Local anesthetics and analgesics

Bupivicaine and Tetracaine

High pKa, moderate rate of onset but LONG duration

1. Membrane expansion theory: lipophilic  anesthetics inciorporate themselves into membrane

• 2. (Major) receptor mechanism: physical occulsion of na channel
•                   a. allosterically mediated
•                   b. distort local electrical field

Physiochemical interaction of the base form with membrane

Autonomic loss first (that is why we give epi to constrict because autonomics shutdown)

Temp>Pain>Touch>Pressure>Motor

• 1. fiber length
• 2. use-dependent block
• 3. peripheral nerve organization
• 4. local anesthetic selectivity

Vasoconstrictors slow

Sympathomimetic agents are topically ineffective

• 1.bind to plasma proteins
• 2. Unbound diffuses to tissues freely
• 3. Enter CNS and can cross placenta
•              a. lido, prilo, etido Cat B
•              b. Mepiv, Bupi Cat C

Esters by plasma cholinesterase

Amides by hepatic oxidase system (lido T1/2 1.5-3.5hrs but Tetra is 25 minutes because it has an ester)

Metabolite of prilocaine, articaine, benzocaine (O-toluidine) can cause methehemeglobinemia

Lido has some metabolites too that are toxic

Renal

Inversely to their protein binding

Inversely to the pH of urin

Lipophilic ones like etido and bupivacaine

depress myocardial contractility

note: locally do affect myogenic activity and autonomic tone

Based on child's body weight

Or Young's rule which is based on patient's age

7mg/kg max of 500mg

lido no epi 3mg/kg 300mg max

• 1. Local anest
• 2. Vasoconstrictor
• 3. Metabisulfite (only if epi present)
• 4. Isotonic NaCl
• 5. HCL or NaOH to adjust pH

CNS acting agents can cause permanent deficits

potential elevation of BP with tricyclic antidep

NO interaction with epi and MOA

also...alpha blocker (epi reversal=hypotension)

beta blocker (vasoconstriction with epi causing hypertension)

alpha-adrenergic blocking agent, vasodilates removes anesthetic quicker from site

BUT will not reverse CNS and cardio effects

Paresthesia

Antipyretic, analgesic, antiinflammatory, antiplatelet

Can cause analgesic nephropathy, reye's syndrome, GI bleeding

Diflunisal: derivative of salicylic acid

not metabolized to salicylate

extended duration

Tinnitis, nausea, headache, hyperventiliation, confusion

IRREVERSIBLE binding to COX

Hyperthermia, respiratory alkalosis, acidosis

TX: alkalization of urine, gastric lavage, respiratory support

Rhinitis to severe asthma because lipoxygenase pathway is predominating

DO NOT switch to NSAIDs since they are cross-sensitive

antipyretic, analgesic, but little antiinflammatory effects (that is it is good for aspirin sensitive folks, no COX blocking)

Hepatotoxicity (metabolite n-acetyl-benzoquinoneimine), max 4g/day

Tx: gastric lavage, within 36hrs give n-acetylcysteine

like aspirin

adverse effects like aspirin but REVERSIBLY binds to COX

ALL NSAIDS have ceiling effect! you give more and less therapy but more side effects

Renal disease

Hematologic malignancies w/thrombocytopenia

Asthma/nasal polyps

NSAID mainly formulated for IV use

no more than 5 days due to risk of renal toxicity, has anitplatelet activity

Papaver somniferm

10-12% morphine

.5-1% codeine

alkaloids derived and isolated from opium

Morphine like pharm properties but not derived from opium

This and opiates are now called opioid analgesics

Opium, morphine, codeine

Heroin, hydromorphone, hydrocodone, oxycodone

Meperidine, Fentanyl, sufentanyl (extremely potent, the last two)

Naloxone, Naltrexone

Endorphins>dynorphins>enkephalins

Four types, many subtypes

• Main is mu
•  mu1 is supraspinal
•  mu2 is spinal analgeisa

Central and peripheral (not neuropathic or sharp)

no ceiling effects

effective against continuous, dull, aching pain

• 1. dec sensitivity to pain
• 2. reduced ability to clear morphine
• 3. more pain relief with dose compared to younger patient

Dec in tidal volume and rate

dec response of brainstem to CO2 tension

supress respiration

Side effect, but wanted

codeine and dextrometrophan

supression is lower does than needed for analgesic eeffect or respiratory effect

No tolerance to this excitation

pinpoint pupils in addicts

Vomiting, stimulate CTZ in medulla causing emesis

vestibular component, if patient lays down all good but not when walking

Constipation, inc sm tone and dec propulsive motility

Billary spasms, inhibits intestinal hypersecretion (great for diarrhea tx)

Dec urine flow due to effects on sm cells of ureter, bladder, uterus

bronchoconstriction

May propentiate, due to histamine release

Dec BP due to hypoxia (vasodilation to counteract)

Dec peripheral vascular tone (helps in pulmonary edema)

Orthostatic hypotension

Cerebral vasodilation

Analgesia

Pulmonary edema

Inducing sleep

Inc oral effectiveness (60% bioavailable)due to methoxy group

analgesic postoperative (30-60mg), antitussive (15-20mg)

10 morphine=120mg codeine

biotransformation is inhibited by cimetidine or antidepressants

onset 30-45mins

Poor CV stability during IV

Acute intoxication is CNS excitation (tremors, convulsions opposite of coma and stupor with morphine)

must be given IV, poor orally

Less pupillary and billary due to atropine like activity

80-100 times more potent due to lipid soluble, short duration of action

ADVantage: cardiac stability, reduces endocrine response to surgery

Short acting IV admin

antidote for respiratory depression

Long acting- oral admin

48-72 hrs effectiveness

agonist at K and partial agonist or weak antagonist at mu recpetors

new drug Talwin has this and naloxone to prevent injection abuse.

Less potent than morphine

Can increase HR and BP, unlike other opioids

does not cause as severe resp depression

weak Mu agonist and reuptake of NE and 5HT

mod-severe pain, good orally

n/v and drowsiness common side effects

Opioid agonist and inhibits NE reuptake

schedule II drug

not first line drug

Analgesic: mobilizes endogenous opioids

Anxiolytic: GABA inhibition

Rapid induction and recovery

High MAC 100% low potency, can be titrated

protects cough reflex

n/v worsened by longer duration, inc concentration, or fluctations of administration

fasting not necesssary but light meal recommeneded

drowsiness, relaxation, calmness, dev motor activity with no loss of consciousness

loss of unconsciousness that resembles natural sleep, dec motoractivity, impaired sensory responsiveness

Diazepam and Midazolam

Diazepam and chlordiazepoxide

alprazolam, diazepam, triazolam, oxazepam

site of action is subcortical but evidence of spinal interneurons are also affected

respiratory depression and apnea, worse with opioid

Drowsiness

CNS depression (elderly more susceptible)

inc incidence of nightmares, hyperactivity, insomnia

paradoxical excitement

Hydroxyzine and Promethazine,

Antiemetic, antihistamines

hydroxy: also anticholinergic

(e.g. SOMATOFORM PAIN DISORDER and MUNCHAUSEN SYNDROME.