Pharm Unit 2 Flashcards
What can be given for pre-eclampsia?
Magnesium sulfate
What are the 5 components of anesthesia?
Hypnosis, analgesia, muscle relaxation, sympatholysis and amnesia
How do barbiturates exert their effect?
Potentiating GABA-a channels, also act on glutamate/adenosine/neuronal nicotinic ACh receptors
What do barbiturates do the CBF/CRMO?
Act as a cerebral vasoconstrictor, reduce CBF and CRMO by about 55%
Why do you want to avoid infusions of barbiturates?
Prolonged context-sensitive half time. They also rapidly redistribute into other tissues.
Dose of Thiopental?
4 mg/kg IV
Dose of methohexital?
1.5 mg/kg IV
How does methohexital affect seizures?
Lowers seizure threshold = easier to have one, making it an ideal drug for ECTs
Basic effects of barbiturate’s on ventilation?
Dose dependent depression with slower frequency and lower tidal volume, similar to narcotics
What happens during intra-arterial injection of a barbiturate?
Immediate intense vasoconstriction and pain. Treat with vasodilators: lidocaine or papaverine
List the induction, conscious sedation and maintenance doses of propofol
Induction = 1.5 - 2.5 mg/kg IV
CS = 25 - 100 mcg/kg/min
Main = 100 - 300 mcg/kg/min
Describe Ampofol and Aquavan relative to Propofol
Ampofol = low-lipid emulsion with no preservative, higher incidence of pain on injection (good d/t less effect on triglycerides)
Aquavan = prodrug that converts into active form, no pain on injection, by has unpleasant sensation related side effects
Describe Propofol MOA
Selective modulator of GABA-a = increased Cl conductance and hyperpolarized cell
Describe the BP/HR changes with propofol, etomidate and ketamine
P = decreased BP and HR
E = no change to BP and HR
K = increased BP and HR
T/F: Propofol is safe for alcoholic patients?
T: awakening time does not change with healthy vs ETOH patients
How does the dose of Propofol change with children vs elderly?
Children = increased dose, elderly = decreased dose (by 25-50%)
Why is Propofol advantageous as a sedative?
Prompt recovery, low PONV, anti-convulsant, amnestic, anti-oxidant. Does not provide analgesia however
What is the sub-hypnotic dose of Propofol?
10-15 mg IV followed by 10 mcg/kg/min
Anti-pruritic dose of Propofol?
10 mg IV
What effect does Propofol have on the airway?
Bronchodilation
Anti-convulsant dose of Propofol?
1 mg/kg IV
Effects on CRMO with Propofol?
Decreases CRMO, CBF and ICP. D/t autoregulation, CBF and PaCO2 are maintained
Black box warning for Propofol?
Profound bradycardia leading to asystole in healthy patients
Describe Propofol infusion syndrome including dose
Greater than 75 mcg/kg/min longer than 24 hours. Can cause severe refractory bradycardia in children, lactic acidosis, brady-dysrhythmias and lactic acidosis. Green urine.
Etomidate MOA?
Selective modulator of GABA-a
Dose for Etomidate?
0.2-0.4 mg/kg/ IV
Best indication for etomidate?
In an unstable CV patient
What is the big side effect of etomidate?
Myoclonic movements, very common. Can be prevented with fentanyl 1-2 mcg/kg IV
Contraindication to etomidate?
Adrenal suppression - it makes it worse so you lose your stress response
Relationship of CRMO/CBF to etomidate?
Decrease CBF, CRMO and ICP by 35-45% via cerebral vasoconstriction
Etomidate effects on ventilation?
Is a depressant but less so than barbiturates. Vt decreases are offset by compensatory increases in RR
What is advantageous of ketamine over etomidate/Propofol? Cons?
No pain on injection and profound analgesia at subanesthetic doses. Dose have delirium concerns and abuse potential.
Compare isomers of ketamine
S (the left or -) = more intense analgesia, more rapid recovery, less salivation, lower incidence of emergence reactions
R = (right or +) = cocaine like effect, less fatigue, less cognitive impairment
Where does ketamine work?
NMDA receptors (prevents glutamate from activating them), all opioid receptors (mu, delta and kappa) and weak actions at GABA-a and sigma opioid receptors. Also affects calcium and neuronal nicotinic ACh channels (analgesic effect)
Induction doses IV and IM of ketamine?
IV = 0.5 - 1.5 mg/kg
IM = 4 - 8 mg/kg
Maintenance doses of IV/IM ketamine?
IV = 0.2 - 0.5 mg/kg
IM = 4 - 8 mg/kg
Subanesthetic/analgesic dose of ketamine?
0.2 - 0.5 mg/kg IV
Post op sedation/analgesia dose of ketamine?
1 - 2 mg/kg hour
What anti-sialagogue do you give with ketamine?
Glycopyrrolate
What is the coronary artery disease cocktail (include dosages)?
Valium = 0.5 mg/kg IV
Ketamine = 0.5 mg/kg IV
Ketamine infusion of 15-30 mcg/kg/min
How does ketamine affect ICP? At what dose does the ICP effect plateau?
Potent cerebral vasodilator = 60% increase in CBF, no further increase in ICP at 0.5 - 2 mg/kg IV
Effects of ketamine on the CV system?
Increase in pretty much everything; HR, BP, PAP, CO
Effects of ketamine on ventilation?
No depression of ventilation, airway reflexes are maintained, increase in salivary secretions, bronchodilator
What is the relationship of ketamine to volatiles, NMBDs and Sux?
NMBD = enhanced effect
Sux = prolonged
V = hypotension
Define hyperalgesia and allodynia
Hyper = increased pain sensations to normally painful stimuli
A = perception of pain in response to non-painful stimuli
Where does transduction, transmission, modulation and perception occur in nervous system?
Transduction = signals starting at the nerve endings
Transmission = travel of the electrical impulses to the nerve body connecting to the dorsal horn
Modulation = altering of the signal at the dorsal horn
Perception = discrimination of stimuli in the somatosensory cortex
What is the function of the hypothalamus?
To act as a relay station for incoming pain signals
What medication classes act at peripheral nociceptors or rather affect transduction?
LAs and NSAIDS
What medication classes act on transmission of nerve signals? Where?
LAs and on the a-delta and c-fibers
What medication classes act on modulation and where does this occur?
LAs, opioids, ketamine a2-agonists and in the spinal cord, primarily in the dorsal horn
What medication classes act on perception and where does this occur?
Opioids, a2-agonists, GAs. In the brain -> somatosensory cortex
Describe the process a stimulus would take to travel throughout the CNS
Stimulus -> nociceptor -> exceed resting threshold -> transmission -> modulation -> interpretation/perception
Describe the physiology of c-fibers and type 1 (a-beta) and type 2 (a-delta) fibers including speed
C-fiber = burning pain and sustained pressure pain (2 meters/second)
AB = heat, mechanical and chemical pain
AD = heat
Both alpha = much faster
What are some chemical mediators of pain?
Peptides (substance P, calcitonin, bradykinin, CGRP), eicosanoids, Lipids (PGAs, thromboxane, leukotrienes and endocannabinoids), neutrophins, cytokines, chemokines and extracellular proteases/protons
What are peptide mediators of pain?
Substance P, calcitonin, bradykinin, CGRP
What are lipid mediators of pain?
PGAs, thromboxane, leukotrienes and endocannabinoids
Define primary vs secondary hyperalgesia
P = at the original site of injury, decreased pain threshold, increased response to stimuli, spontaneous pain and expansion of receptive field
SH = uninjured skin surrounding the injury that has been sensitized by central neuronal circuits
Basic function of the dorsal horn
Relay center for nociceptive and other sensory activity
What do the ascending pathways do?
Transmit sensations such as pain to the brainstem and forebrain
What fibers would you find in lamina I?
Afferent C-fibers
What would you find in Lamina II?
The substantia gelatinosa, afferent c-fibers, also where opioids can exert their effect
Where does substance P work?
Lamina III and IV
Where would you find myelinated fibers in the cord? What do they innvervate?
Lamina I, IV, VII and the ventral horn, and they innervate muscles and viscera
Describe the gate theory of pain
If the gate is open, the pain is projected to supraspinal brain regions, if the gate is closed, pain is not felt with simultaneous inhibitory impulses
What happens if you rub an injured area?
The a-beta fibers deliver information about the rubbing/touching which override the slower information from a-delta and c-fibers regarding pain
What does the limbic cortex and thalamus do with pain information?
They are involved with perception of motivational-effective pain components
What does the PAG and RVM (rostro-ventral medulla) do with pain information?
Depress or facilitate the integration of pain information in the spinal dorsal horn
What does tissue injury release?
Substance P and glutamate
What are things damaged cells can release that cause pain?
Bradykinin, histamine, PGAs, serotonin, hydrogen ions and lactic acid
What are some excitatory impulses? Inhibitory?
E = glutamate, calcitonin, neuropeptide Y, aspartate, substance P
I = GABA, glycine, enkephalins, norepi, dopamine
What information travels the spinothalamic tract? Lamina?
Pain, temperature and itch, I VII and VIII
What information travels the spinobulbar tract? Lamina?
Behavior towards pain, I V and VII
What information travels the spinohypothalamic tract? Lamina?
Autonomic, neuroendocrine and emotional aspects of pain, I V VII and X
Describe the descending inhibitory pain pathway
Brain -> PAG/ RVM -> synapse in dorsal horn
What are the neurotransmitters used in the descending inhibitory tracts?
Endorphins, enkephalins, serotonin
What happens when you hyperpolarize a-delta and c-fibers?
Decreased release of substance P via opening of K channels and closing of Ca channels
What are the receptors for the PAG-RVM system?
Mu, Kappa and Delta receptors
Treatment for neuropathic pain?
Common to have allodynia and hyperalgesia, opioids, gabapentin, anti-depressants and cannabis
Describe visceral pain
Diffuse and poorly localized, if it is referred to the muscle/skin it become somatic pain
When does pain become perceivable in an neonate?
23 weeks
What are some endocrine responses to pain?
Increase catabolic hormones (catecholamines, cortisol, glucagon) and decrease anabolic hormones (insulin, testosterone) combined = negative nitrogen balance, carb intolerance and increased RAAS
What are some examples of phenanthrenes?
Morphine, codeine and thebaine