Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
general and local anesthesia
1. General and local anesthesia
Prepared by SONAL VIJAY PANDE
MPHARM
DEPARTMENT : PHARMACOLOGY
2. What is Anaesthesia ???
Anesthesia – is a reversible condition of comfort and quiescence for a patient
within the physiological limit before, during and after performance of a
procedure.
Types of anesthesia
General anesthesia
Local anesthesia
3. General anesthesia – for surgical procedure to render the patient
unaware/unresponsive to the painful stimuli.
Drugs producing General Anaesthesia – are called General
Anaesthetics
Local anesthesia - reversible inhibition of impulse generation and
propagation in nerves. In sensory
nerves, such an effect is desired when painful procedures must
be performed, e.g., surgical or dental operations.
Drugs producing Local Anaesthesia – are called Local
Anaesthetics e.g. Procaine, Lidocaine and Bupivacaine etc.
4. DIFFERENCE BETWEEN GENERAL ANAESTHESIA &
LOCAL ANAESTHESIA
FEATURES Gen.Anaesthsia Local Anaesthsia
• Site of action CNS Peripheral nerves
• Area of body involved Whole body Restricted area
• Consciousness Lost Unaltered
• Care of vital functions Essential Usually not needed
• Poor health patients Risky Safer
• Use in non cooperative
patients Possible Not possible
• Major surgery Preferred Cannot be preferred
• Minor surgery Not preferred preferred
5. General anesthesia
General Anaesthetics are the drugs which produce
reversible loss of all modalities of sensation and
consciousness, or simply, a drug that brings about a
reversible loss of consciousness.
General anaesthetics are – mainly inhalation or
intravenous.
These drugs are generally administered by an
anesthesiologist in order to induce or maintain general
anesthesia to facilitate surgery.
7. Stage 1 analgesia
Starts from beginning of anaesthetic inhalation and lasts
upto the loss of consciousness
Pain is progressively abolished during this stage
Patient remains conscious, can hear and see, and feels a
dream like state
Reflexes and respiration remain normal
It is difficult to maintain - use is limited to short
procedures only
8. From loss of consciousness to beginning of regular respiration
Excitement - patient may shout, struggle and hold his breath
Muscle tone increases, jaws are tightly closed.
Breathing is jerky; vomiting, involuntary micturition or defecation
may occur.
Heart rate and BP may rise and pupils dilate due to sympathetic
stimulation.
No stimulus or operative procedure carried out during this stage.
Breatholding are commonly seen. Potentially dangerous responses
can occur during this stage including vomiting, laryngospasm and
uncontrolled movement.
This stage is not found with modern anaesthesia – preanaesthetic
medication, rapid induction etc.
StageII: Stageof Deliriumand Excitement
9. Extends from onset of regular respiration to cessation of
spontaneous breathing.
This has been divided into 4 planes: Plane
1: Roving eye balls. This plane ends when eyes become
fixed.
Plane 2: Loss of corneal and laryngeal reflexes.
Plane 3: Pupil starts dilating and light reflex is lost
.
Plane 4: Intercostal paralysis, shallow abdominal
respiration, dilated pupil.
Stage III Stageof Surgicalanaesthesia
10. Cessation of breathing failure of circulation death
Pupils: widely dilated
Muscles are totally flabby
Pulse is imperceptible
BP is very low.
Stage IV Medullary/ respiratory paralysis
11. Theories
The three main theories of general anaesthseia
LIPID THEORY
PROTEIN THEORY
BIOCHEMICAL THEORY
12. LIPID THEORY
Suggests that the anesthetic acts nonspecifically on the lipid
portions of the neuronal membrane to cause a general
disturbance that causes the ion channels to change structure
thereby changing their function.
Interactions here cause a physical change in the membrane
13. MAYER AND OVERTON THEORY
Mayer and Overton separate studies identically
postulated that anaesthetic potency varies with the lipid
solubility.
More the lipid soluble a drug is the greater is its
anaesthetic potency.
This theory does not suggest any particular mechanism
but reflects only capacity of anaesthetic agent to enter
into CNS and attain sufficient concentration in neuronal
membrane.
It is now known that all highly lipid soluble substance s
are not anaesthetics and some potent anaesthetic are not
lipid soluble.
Various lipid theory are given below
14. PAULING AND MILLER THEORY/HYDRATE
THEORY
This theory was given in 1961 .
According to this theory simple molecules like water
may be linked together by hydrogen bonding to form ice
like structures which are occupied by anaesthetic agent
to form anaesthetic hydrate crystals .
These hydrates could then impede ionic mobility,
electrical charge, and chemical and enzymatic activity
of the brain to produce depression and unconsciousness.
This theory does not explain anaesthesia produce by
barbiturate and some other anesthesia
15. MEMBRANE EXPANSION THEORY
This theory postulates that anaesthetic molecules
penetrate into hydrophobic region of the cell membrane
and causes its expansion.
The mechanism of membrane expansion has not been fully
explained but may be attributable to formation of
hydrates.
16. MEMBRANE FLUIDISATION THEORY/
LATERAL PHASE SEPARATION THEORY
This theory postulates that anaesthetic agents by
dissolving in the membrane lipids cause loosening
or fluidisation of lipid bilayer region of the
membrane .
17. PROTEIN THEORY
This theory suggests that the anaesthetic must act
specifically with hydrophobic pockets on certain
membrane proteins to produce the effect
Lock and Key
Problem: Too many keys that would have to all fit the
same lock
18. BIOCHEMICAL THEORY
A number of biochemical theories have also been
postulated and reviewed .
These include- inhibition of glucose metabolism in
brain cells, interference in production of ATP.
Interference in oxygen utilization and cellular
respiration.
20. Mechanism
For inhalation anesthetics
Minimum Alveolar Concentration (MAC) – 1 (one) MAC is defined as the
minimum alveolar concentration that prevents movement in response to
surgical stimulation in 50% of subjects. Correlates with oil/gas partition
coefficient
Practically – Alveolar concentrations can be monitored continuously by
measuring end-tidal anesthetic concentration using spectrometry
End point (immobilization) – can me measured
. Other end points – Verbal commands or memory etc.
21. For Intravenous agents
Potency of IV agent is defined as the free plasma
concentration (at equilibrium) that produces loss of
response to surgical incision in 50% of subjects.
Difficult to measure:
no available method to measure blood or plasma
concentration continuously
Free concentration at site of action cannot be
determined (MAC explains only capacity of anaesthetics
to enter in CNS and attain sufficient concentration, but
not actual MOA)
22. Properties of General anesthesia
For Patient: -
Pleasant, non-irritating and should not cause
nausea or vomiting –
Induction and recovery should be fast
For Surgeon: - analgesia, immobility and muscle
relaxation - nonexplosive and noninflammable
For the anaesthetist:
1. Margin of safety: No fall in BP
2. Heart, liver and other organs: No affect
3. Potent
4. Cheap, stable and easily stored
5. Should not react with rubber tubing or soda lime
6. Rapid adjustment of depth of anaesthesia should
be possible
23. Diethyl ether (C2H5 – O – C2H5)
o Colourless, highly volatile liquid with a pungent odour.
o Boiling point = 35ºC, Produces irritating vapours and are
inflammable and explosive.
Pharmacokinetics: - 85 to 90 percent is eliminated through lung
and remainder through skin, urine, milk and sweat - Can cross the
placental barrier Ether – contd.
Advantages - Can be used without complicated apparatus - Potent
anaesthetic and good analgesic - Muscle relaxation - Wide safety of
margin - Respiratory stimulation and bronchodilatation - Does not
sensitize the heart to adrenaline - No cardiac arrythmias - Can be
used in delivery - Less likely hepato or nephrotoxicity
Disadvantages - Inflammable and explosive - Slow induction and
unpleasant - Struggling, breath holding, salivation and secretions
(drowning) - atropine - Slow recovery – nausea & vomiting - Cardiac
arrest - Convulsion in children - Cross tolerance – ethyl alcohol
24. Nitrous oxide/laughing gas (N2O)
NH4NO3 (s) → 2 H2O (g) + N2O (g)
Colourless, odourless inorganic gas with sweet taste
Noninflammable and nonirritating, but of low potency
Very potent analgesic, but not potent anaesthetic
Carrier and adjuvant to other anaesthetics – 70% + 25-30%
+ 0.2-2%
As a single agent used wit O2 in dental extraction and in
obstetrics
Advantages: -
Non-inflammable and nonirritant –
Rapid induction and recovery
- Very potent analgesic (low concentration)
- No effect on heart rate and respiration – mixture advantage
- No nausea and vomiting – post anaesthetic not marked -
Nontoxic to liver, kidney and brain
25. Disadvantages:
Not potent alone (supplementation)
Not good muscle relaxant, not
Hypoxia, unconsciousness cannot be produced without
hypoxia
Inhibits methionine synthetase (precursor to DNA
synthesis)
Inhibits vitamin B-12 metabolism
Dentists, OR personnel, abusers at risk
Gas filled spaces expansion
26. Halothane
Fluorinated volatile liquid with sweet odour, nonirritant non-
inflammable and supplied in amber coloured bottle
Potent anaesthetic (if precise control), 2-4% for induction and 0.5-1%
for maintenance
Boiling point - 50ºC
Pharmacokinetics: 60 to 80% eliminated unchanged. 20% retained in
body for 24 hours and metabolized
Delivered by the use of a special vapourizer
Not good analgesic or relaxants Potentiates NM blockers
Advantages: -
Non-inflammable and nonirritant –
Abolition of Pharyngeal and laryngeal reflexes
bronchodilatation – preferred in asthmatics
Potent and speedy induction & recovery
Controlled hypotension
27. Disadvantages: -
Special apparatus - vapourizer –
Poor analgesic and muscle relaxation –
Myocardial depression – direct depression of Ca++ and also failure of
sympathetic activity – reduced cardiac output (more and more)
Hypotension – as depth increases and dilatation of vascular beds –
Heart rate – reduced due to vagal stimulation, direct depression of SA
node and lack of Baroreceptor stimulation - Arrythmia - Sensitize
heart to Adrenaline - Respiratory depression – shallow breathing (PP
of CO2 rises) assisted ventilation –
Decreased urine formation – due to decreased gfr - Hepatitis: 1 in
10,000 –
Malignant hyperthermia: Abnormal Ryanodine receptor - Prolong
labour
Inhibits intestinal and uterine contractions – external or internal
version
- - Popular anaesthetic in developig countries - can be used in
children for induction and maintenance and adult maintenance
28. Enflurane:
Non-inflammable, with mild sweet odour and boils at
57ºC
Similar to halothane in action, except better muscular
relaxation
Depresses myocardial force of contraction and sensitize
heart to adrenaline
Induces seizure in deep anaesthesia and therefore not
used now - Epileptiform EEG
Metabolism one-tenth that of halothane-- does not
release quantity of hepatotoxic metabolites
Metabolism releases fluoride ion-- renal toxicity
29. Isoflurane:
Isomer of enflurane and have similar properties but
slightly more potent
Induction dose is 1.5 – 3% and maintenance dose is 1
– 2%
Rapid induction (7-10 min) and recovery By special
vapourizer
30. LOCAL ANESTHESIA
DEFINITION:
They are drugs which, when applied directly to
peripheral nervous tissue, block the nerve
conduction and abolish all sensations in the part
supplied by the nerve without loss of
consciousness.
All local anesthetics are weak bases, they have
amphiphilic properties
31. FEATURES OF LOCAL
ANAESTHETICS
Should have quick onset of action
Should have low Systemic toxicity
Duration of action must be long enough to allow
desired surgery to be completed
Should be effective on both injection & local
application
32. INJECTABL ANAESTHETIC
Low potency short
duration
• procaine
chloroprocaine
Intermediate
potency and
duration
• Lidocaine
prilocaine
High potency and
long duration
• tetracaine
• bupivacaine
• ropivacaine
• dibucaine
34. MECHANISM OF ACTION OF LAs
LA blocks the nerve conduction by reducing entry of
Na+ through the voltage gated channels
Due to this, they block the initiation & propagation of
nerve impulse.
At higher doses it also blocks 1. Voltage gated Ca2+
channels 2. K+ channels
35.
36. PHARMACOKINETICS Absorption Local anesthetics are absorbed
when ingested. Some local anesthetics may be absorbed in toxic
amounts after topical use. Absorption after an injection depends
on drug solubility in lipid and in water, tissue vascularity and local
anesthetic and vasoconstrictor effects on local circulation.
Distribution: amides-wide distribution –I.V-lipophilics taken up by
highly perfused organs-then moderately perfused Ester type- short
plasma half life
Metabolism and excretion Esters are hydrolyzed by plasma and
liver esterases. Longer-acting esters are often metabolized more
slowly.. Patients with altered pseudo-cholinesterase activity may be
highly sensitive to these drugs. Amides are metabolized in the liver
by cyp450.-Ndealkylation then hydrolysis except prilocainehydrolysis
first-o toludine-can cause methhamoglobinemia
37.
38.
39. Techniques of Local Anaesthesia
Surface Anaesthesia
Application of a local anesthetic to nose, mouth, throat, tracheobronchial
tree, esophagus. Onset & duration depends on the site, the drug, its
concentration and form. Absorption of soluble LAs from mucous membrane
is rapid.
40. Infiltration Anaesthesia
Injection of LA directly into tissue under the skin. used primarily
for surgical procedures. LAs most frequently used are lidocaine
(1%), bupivacaine (0.25%), etidocaine(0.5-1%), ropivacaine(0.5-1%),
mepivacaine(1-3%) and prilocaine(1-4%). mix with adrenaline
(1:20000) to prolong the action
41. Conduction block:
Injected around nerve trunks so that area
distal to injection is anaesthetised and
paralyzed.
Choice of LA and concentration is mainly
determined by the required duration of
action.
Lidocaine for intermediate duration of
action.
longer lasting anesthesia bupivacaine may
be selected.
42. Field block: - produced by injecting the LA subcutaneously in the
surrounding area of nerve so that all nerves coming to particular
field are blocked. - herniorrhaphy, appendicectomy, dental
procedures, scalp stitching, operations on forearms and legs etc. -
- Larger area can be anaesthetized with lesser drug compared to
infiltration.
Nerve Block:
local anesthetic is injected around a nerve that leads to the
operative site.
Usually more concentrated forms of local anesthetic solutions are
used eg: radial nerve block, ulner nerve block so on. Nerve
block lasts than field block or infiltration anaesthesia. Lidocaine
(1.5%), mepivacaine(1.5%), bupivacaine (0.25- 0.35%) can be used.
43. Epidural Anaesthesia.
Spinal dural space is filled with semi liquid fat
through which nerve root travel. Injected in
this space- acts primarily on nerve roots and
small amounts permeates through
intravertebral foramina to produce multiple
paravertebral blocks. used to produce
analgesia or anaesthesia in surgical and
obstretric.
Divided into 3 categories depending on site of
action:
1. Thoracic:
2. Lumbar:
3. Caudal:
44. Spinal Anaesthesia
Injected into the subarachnoid space between L2-3 or L3-4 of the
spinal cord . Suitable LA like lidocaine (3-5%), bupivacaine (0.5-
0.8%), tetracaine(0.3-0.5%). Primary site of action is cauda equina
rather than spinal cord. Used to anaesthetize lower abdomen and
hind limbs.
45. Advantages over general anaesthesia are: Safer Produces
good analgesia and muscle relaxation without loss of
consciousness. Cardiac, pulmonary, renal disease and
diabetic pose less problem
Complication of spinal anaesthesia: Respiratory paralysis
Hypotension Headache Cauda equina syndrome Septic
meningitis Contraindications: Hypotension & hypovolemia
Infant & childrens- control of level is difficult Vertebral
abnormalities - kyphosis
46. Intravenous regional anaesthesia
Also referred as Bier’s block & used for upper limb and orthopedic
procedures. Regional analgesia produced within 2-5min and last
till 5- 10min. Only ¼ of the injected drug enters systemic
circulation when tourniquet is removed. Bradycardia can occur
and bupivacaine should not be used because of higher cardio
toxicity
47. Should not cause any permanent damage on any tissue.
Should be relatively free from producing allergic reaction.
Should be stable in solution and readily undergo
biotransformation.