This document summarizes drugs used to treat Parkinson's disease, primarily focusing on levodopa. It discusses how levodopa is converted to dopamine in the brain to treat Parkinson's symptoms. It notes levodopa must be given with a peripheral decarboxylase inhibitor like carbidopa to increase its efficacy. The document also briefly outlines other drug classes used including dopamine agonists, COMT inhibitors, MAO-B inhibitors, and anticholinergics, and potential adverse effects of levodopa therapy.
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
This presentation is about the drugs of class Quinolones. Quinolones are broad spectrum bactericidal mainly used to treat urinary tract infection, or we can say bacterial infections. In the end of this ppt you will get a clear knowledge about the drugs of this class and their side-effects too.
Nasal decongestants and Respiratory Stimulants.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Discuss definition and therapeutic uses, limitation, classification and pharmacology of nasal decongestant.
B. Explain definition and uses, limitation, classification and pharmacology of respiratory stimulants.
I am happy to share lecture series on different topics of Pharmacology experiments, Pharmacy practice, Clinical pharmacy and Pharmacology. Wish you all happy learning.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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For 5+ video lecture series on Pharmacoepidemiology refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbqIaLoMmuF0Bf66SMFZtnb
For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
For 26+ video lecture series on Drugs act on central nervous system refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY9xHaplYCYG26ALtIQp5aC
For 6+ video lecture series on drugs act on Gastrointestinal tract refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BYgHRHwuarKTt96bu_2L5WK
To support this channel you can through UPI ID: abushaikh07-yahoo.com@okhdfcbank
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classification , mechanism of actions, pharmacokinetics, adverse effects, uses and contra indications of antiparkinsonian drugs. with a note on other movement diorders and treatment
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
This presentation is about the drugs of class Quinolones. Quinolones are broad spectrum bactericidal mainly used to treat urinary tract infection, or we can say bacterial infections. In the end of this ppt you will get a clear knowledge about the drugs of this class and their side-effects too.
Nasal decongestants and Respiratory Stimulants.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Discuss definition and therapeutic uses, limitation, classification and pharmacology of nasal decongestant.
B. Explain definition and uses, limitation, classification and pharmacology of respiratory stimulants.
I am happy to share lecture series on different topics of Pharmacology experiments, Pharmacy practice, Clinical pharmacy and Pharmacology. Wish you all happy learning.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
For 2+ video lecture series on Pharmacoeconomics refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY8U1TnlcHttsRB8hwpoJRL
For 5+ video lecture series on Pharmacoepidemiology refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbqIaLoMmuF0Bf66SMFZtnb
For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
For 26+ video lecture series on Drugs act on central nervous system refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY9xHaplYCYG26ALtIQp5aC
For 6+ video lecture series on drugs act on Gastrointestinal tract refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BYgHRHwuarKTt96bu_2L5WK
To support this channel you can through UPI ID: abushaikh07-yahoo.com@okhdfcbank
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classification , mechanism of actions, pharmacokinetics, adverse effects, uses and contra indications of antiparkinsonian drugs. with a note on other movement diorders and treatment
The presentation will give a brief summary of Barbiturates from the Medicinal chemistry point of view. the contents are not exact, so if there is any discrepancy in it please make corrections. thanks
Amjad Anwar
Prodrug is a pharmacological substance administered in an inactive form.
Once administered, the prodrug is metabolized in vivo into an active drug within the body through metabolic process, such as hydrolysis of an ester form of the drug.
Phase I Vs Phase II Drug metabolism and factors affectiing drug metabolism.
Enzyme induction, Enzyme inhibitor, physicochemical properties wthich acan affect the drug metabolism
This ppt covers the classification of anti psychotics with structures and IUPAC names, MOA, uses, metabolism and side effects. Dopaminergic pathways also given
Chronopharmacology is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm.
(Chronos: time; Pharmacon: drug; Logos: study)
It is concerned with the effects of drugs upon the timing of biological events and rhythms.
It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.
History:
Jean-Jaques d’Ortous de Mairan: Described circardian rhythm in plants in the 18th century.
Franz Halberg : coined the term ‘Circardian’ in 20th century (about 24 hr or about a day)
Franz Halberg : Founder of Chronobiology.
Biological Rhythm:
Biological rhythm: It is the determined rhythmic biological process or function within a defined time period.
TYPES OF RHYTHM
Circadian (last for 24 hr) – Sleep wake cycle
Infradian (> 24 hr) – Menstrual cycle
Ultradian (< 24 hr) – Neuronal firing time
Biological Clock:
An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body.
It is responsible for circadian rhythms and annual/seasonal rhythm.
The SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)
Application:
Chronotherapy found useful in
Asthma therapy, Strokes, Sleep disorders, GI tract disorders, Allergies, Oncology etc
Recent Advances:
Casein Kinase 1 (CK-1) inhibitor: Potential new drug
Reset the circadian clock enzymes.
Uses: Jet lag, sleep disorder, bipolar disorder
Animal trials completed.
Clinical trials are awaited.
The presentation will give a brief summary of Barbiturates from the Medicinal chemistry point of view. the contents are not exact, so if there is any discrepancy in it please make corrections. thanks
Amjad Anwar
Prodrug is a pharmacological substance administered in an inactive form.
Once administered, the prodrug is metabolized in vivo into an active drug within the body through metabolic process, such as hydrolysis of an ester form of the drug.
Phase I Vs Phase II Drug metabolism and factors affectiing drug metabolism.
Enzyme induction, Enzyme inhibitor, physicochemical properties wthich acan affect the drug metabolism
This ppt covers the classification of anti psychotics with structures and IUPAC names, MOA, uses, metabolism and side effects. Dopaminergic pathways also given
Chronopharmacology is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm.
(Chronos: time; Pharmacon: drug; Logos: study)
It is concerned with the effects of drugs upon the timing of biological events and rhythms.
It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.
History:
Jean-Jaques d’Ortous de Mairan: Described circardian rhythm in plants in the 18th century.
Franz Halberg : coined the term ‘Circardian’ in 20th century (about 24 hr or about a day)
Franz Halberg : Founder of Chronobiology.
Biological Rhythm:
Biological rhythm: It is the determined rhythmic biological process or function within a defined time period.
TYPES OF RHYTHM
Circadian (last for 24 hr) – Sleep wake cycle
Infradian (> 24 hr) – Menstrual cycle
Ultradian (< 24 hr) – Neuronal firing time
Biological Clock:
An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body.
It is responsible for circadian rhythms and annual/seasonal rhythm.
The SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)
Application:
Chronotherapy found useful in
Asthma therapy, Strokes, Sleep disorders, GI tract disorders, Allergies, Oncology etc
Recent Advances:
Casein Kinase 1 (CK-1) inhibitor: Potential new drug
Reset the circadian clock enzymes.
Uses: Jet lag, sleep disorder, bipolar disorder
Animal trials completed.
Clinical trials are awaited.
Parkinson's disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra. ... People with PD may experience: Tremor, mainly at rest and described as pill rolling tremor in hands .
Parkinsonism
It is an extra-pyramidal motor disorder characterized by rigidity, tremor and hypokinesia with secondary manifestations like defective posture and gait, mask-like face and sialorrhoea; dementia may accompany. If untreated the symptoms progress over several years to end-stage disease in which the patient is rigid, unable to move, unable to breathe properly; succumbs mostly to chest infections / embolism
Drugs used in Parkinsons Disease ( anti- Parkinson drugs) Ravish Yadav
detail and complete study on the topic of anti parkinson drug. the study is done under the guidance of faculty member. the learning content complete information of the topic
Anti Parkinson Disease | PDF | Pharmacology | Assignment MrHotmaster1
An anti-parkinson is a type of drug which is intended to treat and relieve the symptoms of parkinson’s disease.
Most of these agents act by either increasing dopamine activity or reducing acetylcholine activity in the central nervous system.
In clinical practice, anti-cholinergic drugs, amantadine, and the anti-histamines have their primary use of treatment for medication induced parkinsonism, acute dystonia, and medication induced tremor.
Explore animal anatomy with our latest presentation! Discover animal tissues, organs, and organ systems in simple terms, perfect for NEET UG exam prep. Get ready to ace your exam with this easy-to-understand guide! #NEETUG #Biology
Effect of Drugs on Dog's Blood Pressure using CAL (Computer aided learning)Shivankan Kakkar
NATIONAL MEDICAL COMMISSION (N.M.C.)
M.B.B.S. UNDERGRADUATE CURRICULUM Vol. I
PHARMACOLOGY (CODE: PH)
NUMBER -PH4.2
COMPETENCY- The student should be able to: Demonstrate the effects of drugs on blood pressure (vasopressor and vasodepressors with appropriate blockers) using computer aided learning
NATIONAL MEDICAL COMMISSION (N.M.C.)
M.B.B.S. UNDERGRADUATE CURRICULUM Vol. I
PHARMACOLOGY (CODE: PH)
NUMBER –PH2.1
COMPETENCY- The student should be able to: Demonstrate understanding of the use of various dosage forms(oral/local/parenteral; solid/liquid)
In this lecture, we will discuss essential medicines lists, including the WHO EML and NLEM. We will discuss the criteria for inclusion on these lists, the benefits of having an essential medicines list, and how to develop an essential medicines list for a specific setting.
This lecture is intended for healthcare professionals, medical students and the general public.
Understanding pA2 and pD2' Values: Calculation and Significance in PharmacologyShivankan Kakkar
This lecture will provide a detailed explanation of pA2 and pD2' values in pharmacology. Participants will learn the concepts of dose-response curves, receptor binding, and the mechanisms of drug action. The lecture will then focus on the calculation of pA2 and pD2' values, their interpretation, and their significance in drug development and clinical practice. The lecture will also cover the factors that can influence these values, such as pH, temperature, and co-administration of other drugs. By the end of the lecture, participants will have a thorough understanding of how to calculate and interpret pA2 and pD2' values and their importance in pharmacology.
Mastering the Art of Setting up an IV Drip: A Step-by-Step GuideShivankan Kakkar
This lecture will provide a comprehensive guide on setting up an IV drip. Participants will learn the importance of IV therapy, the different types of IV fluids and equipment used, and the step-by-step process of setting up an IV drip. The lecture will also cover troubleshooting common problems and potential complications of IV therapy. By the end of the lecture, participants will have a thorough understanding of how to safely and effectively set up an IV drip.
Prepare for NEET PG with these topic-wise recall one-liners. Master the subject by reviewing the key concepts and mechanisms of action for each drug, as well as their indications, adverse effects, and toxicities. With this approach, you can effectively learn and retain the essential information necessary to excel in your exam.
Mastering the Art of Prescribing IV Fluids: A Comprehensive GuideShivankan Kakkar
This presentation provides a detailed overview of how to prescribe IV fluids, including the types of fluids, dosages, and administration methods. It also covers common clinical scenarios where IV fluids may be necessary, such as dehydration, electrolyte imbalances, and shock. This presentation is ideal for healthcare professionals looking to improve their knowledge and skills in IV fluid management.
Tags: IV fluids, fluid management, prescribing, dosages, administration, dehydration, electrolyte imbalances, shock, healthcare professionals.
Alpha Blockers: Mechanisms and Clinical ApplicationsShivankan Kakkar
This presentation provides an overview of alpha blockers, a class of drugs used in the treatment of various medical conditions such as hypertension, benign prostatic hyperplasia, and Raynaud's disease. The presentation discusses the mechanism of action of alpha blockers, their classification, and their clinical applications. It also covers the adverse effects associated with their use and precautions that need to be taken while prescribing these drugs. This presentation is useful for healthcare professionals who want to gain a better understanding of alpha blockers and their use in clinical practice.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
1. 1
Dr. Shivankan Kakkar, MD
Antiparkinsonian drugs
Parkinson’s disease (PD) was first described by Sir
James Parkinson. It is characterized by tremor, rigidity,
bradykinesia (slowness of movements) and the loss of
postural reflexes.
In idiopathic parkinsonism, there is degeneration of the
dopamine-containing neurons in the substantia nigra,
resulting in dopamine deficiency.
2. 2
Dr. Shivankan Kakkar, MD
Hence, the balance between inhibitory dopaminergic
neurons and excitatory cholinergic neurons is disturbed
resulting in relative cholinergic overactivity.
4. 4
Dr. Shivankan Kakkar, MD
2. Drugs influencing brain cholinergic system :
(a) Centrally acting anticholinergic drugs:
Benztropine, benzhexol (trihexyphenidyl),
procyclidine, biperiden.
(b) Antihistaminics (H1-blockers) with
anticholinergic activity: Promethazine,
diphenhydramine, orphenadrine.
The main aim of drug therapy in parkinsonism is to
either enhance dopamine activity or reduce cholinergic
activity in the striatum.
5. 5
Dr. Shivankan Kakkar, MD
Dopamine precursor: Levodopa
Levodopa (L-Dopa) is the main drug for the treatment
of idiopathic parkinsonism. Dopamine does not cross
BBB, hence its immediate precursor levodopa (prodrug)
is used. It is converted to dopamine by decarboxylase
enzyme in the dopaminergic neurons of the striatum.
Dopamine produced then interacts with D2 receptors in
the basal ganglia to produce antiparkinsonian effect. In
early stages of the disease, improvement is almost
complete.
6. 6
Dr. Shivankan Kakkar, MD
All the clinical symptoms (rigidity, bradykinesia and
tremor) of parkinsonism improve, but the progression of
the disease is not stopped. A large amount of the drug is
converted to dopamine in the peripheral tissues by
peripheral decarboxylase enzyme. Only a small amount
(2–3%) of levodopa enters the brain. Therefore,
levodopa is used in combination with
carbidopa/benserazide (peripheral decarboxylase
inhibitor) which does not cross the BBB; the peripheral
metabolism of levodopa is reduced, thus increasing its
bioavailability in the basal ganglia.
8. 8
Dr. Shivankan Kakkar, MD
Pharmacokinetics.
On oral administration, levodopa is rapidly absorbed
from the small intestine by an active transport system.
Amino acids present in food may interfere with the
absorption of levodopa, hence it should be given 30–60
minutes before meal. Active transport of levodopa into
the brain may be inhibited by competition from dietary
amino acids.
9. 9
Dr. Shivankan Kakkar, MD
The main metabolic products of levodopa are
homovanillic acid (HVA) and 3,4-
dihydroxyphenylacetic acid (DOPAC). The metabolites
are excreted in urine.
11. 11
Dr. Shivankan Kakkar, MD
Adverse effects
1. GIT: Nausea, vomiting and anorexia are common
during initial treatment with levodopa. Tolerance to
emetic effect develops slowly.
2. CVS: The commonest cardiovascular side effect is
postural hypotension, which is usually asymptomatic. It
can also cause tachycardia, palpitation and rarely
cardiac arrhythmias.
12. 12
Dr. Shivankan Kakkar, MD
3. Dyskinesias (abnormal involuntary movements):
Tics, tremors and choreoathetoid movements may
occur. Tolerance does not develop to abnormal
movements.
4. Alteration in taste sensation.
5. Mental changes like insomnia, confusion, delusions,
euphoria, depression, anxiety, hallucinations and
nightmares.
13. 13
Dr. Shivankan Kakkar, MD
6. Fluctuations in response: After 3–5 years of
therapy, with progressing disease, control becomes poor
and fluctuations in symptoms occur frequently.
Wearing off (end-of-dose) is due to decrease in plasma
concentration of levodopa towards the end-of-a-dose
interval. Patient may show fluctuation in response—
being ‘off’ (loss of beneficial effect of the drug) and
being ‘on’ (relief of most of the symptoms but with
disabling dyskinesias) called the on/off phenomenon.
Sustained release formulation of levodopa–carbidopa
produces more stable plasma levodopa levels and helps
to reduce fluctuation in response (on/off phenomena).
14. 14
Dr. Shivankan Kakkar, MD
End-of-dose deterioration can also be improved by
administering levodopa in smaller and more frequent
doses.
Peripheral decarboxylase inhibitors: Carbidopa and
benserazide
Carbidopa and benserazide are peripheral
decarboxylase inhibitors.
15. 15
Dr. Shivankan Kakkar, MD
These drugs do not cross BBB. Levodopa is always
given in combination with carbidopa/benserazide. The
currently used combinations are:
Levodopa + carbidopa (4:1 or 10:1 ratio).
Levodopa + Benserazide (4:1).
The advantages of these fixed-dose combinations
are:
1. Increased bioavailability of dopamine in the basal
ganglia. Hence, the dose of levodopa can be reduced by
75%.
2. Prolongation of plasma half-life of levodopa.
16. 16
Dr. Shivankan Kakkar, MD
3. Reduction in the incidence of GI side effects like
nausea and vomiting.
4. Cardiovascular side effects like tachycardia,
hypotension and cardiac arrhythmias are minimized.
5. Better patient compliance.
6. Sustained release preparation of levodopa–carbidopa
helps to reduce on/off phenomenon.
17. 17
Dr. Shivankan Kakkar, MD
Dopamine receptor agonists: Bromocriptine,
ropinirole and pramipexole
These drugs have direct action on dopamine receptors.
Like levodopa, they can relieve signs and symptoms of
parkinsonism. They are administered orally. The
duration of action of these drugs is longer than that of
levodopa and these are used particularly in patients who
have frequent fluctuation of symptoms (on/off
phenomena).
18. 18
Dr. Shivankan Kakkar, MD
Bromocriptine
Bromocriptine is an ergot derivative; has agonistic
action at D2 and partial agonist at D1 receptors.
Adverse effects
Adverse effects include anorexia, nausea, vomiting,
constipation, postural hypotension, cardiac
arrhythmias, digital vasospasm, dyskinesias, headache,
confusion, hallucinations and nasal congestion. It is
contraindicated in patients with history of mental
illness, recent MI, peptic ulcer and peripheral vascular
diseases.
19. 19
Dr. Shivankan Kakkar, MD
Ropinirole and pramipexole
These are non-ergoline derivatives, hence ergot related
side effects are not seen. These drugs are often used in
the initial treatment of parkinsonism. They can be used
as monotherapy or in combination with levodopa–
carbidopa. The other indication of these non-ergolines
is in ‘restless leg syndrome’.
20. 20
Dr. Shivankan Kakkar, MD
Adverse effects.
Nausea, vomiting, confusion, fatigue, somnolence,
hallucinations, postural hypotension, dyskinesia and
rarely sudden attacks of irresistible sleep during day
time.
21. 21
Dr. Shivankan Kakkar, MD
COMT inhibitors: Tolcapone, entacapone
Tolcapone and entacapone are reversible COMT
inhibitors. By inhibiting the peripheral metabolism of
levodopa to 3-O-methyldopa, they increase the half-life
of levodopa and also enhance its bioavailability in the
CNS. The ‘on’ time is prolonged and the dose of
levodopa can be reduced. Tolcapone has both peripheral
and central actions with relatively longer duration of
action, whereas entacapone inhibits COMT only in the
periphery.
22. 22
Dr. Shivankan Kakkar, MD
These drugs are used as adjunct to levodopa-carbidopa
for advanced cases of PD. Combined preparation of
levodopa + carbidopa + entacapone is available.
Adverse effects.
These include dyskinesia, nausea, diarrhoea, confusion,
hypotension and hallucinations.
Tolcapone may rarely cause fulminant hepatitis, hence
it should be avoided in patients with liver disease.
Entacapone does not cause hepatotoxicity.
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Dr. Shivankan Kakkar, MD
MAO-B inhibitors: Selegiline and rasagiline
They selectively and irreversibly inhibit MAO-B
enzyme in the brain. They are administered orally. They
do not inhibit MAO in the periphery. They retard the
metabolism of DA in the brain and prevent the
formation of toxic metabolites. Thus, they produce
neuroprotective effect in idiopathic PD and retard the
progression of disease. They enhance as well as prolong
the effect of levodopa. They also reduce ‘on-off’ and
‘wearing off’ phenomena.
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Dr. Shivankan Kakkar, MD
Rasagiline is more potent and longer acting than
selegiline; hence single daily dose is adequate. The
metabolites of selegiline are amphetamine and
methamphetamine which cause side effects like
insomnia, anxiety, nausea and vomiting.
NMDA receptor antagonist: Amantadine
Amantadine is an antiviral drug used for the treatment
and prophylaxis of influenza A. It is also used in
parkinsonism. It facilitates the synthesis and release of
dopamine from dopaminergic neurons in the brain.
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Dr. Shivankan Kakkar, MD
It also has NMDA receptor antagonist action –
decreases glutamate neurotransmission in the basal
ganglia which could contribute to its beneficial effect in
parkinsonism. It is less effective than levodopa and
hence used for the initial treatment of mild
parkinsonism. Its therapeutic activity may be increased
by combining with levodopa. It is given by oral route
and is well tolerated.
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Dr. Shivankan Kakkar, MD
Adverse effects
They include headache, heart failure, hypotension,
hallucinations, nausea, vomiting, constipation, dry
mouth, insomnia and livedo reticularis (discoloured
patches on the skin).
Central anticholinergics
Centrally acting anticholinergics like benzhexol
(trihexyphenidyl) and benztropine are the treatment of
choice in drug-induced parkinsonism and are also
effective in idiopathic parkinsonism. They have mainly
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Dr. Shivankan Kakkar, MD
central action with minimal peripheral action. They act
by reducing the increased cholinergic activity in the
striatum. They are less effective than levodopa, but are
cheap and better tolerated. They are mainly effective in
relieving tremor and rigidity of parkinsonism with little
effect on hypokinesia. Adverse effects are dry mouth,
confusion, constipation, blurring of vision, drowsiness,
hallucinations and urinary retention.
Antihistaminics with anticholinergic effects like
promethazine, diphenhydramine, orphenadrine, etc. are
also effective in decreasing cholinergic overactivity in
basal ganglia.
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Dr. Shivankan Kakkar, MD
Levodopa is not effective in drug-induced
parkinsonism, because:
(a) dopamine receptors are blocked.
(b) there is no deficiency of dopamine.
Drug interactions
1. Levodopa × MAO inhibitors (nonselective):
Inhibition of MAO retards the metabolism of dopamine
. plasma concentration of dopamine increases . may
precipitate hypertensive crisis.
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Dr. Shivankan Kakkar, MD
2. Levodopa × pyridoxine: Pyridoxine promotes the
peripheral conversion of levodopa to dopamine and
reduces the therapeutic effect of levodopa.
3. Levodopa × antihypertensive agents: Worsening of
postural hypotension.
4. Levodopa × metoclopramide: Metoclopramide
crosses the BBB, blocks the D2 receptors in the basal
ganglia and causes drug induced parkinsonism (i.e.
interferes with antiparkinsonian effect of levodopa);
domperidone poorly crosses BBB, hence there is no
interference with therapeutic effect of levodopa.