This document summarizes key differences between typical and atypical antipsychotics. It discusses their mechanisms of action, efficacy, side effect profiles, pharmacokinetics, and drug interactions. Typical antipsychotics work mainly through D2 receptor antagonism and have higher rates of extrapyramidal side effects, while atypicals have additional 5-HT2A antagonism and generally cause more metabolic side effects like weight gain. Both classes present risks like QT prolongation, NMS, and low seizure thresholds that require monitoring.
antipsychotics history, managment of psychosis,side effect of antipsychotics, mechanism of antipsychotics, atypical antipsychotics,2nd generation antipsychotics.
antipsychotics history, managment of psychosis,side effect of antipsychotics, mechanism of antipsychotics, atypical antipsychotics,2nd generation antipsychotics.
Background, physiology, immunology and recommended managements for patients in chemotherapy-induced hypersensitivity reactions. Details both cytotoxic and monoclonal antibody therapies. Delivered at HSE South East Regional Ongology Meeting March 2016.
Similar to Classical versus atypical antipsychotics (20)
Pharmacovigilance AND ADVERSE DRUG REACTIONS.
MONITORING REPORTING ROLE OF PHARMACIST.
CLASSIFICATION OF ADR. MECHANISM OF ADR
ROLE OF PHARMACIST IN MANAGING ADR. AUGMENTED, BIZZARE, CONTINOUS, DELAYED, END OF TREATMENT, ABCD, ABCDE.
DETAILED DISCUSSION OF NECROTIZING FASCIITIS.
A SOFT TISSUE INFECTION. USUALLY CALLED AS FLESH EATING BACTERIAL INFECTION. CAUSED BY BACTERIA. AFFECTS THE SOFT SKIN TISSUES
CASE PRESENTATION ONCIRRHOSIS OF LIVER WITH PORTAL HYPERTENSION, HEPATIC EN...Akhil Joseph
A DETAIL CASE PRESENTATION ON CIRRHOSIS OF LIVER WITH PORTAL HYPERTENSION, HEPATIC ENCEPHALOPATHY AND GRADE II OESOPHAGEAL VARICES WITH CONGESTIVE GASTROPATHY. LIVER CIRRHOSIS AND ALL ITS COMPLICATION IN A PATIENT.
Mental and behavioural disturbances due to use of alcohol with simple withdrwalAkhil Joseph
a case study on Mental and behavioural disturbances due to use of alcohol with simple withdrwal. etiology, epidemeology, pathophysiology all covered. pharm.d 4th year topic. alcohol abuse.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
2. ANTIPSYCHOTICS
First-generation antipsychotics, known as typical antipsychotics, were discovered in
the 1950s. Chlorpromazine is the first Antipsychotic agent. It was synthesized by a
French pharmaceutical company Rhône-Poulenc in 1951.
Most second-generation drugs, known as atypical antipsychotics, have been
developed more recently, although the first atypical antipsychotic, Clozapine, was
discovered in 1958 and introduced clinically in the 1970s. Clozapine was
synthesized by Wander AG, a Swiss pharmaceutical company.
5. TYPICALANTIPSYCHOTICS
Mechanism of action : The antipsychotic effect of these
medications is primarily mediated through the blockade of
dopamine receptors (D2 antagonists).
Potency: Typical antipsychotic agents are classified by their
potency for the dopamine receptor into high and low-potency
antipsychotics. Low potency AP have low affinity for dopamine
receptor thus low EPS.
Efficacy : When dosed in equivalent doses, the various typical
antipsychotics have similar efficacy. Equivalent doses are
described using chlorpromazine (CPZ) equivalents . Typical
antipsychotics are thought to be as effective as atypical
antipsychotics for positive symptoms but are less effective for
negative symptoms.
ATYPICALANTIPSYCHOTICS
The mechanism of action : The atypical antipsychotics are
dopamine antagonists but also block 5-HT2A-receptors. They
block 5-HT to a greater extent than dopamine. D2 partial agonist.
Potency : All atypical antipsychotics have activity at the 5-HT2A-
receptor and dopamine receptor. Different agents have different
activity for histamine, α-, and muscarinic receptors.
Efficacy : Atypical antipsychotics have increased efficacy for
negative symptoms compared to typical antipsychotics. With the
exception of clozapine, all antipsychotics are thought to have similar
efficacy for positive symptoms. Clozapine has demonstrated efficacy
for treatment-resistant schizophrenia.
7. General Adverse Effects of Antipsychotics
Typical Antipsychotics Atypical Antipsychotics
Sedation Sedation
Anticholinergic effects
Blurred vision
Constipation
Dry mouth
Urinary retention
Anticholinergic effects (clozapine, olanzapine)
Orthostatic hypotension
Moderate to severe weight gain
Diabetes mellitus
Hypercholesterolemia
Extrapyramidal symptoms Extrapyramidal symptoms
Lowered seizure threshold Lowered seizure threshold
QT prolongation QT prolongation
Hyperprolactinemia Hyperprolactinemia (risperidone)
Moderate weight gain Extrapyramidal symptoms
Sexual dysfunction Sexual dysfunction
Neuroleptic malignant syndrome Neuroleptic malignant syndrome
Photosensitivity
Temperature dysregulation
Elevated liver enzymes
Orthostatic hypotension
8. Atypical : high rate of metabolic side effects.
Typical : high rate of neurologic side effects.
Hence variety of antipsychotics are available, using an alternative drug should be
considered if patient complains of poor tolerability and side effects. Because
medication side effects are the main reason for patient non-adherence.
9. ENDOCRINE SYSTEM
TYPICAL
GALACTORRHEA – 57%
AMENORRHEA OR IRREGULAR MENSTRUAL CYCLE – 97%
HYPERPROLACTINEMIA (D2 blockade in tuberoinfundibular tract)
GYNECOMASTIA
These effects are also seen with RISPERIDONE (atypical)
Switching to atypical Quetiapine, Ziprasidone or Aripiprazole is the alternative choice.
ATYPICAL
WEIGHT GAIN – 40% patient taking CLOZAPINE / OLANZAPINE have significant weight gain ( blockade of
5HT2C receptor ).
Risperidone and quetiapine also causes weight gain but low as compared to above.
Weight gain (obesity) increase the risk of Cardiovascular diseases and DM, as well as is the reason for poor
adherence.
DIABETES – CLOZAPINE have 52% rate of onset.
Switching to Quetiapine, Ziprasidone or Aripiprazole is less likely to cause weight gain.
10. CARDIOVASCULAR SYSTEM
ORTHOSTATIC HYPOTENSION – 20mmHg drop in systolic pressure that causes syncope. Seen in
low potency-typicals and atypicals, especially on IM & IV administration. High risk in patient with
pre-existing cardiovascular diseases and DM.
ECG CHANGES : In both typicals and atypicals. Thioridazine, Mesoridazine, Clozapine and
Ziprasideone are most likely to cause ECG changes, it include increase in HR, flattened T wave, QT
and PR interval prolongation.
QT PROLONGATION : associated with ventricular arrhythmia including torsades de point syndrome.
Thioridazine (20ms) & Ziprasidone (10ms). Its longer than haloperidol, risperidone, olanzapine and
quetiapine.
11. LIPID CHANGES
TYPICALS ( phenothiazines ) and ATYPICALS ( olanzapine & clozapine ) –
elevation in serum TRIGLYCERIDES & CHOLESTEROL.
Low risk of dyslipidemia in Aripiprazole, Ziprasidone and Risperidone.
High risk for development of Metabolic Syndrome in ATYPICALS.
• TGL > 150mg/dl.
• HDL < 40mg/dl.
• FBS > 100mg/dl.
• BP > 135/85mmHg.
• AG > 102 cm in men.
> 88 cm in women.
12. Patients receiving antipsychotics, or antipsychotics in combination with
anticholinergics, may experience anticholinergic side effects (e.g., dry mouth,
constipation, tachycardia, blurred vision, inhibition or impairment of ejaculation,
urinary retention, or impaired memory).
Particularly seen with low-potency typicals ( thioridazine and chlorpromazine )
among the elderly.
Among the atypicals, clozapine and olanzapine have moderately high rates of
anticholinergic effects.
AUTONOMIC NERVOUS SYSTEM
13. CENTRAL NERVOUS SYSTEM
EXTRAPYRAMIDAL SYSTEM
DYSTONIA – a state of abnormal tonicity.
Occurs primarily with Typical antipsychotics.
High risk in males and with increase in dose.
Usually occurs within 24-96 hours of dosage initiation or dose increase.
Incidence rate is 64% with high potency antipsychotics, can be minimised by using
low dose initiation.
Risk is highly reduced with atypiclas. Olanzapine and Ziprasidone inj. gives rapid
action with low risk of Dystonia.
Anticholinergics can be used to treat dystonia – diphenhydramine 50mg IM/IV.
14. AKATHISIA – it’s the inability to sit still and being functionally motor restless.
Occurs in 20-40% patients treated with high potency typical antipsychotics.
Reduction in typical antipsychotics dosage is the best intervention or switching to
an atypical antipsychotic.
Akathisia may occur ocassionally with Atypical antipsychotics and is the most
common EPS like symptom reported with atypical.
Quetiapine and Clozapine have lowest risk of producing akathisia.
15. PSEUDOPARKINSONISM – akinesia. Bradykinesia, cogwheel rigidity, postural abnormalities.
Occurs due to D2 blockade in nigrostriatum
The incidence of pseudoparkinsonism from FGAs ranges from 15.4% to 36%.
Akinesia alone can be seen in 59% of patients on high-potency FGAs.
The onset of symptoms is typically 1 to 2 weeks after initiation of antipsychotic therapy or a dose increase.
The risk of pseudoparkinsonism with SGAs is extremely low.
When risperidone is used in doses greater than 6 mg/day, the risk of pseudoparkinsonism symptoms approaches
that with FGAs.
Quetiapine, aripiprazole, or clozapine are reasonable alternatives in a patient experiencing EPS with other
SGAs.
16. TARDIVE DYSKINESIA – abnormal involuntary movements occuring late in onset to initiation of
antipsychotic therapy.
Classical description is Buccolingual Masticatory Syndrome (BLM).
Late in onset in initiation to antipsychotics therapy.
With FGA’s incidence rate is 0.5-63%.
In elderly overall risk with 3 year FGA’s treatment, the prevalence is 53%.
Risk with SGA’s is extremely low.
SGA’s treatment lasting more than 1 year – risk is 0.8% / year in adult and 5.3% in elderly.
Olanzapine – 0 - 0.5% incidence rate.
Risperidone & Quetiapine – 0.6 -0.7% incidence rate.
Prevention of TD is important.
17. SEDATION AND COGNITION
Sedation is a common side effect in both Typical and Atypical Antipsychotics.
Several studies shows that SGA’s have cognitive benefits over FGA’s.
THERMOREGULATION
Thermoregulatory problems are reportedly more common with use of low-potency
FGA’s and may also occur with more anticholinergic SGA’s.
Poikilothermia is important. Hyperpyrexia can be dangerous in extreme hot weather.
Reduced sweating due to anticholinergic effect also causes elevated body temp.
18. SEIZURES
Antipsychotics lower seizure threshold by GABA depletion.
Increased risk of Seizures in Antipsychotic treatment in both FGA’s and SGA’s.
Usually with high dose, upon initiation and rapid dose increase.
When seizure occurs Rapid reduction in dose is recommended.
High risk with clozapine and chlorpromazine, if change is required then
Risperidone, Haloperidol and Fluphenazine is associated with lowest potential.
19. NEUROLEPTIC MALIGNANT SYNDROME ( NMS )
NMS is a life threatening reaction that occurs mainly with antipsychotic medication. Include symptoms like high
fever, confusion, rigid muscles, variable BP, increased HR, sweating.
NMS occur in 0.5 to 1% of patients receiving FGA’s. High incidence with high-potency, injectable / depot FGA’s.
More commonly seen with Haloperidol and Chlorpromazine.
Although less common than FGA’s NMS is also seen with SGA’s including Clozapine.
Onset is 24-72 hrs.
Also seen when Depot FGA’s are discontinued.
Only SGA’s should be used for rechallenge following an episode of NMS.
PSYCHIATRIC SIDE EFFECTS
Delirium and Psychosis are reported with larger doses of FGA’s or combination of anticholinergics with FGA’s.
20. HEPATIC SYSTEM
Cholestatic hepatocanalicular jaundice has been reported in up to 2% of patients
receiving phenothiazines.
LFT abnormalities ( ELEVATED AST, ALT & ALP ), often asymptomatic, were
reported in up to 50% of patients.
LFT abnormalities are uncommon with SGAs.
Cholestatic hepatitis has been reported with risperidone and LFT abnormalities,
mostly transient, have been reported to be more frequent with clozapine than
haloperidol.
21. GENITOURINARY SYSTEM
Urinary hesitancy and retention is reported with low-potency FGAs and with
clozapine.
Urinary incontinence among the SGAs ( due to alpha-blockade ), it appears to be
particularly problematic with clozapine . The incidence has been reported to be as
high as 44%, and it may be persistent in 25% of patients.
Risperidone produces at least as much sexual dysfunction as FGAs, other SGAs,
which have weak effects on prolactin or are “prolactin-sparing,” produce less
sexual dysfunction.
22. HEMATOLOGIC SYSTEM
Agranulocytosis reportedly occurs in 0.01% of patients receiving FGAs, and more
frequently with chlorpromazine and thioridazine.
The onset is usually within the first 8 weeks of therapy.
In SGA’s Clozapine has 0.8% risk of developing Agranulocytosis in 1 year
treatment.
In 18 months treatment the risk is 0.91%.
Agranulocytosis with clozapine significantly limits the clinical utility of this agent.
Increasing age and female gender are associated with greater risk.
23. DERMATOLOGIC SYSTEM
Allergic reactions are rare and usually occur within 8 weeks of initiating therapy.
Both SGAs and FGAs cause photo sensitivity. Erythema and severe sun burns can
occur.
MISCELLANEOUS ADVERSE EFFECTS
Sialorrhea - which may occur in up to 54% of patients taking clozapine.
24. USE IN PREGNANCY AND LACTATION
Epidemiologic studies show a slightly increased risk of birth defects with low-
potency FGAs.
Haloperidol is the best studied of all antipsychotics, and no relationship between
its use and teratogenicity has been found, But is found excreted greatly through
breast milk. 30mg/day for 6 days – 5ng/ml of haloperidol concentration in breast
milk.
In SGA’s - use of clozapine in pregnancy is not recommended. The weight gain
associated with olanzapine and clozapine and potential risk of gestational diabetes
should be considered in drug selection.
Antipsychotics appear in breast milk with milk : plasma ratios of 0.5 to 1.
However, 1 week after delivery, clozapine milk concentrations have been found to
be as much as 279% of serum concentrations.
Its use during breast-feeding is not recommended.
25. DRUG INTERACTIONS
Excess sedation - antipsychotics are used concomitantly with other medications that have
sedative side effects (e.g., mood stabilizers, hypnotics, alcohol, antidepressants, anxiolytics,
or antihistamines).
Antipsychotics used with other medications with antimuscarinic effects (e.g., antihistamines,
antidepressants, or antiparkinsonism agents) may result in urinary retention, constipation,
blurred vision, or other anticholinergic side effects.
Orthostatic hypotension - Antipsychotic is used with other medications that cause orthostasis
(e.g., antidepressants with α-blockade, antihypertensive agents, or diuretics).
patients are more likely to experience akathisia and other extrapyramidal side effects if
metoclopramide is used concomitantly with antipsychotics.
A potentially more dangerous interaction may occur when medications that slow myocardial
conduction(e.g.,quinidine, procainamide, or tricyclic antidepressants), and thus prolong the
QTc interval, are used in combination with antipsychotics that significantly prolong the QTc
interval, such as ziprasidone, thioridazine, or mesoridazine.
26. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice,
or erythromycin) is added to quetiapine, increased side effects (e.g.,sedation or
orthostasis) may occur.
If an enzyme inducer such as carbamazepine or St.John’s wort is added to quetiapine,
then decreased antipsychotic effects may occur.
inhibitors of CYP 1A2 have the greatest potential for causing interactions with
olanzapine.109 Examples include cimetidine, fluvoxamine, and fluoroquinolone
antibiotics (e.g., ciprofloxacin).
fluvoxamine has been reported to increase clozapine serum concentrations by an
average of two to three fold and up to five fold. ( risk of seizures ).
Mean clozapine serum concentrations are reported to be 32% lower in smokers
compared with nonsmokers. Carbamazepine may also induce clozapine metabolism
and lead to lower serum concentrations.
27. PHARMACOECONOMIC CONSIDERATIONS
Outcomes and related economics of treating patients with the SGAs compared
with the traditional, largely generic FGAs were examined.
Although medication costs are higher with SGA’s than with FGA’s, studies with
various SGA’s have fairly consistently shown total mental health costs to be no
higher or even lower with SGA’s.
Some studies have shown clozapine to result in lower overall mental health care
costs, while others have shown no difference in costs compared to FGAs.
Clozapine decreases suicidality more than comparator antipsychotics, and it is
more effective in treatment-resistant schizophrenia.
Of greater debate is whether differences in cost-effectiveness exist among the
SGAs.
28. Atypical antipsychotics may have advantages in four areas,
1. Tolerability and compliance appears to be better , in particular with less likelihood of inducing
the extrapyramidal effects and hyperprolactinaemia ( although its common with risperidone and
amisulpride ) .
2. Greater efficacy against the negative symptoms of schizophrenia, which are particularly
debilitating in chronic illness.
3. Clozapine ( but not any other newer atypicals ) is more effective than classical agents in
treatment - resistant schizophrenia.
4. Although medication costs are higher with SGA’s than with FGA’s, studies with various SGA’s
have fairly consistently shown total mental health costs to be no higher or even lower with SGA’s.
29. In a meta-analysis the effect sizes of olanzapine, risperidone, amisulpride, and clozapine were
respectively 0.21, 0.25, 0.29, and 0.49 times greater than those of first generation neuroleptic drugs.
An independent cross-sectional survey, in schizophrenic outpatients clinically stabilized on a neuroleptic
drug for a period of 6 months showed that quality-of-life not differ significantly in patients taking
typical neuroleptic drugs and novel ones.
Adverse effects have been studied in people with mental retardation treated with atypical neuroleptic
drugs, typical neuroleptic drugs or no drugs. The patients taking atypical neuroleptic drugs did not have
different overall adverse events from those taking no medications, and both had significantly fewer
overall adverse effects than those taking typical neuroleptic drugs.
30. ATYPICAL DRUGS VERSUS HALOPERIDOL
In a randomized double-blind trial in inpatients with chronic schizophrenia, clozapine, olanzapine, and
risperidone, but not haloperidol, produced statistically significant improvements in total scores on the Positive and
Negative Syndrome Scale after 14 weeks.
There was a significant fall in the Extrapyramidal Symptom Rating Score with the three atypical drugs at the end
of the study and no change with haloperidol.
One patient developed agranulocytosis, two had hypertensive episodes, and four had seizures while taking
clozapine.
31. CLOZAPINE VERSUS TYPICAL NEUROLEPTIC DRUGS
A meta-analysis of randomized controlled comparisons of clozapine with typical neuroleptic drugs
shows, Clozapine was more effective in reducing symptoms in patients with both treatment-
resistant and non-resistant schizophrenia.
In a subset of 13 trials hematological problems tended to be more frequent in patients taking
clozapine; hypersalivation was also more frequent, as were fever and sedation.
Extrapyramidal symptoms were more frequent in the patients treated with typical neuroleptic
drugs.
There was no difference between the two groups in weight gain, hypotension or dizziness, or
seizures.
32. CLOZAPINE VERSUS HALOPERIDOL
Clozapine and haloperidol have been compared in 75 schizophrenic outpatients.
Long-term clozapine was associated with significant improvements in social and
occupational functioning, but not in overall quality of life.
There were no significant differences between the two groups in adverse effects from
previous neuroleptic drug treatment, and dizziness, Salivation and nausea were significantly
more common in patients treated with clozapine. In contrast, dry mouth was significantly
more common with haloperidol.
Patients who completed the double blind study entered a 1-year open clozapine study. Over
the course of that year, there was a small reduction in adverse effects, apart from
hypersalivation, which increased significantly.
Clozapine responders were rated as less severely ill, had fewer negative symptoms, and had
fewer extrapyramidal adverse effects at baseline compared with haloperidol.
33. REFERENCES
MEYLERS’S SIDE EFFECTS OF PSYCHIATRIC DRUGS.
COMPREHENSIVE PHARMACY REVIEW 7TH EDITION.
PHARMACOTHERAPY A PATHOPHYSIOLOGICALAPPROACH – JOSEPH T DIPIRO.
MICROMEDEX.
STAHL’s ESSENTIAL PSYCHOPHARMACOLOGY.