics )

3. Introduction
The term “psychosis” denotes a variety of mental disorders. Schizophrenia is a particular kind of psychosis
It is suggested that central dopamine overactivity plays an important role in the pathogenesis.
It is also found that serotonin agonist can cause hallucination and schizophrenia like syndrome.

4. Antipsychotic drugs Classified into: Typical (classic) neuroleptics:
Phenothiazines:e g chlorpromazine.
Butyrophenones: e .g.haloperidol.
Thioxanthenes:e .g .thiothixene.
Atypical (newer) neuroleptics:
Risperidone – Olanzapine – Clozapine

5. Mechanism of action:
Neuroleptics block many different receptors.
The therapeutic effects of neuroleptics are though to result from competitive blockade of dopamine (mainly D2) and/or serotonin (mainly 5-HT2A) receptors.
Typical agents
These drugs have high D2 antagonism and low 5-HT2A antagonism.
Atypical agents
These drugs have low (clozapine) or moderate D2 antagonism and high 5-HT2A antagonism.

6. Receptor Affinity of Typical and Atypical Neuroleptics
5-HT2A H1 M
Alpha1
Typical agents (first generation neuroleptics)
Chlorpromazine
+++ ++
Thioridazine +
Fluphenazine
Haloperidol
Atypical agents (second generation neuroleptics)
Clozapine
Aripiprazole
Quitiapine
Olanzapine
Risperidone
kwe TYE a peen

7. Therapeutic effect:
Positive schizophrenic symptoms usually subside in weeks and are about equally affected by typical and atypical agents.
Negative schizophrenic symptoms are minimally affected by typical neuroleptics but more so by atypical neuroleptics (the higher blockade of 5-HT2 receptors may contribute to this effect).

8. Therapeutic uses:
Schizophrenia: Antipsychotic drugs produce an immediate quieting action. However, their antipsychotic effects typically take longer time to occur (a week or more).
Depression with psychotic manifestations.
Tourette syndrome (haloperidol or risperidone).
Agitation, delirium (in mentally retarded or demented patients)
Irritability, in autistic children (risperidone)
Huntington’s disease
Alcoholic hallucinosis

9. Severe nausea or vomiting associated with, due to D2-receptor blockade in the chemoreceptor trigger zone (CTZ) of the medulla. The most commonly used are the phenothiazines chloropromazine and promethazine.
Neuroleptanalgesia (an anesthetic process that involves combining a major neuroleptic and a potent opioid analgesic to produce a detached, pain-free state. (droperidol & fentanyl)
Pruritus (promethazine)

10. Adverse effects:
1. CNS:
Extrapyramidal side effects:
They occur most likely with typical.
They include:
Parkinsonian-like syndrome
Dystonia: Spasms of muscles of tongue, face, and neck
Tardive dyskinesia: involuntary facial, lip, and tongue movements occurs with chronic therapy. It may be irreversible.
Akathisia: Motor restlessness

11. Neuroleptic malignant syndrome:
It consists of autonomic disturbance, muscle rigidity, hyperthermia, and sweating.
Sedation and memory disturbance.
Seizures, (neuroleptics lower the convulsive threshold).

12. CVS
Postural hypotension. (α-receptor blockade)
Cardiac arrhythmia
GU:
Impotence and inhibition of ejaculation.
Urinary retention, urinary incontinence.
GIT:
Xerostomia, constipation.
Cholestatic jaundice (mainly with chlorpromazine)
Sialorrhea (with clozapine. Up to 70 %)

13. Endocrine disturbance:
Weight gain
Hyperglycemia and precipitation of DM.
Hyperprolactinemia (with typical agents)
Other adverse effects:
Cornea, lens and retinal deposits (mainly with thioridazine)
Blurred vision
Urticaria, skin rash (phenothiazines, 1-5%).
Photosensitivity (phenothiazines)
Agranulocytosis (with clozapine. About 1%)

14. Neuroleptic Drug Interactions of Clinical Importance
Interacting drug
Effect of the interaction
All
-Class 1 and class 3 anti-arrhythmics
-Quinolones
Life threatening arrhythmias
typical and most atypicals
Anti-cholinergics
Increased anti-muscarinic effects
Phenothiazines
SSRIs
Inhibition of phenothiazine metabolism
Haloperidol
Azoles
Inhibition of haloperidol metabolism
Ritonavir, with trade name Norvir (Abbott Laboratories), is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS.
Ritonavir is frequently prescribed with HAART, not for its antiviral action, but as it inhibits the same host enzyme that metabolizes other protease inhibitors. This inhibition leads to higher plasma concentrations of these latter drugs, allowing the clinician to lower their dose and frequency and improving their clinical efficacy.
INTRODUCTION
Azole antifungal agents have added greatly to the therapeutic options for treatment of systemic fungal infections. The azoles that are available for systemic use can be classified into two groups: the triazoles (fluconazole, itraconazole, voriconazole, posaconazole) and the imidazoles (ketoconazole).
The use of azole agents for the treatment of various systemic fungal infections will be reviewed here. Other systemic antifungal agents, such as amphotericin B and flucytosine, are discussed separately. The use of topical antifungals for onychomycosis and dermatophyte infections is reviewed elsewhere. (See "Pharmacology of amphotericin B" and "Pharmacology of flucytosine (5-FC)" and "Dermatophyte (tinea) infections" and "Onychomycosis".)
OVERVIEW OF CLINICAL USE
Members of the triazole family are some of the most widely used antifungal agents [1]. The drugs in this class offer activity against many fungal pathogens without the serious nephrotoxic effects observed with amphotericin B. Newer azole agents have emerged as first-line therapies for several severe fungal diseases, such as invasive aspergillosis, for which voriconazole has become the standard of care.
There are currently four members of the triazole class licensed for use in the United States (fluconazole, itraconazole, voriconazole, and posaconazole).
Agents within the azole class vary importantly with regards to spectrum of activity, pharmacokinetic profiles, and toxicities [2]. For example, fluconazole has excellent activity against yeasts, but offers no protection against mold infections. An extended spectrum is provided by itraconazole, but inconsistent bioavailability limits use of this agent in severely ill patients. Voriconazole is the first-line agent for the treatment of invasive aspergillosis, but its bioavailability is unpredictable and genetically determined, it is associated with unique side effects, and lacks activity against the Mucorales, the agents of mucormycosis. Posaconazole has the broadest spectrum of activity and fewest drug interactions, but absorption is problematic and it is available only as an oral formulation. Thus, it is important for clinicians to appreciate the unique characteristics of each member of this class in order to use azoles appropriately.

15. Effect of the interaction
Neuroleptic
Interacting drug
Effect of the interaction
Haloperidol
Lithium
Extrapyramidal effects and/or lithium toxicity are increased
Clozapine
Caffeine
Inhibition of clozapine metabolism
SSRIs
Ritonavir
Strong inhibition of clozapine metabolism
Risperidone
Inhibition of risperidone metabolism

16. Contraindications and Precautions of Neuroleptics
Contraindications / Precautions
Explanations
States of CNS depression
Additive effect
Parkinson’s disease
Blockade of D2 receptors can worsen the disease
Seizure disorders
Neuroleptic lower the seizure threshold
Catatonia
The risk of neuroleptic malignant is increased
Long Q-T intervals, cardiac arrhythmias
The risk of polymorphic ventricular tachycardia is increased
Glaucoma
Several neuroleptics have pronounced anti-muscarinic effects
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described, in 1874, by Karl Ludwig Kahlbaum in Die Katatonie oder das Spannungsirresein[1] (Catatonia or Tension Insanity).
In the current Diagnostic and Statistical Manual of Mental Disorders published by the American Psychiatric Association (DSM-IV-TR) it is not recognized as a separate disorder, but is associated with psychiatric conditions such as schizophrenia (catatonic type), bipolar disorder, post-traumatic stress disorder, depression and other mental disorders, as well as drug abuse or overdose (or both). It may also be seen in many medical disorders including infections (such as encephalitis), autoimmune disorders, focal neurologic lesions (including strokes), metabolic disturbances and abrupt or overly rapid benzodiazepine withdrawal.
It can be an adverse reaction to prescribed medication. It bears similarity to conditions such as encephalitis lethargica and neuroleptic malignant syndrome. There are a variety of treatments available; benzodiazepines are a first-line treatment strategy. Electro-convulsive therapy is also sometimes used. There is growing evidence for the effectiveness of NMDA antagonists for benzodiazepine resistant catatonia.[5] Antipsychotics are sometimes employed but require caution as they can worsen symptoms and have serious adverse effects.
Patients with catatonia may experience an extreme loss of motor skills or even constant hyperactive motor activity. Catatonic patients will sometimes hold rigid poses for hours and will ignore any external stimuli. Patients with catatonic excitement can suffer from exhaustion if not treated. Patients may also show stereotyped, repetitive movements.
They may show specific types of movement such as waxy flexibility, in which they maintain positions after being placed in them by someone else, or gegenhalten (lit. "counterhold"), in which they resist movement in proportion to the force applied by the examiner. They may repeat meaningless phrases or speak only to repeat what the examiner says.
While catatonia is only identified as a symptom of schizophrenia in present psychiatric classifications, it is increasingly recognized as a syndrome with many faces. It appears as the Kahlbaum syndrome (retarded catatonia), malignant catatonia (neuroleptic malignant syndrome, toxic serotonin syndrome), and excited forms (delirious mania, catatonic excitement, oneirophrenia). It has also been recognized as grafted on to autism spectrum disorders.
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor.

17. Contraindications and Precautions of Neuroleptics
Contraindications / Precautions
Explanations
Bone Marrow suppression
(clozapine)
The risk of clozapine induced agranulocytosis is increased
Hypovolemia, hypotension
Several neuroleptics have alpha1 blocking activity
Prostatic hypertrophy
Several neuroleptics have pronounced anti-muscarinic effects
History of breast cancer
Some breast cancers are prolactin-dependent
Elderly
Sensitivity to anti-cholinergic effects is increased.

18. Good luck