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What is the MOA of Ketamine?
- -blocks polysynaptic reflexes in the spinal cord
- -interacts with opioid receptors and possibly ketamine receptors
- -inhibits excitatory neurotransmitters
- -dissociates thalamus from the limbic system (dissociative anesthesia)
What is the MOA of Propofol?
Increases activity of GABA synapses
What is the MOA of Benzodiazepines?
bind to receptors that are separate from but adjacent to GABA receptors, these receptors cause opening of Cl ion channels that result in a hyperpolarization of the neuron
What is the MOA of Etomidate?
- -depresses the RAS
- -mimics inhibitory effects of GABA
- -possible inhibitory effect on part of CNS that controls extrapyramidal motor activity
What is the MOA of Barbiturates?
- -depresses RAS
- -suppress excitatory neurotransmitters
- -augment inhibitory neurotransmitters
- -decreases transmission impulses to SNS
Etomidate CNS Pharmacodynamics?
- -sedative/hypnotic effects
- -decrease CBF, CMRO2 and ICP in dose dependant manner
- -activates seizure foci
Etomidate CV Pharmacodynamics?
- -etomidate induction agent of choice for cardiovascular compromise
Etomidate Resp Pharmacodynamics?
- -dose dependent decrease in RR and TV
- -less effect on respiration than other agents
Dose of Etomidate?
Pharmkinetics of Etomidate?
- A: IV
- D: higly lipid soluble
- B: metabolized in liver to inactive, metabolites; metabolized by plasma esterases
- E: renal
Side Effects of Etomidate?
- -myoclonus (decresed with opioid administration)
- -nausea and vomitting
- -venous irritation
- -fentanyl increases elimination 1/2 life
Pharmacokinetics of Benzodiazepienes?
- A: Oral, IV, IM
- D: highly lipid soluble at physiologic pH, small, midazolam and diazepam more lipid soluble than lorazepam
- B: liver to water soluble metabolites, midazolam 5X faster than lorazepam and 10X faster than diazepam, diazepam has active metabolites, duration of action determined by metabolisma and excretion
- E: renal
CNS Pharmacodynamics of Benzo's?
- decrease anxiety
- prevention and control of grand mal seizure (especially diazepam)
- spinal cord mediated muscle relaxationanterograde amnesia
- decreased CBF
CV pharmacodynamics of benzo's
- mild systemic vasodilation and decreased CO
- possible vagolytic increase in HR
- dose dependend hemodynamic changes
Respiratory pharmacodynamics of Benzo's?
- decreased ventilatory response to increased CO2
- dose dependent decrease in RR and TV
Side effects of Benzo's?
- drug interactions: valproate-psychotic effects
- heparin-displaces diazepam from protein
- erythromycin-inhibits midazolam metabolism
- Benzo's and opioids: decreased HR and SVR, birth defects (cleft lip and palate), crosses placenta
- Midazolam: 0.5-2.5 mg/kg
- Diazepam: 2.5-5.0 mg/kg
- Lorazepam: 0.5-2.0 mg/kg
Pharmacokinetics of Propofol?
- A: IV
- D: highly lipid soluble
- B: metabolized in liver to inactive metabolites
- E: 0.3% excreted unchanged in urine
CNS pharmacodynamics of Propofol?
- unconciousness or sedation
- decrease CPP, CBF and ICP
- anticonvulsant properties
- decreases intraocular pressure
CV pharmacodynamics of Propofol?
- dose dependent decrease in BP (greater with hypovolemic, elderly and the cv compromised)
- unchanged HR (occassional bradycardia and heart block
Respiratory pharmacodynamics of Propofol?
- decrease ventilation
- transient apnea
- opioids enhance respiratory depression
- bronchodilation with COPD
GI/GU pharmacodynamics with Propofol?
- care with pancreatitis and hyper lipidemia
- antiemetic effects (10-20 mg)
- phenols turn urine green
Side effects of Propofol?
- containdicated with egg yolk allergy
- pain on injection
- good bacterial growth medium (only keep 6 hours after drawn)
- crosses placenta
- decreases pruritus with neuroaxial opiods
Side effects of Propofol additives?
- Baxter (Sodium Metabisulfite): sulfite sensitivities-anaphylaxis or asthmatic episode
- Stewart (EDTA): chelating effects (Ca, Mg and Zi homeostasis effects), nephrotoxicity, negative effect on cardiac conduction, increased toxicity with long term use
- Induction: 2-2.5 mg/kg
- Sedation: 25-100 mcg/kg/min
- GA: 20-200 mcg/kg/min
Pharmacokinetics of Ketamine?
- A: IV, IM
- D: highly lipid soluble (greater than thiopental), less PRO bound than thiopental, equally ionized at body pH, redistribution
- B: liver with some active metabolites (Norketamine 1/3-1/5 as potent)
- E. Renal
CNS pharmacodynamics of Ketamine
- dissociative state
- amnesia and analgesia
- increased CBF and CMRO2
- cerebral vasodilation
- increased ICP
- activates seizure foci (with known seizure disorders)
CV pharmacodynamics of Ketamine
- increased HR, BP and pulmonary pressures
- myocardial depressent if hypovolemic, ANS blockade or maximal SNS stimulation
Respiratory pharmacodynamics of Ketamine
- mild decrease in RR and TV
- minimal effect on response to hypercarbia
- maintains laryngeal reflexes longer
- alleviates bronchospasm
Side effects of Ketamine
- increased oral secretions
- emotional disturbances (increases with age, female and >2mg/kg)
- myocardialo depression
- increased ICP, CMRO2 and CBF
- increased muscle tone
- eye movements (nystagmus, diplopia and blepharospasms)
- increased intraoccular pressure
- difficult to assess depth
- Induction: IV 1-2 mg/kg, IM 5-10 mg/kg
- Sedation: 0.2 mg/kg
Pharmacokinetics of Barbiturates
- A: IV, IM, Oral, Rectal
- D: highly lipid soluble, 1 arm to brain circulation time, dependent on redistribution (quick recovery), thiopental highly PRO bound
- B: liver to inactive metabolites
- E: Renal, methohexital fecal
CNS pharmacodynamics of Barbiturates
- unconsciousness (hyperalgesia in subhypnotic doses)
- cerebral vasoconstriction
- decreased CMRO2 and ICP
- anticonvulsant (except methohexital)
CV pharmacodynamics of Barbiturates
- decreased BP and CO
- increased HR
Respiratory pharmacodynamics of Barbiturates
- dose dependent decreased RR ad TV (may cause apnea)
- laryngeal reflex and cough not depressed
- histamine release
Enzymatic pharmacodynamics of Barbiturates
induces cytochrome P-450
Side effects of Barbiturates
- myoclonus and hiccupping
- CI in pt with Porphiriapain at injection site
- tissue necrosis with infiltration
- histamine release
- thiopental may cause bronchospasm in asthmaticsdecreased effect of theophylline, beta adrenergic blcokers, corticosteroids, digitoxin and tricyclic antidepressents (induction of P-450)
- thiopental induction 3-5 mg/kg
- methohexital induction 1-2 mg/kg
Which agents are highly protein bound?
Which agents provide brain protection?
Which agents help reduce the myoclonic effect of etomidate?
What agents are metabolized by plasma esterases?
What agents would you use to induce a patient with a significant cardiac history?
Which drugs cause pain om injection?
- diazepam, lorazepam
Which agents are effective at controlling grand mal seizures?
Which agents provide analgesia?
Which agents release histamine?
Which agents cause significant chest wall rigidity?
Which agents have a high incidence of N/V?