91 terms

NUNA1 Pharm Exam 1 Intro & IV Induction drugs

The study of drugs; observable interaction between drug and body constituent; includes how the drug is transformed by body tissues
A more precise description of the fundamental action of a drug on a physiological, biochemical, or molecular level
Drug concentrations in body fluids and tissues that influence how those concentrations vary with time
Specific macromolecule, peptide, protein, organ, cell type, enzyme, membrane component, nucleic acid, etc. where the initial molecular event occurs with the drug, leading to the therapeutic response
Drug receptor
Field of pharmacology that examines relationship of genetic factors to variations in drug response
Study of effects, antidotes, and detection of poisons and descriptions of effects of drug overdoses
A drug that binds to the same site as the endogenous ligand and produces same signal
A drug that binds to the side used by the endogenous ligand and acts competitively to diminish or block the signal produced by the endogenous ligand
Which route of medication administration goes right to distribution?
Two types of absorption
enteral (GI tract) and parenteral
What is the major determinate of how much drug reaches the site of action?
Blood flow (part of distribution)(no blood flow to area equals no drug flow to area)
Three routes of elimination
Kidney, liver and respiratory (in that order)
A. D. M. E. ("Mantra" for how we look at drugs)
Absorption, Distribution, Metabolism and Elimination
Alpha distribution
First phase of distribution (initial crossing of blood brain barrier)
The majority of drugs are metabolized in the _______?
Liver (liver adds charges to the cell so they are more hydrophilic)
Drugs must be ______philic /______ soluble to cross blood brain barrier.
lipophilic / lipid
Once a drug has a ionic charge is can be excreted by the ______.
Once a drug has an ionic charge is becomes ______philic.
What is ester hydrolysis?
So far he has said the breakdown of a medication before it goes through the liver. The medication structure is such that it is broken down before hepatic circulation. Very short acting drugs. Utilizes esters to break down meds.
What is GABA type A?
A ligand-gated ion channel that inhibits neurotransmission in inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring. Thus is we give a GABA type A drug people go to sleep
What is the relationship between GABA A and NMDA (n-methyl-D-asparate)?
Stimulation of GABA A will put someone to sleep while stimulation of NMDA will excite and arouse the patient. Blockage of GABA A will make the patient awake and blockage of NMDA will pt the pt to sleep.
What is the ligand-gated ion channel neurotransmitter that inhibits pain response.
True or false
NMDA play a role is pain response.
If medication increase glycine activity you should expect a(n) (increase/decrease) in pain.
GABA A and Glycine allow what electrolyte to enter the cell thus decreasing the action potential of the cell?
Glycine receptors are abundant in _______ and _________.
Spinal cord and brainstem
GABA A receptors are found in ________ regions.
Higher brain regions.
Barbiturates activate the _______ receptors. (6 of them, but 1 important one)
GABA A(the important one), AMPA, kainate glutamate, adenosine, neuronal nicotinic acetylcholine receptors.
Do barbiturates have activity at glycine or NMDA receptors?
True or False
Barbiturates enhance and directly activate GABA A receptors.
Etomidate is a selective ________modulator.
Propofol is a GABA A receptor ________ (agonist/antagonist)?
Agonist (does not need GABA to work)
Propofol is an weak ________.
Propofol also inhibits __________ which will inhibit blood pressure and heart rate.
Neuronal acetylcholine.
Ketamine provides "__________ anesthesia".
"dissociative anesthesia"
What drug provides sedation, immobility, amnesia, marked analgesia and dissociation from environment all without true unconsciousness.
30% of adults have _________ as an adverse reaction to ketamine.
On what receptor and how does ketamine work?
inhibition (blocks) on NMDA receptors and does not affect GABA A.
4 types of barbiturates
Oxybarbiturates, thiobarbiturates, methylbarbiturates and methlthiobarbiturates
Pale yellow powder with poor water solubility; dissolves in alkaline solution of sodium carbonate with resultant pH of 10.5
Which barbiturate has delayed onset and prolonged duration of action?
Which barbiturate has a rapid onset?
Another name for methylbarbiturates (methohexital)
Thiopental characteristics of absorption
rapid onset
related to rapid uptake across BBB
highly lipid soluble
Disadvantages of thiopental
extremely caustic if infiltrated (thrombophlebitis)
not compatible with other IVFs
minimal increase in sensitivity to somatic pain
Advantages of thiopental
minimal cardiovascular depression
cerebral protection during ischemic episodes
Dosing of thiopental
induction → 3-5 mg/kg (gives you 15-20 min)
peds → 2-7 mg/kg
anticonvulsant → 1.5-3 mg/kg PRN or 3-10 mg/kg/hr (cont infusion)
Emergence and metabolism of thiopental
t ½ alpha → 2-7 minutes
decline in blood/brain concentration due to redistribution
Indications of thiopental
induction of anesthesia
maintenance of anesthesia (intermittent bolus or infusion)
sedation & control of ICP
Advantages of Methylhexital over thiopental
Better kinetic profile for both induction and maintenance of anesthesia when compared to thiopental
Disadvantages of methylhexital (brevital)
excitatory movements
depresses both BP and CO
pain on injection
lowers seizure threshold
opiate + N2O + methohexital
severe respiratory depression
What is porphyria?
"A blood disorder where they produce to much heme, thus we give them heme to stop the production. (Remember that p450 is cytochrome p450 - it uses a heme molecule in the active site for electron transfer. More demand for cytochrome
more demand for heme; in someone with porphyria, that means more buildup of substrates from behind the messed-up link in the pathway...)
Contraindications of barbiturates
proven allergy to barbiturates
airway obstruction (or potential)
hx of epilepsy (methylhexital is proconvulsive)
Precautions with barbiturates
CV collapse
severe uremia
severe asthma
severe cardiac disease
Is methylhexital cardiac stable when given as an induction dose?
Yes, infusion depresses both blood pressure and cardiac output
Physical characteristics of etomidate
unstable in water
soluble in propylene glycol or as emulsion pH 8.1
pKa 4.2
99% unionized in blood
75% protein binding
Metabolism of etomidate
ester hydrolysis
Excretion of etomidate
>2% unchanged in urine
Dosing of etomidate
induction→ 0.3 mg/kg
elderly→ 0.15-0.2 mg/kg
peds→ up to 0.4 mg/kg
Advantages of etomidate
reduction of cerebral blood flow/metabolic rate and ICP
no histamine release (low allergy prevalence)
minimal respiratory depression
ideal for decreased cardiac fxn or hypovolemia
Disadvantages of etomidate
pain on injection/thrombophlebitis
excitatory movements/myoclonia
reversible inhibition of adrenal steroidogenesis
Contraindications of etomidate
adrenal insufficiency (Addisons Disease)
known sensitivity
Dose of etomidate old, normal pediatric
0.2 mg/kg, 0.3 mg/kg, 0.4mg/kg
What is propofol pH, pKa and lipid solubility?
pH 7.4, pKa 11.0 and 96% lipid soluble
What makes up propofol emulsion?
soy bean oil and egg phosphatide
Where is propofol metabolized?
Liver (by the P450/P2C9 enzymes)
What has a faster time to recovery propofol or thiopental?
Propofol has a smooth induction, but a delayed in what?
eye closing (better endpoint for induction is loss of verbal contact)
Induction dose of propofol
2mg/kg (give 0.5mg to 1mg/kg and see how it goes)
How does propofol make a patient hypotensive?
Decreases SVR, blunts baroreflex in heart and blunts sympathetic response thus no compensatory mechanism is in place
What induction drug decreases hepatic blood flow thus decreasing clearance in other drugs?
What does propofol do to ventilatory effect?
decrease TV and MV, episodes of apnea and decreased accessory muscle use
What non-hypnotic effects does propofol have?
Antiemetic effects and antipruretic effects {opioids induced itching}
What effect does propofol have on central nervous system?
Decreased cerebral blood flow, ICP {cerebral protection controversial} and EEG {way to sleep for protection}
Cardiorepiratory effects of propofol
Rare cases of bradycardia, sinus arrest, heart blocks and aystole when used with other vagotonic drugs
Drawbacks of using propofol
Burns IV site, hypotension, bradycardia, apnea and epileptiform movements, ALLERGIC REACTION, emulsion bacteria breading ground
What is PRIS?
Propofol Infusion Syndrome
Cardiac failure{bradyarrhythmias}, rhabdomyolysis, metabolic acidosis and renal failure
Risk factors of PRIS?
Severe TBI, severe sepsis, prolonged infusion time and doses > 5mg/kg/hr (83mcg/kg/min)
Infusion dose of propofol
65-200mcg/kg/min {should not be used in patients <17 y/o for ICU sedation}
Absolute contraindications for propofol
Hypersensitive to propofol or related compounds {soy products, egg products and sulfite compounds} or disorders of fat metabolism
Fospropofol sucks why?
long on time and long off time, not only that but they get the paresthesias {aka burning bush syndrome}
What is the mechanism of action of ketamine?
antagonist of NMDA
Which drug is water soluble; propofol, thiopental or ketamine?
Ketamine pH, pKa an how much is protein binding?
5.6 pH, 7.5 pKa and 12-35% protein binding
What metabolizes ketamine?
Liver (by the P450 enzyme) and has a metabolite norketamine that has a 30% potency of parent compound
What eliminates ketamine?
What are the 4 uses of ketamine?
induction of anesthesia
maintenance of anesthesia
sedation as a continuous infusion
analgesia as a continuous infusion
Ketamine dosages; induction, maintenance and analgesia
Induction 2mg/kg IV or 10 mg/kg IM
Maintenance 10-45 mcg/min infusion
Analgesia bolus of 0.1-0.25 mg IV followed by 0.2-1 mg/kg/hr
Drawbacks of using ketamine
30% emergence reactions
Elevations of HR, BP and ICP {no not give to head injury patients}
Caution in patients with poor cardiac reserve
Excessive salivation {glycopyrrolate may be given}
Absolute contraindications for ketamine
Elevated ICP or intraocular pressure
severe cardiac disease
psychotic disorders
What is the allergic reaction rate for the induction cocktail/
1/5,000 to 1/20,000 {most common with propofol and barbiturates}