ITE CA2 pharm 2 Flashcards
Meperidine’s beneficial effects which receptor
Meperidine’s beneficial effects are multimodal and center around the kappa opioid receptor.
opioid associated with increases in heart rate and why
Meperidine has structural similarities to atropine. Which is why meperidine is the only opioid associated with increases in heart rate following administration. Meperidine also has some weak local anesthetic effects.
mu receptor subclasses
The µ1 receptor produces the analgesic and physical dependence properties of most opioids
µ2 receptor results in respiratory depression, miosis, euphoria, decreased gastrointestinal motility, and physical dependence.
µ3 receptors are unknown but may mediate some anti-inflammatory activity.
kappa receptor
The κ receptor mediates analgesia but also dysphoria, sedation, miosis, and inhibits antidiuretic hormone release.
delta receptor
The δ receptor is responsible for analgesia, physical dependence, and perhaps antidepressant effects.
nalbuphine recetpors
Nalbuphine works as a kappa-agonist/mu-antagonist analgesic.
methadone
receptors
types of pain to use it for
important side effect
Methadone exerts significant effects on the mu opioid receptor.
Methadone also acts on the NMDA receptor as an antagonist. NMDA receptor antagonism explains methadone’s effect for neuropathic pain and in opioid tolerance. Furthermore, the NMDA antagonism and serotonin reuptake inhibition make methadone an effective choice for chronic neuropathic pain as well as modulation of some of the psychological concerns of patients living with chronic pain.
Methadone does prolong the QT interval and should be monitored.
morphine
- receptor
- metabolism
- active metabolite
Morphine has its main effect on the mu opioid receptor.
Morphine is metabolized by the liver to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). More morphine is metabolized to M3G than M6G.
However M6G is an active metabolite of morphine.
Remifentanil
- receptor
- metabolism
Remifentanil has its main effect upon the mu opioid receptor. Remifentanil is unique with a very short half-life which is not affected by the infusion time. Remifentanil is metabolized by nonspecific plasma and tissue esterases.
Mesna
Mesna is an antioxidant that prevents cyclophosphamide induced hemorrhagic cystitis.
Common Chemo-Toxicities: Cisplatin, Carboplatin: Vincristine: Bleomycin, Busulfan: Doxorubicin: Trastuzumab: Cyclophosphamide: 5-FU, 6-MP, methotrexate:
Common Chemo-Toxicities: Cisplatin, Carboplatin: acoustic nerve damage, nephrotoxicity Vincristine: peripheral neuropathy Bleomycin, Busulfan: pulmonary fibrosis Doxorubicin: cardiotoxicity Trastuzumab: cardiotoxicity Cyclophosphamide: hemorrhagic cystitis 5-FU, 6-MP, methotrexate: myelosuppression
Roc clearance
Approximately 25-30% of rocuronium is renally excreted. It is cleared primarily by hepatic uptake and hepatobiliary excretion.
More importantly, rocuronium is primarily excreted through the hepatobiliary system and prolonged paralysis can be seen in patients with cirrhosis and liver failure.
NMBs not affected by renal failure
Of the commonly used NMBs, only succinylcholine and cisatracurium have minimal renal excretion and predictable durations of action in patients with renal failure.
Renal disease effect of half life on
Roc
vec
panc
The half-lives of vecuronium and pancuronium are significantly prolonged due to the accumulation of active metabolites that are renally excreted. In fact, 80% of pancuronium is renally excreted unchanged in the urine. By contrast, the half-life of rocuronium is only slightly prolonged (1.2-1.6 hours in normal patients vs. 1.6-1.7 hours in patients with end stage renal disease) since there are no active metabolites
Metabolites and their effects
Meperidine
Morphine
How they’re excreted and why it matters
The active metabolite in meperidine, normeperidine, causes seizure activity.
Morphine’s primary active metabolite, M6G, has a 100-fold greater potency, but exhibits an equal or decreased affinity for μ-receptors compared to morphine. Accumulation of M6G can result in respiratory depression. Morphine’s inactive metabolite, M3G, may cause myoclonus and allodynia. As morphine and meperidine metabolites are typically excreted via the kidneys, their side effects are prolonged in the setting of renal failure. ≈
Barbiturates in renal failure
Barbiturates have decreased protein binding in renal failure which leads to higher concentrations of free active molecules.
Allodynia
feeling pain from stuff that shouldn’t cause pain
Mivacurium in renal failure
How is it metabolized
Mivacurium activity is also independent of renal dysfunction because it is hydrolyzed by pseudocholinesterase.
Propofol in renal failure
In general, propofol pharmacokinetics are similar between healthy patients and those with renal failure. Volume of distribution may be larger in uremic patients due to decreased albumin concentrations in that population. Total body clearance of propofol has been shown to be increased in uremic patients, which may seem counterintuitive. This is thought to be due to accelerated hepatic biotransformation in patients with renal failure. After a bolus dose of propofol, blood concentrations have been found to be lower between the 2-10 minute mark in renal failure patients.
2 categories of calcium channel blockers and 3 drugs in each
Dihydropyridine calcium channel blockers -Nifedipine -Nicardipine -Amlodipine Non-dihydropyridine calcium channel blockers: -Nimodipine -Diltiazem -Verapamil
Compare DHP CCB to non-DHP CCBs
Dihydropyridine CCB: decrease SVR
Non-DHP CCB: increased selectivity for myocardium, cardiac conduction system, coronary arteries; decreased platelet aggregation
Digoxin mechanism potentiated by results in what electrolyte change half life antidote
Decrase Na/K ATPase activity, leads to increased intracellular Na/Ca exchange leads to increased contractility
potentiated by hypokalemia, thiazide diuretics, amiodarone, decreased renal fxn
results in hypercalcemia
half life 40 hours
antidote: digibind
Cardiovascular effects of milrinone
The cardiovascular effects of milrinone can be summarized as: increased inotropy, increased lusitropy, increased ejection fraction, increased stroke volume, increased cardiac output, decreased afterload, decreased preload, pulmonary vasodilation, and systemic vasodilation.
TrueLearn Insight : Milrinone has been shown to improve mixed venous admixture through its reduction in myocardial oxygen consumption.
Since it does not act on the adrenergic alpha and beta receptors, milrinone has been proven effective as an inotrope in the setting of beta blockade and in the setting of beta receptor down-regulation (e.g. CHF). Milrinone is commonly used synergistically with adrenergic agents (e.g. epinephrine, norepinephrine). Milrinone is unique in its ability to increase cardiac index without increasing myocardial oxygen demand. It also improves myocardial relaxation (lusitropy) and augments coronary circulation.
milrinone MoA
Milrinone is a phosphodiesterase III (PDE3) inhibitor which increases inotropy. Both an arterial and venodilator.
Milrinone, therefore, increases cAMP levels which causes its inodilator properties.
Ketamine psychomimetic reactions decreased by
Ketamine is associated with a high incidence of psychomimetic reactions early in the recovery period. The incidence of these reactions can be decreased by coadministration of benzodiazepines, propofol, or barbiturates.
Etomidate
effects on cortisol
mechanism of effects on cortisol
Etomidate inhibits the synthesis of cortisol transiently in all patients and should be avoided in patients with adrenal insufficiency. Etomidate specifically inhibits 11β-hydroxylase and 17α-hydroxylase in the cortisol pathway in a reversible dose-dependent fashion.
Nicardipine metabolism and elimination
Nicardipine is metabolized by the liver and eliminated via gastrointestinal tract. Renal insufficiency has no effect on nicardipine use. Severe hepatic insufficiency results in significantly prolonged nicardipine half-life (normal half life is 60-100 min).
Nicardipine effects
coronary and peripheral arterial dilator.
Nicardipine (intravenous and oral) can cause an increase in heart rate in about 25% of the people. This tachycardia is NOT due to baroreceptor response, rather due to sympathetic activation. Nicardipine decreases systemic vascular resistance, but also increases cardiac contractility (C). The exact mechanism of this positive inotropic effect is unknown.
Nicardipine affected how by renal insufficiency effect on renal blood flow effect on GFR effect on renovascular resistance
Nicardipine dosage is not affected by renal insufficiency (D). The use of nicardipine increases both renal blood flow and glomerular filtration rate and also decreases renovascular resistance.
Metoclopramide
effects at what dosing
It is used perioperatively as an antiemetic. By promoting gastric emptying and increasing gastroesophageal sphincter tone, it may decrease the risk of pulmonary aspiration.
Per ASA guidelines, “Metoclopramide is a weak antiemetic and at a dose of 10 mg is not effective in reducing the incidence of nausea and vomiting.”
Higher doses (25-50 mg) may be necessary to have discernible benefit, but carry the risk of more side effects such as extrapyramidal symptoms. Metoclopramide has little effect on gastric acidity
Metoclopramide and succinylcholine interaction
Metoclopramide inhibits plasma cholinesterase and can increase the duration of action of succinylcholine
half life of
flumazenil
midazolam
The duration of action of midazolam (half-life 1.7-2.6 hours) exceeds that of flumazenil (half-life 0.7-1.3 hours).
This makes recrudescence of benzodiazepine-induced somnolence after metabolism of flumazenil likely in this context.
what reversal agent can cause pulm edema
naloxone with large bolus doses
Milrinone metab/excretion?
Milrinone is excreted via the kidneys in its unconjugated form and therefore dosage should be adjusted in the setting of renal failure.
MIlrinone side effects
Common side effects of milrinone include tachycardia and hypotension. Thrombocytopenia was a clinical concern with the use of amrinone (renamed inamrinone) but is not significant with milrinone use after 48 hours of infusion. Higher doses of milrinone have been associated with atrial fibrillation.
Hepatopulmonary syndrome
- definition
- etiology
- how diagnose
- treatment
Hepatopulmonary syndrome is the triad of intrapulmonary vascular dilatations IPVDs, increased A-a gradient, and hepatic failure. Excessive levels of circulating NO result in significant ventilation-perfusion mismatching. A positive contrast-enhanced echocardiography (CEE) supports the diagnosis in a patient without underlying cardiopulmonary disease. Liver transplantation is the only definitive treatment and complete resolution of abnormal gas exchange may take up to a year following transplantation.
Hypoxia is improved when the patient lies flat (platypnea) and is worsened when the patient stands (orthodeoxia). The intrapulmonary vascular dilations cause increased perfusion relative to ventilation. Standing further worsens this ventilation-perfusion mismatch since gravity causes increased perfusion and pooling in the less-ventilated lower lung segments.
Common side effects of ondansetron include
Common side effects of ondansetron include QTc prolongation (20%, very rarely clinically significant), headache (11%), transient AST/ALT increases (5%), constipation (4%), rash (1%), flushing/warmth (< 1%), and dizziness (< 1%).
Intravenous administration of etomidate is associated with
Intravenous administration of etomidate is associated with pain on injection, postoperative nausea and vomiting, and superficial thrombophlebitis. Ways to prevent thrombophlebitis are to use larger veins, increasing the speed of injection, and pretreatment with lidocaine. Treatment options are controversial but include the use of NSAIDS and elastic stockings.
PGE1
uses
side effects
PGE1 is used to maintain patency or reopen the ductus arteriosus in “ductal dependent lesions” to improve blood flow to the lungs or systemic circulation depending on the nature of the congenital lesion. Side effects include apnea, hypotension, fevers, and CNS irritability.
Dexmedetomidine metabolism and excretion
Dexmedetomidine is extensively metabolized in the liver before being excreted in urine and feces.
