IV Drugs Flashcards
Describe the metabolism of NMBs
Succinylcholine - plasma cholinesterase
Atracurium / Cisatracurium - Hofmann elimination
Vecuronium / Rocuronium - primarily hepatic
Pancuronium - primarily renal
List the cardioselective B blockers
Block only B1 receptors
“BEAM”
Betaxolol Bisoprolol Esmolol Atenolol Acebutolol Metoprolol
Which drugs are contraindicated in Parkinson’s disease?
Drugs which may produce extrapyramidal effects such as dopamine antagonists droperidol, promethazine; and metoclopramide (dopamine and serotonin antagonist)
Describe the solubility of Midazolam
Water-soluble drug that is converted to a lipid-soluble drug when exposed to the blood’s pH
Describe the effects of anticholinergics (Atropine, Glyco, Scop)
Decreased gastric acid secretion
Decreased salivary secretion
Decreased LES tone
Tachycardia
Mydriasis (pupil dilation)
May cause urinary retention
Which anticholinesterase drug can cross the BBB?
Physostigmine is a tertiary amine and is able to cross the BBB (useful in treating central anticholinergic syndrome)
Neostigmine, Pyridostigmine, and Edrophonium are quarternary ammonium compounds and cannot cross the BBB
What makes Meperidine unique?
Meperidine is an opioid that is structurally similar to atropine and possess mild anticholinergic properties. Instead of the usual bradycardia seen with opioids, tachycardia can be seen with Meperidine. Meperidine can also cause decreases in contractility at large doses.
Normeperidine is a metabolite of Meperidine and can lead to delirium and seizures, especially in patients with renal or hepatic impairment
Does Ketamine have any active metabolites?
Norketamine, which is about 1/3 as potent at Ketamine
How does Ephedrine work to increase BP?
Indirectly by stimulating the release of norepinephrine from sympathetic nerve fibers and to a lesser degree, by directly binding to adrenergic receptors
Which induction agent is most likely to cause myocardial depression? Why?
Thiopental
Dose dependent negative inotropic effect results from a decrease in calcium influx in the myocardium
What drug should be avoided in patients taking Ecothiophate for glaucoma?
Succinylcholine, as it’s effects can be prolonged by Ecothiophate’s inhibition of acetylcholinesterase
Which muscle relaxant causes slight histamine release?
Atracurium
Termination of action of norepinephrine is achieved primarily through what mechanism?
80% of released norepinephrine rapidly undergoes reuptake into the sympathetic nerve terminals (uptake 1) and reenters storage vesicles for future use
How does Metoclopramide (Reglan) work?
It is a dopamine antagonist that increases lower esophageal sphincter tone and stimulates gastric and upper GI tract motility
How much will administration of Succinylcholine raise serum [K+]?
0.5 mEq/L
What conditions or drugs can enhance neuromuscular blockade?
Volatile anesthetics
Aminoglycoside antibiotics (Tobra-/Genta-/Neo-/Streptomycin)
Magnesium
Local anesthetics
Furosemide
Dantrolene
Calcium channel blockers
Lithium
Hypothermia
Hypokalemia
Acidosis
Laudanosine is a metabolite of which drug?
Atracurium
Laudanosine is a tertiary amine that can cross the BBB and cause CNS stimulation at very high levels
Pre-treatment with a non-depolarizing muscle relaxant will have what effect on the expected side effects of Succinylcholine?
Attenuates, but does not eliminate: Cardiac dysrhythmias Elevations in infra gastric pressure Elevations of ICP Myalgias
Does not eliminate hyperkalemia
List the order of onset of anticholinesterase drugs
Edrophonium (1 to 2 minutes)
Neostigmine (7 to 11 minutes)
Pyridostigmine (16 minutes)
List some conditions that may lead to an increased hyperkalemic response to Succinylcholine
Denervation injuries Burns Acute upper motor neuron injuries (stroke) Muscle trauma Severe abdominal infections
Risk usually peaks 10 to 50 days after injury, but should be avoided if possible anytime after 24 hours from injury
What is the percentage of neuromuscular receptors which may be blocked and still allow a 5 second head lift?
50% (considered adequate recovery)
What is pseudocholinesterase? Where is it produced? What is its half-life?
Pseudocholinesterase (also known as plasma cholinesterase or butyrylcholinesterase) is an enzyme found in plasma that metabolizes acetylcholine, succinylcholine, ester-type local anesthetics, heroin, and cocaine
- Does NOT metabolize Remifentanil or Esmolol (red cell esterase for both)
It is produced by the liver
Its half-life is approximately 8 to 16 hours
How do NSAIDs work?
NSAIDs inhibit cyclooxygenase, which is necessary for prostaglandin synthesis
Prostaglandins are mediators of pain and inflammation and act at the site of injury (peripherally)
Why is Succinylcholine avoided in children?
Fear of un-diagnosed muscular dystrophy that could lead to sever hyperkalemia and cardiovascular collapse
- hyperkalemia is 2/2 rhabdomyolysis
Describe the onset of paralysis in central vs peripheral muscles
Neuromuscular blockade develops faster, lasts a shorter time, and recovers more quickly in the central muscles of the airway than in more peripheral muscle groups
Observation of the pattern of blockade of the orbicularis oculi is similar to that of the laryngeal muscles and diaphragm
How does Pancuronium effect the cardiovascular system?
Pancuronium may cause increased heart rate, MAP, and CO
Several mechanisms for this, including a vagolytic effect, norepinephrine release, and decrease reuptake of norepinephrine
Which opioid is resistant to reversal with naloxone?
Buprenorphine
What is Fospropofol an what are it’s advantages?
Fospropofol is a prodrug of Propofol
Because it is water soluble, it causes no pain on injection and carries no risk of hypertriglyceridemia, PE, or sepsis
Describe Clonidine
a2 agonist
Primarily stimulates central adrenergic receptors and decreases sympathetic response
Decreases MAC requirements
Decreases extremes in blood pressure
Has analgesic properties and decreases opioid requirements
Can decrease post-anesthetic shivering
Can be given orally, IV, epidurally, intrathecally, and in peripheral nerve blocks
When given intrathecally, has been shown to decrease persistent postsurgical pain
What is the dibucaine number?
A test to evaluate function of pseudocholinesterase
80 - normal function (up to 10 minutes of paralysis)
50 to 60 - heterozygous (up to 30 minutes of paralysis)
20 - atypical pseudocholinesterase (over 3 hours of paralysis)
List the a blockers
Phentolamine - short-acting non-selective antagonist used primarily in hypertensive emergencies from pheochromocytoma
Phenoxybenzamine - long-acting non-selective antagonist (irreversible) that is commonly used for pre-operative treatment of pheochromocytoma
Prazosin/Terazosin/Doxazosin - selective a1 antagonists used most commonly for BPH
Mirtazapine - selective a2 antagonist used in the treatment of depression
How does Norepinephrine work?
Mostly alpha stimulation
Results in increased SVR
How does Epinephrine work?
Mostly beta-1 stimulation
- increased cardiac output
At high doses, alpha effects increase
- increased SVR
How does Isoproterenol work?
Non-selective B-agonist
Results in increased cardiac output and decreased SVR
How does Dobutamine work?
B1-receptor agonist
Increases CO with little change in SVR
How does Dopamine work?
Low doses (up to 5 nanos) stimulate DA receptors - vasodilation
Middle doses (5-10) stimulate beta-1 receptors - increases CO
High doses (>10) stimulate alpha receptors - increased SVR
Which opioid receptor responsible for increase in prolactin?
u1-receptor
Which opioid receptor responsible for respiratory depression, muscle rigidity, constipation, and biliary spasm?
u2-receptor
Which opioid receptor responsible for dysphoria and sedation?
k-receptors
Describe the phases of depolarizing blockade
Phase I - occurs with depolarization of the postjunctional membrane
Phase II - occurs when the postjunctional membranes have become repolarized but do not respond normally to acetylcholine
Phase II blockade responds similarly to non-depolarizing blockade
List the induction doses of common agents
Propofol: 1.5 - 2.5 mg/kg
Thiopental: 3 - 6 mg/kg
Etomidate: 0.2 - 0.5 mg/kg
Ketamine: 1 -2 mg/kg
What is Thiopental? How does it work? What is unique about it?
A barbiturate
Binds to GABAa receptor, increasing duration of opening of a chloride-specific ion channel
Causes hypotension via vasodilation, with profound reflex tachycardia
Decreases ICP more than BP, thus maintaining CPP
Contraindicated in porphyria and sulfa allergy
What is Midazolam? How does it work? What is unique about it?
A benzodiazepine
Binds to GABAa receptor, increasing the frequency of opening of a chloride-specific ion channel
Water-soluble, but converts to lipid-soluble drug at physiologic pH
Produces anterograde amnesia
Pts with kidney failure may accumulate high levels of metabolite a-hydroxymidazolam
What is Ketamine? How does it work? What is unique about it?
Analog of phencyclidine (PCP)
Acts as an NMDA receptor antagonist, giving it some additional analgesic properties
Dissociates thalamus from limbic cortex, creating a state of dissociative anesthesia
Has an active metabolite, norketamine
Increases BP, HR, CO, PA pressures, and myocardial work
- Indirectly via stimulation of sympathetic nerves and inhibition of norepinephrine reuptake
- Direct myocardial depressant effects only apparent during catecholamine depletion
Bronchodilator, but also increases secretions
Increases cerebral O2 consumption, CBF, and ICP
Tolerance may develop after multiple exposures within a short period of time
Intra-operative infusions at sub-anesthetic doses have been shown to have opioid sparing effects
What is Etomidate? How does it work? What is unique about it?
A carboxylated imidazole ring
Binds to subunit of GABAa receptor, increasing the receptor’s affinity for GABA
Minimal effects on the CV system compared to other induction agents
Can cause pain on injection, myoclonus, and adrenal suppression of cortisol and aldosterone synthesis via inhibition of 11-B-hydroxylase
What is Propofol? How does it work? What is unique about it?
An alkylphenol
Allosterically increases the binding affinity of the GABAa receptor for GABA
Long-term infusion has been associated with Propofol Infusion Syndrome - lactic acidosis, hyperkalemia, rhabdomyolisis, lipemia, and death
Causes decreased BP via decreased SVR, decreased preload, and decreased contractility
Has antipruritic and antiemetic properties
Describe the mechanism of depolarizing vs non-depolarizing muscle relaxants
Depolarizing relaxants (Succinylcholine) resemble ACh and act as receptor agonists
- Cause continuous end-plate depolarization via the opening of peri-junctional Na+ channels
- After initial opening and excitation, Na+ channels inactivate and cannot re-open until end-plate repolarizes
Non-depolarizing relaxants bind ACh receptors,but do not cause the necessary conformational change
- Act as competitive antagonists
List the intubating doses of NMBs
Succinylcholine: 1 - 2 mg/kg Atracurium: 0.4 - 0.5 mg/kg Cisatracurium: 0.1 - 0.15 mg/kg Pancuronium: 0.1 mg/kg Vecuronium: 0.1 mg/kg Rocouronium: 0.6 mg/kg
What type of drug is Succinylcholine? What is unique about it?
The only depolarizing NMB currently in use
Consists of 2 joined ACh molecules
Is rapidly metabolized by plasma pseudocholinesterase
Many side effects
- Cardiac arrhythmias, especially bradycardia
- Fasciculations and subsequent myalgias
- Increased intra-gastric, intra-ocular, and intra-cerebral pressures
- Hyperkalemia
- Possible trigger of MH
Describe the types of non-depolarizing NMBs
Benzylisoquinolones
- Atracurium
- Cisatracurium
Aminosteroids
- Pancuronium
- Vecuronium
- Rocuronium
What type of drug is Atracurium? What is unique about it?
An intermediate-acting benzylisoquinolone
Metabolized by both nonspecific ester hydrolysis and by Hofmann elimination
- Unaffected by renal or hepatic function
Triggers dose-dependent histamine release, resulting in hypotension and tachycardia (bronchospasm in asthmatics)
Toxic metabolite called laudanosine that can accumulate in individuals with renal failure
What type of drug is Cisatracurium? What is unique about it?
An intermediate-acting benzylisoquinolone
Metabolized by Hofmann elimination
Does not cause histamine release
What type of drug is Pancuronium? What is unique about it?
A long-acting aminosteroid
Mostly renal metabolism
Causes vagal blockade and sympathetic stimulation, leading to hypertension and tachycardia
What type of drug is Vecuronium? What is unique about it?
An intermediate-acting aminosteroid
Mostly hepatic metabolism
Has an active metabolite
What type of drug is Rocuronium? What is unique about it?
An intermediate-acting aminosteroid
Mostly hepatic metabolism
Can be given “double-dose” with onset of action that almost approaches that of Succinylcholine
What are the side effects of cholinesterase inhibitors (ie. Neostigmine, Edrophonium, Pyridostigmine)?
Bradycardia
Bronchospasm and increased respiratory secretions
Increased GI activity (nausea/vomiting/incontinence)
Define half-life. What are the 2 types?
Half-life (t1/2) is the time it takes for blood levels of drug to decrease to half of what it was at equilibrium
Alpha (distribution) half-life is due to distribution to tissue reservoirs
Beta (elimination) half-life is due to the drug being metabolized and excreted
What is the equation for volume of distribution (Vd)?
(amount of drug in the body) / (concentration of drug in plasma)
What does the volume of distribution (Vd) tell us about the amount of drug in plasma vs tissue?
Small Vd - drug stays mainly in plasma, with little in tissues
Medium Vd - similar concentration of drug in plasma and tissue
Large Vd - drug mostly in tissues, with little staying in the plasma
What is the equation for half-life?
t1/2 = 0.69 x (volume of distribution/clearance)
What is the mechanism of Acetazolamide?
Inhibits carbonic anhydrase
Results in decreases H+ secretion and increased loss of Na, HCO3-, and water
What is Amiloride? Any side effects?
A K+ sparing diuretic that inhibits the epithelial Na channel (ENaC), reducing Na reabsorption
Can result in hyperkalemia
What is Amiodarone? How does it work? Any side effects?
An anti-arrhythmic that blocks myocardial K and Ca channels, slowing conduction speed in SA node causing prolongation of the refractory period
Can cause hypotension and bradycardia
Associated with abnormal TFTs, PFTs, and LFTs
Describe anti-platelet drug mechanisms
ASA/NSAIDs:
Inhibit COX, decreasing TXA2
Clopidogrel/Prasugrel/Ticlopidine:
Block ADP receptor, decreasing activation of platelets
Abciximab/Eptifibatide/Tirofiban:
Inhibit glycoprotein IIb/IIIa, decreasing platelet aggregation
What type if drugs are Hydrochlorthiazide and Metolazone? Any side effects?
Thiazides diuretics that inhibit the Na-Cl cotransporters of the renal tubules
Results in decreases reabsorption of Na and Cl
Can cause hypercalcemia and hyperglycemia
What type of drug is Furosemide? Any side effects?
A loop diuretic that inhibits the Na-K-2Cl cotransporter
Results in decreased Na and H2O reabsorption
Can cause metabolic alkalosis due to increased Cl excretion
How do burns effect NMB?
More sensitive to succinylcholine
More resistant to non-depolarizing NMBs
How does Phenytoin effect NMB?
Acute administration potentiates the effects of NMBs
Chronic administration results in decreased effect of NMBs
What is unique about Alfentanil?
Rapid onset due to very low pKa
Very short duration of action due to very low volume of distribution
How does renal failure effect Neostigmine
Neostigmine is almost completely eliminated by the kidneys
Renal failure prolongs the duration of action of Neostigmine
- dosage must be reduced around 50 to 75%
Why is fentanyl a “short-acting” opioid when it has the same elimination half-life of Morphine and Dilaudid?
Fentanyl is much more lipophilic so it has a much shorter alpha-half-life (distribution)
Why is it okay to use Succinylcholine in pregnant women?
An insignificant amount of Succinylcholine crosses the placenta due to its high ionization and low lips solubility
List the drugs that should be dosed based on ideal body weight (IBW)
Propofol (infusion)
Vecuronium
Rocuronium
Remifentanil
If you use succinylcholine to re-intubate a patient after reversal with neostigmine, how is the duration of action of succinylcholine affected and why?
Prolonged duration of action due to Phase 1 Block augmentation
Which pressor increases cerebral oxygenation in addition to increasing CPP?
Vasopressin
Why is sodium bicarbonate given? What are its effects?
Sodium bicarbonate is often given peri-operatively to correct an acidosis
Associated with a transient increase in paCO2, EtCO2, and intracranial pressure
Can cause hypotension due to hypocalcemia, ventricular depressant effects, and redistribution of blood volume from pulmonary vasculature
Describe sodium nitroprusside toxicity
Sodium nitroprusside administration has potential for causing toxicity due to accumulation of its metabolic byproducts: cyanide and thiocyanate
Cyanide toxicity:
- elevated mixed venous oxygen
- tachyphylaxis to SNP
- metabolic acidosis
- flushing
Thyiocyanate toxicity:
- hypoxia
- nausea
- tinnitus
- muscle spasm
What are the pharmacologic implications of major burns?
Severe burns lead to hypoalbuminemia, which can increase the free fraction of anesthetic drugs
- lower doses of benzos required
- higher doses of opioid required due to tolerance, despite higher free fraction
Increased catecholamine and corticosteroid levels
- insulin resistance, usually requiring larger doses
Proliferation of extrajunctional Ach receptors
- exagerated response to succinylcholine
- resistance to non-depolarizing NMBs
What is the correct de-fasciculating dose for non-depolarizing NMBs prior to giving succinylcholine?
10% of ED95 dose
- NOT 10% of intubating dose
