Drug classes likely to be used in patient with head injury

Muscle relaxants
o
If the patient is unconscious due to head injury, then you have to put him on
ventilator, but to make the respiration comes only from the ventilator you have to
paralyze the respiratory muscles by giving muscle relaxants.

General anesthetics

Pre-anesthetic medication
o

Post-operative medications
o

are given before General Anesthetics (GA) to avoid the adverse effects of GA
to stop the effects of GA after the surgery is done.
IV mannitol
Muscle relaxants

This class of drugs is classified into neuromuscular blockers & spasmolytics
o
Spasmolytic are used to ↓ the tone of spastic muscle

Remember that spasm means ↑ muscle tone & it can be seen in disease
like tetanus & upper motor neurons & cerebral palsy & spinal shock.

It can be sub-classified into
Centrally acting
Directly acting – act directly
on muscle fibers
Diazepam
Dantrolene
Chlorzoxazone
Tizanidine
Baclofen
o
NM junction blockers used to ↓ the tone of normal muscle, it act NM junction
receptors.

It can be sub classified into
Non depolarizing = competitive blockers
Depolarizing (non-competitive)
D-tubocurarine
Succinylcholine
Pancuronium
Vecuronium
Atracurium

This is composed of two Ach
molecules so it is harder to break it
Mivacurium
by acetylcholinesterase (it will take
time)
Decamethomium


This class of drug consider as

competitive inhibitor
exposure to agonist) the nicotinic
Neostigmine (atropine a priori)
receptor to Ach
reverses the neuromuscular

blockage – remember the effect of
Fasciculation followed by flaccid
paralysis
competitive inhibitors can be

De-sensitizes (by continuous/repeated
o
Depolarizing agents initially
overcome by ↑ the level of the Ach
stimulate NM receptor, and
(physiological agonist) & tht can
so they cause muscle
be reached by inhibiting the
contraction  fasciculation
breakdown of Ach (inhibit
is observed in depolarizing
acetylcholinesterase)
agents. (cus there is entry
Causes flaccid paralysis ONLY
of Na)

This class shouldn’t be given to
patient w/ extensive burns or
extensive crush injuries of long
bones (both conditions causes
hyperkalemia) as they cause
liberation of K+& the drug itself ↑ K
level in blood  so its
contraindicated  cause cardiac
arrest  death.

Drugs tht end w/CURIUM can cause hypotension as they release
histamine so BP monitoring must be taken care off. Whereas drugs that
end w/CURONIUM are vagolytic (reduces the vagal tone “vagolytic
property”  abnormalities in CVS) & can inc the HR, BP by reducing the
affect of parasympathetic system
 Succinylcholine also results in increase of histamine release.
General anesthesia

Aiming to cause unconsciousness, analgesia, inhibition of autonomic reflexes, muscle
relaxation & amnesia – temporary loss of memory -. BUT no single drug can cause all of
these effects so usually combination of anesthetics is given.

Stages of general anesthesia are 4: analgesia, delirium, surgical anesthesia (this 3rd
stage is where we can operate on a patient & we shouldn’t increase the dosage in order
to avoid entrance to stage 4)& medullary paralysis (lethal stage).
o
st
Ether anesthetic was 1 GA used before, but now it’s only used for killing
animals. This ether is very slow GA.
o
When small dose of ether was given to humans, initially the patient was not
responding to pain  stage one “analgesia”
o
When some more amount of ether was administered, in addition to loss of pain
sensation the patient was found with Delirium  stage two “Delirium”
o
rd
When the patient was given further more ether, he went to the 3 stage which is
called “surgical anesthesia”

rd
In 3 stage: disturbance of respiration, so u need a ventilator, B.P & H.R.
are altered, and reflexes are abolished.
o
th
4 stage is called Medullary Depression depression of vasomotor & respiratory
centers – coma & death.

Phases of general anesthesia are:

Induction  we prefer administering
IV GA until we reach stage 3.

maintenance  we can use
inhalation GA alone or we can use it in
combination w/ low dose of IV GA.

emergence  phase we need to
reverse the effect of anesthetic drugs
(recovery).

Mechanism of general anesthetics is
either by stimulating GABA receptor, or by
blocking NMDA - The N-methyl-Daspartate receptor is a glutamate receptor
and ion channel protein found in nerve
cells- receptor. Blocking NMDA receptor
means getting analgesic effect.

The most commonly used for intravenous
GA are Benzodiazepines, Barbiturates, Propofol, Ketamine & Etomidate.
o
Barbiturates: it’s one of the drug w/ extensive
lipid solubility, immediate absorbed  enter
the brain fast  rapid onset & it reaches stage
3 in 30 sec. its only used for induction & we
will use benzodiazepines (cus when
barbiturate level start to go down their effect
will start)
o
are enzyme inducer and can also be used for
neonate Jaundice. *coz the neonates are very
poor liver reservoirs, the enzyme will be
deficienct and when there is hemolysis,
Jaundice will occur.

Causes central nervous system depression. They enhance the action of
GABA, a neurotransmitter that inhibits the activity of nerve cells in the brain.
o
Thiopental sodium & methohexital are Barbiturates used for GA purpose. They are
highly lipophilic which means they can cross the blood-brain-barrieir very effecienlty
Within 30 to 40 seconds they cross the BBB and act on the higher center and make
the patient unconscious, so their induction is very fast.
o
After 1 to 3 minutes, the blood concentration of Barbiturates will decline, so the
thiopental will come back from the brain to the blood and finlay distribute in muscles
& adipose tissues (redistribution)  this will happen around 10 minutes, the con. of
thiopental in the brain far lower than threshold level which is needed for causing
general anesthesia.  this why Barbiturates are short acting drugs.
Ketamine & nitrous oxide are NMDA receptor antagonists.
*Ketamine is the best analgesic agents among IV general anesthetics.
*nitrous oxide is the best analgesic agents among inhaled general anesthetics.
NO is highly soluble.
Mechanism of ketamine  NMDA receptor antagonist  In the pain pathway the
pain is transmitted from the 1st order neuron to 2nd ON thru NMDA receptor
stimulation by glutamate.

Ketamine – hemodynamically compromised patients; refractory status asthmaticus and
refractory bronchospasm;
Ketamine has sympathetic nervous system stimulation: advantage  vasoconstriction of
the blood vessels, its best in patients w/ hypotension, so we can use Ketamine as GA for
patient who has car accident, hypovolemia, BUT not in head injuries) also it leads to
bronchodilation  refractory status asthmaticus or refractory bronchospasm. (severe
asthma)
Muscle relaxed and eyes are closed in normal patient under GA. But if u see a patient
who is given Ketamine as GA, the patient will keep his eyes open and move his limbs
 Although the patient’s eyes are open, he is not conscious  Dissociation
between certain components of anesthesia  “Dissociative anesthesia”
Ketamine increases the intracranial tension, so it’s contraindicated in head injury.

Etomidate – minimal changes in the blood pressure, heart rate.

Complications of general anesthesia
o
Pre-anesthetic drugs are given before General Anesthetics (GA) to avoid the
adverse effects of GA. Post-operative drugs to stop the effects of GA after the
surgery is done.
During anesthesia
After anesthesia
Respiratory depression
Nausea & vomiting
Salivation, respiratory
Pneumonia
secretion
Persistent sedation
Aspiration
Organ damage (liver &
Hypotension
kidney)
Awareness
Delirium ‫هذيان‬

Pre-anesthetic medications TO:
Decrease secretions:

Anticholinergics-atropine

Glycopyrrolate
Relieve anxiety:

Benzodiazepines,Midazolam,
Supplement amnesia &

Diazepam
analgesia:

Lorazepam

Opioid,Morphine

pethidine

Histamine blockers
Decrease acidity, volume of
gastric juices & vomiting:
Ranitidine

Proton pump inhibitors
Omeprazole

Pantoprazole

Anti-emetics
Metoclopramide,


Ondansetron
Post-operative medications
In case of non-emergence w/
Flumazenil
benzodiazepines
Residual paralysis
Neostigmine (atropine a
priori)
Nausea & vomiting
Metoclopramide
Mannitol in head injury

Mannitol is sometimes effective in reversing acute brain swelling when given to ppl
w/increased ICP.Because it is osmotically active

It’s a diuretic, it has a large molecular weight so it can’t cross the capillaries  it ↑ osmolarity
of blood  fluid will move from hemorrhagic site into blood (it will shrink, ↓ ICP).

It has 2 mechanisms: 1) thru hyperosmolarity. 2) the hemorrhagic site reduces in size that
will ↑ blood flow to brain & allow more O2 to be delivered  & thru a reflex it will cause
vasoconstriction & reduce ICP.
o
Osmotic concentration gradient across BBB will lead to movement of free water
from IS space to IV compartment (from the brain to the BVs). Tht will reduce the
brain volume & dec the intracranial pressure
o
It can also optimize blood viscosity (improve the CBF) inc oxygen delivery, which will
lead to compensatory vasoconstriction. Dec cerebral blood volume & dec the ICP