Adverse Drug Reactions of Lithium Monotherapy in Bipolar Affective Disorder: ...BRNSS Publication Hub
Introduction: Lithium is the most effective long-term therapy for bipolar affective disorder (BPAD). Its therapeutic benefits may be restricted by frequent adverse drug reactions (ADRs) and low therapeutic index. We evaluated the pattern of ADR of lithium monotherapy in patients with BPAD. Materials and Methods: An observational study was conducted in 213 patients presenting to psychiatric outpatient department and diagnosed with BPAD and taking lithium monotherapy at least for 3 months. Data collection was done from December 15, 2018, to December 14, 2019. Sociodemographic profile, relevant laboratory investigations, and ADRs were recorded on a self-designed proforma. Descriptive statistics were used to analyze the data. Chi-square test was used to correlate the association between ADR and baseline variables using Statistical Package for the Social Sciences (Version 22.0). P < 0.05 was considered statistically significant. Results: Out of 213 patients, 110 (51.6%) were male. Mean age was 32.06 ± 1.80 years. Sixty-nine (32.4%) patients were substance user. The prescribed dose of lithium ranged from 300 to1200 mg/day. At least one ADR was observed in 139 (65.3%) patients. Tremor (45%) was the most common ADR followed by nausea (9.5%) and sedation (7.8%). Discussion: Daily administration of lithium 1000 mg or more was found to be a significant risk factor for occurrence of the ADRs. Weight gain might result in lithium non-compliance and hence the patients must be counseled regarding this to improve medication adherence. Conclusion: The prevalence of ADR was high in the patients taking maintenance dose of lithium. The patients need regular follow-up to detect and manage ADR which help to increase the medication adherence. There is an urgent need of active pharmacovigilance to detect the ADR in the patients with BPAD.
ADE
INCIDENCE OF ADR
GREADING OF SEVERITY OF ADR
CLASSIFICATIONS
PHARMACOVIGILANCE
CATAGORIES
CAUSES OF ADR
DRUG INDUCED HEPATIC DYSFUNCTION
DRUG INDUCED ENDOCRINE DYSFUNCTION
DRUG INDUCED PHERIPHERAL NEUROPATHY
MANAGEMENT OF ADR
Drug induced disease is defined as the unintended effect of a drug that results in mortality or morbidity with symptoms sufficient to prompt a patient to seek medical attention and/or to require hospitalization and may persist even after the offending drug has been withdrawn. Drug induced diseases also called as iatrogenic diseases, are well known but least studied entity. In this review, we have collected the information from review and research articles related to the drug induced diseases. This review is intended to aid the understanding of some basic concepts regarding the drug induced diseases. This tends to provide information about the some commonly occurring drug induced disorders, the drugs responsible for inducing disorders, their prevention and some of the treatments.
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
Adverse Drug Reactions of Lithium Monotherapy in Bipolar Affective Disorder: ...BRNSS Publication Hub
Introduction: Lithium is the most effective long-term therapy for bipolar affective disorder (BPAD). Its therapeutic benefits may be restricted by frequent adverse drug reactions (ADRs) and low therapeutic index. We evaluated the pattern of ADR of lithium monotherapy in patients with BPAD. Materials and Methods: An observational study was conducted in 213 patients presenting to psychiatric outpatient department and diagnosed with BPAD and taking lithium monotherapy at least for 3 months. Data collection was done from December 15, 2018, to December 14, 2019. Sociodemographic profile, relevant laboratory investigations, and ADRs were recorded on a self-designed proforma. Descriptive statistics were used to analyze the data. Chi-square test was used to correlate the association between ADR and baseline variables using Statistical Package for the Social Sciences (Version 22.0). P < 0.05 was considered statistically significant. Results: Out of 213 patients, 110 (51.6%) were male. Mean age was 32.06 ± 1.80 years. Sixty-nine (32.4%) patients were substance user. The prescribed dose of lithium ranged from 300 to1200 mg/day. At least one ADR was observed in 139 (65.3%) patients. Tremor (45%) was the most common ADR followed by nausea (9.5%) and sedation (7.8%). Discussion: Daily administration of lithium 1000 mg or more was found to be a significant risk factor for occurrence of the ADRs. Weight gain might result in lithium non-compliance and hence the patients must be counseled regarding this to improve medication adherence. Conclusion: The prevalence of ADR was high in the patients taking maintenance dose of lithium. The patients need regular follow-up to detect and manage ADR which help to increase the medication adherence. There is an urgent need of active pharmacovigilance to detect the ADR in the patients with BPAD.
ADE
INCIDENCE OF ADR
GREADING OF SEVERITY OF ADR
CLASSIFICATIONS
PHARMACOVIGILANCE
CATAGORIES
CAUSES OF ADR
DRUG INDUCED HEPATIC DYSFUNCTION
DRUG INDUCED ENDOCRINE DYSFUNCTION
DRUG INDUCED PHERIPHERAL NEUROPATHY
MANAGEMENT OF ADR
Drug induced disease is defined as the unintended effect of a drug that results in mortality or morbidity with symptoms sufficient to prompt a patient to seek medical attention and/or to require hospitalization and may persist even after the offending drug has been withdrawn. Drug induced diseases also called as iatrogenic diseases, are well known but least studied entity. In this review, we have collected the information from review and research articles related to the drug induced diseases. This review is intended to aid the understanding of some basic concepts regarding the drug induced diseases. This tends to provide information about the some commonly occurring drug induced disorders, the drugs responsible for inducing disorders, their prevention and some of the treatments.
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
Now that medical cannabis is available in Maryland as well as DC, patients are looking for guidance from clinicians – who have received little or no information about this substance in their formal training. Furthermore, much of the information being offered about the dangers and benefits of cannabis tends to be distorted positively or negatively according to the philosophical orientation of the source.
This presentation is designed to assist those working in the Youth Work and AOD sector in identifying and assessing at risk young people within Australia. Whilst exploring contemporary theories relating to drug use, prevention and harm reduction, drug use types and drugs in a cultural and social construct within Australia.
Current recreational drugs: RX462 Drug Abuse & Society, Spring 2015 Class pre...Brian Piper
These are the presentations from 2nd and 3rd year pharmacy students from semester long projects on a recreational drug of their choosing. Each presentations contains what was currently known (as of spring, 2015) about the history, epidemiology, pharmacokinetics, and pharmacodynamics of a recreational drug of their choosing.
Drug Abuse & Society (RX 462) Presentations-Spring 2014Brian Piper
This includes end of the semester presentations made by 2nd and 3rd year pharmacy students as part of an elective course. Each student was asked to provide information about history, epidemiology, pharmacodynamics, pharmacokinetics, and toxicology. Older "classic" (psilocybin, ayahuasca, crack), newer (JWB-018, mephedrone, MDA) drugs were covered as well as agents that have appreciable use outside the U.S. (desomorphine, areca nut, kava).
Overview of electronic cigarettes including history, components, safety and adverse events, efficacy in smoking cessation, pharmacokinetics and epidemiology. This presentation was originally delivered to 2nd year pharmacy students as part of a two semester class on pharmacology and toxicology.
Examination of Sexually Dimorphic Behavior on the Novel-Image Novel-Location ...Brian Piper
Objectives: Sex differences in object location memory favoring females appear to be a replicable phenomenon but may also depend on the task demands. This investigation evaluated if females outperformed males at both a short (immediate) and long (half-hour) interval between the learn and test condition using a recently developed version of the Novel-Image Novel-Location (NINL) test (Piper et al. 2011, Physiology & Behavior,
103, 513 - 522). Methods: Young-adults (N = 184) completed a standardized handedness inventory and the NINL. Results: Participants assigned to the Immediate and Delayed conditions did not differ in age, sex, or handedness. The NINL total score was higher among females at the Immediate, but not Delayed, interval. However, within the Delayed condition, females excelled at correctly identifying the unchanged items with a similar pattern for the Novel-Location (NL) scale. Conclusions: These findings are consistent with the view that sexually dimorphic performance favoring females in neurocognitive function can also extend to tasks that have a spatial component.
Drug abuse and society drug presentations: Spring 2013Brian Piper
This presentation is on recreational drugs as part of a elective course for 2nd and 3rd year pharmacy students. The instructions were to include what is known about history, pharmacodynamics, pharmacokinetics including common routes of administration, overdose potential, and recent epidemiology.
The class chose some older agents (peyote, LSD, mushrooms, cocaine), others that have only become more popular recently (bath sats, synthetic cannabinoids), and some medical drugs (methylphenidate, oxycontin).
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
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.
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.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
Neuropharmacological Treatments of Drug Addiction
1. Neuropharmacological
Treatments of Drug Addiction
Brian J Piper, Ph.D., M.S.
Department of Basic Pharmaceutical Sciences
Husson University, Bangor, Maine
3. Importance
• 18 million Americans are alcoholics (loss of
control, tolerance, physical dependence, or craving)-
NIAAA, 2012
• 79,000 deaths are attributable to excessive
alcohol/year: CDC, 2012
• 1.6 million hospitalizations and 4 million ER
visits/year: CDC, 2012
4. Importance
• Cigarette smoking results in 443,000
premature deaths/year
• Smoking is the primary causal factor for at
least 30% of all cancer deaths
• 8.6 million people suffer from a serious illness
caused by smoking/year
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5745a3.htm
5. Importance
• 1.2 million regular heroin users in the U.S., 0.6% of adult
population (UNODC, 2010)
• Economic costs due to nonmedical use of opioids is $53.4
billion/year (Smoking: $193B; Obesity: $139B)
Hansen et al. (2011) Clin J Pain, 27(3), 194-202.
6. Prenatal Drug Exposure
• Fetal Alcohol Syndrome
– 2/1000 births in U.S.
– 50/1000 births in South Africa
• Prenatal smoking is a risk for
stillbirth, SIDS, ADHD
May et al. (2009). Dev Dis Res Review, 15, 1761-92, Arnold et al. (1994) Pediatrics, 93, 216-220.
7. Sex Differences
• Epidemiology:
– opiates (1800s)
– Amphetamines & barbiturates (1960s)
• Reasons for Use
– Males: experimentation (substance abuse -> mood)
– Females: self-medication (mood -> substance abuse)
Becker et al (2012-in press). Biology of Sex Differences, 3, 14.
8. Paradigms
• Moral (Criminal) Model: only acceptable
intervention is one that involves complete
abstinence
• Harm-Reduction Model: any intervention that
reduces harms to drug-user and society is
worthy of consideration
Marlatt (1996) Addictive Behaviors, 21(6), 779-788.
9. Therapeutic Approaches
• Pharmacodynamic: therapeutic drug blocks
the cellular response of a recreational drug
• Pharmacokinetic: therapeutic drug interferes
with recreational drug metabolism or
distribution
• Serendipity: biological mechanism not
Charles
understood (yet) Schuster
Benjamin Rush
1746-1813 1930-2011
10. History
• Ernst von Fleischl-Marxow had his infected
thumb amputated and subsequently became
an opiate addict
• Sigmund Freud recommend cocaine as
a treatment for heroin addiction
• Dr. Marxow developed a cocaine
addiction and died at age 45
1846-1891
12. Alcohol Metabolism
ACDH
Alcohol -------> Acetaldehyde ----------> Acetic Acid
Acetaldehyde is responsible for
nausea, vomiting, skin flushing
1948: discovery that Antabuse inhibits acetaldehyde dehydrogenase
1951: FDA approval for treatment of alcoholism
13. Sounds good in theory but …
• Large, single-blind randomized controlled trial
of:
– Placebo
– 1 mg disulfiram
– 250 mg disulfiram
• Patients monitored by blood/urine analysis
and by family intermittently for 1 year
Fuller et al. (1986) JAMA, 256(11), 1449-1455.
15. Pharmacodynamics of Alcohol
• GABAA agonist
• Glutamate (NMDA) antagonist
• Acamprosate
– small molecule with an unclear mechanism
(possible inhibitor of glutamate release)
– 2004: FDA approved for alcoholism
16. Meta-Analysis of
Acamprosate
• 24 randomized controlled
trials (N=6,894)
– double-blind
– Treatment duration of > 1
month
– Relative risk of return to
drinking (RR = 0.86)
Rosner et al (2011) Cochrane Database of Systematic Reviews, 2011(2), 1-122.
17. Acamprosate: Statistically Significant
• Among patients both tolerating side-effects &
completing psychosocial therapies:
– Acamprosate patient complying with medication is
14% more likely to remain abstinent
– “Acamprosate is expected to prevent drinking
after detoxification in one out of nine patients
who would have otherwise relapsed.” (p. 25)
Rosner et al (2011) Cochrane Database of Systematic Reviews, 2011(2), 1-122.
18. Kudzu
• Pueraria lobata is a vine native to Japan (Kuzu)
and China
• Extended history to treat inebriation and
symptoms of hangover
19. Kudzu root
• 14 volunteers with a history
of heavy drinking received
placebo or kudzu extract
(1000 mg x 3/day) for one
week
• Drinking behavior in a
naturalistic environment
monitored
Lucas et al. (2005) Alcoholism: Clinical & Experimental Research, 29(5), 756-762.
20. Puerarin
• Isoflavones
daidzin, daidzein, &
puerarin have efficacy in
animal models
• 600 mg puerarin x 2/day or
placebo (N=10)
Penetar et al. (in press) Drug & Alcohol Dependence.
21. Drug Abuse Warning Network
Counties
Clackamas
Columbia
Multnomah
Washington
Yamhill
22. Drug Abuse Warning Network
Counties
Clackamas Multi-Drug (Single)
Columbia Total: 233 (102)
Multnomah Heroin: 102 (45)
Washington Methadone: 54 (22)
Yamhill Other opiate: 59 (14)
23. Heroin for Heroin Addicts?!
• Supervised heroin administration ongoing in
Canada, Spain, Germany for severely
dependent long-term heroin addicts who have
been unsuccessful with other treatment (e.g.
methadone) options.
Advantages Disadvantage
New (last?) option Politics
Less likelihood of over-dose relative to Less safety than methadone, etc.
street heroin
Possible reduction in criminal activity?
24. Trial
• Heroin dependent patients (N=1,015) were
randomized to receive methadone or
supervised heroin injections (3x/day; upto
1,000 mg/day).
Hassen et al. (2007). British Journal of Psychiatry, 191, 55-62.
25. Results
• Adverse events: Heroin: 32.8%; Methadone: 10.9%
Hassen et al. (2007). British Journal of Psychiatry, 191, 55-62
26. Meta-Analysis
• Heroin administration (iv or oral), relative to
methadone, resulted in:
– greater likelihood (44%) of completing treatment
– reduced mortality (23%)
– decreased criminal behavior (possibly)
• Prescription heroin may be an option for
addictions that have failed other
interventions.
Ferri et al. (2012). Cochrane Reviews, 2012(3), e1-e57.
27. Nicotine
• Nicotine: active ingredient of tobacco
leaves with half-life of 2 hours
• Cotinine: inactive metabolite (?) of Nicotiana
nicotine with half-life of 20 hours
1530-1600
29. The nicotinic cholinergic receptor
Varenicline: partial α4β2 agonist
Cytisine: partial α4β2 agonist
Bupropion: nACh antagonist
Nicotinic Replacement Therapy (NRT): nACh agonist
30. Cytisine
• Cytisus Laburnum L. (Golden
rain) is native to central and
southern Europe
• Tabex® developed in 1964
31. Cytisine Trial
• Regular smokers (N=740) randomized to
cytisine (step-down dosing) or placebo for 4
weeks and followed for 1 year
• Minimal counseling
West et al. (2011). New England Journal of Medicine, 365, 1193-1200.
32. Cytisine Trial
• Regular smokers (N=740) randomized to
cytisine (step-down dosing) or placebo for 4
weeks and followed for 1 year
• Minimal counseling
6 month abstinence 12 month abstinence
West et al. (2011). New England Journal of Medicine, 365, 1193-1200.
33. Varenicline
6 month abstinence with
• Partial agonist for α4β2, full agonist 1 mg x 2/day
α7
• Approved in 2004; suicidal ideation
• Meta-analysis (20 trials, 17 by
Pfizer, N=12,000)
• Relative Risk = 2.27
Calhill et al. (2012) Cochrane Review, 2012(4), 1-114.
34. Nicotine Vaccine
• Rationale: nicotine conjugate produces
antibodies which prevent distribution to brain
Maurer et al. (2005). European Journal of Immunology, 35, 2031-2040.
35. Immunopharmacotherapy for
Addiction
Advantages Disadvantages
• No neurobiology knowledge • Switching
• Limited side effects • Motivation
• No drug interactions • Withdrawal/craving
Gorelick (2012). Future Medical Chemistry, 4(2), 227-243.
36. Nicotine QB trial
• Regular smokers (1/2 pack/day for 3 years, N =
239) were randomized to receive 100 μg
Nicotine QB (week 0, 4, 8, 12, 16) or adjuvant
• Counseling at week 3, target quit date of week
4
• Followed for 8 months after last dose
• Smoking status determined based on self-
report and carbon monoxide
Cornuz (2008). PLOS ONE, 3(6), e2547.
37. Limited Efficacy
• No compensatory increase in smoking
• Mild (flu like) Adverse Events: V-96.5%, P-84.8%)
• % Abstainers (2-6): H-56.6%, P-31.3% but no
difference after
Cornuz (2008). PLOS ONE, 3(6), e2547.
38. Immunopharmacotherapy Pipeline
Target Company Product Immunization Status
nicotine Cytos Biotech Nic002(QB) Active Phase II
nicotine Nabi Biopharm NicVAX Active Phase III
PCP InterveXion mAB6B5 Passive preclinical
cocaine Xenova TA-CD Active Phase III
oxycontin Minneapolis MRF ‘OXY-KLH’ Active preclinical
morphine Minneapolis MRF ‘M-KLH’ Active preclinical
Methamphetamine InterveXion mAb4G9 Passive Phase I
Raupach et al. (2012). Drugs, 72(4), e1-e16.
39. Ethics
• Assuming safety, should these vaccines be
administered to women with a drug abuse
history planning on becoming pregnant?
• What about children (i.e. prior to drug
experimentation)?
• Confidentiality of prolonged high levels of
antibodies?
40. Conclusions
• Multimodal & Interdisciplinary
• Reasonable expectations
• Sensitivity to sex differences
Pre-cessation Early Middle Late
41. Key References
Becker J. B. et al. (2012-in press). Sex differences in the neural mechanisms mediating addiction: A new
synthesis and hypothesis. Biology of Sex Differences, 3, 14.
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