1. Kenya Medical Training College
Department of Orthopaedic and Trauma
Medicine
PHARMACOLOGY II
Year: 2022 Semester: 2 Session 9&10
Topic: Muscle relaxants, Sedative Hypnotics,
Spasmolytics, Emergency drugs, Local
anaesthetics, Intravenous Fluids
Date: 18th May 2022
By: Carol Babu

2. Learning Objectives
 Definition of Pharmacologic agents
 Indications of the Pharmacologic agents
 Side effects of The pharmacologic agents

3. Muscle Relaxants
Skeletal Muscle Relaxants
Sedatives and Hypnotics

4. Skeletal Muscle Relaxants
• Skeletal muscle relaxants are drugs that are used to
relax and reduce tension in muscles. They are more
simply referred to as muscle relaxants.
• They are grouped into two based on therapeutic
activity:
1. Neuromuscular blockers
• Most are used during surgical procedures and in
intensive care units to produce muscle paralysis
during tracheal intubation, control of ventilation and
treatment of convulsions

5. 2. Spasmolytics
• Centrally acting muscle relaxants
• Are commonly used to reduce spasticity in
neurologic conditions

6. Neuromuscular Blocking Drugs
• They compete with acetylcholine and interfere
with the transmission of nerve impulses resulting
in skeletal muscle relaxation.
• They are highly polar and must be administered
parenterally
• They should be used with caution in patients
with renal failure

7. • Neuromuscular blockers are grouped into two:
a). Non depolarizing relaxants/agents
b). Depolarizing muscle relaxants

8. Non Depolarizing agents
• Are competitive agonists of acetylcholine
• Tubocurarine is the prototype drug
• Other drugs in this group include:
Vecuronium
Rocuronium
Pancuronium
Atracurium- Cisatracurium, Mivacurium
doxacurium

9. Tubocurarine
• An isoquinoline derivative just like atracurium and
doxacurium
• Causes motor weakness and skeletal muscle
paralysis
• It is a long acting neuromuscular blocker just like
pancuronium
• Effect lasts 45-60 minutes
• Dose 0.1 - 0.4mg/kg IV

10. Pancuronium
• Long acting neuromuscular blocker without
histamine release
• Causes cardiovascular effects leading to
moderate rise in heart rate and cardiac output
• Is given IV

11. Rocuronium
• A steroid derivative just like pancuronium and
vecuronium
• It is the least potent but most rapid
• Has the fastest onset and shortest duration of
action
• Has minimal cardiovascular effect

12. Depolarizing relaxants/agents
• Depolarizing neuromuscular blockers are drugs used
to induce anesthesia and relax skeletal muscles
(paralysis) during intubation, mechanical
ventilation, and surgical procedures.
• Neuromuscular blockers prevent the action of
acetylcholine at the neuromuscular junction, thereby
preventing skeletal muscle contraction.
• Have effects like those of acetylcholine
• Examples include:
Succinylcholine
Suxamethonium

13. Succinylcholine
• Causes rapid paralysis and is commonly used in
rapid sequence intubation
• Dose 0.75 -1.5mg/kg IV

14. Adverse effects of depolarizing agents
 Hyperkalemia - Avoid in pts with multiple injuries,
closed head injury, extensive muscle necrosis and
pts with burns
 Increased intra-ocular pressure
 Increased intra-gastric pressure
 Myalgia/muscle pain
 Malignant hyperthermia especially with
suxamethonium

15. Drug interactions of neuromuscular
blockers
 Inhaled anaesthetics - Synergistic/additive effects
esp. with sevoflurane, halothane, nitrous oxide
leading to malignant hyperthermia
 Antibiotics -Aminoglycosides have additive
effect
 Local anaesthetics - Cardiac arrhythmias

16. NB:
 Myasthenia gravis enhances the effects
of neuromuscular blockade
 Advanced age is associated with a
prolonged duration of action esp. with
non-depolarizing agents

17. Reversal of non depolarizing neuromuscular
blockers:
 Cholinesterase inhibitors antagonize the effects of
neuromuscular blockade
 They increase the availability of acetylcholine at the
motor end plate through inhibition of
acetylcholinesterase
 Examples include:
 Neostigmine
 Pyridostigmine

18.  Sugammadex - A drug that can rapidly inactivate
steroidal neuromuscular blocking drugs through
a chelation process

19. Spasmolytics
 Spasmolytics, also known as "centrally acting"
muscle relaxant, are used to alleviate
musculoskeletal pain and spasms and to reduce
spasticity in a variety of neurological conditions.
 Common drugs used as spasmolytics include
diazepam, gabapentin, and dantrolene

20. Diazepam/Valium
 A benzodiazepine
 Facilitates the action of GABA (a
neurotransmitter that blocks impulses between
nerve cells in the brain.)
 Produces sedation, decreases anxiety and reduces
muscle tone
 Useful in seizure disorders
 Dosage formulations; oral 5-10mg in 24hrs,
parenteral 0.1-0.15mg/kg

21.  Other drugs used to treat acute local muscle
spasms:
 Chlorzoxazone
 Cyclobenzapine
 Metaxalone

22. Assignment
 Read on:
 Non competitive depolarizing agents
 Suxamethonium
 Decamethonium
 Difference between a sedative and a hypnotic

23. Sedatives and Hypnotics
Sedatives and hypnotics are two classes of
prescription drugs that are commonly called
“tranquilizers,” “sleeping pills,” or
“sedatives.” They affect your central
nervous system – your brain and spinal cord
– and have a relaxing, calming effect.

24. Benzodiazepines
• The most widely used sedatives
• Examples:
Diazepam
Midazolum
Lorazepam
Alprazolam
Clonazepam

25.  Barbiturates
 Thiopental
 Phenobarbitone
 Antipsychotics
 Anticonvulsants
 Others
 Propofol
 Ketamine

26. Midazolum
 Rapid onset sedative
 Requires titration
 Has variable potency
 Dose 0.1mg/kg IV

27. Ketamine
 Possesses both analgesic and amnestic properties
 Rapid sedation < 1 minute
 Has a brief duration of action
 It is a dissociative anaesthetic
 It is good in pts with bronchospasms because of
its bronchodilatory effect

28.  Good even in patients with septic shock,
haemorrhagic shock
 The limitation of ketamine is that it is a potent
cerebral vasodilator
 Dose 1-2mg.kg IV

29. Propofol
 Causes light sedation to comatose state
 Has a rapid onset
 Decreases cerebral metabolism
 Causes myocardial depression leading to decreased
MAP and decreased oxygen delivery
 Dose 2-3mg/kg IV

30. Assignment
 Read on Etomidate

31. Emergency and other drugs in trauma
 Oxygen
 Adrenaline
 Local anaesthetic
 IV fluids

32. Oxygen
 Oxygen therapy or supplemental oxygen is the
use of oxygen as a medical treatment
 Oxygen is a medical gas and is one of the most
common medical gases used in trauma patients
 It is usually administered via inhalation
 The conc. of O2 prescribed aims to bring O2
saturation (SPO2) to normal or near normal
oxygen saturations at rest.

33.  Oxygen saturation varies with age:
 Preterm babies 88-92 %
 Term babies and children 92-96 %
 Adults 96 -98 %

34.  Oxygen delivery of more than 5L/min for more
than 30min must be attached to a humidification
device in order to reduce the risk of side effects
associated with dry gas administration and
promote patient comfort.

35. Indications for O2 therapy
 Mainly to prevent or treat hypoxia and
hypoxaemia as in:
 Peri - operative care
 Post -operative state
 Acute hypoxaemia as in shock
 Ischaemia - MI
 Pneumothorax
 Abnormalities in quantity, quality or type of
Hb as in blood loss from trauma, GI blood loss
or carbon-monoxide poisoning

36. Modes of O2 delivery
 Nasal cannular/catheter
 This can not be used for pts requiring >4L/min
(40%)
 The concentration of oxygen is dependent on flow
rate and cannulars can deliver up to 1-4L of O2
per minute
 Nasal prongs
 By mask – Non re-breather O2 mask
 Endotracheal tube (ETT)

37. Non Re-breather O2 mask
 Commonly referred to as “ Trauma mask”
 It is good for high percentage of O2
administration (> 60-90 %) when the patient
is not at risk of retaining CO2 or loosing their
hypoxic drive
 It is suitable for trauma patients on a short
term basis only.
 There is risk of O2 toxicity and reabsorption
atelectasis ( Failure of the alveoli to expand).
 It requires a tight seal around the mouth

38. Non Re-breather O2 mask
 Commonly referred to as “ Trauma mask”
 It is good for high percentage of O2 administration
(> 60-90 %) when the patient is not at risk of
retaining CO2 or loosing their hypoxic drive
 It is suitable for trauma patients on a short term
basis only.
 There is risk of O2 toxicity and reabsorption
atelectasis ( Failure of the alveoli to expand).
 It requires a tight seal around the mouth

39. High flow O2 therapy
 This is for patients unable to maintain adequate
arterial saturation of O2 despite convectional low
flow O2 therapy
 Oxygen supply must be via a humidified circuit
and not piped O2

40. Hazards of high flow O2 therapy
 Fires as O2 supports combustion
 Loss of hypoxic drive
 Oxygen toxicity and alveolar damage
 Coronary and cerebral vasoconstriction

41. Monitoring for O2 therapy
 Respiratory rate
 Blood Pressure
 Pulse Oximetry
 Patient colour
 Features of respiratory distress
 Conscious level

42. Adverse effects of O2 therapy
 Oxygen toxicity
 Hyperoxia
 Convulsions
 Retinopathic conditions
 Haemolysis
 Carbondioxide narcosis

43. Assignment
 Adverse effects of O2 therapy in newborns
Infants receiving oxygen may get cold if the
temperature of the oxygen is not warm enough.
Some nasal cannulas use dry oxygen. At higher
flow rates, this can irritate the inner nose, causing
cracked skin, bleeding, or mucus plugs in the nose.
 Hyperbaric oxygen therapy
conditions treated with hyperbaric oxygen therapy
include serious infections, bubbles of air in your
blood vessels, and wounds that may not heal as a
result of diabetes or radiation injury.

44. Adrenaline/Epinephrine
 A catecholamine and a sympathomimetic drug
 It is an alpha and beta agonist and a very potent
vasoconstrictor and cardiac stimulant
 It is a positive inotropic and chronotropic agent
(Beta 1 receptors) and also a powerful
vasoconstrictor (alpha receptors).

45.  Activation of beta 2 receptors may lead to dilation
of skeletal muscle blood vessels
 Epinephrine increases systolic BP and decreases
diastolic BP
 Formulations:
 Parenteral for S/C, IM, IV
 Nasal spray
 Inhalation (Nebulization)
 Eye drops (Topical)

46. Clinical uses of Adrenaline
 Asthma esp in nebulization
 Anaphylactic shock
 Cardiac arrest
 Local anaesthetic additive

47. Clinical uses of Adrenaline
 Asthma esp in nebulization
 Anaphylactic shock
 Cardiac arrest
 Local anaesthetic additive

48. Side effects
 Hypertension
 Vasoconstriction
 Reflex tachycardia and ventricular dysarrythmias

49. Noradrenaline/Noradrenaline
 Has similar effects on beta 1 receptors but has
relatively little effect on beta 2 receptors
 Generally increases peripheral resistance and both
diastolic and systolic BP
 Noradrenaline is commonly used as inotropic
agent

50. Local Anaesthetics (LA)
 These are agents that produce reversible nerve
conduction blockage when applied locally
 They can act on any type of nerve or fiber
 They cause both sensory and motor paralysis
 Recovery is complete without structural damage

51.  Most LA consists of a lipophilic group (aromatic
ring) connected by an intermediate chain via an
ester or amide to an ionizable group
 Ester links have shorter duration of action
compared to amide links because they are prone
to hydrolysis

52.  Most are weak bases. Alkalinization shortens
onset of blockage and enhances sensory and
motor blockage
 Local anaesthetics are much less effective in
infected tissues because a smaller percentage of
the drug is non-ionized and available for
diffusion across the membrane in an environment
with a low extracellular PH.

53. Classification of LA
1. Natural alkaloids
 Cocaine
2. Synthetic LA
 Esters
 Procaine
 Tetracaine
 benzocaine

54.  Amides
 Lidocaine
 Mepivacaine; new amides and isomers of
mepivacaine include:
 Levobupivacaine
 Ropivacaine
 Bupivacaine
 Prilocaine

55. Mechanism of action
 Blockage of voltage-gated sodium channels

56. Pharmacokinetics
 Preparations
 Parenteral
 Injection in the vicinity of peripheral nerve
endings/infiltration and major nerve trunks
(blocks) or into epidural or subarachnoid
spaces
 Topical
 Transmucosal
 Transdermal
 Wound margins

57.  Absorption is dependent on:
 Dosage
 Site of administration
 Drug tissue binding
 Blood flow

58.  Vasoconstrictor substances such as epinephrine
reduce systemic absorption of short acting LA;
Procaine, Lidocaine and mepivacaine by
decreasing blood flow up to 30 % in the tissues
 The advantages of vasoconstrictors added to LA
include:
 Enhanced localized neuronal uptake because of
higher local tissue concentration
 Reduced systemic toxic effects
 Enhanced and prolonged anaesthetic effect by
acting on alpha 2 adrenoreceptors

59.  Distribution of LA is widely into tissues and
highly perfused organs
 Metabolism and excretion is mainly in the liver
or plasma to water soluble metabolites which are
then excreted in urine

60. Clinical uses of LA
1. Infiltration analgesia
2. Regional anaesthesia
 Epidural
 Spinal
 Cordal
 Intravenous

61. 3. Topical uses
 Cocaine
 Tetracaine
4. Entectic mixture of LA (EMLA)
 2.5 % lidocaine or prilocaine for skin procedures like
branulars, BM aspirate
5. Peripheral nerve blocks
6. Intravenous “Biers” block- Regional anaesthetics

62. 7. Anti-arrythmias; Lidocaine to terminate
arrythmias and ventricular tachycardia
8. Suppression of grandmal seizures
 Lidocaine
 Mepivacaine
9. Tumescent liposuction
10. Bronchodilation
11. Anti-inflammatory effect
12. In ophthalmology analgesia-Proparacaine

63. Adverse effects/Toxicity
 Allergic Rxns-Rare
 Commonly with ester derivatives
 Systemic toxicity
 CNS
 Circumoral/tongue numbness and metallic taste
are early warning symptoms of toxicity
 Sleepiness, light headaches, visual/auditory
disturbances, restlessness

64.  Nystagmus, seizures/convulsions
 Slurred speech
 Coma and death from cardiopulmonary
collapse and global depression of CNS
Mnx – Benzodiazepines, Oxygen

65.  Neurotoxicity
 Results from local effects:
 Transient radicular irritation on transient neuropathic
symptoms
 Cauda Equina syndrome
 CVS
 Depressed cardiac activity; prolonged PR interval and
widened QRS complex on ECG monitor

66.  Bupivacaine is more cardiotoxic. The cardiotoxicity is
increased by:
 Hypoxaemia
 Acidosis
 Hypercarbia
 Haematological effects
 Methemoglobinemia
 Others
 Hepatoxicity
 Dysphonia

67. Specific Local Anaesthetics
Lidocaine
 Has a faster onset of action, more intense and
longer lasting analgesia
 Has been used in all kinds and at all sites; mucus,
skin or systemic for any procedure
 It is anti- arrythmic
 Suppresses seizures and can also cause seizures

68.  Preparations:
 0.5, 1, 1.5, 2, 4 % for injection
 0.5, 1, 1.5, 2 % with 1:200, 000 epinephrine or
1, 2 % with 1: 100, 000 epinephrine
 Dose 1-3mg/kg

69. Bupivacaine/Macaine
 One of the potent LA
 Has longer duration of action, slow onset
 It is very toxic and cardiotoxicity occurs earlier
than CNS features
 Parenteral preparations; 0.25 %, 0.5 %, 0.75 %
Or epinephrine in 1: 200, 000

70. Etidocaine
 A long acting amide
 Faster onset of action than mepivacaine
 Has similar duration of action as mepivacaine
 Causes preferential motor blockade and is good
for orthopaedic surgery but disadvantageous in
labour and post-operative states

71. Mepivacaine
 An intermediate acting amide
 Has similar properties to lidocaine
 It is not effective topically
 It is toxic to the neonate and therefore
contraindicate3d in obstetrics
 Preparations; 1, 1.5, 2, 3 %

72. Questions?????

73. Intravenous Fluids
 Intravenous therapy is an effective and efficient
method of supplying fluid directly into
intravenous fluid compartment leading to rapid
effect
 IV fluids contain dissolved salts of varying
quantities

74.  Fluids may be given as:
a) Maintenance fluids
 Replaces insensible fluid losses
 May be 5 % dextrose, dextran, 0.45 % Normal
saline
b) Replacement fluids
 Corrects body fluid deficit as in trauma, burns,
diarrhoea, vomiting, gastric lavage
c) Specific fluids
 Hypoglycemics
 Hyperkalemic- KCL
 Metabolic acidosis – Sodium bicarbonate

75. Types of Fluids
1. Crystalloids
 Aqueous solution of mineral salts or other water
soluble molecules
 Are isotonic solutions that have no significant
fluid shifts across cellular or vascular membrane
 Easily gets to all fluid compartments
 Has no direct effect on clotting

76.  Better preserves cellular functions
 Examples of crystalloids include:
 0.9 % Sodium chloride
 Lactated ringers solution
 Hartmans solution
 5 % dextrose

77.  Crystalloids are rapidly lost from plasma
 Good for shock, hypovolaemia
 A greater volume is usually needed

78. 2. Colloids
 Contains larger insoluble molecules
 Stays in circulation (intravascular) longer
 Are good plasma expanders
 May disrupt clotting (Direct/Dilution)
 May cause anaphylaxis and cellular acidosis
 Less volume needed in treatment than
crystalloids

79.  Examples of colloids:
 Semisynthetic colloids
 Gelatin
 Dextran
 Hydroxyethyl starches
 Human plasma derivatives
 Human albumin
 Plasma protein fraction
 Fresh frozen plasma
 Immunoglobulin solutions

80. 3. Others
 Hypertonic solutions
 Commonly hypertonic saline
 Causes sustained BP increase
 Decreases intra-cranial pressure
 Includes 3 %, 5 %, 7.5 %, 10 % of saline

81. Indications for IVF
 IV fluids resuscitation for hypovolaemia is
common in medical practice for critically ill
patients
 Common indications include hypovolaemia
from:
 Trauma
 Burns
 Major surgery
 Dehydration
 Sepsis

82. Side effects/Adverse effects
 Sepsis associated with contamination
 Air embolism
 Cardiac overload/Circulatory overload

83. Fluid therapy in trauma patients
 Two large bore cannular
 2L of fluid – Crystalloid as bolus
 Control bleeding
 Continue replacement therapy until heart rate
normalizes

84. Ahsanteni sana!!!!!!