Drugs For Local And General Anaesthesia

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general anesthesia involves

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1) ANALGESIA (opioids)
2) amnesia (barbs)
3)inhibition of reflexes
4)skeletal muscle relaxation (nueromuscular blocking agents)
5) rapid hypnosis (barbs)

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use a combination of drugs because

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no single drug can produce all 5 effects(analgesia, amnesia, inhbition of reflexes, skeletal muscle relaxation, & rapid hypnosis) & smaller doses of each drug can be used thus decreasing side effects

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Stage I of general anesthesia

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state of analgesia

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stage II of general anesthesia

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excitement

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stage III of general anesthesia

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surgical anesthesia ( 4 phases)

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stage IV of general anesthersia

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imminent death

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nitrous oxide

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inhaled gas anesthetic
dizziness, drowsiness, N/V
can cause malignant hyperthermia (tx with dantrolene), apnea, cyanosis

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Volitale liquid inhaled
general anesthetics

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desflurane
enflurane
halothane
isoflurane
mehoxyflurane
sevoflurane
drowsiness, N/V
can cause myocardial depression, marked hypotension, pulmonary vasoconstriction & hepatotoxicity

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MAC

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minimum alveolar concentration
how dosages are expressed of gases
potency of an inhaled anesthertic at the concentration in which 50% of patients do not move during surgery
% of gas mixture/760 mmHg pressure

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MAC

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steep dose-response curves
inversely propoortonal to potency
lower in elderly (not affected by sex/weight/etc)

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gas anesthetics MOA

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extremely lipophillic & their solubility disrupts the lipid bilayer of cells thus increasing the threshold to fire

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induction is inversely related to

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MAC potency

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MAC is influenced by

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pulmonary ventilation (affects speed of induction)
pulmonary blood flow (faster blood flow due to high BP/blood volume, anesthetic is not absorbed as rapidly, decrease MAC)
water solubility (increased water solubility will decrease MAC)

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general anesthetics pharmalogical effects

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block flow of Na+ channels
enhance GABA
delay impulses and reduce neural activity
produce unconsciousness
produce lack of responsiveness to painful stimuli

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IV anesthetics are used

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for short duration anesthesia for outpatient surgery
supplement inhalation anesthetics
to rapidly induce unconsciousness (administered 1st)

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IV anesthetics include

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barbs
BZDs
opioids
propofol
ketamine

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bards used as anesthetics

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thiopental
methohexital
they have a rapid onset, are potent but do not produce analgesia
produce amnesia & rapid hypnosis

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BZDs used as anesthetics

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diazepam
lorazepam
midazolam
produce sedation but not analgesia
produce amnesia

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hypnosis

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state that resembles sleep but that is induced

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opioids used as IV anesthetics

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fentanyl
good for intra-operative pain
produces good analgesia unlike barbs & BZDs!!

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propofol

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IV anesthetic
used for sedation for surgery or in ICU

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ketamine

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rarely used because it produces delusions
produces good analgesia unlike BZDs & Barbs

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analgesia

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absence of the sense of pain without loss of consciousness

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anesthetic

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Anesthesia: Loss of feeling or awareness. A general anesthetic puts the person to sleep. A local anesthetic causes loss of feeling in a part of the body such as a tooth or an area of skin without affecting consciousness.

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ketamine MOA

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ketamine is classified as an NMDA receptor antagonist.[2] At high, fully anesthetic level doses, ketamine has also been found to bind to opioid μ receptors and sigma receptors.[3][4] Like other drugs of this class such as tiletamine and phencyclidine (PCP), it induces a state referred to as "dissociative anesthesia"[5] and is used as a recreational drug.

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adjuncts to anesthesia

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barbs
opioids
anticholinergics
dopamine blockers
nueromuscular blockers

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promethazine

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# As a sedative.[3]
# For preoperative sedation and to counteract postnarcotic nausea.[
blurred vision, dry mouth
respiratory depression & agranuolysis

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promethazine MOA

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# Promethazine is a phenothiazine derivative that competitively blocks histamine H1 receptors without blocking the secretion of histamine. It also is a very weak dopamine antagonist.[6]
# It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects.[c

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barbs AEs

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drowsiness, lethargy, hang over effect
respiratory depression & larynospasam

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Units and Kinematics (KapCH1)

Final Velocity

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Vi + at

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anticholinergics

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Bethanechol is a parasympathomimetic choline ester that selectively stimulates muscarinic receptors (with further selectivity for M3 receptors) without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action.

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Bethanechol

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Bethanechol is sometimes given orally or subcutaneously to treat urinary retention resulting from general anesthetic or diabetic neuropathy of the bladder, or to treat gastrointestinal atony (lack of muscular tone). The muscarinic receptors in the bladder and gastrointestinal tract stimulate contraction of the bladder and expulsion of urine, and increased gastrointestinal motility, respectively. Bethanechol should be used to treat these disorders only after obstruction is ruled out as a possible cause.

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bethanechol AEs

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salvation, abdominal cramping, sweating
transient complete heart block

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opioids cause

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analgesia & sedation

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dopamine blocker

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droperidol
Droperidol (Droleptan, Dridol, Inapsine) is an antidopaminergic drug used as an antiemetic and antipsychotic. Droperidol is also often used for neuroleptanalgesic anesthesia and sedation in intensive-care treatment.

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droperidol AEs

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post-operative drowsiness, hypotension, tachycardia, EPS symptoms
langospasm & bronchospasm

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succinylcholine AEs

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respiratory depression, malginant hyperthermia, bradycardia, muscle fascitulations

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tubocuraine

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Tubocurarine is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. Unlike a number of other related skeletal muscle relaxants, it is now rarely considered clinically to facilitate endotracheal intubation.

Tubocurarine is classified as a long-duration,[1] non-depolarizing neuromuscular blocking agent that is a competitive antagonist of nicotinic neuromuscular acetylcholine receptors.[2]

Presently, tubocurarine is rarely used as an adjunct for clinical anesthesia because safer alternatives such as cisatracurium and rocuronium are available.

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tubocuraine AEs

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malignant hyperthermia, respiratory depression, apnea, hypotension

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local anesthetics

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amides (procaine)
esters (lidocaine)
stop axonal conduction by blocking Na+ channels

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ester local anesthetic

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procaine

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amide local anesthetic

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lidocaine

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local anesthetics contraindicated in

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CV conditions
antiarrhymatic properties

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local anesthetics are administered with

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vasconstrictors (NE) to concentrate their affect at site of INJ

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short-acting local anesthetic

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procaine (1 hour)

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intermediate acting local anesthetic

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lidocaine (1-2.5 hr)

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long acting local anesthetic

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tetracaine (3-9 hr)

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local anesthetics AEs

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anxiety, restlessness, blurred vision, seizures, CNS depression with unconsciousness followed by respiratory arrest
at high does, myocardial depression, bradycardia, arrhymias, hypotension, cardiac arrest
burning at INJ site
methemoglobinemia

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topical anesthetics

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benzocaine (main)
lidocaine
tetracaine

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muscle relaxants

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nueromuscular blockers & spasmolytics

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nueromuscular blockers

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used to cause paralysis, relax skeletal muscles during surgery, reduce muscle spasms, manage patients fighting mechanical ventilation

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spamolytics

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reduce spasticity in neurological disorders

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NMJ blockers

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nondepolaring agents (block Ach, do not cross BBB, used after anesthesia is induced)
depolarizing agents (succinlycholine) causes excessive depolarization which desnetizes muscles and renders them unresponsive

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nondepolarizaing NMJ blockers

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tuburocaine
pancuronium bromide
peipercuronium
vecuronium

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opium

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Opium (poppy tears, lachryma papaveris) is the dried latex obtained from opium poppies (Papaver somniferum). Opium contains up to 12% morphine, an opiate alkaloid, which is most frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids, such as papaverine, thebaine and noscapine.

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anticholinesterase inhbitors

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can reverse effects of tubercaine (nondepolarizing NMJ blocker)
neostigmine
pyridostigime
edrophonium

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spasiticity is associated with

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MS, cerebral palsy, & stroke
alpha motor nueron excitability causing increase tonic stretch relfexes, muscle spasms, & muscle weakenss

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spasmolytics

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skeletal muscle relaxing agent that relieve acute muscuoskeletal pain, spams, or spasticity

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central spamolytics

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carisoprodol
baclofen
diazepam
tizandine

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carisoprdol

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used to tx acute muscoskeletal condiction from trauma, inflammation & anxiety

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baclofen

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GABA analog acting at GABAb receptors
decreases frequency and degress of muscles spasms and reduces muscle tone
DOC because it produces less sedation than diazepam & less peripheral muscle weakness than dantrolene
use in paraplegic/quadraplegic pts with spinal cord lesions

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intrathecal baclofen

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used to management of severe pain when non-responsive to other routes of administration

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diazepam

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effective for acute spasma & chronic spasticity
indicated for spinal lesions/cerebral palsy
effective in paitents with cord transection
binds to BZDs receptors in spinal cord

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Tizanidine

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Tizanidine (brandnames Zanaflex, Sirdalud) is a drug that is used as a muscle relaxant. It is a centrally acting α-2 adrenergic agonist.(BOTH pre & post synaptically) It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or central nervous system.

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clonidine

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Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone.[5]

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peripheral spasmolytics

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dantrolene
works directly on muscle by inhibiting Ca2+ release
used in MS/cerebral palsy
tx malignant hyperthermia caused by general anesthetics

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general anesthesia

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whole body is asleep unlike local anesthesia
3 stages:
induction
maintenance
recovery

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nitrous oxide

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laughing gas

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stage I analgesia

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voluntary control of movements
no pain
used in dental operations

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stage II analgesia

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excitement
involuntary movements
irregrular respiration
muscles tense up
increase pupil size & eye reflexes
autonomic disturbances
dangerous (want to go from stage I-III)

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volatile liquids

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-flurane

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1 MAC

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50% of patients will not move during surgery

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1.3 MAC

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99% of patients will not move during surgery

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lipophilicity

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methoxyflurane>chloroform (not used flammable & carcinogen)>halothane>enflurane>diethyl ether>fluroxene>cyclopropane>xenon

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MOA of gas anesthetic theories

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- lipophillic they expand lipid membrane which leads to inactivation & lack of response from ion channels
-propogate GABA
-counter excitatory effects of NMDA receptors

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BZDs

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low dose - anti-anxiety
medium dose - sedation
higher dose - muscle relaxation & anesthesia
produce amnesia but not analgesia

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before anesthesia adminster

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anti-cholinergics (want to dry up secretions and ease transition into stage III) & anti-anxiety meds

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during anesthesia adminster

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muscle relaxants

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post-anesthesia administer

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opioids for post-operative pain (morphine)
antibiotics

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methemoblginemia

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AE of local anesthetics
higher levels of methemoglobin which unlike hemoglobin does not bind O2 causing tissue hypoxia
blood is brown

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for acute muscle spasms

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carisoprodol

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dantrolene

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depressed excitation-contraction coupling in skeletal muscle by binding to ryanodine receptor and decreasing intracellular Ca2+
acts peripherially
used in muscle spascity following strokes, paraplegia, cerebral palsy, and MS)