0 Muscle Relaxants - Important Points

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Drugs NOT having Renal excretion : (SMAC)

• Sch
• Mivacurium
• Atracurium
• CisAtracurium

Histamine Release (MAST)

• Mivacurium
• Atracurium
• Sch
• Tubocurrarine

Ganglionic effects

• Stimulation - Sch
• Block - Tubocurrarine

Vagolytic Activiy

• Gallamine
• Pancuronium

Sympathetic Stimulation

• Gallamine
• Pancuronium

Metabolized Completely by Renal

• Gallamine

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MedicoNotebook - Founder : DrShiviMudgal , Co-Founder : DrAyushGoel

0 NDMR (some more points)

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Non-depolarizing Muscle relaxants :

This is the second post on NDMR.
For Previous post - Click here


Drugs which antagonize the NDMR block :

1. Phenytoin
2. Carbamazepine
3. Calcium

Reversal of Block by :

1. Neostigmine

• does not cross BBB
• Muscarinic side effects - therefore give Atropine along with it.

2. Edrophonium

• Short duration of action (therefore chances of recurarization)

3. Pyridostigmine

• Longer duration

Signs of Adequate reversal :

1. Lift head for >5sec - Best Clinical Sign
2. Regular respiration
3. Spontaneous eye opening
4. Spontaneous Limb movements
5. Can protrude tongue
6. Able to cough
7. No Cyanosis

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4 Non Depolarizing Muscle Relaxants (NDMR)

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Non Depolarizing Muscle Relaxants (NDMR) :

• No Muscle fassiculation.

• Slow onset and slow dissociation.

• Reversed by Neostigmine.

• Muscle remains responsive to other stimulus (Therefore Neuromuscular monitor used).

• Fade & Post tetanic stimulation.

• Mild hypothermia antagonizes block.

Atracurium :

• Metabolism - 75% by Hoffman degradation, 25 % by  ester hydrolysis.
• Metabolite - Laudanosine (pro convulsant)
• Does not require any reversal agent

• DOC in :

1. Renal and Hepatic failure cases.
2. Myesthenia Gravis - Use 1/10 th of normal dose

CisAtracurium :

• 3 times more potent
• No histamine release
• Non cumulative
• Only Hoffman degradation
• Laudanosine levels are lower.

Mivacurium :

• Ultra Short
• Metabolism - Plasma Cholinesterase (=Pseudo)
• Ideal Muscle relaxant for Continuous infusion , day care surgery.

Doxacurium :

• Most Potent
• Long acting
• Metabolism - Kidney

D Tubocurarine :

• Long acting 
• Cause hypotension by ganglionic block

Vecuronium Bromide :

• Most Haemodynamically stable
• Minimum Vagolytic
• Metabolism - Liver

Pancuronium :

• Causes Hypertension and tachycardia (therefore good in Shock)
• Long acting
• Vagolytic
• Causes Nor-epinephrine release

Rocuronium bromide :

• Rapid onset (therefore can be used in full stomach)
• Slightly vagolytic
• Largely excreted unchanged in bile

Pipecuronium :

• Longest acting
• No vagolytic activuty

Rapacuronium :

• Fastest Onset (among NDMR) ( Note: Overall Fastest Onset Muscle relaxant is Sch )
• Increases incidence of bronchospasm.

Gallamine:

• Maximum propensity for vagal blockade
• Cross Placenta (therefore contraindicated in Pregnancy)
• Also Contraindicated in Renal disease.

Alcuronium :

• Anaphylaxis is common
• Deterioration on exposure to sunlight.

Fastest onset agents are used in full stomach : (preference order as mentioned below)

1. Succinylcholine
2. Rapacuronium
3. Rocuronium

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2 Succinylcholine

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Succinylcholine = Suxamethonium chloride 

Succinylcholine acts as a Depolarizing neuromuscular blocker (=DMR - Depolarising muscle relaxant)

Mnemonic : SSSS

• FasSiculations
• FaSt dissociation at receptors (Therefore Short acting )

Mnemonic : DND

• Not reversed by Neostigmine
• No fade or Post tetanic stimulation. 

Potentiated by

1. Isoflurane
2. Respiratory Alkalosis
3. Hypothermia
4. Mg

Antagonised by : Acidosis and NDMR

Repeated use  - causes Phase II block (similar to NDMR) -- (MCQ)

Other points about Sch :

• Onset within 30 sec --- lasts 10-12 mins.
• Bradycardia in children (especially after 2nd dose) (MCQ)
• All presures are increased ( BP , ICP , IOP , Intra gastric )
• Enzyme metabolism - by PseudoCholinestrase (= plasma = Butyrylcholinesterase) (read below in short about Cholinestrases )

Dibucaine Number :

• The Dibucaine Number is a measure of the qualitative activity of Pseudocholinesterase and is the percentage of inhibition of the enzyme by the local anesthetic Dibucaine.
Normally 75 - 85 % inhibition , But if homozygous defficiency - then 30%

• It is used to differentiate individuals who have substitution mutations of the Butrylcholinesterase enzyme.

Side effects :

• Increase K+ (especially after Burns , spinal cord injury , stroke , cerebral palsy )

Therefore Sch is Avoided 48hrs - 9months after acute injury. 

• Post Op muscular pain which can be decreased by :

                                  1. Self Taming (Pretreatment with small (10 mg) doses of succinylcholine)

                                  2. Precurarization (NDMR + Sch)

                                  3. Lignocaine

• Malignant Hyperthermia

Note: 

1. Sch is the MC drug which causes Malignant Hyperthermia.
2. All Fluranated inhalational anaesthetics & Lignocaine are other drugs which can cause Malignant Hyperthermia.

• Allergy - releases histamine.

• Contraindicated in Myotonic Dystrophy : as it causes severe muscle rigidity , preventing respiration and intubation.

• Can cause Masseter spasm in children.

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NeuroMuscular monitoring (Adductor Pollicis , Ulnar Nerve)  (No use in Sch block)

1. TOF (Train of 4)
2. PTC ( Post tetanic count )
3. DBS ( Dual burst stimulation )
4. Tetanus

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Cholinesterases :

1. True :  RBC and Grey Matter.
2. Pseudo/False :  Liver and Plasma.

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2 Neuromuscular-blocking drugs

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Neuromuscular-blocking drugs

These drugs fall into two groups:

• Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors.
• Depolarizing blocking agents: These agents act by depolarizing the plasma membrane of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh.

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0 Sevoflurane

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Sevoflurane :

• BG coeff. > Desflurane's

• Low solubility , non pungent.

• Excellent inhalational induction (Used in children) (before this halothane was used).

• May prolong QT interval on ECG.

• 5% Metabolized.

• Fresh gas flow is recommended.

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0 Desflurane

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Desflurane :

Boiling point - 23 *C
Therefore can boil at room temperature.
Hence require special vaporizer ( Tec 6)

• Lowest Blood gas coefficient - therefore fastest acting. 

(Remember the order of speed/BG coeff/MAC/Potency etc. as discussed before - Click here to read about it.)

Potency depends on Oil Gas partition coefficient.
Desflurane is least potent (Mn: Meeting Halo i.e super dangerous)

• Least metabolized (therefore least nephrotoxic)

Contraindications :

• Malignant hyperthermia
• Hypovolemia
• Intra Cranial hypertention.

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0 Isoflurane

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Isoflurane : MC used today

• Pungent, musty, ethereal odor

• Isomer of enflurane

• Minimal Cardiac depression.

• Hypotention by peripheral vasodilatation.

• Tachycardia

• Can cause Coronary steel syndrome.

Inhalational agent of choice in 

• Cardiac Surgery.
• Neurosurgery patients.
• Liver Transplant (as it maintains hepatic venous O2 saturation)

Contraindications :

• Malignant Hyperthermia
• Severe hypovolemia

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1 How to remember - Anaesthetic drugs for MCQs

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Few important points - simplified :

In all of the following Mnemonics - order is DECREASING i.e Max. to Least


Respiratory depression 

            EDISH
Max by >>>>>Least by



Decrease Cardiac output  

           EHSI
Max By>>>>Least by




ICT increase 

            EHSI
Max By>>>>Least by



Potency

Meeting Halo That is (i.e) Super Dangerous. 
   MH IE SD
Max >>>>Least



Speed Fastest - Slowest

Just reverse the potency order but keep " i.e " unchanged.
thus the order now is
   DS IE HM
Fast >>>> Slow


Blood Gas Coefficient

ISD
>>>


MAC

DSI
>>>

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E - Enflurane
D - Desflurane
H - Halothane
S - Sevoflurane
I - Isoflurane
M - Methoxyflurane

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0 Enflurane

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Enflurane : Points to remember

• Lowers CO

Contraindications:

1. Malignant Hyperthermia
2. PreExisting Kidney disease
3. Seizures (MCQ)
4. Intra Cranial hypertention.

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0 Halothane

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Halothane :

• Spontaneous oxidative decomposition retarded by - thymol preservative.

• Smooth induction

• Least decrease in Systemic vascular resistance.

• Lowers CO by direct myocardial depression

• Decrease HR

• Enhances myocardial sensitivity to dysrhythmogenic effects of epinephrine. (therefore not given in Pheochromocytoma)

• Reacts with metals in Vaporizers in presence of moisture.

• Maximum reduction in total hepatic blood flow and portal vein flow.

• Fast and shallow breathing

• Severe depression of hypoxic ventilatory drive.

• Potent Bronchodialator

• Depresses mucociliary function (Remember : Ether maintains ciliary function)

• Cerebro Vasodialator

• Prior hyperventilation required (to prevent increase in ICT)

• No Pain relief

• Uterine relaxant (Therefore DOC for Manual removal of placena ) ; (can cause PPH)

• Halothane hepatitis - Centrilobular necrosis (Inhalational agent of choice then is Sevoflurane)

Contraindications:

1. Malignant hyperthermia
2. Liver Dysfunction
3. Hypovolemia
4. Intra crania mass
5. Aortic Stenosis
6. Pheochromocytoma
7. with Aminophyline

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0 Droperidol

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Droperidol :

• Dopamine antagonist

• Sedative and powerful antiemetic.

• Mild alpha block

• Does not reduce cerebral O2 demand.

• Contraindicated in Pheochromocytoma.

In combination with Fentanyl 
Known As - Neurolept Analgesia (INOVAR)
Used in ratio of 50:1 (i.e 2.5mg Droperidol & 50microgram Fentanyl)


NeuroleptAnalgesia + N2O = NeuroleptAnaesthesia.

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0 Propofol

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Propofol = 2,6- diisopropyl phenol

1% / 2% emulsion in a lipid vehicle containing soybean oil, egg lecithin, and glycerol.

therefore - bacterial growth (thus discard after 6hrs)
Only IV use.

Pain on injection which can be decreased by :

1. injecting in larger vein.
2. Mixing with lignocaine
3. by cooling propofol

Other points:

• Recovery is rapid and clear (Therefore DOC for Day Care Surgery)

• Hepatic and Extrahepatic (Lungs) clearance.

• Decrease BP and Decrease Heart rate ( propofol blunts carotid body receptor response & hence no compensatory increase in heart rate)

• Causes maximum depression of upper airway reflexes (therefore DOC - for LMA insertion)

• Antiemitic & Antipruritic

• No anticonvulsant.

• Decrease IOP.(intraoccular pressure)

• AntiOxidant

• DOC in hepatic disease/Liver transplant (because it can be metabolized extrahepatic too.)

• Potentiates NMDR and fentanyl.

• DOC in Acute intermittent porphyria (here Thiopentone is Contraindicated)

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Propofol Infusion syndrome :

Triad of

• Metabolic Acidosis
• Skeletal Myopathy
• Acute Cardiomyopathy

On prolonged infusion (>48hrs) of high dose in child.

Occurs due to failure of metabolism of free fatty acids.

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0 Etomidate

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Etomidate :

• dissolved in propylene glycol

• only IV injection

• Most Cardiostable 

• Slight decrease in BP

• Maximum incidence of post op Nausea and Vomiting.

• lacks Analgesic property.

• Causes AdrenoCortical depression - therefore inhibit steroid - therefore mortality - thus Withdrawn.

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0 Ketamine

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Ketamine (Phencyclidine derivative):

Dissociative anaesthesia i.e dissociates thalamus from limbic system.

Metabolized in Liver to Nor-Ketamine (this also has anaesthetic potency)

CVS : 

• Increase HR, BP and Cardiac Output. (Therefore DOC for Hypovolumic shock patients)
• Myocardial O2 demand increases -- therefore avoid in Ishaemic heart disease , Hypertention and aortic aneurysm.

Respiratory system : 

• Minimal effect
• Potent Bronchodialator (therefore agent of choice in Asthma)
• Maintain upper airway reflex (therefore DOC for Full stomach patients)
• increases salivation (thus Anticholinergics are given to reduce this)

CNS :

• Increase cerebral O2 consumption (therefore contraindicated in Space occupying lesion and Head injury)
• Increases ICT
• causes hallucinations (decreased by BZDs)
• causes increase in IntraOccular Pressure (therefore Contraindicated in Glaucoma patients)
• NDMR are potentiated by ketamine.

Strongly analgesic. Therefore - Other uses:

• Field Anaesthesia
• Short surgical procedures
• Burn dressings

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Blue Colour : USE

Red Colour : NOT

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1 GABA & 5HT

0 BZD vs Barbiturates

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BZD	Barbiturates
1.       GABA facilitator	GABA mimetic
2.       DRC- flat	Steep
3.       No drug interaction	Enzyme Inducer
4.       Specific antagonist – Flumazenil	Not (therefore do alkaline diuresis in case of poisioning)
5.       Less Respiratory depression	More

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0 Benzodiazepines

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Benzodiazepine 

Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABA_A eceptor (pharmacodynamics: This increases the efficacy of GABA), 

whereas 

Benzodiazepines increase the frequency of the chloride ion channel opening at the GABA_A receptor (pharmacodynamics: This increases the potency of GABA).

Diazepam : Oil based , IM painful

Midazolam : Water Soluble , can be used as Anticonvulsant

                      It is the 1st drug to decrease seizures in ICU.

Awakening due to redistribution.

CVS : Minimal CVS depression.

Respiratory syatem : decrease Ventilatory response to CO2

• Diazepam : Retrograde Amnesia

• Midazolam : Anterograde Amnesia

They decrease MAC by 30%

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0 Methohexitol

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Methohexitol ( is a barbiturate derivative)

 MOA : binds to a distinct site which is associated with Cl− ionophores at GABA_A receptors and increases the length of time which the Cl− ionopores are open, thus causing an inhibitory effect.

Important points :

• Drug of Choice (DOC) for ECT

• It is a ProConvulsant

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0 Thiopentone

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Thiopentone = Sodium Thiopental
Thiopental, a barbiturate, is used for the induction of anesthesia

First used in 1934 by Lundy' and Waters

Yellow amorphous powder.

pH 10.5 - 11 , therefore not to be given with Normal Saline & RL

Dose - 3-5mg/kg ;  Route: IV

Adequate induction dose will cause loss of eyelash reflex.

Used in concentration of 2.5%

Given Commonly at outer aspect of forearm (Never in anticubital fossa)

If Concentration >2.5%

• Pain on injection
• Venous thrombosis

Mechanism of action :

• depress RAS
• binds at a distinct binding site associated with a Cl- ionopore at the GABA_A  receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Duration of action 

• Determined by redistribution (not by elemination)
• Patient looses consciousness in 30 sec and regains in 20 min.
• With repeated doses - duration depends on elimination (Metabolized in Liver)

Systemic effects:

• Decrease BP (Compensatory increase in Heart Rate)
• Decreased response to hypoxia & hypercarbia.
• Apnea (Treat with Positive pressure resp. -  IPPV)
• Decrease Tidal Volume and Respiratory Rate 
• Can cause bronchospasm & laryngospasm
• Decreases Cerebral blood flow
• Decreases Cerebral O2 consumption ( Therefore Cerebroprotective ; DOC - in Head Injury )
• Lowers threshold for pain ( it is AntiAnalgesic)
• Does not cause Muscle relaxation
• Powerful anticonvulsant (refractory seizures can respond to it)
• Decreases Renal blood flow and GFR
• Crosses Placenta and has some antithyroid activity.

It is Microsomal enzyme inducer.

Induction of hepatic enzymes increase the rate of metabolism.

Contraindications:

Acute Intermittent Porphyria and Variegate Porphyria

Can be used in Porphyria Cutaneous Tarda

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In case of inadvertent intra-arterial injection (eg: if in anticubital fossa)

• pain , 
• blanching hand , 
• absent radial pulse , 
• Secondary thrombosis

Treatment - 

• Stop injection & Leave the needle in situ (most important)
• Flush with saline
• Give Vasodialator
• Brachial or stellate ganglion block
• Anticoagulant

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