37. Benzodiazepines Flashcards
DIAZEPAM
DOSE
MOA
USES
Benzodiazepine
- Tablets: 2/5/10 mg
- IV white solution: 2/4 mg/mL
DOSE
• IV for sedation:
5–20 mg, titrate to effect
• Alcohol withdrawal:
20–30 mg q.d.s.,
reducing dose regime
• Status epilepticus: 10 mg IV or PR repeated prn
MOA
• Agonist at the benzodiazepine
receptor which is coupled to GABA receptor
• Stimulation causes ↑ frequency of
opening of GABA’s Cl– ion channel
• This causes hyperpolarisation and
stabilisation of membrane by increasing flux
of Cl– ions into cell
USES
- Tonic-clonic seizures and status epilepticus
- Anxiolysis
- Alcohol withdrawal
- Muscle spasm
- Sedation
- Premed
DIAZEPAM
AD
ME
METABOLISM AND EXCRETION
- Hepatic metabolism to active compounds
- Desmethyldiazepam,
- Oxazepam and Temazepam
- Metabolites excreted in urine
ABSORPTION/ DISTRIBUTION
• Oral bioavailability up to 100% as very
lipid soluble
- Protein binding 99%
- VD 0.8–1.4 L/kg
- Active metabolites have t½ >100 hours!
EFFECTS
CVS
• Slight, transient ↓ BP
- ↑ Coronary artery vasodilation
- ↓ Myocardial oxygen demand
RS
- ↑ RR
- Apnoea in high doses
CNS
• Anticonvulsant
- Hypnosis
- Sedation
- Anxiolysis
- Amnesia (anterograde)
- ↓ MAC
- Drowsiness
- Ataxia
- Tolerance and dependence
MIDAZOLAM
Imidazolbenzodiazepine
• Clear colourless solution:
1/2/5 mg/mL
• Oral/nasal/PR/IM/IV/ intrathecally/epidural
DOSE
- Oral: 0.5 mg/kg (max 20 mg)
- IV: 0.02–0.1 mg/kg for sedation, titrate to effect
- Spinal: 0.3–2 mg
- Epidural: 0.1–0.2 mg/kg
MOA
• Agonist at the benzodiazepine receptor coupled
to GABA receptor
• Stimulation causes ↑ frequency
of opening of GABA’s Cl- ion channel
• Causes hyperpolarisation of membrane by
increasing flux of Cl- ions into cell
USES
• Sedation
• Anxiolysis
• With morphine for induction of anaesthesia
in unstable patients
MIDAZOLAM
CHEMICAL PROPERTIES
• Contains tautomeric diazepine ring structure
• The ring can be open or closed
depending on ambient pH
- > 4 ring closed = non-ionised and lipid soluble
- < 4 ring open = ionised and less lipid soluble
- pH in ampoule = 3
- pKa = 8.5 so at pH 7.4, 89% un-ionised
- Drug is water soluble, so no pain on injection
- Effects can be reversed with flumazenil
METABOLISM
AND EXCRETION
• Hepatic metabolism
• Hydroxylation to 1a hydroxymidazolam
(active).
This is conjugated and excreted in urine
• <5% converted to oxazepam
• Alfentanil metabolised by same enzymes
(P450 3A3/4) therefore they may potentiate
each other’s effects
ABSORPTION/ DISTRIBUTION
• Oral bioavailability ~ 40%
• Protein binding 95%
• High hepatic extraction ratio, so if
hepatic blood flow is poor/poor liver
function, half-life will increase
• t½ 1–4 hours
• Shorter action than other BDZs
because of redistribution
MIDAZOLAM
EFFECTS CVS • ↓ SVR by one-third • ↑ HR • Obtunds response to laryngoscopy when combined with opioid
RS
- ↑ RR
- ↓ VT
- No change in MV
- Apnoea in some
- Blunts response to pCO2
CNS
• Hypnosis
- Sedation
- Anxiolysis
- Amnesia (anterograde)
- ↓ Cerebral metabolic oxygen requirements
- ↓ Cerebral blood flow
- ↓ MAC by 15%
GI
• ↓ Hepatic blood flow
GU
• ↓ Renal blood flow
TEMAZEPAM
CHEMICAL PROPERTIES
• Nil
TEMAZEPAM
Benzodiazepine
- Tablets: 10 mg
- Oral solution: 2 mg/mL
DOSE
• 10–40 mg at night
MOA
• Agonist at benzodiazepine receptor coupled
to GABA receptor
• Stimulation causes ↑ frequency of
opening of GABA’s Cl- ion channel
• Causes hyperpolarisation of membrane
by increasing flux of Cl- ions into cell
USES
• Sedation – especially for insomnia
- Anxiolysis
- Pre–med
FLUMAZENIL
Imidazobenzodiazepine
• Clear, colourless solution:
100 μg/mL
DOSE
• 100 μg boluses.
Titrate to effect, max = 1 mg
• Works in 1 min,
lasts 15 min–2 hours
• Can give as infusion at 100–400 μg/hr
as half-life of benzodiazepine taken in
overdose may be longer
MOA
• Competitive antagonist at benzodiazepine receptors
ABSORPTION/
DISTRIBUTION
• Significant first-pass metabolism
- Protein binding 50%
- VD 0.9 L/kg
- t½ 53 min
METABOLISM
AND EXCRETION
• Hepatic metabolism
- No significant active metabolites
- Excreted in urine
EFFECTS
CNS
• Can precipitate seizures
• Can reduce post–operative shivering
FLUMAZENIL
Imidazobenzodiazepine
• Clear, colourless solution:
100 μg/mL
DOSE
• 100 μg boluses.
Titrate to effect, max = 1 mg
• Works in 1 min,
lasts 15 min–2 hours
• Can give as infusion at 100–400 μg/hr
as half-life of benzodiazepine taken in
overdose may be longer
MOA
• Competitive antagonist at benzodiazepine receptors
ABSORPTION/
DISTRIBUTION
• Significant first-pass metabolism
- Protein binding 50%
- VD 0.9 L/kg
- t½ 53 min
METABOLISM
AND EXCRETION
• Hepatic metabolism
- No significant active metabolites
- Excreted in urine
USES
• To reverse effects of benzodiazepines, e.g. if
taken in overdose or administered in excess
EFFECTS
CNS
• Can precipitate seizures
• Can reduce post–operative shivering
