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BENZODIAZEPINES PREOPERATIVE MEDICATIONS

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Discuss the principal pharmacologic effects of benzodiazepines. ... Buccal: (0.07 mg/Kg) Sublingual: (0.1 mg/Kg) Premedication IM: (0.07-0.15 mg/Kg) ... – PowerPoint PPT presentation

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Title: BENZODIAZEPINES PREOPERATIVE MEDICATIONS


1
BENZODIAZEPINESPREOPERATIVE MEDICATIONS
  • DENNIS STEVENS MSN, CRNA, ARNP
  • OCTOBER 2005
  • FLORIDA INTERNATIONAL UNIVERSITY
  • PHARMACOLOGY OF ANESTHESIOLOGY NURSING
  • NGR 6173

2
OBJECTIVES
  • Discuss the principal pharmacologic effects of
    benzodiazepines.
  • Explain mechanism of action associated with
    benzodiazepines and their interaction with the
    CNS.
  • Compare the unique chemical structure of
    midazolam and how it differs at various pH
    levels.
  • Discuss the pharmacokinetic properties specific
    to benzodiazepines.
  • Explain the effects on organ systems of
    benzodiazepines.
  • State the clinical indications of midazolam and
    diazepam.
  • Discuss the action and dosing regime of
    flumazenil.

3
REFERENCES
  • Morgan, G.E., Mikhail, M.S., and Murray, M.J.
    (2002).
  • Clinical Anesthesiology. (3rd Ed.) New York, NY
  • McGraw-Hill.
  • Nagelhout, J.J. and Zaglaniczny, K.L. (2005).
    Nurse Anesthesia. (3rd Ed.) St. Louis, MO
    Elsevier-Saunders.
  • Stoelting, R.K. (1999). Pharmacology Physiology
    in Anesthetic Practice. (3rd Ed.) Philadelphia,
    PA
  • J.B. Lippincott Company.

4
CLINICAL CONSIDERATIONS
  • Benzodiazepines exert five principal
    pharmacologic effects
  • Sedation
  • Anxiolysis
  • Anticonvulsant actions
  • Spinal cord-mediated skeletal muscle relaxation
  • Anterograde amnesia
  • Benzodiazepines have replaced barbiturates for
    preoperative medication and production of
    sedation during monitored anesthesia care

5
MECHANISM OF ACTION
  • Benzodiazepines interact with specific receptors
    in the central nervous system
  • Benzodiazepine-receptor binding enhances the
    inhibitory effects of various neurotransmitters
  • Facilitates GABA receptor binding which increases
    the membrane conductance of chloride ions
  • Causes a change in membrane polarization that
    inhibits normal neuronal function
  • Receptor occupancy
  • Receptor subtypes

6
STRUCTURE-ACTIVITY RELATIONSHIPS
  • Benzodiazepines are similar structurally and
    share many active metabolites
  • Benzodiazepine refers to the portion of the
    chemical structured composed of a benzene ring
    fused to a seven-membered diazepine ring
  • Substitutions at various positions on these rings
    affect potency and biotransformation
  • Benzodiazepines differ markedly in speed that
    they are metabolized and eliminated

7
CHEMICAL STRUCTUREDIAZEPAM LORAZEPAM
8
CHEMICAL STRUCTUREMIDAZOLAM
9
PHARMACOKINETICS
  • Absorption
  • Commonly administered orally, intramuscularly,
    and intravenously
  • Diazepam and lorazepam are well absorbed from the
    GI tract, peak plasma levels usually achieved in
    1 and 2 hours
  • IM injection of diazepam is painful and
    unreliable
  • Oral midazolam popular for pediatric
    premedication
  • Intranasal (0.2-0.3 mg/Kg)
  • Buccal (0.07 mg/Kg)
  • Sublingual (0.1 mg/Kg)
  • Premedication IM (0.07-0.15 mg/Kg)
  • Sedation IV (0.01-0.1 mg/Kg)

10
PHARMACOKINETICS
  • Distribution
  • Diazepam quite lipid-soluble and rapidly
    penetrates the blood brain barrier
  • Midazolam water-soluble at low pH and at
    physiologic pH increase in its lipid solubility
  • Moderate lipid solubility of lorazepam
  • Redistribution fairly rapid for the
    benzodiazepines
  • Benzodiazepines highly protein-bound

11
BIOTRANSFORMATION AND EXCRETION
  • Rely on the liver for biotransformation into
    water-soluble glucuronide end products
  • Phase I metabolites of diazepam are
    pharmacologically active
  • Elimination half-life time necessary to
    eliminate 50 of a drug from the body after its
    rapid IV injection
  • Long elimination half-life for diazepam
  • Lorazepam shorter elimination half-life
  • Midazolam shortest elimination half-life
  • Metabolites of benzodiazepine biotransformation
    are excreted chiefly in the urine

12
EFFECTS ON ORGAN SYSTEMS
  • Cardiovascular
  • Minimal cardiovascular depressant effects
  • Arterial blood pressure, cardiac output, and
    peripheral vascular resistance usually decline
    slightly and heart rate sometimes rises
  • Midazolam tends to reduce blood pressure and
    peripheral vascular resistance more than diazepam

13
EFFECTS ON ORGAN SYSTEMS
  • Respiratory
  • Benzodiazepines depress the ventilatory response
    to CO2
  • Ventilation must be monitored in all patients
    receiving IV medications
  • Cerebral
  • Reduce CMRO2, cerebral blood flow, and
    intracranial pressure
  • Effective in preventing and controlling grand mal
    seizures
  • Provides antianxiety, amnesic, and sedative
    effects
  • Possesses mild muscle-relaxant properties
  • No direct analgesic properties

14
DRUG INTERACTIONS
  • Cimetadine binds to cytochrome P-450 and reduces
    the metabolism of diazepam
  • Erythromycin inhibits midazolam metabolism and
    causes prolongation and intensification of its
    effects
  • Heparin displaces diazepam from protein-binding
    sites and increases free drug concentration
  • Combination of opioids and diazepam markedly
    reduces arterial blood pressure and peripheral
    vascular resistance
  • MAC of volatile anesthetics reduced as much as
    30
  • Ethanol, barbiturates, and other CNS depressants
    potentiate sedative effects

15
MIDAZOLAM CLINICAL USES
  • Most commonly used benzodiazepine for
    preoperative medication and IV sedation
  • Provides amnesia
  • Potent anticonvulsant for the treatment of grand
    mal seizures
  • Administration
  • PO 0.5 mg/Kg
  • IV 0.01-0.1 mg/Kg
  • IM 0.05-0.10 mg/Kg
  • Doses of 1.0-2.5 mg IV effective for sedation
    during regional anesthesia and brief therapeutic
    procedures
  • Administered as a supplement for maintenance of
    anesthesia

16
DIAZEPAM CLINICAL USES
  • Diazepam dissolved in organic solvents and is
    associated with pain on injection and
    thrombophlebitis
  • Popular drug for preoperative medication of
    adults, management of delirium tremens, and
    treatment of local anesthetic-induced seizures
  • Produces anterograde amnesia
  • Skeletal muscle relaxant
  • Preoperative PO 10-15 mg
  • Extensively bound to plasma protein

17
FLUMAZENIL
  • An imidazobenzodiazepine, specific and
    competitive antagonist of benzodiazepines at
    benzodiazepine receptors
  • Useful in the reversal of sedation and overdose
  • Prompt onset (lt 1 minute)
  • Slow titration of 0.2 mg doses IV (up to 1 mg)
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