SEDATIVE HYPNOTICS

- RAMELTEON : not metabolized by CYP3A4

- RAMELTEON and BUSPIRONE: active metabolites
MOA
BENZODIAZEPINES
-Shorter half-lives direct to Phase II (conjugation)
■ Estazolam, Lorazepam, Oxazepam (mnemonic: ELO)
Enhance the inhibitory effects of
GABA
GABAA receptor-chloride ion channel
Major isoform: 2 α1, 2 β2 and 1 γ2
subunits
GABAA receptor for GABA: a1, b2
BZ site: a1, y2
A1 - sedation, amnesia, ataxic effects
(zolpidem, zaleplon, eszopiclone)
A2 and a3 - anxiolytic and muscle
relaxing actions
A5 - memory impairment
PHARMACOKINETICS INDICATIONS AE CI
Sedation Enhance Porphyrin Synthesis
○ Euphoria
○ Anterograde amnesia
Anesthesia
○ Adjunct in general anesthesia
○ Rapid tissue redistribution
Muscle Relaxation
○ Inhibit polysynaptic reflexes and
internuncial transmission’
Anticonvulsant Effect
○ Benzodiazepines: Clonazepam
(absence seizure), Lorazepam,
Diazepam (drug of choice for status
epilepticus)
○ Barbiturates: Phenobarbital,
Metharbital

FLUMAZENIL Benzodiazepine antagonist Abstinence symptoms in

dependent patients
Competitive antagonism at GABAA
receptor
NEW ANXIOLYTICS
BUSPIRONE For relief of anxiety Not for panic states NO marked sedation/euphoria

Partial agonist at 5-HT1A receptor

Facilitate GABA-mediated inhibition at GABAA receptor sites

■ Direct activation
● Inhaled anesthetics, barbiturates, etomidate, propofol
○ Facilitate GABA action:
■ Benzodiazepines, inhaled anesthetics
■ Barbiturates, etomidate, propofol (low concentration)
○ Antagonist at NMDA receptor (glutamate receptor)
■ Ketamine, possibly nitrous oxide

MOA PHARMACOKINETICS INDICATIONS AE CI

GENERAL ANESTHETICS
Synapse as prime focus of anesthetic - Elimination (HESIDN) DESFLURANE: most volatile Nephrotoxicity; enflurane,
effect: :Halothane > enflurane > sevoflurane
○ PRESYNAPTIC - alter release of sevoflurane > isoflurane > Hepatotoxicity: halothane
neurotransmitters desflurane >N2O
○ POSTSYNAPTIC - change frequency
or amplitude of impulses Anesthetics with LOW blood solubility
from the synapse - Desflurane, Nitrous oxide
 Anesthetics with MODERATE to HIGH
blood solubility
- Methoxyflurane, halothane
Depress cardiac contractility → ↓
arterial BP
- Halothane and enflurane >
isoflurane, desflurane,
sevoflurane
Peripheral vasodilation and minimal
effect on CO: isoflurane, desflurane,
sevoflurane

Baroreceptor Reflex ( ↓ BP⟶ ↑ HR)

■ Depressed by halothane, enflurane,
sevoflurane
■ Unaffected by isoflurane, and
desflurane
MALIGNANT HYPERTHERMIA
DANTROLENE DOC Muscle weakness
A spasmolytic Sedation
Interferes with the release of calcium Occasional hepatitis
from the sarcoplasmic reticulum via
ryanodine receptor channel (RyR1)
INTRAVENOUS ANESTHETICS
THIOPENTAL Ultra-short-acting
Taste of garlic evoked just prior to
inducing anesthesia

Methohexital:excitement phenomena

GIVE RECTAL PARA 10 FOLD NG IV

PROPOFOL Rapidly metabolized in Liver, Kidney, Most widely-used IV anesthetic
Lungs ● Rapid induction and awakening
● ↓cerebral blood flow and ICP
X analgesic and amnesic prop
FENTANYL Opioid analgesic:μ receptor agonist High-dose used for cardiovascular
anesthesia
balanced anesthesia
ETOMIDATE Hemodynamic stability Effect Terminated By Redistribution
Cerebral Protection
KETAMINE NMDA receptor antagonism Intracranial effects Catalepsy, sympathetic
○ Blocks membrane effects of the ○ ↑ ↑ ↑: cerebral blood flow, O2 stimulation, profound analgesia
excitatory glutamate consumption, ICP and agitation
● Respiratory effects
○ ↓ respiratory rate
○ Maintains airway muscle tone
○ Usually preserves airway reflexes

S(+) stereoisomer is more potent than

the R(-)
DEXMEDETOMIDI Alpha2 adrenergic agonist Maintains spontaneous respirations
NE ○ Hypnosis/Sedation: Locus
coeruleus in the brain
○ Analgesia: spinal cord
 1600-fold greater selectivity for α2
than α1

LOCAL ANESTHETICS
Differential Block:all nerves can be blocked by LAs
○ Desired block: sensory ± motor block
○ Sympathetic NS blockade
■ Hypotension
■ Urinary retention

State-dependent and use-dependent mechanism of LA

■ Sensory fibers: rapid firing and long duration of AP
■ Motor fibers: slow firing and shorter duration of AP
■ A delta and C fibers for pain are rapid firing: blocked earlier

ESTERS
- Prototype: procaine (basta isang i lang)
- Butyrylcholinesterase
- Allergic rxn bc: PABA
- metab : liver and plasma
ARTICAINE Blockade of voltage-gated sodium Persistent paresthesia
channels
BENZOCAINE Atypical kasi walang side chain pota Potential for methemoglobinemia
COCAINE EENT use systemic toxicity
AMIDES
- Prototype: Lidocaine
- Metab: liver only
- Alt for those with PABA allergy
- Rate of metabolism
- ■ Prilocaine (fastest) > lidocaine > mepivacaine > ropivacaine= bupivacaine = levobupivacaine (slowest/long-acting)

BUPIVACAINE Spinal anesthesia Cardiotoxicity

Epidural anesthesia

LEVOBUPIVACAINE S(-) enantiomer of bupivacaine Epidural anesthesia Epidural anesthesia

○ Labor ○ Labor
○ Post-operative pain control ○ Post-operative pain control
○ Caudal block in children ○ Caudal block in children

LIDOCAINE TNS with spinal anesthesia

● Used in arrhythmias
● Used in suppressing responses
to laryngoscopy and extubation
ROPIVACAINE S(-) enantiomer in a homologous Epidural analgesia for labor and
series that include bupivacaine and postoperative pain control
mepivacaine