Post on 15-Apr-2017
transcript
Bupivacaine
By: Martinez
EXECUTIVE SUMMARY Brand name - Marcaine
Molecule - Bupivacaine
Inj – 5 mg/mL in 10 mL ampule
Target Doctors – Dentists, Surgeons, Anaesthetists, General Physicians and other doctors.
Total market for Bupivacaine is Php 1802.25 cr
Market growth – 18%
DRUG USE AND MARKET DEFINITIONLocal Infiltration
Pain Relief during and after relatively minor procedures like:
Filling or wisdom tooth removalMinor skin operation, such as removal of
moles and wartsEye surgery (cataract removal)Biopsy
DRUG USE AND MARKET DEFINITIONEpidural anaesthetic Injected
through a tube into the epidural space
E.g. prostate surgery
DRUG USE AND MARKET DEFINITIONEpidural Test Dose
Determine accidental intravenous or intrathecal catheter placement
Peripheral nerve block Injection administered to nerves at
an appropriate area of one’s body extremity requiring surgeryE.g. arm, leg
DRUG USE AND MARKET DEFINITIONCaudal anaesthesia
Analgesia for urgent procedures involving the lower body below umbilicus
Superficial operations like Skin graftingPerineal proceduresLower limb surgery
DRUG USE AND MARKET DEFINITION Sympathetic nerve
block Diagnostic to
determine presence of damage at sympathetic nerve chain found on spine
Sympathetic nerve - control involuntary functions of the body E.g. opening and
narrowing blood vessels
PAIN - INTRODUCTION Provides the body with a warning of
potential or actual injury
Triggered by activation of nociceptors Distributed throughout the body like skin,
viscera, muscles
Stimuli that activate nociceptors Mechanical Thermal Chemical
PAIN –ACCORDING TO DURATION Acute pain
sudden and limited duration caused by damage to tissue such as bone,
muscle, or organs, Initially accompanied by anxiety or emotional
distress
Chronic pain Longer than acute pain Associated with a long-term illness like
osteoarthritis
PAIN –ACCORDING TO TYPE OF DAMAGE Nociceptive pain
Damage or injury to the body's tissues E.g. bone, soft tissue, or organs Caused by
Disease like cancer or inflammationPhysical injury such as a cut or a broken
bone.
PAIN –ACCORDING TO TYPE OF DAMAGE
E.g. burning sensation present although no heat is applied to the area that burns
Nerves damaged
Transmission of pain signals
affected/hindered
Abnormal pain signals are
transmitted to the brain
Neuropathic pain
MECHANISM OF NEUROTRANSMISSION Action potentials
Produced to transmit information from neurons to other body tissues such as muscles
Voltage or difference in electrostatic potential, always exists between the inside and outside of a cell Ion distribution Permeability of the membrane to these ions
MECHANISM OF NEUROTRANSMISSION
1. Resting Potential2. Depolarization3. Repolarization4. Return to Resting Potential
MECHANISM OF NEUROTRANSMISSION 1. Resting potential of inactive cell
Negative value (inside relative to outside the cell)
Maintained by the active transport of potassium and sodium ions into and out of the cell, respectively Via sodium-potassium pumps scattered
across cell membrane More sodium outside the cell than inside More potassium inside the cell than outside
MECHANISM OF NEUROTRANSMISSION 2. Depolarizationa) Stimulus causes voltage-gated Na+
channels in the neuron cell membrane to open
b) Sodium ions diffuse into the cell through channels along electrochemical gradient
c) As sodium ions enter, the membrane potential becomes less negative
MECHANISM OF NEUROTRANSMISSION 2. Depolarization – Peak As cell reaches membrane potential
of +30 mVa) Voltage-gated Na+ channels closes
preventing further influx of sodium.
b) Simultaneously, voltage-gated K+ channels begin to open – triggering exit of potassium ions from the cell
MECHANISM OF NEUROTRANSMISSION 3. Repolarizationa) As voltage-gated potassium channels
open, there is a large outward movement of potassium ions
b) While potassium ions diffuse out – causes reversal of the membrane potential from positive to negative
MECHANISM OF NEUROTRANSMISSION 4. Return to Resting Potentiala) As potassium exits the cell, cell membrane
potential continues to be negative
b) K+ channels do not close immediately – potassium continues to flow out of the cell even after the membrane has fully repolarized exceeding -70 mV
c) Na+/K+ pumps opens and transport K+ into cell to reach resting potential
MECHANISM OF DRUGDrug administered at site of administration
Non-ionized drug enters nerve cell
Drug inside cell becomes ionized
Ionized drug binds at Calcium-binding sites at the inside of Na+ channel
MECHANISM OF DRUGNa+ channels become closed preventing entry of
Na+ ions
No Na+ influx leads to decreased depolarization
Action Potential Generation and Propagation stopped
Transmission of sensory signal (e.g. pain) does not reach the spinal cord and brain temporarily
MECHANISM OF ACTION
Mechanism of Action
DOSAGE AND ADMINISTRATION Dose administered for desired result–
small
Factors influencing dosage of local anaesthetics Anaesthetic procedure Area to be anesthetized Vascularity of tissues
DOSAGE AND ADMINISTRATION Factors influencing dosage of local
anaesthetics Degree of muscle relaxation required Duration Individual tolerance Physical condition of the patient (weight and state)
Dosages for the following types of patients - reduced: Elderly and/or debilitated patients Patients with cardiac and/or liver disease
DOSAGE AND ADMINISTRATION Marcaine
complete sensory block at recommended doses effect on motor function differs among three
concentrations 0.75% of Marcaine - abdominal operations to
induce complete muscle relaxationCONCENTRATION SENSORY
FUNCTIONMOTOR
FUNCTION0.25% COMPLETE INCOMPLETE0.50% COMPLETE MODERATE0.75% COMPLETE COMPLETE
DOSAGE AND ADMINISTRATIONTYPE OF BLOCK CONC.
EACH DOSE MOTOR BLOCK(ML) (MG)
Local infiltration 0.25% Up to max. Up to max. -
Epidural
0.75% 10-20 75-150 complete
0.5% 10-20 50-100 Moderate to complete
0.25% 10-20 25-50 Partial to moderate
Caudal 0.5% 15-30 75-150 Moderate to complete
0.25% 15-30 37.5-75 complete
Peripheral nerves
0.5% 5 to max. 25 to max. Moderate to complete
0.25% 5 to max. 12.5 to max. Moderate to complete
DOSAGE AND ADMINISTRATION
Duration of anaesthesia for most indications Single dose is sufficient
TYPE OF BLOCK CONC.
EACH DOSE MOTOR BLOCK(ML) (MG)
Sympathetic 0.25% 20-50 50-125 -
Dental 0.5% with Epi
1.8-3.6 per site
9-18 per site -
Epidural Test Dose
0.5% with Epi 2-3
10-15 (10-15 mcg
epinephrine)
-
DOSAGE AND ADMINISTRATION Maximum dosage limit -
individualized Size Physical status Rate of systemic absorption from
particular injection site
Maximum dosage limit for most patients: Single doses of Marcaine up to 225 mg
with epinephrine 1:200,000 175 mg without epinephrine
DOSAGE AND ADMINISTRATIONFrequency and Daily Limit of Dosing of Marcaine
Repeated as needed - once every 3 hours
In clinical studies to date, total daily doses have been up to 400 mg
Maximum SQ dose 2 mg/kg
INDICATION Local or regional anaesthesia or
analgesia to relieve or prevent pain during: Surgery Dental Oral surgery procedures Diagnostic procedures Therapeutic procedures Obstetrical procedures
Does not lead to loss of consciousness
KEY ISSUES – SIDE EFFECTS Hypotension Bradycardia Ventricular arrhythmia Cardiac arrest excitation CNS depression Convulsion Allergic reaction
KEY ISSUES - CONTRAINDICATIONS Hypersensitivity to bupivacaine or
other amide-type anaesthetics or any component of drug
Obstetrical paracervical block anaesthetic
KEY ISSUES - WARNINGS DENTAL
Inform patient receiving dental injection Avoid chewing solid foodAvoid biting or probing area injected
CAUDAL OR EPIDURAL ANAESTHESIA Warn patient of temporary loss of
sensation and motor activity at lower body
KEY ISSUES – ADVERSE DRUG REACTIONS [SERIOUS] Cardiovascular
Cardiac arrest Hypotension Negative inotropic effect on heart Ventricular Arrhythmia
Immunologic Allergic reaction - Rare
Musculoskeletal Chondrolysis of articular cartilage
KEY ISSUES – ADVERSE DRUG REACTIONS [SERIOUS] Neurologic
Bacterial meningitis Central Nervous System Depression Central Nervous System Stimulation Paraplegia (paralysis of lower body) Seizure (0.1%, rare) Total spinal nerve blockade following local
anaesthetic injection Respiratory
Respiratory arrest
KEY ISSUES – ADVERSE DRUG REACTIONS (TREATMENT) CENTRAL NERVOUS SYSTEM TOXICITY First-line treatment of local
anesthetic-induced seizure Benzodiazepines – less potential to cause
cardiac depression
If benzodiazepines not available, other alternatives at lowest effective dose include Propofol Thiopental
KEY ISSUES – ADVERSE DRUG REACTIONS (TREATMENT) ALLERGIC REACTIONS - rare Mild cutaneous reactions
Oral or IV dipenhydramine – 25-50 mg Serious allergic reactions – respiratory
distress & hypotension SubQ Epinephrine – 0.3mL of 1:1000 dilution Corticosteroids
125 mg methylprednisolone IV push60 mg prednisone oral
KEY ISSUES – ADVERSE DRUG REACTIONS (TREATMENT)
CARDIOVASCULAR TOXICITY – Cardiac Arrest
Use standard Advanced Cardiac Life Support (ACLS) with the following modifications:
Epinephrine Small initial doses (10-100 μg boluses in adults)
Vasopressin - not recommended Avoid calcium channel blockers and beta-
blockers Ventricular arrhythmias develop
Amiodarone
KEY ISSUES – ADVERSE DRUG REACTIONS (TREATMENT)
CARDIAC TOXICITY Avoid lidocaine and 1B antiarrhythmic
agents (mexiletine, tocainide)
KEY ISSUES – DRUG INTERACTIONSDRUGS SEVERITY SUMMARY
Bupivacaine – Propanolol Major
Concurrent use of these may result in
increased bupivacaine toxicity
Bupivacaine – Verapamil Major
Concurrent use may result in increased risk of heart block
Bupivacaine – Propofol Major
Concurrent use may result in hypnotic effect of propofol
KEY ISSUES – DRUG INTERACTIONSDRUGS SEVERITY SUMMARY
Bupivacaine – Hyaluronidase Major
Result in increased incidence of
systemic reaction to anaesthetic
St. John’s Wort – Anaesthetic Major
Increased risk of cardiovascular collapse and or
delayed emergence from anaesthesia
Bupivacaine – ACE Inhibitors Moderate
Concurrent use may result in bradycardia
and hypotension with loss of
consciousness
KEY ISSUES – DRUG INTERACTIONSSOLUTION: PREVENTION
Advise patients to make list of all medicines being taken Share this with pharmacist and doctors
Update taking new medicine
Pharmacist or doctors inform patient about benefits and potential risks of medications being taken
KEY ISSUES – DRUG INTERACTIONSSOLUTION: PREVENTION
Patient educationExpected side effects and adverse reactions during medication use
Encourage patient to inform pharmacist or doctors if side effects or adverse reactions are experienced
PRECAUTIONS Obstetrical epidural anaesthesia
Never use 0.75% bupivacaine solution. Use causesCardiac arrest with difficult resuscitationDeath
Epidural or Caudal Anaesthesia Do not use solutions containing
antimicrobial preservatives Repeated Local Administration
Risk of significant increase in plasma concentration
PRECAUTIONS Head and neck administration
Related to events occurring with systemic toxicityConvulsion, confusion, Respiratory depression and or
respiratory arrestCardiovascular stimulation or
depression Recommended monitoring
Intravenous Regional Anaesthesia Cardiac arrest and death reported
PRECAUTIONS Cardiovascular
Serious dose-related arrhythmia – using bupivacaine with vasoconstrictors like epinephrine
Use cautiously in patients with history of cardiac rhythm disturbances, shock, hypotension
Endocrine and Metabolic Familial malignant hyperthermia may
be triggered
PRECAUTIONSDebilitated, elderly and acutely ill patients Lower tolerance to elevated blood
levels Recommended: Dose adjustment
Hepatic Increased risk of developing toxic
plasma concentrations in patients with hepatic disease
SWOT Analysis
Strengths
Multiple indications (pain relief, diagnostic)
Long duration of action
Post-procedural pain management
SWOT Analysis
OpportunitiesAlternative to Narcotics for Pain
relief of knee replacement patient
New Combination with other drugs
COMPETITIVE ANALYSIS
Mepivacaine (1-4%)
Prilocaine (1-2%)
Lidocaine (1-2%)
Bupivacaine (0.25-0.75%)
3
3
4
5
5
4
6
11
ONSET OF ACTIONMaximum (min.) Minimum (min.)
COMPETITIVE ANALYSIS
Bupivacaine Lidocaine Prilocaine Mepivacaine
1.50.75 0.5 1
8
1.5 12
DURATION OF ACTIONMinimum (h) Maximum (h)
COMPETITIVE ANALYSIS
Bupivacaine Lidocaine Prilocaine Mepivacaine
3
4.5
8
4.5
Max Dose (mg/kg)
COMPETITIVE ANALYSIS
Bupivacaine
Lidocaine
Mepivacaine
2.7
1.5
1.9
2.7
2
3.2
Elimination Half-lifeMaximum (h) Minimum (h)
BUPIVACAINE’S 5 C’S INSIGHTSCustomer Consumer Competitio
nCompound Channel
• Doctors need to continuously monitor patient during drug use
• Doctors acknowledge importance of Local Anaesthetic
• Address specific cases because of drug characteristics
• Instruct patients to monitor and report side effects and adverse drug effects during drug use
• Sales measured quarterly, then semi-annually 2016
• Observe and analyze activity of competitor and market
• Safe
• Long-acting Local Anaesthetic
• Possible alternative to narcotics for pain relief of knee replacement patients
• Seminars provided to groups of hospitals to convey message to doctors
• Websites as online sources for physicians
REFERENCE – INFORMATION American Society of Regional Anaesthesia and Pain Medicine.
(2016). Regional anaesthesia for surgery. Retrieved from https://www.asra.com/page/41/regional-anesthesia-for-surgery.
American Pharmaceutical Association. (2013). Frequently Asked Questions About Drug-Drug Interactions Involving OTC Medications. Retrieved from: http://www.bemedwise.org/quiz_facts/facts.htm.
Bernardino, C. R. (15 July 2008). In-Office Surgery: Preventing and Treating Surgical Pain. Review of Ophthalmology. Retrieved from: https://www.reviewofophthalmology.com/article/in-office-surgery-preventing-and-treating-surgical-pain
Blahd, W. (14 August 2015). Pain Types and Classifications. WebMD Medical References. Retrieved from: http://www.webmd.com/pain-management/guide/pain-types-and-classifications.
REFERENCE – INFORMATION Bupivacaine. (2016). Truven Health Analytics-
Micromedex Solutions. Retrieved from: http://www.micromedexsolutions.com/micromedex2/librarian/CS/79FAB7/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/65B8CC/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.DoIntegratedSearch?SearchTerm=bupivacaine&UserSearchTerm=bupivacaine&SearchFilter=filterNone&navitem=searchALL#
Bupivacaine Formula Cuts Narcotic Use. (2014). MedPageToday. Retrieved from http://www.medpagetoday.com/meetingcoverage/aaos/44735
REFERENCE - INFORMATION Dougherty, P., & Tsuchitani, C. (2016). Chapter 2: Somatosensory
Systems. University of Texas-Health. Retrieved from: http://neuroscience.uth.tmc.edu/s2/chapter02.html.
Kapitanyan, R., & Su, M. (2016). Local Anesthetic Toxicity Treatment and Management. Medscape. Retrieved from: http://emedicine.medscape.com/article/1844551-treatment#d10.
Local Anaesthesia. (2015). NHS. Retrieved from: http://www.nhs.uk/conditions/anaesthetic-local/Pages/Introduction.aspx.
Local anesthetics: systemic toxicity. (2016). Open Anesthesia-International Anesthesia Research Society. Retrieved from https://www.openanesthesia.org/local_anesthetics_systemic_toxicity/
Marcaine. (2012). RxList. Retrieved from: http://www.rxlist.com/marcaine-drug/indications-dosage.htm.
REFERENCE – INFORMATION Press, C. D. (18 November 2015). Infiltrative Administration
of Local Anaesthetic Agents. Medscape. Retrieved from http://emedicine.medscape.com/article/149178-overview.
Reddi, D. (2009). An introdution to pain pathways and mechanisms Feb12. [doc]. University College London. Retrieved from: https://www.ucl.ac.uk/anaesthesia/StudentsandTrainees/PainPathwaysIntroduction.
WebMD.(9 September 2014). Dealing with Medicine Side Effects and Interactions-Using Medicines Safely. Healthwise, Incorporated. Retrieved from http://www.webmd.com/a-to-z-guides/dealing-with-medicine-side-effects-and-interactions-using-medicines-safely.
REFERENCE - IMAGES https://psnet.ahrq.gov/media/cases/images/
case90_fig1.jpg http://newbridgespine.com/wp-content/
uploads/2013/07/nerve_block_procedure.jpg https://www.completenaturecure.com/wp-
content/uploads/2015/04/burning-sensation.jpg
http://www.vce.bioninja.com.au/_Media/action_potential_med.jpeg
http://pocketdentistry.com/wp-content/uploads/285/QE06_Meechan_fig002.jpg