PHARMACOLOGY BY Dr.

Fahad Rafiq Butt

1- MUSCLE RELAXANTS:
Depolarizing:
Suxamethonium
Metabolism of Suxa by plasma cholinesterase.

What is half life of cholinesterase?

Ans: 12 hours.

Plasma cholinesterase levels fall down in:

 Liver failure
 Plasmaphoresis
 Cardiopulmonary Bypass (CPB)

Suxamethonium Apnoea:
There is a Dibucaine number; It is a number that tells us how much chances are there in this patient to develop sux apnoea.
It can be homozygous, heterozygous or atypical homozygous.
Dibucaine number in;
Homozygous is: more than 70 (normal). Sux will metabolize in 2 to 5 min.
Heterozygous is: 30-70. If suxa given it will remain in effect from 20 – 30 min.
Atypical homozygous: less than 30. Suxa will remain in effect for minimum 2-3 hours.

Sux Apnoea in a patient… how to manage?

Sedate and ventilate only … till suxa wears off.

Sux Apnoea ptient what advice for future.

He should wear a band/locket with written on it that he has had sux apnoea.

Suxa Side effects:

Most causative for allergic reactions Suxa > Muscle relaxants.
Suxa causes tachycardia via stimulation of autonomic ganglia of peripheral nervous system.
Suxa causes bradycardia by stimulation of muscarinic receptors of the heart.

Most bradycardia occurs in children.

One suxa intubating dose will increase Potassium by 0.5 mEq

Which side effect of suxa will not be end by precurarization?

Intraoccular pressure increase will not end by precurarization.

Precurarization is recommended to minimize which side effect of suxa?

Muscle Fasciculations (Myalgias)

Patient with raised ICP. Full stomach patient. How will you intubate this patient?
Rocuronium > Suxamethonium (because airway before ICP)

Suxa causes Malignant Hyperthermia.

Non-Depolarizing Muscle Relaxants:
Which one is most excreted by kidney?
Galamine, Pancuronium

Asthmatic patient, which muscle relaxant to avoid?

Atracurium.

Asthmatic Patient, muscle relaxant of choice?

Cisatracurium

Which stimulates most autonomic ganglia?

Pancuronium

Which least stimulates autonomic ganglia?

Vecuronium

Thyrotoxicosis, muscle relaxant of choice?

Vecuronium

Pheochromocytoma, muscle relaxant of choice?

Vecuronium

Sugammadex used most commonly with?

Rocuronium > Vecuronium

1.25mg/kg dose of rocuronium to effect in 30-60 sec for RSI.

Intubating RSI dose of rocuronium given, and you are unable to intubate or ventilate?
Sugammadex 16mg/kg
0.6mg/kg dose of rocuronium to effect in 3-5 min (non RSI intubation).
Sugammadex dose???

If rocuronium used for non RSI intubation dose is

0.3 mg/kg
Sugammadex dose?

What is structure of sugammadex?

It is a modified gamma cyclodextrin

Directly binds in 1:1 ratio with rocuronium

Kidney failure sugammadex duration of action is prolonged.

Most dose of sugammadex is used with rocuronium than vecuronium. This is because less dose of vecuronium is required because vecuronium is
more potent. So less molecules of vecoronuium are required.

Rocuronium given, unable to intubate…?

DAS guidelines…
If RSI bag mask ventilate
If non RSI LMA

Different muscle groups where

Action and
Eye mucles, diaphragm, and laryngeal (axial skeletal muscles)….. get the effect first and recover first.
Adductor Pollicis muscles (peripheral muscles) get the effect most late and are recovered most late.

During intubation to see if muscle relaxant done… see orbicularis oculi, and facial nerve… this will mean laryngeal muscles are gone.

While recovery see adductor pollicis… if it has recovered, then skeletal muscles would have recovered.

Different conditions affecting neuromuscular blockers..

Table in comprehensive.
Myasthenia Gravis… resistenace occurs to?
Depolarizing muscle relaxants. (Suxa)

Rest muscular dystrophies like Duchene etc… suxa sensitivity is increased. If suxa given to these.. they die of hyperkalemia.. because they have
prejunctional acetylcholine receptors, as in burns, prolonged bed ridden patient and muscular dystrophy patients like Duchene

In trauma patients within 24 hours do not use suxa

Patient with burns do not use suxa upto 1 year. Can be given in first 24 hrs only (burns and spinal injury).

CP child (cerebral Palsy) suxa can be given.

Patient undergoing neurofibroma excision?

Atracurium infusion.

Wilms tumor?
Atracurium infusion.

Huntington chorea
Suxa can be given.

2- OPIOIDS:
Lipid solubility low: Morphine
Onset slow, duration of action Prolonged …….

Kidney failure: Dec dose of morphine

CKD: Fantanyl stat dose can be given, not infusion
CKD: Remifentanyl infusion is best to give

CKD patient?
PCA Remifentanyl.

Epidural dose of morphine: 3-5 mg

Spinal dose: 0.3-0.5 mg
Duration of action: 24 hours.

Most common side effect of central neuraxial opioid use is?

Pruritis.

Most dangerous side effect of central neuraxial opioid use is?

Delayed resp depression.
Mechanism: It spreads cephalad with every respiration, when it reaches and acts at level of medulla,… it causes resp depression.

If someone is taking i.v, convert to oral it will be 3 times the i.v dose. And converting from oral to i.v give 1/3 dose.

Most lipid soluble:

Sufentanyl

Quickest onset of action: Alfentanyl (because it has low pKa… 90% unionized.)

Remifentanyl most common side effect:

Post-op pain

Erythrocyte pseudocholinesterase: which drugs are metabolized?

Remifentanyl, Esmolol

Tissue esterases, which drugs are metabolized?

Patient on SSRI.. contraindicated opioid?

Tramadol, Meperidine/Pethidine

Meperidine and Pethidine are two names of same thing.

Drug of choice for post-op shivering?

Pethidine

Antmuscarinic effects?
Pethidine

MI patient. Which opioid best?

Morphine (because it causes bradycardia and its safe in cardiac) (part of MONA)

Long acting opioid (morphine) to be avoided?

COPD, morbid obese, neuro surgery patients

i.v morphine causes respiratory depression by?

By decreased CO2 sensitivity in central chemoreceptors.

Which causes greatest cardiac depression?

Morphine
Nausea Vomiting occurs by?
Triggering of chemoreceptor zone in medulla
Which opioid side effect against which tolerance is not developed?
Miosis and Constipation

Constipation mechanism?
Via agonism at meu receptor in myenteric plexus.

Patient having constipation? You just want to treat his constipation.

Give methyl naltrexone. It acts at meu receptor in myenteric plexua

Smooth muscle spasm most due to? (e.g., biliary colic)

Morphine

Morphine contraindicated in biliary colic.

If smooth muscle spasm due to morphine.. treat with

Naloxone

Which drugs do not cause smooth muscle spasm?

Buprinorphine, and Tramadol

Which when given in rapid i.v bolus can cause skeletal muscle rigidity (also called wooden chest syndrome)?
Fantanyl

Patient induced with propofol, and fantanyl… patient unable to bag mask
ventilate?
Give (muscle relaxant) suxamethonium.

Which causes most histamine release?

Morphine

Patient opioid addict, now clean what to give for analgesia?

Give buprinorphine or methadone or PCA Tramadol (give partial agonist and not
direct agonist)

Patient currently opioid addict…

Donot give any antagonist like Naloxone/Naltrexone etc…
If nalaxone given he will go into severe withdrawal and even have seizures..

In current addict how to achieve analgesia?

PCA of opioid and background infusion of opioid together.

Pregnant female, opioid addict.. how to treat child…

Just Observe….. if resp depression intubate and ventilate.

3- PONV:
Patient with history of PONV.
0.1mg/kg Dexamethasone and 0.1mg/kg Ondensetron

Patient already received Onset, donot give more Onset.

Apprepetant?
Acts on substance P.

Contraindicated in Parkinson?
Metoclopramide. Droperidol, Prochlorperazine.

What to give in Parkinson patient for PONV?

(Pneumonic DOC-Drug of Choice) Domperidone, Ondensetron, Cyclizine

SAMBA guidelines 2020:

 4- PROPOFOL:
Most questions on TIVA related to propofol.

Highly lipid soluble.

Most common side effect that patient remembers?

Pain on injection.

Slight sedation needed. What should be blood level

1.4-4 mcg/ml

General Anesthesia blood level?

2-6 mcg/ml

Systemic Effects:
CMRO2 along with cerebral flow decreased by all i.v anesthetics. Other than ketamine

Patiwnt with history of PONV.

Propofol is best agent to use.

Propofol allergy happens due to?

Egg phosphatide

Patients of mitochondrial disease

Do not use propofol

Pain on injection, how to reduce?

Add 2ml of 2% lignocaine
Or
Use propofol of long chain fatty acids

Once vial is opened. Use within 6 hours to avoid infection.

TIVA benefits?
Best agent in neurosurgery

Has no effect on hypoxic pulmonary vasoconstriction.

So its good option in thoracic surgery.

Malignant hyperthermia patient.

Best option is TIVA

Malignant hyperthermia patient, You can’t change machine. What to do?

Circuit flush at 10-15 litres and flush for 30 min.

Laryngeal surgery like foreign body or vocal cord surgery, best?

TIVA

Female staff pregnant.. safety is with?

TIVA

ICU use of propofol:

Nutrition addition by propofol. 1kcal added by 1ml of propofol.

Hypertriglyceridemia caused by propofol

Pancreatitis caused by propofol
PRIS (Propofol related infusion syndrome):
Five things.
1. Metabolic acidosis
2. Liver failure
3. Cardiac Failure
4. Hypertriglyceridemia
5. Rhabdomyolysis

Urine color turns green due to propofol.

In PRIS due to rhabdomyolysis… urine can be muddy colored

Which patients at risk?

 Young age
 Severe illness
 Mitochondrial disease
 Infusion of more than 4mg/kg/hr for 48 hrs.

Treatment:
Hemodynamic support

Two similar scenarios similar to PRIS

Propofol infusion Patient. Develops Bradycardia and hypotension  he is having Heart Failure along with with metabolic acidosis?
Ans: PRIS

Patient on propofol, with hypertensive crisis, being given GTN infusion or nitroprusside… develops metabolic acidosis and hypertension
(tachyphylaxis)
Ans: Cyanide Toxicity
 5- BENZODIAZEPINES and BARBITURATES:
Which 2 drugs are water soluble outside body and lipid soluble in body?
Midazolam and Etomidate.

Patient of AIDS, taking antiretroviral.

Action of benzos prolonged.

Flumezenil:
Onset time: 1-2 min (less than midazolam)
Duration of action 60 min
Dose: 0.2mg starting upto 3mg.

It cant be used in Chronic benzo users because it will cause seizures.

Patient for first ECT.. drug of choice?

Propofol

Patient for repetitive ECT.. drug of choice?

Etomidate… so that seizure is good (seizure threshold is reduced).

Diazepam, most common side effect in fetus, when given to pregnant lady?
Fetal hypotonia

THIOPENTAL
Thiopental is drug of choice for?
Thyrotoxicosis patient.

Thiopental given in artery?

What not to do?
Do not remove cannula

What to do?
First immediate action will be to flush cannula with 500ml saline

Patient gets pain after getting thiopental in artery, what to do?

Give papavarine in cannula. If hand is still pink.
If hand is blue and pain, then?
Give Heparin infusion in artery
or
Stellate ganglion block.

Lorazepam
Patient with liver failure, what can be used?
(OUTSIDE THE LIVER)
Oxazepam
Temazepam
Lorazepam

Duration of action after stat dose: 20 hours.

Infusion… contact sensitive half life is 32 hours.

Benzodiazepines vs Clonidine:
Why clonidine is superior to benzos as pre medication?
 Analgesia
 Decreased PONV
 No respiratory depression
 6- ETOMIDATE:
3 Advantages and 5 Disadvantages
3 Advantages:
1. Drug of choice in repetitive ECTs (reduced seizure threshold or increase seizure activity)
2. Minimum respiratory and CVS interruption (So induction agent of choice in cardia patients like in CABG is Etomidate)
3. CMRO2 and cerebral blood flow is decreased

5 Disadvantages:
1. Contraindicated in Epilepsy along with ketamine
2. Patient remembers experience of PONV after etomidate the most
3. Pain on injection
4. Inhibits pseudocholinesterase
5. Causes Adrenocortical suppression

Patient with repeated wound dressing and debridements. Contraindicated?

Etomidate (due to cortisol deficiency due to etoidate)

Most allergic reactions reported with which Induction agent?

Thiopental

Least incidence of allergic reactions reported with which Induction agent?

Etomidate

7- KETAMINE:
Causes high sympathetic outflow
Ketamine not to be given to MI patients.

Ketamine raises ICP

Do not use ketamine in Neurosurgery and head trauma

Patient with sepsis, sympathetic drive lost…

Ketamine is a direct myocardial depressant.

Ketamine hallucinating side effects can be minimized by?

Midazolam

Ketamine is contraindicated in?

Liver Failure

Ketamine analgesia dose: 0.2 – 0.5 mg.kg

Sedation dose: 0.5-1mg/kg
Anesthesia dose: 1-2 mg/kg

Patient with MI, for CABG, induction agent of choice?

Etomidate (minimal CVS and resp depression)

Patient known asthmatic, induction agent of choice?

Ketamine

Patient known asthmatic, pain relief agent of choice?

Ketamine

Pregnant Asthmatic, induction agent of choice?

Propofol
(Because ketamine causes inc uterine contractions, and uterine blood flow in reduced)

Pregnant patient in hypovolemic shock, induction agent of choice?

Ketamine (because fetus doesn’t matter here, first save mother)
Shock, induction of choice?
Ketamine

Neurosurgery patient, induction of choice?

Propofol

Eye injury patient, contraindicated?

Ketamine (because it raises IOP)

8- DEXMEDETOMIDINE (ALPHA AGONIST):

Best sedation agent that resembles normal sleep

Dexmed causes QT prolongation

Dexmed has 8 times more action on Alpha 2, than Alpha 1.

Which effect not seen with Dexmed?

Tachycardia
 9- VASOPRESSORS & DEPRESSORS:
Dopamine:
Dopamine has dose dependant action
If less than 2 mcg/kg/min: it will only act on D A recpeptors, and it will cause vasodilatation and natriuresis.
If 2-5 mcg/kg/min dose given: Beta 1 activity… tachycardia and inc contraction (inotropic effect)
5-20 mcg/kg/min: hypertension by alpha 1 action

Dobutamine:
Dobutamine acting more on Beta 1 > Beta 2 > Alpha
Only used in Cardiogenic shock.

Patient with septic shock and with Noradrenaline MAP is not going up…
Add low dose Dopamine.

Nitroglycerine:
Acts on capacitance vessels (its venodilator)

Most common side effect:

Headache

GTN main effect in heart failure:

Reduce Preload

Coronary blood flow increased by GTN

GTN: Methemoglobinemia
Nitroprusside:
Nitroprusside acts on resistance vessels (arteries).
Arteriodilator

Reduces Afterload

Patient has myocardial ischemia.

Nitroprusside will cause coronary steal phenomenon

Nitroprusside: Cyanide toxicity

MISC:
23 yr male trauma, massive TFx… 4 units O neg given… more blood of O
neg PRBCs only

CKD for knee surgery, best opioid?

Fentanyl

56 yr old in MVA.. multiple inuries, on vent… 10 units PRBC, 5 platelets, and FFPs… Metabolic alkalosis on ABGs… ?
Citrate being converted to bicarb by liver, because liver is fine.
If liver failure… then citrate toxicity.

22 yr for hernia… 5 yrs back had CO poisoning. Which to avoid?

Desflurane

10 yr old, with testicular torsion, 6 hours back full meal taken…?

RSI

Halothane induction bradycardia  atropine  junctional tachycardia, why?

20 yr old trauma required more dose of propfol for induction… agitated, what to give to sedate without depressing resp?
Dexmed

Anorexia nervosa…
Phosphate

Spine surgery.. emergence… ETT bite, sats drop… pink frothy sputum.. this could have been avoided by?
Bite block

42 yr old man icu 65% burn.. analgesia by morphine and hydromorphone… sedation best agent?
Ketamine