Ideal Sedative Agent. Benzodiazepines 11/12/2013. Pharmacology of Benzodiazepines Used for Conscious Sedation in Dentistry.
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1 Pharmacology of Benzodiazepines Used for Conscious Sedation in Dentistry Peter Walker Ideal Sedative Agent Anxiolysis Analgesic No effect on CVS No effect on respiratory system Not metabolised Easy and quick to change level of sedation Reversible No interactions with other drugs Long shelf life Cheap Benzodiazepines Discovered in 1955 Librium marketed in 1960 Diazepam discovered 1959 First used in anaesthesia
2 Pharmacokinetics What the body does to the drug Half life metabolism Excretion Pharmacodynamics This is what the drug does to the body Sedation Analgesia Anxiolysis etc. Clinical Effects of Benzodiazepines Pharmacodynamically the same Differences Affinity for receptors (potency) Pharmacokinetic properties Half life Presence active metabolites 2
3 Benzodiazepines Actions Anxiolysis Anticonvulsion Slight Sedation reduced attention Amnesia Intense sedation Muscle relaxation Anaesthesia Increasing Dose Increasing dose Clinical Effects of Benzodiazepines Anxiolysis (relief from anxiety) First effect at low dose High anxiety requires higher dose Sedation Decreased response to constant stimulus Clinical Effects of Benzodiazepines Anticonvulsion (Prevent epileptic fits) Benzodiazepines terminate or prevent fits Emergency drug for epilepsy Amnesia IV give anterograde amnesia Most intense for minutes Unpredictable 3
4 Clinical Effects of Benzodiazepines Effect on Pain experience BZD are NOT analgesic Respond to pain/stimulus Patients may move more during administration of Local. Benzodiazepine Mechanism of Action Principles. GABA (Gamma-aminobutyric acid) 1.GABA causes sedation to CNS 2.BZD bind to BZD receptors 3.When bound will increase GABA effect. Glycine 1.Glycine causes anxiolysis and muscle relaxation 2.Midazolam (BZD) mimics Glycine At the Synapse 4
5 Peripheral Benzodiazepine Receptors Found in myocardium, kidney and adrenals Role unknown Maybe implicated in cardiovascular effects Side effects of Benzodiazepines Depression of Respiration (breathing) Central nervous system depression and muscle relaxation Decrease cerebral response to CO 2 (carbon dioxide) Synergistic interaction with opioids Enhanced in patients with chronic bronchitis 5
6 Side effects of Benzodiazepines Cardiovascular effects Reduce blood pressure by decrease in vascular resistance Heart rate increases via baroreceptor reflex Cardiac output uneffected Side effects of Benzodiazepines Drug interactions Enhanced respiritory depression with CNS depressants Synergistic reaction with opioids Pharmacokinetic interactions Eg ketoconazole or erythromycin and midazolam St johns wart and grapefruit juice Side effects of Benzodiazepines Sexual fantasy Reported in both male and female patients Usually patient and dentist opposite sex Dose related (midazolam >0.1mg/kg) 6
7 Unwanted effects of benzodiazepines Tolerance Patients taking oral BZDs become tolerant to some effects Dependence Long term oral administration will cause addiction and will experience withdrawal reactions if cease Dependence can be activated by acute administration Acute withdrawl can be caused by BZD antagonist Midazolam Water soluble Water soluble ph <4.0 Lipid soluble at physiological ph Lipid soluble means it can cross blood brain barrier No rebound sedation Midazolam or 5mg/5ml 7
8 Midazolam Metabolised Liver Significant extra hepatic metabolism Less effected by liver disease In acute administration pharmacokinetics not effected by renal (kidney) disease Formulation 10mg 20mg tablets 10mg/5ml solution Dose 10mg to 40mg 60min prior to surgery Elimination half life 20 hours Temazepam Flumazenil - Anexate Reversal agent Antagonist IV injection 500microgram/ml 5ml ampoule High receptor affinity Low intrinsic action 8
9 Flumazenil - Anexate Mode of action Competitively displaces active benzodiazepine from receptor site. Elimination half life 53 minutes Uses of Flumazenil Not used as a routine Essential emergency drug Should present but not used Residual Sedation after Flumazenil Sedation When flumazenil runs out the patient is still sedated Time 9
10 Residual Sedation after Flumazenil Due to the different half life's flumazenil is metabolised before midazolam has been made inactive Contraindications to flumazenil Suspected allergy to benzodiazepines Never use for anaphylaxis Patients taking benzodiazepines to treat epilepsy Patient dependent on BZDs 10
Ideal Sedative Agent. Pharmacokinetics. Benzodiazepines. Pharmacodynamics 11/11/2013
Ideal Sedative Agent Pharmacology of Benzodiazepines Used for Conscious Sedation in Dentistry Peter Walker Anxiolysis Analgesic No effect on CVS No effect on respiratory system Not metabolised Easy and
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