Benzodiazepam/ Barbs/ anti seizure Flashcards
Midazolam (versed)
Benzodiazepam
Uses;
- Induction and Maintenance of Anesthshia
- Anxiolysis
- Sedation
- Anterograde amnesia
- Anticonvulsant
- Muscle relaxation
MOA;
- enhances the affinity of GABA at the GABA receptor
- increases Chloride; which hyper-polarizes the cell
Dose;
- Pre med; 0.04 - 0.08 mg/kg
- Induction; 0.05 - 0.35mg/kg
- Maintenance; 0.05 mg/kg or 1 mcg/kg/min
- decrease dose 30% if other narcotics or CNS depressants are being used
**Antagonist; Flumazenil
Pharmacokinetics;
-Onset; Rapid
- E1/2 time; 14 hours
- prolonged in elderly
-DOA; 15 - 80 min (IV)
highly lipid soluble and rapid redistribution
- Vd; 1 - 1.5 L/Kg
- Pb; 94%
- metabolized by CYP450 enzymes in liver
- 2 active metabolite
- 1-hydroxymidazolam (has 1/2 the activity of midazolam)
- 4-hydroxymidazolam
- then conjugated and cleared by the kidneys
Side Effects;
- respiratory depression
- dose dependent decrease in ventilation
- apnea can occur after large doses
CV; induction dose can cause decrease in BP and increase in HP
CNS; risk for paradoxical excitement
Contraindicated;
- pregnancy; category D
- narrow angle glaucoma
Caution;
- elderly
- drugs that inhibit or enhance CYP450 enzymes will alter DOA of drug
- decrease dose 30% when used with other narcotics or CNS depressant drugs (opioids, ETOH, barbs)
Lorazapam (Ativan)
Benzodiazepam
Uses;
- limited use for anesthesia induction, sedation and anticonvulsant bc of slow onset
- anxiolysis
- sedative hypnotic
- anterograde amnesia
- anticonvulsant
- muscle relaxation
- most potent sedative and amnestic of Benzos
MOA;
-enhances the affinity of GABA at the GABA receptors; increases chloride conductance; hyper-polarizes cell
IV: 1 - 4 mg
*do not to exceed 4mg
Antagonist; Flumazenil
Pharmacokinetics
- Onset; 1 - 2 min (slow for effects to occur)
- Peak effect; 20 - 30min
- E1/2time; 10 - 20hrs
- DOA of sedative effects 6 - 10hrs
- Vd; 0.8 - 1.3 L/kg
- Pb; 80%
Metabolism; conjugated by the liver
80% excreted by the kidneys
Side Effects;
- Dose related respiratory depression
- decreased CBF and CMR02 minimal ICP changes
- venous irritation/ thrombophlebitis
Contraindicated;
-narrow angle glaucoma
Caution
- pregnancy
- obstructive airway disease
Synergistic effects with other CNS depressants
Diazepam (Valium)
Benzodiazepam
Uses;
- Pre-op anxiolytic
- Local Anesthetic induced seizures
- Induction/ Maintenance of GA
- anxiolysis
- sedative hypnotic
- anterograde amnesia
- anticonvulsant
- skeletal muscle relaxation
MOA;
enhances affinity of GABA at GABA receptor; increases chloride conductance; hyper-polarizes cell
Dose;
induction; 0.3 - 0.6 mg/kg
Pre-op anxiolytic; 2.5 - 10 mg (0.5mg increments)
PO; 5 - 15 mg
Antagonist; Flumazenil
Pharmacokinetics;
- onset;
- E1/2time; 20 -50 hours
- DOA;
- Vd; 0.7 - 1.7 L/kg
- Pb; 98%
Metabolism; CYP450 liver enzymes *active metabolite desmethydiazepam E1/2 time; 48 - 96 hours (slower metabolism and likely causes return of drowsiness 6 - 8 hrs after initial dose)
Elimination; excreted by the kidneys as oxidized metabolites
Side Effects;
- minimal CV and respiratory effects
- Large dose for induction can decease SVR and BP
- fatigue
- dry mouth
- muscle weakness
- dizziness
Contraindicated;
-glaucoma
Caution;
- hypoalbuminemia r/t liver and renal disease adjust dose (bc of protein binding)
- elderly
- liver dysfunction
- synergistic effects with other CNS depressants
Phenytoin (Dilantin)
Anti-epileptic
Anti-arrhythmic (Class Ib)
Uses;
- tx partial & generalized tonic/ clonic seizure
- seizure prevention in neurosurg
- seizures r/t eclampsia
- tx arrhythmias unresponsive to lidocaine
- chronic pain syndrome
MOA;
- binds to VGNa channels and regulates Na ion transport across cell membranes
- decreases neuronal excitability and inhibits neurotransmission
Dose;
q dose is given slow <50 mg/min
-Status Epilepticus; 10 -15 mg/kg
-Neurosurg prophylaxis; 100 - 200 mg IV q 4
-Dysrhythmias; 50 - 100 mg IV q 10 min until stopped; max 10 -15 mg/kg
Pharmacokinetics;
- onset; 30 - 60 min
- E1/2t; dose dependent
- DOA; dependent on preparation
Vd; 0.7 L/kg
Pb; 90%
pH; 12 (precipitates w/ pH <7.8
Metabolism;
- 98% metabolized by hepatic enzymes
- metabolism is dose dependent < 10mcg/ml first order of kinetics > 10 mcg/ml zero order of kinetics
Elimination;
-2% excreted unchanged. by kidneys
Side Effects;
- IV phenytoin;
- hypotension
- bradycardia
- arrhythmias
- CV collapse
- venous irritation/ pain
- thrombophlebitis
- Steven johnson syndrome
- Systemic Lupus Erythematous
- purple glove syndrome
- gingival hyperplasia
- acne
- GI irritation
- hepatotoxicity
-dose related CNS toxicity; nystagmus, diplopia, vertigo, peripheral neuropathy, cognitive impairment
Contraindicated;
-pregnancy
-Undiluted phenytoin >50mg/min IV can cause hypotension, arrhythmias and death
(should be diluted in NS/LR 1 - 10mg/ml
Caution;
-phenytoin induces metabolism of drugs; pts usually require more frequent doses of NMBD
Phenobarbital
Barbiturate
Uses;
- Pre-op sedation
- Anticonvulsant
- treats partial and tonic/clonic seizures
MOA;
- binds to allosteric receptor site on GABA
- increases chloride conductance; causes hyper-polarization; causing sedation
- high doses anticonvulsant
Dose;
- Pre-op sedation; 100 - 200 mg IM 1 hr before surgery
- Anticonvulsant; 1 - 5 mg/kg/day ini divided doses
Pharmacokinetics;
- onset; 5 min (IV)
- E1/2t; 53 - 140 hours (varies with kids)
- DOA; 4 - 10 hours (IV)
- peak; 30 min (IV)
- Pb; 20 - 45%
Metabolized in liver
*CYP450 inducer
Excreted 60 - 90% unchanged by kidneys
Side Effects;
- Depression
- Confusion in elderly
- Sedation in adults
- Hyperactivity in kids
- bone marrow suppression
- liver toxicity
- Steven Johnson syndrome
- Respiratory depression
- N/V/ constipation
- Many other Cognitive and behavior side effects; limited usefulness (2nd line drug)
Contraindicated;
- PORPHYRRIA
- Hypersensitivity
- respiratory disease
- dyspnea
- airway obstruction
- severe liver dysfunction
- pregnancy
Caution;
CYP450 enzyme inducer; caution with drugs metabolized by the liver
-CNS depressants can cause additive effects
*IV form is incompatible with many drugs – administer with care
Thiopental
Barbiturate
thiobarbiturate r/t sulfur @ position 2
(currently not made, but best at tx ICP, hopefully it comes back)
Uses;
- anesthesia induction agent
- Tx of increased ICP
MOA;
-Binds to GABA receptor and incases Chloride conductance; hyper-polarizes
Dose dependent MOA;
low dose; decreases dissociation of GABA from GABA receptor
high dose; directly open chloride channel
Dose;
induction 3 - 5 mg/kg IV
Maintenance; 50 - 100 mg q 10 - 12 min
Pharmacokinetics; -onset; Rapid; 10 -30 sec for induction dose -E1/2 time; "11.6 hrs" Dr E -DOA; "5 - 8 min" Dr E -redistribution 1/2 life; 25 minutes depends on cardiac output
Pb; 70 - 85%
Vd; 2.5 L/kg
Metabolism;
-99% metabolized by liver
10 - 20% metabolized to hydroxythiopental
large doses of thiopental can cause formation of pentobarbital
-normal doses; first order kinetics
-higher doses; zero order kinetics
*hepatic enzyme induced
Elimination; <1 % excreted unchanged in urine
Side Effects;
- Anaphylaxis is rare but fatal when it occurs
- Peripheral vasodilation –> venous pooling
- myocardial depression r/t decreed contractility
- Respiratory depression
- “Double apnea” 20% of pt go apenic for 25 seconds when inducted with thiopental and then have a second longer apenic period a few minutes later
- “vasoconstricts normal brain more than ischemic brain, maintain nice vasodilation and optimization of flow in ischemic area (steals from rich and gives to poor)” CB
- “decreases ICP, CBF, CMR02” Dr. E
Contraindications;
- PORPHYRIA
- difficult airways / airway obstructions
- status asthmatics
- CV instability/ shock
*always have appropriate airway equipment when administering this drug
Methohexital
Barbiturate
methyl radical group (causes seizure activity)
Uses; Electro-convulsant therapy (ECT)
MOA;
- Decreases dissociation of GABA at GABA receptor
- Binds to GABA and increases chloride conductance; hyper-polarizes the cell
Dose; 1 - 2 mg/kg IV
*most potent barb
Pharmacokinetics; Onset; Rapid E1/2 time; 3.9 hours DOA; 5 -8 min (Rapid Termination of Effect)
Extensive Metabolism
*hepatic enzyme inducer
<1% excreted unchanged by kidneys
Side Effects;
- dose dependent respiratory depression
- myocardial depression
- Myoclonus
- Hiccups
Contraindicated;
Porphyria
Flumazenil
Competitive Benzodiazepine receptor antagonist
1,4-imidazobenzodiazepine derivative
Uses; Reverse sedation, and respiratory depression from benzodiazepine
MOA; COMPETITIVELY antagonizes benzodiazepine effects by inhibits the activity of benzodiazepines on the GABA/ benzodiazepine receptor
Dose; 0.1 mg repeated dose q min to max of 1 - 3 mg
(failure to respond after more than 5 mg may indicate other intoxicant involved)
Pharmacokinetics;
- onset; 1 -2 min
- E1/2t; 1 hr
- DOA 30 - 60 min
- Vd; 1 L/kg
- Pb; 50%
Metabolized; 99% by liver
Excretion; less than 1% excreted unchanged in urine
Side Effects;
- Cutaneous vasodilation (sweating, hot flash, flushed)
- N/V
- Agitation/ confusion
- Headache
- Fatigue
- abnormal hearing and vision
Contraindications;
- hypersensitivity
- if given a benzo for control of life threatening condition
- pts with epilepsy on anti seizure drugs
- TCA overdose
