ITE CA2 Pharm 3 Flashcards
Ancef with hx penicillin allergy
Higher Risk
If the patient’s penicillin reaction was less than 10 years ago OR they had IgE-mediated symptoms after receiving a penicillin OR they had a severe non-IgE-mediated reaction, do not give cephalosporins. Recommend skin testing to the patient before future surgical procedures. If unsure about the reaction and timing, recommend skin testing prior to the administration of penicillins. Skin testing should not be recommended to patients who had a severe exfoliative past reaction to penicillin, such as toxic epidermal necrolysis.
Low Risk
If patient’s penicillin reaction is more than 10 years ago AND they had no IgE-mediated symptoms AND they had no severe non-IgE-mediated reactions, then they are low risk (< 1%) for having a reaction if they receive cephalosporins. The risk of anaphylaxis is very small in these patients.
mechanism of action of echinocandins and name some
caspofungin, micafungin and anidulafungin
Echinocandins are the preferred first line treatment of candidemia. They act by inhibiting 1,3-beta-D-glucan synthase and cell wall synthesis.
-azoles
name some
MoA
other considerations
The azole class of antifungals includes voriconazole, fluconazole, and itraconazole. These act by inhibiting the P-450 dependent enzyme 14-alpha-demethylase which converts lanosterol to ergosterol for the cell membrane. Both fluconazole and voriconazole have been used to treat candidemia. Itraconazole is not used for systemic infections. The azoles will inhibit cytochrome P-450 enzymes including CYP2C19, CYP3A4, and CYP2C9. Care must be taken when giving azole antifungals with other cytochrome metabolized medications.
Amphotericin B
MoA
side effects
Amphotericin B was the drug of choice for decades. It acts by binding ergosterol in fungal cell membranes causing cellular leaking and cell death. However several randomized clinical trials have shown non-inferiority with azole and echinocandin antifungals. Therefore these classes are now the preferred first line treatment of candidemia as amphotericin can be nephrotoxic, cardiotoxic, and associated with hypokalemia and anaphylaxis
Candida glabrata is intrinsically resistant to .
Candida glabrata is intrinsically resistant to fluconazole.
obesity and butyrylcholinesterase activity
increased
what drugs cause direct cerebral vasodilation
Calcium channel blockers, nitroglycerin, hydralazine, nitroprusside, and adenosine cause direct cerebral vasodilation.
Midaz in uremia
Uremia will result in a higher concentration of free-fraction, unbound midazolam. The dosage should, therefore, be decreased especially when used as premedication
where is angiotensinogen made
liver
what clotting factors are made outside the liver
3, 4, von willebrand (von w is made in liver and also in endothelial cells)
where are platelets made
megakaryocytes in the plasma
most common complication of retrobulbar block
retrobulbar hemorrhage
Clevidipine
class
metabolism
how are other drugs in its classed metabolized
Clevidipine is an intravenous, ultra-short acting, dihydropyridine calcium channel antagonist with selectivity for arteriolar vasodilation that is rapidly metabolized by plasma and red cell esterases providing its short duration of action. The other calcium channel blockers are metabolized by the cytochrome P450 system in the liver.
Muscarinic effects of cholinergic drugs include
Nicotinic effects of cholinergic drugs include
Muscarinic effects of cholinergic drugs include bradycardia, bronchospasm, miosis, salivation, lacrimation, defecation, urination, and sweating.
Nicotinic effects of cholinergic drugs include muscle fasciculations, weakness, paralysis, and tachycardia.
Muscarinic effects with mnemonic
Mnemonic devices for muscarinic effects:
SLUDGE-Mi “Sludge Me”: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis, Miosis
DUMBELS: Defecation/Diaphoresis, Urination, Miosis, Bradycardia/Bronchospasm, Emesis, Lacrimation, Salivation
how do dex and clonidine work
Alpha-2 receptors are found presynaptically and inhibit norepinephrine release. Clonidine and dexmedetomidine are alpha-2 agonists. They cause a decrease in sympathetic outflow from the central nervous system, leading to sedation and bradycardia. Clonidine has a 200:1 selectivity for alpha-2 compared to alpha-1. Dexmedetomidine preferentially binds alpha-2 with a ratio of 1600:1.
The mechanism of beta-agonist induced bronchodilation is
The mechanism of beta-agonist induced bronchodilation is via Gs effects, cAMP generation, activation of protein kinase A, decreased intracellular calcium, and resulting airway muscle relaxation.
Stimulation of central (nicotinic or muscasrininc?) acetylcholine receptors can lead to seizures.
Stimulation of central nicotinic acetylcholine receptors can lead to seizures. Caution should be used in patients who are taking nicotinic acetylcholine receptor agonists such as varenicline when considering the use of physostigmine to reverse central depressant effects of anticholinergic medications.
medications with nicotinic properties
medications with nicotinic properties include varenicline, bupropion, dextromethorphan, hexamethonium, and several nondepolarizing neuromuscular agents.
What is the anti-inflammatory mechanism of dexamethasone
Dexamethasone is a glucocorticoid that agonizes the NR3C1 receptor (also known as glucocorticoid receptor or GCR) to upregulate anti-inflammatory proteins and repress inflammatory mediator production. Steroids also inhibit prostaglandin synthesis at the beginning of the arachidonic acid pathway.
CYP 450 inducers
Rifampin Phenytoin Carbamazepine Glucocorticoids St. John's Wort Tamoxifen Phenobarbital, Primidone
CYP 450 inhibitors
Grapefruit juice
Protease inhibitors (ritonavir, indinavir)
Azole antifungals (ketoconazole, itraconazole)
Select SSRIs (above)
Cimetidine
Quinidine
Macrolide antibiotics (erythromycin, clarithromycin)
SSRIs and inhibition of CYP enzymes Fluoxetine (Norfluoxetine) Fluvoxamine Paroxetine Sertraline Escitalopram Citalopram
Fluoxetine (Norfluoxetine) 3A4, 2D6 Fluvoxamine 3A4, 2D6, 2C9, 2C19 Paroxetine 2D6 Sertraline 2D6 Escitalopram None Citalopram None
Cimetidine vs ranitidine
Of the two H2-receptor antagonists commonly used in the perioperative setting (cimetidine and ranitidine), ranitidine offers a longer duration of action and fewer side effects.
epi effect on blood vessels
The effect of epinephrine on blood vessels depends on the receptor. Alpha receptors cause vasoconstriction but beta receptors cause vasodilation.
Buprenorphine
Buprenorphine, a partial μ-receptor agonist, is a very effective agent at mitigating opioid withdrawal given its action at the μ-receptor itself. As a partial agonist, it has a ceiling effect for its analgesic and euphoric properties, as well for its respiratory depressive effects. It is often administered in combination with naloxone in an oral formulation to discourage its abuse.
Naloxone vs naltrexone
Naltrexone is an orally bioavailable opioid antagonist. It may be utilized during medication-assisted opioid withdrawal as the withdrawal period nears the end in order to antagonize the effects of opioids. This diminishes any benefit that a patient with an opioid-use disorder may experience should they attempt to further abuse opioids while on this therapy. Acute ingestion of naltrexone in a patient on chronic opioid therapy would precipitate or worsen withdrawal symptoms.
Because naloxone is not orally bioavailable, it has no clinical effect when taken orally in combination with buprenorphine. Should this formulation be abused, however, and either be injected or snorted, the naloxone bypasses first-pass hepatic metabolism and exerts its antagonistic effect, precipitating an acute withdrawal. In this way, this formulation encourages the proper and safe use of the buprenorphine.
Omalizumab
Omalizumab is a monoclonal anti-IgE antibody. It is used as an antihistamine anti-inflammatory for patients with severe asthma.
Budesonide
Budesonide is an inhaled corticosteroid that blocks late-phase reactions to allergens, reduces airway hyperresponsiveness, and inhibits inflammatory cell migration and activation.
Mepolizumab
Mepolizumab prevents eosinophil action by blocking interleukin-5.
Montelukast
Montelukast is a leukotriene modifier used as an alternative to long-acting beta agonist in treating mild intermittent asthma
Immunoglobulin E (IgE)
Immunoglobulin E (IgE) is an antibody synthesized by plasma cells essential in type I hypersensitivity as well as in anti-parasitic immunity. Type I hypersensitivity involves an immunologic reaction to a repeat allergen exposure. This reaction may manifest in a variety of ways including mild allergic rhinitis as well as anaphylactic shock.
Tramadol receptors
It is a μ-opioid receptor agonist, NMDA antagonist, and norepinephrine and serotonin reuptake inhibitor
gabapentin mechanism
The mechanism is decreased transmission of pain resulting from inhibition of voltage-gated calcium channels via binding of the α2-δ subunit.
that results in decreased release of glutamate
which results in decreased production of pain mediator substance P
examples of direct muscarinic acetylcholine agonists.
Bethanechol, carbachol, and pilocarpine are examples of direct muscarinic acetylcholine agonists. These drugs are resistant to breakdown by acetylcholinesterase.
hydrophilic vs lipophilic opioids in spinal
Hydrophilic opioids, which tend to remain within the CSF, have the potential to produce a delayed but longer duration of analgesia. They also cause a generally higher incidence of side effects because of cephalic or supraspinal spread of these compounds. Lipophilic opioids, such as fentanyl and sufentanil, tend to provide a rapid onset of analgesia and their rapid clearance from CSF may limit cephalic spread and the development of certain side effects such as delayed respiratory depression.
Dexamethasone site of action
Dexamethasone’s antiemetic activity is likely mediated via central inhibition of the nucleus tractus solitarii.
Muscle weakness from high magnesium concentrations results from
Muscle weakness from high magnesium concentrations results from inhibition of calcium influx, leading to reduced acetylcholine release.
lidocaine and seizures
Lidocaine decreases seizure duration and should be avoided during ECT.
Terbutaline moa
Terbutaline can be used to slow or halt premature labor via its selective ß2-agonism, which results in uterine relaxation. Like all catecholaminergic agents, it exhibits dose-dependent interaction with other catecholaminergic receptors. Further, this interaction varies from patient to patient.
Glucose intolerance as a consequence of oral terbutaline treatment.
Diltiazem
Diltiazem is unique among the calcium channel blockers in its ability to act on both smooth muscle and cardiac muscle at clinically-relevant doses. Thus, it acts as both a vasodilator and a cardiac depressant, decreasing peripheral vascular resistance and dilating coronary arteries with little-to-no reflex tachycardia.
atropine paired with what for reversal
Neostigmine is typically combined with glycopyrrolate while edrophonium is paired with atropine.
echothipohate eye drops effect on NMBD
Reduction in plasma cholinesterase levels after prolonged administration of echothiophate iodide eye drops occurs, which would result in prolongation of succinylcholine as well.
cyanide tox tx
Hydroxocobalamin is first line therapy for patients with cyanide toxicity.
combustion of synthetic materials can lead to
cyanide toxicity
how ACI-i cause cough
ACE inhibitors prevent the breakdown of bradykinin and substance P, which accumulates in the upper respiratory tract or lungs thereby causing coughing.
nitroprusside moa
mechanism of action relies on its breakdown to nitric oxide
how does a spinal wear off
Redistribution of local anesthetics from the intrathecal space is responsible for the termination of neuraxial blockade. Factors that speed this recovery include the cerebrospinal fluid volume, large distribution of local anesthetic, and use of a hydrophilic local anesthetic. No drug metabolism of local anesthetics occurs within the intrathecal space.
Meperidine metabolite
Meperidine is metabolized in the liver to normeperidine, which can cause seizures.
Ketamine CMRO2.
Ketamine increases CMRO2.
Ketamine heart
The predominant hemodynamic effect of ketamine is indirect myocardial stimulation. Some direct myocardial depression is seen, however this is almost never clinically significant due to the indirect stimulation effects, even in critically ill patients.
Drug - Dosing weight Thiopental Propofol Fentanyl Remifentanil Succinylcholine Vecuronium Rocuronium Cisatracurium
Thiopental LBW (Induction); TBW (Maintenance) Propofol LBW (Induction); TBW (Maintenance) Fentanyl LBW (lean) Remifentanil LBW Succinylcholine TBW (total) Vecuronium IBW (ideal body weight) Rocuronium IBW Cisatracurium IBW
Hydromorphone metabolism
Hydromorphone is primarily metabolized to hydromorphone-3-glucuronide which provides no analgesic effects. Buildup of renally-excreted hydromorphone-3-glucuronide can lead to neuroexcitatory effects including agitation, restlessness, and myoclonus.
botulism treatment
The mainstay of treatment for botulism includes human derived immune globulin in patients less than one year of age and equine derived antitoxin in patients over one year of age. Supportive therapies are also important and includes intubation as needed.
drug of choice for morphine spinal itching
Pruritus is a very common side effect of neuraxial morphine. Nalbuphine is the drug of choice and antihistamines have little or no effect (other than causing sedation).
Alfentanil pKa and fraction of nonionized drug at physiologic pH
Alfentanil has the lowest pKa (6.5) and highest fraction of nonionized drug at physiologic pH.
what determines opioid duration of action
The duration of effect of opioids, unlike many other drugs, is not primarily determined by drug elimination, but more importantly, by lipid solubility. Morphine has a longer onset time and duration of action because it has a more difficult time crossing and then leaving the blood-brain (or blood-spinal cord) barrier due to a lower lipid solubility. By contrast, the more lipid-soluble fentanyl has a shorter onset and duration of action since it readily crosses, and leaves, the blood-brain barrier.
Treatment for status epilepticus includes:
Treatment for status epilepticus includes:
First Line: benzodiazepines.
Second Line: fosphenytoin, phenytoin, valproic acid, or levetiracetam.
Third Line: propofol or phenobarbital.
benzo dosing for status epilepticus
IV - lorazepam - 4mg slow - 0.1mg/kg peds
IM - midazolam - 10mg - 0.2mg/kg peds
Rectal - Diazepam - 10mg - 0.5 mg/kg peds
midaz can also be given IV
selectivity of beta blockers
Nonselective β antagonist Propranolol Nadolol Timolol Pindolol Sotalol
Nonselective β and selective α1 antagonist
Carvedilol
Labetalol
Selective β1 antagonist Bisoprolol Betaxolol Esmolol Atenolol Acebutolol Metoprolol
The cardioselective beta blockers
list
effects
The cardioselective beta blockers include esmolol, atenolol, and metoprolol, which reduce chronotropy (heart rate), dromotropy (AV node conduction), and inotropy (contractility) to decrease myocardial oxygen demand and increase supply (more time in diastole).
TrueLearn Insight : A mnemonic to recall the beta-1 selective beta-blockers is “BEAM” (β1, bisoprolol, betaxolol, esmolol, atenolol, acebutolol, metoprolol).
Alvimopan
Alvimopan is a potent µ-receptor antagonist which does not cross the blood-brain barrier. It is used to help prevent postoperative ileus while allowing continuation of pain management with opioids.
Diphenoxylate
Diphenoxylate is a phenylpiperidine opioid that is used clinically in the management of severe diarrhea. It acts primarily as an agonist at enteric µ-receptors but can cross the BBB and, in adequate doses, produces euphoria. The drug is typically administered orally in combination with atropine to limit its addictive potential via undesirable anticholinergic side effects. Given its clinical application, this drug may worsen POI
opioid receptors are what coupled
g protein
opioid receptors µ1: µ2: κ: δ:
µ1: supraspinal analgesia, physical dependence
µ2: respiratory depression, miosis, euphoria, reduced gastrointestinal motility, physical dependence
κ: Spinal analgesia, sedation, miosis, inhibition of antidiuretic hormone release
δ: Analgesia, euphoria, physical dependence
Sympathetic drugs metabolic effects
Sympathetic drugs have effects across multiple organ systems and can cause metabolic effects including hyperglycemia, increased free fatty acids, and hypokalemia through alpha- and beta-receptor activation.
Thiopental in neuro
Barbiturate
The cerebral flow-metabolism relationship and cerebral autoregulation remain intact with the use of thiopental. Thiopental decreases both CBF and CMRO2 by 30% with induction doses and by 50% upon achievement of an isoelectric EEG.
Codeine metabolism
The CYP 2D6 enzyme pathway is responsible for the metabolism of codeine to morphine, its active metabolite. Individuals with poor activity of this enzyme pathway are likely to experience treatment failure with codeine therapy.
2C19
metabolism of proton pump inhibitors (PPIs), diazepam, propranolol, and several antidepressants.
2C9
glipizide, losartan, phenytoin, and warfarin
norepi receptors
norepinephrine binds primarily alpha receptors causing intense vasoconstriction but also beta-1 receptors. Thus norepinephrine is indicated for hypotension due to vasodilation such as sepsis.
Isoproterenol
Isoproterenol is a beta receptor agonist only leading to increased inotropy and chronotropy, but also causes vasodilation. Isoproterenol is indicated for bradycardia in third-degree heart block or in a denervated heart after recent cardiac transplant.
Bronchospasm algorithm, especially the other IV drug
Treatment includes removing the offending stimulus, applying positive airway pressure, increasing FiO2, and administering inhaled beta-agonists. For bronchospasm that does not resolve with the preceding measures, intravenous epinephrine or the beta-agonist salbutamol may be needed in order to relax bronchial smooth muscle.
non-depolarizing NMBDs, competitive or non-competitive
competitive
why precedex cause bradycardia
Certain adrenergic agonists, specifically the alpha2-agonists dexmedetomidine and clonidine, are able to cross the blood-brain barrier. Thus they are able to bind to presynaptic alpha-2 receptors which decrease norepinephrine release leading to a decrease in sympathetic tone. This is responsible for the cardiovascular effects such as bradycardia and the CNS effects of sedation.
how do we get dopamine to the brain
Dopamine is unable to cross the blood-brain barrier. In order to have its effects in the CNS, dopamine must be synthesized in the brain, be given as the precursor levodopa, or be affected by indirect sympathomimetics.
what drug can increase tracheal tone
Succinylcholine, a depolarizing neuromuscular blocking drug, has been infrequently observed to increase tracheal tone. This is postulated to be a result of its ability to act as a surrogate for acetylcholine at the muscarinic receptors, leading to undesirable vagal stimulation.
treatment for absence seizures and MoA
only ethosuximide is used exclusively for the treatment of absence seizures. Its mechanism involves blockade of T-type calcium channels (which possess a corticothalamic distribution), resulting in a reduction in excessive excitatory activity.
The opioid antagonist naloxone binds the opioid receptor with the greatest affinity
The opioid antagonist naloxone binds the μ opioid receptor with the greatest affinity. Antagonism of the μ receptor reverses opioid-induced respiratory depression but may also reverse analgesia.
Dobutamine MoA
Dobutamine is a synthetic adrenergic agonist that increases cardiac contractility by stimulating the β1 receptor. Other cardiac effects of β1 stimulation include increased dromotropy, chronotropy, and lusitropy. Epinephrine and norepinephrine also bind β1 receptors.
α2 receptor stimulation causes peripheral
α2 receptor stimulation causes peripheral vasodilation
Stimulation of β2 receptors results in peripheral
Stimulation of β2 receptors results in peripheral vasodilation and bronchodilation
β3 stimulation results in .
β3 stimulation results in increased lipolysis.
Stimulation of β1 receptors causes
Stimulation of β1 receptors causes increased cardiac inotropy (contractility), chronotropy (heart rate), dromotropy (speed of conduction through the atrioventricular node), and lusitropy (rate of relaxation).
α1 receptors in the iris
Mydriasis occurs when α1 receptors in the iris are stimulated, causing contraction of the radial muscle
what do epi and norepi bind
Epinephrine binds all 5 adrenergic receptors. Norepinephrine has a high affinity for α1 receptors. It also binds β1 and β2 receptors although the affinity for β1 is much higher.
onset and duration of H2 blockers
Drug Onset (hours) Duration (hours)
Cimetidine 1-1.5 3-4
Ranitidine 1 9-10
Famotidine 1 10-12
preop lorazepam
Lorazepam premedication can prolong extubation times and does not improve patient satisfaction scores.
preop clonidine
Clonidine decreases MAC but can increase the risk of hypotension and bradycardia.
preop fentanyl
Fentanyl premedication may actually sensitize patients to pain postoperatively.
preop scopolamine
Scopolamine is more likely than atropine to cause central anticholinergic syndrome.
propofol FDA handling guidelines
Due to reports of bacterial contamination and patient reactions, strict aseptic technique should be used when handling propofol, it should be used within 12 hours of opening the vial, all vials should be used for only 1 patient, and it should not be given through the same line as blood or plasma products.
what do you give after nuclear bomb exposure
Potassium iodide is effective at reducing I-131 uptake by the thyroid and reduces the incidence of radiation exposure related thyroid complications.
max dose of neostigmine and what happens if exceeded
Patients who receive an excessive amount of acetylcholinesterase (AChE) inhibitor are at an increased risk of developing weakness. The recommended maximum dose of neostigmine is 0.07 mg/kg.
how does neostigmine affect succinylcholine.
Acetylcholinesterase inhibitors also inhibit plasma butyrylcholinesterase, which can prolong the effects of succinylcholine.
what does NDNB pretreatment do for succ administration and what does it not do
The occurrence of succinylcholine-induced fasciculations and increases in ICP and intragastric pressure may be decreased by NDNB pretreatment. Increases in IOP will occur despite pretreatment and current recommendations are to avoid succinylcholine in open-eye injuries.
n extreme hemodynamic instability, such as multi-system trauma with refractory shock, an option to provide amnesia.
n extreme hemodynamic instability, such as multi-system trauma with refractory shock, scopolamine 5 mcg/kg IV (0.2-0.4 mg for an adult) is an option to provide amnesia. It is worth noting that this may interfere with subsequent neurologic examinations because of its long half-life.
what type of receptor is
postganglionic parasympathetic
NMJ
postganglionic parasympathetic receptors (muscarinic) and neuromuscular junction receptors (nicotinic).
treatment for organophosphate poisoning
Pharmacologic treatment consists of pralidoxime and atropine, although there is debate on the effectiveness of pralidoxime. Pralidoxime works by binding to the organophosphate molecules and reactivating acetylcholinesterase. By reactivating acetylcholinesterase, it is effective in treating both muscarinic and nicotinic symptoms. It generally only works if given within the first 48 hours of exposure. Atropine is a cholinergic antagonist at the muscarinic receptors, therefore preventing cholinergic parasympathetic activity. It is therefore most useful for drying pulmonary secretions and treating bradycardia.
treat the hypertension and hypokalemia associated with primary hyperaldosteronism.
Spironolactone, a competitive aldosterone receptor antagonist, is used to treat the hypertension and hypokalemia associated with primary hyperaldosteronism. Potassium supplementation and additional antihypertensives are usually required when first initiating treatment.
