This presentation was given by me during my M.pharm.
It contains description, classification, mechanism of actions and therapeutic uses of Neuromuscular blockers.
This presentation was given by me during my M.pharm.
It contains description, classification, mechanism of actions and therapeutic uses of Neuromuscular blockers.
It is detailed presentation on skeletal muscle relaxants it is more elaborative and detailed version of drugs involved in skeletal Muscle physiology Skeletal muscle relaxants consist of both antispasticity and antispasmodic agents, a distinction prescribers often overlook. The antispasticity agents-baclofen, tizanidine, dantrolene, and diazepam-aid in improving muscle hypertonicity and involuntary jerks
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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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.
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
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
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Skeletal muscle relaxants presentation
1. SKELETAL MUSCLE RELAXANTS.
•Skeletal muscle relaxants are drugs which act
peripherally at the neuro muscular junction(NMJ)
and centrally in the cerebrospinal axis to relax
muscles.
•The drugs which act at the NMJ or neuro
muscular blocking drugs are used in conjunction
with general anaesthetics to provide muscle
relaxation during surgery.
•The centrally acting muscle relaxants are used
mainly for painful muscle spasms and spastic
neurological conditions.
2. NEURO MUSCULAR BLOCKING AGENTS.
CLASSIFICATION.
• A) Non depolarizing (competitive) blockers.
• Long acting: d-Tubocurarine, Pancuronium,
Doxacurium, Pipecuronium.
• Intermediate acting: Vecuronium, atracurium,
cisatracurium, Rocuronium, Rapacuronium
• Short acting: Mivacurium.
• B) Depolarizing blockers.
• Succinyl choline (suxamethonium).
• Decamethonium.
3. CLASSIFICATION CONT..
• C) Directly acting agents
• Dantrolene sodium.
• Quinine.
Other agents that interfere with neuro
muscular transmission.
• Aminoglycosides, tetracycline, polypeptide
antibiotics: these are not used as muscle
relaxants.
4. MECHANISM OF ACTION OF NON-
DEPOLARIZING NEURO MUSCULAR
BLOCKERS.
• These are competitive inhibitors of acetyl
choline at the motor end plate.
• The motor end plate is found at the
junction of the motor nerve and the
skeletal muscle and it contains nicotinic
Nm or N2 receptors of acetylcholine.
• ACH Combines with these post synaptic
receptors leading to influx of sodium ions
and the development of end plate
potential causing muscle contraction.
5. MECHANISM OF ACTION OF NON-
DEPOLARIZING NEURO MUSCULAR BLOCKERS.
CONT..
• The competitive neuro muscular blockers are
generally bulky in nature and therefore block
access of the nicotinic receptors to ACH with no
generation of end plate potentials and causing
flaccid paralysis.
• ACH also acts presynaptically on cholinergic
neurons and augments its own release(positive
feedback).
• Tubocurarine can reversibly block both
presynaptic and post synaptic receptors while α-
bungarotoxin blocks only post synaptic receptors
but not presynaptic receptors.
6. MECHANISM OF ACTION OF NON-
DEPOLARIZING NEURO MUSCULAR
BLOCKERS. CONT..
• Gallamine also inhibits neuronal release of
ACH by acting on presynaptic cholinergic
M2 receptors.
• 80-90% of nicotinic receptors must be
blocked before neurotransmission fails.
• Anticholinesterases agents like
neostigmine are able to reverse the
effects of neuromuscular blockers by
building up the concentration of the
agonist (ACH).
7. PHARMACOKINETICS OF COMPETITIVE
NEURO MUSCULAR BLOCKERS.
• All competitive neuro muscular blockers are
quaternary ammonium compounds: They are:
• Poorly absorbed after oral administration
• Low volume of distribution because they don’t
cross membranes.
• Do not penetrate placenta or blood brain barrier.
They are safe in obstetrical surgery except
gallamine)
• They are always administered by IV route
although the IM route is also possible.
8. PHARMACOKINETICS OF COMPETITIVE
NEURO MUSCULAR BLOCKERS. CONT..
• The drugs are first distributed to muscles
with higher blood flow and these muscles
are affected first. Redistribution to non-
muscular tissues plays a role in
terminating the activity of the NMJ blocker.
• Duration of muscle relaxation following IV
administration : tubocurarine 30 min,
gallamine 15 mins, pancuronium 60 min,
atracuronium 10 min, alcuronium 30
mins.
9. PHARMACOLOGICAL ACTIONS OF D-
TUBOCURARINE
• When injected I.V there is immediate onset of
action, peak effect within 5-7 mins. and duration
of action of between 30- 60 mins.
• Effects of d-tubocurarine on skeletal
muscles.
• There is flaccid paralysis of the muscles.
• Muscles of fine movements are more sensitive
than larger and stronger muscles of coarse
movements.
• Small rapidly moving muscles of the face,neck,
eyes and pharynx are affected first, leading to
difficulty in speaking, accumulation of secretions
in throat, and diplopia.
10. PHARMACOLOGICAL ACTIONS OF D-
TUBOCURARINE CONT..
• Other small muscles of fingers, toes,
hands and intercostal muscles are
affected next leading to difficulty in
performing delicate motor tasks.
• Muscles of limb, trunk, abdomen, chest
and finally diaphragm are paralyzed with
cessation of respiration.
• Recovery of paralysis occurs in reverse
order.
11. Effects of d- tubocurarine on other
systems.
• Blocks transmission at autonomic ganglia
and decreases secretion of adrenaline
from the adrenal glands leading to fall in
blood pressure.
• Releases histamine from mast cells leads
to fall in blood pressure and
bronchospasm. Contraindicated in
patients of bronchial asthma and other
allergic states.
12. Important Pharmacological Effects of
Other Agents.
• All are quaternary ammonium compounds
with same pharmacokinetic profile as d-
tubocurarine.
Gallamine.
• Does not release histamine or block
autonomic ganglia.
• Blocks M2 muscarinic receptors of the
heart and releases NA, inducing
tachycardia.
13. Pancuronium
• Does not release histamine or block
autonomic ganglia.
• Blocks M2 muscarinic receptors of the
heart and releases NA leading to
tachycardia.
• Duration-60-120 mins.
• Inhibits plasma cholinesterase.
14. Atracurium
• 4 times less potent than pancuronium and
shorter acting (20-35mins.)
• Neostigmine reversal not required because of
short duration of action.
• It is inactivated by plasma cholinesterase and
spontaneous non enzymatic degradation in the
plasma (Hofmann elimination) therefore duration
of action is not altered by liver diseases.
• Preferred muscle relaxant for patients of hepatic
diseases, neonates and the elderly.
• Releases histamine and may cause
hypotension.
15. Pipecuronium.
• Slow onset and long duration of action
(onset2-4min Duration-50-100mins)
• Recommended for prolonged surgeries.
• Has little cardiovascular action, though
there may be transient hypotension and
bradycardia.
16. Vecuronium.
• A close congener of pancuronium with a shorter
duration (30-60mins) due to rapid distribution
and metabolism.
• Recovery is generally spontaneous not requiring
neostigmine reversal unless repeated dose has
been given.
• Cardiovascular stability is better due to lack of
histamine release and ganglion blockage,
tachycardia occasionally occurs.
• Currently the most commonly used muscle
relaxant for routine surgery.
17. Doxacurium
• Has the least rapid onset (4-8 mins) and the
longest duration of action (60-120 mins).
• Suitable for long surgeries.
• Minimal cardiovascular effects.
• Mivacurium
• Shortest acting (onset 2-4 and duration 12-20
mins).
• Does not need neostigmine reversal.
• Cause slight histamine release leading to fall in
BP but minimal effect on heart rate.
• Hydrolyzed by plasma cholinesterase and
prolonged paralysis can occur in pseudo
cholinesterase deficiency.
18. Rocuronium.
• New compound with rapid onset (1-2 mins) and
intermediate duration of action (25-40 mins).
Onset is dose dependent.
• Can be used as an alternative to succinyl
choline for tracheal intubation without the
disadvantages of depolarizing block and
cardiovascular changes.
• May serve as maintenance muscle relaxant.
• Seldom needs neostigmine reversal.
19. ADVERSE REACTIONS OF COMPETITIVE
NEUROMUSCULAR BLOCKERS
• Hypoxia and prolonged respiratory
paralysis. Managed by artificial
respiration, maintenance of patient’s
airway and injection of neostigmine (1-
3mg i.v) and atropine sulfate (0.6 mg
i.v). Atropine is used to block the
peripheral muscarinic actions of ACH
e.g. bronchospasm and hypotension.
20. ADVERSE REACTIONS OF COMPETITIVE
NEUROMUSCULAR BLOCKERS CONT..
• Bronchospasm due to histamine
release as with tubocurarine.
• Hypotension due to autonomic
ganglion blockage and histamine
release. Less likely with the new
compounds.
• Neuro muscular paralysis especially
in children, myasthenia gravis and
patients with hepatic and renal failure.
21. DRUG INTERACTIONS INVOLVING
COMPETITIVE NEUROMUSCULAR BLOCKERS.
• Neuro muscular block and paralysis are
potentiated by:
• Inhalation anaesthetics (ether, halothane,
cyclopropane, enflurane.
• Lignocaine, quinidine, beta blockers,
calcium channel blockers and lithium
which inhibit ACH release or action.
22. DRUG INTERACTIONS INVOLVING COMPETITIVE
NEUROMUSCULAR BLOCKERS. CONT..
• Antibiotics (aminoglycosides, clindamycin)
which inhibit ACH release.
• Anticholinesterases reverse the action of
competitive blockers. Neostigmine (0.5-
2mg i.v) is routinely used after
pancuronium and other long acting
blockers to hasten recovery at end of
operation.
23. SUMMARY OF ADVANTAGES OF NEW
COMPETITIVE NEURO MUSCULAR BLOCKERS.
• No or minimal ganglionic, cardiac or
vascular effects.
• No or minimal histamine release.
• Many are short acting and easy reversal
• Some are rapid acting: provide alternative
to Succinyl choline without the attendant
complications.
24. DEPOLARIZING BLOCKING AGENTS.
• The group is also referred to as persistent
depolarizing agents and includes succinyl
choline and decamethonium.
• Mechanism of action: the drugs cause persistent
depolarization at the motor end plate and
prevent any response due to acetyl choline
combining with the nicotinic receptors at the
motor end plate.
• Persistent depolarization means there is no
resting phase of the action potential and hence
no response to ACH.
• It is caused by sustained opening of sodium
channels by the depolarizing neuro muscular
blocker.
25. PHARMACOKINETICS OF DEPOLARIZING
NEURO MUSCULAR BLOCKERS.
• Onset of action of succinyl choline is 1-1.5 minutes
after IV injection ad duration of action is 3-6 minutes.
• It is rapidly hydrolyzed by plasma and tissue
pseudo- CHE.
• Duration of action of succinyl choline is prolonged in
patients withpseudo CHE deficiency or with atypical
pseudo –CHE which may lead to respiratory
paralysis or succinyl apnea.
• Decamethonium is not easily metabolized having
longest duration of action, hence not used clinically.
26. PHARMACOLOGICAL EFFECTS OF SUCCINYL
CHOLINE
• It causes transient fasciculation of groups
of muscle fibres for 10-15 seconds
followed by flaccid paralysis. This is called
phase one block.
• In this depolarized state(phase), the block
cannot be reversed by anticholinesterases
like neostigmine or edrophonium.
• Paralysis of neck and limb muscles occurs
before those of face and pharynx.
27. PHARMACOLOGICAL EFFECTS OF
SUCCINYL CHOLINE CONT..
• With continued exposure to Succinyl choline, the initial
depolarization decreases, the membrane is repolarized
but now cannot be depolarized again as long as the
succinyl choline is present in the receptor sites. This is
called phase II or desensitization block, which can be
antagonized by anti cholinesterases.
• Succinyl choline has muscarinic and ganglion stimulating
actions but does not release histamine.
• It may cause bradycardia in therapeutic doses and
tachycardia in larger doses. It may also cause cardiac
arrhythmia (extra systole).
• Muscle power recovery occurs within minutes.
28. ADVERSE EFFECTS OF SUCCINYL CHOLINE.
• Muscle fasciculation and post-operative
muscle pain are common and are due to
depolarizing effect of the drug.
• Muscarinic effects are manifested as
bradycardia, hypotension, salivation and
increases gut motility.
• Raised intra ocular tension due to
prolonged contraction of extra- ocular
muscles and transient dilation of choroidal
blood vessels. It may be dangerous in
acute glaucoma.
29. ADVERSE EFFECTS OF SUCCINYL
CHOLINE. CONT..
• Hyperkalemia may be due to persistent
depolarization, especially in patients of deep
burns and muscle damage. Cardiac arrhythmias
and arrest can also be caused.
• Succinyl apneas in patients with atypical pseudo
–CHE (genetic variant) which does not hydrolyze
succinyl choline.
• Malignant hyperthermia, a rare congenital
abnormality characterized by intense muscle
spasm and sudden rise in body temperature.
Treated with dantrolene.
30. DRUG INTERACTIONS INVOLVING SUCCINYL
CHOLINE
• The action of Succinyl choline is
potentiated by:
• Drugs which inhibit neuro muscular
transmission-aminoglycosides, quinidine,
calcium channel blockers, local
anaesthetics and magnesium ions.
• Drugs which inhibit pseudo
cholinesterase-anticholinesterases, MAOI
and cytotoxic agents.
31. FACTORS TO BE CONSIDERED WHEN
CHOOSING AN NMB.
• Neuromuscular blockers are used whenever
relaxation of skeletal muscles is desirable.
• The following factors must be considered when
selecting appropriate NMBs
• The duration of the surgical procedure: Succinyl
choline (duration of action 3-6 mins) is employed for
brief procedures e.g. endotracheal intubation,
laryngoscopy, bronchoscopy, esaphogoscopy,
reduction of fractures, dislocations and to treat
laryngospasms.
• Onset of action of the NMB.
• Cardiovascular effects of the drug.
• Patient’s hepatic, renal and hemodynamic status.
32. THERAPEUTIC USES OF NMBs
• As an adjunct to general anaesthetics: For skeletal
muscle relaxation, both non-depolarizing and
depolarizing neuro muscular blockers are used
clinically.
• For operations lasting more than 30 minutes e.g.
intra-abdominal operations or orthopedic
manouvres, d –tubocurarine is used for these
reasons:
• It relaxes muscle tone
• It reduces the dose of anaesthetic agents and the
post anaesthetic complications and keeps the blood
pressure on the lower side.
• D- Tubocurarine has been largely replaced by
synthetic derivatives which have fewer side effects
(atracurium-duration 20-35 mins, pipecuronium 50-
100 mins, vecuronium, 30-60 mins).
33. THERAPEUTIC USES OF NMBs CONT..
• b. In obstetric conditions- any of the non-
depolarizing drugs (except gallamine) can be
used.
• c. In selected cases of arterial surgery,
pancuronium is used.
• d. For producing transient muscle relaxation
as required in endotracheal intubation,
bronchoscopy, direct laryngoscopy,
esophagoscopy and electroconvulsive therapy
(ECT).
• Succinyl choline is the drug of choice as the
onset of action is immediate and recovery is
within 5 minutes.
34. THERAPEUTIC USES OF NMBs CONT..
• The intravenous muscle relaxant doses in mg
are: tubocurarine 10-15, gallamine1-2,
pancuronium, 1-2, pancuronium1-2 and
altracurium 0.5-1.
• 2. In the treatment of painful muscle spasm-
as in tetanus, muscle relaxation is the key to
therapy and mild sedation is also desirable.
• Diazepam i.v as a running drip is given in adults
(60-240 mg /24 hours, in children (30-40 mg/24
hours) and in neonates (20-40mg/24 hours).
Maintenance on intermittent positive pressure
respiration is necessary.
35. THERAPEUTIC USES OF NMBs CONT..
• 3. In very small doses (1/10) atracurium
may be used for diagnosis of myasthenia
gravis.
• 4. Severe cases of status epilepticus
which are not controlled by diazepam or
other drugs may be paralyzed by an NMB
(repeated doses of competitive blocker)
and maintained on intermittent positive
pressure respiration till the disease
subsides.
36. INDIRECTLY ACTING MUSCLE RELAXANTS.
• DANTROLENE.
• It exerts a direct action on the skeletal
muscle by interfering with the release of
calcium from the sarcoplasmic reticulum.
• It interfers with the excitation- contraction
coupling
• Cardiac and smooth muscles are not
affected by dantrolene as the mechanism
of calcium entry is different in these
tissues.
• It has no effect on CNS and neuro
muscular junction.
37. PHARMACOKINETICS OF DANTROLENE
• It is absorbed after oral administration, but
the absorption is slow and incomplete.
• It penetrates the brain and produces some
sedation, but has no selective action on
polysynaptic reflexes responsible for
spasticity.
• It is metabolized in the liver and excreted
by the kidneys with a half- life of 8-12
hours.
38. THERAPEUTIC USES OF DANTROLENE.
• 1. Neurological spastic disorders e.g. multiple
sclerosis, cerebral palsy, spinal injury,
hemiplegia and paraplegia.
• The initial oral dose is 25mg once a day which is
gradually increased to 100mg QDS daily. The
dose limiting toxicity is generalized muscle
weakness.
• 2. Malignant hyperthermia following use of
succinyl choline or halothane in genetically
predisposed people.
• Dantrolene is given initially 1 mg /kg IV and
repeated up to 100 mg/kg IV which is followed
by 50-100mg QDS for 2-3 days.
39. ADVERSE EFFECTS OF DANTROLENE.
• Muscle weakness is the dose limiting toxicity.
• Sedation, malaise lightheadedness and other
central effects occur, but are less pronounced
than centrally acting muscle relaxants.
• Troublesome diarrhea.
• Long term use cause dose dependent liver
toxicity in 0.1-0.5 % of patients. This has
restrictedits use in chronic disorders.
40. QUININE.
• It increases refractory period and
decreases excitability of motor end plates,
thus reducing response to repetitive nerve
stimulation.
• It reduces muscle tone in myotonia
congenita.
• When taken at bedtime (200-300mg) it
may abolish nocturnal leg cramps in some
patients.
41. CENTRALLY ACTING MUSCLE
RELAXANTS.
• These are drugs which reduce skeletal
muscle tone by a selective action in the
cerebrospinal axis, without altering
consciousness.
• They selectively depress spinal and supra
spinal poly synaptic reflexes involved in
the regulation of muscle tone.
• Polysynaptic pathways in the ascending
reticular formation which are involved in
wakefulness are also depressed, though
to a smaller extent.
42. CENTRALLY ACTING MUSCLE
RELAXANTS. CONT..
• All centrally acting muscle relaxants cause
sedation.
• They have no effect on neuro muscular
transmission and on muscle fibres but
reduce decelebrate rigidity, upper motor
neuron spasticity and hyperreflexia.
• Note the differences between peripherally
and centrally acting muscle relaxants in
table 25.3.
43. CLASSIFICATION OF CENTRALLY ACTING
MUSCLE RELAXANTS.
• Mephenesin congeners: Mephenesin,
Carisoprodol, Chlozoxazone,
Chlormezanone, Methocarbamol.
• Benzodiazepines: Diazepam. Trizolam
and others.
• Gabba derivative: Baclofen
• Central α2agonist: Tizanidine
44. PROPERTIES OF CENTRALLY ACTING
• MUSCLE RELAXANTS.
• MEPHENESIN
• First drug to be discovered as a muscle
relaxant.
• Modulates reflexes maintaining muscle
tone.
• It is not used clinically because it causes
gastric irritation, and when administered IV
it causes thrombophlebitis, hemolysis and
marked fall in BP.
45. • CARIS0PRODOL.
• Has favorable muscle relaxant, sedative,
analgesic antipyretic, and anticholinergic
properties.
• It is used in musculo skeletal disorders
associated with muscle spasm.
• CHLOZOXAZONE.
• Pharmacologically similar to mephenesin, has a
longer duration of action and is better tolerated
orally.
• CHLORMEZANONE.
• Has anti- anxiety and hypnotic actions and is
used for tension states associated with
increased muscle tone.
46. • METHOCARBAMOL.
• Less sedative and longer acting than
mephenesin.
• Orally used in reflex muscle spasm and
chronic neurological diseases.
• It can be given IV without producing
thrombophlebitis and hemolysis-used for
orthopedic procedures and tetanus.
47. DIAZEPAM.
• A benzodiazepine (BDZ) which acts in the brain on
specific receptors, enhancing transmission by the
inhibitory amino acid neurotransmitter GABA.
• Muscle tone is reduced by supraspinal rather than spinal
action.
• It has more sedative activity than muscle relaxation and
sedation limits the dose that can be used for muscle
relaxation.
• Diazepam is particularly valuable in tetanus and spinal
injuries.
• When combined with analgesics, it is useful for
rheumatic disorders associated with muscle spasm.
48. • BACLOFEN.
• Is a GABA B receptor agonist which depresses
both polysynaptic and monosynaptic reflexes in
the spinal cord.
• It does not produce muscle weakness like
diazepam because it does not affect chloride
conductance.
• ( BDZs facilitates the effect of GABA on GABA
A receptors increasing chloride conductance
while baclofen acts on GABAB receptors,
hyperpolarizing neurons by increasing K+
conductance and altering Ca2+ flux.).
49. BACLOFEN. CONT..
• It reduces spasticity in many neurological
disorders like multiple sclerosis, spinal
injuries and flexor spasms.
• It is relatively in effective in stroke,
cerebral palsy, rheumatic and traumatic
muscle spasms and Parkinsonism.
50. • TIZANIDINE.
• It is a new skeletal muscle relaxant which
is a congener of clonidine.
• It is a central α2-adrenergic agonist which
inhibits the release of excitatory amino
acids e.g. aspartate in the spinal
interneurons while facilitating the inhibitory
amino acid neurotransmitter glycine.
51. TIZANIDINE. CONT..
• It inhibits polysynaptic reflexes; reduce
muscle tone and frequency of muscle
spasms without reducing muscle strength.
• Efficacy similar to baclofen and diazepam
has been noted in multiple sclerosis,
spinal injury and stroke with fewer side
effects.
• It is well absorbed and is administered as
tablets of 2 and 4 mg.
52. ADVERSE EFFECTS OF CENTRALLY
ACTING MUSCLE RELAXANTS (CAMs)
• Gastric irritation except for diazepam.
Baclofen and tizanidine.
• All CAMs cause drowsiness and sedation.
• Baclofen can cause tachycardia,
hypotension and rarely visual and auditory
hallucinations. It can also cause ataxia
and elevation of serum transaminase.
53. ADVERSE EFFECTS OF CENTRALLY ACTING
MUSCLE RELAXANTS (CAMs) CONT..
• Tizanidine may cause dry mouth, drowsiness,
night time insomnia and hallucinations. Dose
dependent elevation of liver enzymes has been
noted.
• No consistent effect on BP has been noticed but
should still be avoided in patients receiving anti
hypertensives, especially clonidine.
END.
DR. OCHOLA.F.O, DEPT OF PHARMACOLOGY AND
TOXICOLOGY- MOI UNIVERSITY, SCHOOL OF
MEDICINE.