Exam 1 Kane Flashcards
A drug induced loss of consciousness during which pts are not arousable, even by painful stimulation.
General Anesthesia
A medication that includes more than one enantiomer
racemic
Agents with chiral molecules that are mirror images of each other are known as
enantiomers
An agent that activates a specific molecule in a biologic system
Agonist
Half-life is known as the amt of time to clear ½ of drug from the
body
Describe Minimal Sedation
anxiolysis; normal response to verbal commands, airway unaffected, ventilation unaffected, cardiac unaffected
Describe Moderate Sedation
Drug-induced depression of consciousness but respond to tactile stimulation, no assistance needed for airway, adequate ventilation, cardiac usually maintained
Describe Deep Sedation
Stimulation after repeated verbal/touch, Independent ventilation may be impaired; assistance for airway may be required, cardiac usually maintained,
Describe allodynia
Due to a Stimulus that does not normally cause pain
The term that describes Increased pain perception from a stimulus that normally provokes pain
Hyperalgesia
Increased transduction/transmission of nociception; the process that causes hyperalgesia or allodynia
sensitization
Pain caused by a lesion or disease of somatosensory nervous system ; Characterized by reduced sensory and nociceptive thresholds
Neuropathic Pain
Pain transmitted to brain through spinal or cranial nerves
Somatic Pain
Pain transmitted to brain through autonomic nerves (internal organs)
visceral pain
Pain in the distribution of a nerve or group of nerves
neuralgia pain
An agent that activates/inhibits the action of a specific molecule but doesn’t form a permanent bond; other agents may also affect the same site
competitive
Competitive or noncompetitive agent that activates or inhibits the action of a neurotransmitter but does not function at the binding site
Indirect agent
Two agents administered at the same time who potentiate each other 1+1=3
Synergistic
Agents that activates a specific molecule but does not act at the SAME binding site as the neurotransmitter in question
Allosteric
Acquired hyporeactivity to an agent
Tolerance
An agent that activates or inhibits a specific molecule and forms a strong or permanent bond so that the other agents may not affect the same site
Non-competitive
Competitive or non-competitive agent that activates or inhibits the action of a molecule at the same site of action
Direct agent
Acquire hyporeactivity to an agent that occurs very rapidly
Tachyphylaxis
Two agents administered at the same time where the total response in the same as the response of one added to the other: 1+1=2
Additive
An agent that activates or inhibits an action but does not have a high affinity or efficacy for the desired effect
Partial
That action of specific molecules are inhibited or blocked by
Antagonist
The amount of drug totally cleared from the plasma over time and expressed in L/min
Clearance
The dose required to produce a therapeutic response is called
Potency
The inability to recall past experiences
Amnesia
The maximum therapeutic effect of a drug is known as
Efficacy
Which type of pain is described as “unpleaseant sensory and emotional experiences with actual or potential tissue damage” ?
both acute and chronic pain
Which type of pain is said to exist BEYOND the healing process
Chronic pain
Therapeutic index
Ratio between LD50/ED50 denoting the relative safety of the medication. The higher the ratio the safer the drug
Recall
Conscious memory
Chirality
subset of stereochemistry that has a center or centers of 3 dimensional asymmetry
Stereochemistry
the study of how molecules are structured in three dimensions
Pharmacodynamics
Study of the intrinsic sensitivity or responsiveness of the body to a drug and mechanisms by which theses effects occur.
Context-sensitive half-time
- The time required for blood or plasma concentrations of a drug to decrease by 50% after discontinuation of drug administration. Ex: Continuous fentanyl infusion causing half-life to build up over time.
First-order processes
Processes where the rate of change varies over time. Processes that occur at a rate proportional to the amount.
Zero-order processes
Processes where the rate of change is constant
Vessel rich group
Tissues that receive the bulk of arterial blood flow
Pharmacokinetics
The quantitative study of the absorption, distribution, metabolism and excretion of injected and inhaled drugs and their metabolites
Inverse agonists
Bind at the same site of the agonist but produce the opposite effect of the agonist. Turn off constitutive activity of the receptor
Regional Anesthesia
Regional Anesthesia- interrupts sensory nerve conduction of a particular region of the body ( examples include: peripheral blocks, spinals, epidurals), does NOT change level of consciousness ( unless you sedate as well) , can still use airway
Dioscorides 40-90 AD (surgeon in NERO’s army)
Materia Medica; Mandragora and wine (harry potter thing) – hallucinogenic, human shaped, magical
What is Ether the Greek word for?
Ignite
Sir Christopher Wren and Robert Boyle (1650s)
Utilized a goose quill as an IV to give a dog alcohol, probably the first sense of pharmacokinetics
Joseph Priestly 1773
Discovers oxygen and nitrous oxide
Humphry Davy 1800
Discovered potassium, sodium, calcium, magnesium and suggested Nitrous Oxide as pain control
Horace Wells 1815-1848; Dentist
Noticed that a man under the influence of N2O had no recall of pain/injury
What was the result of Horace Wells demonstrating the use of N2O for an amputation @ Mass General?
The patient rolled around and groaned as if in pain, Wells was then ridiculed and this was shown as a failure
Who realized that the administration of nitrous + oxygen resulted in no cyanosis of the patient?
Dr. Andrews
Who invented the first anesthesia machine that had nitrous and oxygen chained together?
Hewitt
What was the major side effect of Ether use?
Massive nausea and vomiting
Crawford Long 1842
Delivered either for a patient with 2 vascular neck tumors
William Morton 1819-1868; Dentist
1846, 1st successful public demonstration of ether…vascular tumor of neck in sitting position
Dr. Robinson Squibb
Developed process for pure ether
Where was chloroform discovered?
Independently in 1831 by the USA, France, Germany, and Great Britain
Sir James Simpson 1847; Obstetrician in Scotland
Defined pain: “actual or potential tissue damage,” encountered religious opposition
Dr. John Snow - Anesthetist
“discovered” epidemiology when he traced London cholera outbreak to water source
First well-known person to have anesthesia for child birth administered by Dr. John Snow?
Queen Victoria
Guthrie, 1894
delayed chloroform hepatotoxicity in children
Levy (1856-1954
Light chloroform anesthesia and adrenaline….fatal vf in animals
What were deaths under chloroform use attributed to?
Overuse of the medication and lack of adequate supervsion
Characteristics attributed to Sister Mary Bernard in 1877
Low pay, Intelligent, Focus
Alice Magaw 1860-1928
“mother of anesthesia,” 14,000 open drop ether cases without death
Characteristics of Agatha Hodgins 1877-1945
Opened one of 1st nurse anesthesia schools, Taught in France, Developed nitrous/oxygen techniques, Founded AANA
Why is cyclopropane not on the market?
Violently explosive
Halothane
Halothane hepatitis, Slow onset, slow offset
Who realized that volatile anesthetics go to the brain and tissues?
Edmund Egar
Isoflurane (Suprane) characteristics
Oldest but not cheapest, slowest onset and slowest offset, less nausea and vomiting, quicker onset than halothane
Desflurane
rapid onset and offset, large quantity needed for anesthesia, does not sit in the fat, irritable to airway so not good for asthma or COPD
Sevoflurane
intermediate action between iso and des, used for kids, not irritable to airway, unstable in soda lime
What is Dr. Lister (Morton) famous for?
3 deaths during 1 amputation operation
George Crile (1864-1943)
Preemptive analgesia, local infiltration of procaine
Harvey Cushing (1869-1939)
Regional blocks prior to emergence from ether, Anesthetic records, BP/HR measurements
Adverse effects of neuroleptic anesthesia through medications such as raglan or anapsine
Blocked autonomic and endocrine response to stress, High incidence of awareness, dysphoria, extrapyramidal movements
What was cocaine utilized for?
Ophthalmic and sinus surgery
Dr. August Bier
1st spinal with cocaine, developed bier block
Bier block
Tourniquet utilized, lidocaine, numbs extremity
Preoperative period of anesthesia drugs
BZD, H1 and H2 blockers, bronchodilators
Maintenance phase of anesthesia
Inhalation drugs, neuromuscular blockers, pressors, blockers
Emergence phase of anesthesia
NMB reversal, local anesthetics
4 Phases of Anesthesia
Perop, maintenance, emergence and postop
Stage 1 of Anesthesia
beginning of induction of general anesthesia to loss of consciousness 1st plane: no amnesia or analgesia 2nd plane: amnestic but only partially analgesic 3rd plane: complete analgesia and amnesia
Stage 2 of Anesthesia (MOST DANGEROUS STAGE)
loss of consciousness to onset of automatic breathing (irritable, dangerous stage), eyelash reflex disappears, coughing, vomiting, struggling may occur, irregular respirations with breath-holding Want to get through this stage quickly
Stage 3 of Anesthesia
onset of automatic respiration to respiratory paralysis (surgical plane)
Anesthesia Stage 3 Plane 1
automatic respiration to cessation of eyeball movements
Anesthesia Stage 3 Plane 2
cessation of eyeball movements to beginning of intercostal muscle paralysis
Anesthesia Stage 3 Plane 3
beginning to completion of intercostal muscle paralysis, pupils dilate Desired Plane prior to muscle relaxants
Anesthesia Stage 3 Plane 4
complete intercostal paralysis to diaphragmatic paralysis (apnea)
Stage 4 of Anesthesia
stoppage of respiration till death; Gone too far
What allows agonists/antagonists to be reversible?
The bond type of the molecule
What are the 3 types of bonds that substrates use to activate a receptor?
- Ion 2. Hydrogen 3. Van der Waals
What does the drug effect relate to?
Number of bound receptors, the more the merrier
When will you see the greatest effect from a drug?
All of the receptors are bound
What type of receptor are we usually dealing with?
proteins
Can you overcome non-competitive antagonism?
No, you can only overcome competitive antagonism
What can cause the number of receptors to increase or decrease?
Comorbidities and drug therapies
What do we see happen to receptors when a patient chronically uses albuterol for asthma?
Downregulation of receptors due to repetition
What does drug concentration in the plasma tell us?
How fast a drug is being distributed and where it is going
Are anesthetics active in the plasma?
No
Where are the effector sites located for anesthetic drugs?
Brain, spinal cord, lungs
What type of pharmacology determines the concentration of a drug?
Pharmacokinetics
What is the 1 compartment model of distribution?
Concentration of drug is immediately diluted by the plasma by a central compartment in the first minute of admin that determines Vd
What is Vd?
Volume of distribution tells us if the drug prefers to stay in the plasma or distribute to other areas of the body
What is the sequence areas that blood flows starting from the venous blood in arm?
- Venous blood in arm 2. Inferior vena cava 3. Right heart 4. Pulmonary vessels 5. Left heart 6. Aorita
What are 2 examples of vessel poor groups?
Ligaments and tendons
Why do men require more NMBD than women?
Larger amount of muscle mass in men
What makes propofol Vd 5000?
It is highly lipophilic
What increases the Vd?
Adding more areas where the drug is likely to go
What type of drugs primarily bind to albumin?
Acidic drugs
Where do alkaloid drugs primarily bind to?
A1-Acid Glycoprotein
What state of drug is able to cross cell membranes?
Free drugs
What state of drug, free or bound, determines concentration available to receptor (potency)
Free drug
Patient A shows to have more unbound drug than Patient B, which patient will show the greatest effect from the medication?
Patient A
4 Variables that would decrease amount of plasma proteins?
- Age 2. Hepatic Disease 3. Renal failure 4. Pregnancy
What is the final free fraction of a drug who’s normal free fraction is 2% when there is a net loss of 50% of proteins?
4%, which means the effect is increased
What type of Vd would drugs that have poor protein binding and lipid solubility show?
High volume of distribution, an example would be propofol
What type of Vd would drugs who are highly protein bound show?
Small volume distribution, an example would be warfarin
What does metabolism of a drug do?
Converts active, lipid soluble drugs to water soluble drugs to allow excretion of the drug through the kidneys
4 examples of drug metabolism?
- Hepatic microsomal enzymes 2. Hoffman Elimination 3. Ester Hydrolysis 4. Tissue Esterase
3 Types of phase 1 reactions
- Oxidation 2. Reduction 3. Hydrolysis
What does Phase I metabolism do to prepare for Phase II metabolism?
Makes the drug more polar
What occurs in Phase II metabolism?
Covalent link with a highly polar molecule to become water soluble through conjugation
4 Characteristics of CYP450 enzymes?
- Large family 2. Membrane bound 3. Contains heme cofactor 4. Involves oxidation and reduction (Phase I)
What is the most common CYP450 enzymes?
CYP3A4, which metabolizes >50% of drugs such as opioids, benzos, locals, immunosuppressants and antihistamines
When CYP450 is induced, what would you expect?
To have to increase the amount of administered to achieve the same effect as normal
What is an example of a drug that induces CYP450 enzymes?
Phenobarbital
What would you expect if CYP450 is inhibited?
The effect of drugs may last longer than desired
What is an example of a drug that inhibits CYP450?
Alcohol and grapefruit juice
What do you need for oxidation to occur?
An electron donor and oxygen
What is reduction in phase I metabolism?
Transfer of electrons directly to the substrate instead of to oxygen
What is phase I metabolism, reduction, good for?
Low PaO2
Where are drugs that undergo glucuronidation excreted?
Bile and urine
What is an example of a condition that interferes with conjugation?
Neonatal hyperbilirubinemia
What type of metabolism does not involve CYP enzymes?
Hydrolysis
Where does hydrolysis often occur and what type of bond does it usually occur at?
Often occurs outside of the liver and at ester bonds
3 examples of drugs that undergo hydrolysis
- Succinylcholine (Anectin) 2. Esmolol (Brevibloc) 3. Ester Local Anesthetic (Procaine, Cocaine)
What are the Phase II enzymes?
“Transferases”
For >50% of anesthetics, what is clearance rate proportional to?
Clearance rate is proportional to concentration; More drug/more clearance
What does flow limited metabolism mean?
Arterial blood flow, Q, limits metabolic rate
What does capacity limited metabolism mean?
Livers ability to metabolize is the limiting factor, SE can build up overtime if re-administration of a drug is too soon
Which drugs, lipid/water soluble, are less likely to be reabsorbed by the kidneys?
Water soluble drugs
What effect does context sensitive half-time ignore?
Plasma-effect site disequilibrium
What increases the context sensitive half-time?
Longer infusion durations
What is an example of a drug class that are weak acids.
Barbiturates such as thiopental
What are examples of drug classes that would be considered weak bases?
Opioids and local anesthetics
What form of a drug is lipid soluble, non-ionized or ionized?
non-ionized
What form of a drug is active, non-ionized or ionized?
non-ionized
How are non-ionized drugs metabolized?
Hepatic metabolism
What is the mnemonic to figure out ionization vs non ionization?
Weak Acids, PK After pH Weak Bases, PK Before pH Nicely negative numbers are non-ionized
What chronic disease would display atypical enzymes?
Renal failure
3 reasons for varying drug responses in the elderly
- Decreased cardiac output 2. Decreased protein binding 3. Increased body fat
Which enantiomer of ketamine is more potent with less delirium?
S-enantiomer
Which enantiomer of bupivicaine has 30% less cardiac toxicity?
L-Bupivicaine
Which isomer of atracurium lacks histamine effects?
Cisatracurium (Nimbex)
What benefit is there to using Xopenex over albuterol?
Xopenex shows no heart rate jump
Midazolam (doses)
Induction: 0.2-0.3 mg/kg IV over 30-60 seconds Sedation: 1-5mg IV (adults) Oral (Pedi): 0.25 - 0.5 mg/kg Post-Op Sedation: 1 - 7 mg/hr IV (max 2 - 3 days)
Diazepam (doses)
Anticonvulsant: 0.1 mg/kg IV Induction: 0.3 - 0.5 mg/kg IV (decrease for elderly/Liver Disease)
Lorazepam (doses)
1 - 4 mg IV (single dose)
Romazicon (doses)
0.2 mg IV then 0.1 mg q1min. until desired effect (1 mg max)
What are Freud’s three levels of mind?
- Conscious mind 2. Preconscious mind 3. Unconscious mind
What anesthetic drugs were used that showed changes in electrical activity on the EEG?
Chloroform and volatile anesthetics
What can the EEG be used for in terms of anesthesia?
Measure effects
What 2 factors related to EEG activity does anesthesia alter?
Cerebral blood flow and cerebral metabolic requirement of oxygen
What did processing the EEG give us?
Bispectral Analysis
What did BIS studies show when utilizing hypnotics?
BIS change correlated to patient movement
What did BIS studies show when utilizing high dose narcotics?
Less correlation between BIS and movement
At what level of BIS showed that a patient was not conscious?
BIS score of <58
What did a BIS score of <65 show?
Less than 5% chance of return to consciousness within 50 seconds
What should the EMG show on a BIS during a procedure?
0, if it is above 0 then it indicates lots of patient movement
What range of BIS correlates with relatively no recall of the procedure?
40-60
What would Ketamine give us on a BIS monitor? Beta-blockers?
Ketamine - false high Beta blockers - false low
When is the best time to give benzodiazepines?
Pre-op environment, especially with patients who have chronic anxiety
What do benzos cause from the spinal cord?
Skeletal muscle relaxation
What is the only thing that causes retrograde amnesia?
Electroconvulsive therapy
What does it mean when we say benzodiazepines cause anterograde amnesia?
Patients will not remember anything after the medication has been administered, the amnesic effect will last longer than sedation
When metabolizing benzos, what do they lack compare to barbiturates?
They do not have hepatic microsomal enzymes
Which benzodiazepine has the shortest elimination half time?
Midazolam
Which benzodiazepines have greater context sensitive half times than midazlolam?
Diazepam and Lorazepam, this effect makes them more attractive for sedation postop
What is the mechanism of action for benzos?
They facilitate GABA agonism, allowing for enhanced opening of Cl- channels
What effect does the GABA alpha-1 site have?
sedative, amnesic, anticonvulsant
Where are the GABA alpha-1 sites found to have effect?
cerebral cortex, cerebellar cortex, thalamus
What effect does the GABA alpha-2 site have?
Anxiolytic, anti-hyperalgesia, skeletal muscle relaxation
Where are the GABA alpha-2 sites found to have effect?
Hippocampus, amygdala
What are 4 other substrates that bind to GABA receptor binding sites and also have a synergistic effect?
- Barbiturates 2. Etomidate 3. Propofol 4. Alcohol
What do benzos bind to in the plasma?
Albumin
Effects of chronic renal failure/cirrhosis on benzodiazepine metabolism?
More free drug, making it more potent
What do we tell the patient if we do not administer benzos in the pre-op area?
The patient will remember the trip to the OR and going to sleep
What effect do benzos have on EEG’s?
decrease alpha and fast-beta activity, meaning the EEG is slower
Do benzos show tachyphylaxis?
Benzos do not show tolerance per EEG
What does it mean that benzos do not produce isoelectric states on the EEG?
They have a high margin of safety
What pathway is Lorazepam (Ativan) metabolized by?
Glucuronidation, it does not have any active metabolites and is safer to give the elderly
What are the effects of metabolism on Diazepam/Midazolam?
Active metabolites
What is the risk factor for postoperative confusion when giving benzos?
Daily use > 1 year
What effect if any do benzos have on platelets?
Benzos have been shown in the lab to inhibit platelet aggregating factor
3 Important facts about midazolam (versed)
- Imidazole ring 2. 2-3x as potent as diazepam d/t greater affinity for receptor 3. Amensia > sedation
What are the two variations of pH dependent ring opening of midazolam?
pH < 3.5, ring opens and is water soluble pH >4.0 ring closes and is lipid soluble
What is the onset of action and peak effect time of midazolam?
onset of action: 1-2 minutes IV peak effect time: 5 minutes
What is the issue with giving midazolam oral?
Significant 1st pass effect
What is the elimination half time of midazolam?
2 hours, this effect is doubled in elderly patients
What enzymes metabolize midazolam?
CYP3A4
What is the active metabolite of midazolam and where is it eliminated through?
1-hydroxymidazolam is cleared through the kidneys
5 drugs that inhibit CYP40 enzymes
- Cimetidine 2. Erthromycin 3. CCB 4. Antifungals 5. Fentanyl
What effect does not allow midazolam to produce an isoelectric EEG?
Ceiling effect
What is the effect of midazolam on ICP?
No change in ICP, making it good for induction with neuro pathologies
What is the effect of midazolam on the pulmonary system?
Dose dependent decreases in ventilation, which is exaggerated with opioids/CNS depressant drugs. Midazolam also depresses swallowing reflective and decrease upper airway activity.
What is the effect of midazolam on the CV system?
Dose dependent increases in HR and decreases in BP. No change in cardiac output, hypotension is enhanced with hypovolemic patients. No BP/HR response to intubation
When and what route do we give midazolam to pedi patients?
Oral admin 30 minutes before induction
What effect does midazolam have on volatile anesthetics?
Dose dependent decreases in volatile requirements
What does clearance of midazolam depend on?
Hepatic metabolism, the activite metabolites will accumulate and delay awakening
What is the recommended time period for post-op sedation with midazolam per the Society of Critical Care Medicine?
2-3 days
How is the duration of action of diazepam when compared to midazolam?
much longer
When diazepam is mixed in propylene glycol, what is the side effect?
pain on injection/glycol toxicity
When diazepam is mixed with soybean formula, what is the side effect?
less painful
What is the onset of action and elimination half time of diazepam?
onset of action: 1-5 minutes elimination half time: 20-40 hours
What does diazepam bind to in the plasma?
Extensively protein bound
How is the duration of action and elimination half time of diazepam when compared to lorazepam?
Duration of action is shorter and elimination half time is longer. Diazepam dissociates from GABA faster than lorazepam
What pathway does diazepam follow for metabolism?
CYP3A
What is the active metabolite of diazepam?
Desmethyldiazepam and oxazepam
When do we se a return of drowsiness with diazepam?
6-8 hours
Where are the active metabolites of diazepam excreted?
in the urine
What can diazepam abolish at 0.1mg/kg IV?
DT’s, Status epileptics, lidocaine toxicity
What benzodiazepine can produce an isoelectric EEG?
Diazepam
What are the effect of diazepam on ventilation?
Minimal effects: 1. Slight decrease Vt 2. After 0.2 mg/kg IV increases in PaCO2 3. Exaggerated with opioids, alcohol, COPD
What can reverse the ventilatory depressant effects of diazepam?
Surgical stimulation
Cardiovascular effects of diazepam?
Minimal decreases in BP, CO and SVR with induction doses. BP changes are additive with opioids
What benzodiazepine has transient depression of baroreceptor mediated HR response?
diazepam
What are the neuromuscular effects of diazepam?
Skeletal muscle tone decreased through spinal neurons
How much do we decrease the dose of diazepam by in the elderly, liver disease patients or in the presence of opioids?
25-50% dose reduction
What does lorazepam resemble?
Oxazepam, it has an extra Cl- atom
When compared to midazolam and diazepam, how are the sedative and amnestic effects of lorazepam?
more potent
What is lorazepam prepared in?
Propylene glycol
Why does lorazepam have slower entrance to the CNS than midazolam or diazepam?
lower lipid solubility
What is the peak effect and elimination half time of lorazepam?
Peak effect: 20-30 minutes (1-4mg IV) Elimination half time is 14 hours (slower than midazolam)
Which benzodiazepine is less affected by hepatic function, age, drugs (cimetidine)?
lorazepam
What does flumazenil antagonize with the BZD/opioid combo?
ventilatory depression
What does flumazenil prevent/reverse?
All agonist activity of Benzos
What is flumazenil a derivative of?
1,4 imidazobenzodiazepine
What is flumazenil metabolized by?
Hepatic microsomal enzymes into inactive metabolites
When is flumazenil contraindicated?
Use of antiepileptic drugs and predicates acute withdrawal seizures
When reversing benzos with flumazenil, will we see acute anxiety, hypertension, tachycardia, or change in MAC?
No
What did Hippocrates contribute to anesthesia?
- Accommodate the operator 2. Avoid sinking down and turning away
What did Dr. Koller contribute to anesthesia?
Utilized cocaine as an anesthetic for eye surgery (Collegague of Sigmund Freud)
What did Dr. Halsted contribute to anesthesia?
1st regional mandibular nerve block with cocaine
What does Histamine induce?
endogenous substance involving basophils and mast cells Contraction of SM in airways Acid secretion in the stomach Neurotransmitter release in CNS.
H1 Receptors (what do they do when activated)
associated with hyperalgesia and inflammatory pain. weak anticholinergic (anti-muscarinic) activity
3 things that histamine induces in the body?
- Contraction of smooth muscles in airway 2. Secretion of acid in the stomach 3. Release of neurotransmitters in CNS
2 Process that H1 receptors are involved in
- Hyperalgesia and inflammatory pain 2. Weak anticholinergic (Anti-muscarinic) activity
H1 Receptor Antagonists (Drugs and side effects)
Diphenhydramine Promethazine (they are effective AND inexpensive) Side effects include: Blurred vision, urinary retention, dry mouth, drowsiness (1st gen), heart block.
What is the greatest side effect from H1 receptor antagonists and why do we see this effect?
Sleepiness because they cross the blood brain barrier
What are the three MOA’s thought to occur when we give an H1 receptor antagonist?
- Receptors in vestibular system; effective for motion sickness 2. Allergic Rhinoconjunctivitis 3. Helps w/ anaphylactic reactions
H2 Receptors (when activated they…)
elevate Cyclic-AMP increase acid production
H2 Receptor Antagonists (MOA)
decrease gastric volume, but do NOT effect pH
Estimated half time and onset of action of Promethazine (Phenergan)?
half time: 9-16 hours onset of action: 5 minutes
Dose of Promethazine (Phenergan)
12.5-25mg
What precaution was place on phenergan as a black box warning in 2009?
Gangrene if promethazine infiltrated
Dose of Promethazine (Phenergan)
12.5-25mg
Histamine releasing drugs
Morphine Mivacurium Protamine Atracurium we need to antagonize both receptors (H1 and H2) to reduce CV effects. (H2 treatment alone increases CV side effects)
Proton Pump Inhibitors (PPIs MOA)
irreversibly binds to acid secreting “pumps” stopping the movement of protons across the gastric parietal cells decrease gastric volume AND lower pH
PPIs (Drugs and side effects)
Omeprazole Pantoprazole Lansoprazole Dexlansoprazole Side effects inlucde: bone fx, Lupus, acute interstitial nephritis, C-Diff, B-12/Mg deficiency, inhibits warfarin metabolism
Omeprazole (PPI)
released as prodrug in the small intestine (EC), returns to parietal cells. CYP450 metabolized. significantly controls daytime, nocturnal, and meal time acid secretion. Dose: 40 mg in 100 ml over 30 minutes. (PO give >3hrs earlier) but needs up to 5 days to take full effect.
Omeprazole (side effects)
Side effects include: HA, Agitation, confusion, ABD pain, N/V, Flatulence
Dose of diphenhydramine?
25-50 mg
What reflex might be inhibited with diphenhydramine use?
Afferent arc of oculo-emetic reflex
Does benadryl exacerbate opioid-induced depression of hypoxic response?
no
Effects of H2 receptor antagonists?
- Decreased gastric volume 2. No effect on gastric pH
4 Side effects of H2 receptor antagonists
- Diarrhea 2. Headache 3. Skeletal muscle pain if given too quickly 4. Weakend gastric mucosa to bacteria in prolonged administration
3 Examples of H2 receptors antagonists
- Cimetidine (Tagamet) 2. Ranitidine (Zantac) 3. Famotidine (Pepcid)
How is cimetidine metabolized and excreted?
In the liver by CYP450 and cleared in the urine
What effect does cimetidine have on CYP450?
Reduces metabolism
7 drugs associated with CYP450 metabolism that we don’t want to give concurrently with Tagamet?
- Warfarin 2. Phenytoin 3. Lidocaine 4. Tricyclics 5. Propranolol 6. Nifedipine 7. Meperidine
Adverse effects associated with cimetidine?
- HA 2. Confusion (Crosses BBB) 3. Bradycardia 4. Hypotension
Normal dose of Cimetidine and renal impairment dose?
Dose: 150-300 mg IV Renal impairment: 1/2 dose
Metabolism and excretion meshing for ranitidine and famotidine?
Hepatic metabolism and renal clearance
4 known drugs that cause histamine release?
- Protamine 2. Atracurium 3. Mivacurium 4. Morphine
Normal dose and renal impairment dose for ranitidine?
Normal: 50mg diluted to 20CC over 2 min Renal impairment: 1/2 dose
Which H2 receptor antagonist has no effect on CYP enzymes?
Famotidine (Pepcid)
Normal dose and renal impairment dose for famotidine (Pepcid)?
Normal: 20mg IV Renal impairment: 1/2 dose
What are proton pump inhibitors most effective for treating?
- Controlling gastric acidity 2. Decreasing gastric volume
Which Histamine receptor antagonist, if given alone in anaphylaxis, has been shown to worse symptoms?
H2
6 pathologies that PPI’s have been associated with?
- Bone fractures 2. SLE 3. Acute intestinal nephritis 4.. C-diff 5. Vitamin B12/Magnesium Deficiency 6. Inhibits warfarin metabolism
What are proton pump inhibitors most effective for treating?
- Controlling gastric acidity 2. Decreasing gastric volume
3 actions of omeprazole
- Released in small intestine (prodrug) 2. Returns to parietal cells 3. Acid-inhibition increases with repeated dosing
6 pathologies that PPI’s have been associated with?
- Bone fractures 2. SLE 3. Acute intestinal nephritis 4.. C-diff 5. Vitamin B12/Magnesium Deficiency 6. Inhibits warfarin metabolism
4 examples of PPIs
- Omeprazole (Prilosec) 2. Pantoprazole (Protonix) 3. Lansoprazole (Prevacid) 4. Dexlansoprazole (Dexilent)
When do we significantly greater control with prilosec administration?
Daytime, nocturnal and meal acid secretion more so than h2 drugs
What is omeprazole (Prilosec) metabolized by?
CYP enzymes, but causes no clinically significant inhibition of other drugs
Dose of omeprazole?
40 mg in 100 cc NS over 30 minutes or PO >3 hours prior
SE associated with omeprazole?
- HA 2. Agitation 3. Confusion 4. ABDOMINAL PAIN 5. N/V 6. Flatulence
What is pantoprazole (protonix) metabolized by?
CYP enzymes in the liver
What H2 receptor antagonist does protonix work just as fast as?
Ranitidine (Zantac)
How long prior to surgery should we give pantoprazole to see a decrease in gastric volume and pH
1 hour prior
Dose of pantoprazoe (protonix)
40 mg in 100 mL over 2-15 minutes
Treatment of choice for GERD?
PPI (increased pH and decreased gastric volume)
Treatment of choice for gastroduodenal ulcers?
PPI
Treatment of choice for aspiration pneumonitis?
H2 blockers b/c they work faster
Treatment of choice for acute upper GI bleed?
PPI infusion post EGD tx
Treatment of choice for aspiration pneumonitis?
H2 blockers b/c they work faster
Promethazine (H1 receptor antagonist)
Elimination 1/2 time: 9 - 16 hours Dose: 12.5 - 25 mg IV (onset 5 minutes) effective for acute N/V, may reduce pain levels watch for IV infiltration street tip: Key ingredient in Lean.
What is an example of an antacid?
Sodium citrate (Bicitra)
What are the two side effects seen from long term antacid us?
- Acid breakdown of food inhibited 2. Acid rebound can occur
3 side effects associated with magnesium based antacids?
- Osmotic diarrhea 2. Neurologic impairment 3. Neuromuscular impairment (diminished deep tendon reflexes)
3 side effects associated with calcium based antacids?
- Hypercalcemia 2. Kidney stones 3. Dysrythmias
Non-particulate antacids neutralize acid, what cases are these good for?
- Trauma 2. Obese patients with reflux 3. Emergent c-sections
2 effects seen when using Sodium Citrate (Bicitra)
- Protection against aspiration pneumonia 2. Increases intra-gastric volume up to 30cc
What are the two effects seen from long term antacid us?
- Acid breakdown of food inhibited 2. Acid rebound can occur
3 effects associated with magnesium based antacids?
- Osmotic diarrhea 2. Neurologic impairment 3. Neuromuscular impairment (diminished deep tendon reflexes)
3 Patient populations that we assume have a full stomach?
- Insulin dependent diabetics d/t delayed gastric motiity 2. Trauma patients 3. Pregnant women >12 weeks gestation
Effect associated with Sodium based antacids?
Increased sodium load
Dose and Onset of action of sodium citrate?
dose: 15-30 mL PO onset of action: Immediately
When do you lose effectiveness of sodium citrate?
30-60 minutes after administration
What major reaction do we see with administration of metoclopromide (raglan) and how do we dampen this?
Extrapyramidal reactions d/t crossing the BBB and we can dampen by given benadryl first
What is the only drug cleared by the FDA for diabetics gastroparesis?
Reglan
3 examples of dopamine blockers?
- Metocolopramide (Reglan) 2. Domperidone [Associated with cardiac arrest) 3. Droperidol (Inapsine)
SE associated with reglan?
- Abdominal cramping (if rapid IV admin) 2. Hypotension and HR changes 3. Extra pyramidal symptoms and increased sedation with CNS deppressants
Dose of metoclopramide and when to administer it?
10-20mg IV over 3-5 minutes, 15-30 minutes prior to induction
Why is domperidone not FDA approved?
It is associated with Dysrhythmias and sudden death
What does domperidone increase the secretion of?
Prolactin secretion by pituitary gland
Why is domperidone not FDA approved?
It is associated with Dysrhythmias and sudden death
H2 Receptor Antagonists (MOA)
decrease gastric volume, but do NOT effect pH
What two diagnosis was droperidol (inapsine) developed to treat?
- Schizophrenia 2. Psychosis
What is the blackbox warning associated with droperidol?
QT prolongation with higher doses such as 2.5-5mg IV
Dose of droperidol (Inapsine)
0.625-1.25mg IV
Where is serotonin released from in the small intestine?
Chromaffin cells
Where are the 5HT3 receptors found?
Kidneys, colon, liver, lung, stomach
Where are high concentration of 5HT3 receptors found that are linked to vomiting?
Brain and GI tract
5HT3 antagonists have almost no side effects, were great for PONV and were originally use in the treatment of what?
Chemotherapy and Radiation therapy related N/V (CIV)
What are 5HT3 receptor antagonist NOT effective in treating?
motion sickness/vestibular stimulation
3 Examples of 5HT3 receptor antagonist?
- Ondansetron (Zofran) [Works the best] 2. Granisetron (Kytril) 3. Dolasteron (Anzemet)
Which 5HT3 antagonist was the first of its kind and does not have an CNS effects?
Ondansetron (Zofran)
Dose and plasma half life of ondansetron (zofran)?
Dose: 4-8mg IV Plasma 1/2: 4 hours
What are three possible MOA’s of corticosteroids?
- Glucocorticoid receptor in nucleus tractus solitarius 2. Increase effectiveness for 5HT3 antagonists and droperidol 3. Possible inhibition of prostaglandin synthesis and endorphin release
What receptor is droperidol (inapsine) a strong antagonists of?
D2 receptors
What annoying side effect is associated with dexamethasone admin?
perineal burning/itching
What is the dose if corticosteroids are used for PONV?
4-8 mg IV
What is the delay in onset of dexamethasone (decahedron) and how long does its efficacy persist?
Delay in onset of 2 hours and efficacy persists for 24 hours
What annoying side effect is associated with dexamethasone admin?
perineal burning/itching
What class of drug is scopolamine?
Competitive muscarinic antagonist
Where is the thinnest area available for a scopolamine patch?
Post auricular area (behind the ear)
Priming dose of scopolamine?
1.5mg @ 5mcg/hour
SE associated with scopolamine patches?
Dilated pupils and light sensitivity
How long does 1 scopolamine patch last?
24-72 hours
Priming dose of scopolamine?
1.5mg @ 5mcg/hour
What 3 effects are seen cellularly when giving bronchodilators?
- Activate cAMP 2. Decrease Calcium ion entry 3. Decrease contractile protein sensitivity to Calcium ions
Which version of bronchodilators is more lipophilic? SABA or LABA?
LABA (long acting bronchodilator)
What is the advantage of using levo-albuterol (xopenex) over albuterol (proventil)?
Xopenex does not see as big of a jump in HR
H2 Receptor Antagonists (Drugs and Side Effects)
Cimetidine Ranitidine Famotidine Side effects include: Diarrhea, HA, Skeletal muscle pain, Weakened gastric mucosa to bacteria (prolonged use)
Cimetidine (H2 receptor antagonist)
metabolized by CYP450, cleared in urine Dose: 150 - 300 mg IV (half for renal disease) binds heavily to heme group of CYP450 (inhibits) Side effects include: HA, confusion (crosses BBB), bradycardia, hypotension
Ranitidine (H2 receptor antagonist)
hepatic metabolized, urine cleared (moderate CYP450 binding) Dose: 50 mg diluted to 20 ml over 2 minutes (half for renal disease)
Famotidine (H2 receptor antagonist)
hepatic metabolism, urine cleared (none/least CYP450 binding) Dose: 20 mg IV (half for renal disease)
Histamine releasing drugs
Morphine Mivacurium Protamine Atracurium we need to antagonize both receptors (H1 and H2) to reduce CV effects. (H2 treatment alone increases CV side effects)
Proton Pump Inhibitors (PPIs MOA)
irreversibly binds to acid secreting “pumps” stopping the movement of protons across the gastric parietal cells decrease gastric volume AND increases pH
PPIs (Drugs and side effects)
Omeprazole Pantoprazole Lansoprazole Dexlansoprazole Side effects inlucde: bone fx, Lupus, acute interstitial nephritis, C-Diff, B-12/Mg deficiency, inhibits warfarin metabolism
Omeprazole (PPI)
released as prodrug in the small intestine (EC), returns to parietal cells. CYP450 metabolized. significantly controls daytime, nocturnal, and meal time acid secretion. Dose: 40 mg in 100 ml over 30 minutes. (PO give >3hrs earlier) but needs up to 5 days to take full effect.
Omeprazole (side effects)
Side effects include: HA, Agitation, confusion, ABD pain, N/V, Flatulence
Pantoprazole (PPI)
CYP metabolism in liver. works fairly quickly (1 hour prior) to decrease gastric volume. no drug interactions Dose: 40 mg in 100 ml over 2 - 15 minutes.
Induction of anesthesia drugs
Etomidate, ketamine, propofol, narcotics
