ITE CA-2 pharm Flashcards
what syndrome can methylene blue cause?
Methylene blue can increase plasma serotonin concentrations and precipitate serotonin syndrome.
list serotonergic drugs
SSRIs, TCAs, MAO inhibitors, or even St. John’s Wort
symptoms of serotonin syndrome
High CNS concentrations of serotonin can produce mental status changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering, and fever.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (NMS) is a life-threatening reaction that occasionally occurs in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. NMS is often slower in onset (generally over one to three days) and is usually associated with hyperthermia (> 38 degC).
Greatest decrease in BP: midaz or diaz
Midazolam produces a greater decrease in systemic blood pressure than diazepam.
What receptors do volatiles act on
Volatile anesthetics (isoflurane, sevoflurane, desflurane) are thought to manipulate background potassium channels, GABA receptors, and sodium channels. Volatile anesthetics are thought to have an inhibitory effect on sodium channels.
Aminocaproic acid and TXA mechanism of action
Aminocaproic acid and tranexamic acid are lysine analogs that prevent the formation of the ternary complex between plasminogen, tPA, and fibrin, thus inhibiting plasmin formation and fibrin degradation. The 2015 ASA Practice Guidelines for perioperative blood management recommend the use antifibrinolytic therapy for prophylaxis of the use of allogeneic blood transfusion in patients undergoing cardiopulmonary bypass.
what does thrombin do
Thrombin has many prothrombotic actions, it activates factors I, V, VIII, XI, and XIII, as well as platelets. Thrombin is inhibited by argatroban, dabigatran, and bivalirudin.
Other effects of opiods
Opioids have a variety of different effects on many organ systems. They can lead to increased tone of the common bile duct and sphincter of Oddi, immunosuppression, skeletal muscle rigidity, and paralytic ileus.
TrueLearn Insight : Glottic closure is the primary mechanism of poor ventilation secondary to opioid bolus dosing. One study involving high-dose opioid induction in tracheostomy patients showed only small decreases in pulmonary compliance. However, the same dose used in non-tracheostomy patients resulted in failure to mask ventilate.
Phase 1 metabolism
Non-synthetic
Phase I reactions include the process of oxidation, reduction, and hydrolysis. These reactions introduce functional groups (e.g. –OH, –SH, –NH2) that serve to promote subsequent phase II reactions. Phase I reactions usually result in the inactivation of a drug and action termination of the compound. Sometimes metabolism can lead to activation of a drug. Prodrugs are inactive drugs that undergo metabolism to an active drug. Some enzymes catalyzing phase I reactions include cytochrome P450 (CYP), aldehyde dehydrogenase and alcohol dehydrogenase.
Phase II metabolism
Synthetic
Phase II reactions utilize conjugating enzymes and result in the formation of metabolites with increased molecular mass. Phase II reactions can terminate the biological activity of the drug. Phase II reactions are conjugation reactions, involving an enzyme-catalyzed combination of endogenous compounds to functional groups produced from phase I reactions. Enzymes catalyzing phase II reactions include glucuronyl transferase, sulfotransferase, and methylases. Two specific phase II reactions, glucuronidation and sulfation, result in the formation of metabolites with an increased affinity for aqueous environments. This serves to facilitate metabolite transport into the aqueous compartments of cells throughout the body. Phase II reactions are generally considered vital in ensuring efficient elimination and detoxification of most drugs and termination of their pharmacological action.
Phase I or Phase II faster?
The catalytic rates of phase II reactions are significantly faster than the rates of the CYP-mediated phase I reactions. If a drug will under metabolism through both Phase I and Phase II reactions, the overall process will be dependent on the speed of the initial Phase I reaction.
Effects of volatile anesthetics on circulatory system
The effects of volatile anesthetics on the circulatory system include decreased systemic vascular resistance, decreased myocardial contractility, coronary vasodilatation (especially isoflurane), and ischemic preconditioning.
How do volatiles do ischemic preconditioning
Although multifactorial, much of the ischemic preconditioning effects of volatile anesthetics are related to reduced loading of calcium into myocardial cells.
How does N2O affect BP when mixed with volatile
Nitrous oxide is commonly combined with potent volatile anesthetics to maintain general anesthesia. Nitrous oxide has unique cardiovascular actions. It increases sympathetic nervous system activity and vascular resistance when given in a 40% concentration. When N2O is combined with volatile anesthetics, systemic vascular resistance and BP are greater than when equipotent concentrations of the volatile anesthetics are evaluated without N2O. These effects might not be due solely to sympathetic activation from N2O per se, but may be partially attributed to a decrease in the concentration of the coadministered potent volatile anesthetic required to achieve a MAC equivalent when using N2O.
Levodopa on day of surgery?
For patients with Parkinson disease, levodopa should be continued on the day of surgery.
What can you give IV if you can’t give levodopa
Apomorphine is a dopamine agonist that can be administered subcutaneously or intravenously if oral levodopa cannot be given.
Meds to avoid in Parkinsons
Dopamine antagonists such as phenothiazines, droperidol, and metoclopramide should be avoided; note these are commonly used anti-emetics in the post-operative period. Alfentanil and fentanyl may produce dystonic reactions when administered rapidly. Propofol may result in dyskinesias during induction or upon emergence from an infusion. There are no reports of adverse responses to isoflurane, sevoflurane, or desflurane. Patients being treated with dopamine agonists may be at increased risk for neuroleptic malignant syndrome (NMS).
Why give carbidopa
Dopamine does not pass the blood-brain barrier, so its pre-cursor levodopa is used. Unfortunately, levodopa is decarboxylated to dopamine in the periphery and can cause nausea, vomiting, and arrhythmia. To avoid such side effects, levodopa is administered with carbidopa and entacopone. Carbidopa is a peripheral decarboxylase inhibitor and entacopone is a catechol-O-methyltransferase inhibitor that increases the bioavailability of levodopa. Levodopa can cross the blood-brain barrier without the assistance of any other medication.
Benzos protein bound? hydro/lipo philic? Metabolism? Which channel? frequency or duration of channel opening?
Benzodiazepines are highly protein-bound and lipophilic. Differences in these characteristics determine the onset of action and duration of action. Plasma clearance is described by a two or three-compartment model. Metabolism occurs in the CYP 450 system via oxidation and glucuronic conjugation. Midazolam is short acting and a short context-sensitive half-time allows for continuous infusion.
TrueLearn Insight : Mnemonic for GABA-A chloride channel opening: FREnzodiazepines and barbiDURATes. Benzodiazepines increase the frequency of channel opening and barbiturates increase the duration of channel opening.
Benzos in obesity
Elimination half-lives are prolonged in obese patients due to the increased volume of distribution. There is also a delayed return of the drug to the plasma.
Propofol cardiovascular effects
Propofol has a significant effect on a patient’s cardiovascular system. It leads to a dose-dependent decrease in systemic vascular resistance and myocardial contractility, attenuates the body’s natural baroreceptor reflex, and leads to significant arteriolar and venodilation given it’s reduction in sympathetic activity.
Propofol and heart rate
Heart rate does not change significantly after an induction dose of propofol. Propofol either may reset or inhibit the baroreceptor reflex, thus reducing the tachycardic response to hypotension.
Ketamine effect on potentials
Ketamine increases the amplitude of somatosensory evoked potentials. Auditory and visual evoked responses are decreased by ketamine.
Ketamine and secretions
Ketamine use may result in increased salivation and secretions. This effect can be modulated by an anticholinergic drug such as atropine and glycopyrrolate.
Ketamine mechanisms and effects
Ketamine binds noncompetitively to the phencyclidine recognition site on the NMDA receptors. It produces a dose-dependent dissociative anesthesia, characterized by a dissociation between the thalamocortical and limbic systems. Ketamine has also been described to have a beneficial opioid-sparing effect when used as an adjuvant. An important consideration in the use of ketamine anesthesia is the incidence of hallucinations or nightmares during the early recovery period.
CV effects of ketamine
The cardiovascular response of ketamine mimics sympathetic nervous system stimulation. Therefore, increased blood pressure, increased cardiac output, and increased myocardial oxygen consumption. The cardiovascular stimulating effects can be blunted by prior administration of benzodiazepines or inhaled anesthetic. The cardio-depressant effects of ketamine are postulated to lead to hypotension in catecholamine depleted patients (e.g. intensive care unit patients), however the sympathomimetic effects usually overshadow this.
Ketamine in bronchi
Ketamine has bronchodilatory activity, which is effective in attenuating bronchospasm.
Time constants and
How much per each
The time constant (in minutes) for a circle breathing system is circuit volume (in liters) / fresh gas flow (in liters/minute). Thus the smaller the circuit and the greater the fresh gas flow the lower the time constant (the faster the change in concentration). One, two, and three time constants after dialing a new volatile concentration, the circuit will achieve approximately 63%, 86%, and 95% of the desired change.
Succ mech
Succinylcholine is the only depolarizing neuromuscular blocking drug (NMBD) clinically available. It has a fast onset, short duration of action, and great reliability compared to other NMBDs. It resembles acetylcholine (ACh) in molecular structure which allows it to bind to Ach receptors. Succinylcholine depolarizes both postsynaptic and extrajunctional receptors. However, unlike acetylcholine, it is not degraded by acetylcholinesterase so it leaves the muscle membrane in a depolarized state longer, yielding membrane hyperpolarization and desensitization.
Where does pseudocholinesterase act on succ
Hydrolysis of succinylcholine by pseudocholinesterase (also known as butyrylcholinesterase or plasma cholinesterase) occurs in the plasma. Nearly all of the succinylcholine is hydrolyzed before ever reaching the neuromuscular junction.
What conditions change required dose of non-depolarizing NMBDs
Because they are positively charged, nondepolarizing NMBDs are distributed mostly in the extracellular fluid. Patients with renal or hepatic failure or burn patients may require larger initial doses.
Termination of action for small, non-protein-bound and hydrophilic drugs
Renal elimination will terminate drug action for small, non-protein-bound and hydrophilic drugs
_______ is the most important mechanism of drug action termination for most drugs.
Metabolism is the most important mechanism of drug action termination for most drugs.
CO2 Response Curve Changes Benzos Prop Opioids Volatiles Hypoxemia
CO2 Response Curve Changes: Med/Change Effect Benzodiazepines Decreased Slope Propofol Decreased Slope Opioids Right Shift Volatile Agents Decreased Slope & Right Shift Hypoxemia Left Shift
Diuretic Electrolyte Changes Urine sodium Urine potassium Urine calcium Blood pH
Diuretic Electrolyte Changes
Urine sodium - Increased All diuretics: Loop, thiazides, K+ sparing, carbonic anhydrase inhibitors
Urine potassium - Increased: All diuretics except K+ sparing
Urine calcium - Increased: Loop diuretics
Decreased : Thiazide diuretics
Blood pH - Decreased: Acidemia with carbonic anhydrase inhibitors, K+ sparing
Increased: Alkalemia with loop diuretics, thiazides
Where do diuretics act
Loop diuretics impact sodium reabsorption in the thick ascending limb of the loop of Henle. Thiazide-type diuretics act in the distal tubule and potassium-sparing diuretics act in the cortical collecting tubule.
increased drug ionization = increased or decreased vol of dist
decreased
increased lipid solubility = increased or decreased vol of dist
increased
increased protein binding = increased or decreased vol of dist
decreased
skin receives __% of cardiac output
20
bone receives __% of cardiac output
1
heart receives __% of cardiac output
75
kidneys receive __% of cardiac output
75
opioid heart rate
decreased
increased incidence of delayed resp depression caused by lipophilic or hydrophilic opioids
hydrophilic
receptor associated with stiff chest syndrome
mu-receptor and gaba-nergic inhibition
lipid solubility fent compared to morphine
fent is more lipid soluble and therefore crosses blood brain barrier faster
opioid and urine
retention
lipo/hydrophilic for increased diffusion accross vasc membranes
lipophilic
buprenorphine
partial mu agonist, weak kappa antag
opioid with tachycardia risk and why
meperidine bc atropine like structure
opioid pre-load
decreased
mu or kappa?
decreased visceral & somatic pain (GABA-mediated)
mu
increased diffusion accross spinal membranes
lipophilic
histamine release
meperidine, morphine, codeine
increased cephalo-caudal spread (epidural and subarachnoid space)
hydrophilic
opioid with least pulm uptake
remi
how many half-lives required to consider a drug eliminated from the body
5
Adenosine Diphosphate Analogues
Adenosine Diphosphate Analogues – Cyclopentyl Triazolo Pyrimidines - ticagrelor: oral P2Y12 receptor antagonist that binds at a site different from ADP. This results in a reversible block. Ticagrelor is not a prodrug and thus does not require metabolic activity to inhibit platelets. This allows it to have a more consistent effect and less inter-patient variability.
Acetylsalicylic acid -
Acetylsalicylic acid - Aspirin (ASA): Aspirin is rapidly absorbed from the gastrointestinal tract with a half-life of only 15 to 20 minutes. Aspirin inhibits platelet function by permanently inactivating the cyclooxygenase (COX) enzyme. For this reason, despite a short half-life, ASA has a long duration of action. COX is vital for the conversion of arachidonic acid to prostaglandin that then gets converted to prostanoids including thromboxane A2 (TXA2). TXA2 is vital for platelet aggregation and vasoconstriction. This inactivation of COX can only be reversed by the generation of new platelets. Since the platelet life span is 5 to 10 days, 10% to 20% of circulating platelets are replaced daily. Lower doses of ASA are needed for antiplatelet activity; compared to higher doses required for anti-inflammatory activity.
Platelet Receptor Inhibitors –
Platelet Receptor Inhibitors – Thienopyridines - clopidogrel and prasugrel, and ticlodipine: There are three known platelet receptor subtypes P2X1, P2Y1, and P2Y12. The thienopyridines selectively inhibit ADP-induced platelet aggregation. Clopidogrel and prasugrel are both pro-drugs, being rapidly converted to the biologically active compound once ingested. Because there is considerable inter-patient variability, patients have varying response to these medications. The active metabolite of both agents forms a covalent bond to the P2Y12 receptor, rendering it unresponsive to ADP. This bond is essentially irreversible and thus the platelet site remains inactivated for the remainder of the platelet lifespan; return of function requires new platelet generation.
Purinoreceptor antagonist -
Purinoreceptor antagonist - cangrelor: intravenous P2Y12 receptor antagonist. Inhibits platelet aggregation by inhibiting the P2Y12 receptor, leading to an increase in cAMP. Cangrelor has a short half-life and plasma clearance thus return of platelet aggregation is 70% reestablished within one hour of stopping infusion.
Glycoprotein Iib/IIIa Antagonists –
Glycoprotein Iib/IIIa Antagonists – abciximab, eptifibatide, tirofiban: these agents are all administered via the intravenous route. They vary slightly in their mechanism of action, onset of action, and duration of action. They are used mostly in patients with acute myocardial infarction where catheterization or percutaneous intervention is planned. Administration of these agents is monitored by platelet aggregometry and they will not prolong the PT or aPTT.
Barbiturates
Barbiturates cause a decrease in cerebral blood flow, cerebral blood volume, and intracranial pressure (ICP). They decrease renal and hepatic blood flow. Barbiturate-mediated reductions in cerebral metabolic rate (CMRO2) and ICP make them useful in the anesthetic management of patients with space-occupying intracranial lesions.
The context-sensitive half-time is
The context-sensitive half-time is the time required for the plasma concentration of a given drug to decrease by one half following discontinuation of the infusion of the given drug
Context-sensitive half-times for propofol in obese
Context-sensitive half-times for propofol are not significantly different between obese and lean subjects
Etomidate
Etomidate is a sedative-hypnotic medication that has less effect on ventilation compared to propofol. It depresses airway reflexes (less so than propofol), relaxes smooth muscle in the pulmonary vascular system, and does not induce histamine release in patients with reactive airway disease.
Risk factors for QT prolongation
Risk factors for QT-interval prolongation:
Antiarrhythmics – quinidine, procainamide, amiodarone, sotalol
Histamine-receptor antagonists – terfenadine, astemizole
Antibiotics – erythromycin, clindamycin, imidazole, ampicillin
Poisons – organophosphates
Psychiatric medications – tricyclic antidepressants, haloperidol, droperidol, phenothiazines, lithium, risperidone
5-HT receptor medications – ondansetron, ketanserin, fluoxetine
Diuretics – indapamide
Electrolyte disturbances – hypokalemia, hypomagnesemia, hypocalcemia
Cardiac factors – bradycardia, complete AV nodal block
Catabolic/starvation states – anorexia nervosa, celiac disease, post-gastric bypass
CNS injury – subarachnoid hemorrhage, thalamic hemorrhage
Patient factors – female gender
Perioperative QT prolongation management
Beta-blocker therapy should be considered as well as a cardiology consultation, particularly if the QT is significantly prolonged with no clear cause. Serum electrolytes should be optimized (e.g. magnesium) as abnormalities may predispose to delays in ventricular repolarization and a lower ventricular arrhythmia threshold. Avoidance of certain medications in the intraoperative period and close cardiac monitoring will help prevent further prolongation.
Anesthetic meds QT effects
Inhaled anesthetics all cause QT prolongation through inhibition of the IK membrane currents. It is generally considered safe to administer volatile anesthetics in patients with long QT syndrome as long as they are on beta-blocker therapy.
There have been no documented associations between nitrous oxide and prolongation of the QT interval.
Propofol has been shown to have little effect on the QT interval. Actually, propofol has been shown to rapidly reverse the QTc prolongation induced by sevoflurane. Thus, many authors have suggested that propofol may be beneficial for patients with long QT syndrome and could be used as a total intravenous anesthetic.
Benzodiazepines seem to have no major effect on the QT interval and are safe to administer.
Different opioids have differing effects on the QT interval. Most opioids block the hERG channel. Methadone blocks the IKr channel in a dose-dependent manner and prolongs the QT interval. The FDA has issued a black box warning and outpatient administration of methadone requires a baseline ECG and routine monitoring. Fentanyl has no effect on the QTc and is safe to administer.
Succinylcholine is a potent stimulator of the autonomic nervous system and it has effects on heart rate and transmembrane potassium flux. It can cause prolongation of the QT interval and one must consider this in at-risk patients.
There is less data on the nondepolarizing muscle relaxants. Pancuronium has included one case of ventricular fibrillation, while rocuronium and vecuronium are likely safe.
More important for the non-depolarizing agents is the antagonism to reverse the effects. Anticholinesterase and anticholinergic medications can induce arrhythmias in at-risk patients, and they can even prolong of the QT interval in healthy patients without risk factors. The recommendation is that these medications should be avoided in at-risk patients.
Antiemetics have also been known to cause QT interval changes. Droperidol also has an FDA black box warning for the risk of inducing Torsade de Pointes. Serotonin-receptor antagonists (ondansetron, granisetron, dolasetron) all can prolong the QT interval, however, the risk of Torsade de Pointes is rare and very high doses would be needed. It is still wise to use alternative medications when possible in high-risk patients.
Methohexitol CV effects
Methohexital can have numerous deleterious effects on the cardiovascular system such as decreased cardiac output (from decreased ventricular filling), decreased systemic vascular resistance, and a reflex tachycardia that could lead to harm in patients with coronary artery disease
Why hypotension more common with propofol
Propofol blunts the baroreceptor reflex. So, unlike methohexital, the decrease in systemic vascular resistance is not met with a reflex increase in heart rate. This is another reason why hypotension after propofol administration is more common when compared to other anesthetic agents.
Methohexital
Methohexital is a drug which is a barbiturate derivative. It is classified as short-acting and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anesthetics before thiopental was removed. Methohexital can be used for general anesthesia, sedation, and for electroconvulsive therapy as it has been shown to not increase seizure threshold. Adverse effects can include cough, twitching, hiccups, and pain on injection.
Barbiturates CV effects and mech
Cardiovascular depression from barbiturates is a result of central and peripheral (direct vascular and cardiac) effects. The primary cardiovascular effect of a barbiturate during induction of anesthesia is peripheral vasodilation causing a pooling of blood in the venous system. Mechanisms for the decrease in cardiac output include direct negative inotropic action resulting from a decrease of calcium influx into the cells, decreased ventricular filling caused by increased capacitance, and transiently decreased sympathetic outflow from the CNS. The increase in heart rate (10% to 36%) that accompanies barbiturate administration probably results from the baroreceptor-mediated sympathetic reflex stimulation of the heart in response to the decrease in output and pressure. The cardiac index, as well as the MAP, is unchanged or reduced. The increase in heart rate (11% to 36%) encountered in patients with coronary artery disease who are anesthetized with barbiturates is potentially deleterious because of the obligatory increase in myocardial oxygen consumption that accompanies the increased heart rate.
Reverse acupuncture analgesia
Acupuncture can be an effective adjuvant analgesic in the acute and chronic pain settings. Its mechanism of action is unclear, but its effects are reversible by naloxone.
Acupuncture mech
The mechanism of acupuncture is ill-defined and thought to involve endorphin release as well as triggering the release of pain-modulating neurotransmitters such as serotonin and norepinephrine at the level of the spinal cord.
Indications for barbiturates
General indications for barbiturate therapy may include: alternative induction drug for a patient allergic to propofol, cerebral protection during incomplete brain ischemia, and facilitation of electroconvulsive therapy or during identification of epileptic foci during surgery.
The following conditions should be considered contraindications to the use of intravenous barbiturates:
1) Respiratory obstruction or an inadequate airway as barbiturates may worsen respiratory depression
2) Severe cardiovascular instability, shock, or hypovolemic conditions
3) Status asthmaticus as airway control and ventilation may be worsened by barbiturates
4) Porphyria as acute attacks may be precipitated by the administration of barbiturates
Contraindications for barbiturates
General indications for barbiturate therapy may include: alternative induction drug for a patient allergic to propofol, cerebral protection during incomplete brain ischemia, and facilitation of electroconvulsive therapy or during identification of epileptic foci during surgery.
The following conditions should be considered contraindications to the use of intravenous barbiturates:
1) Respiratory obstruction or an inadequate airway as barbiturates may worsen respiratory depression
2) Severe cardiovascular instability, shock, or hypovolemic conditions
3) Status asthmaticus as airway control and ventilation may be worsened by barbiturates
4) Porphyria as acute attacks may be precipitated by the administration of barbiturates
Absorption of a drug depends on
Absorption of a drug directly depends on its lipid solubility and inversely on its polarity, or degree of ionization
Phase II block
Phase II block occurs after repeated doses or a prolonged infusion of succinylcholine. In patients with atypical levels of the enzyme responsible for metabolizing succinylcholine, plasma cholinesterase, phase II block can develop after a single dose of the drug. Characteristics of Phase II block are fade of the train-of-four (TOF) twitch response, tetanic fade, and post-tetanic potentiation. After initial depolarization, the membrane potential returns towards the resting state. Neurotransmission remains blocked throughout.
If phase II block occurs, acetylcholinesterase inhibitors may be attempted to antagonized the blockade. However, the response to acetylcholinesterase inhibitors in this case in unpredictable. Therefore, it may be advisable to simply wait until the block resolves.
Phase I block
Nondepolarizing neuromuscular blocking drugs do not lead to agonist activation of the acetylcholine receptor at the neuromuscular junction; they do not cause depolarization, or a phase I block. A phase I block and is often preceded by muscle fasciculation. This is probably the result of the prejunctional action of succinylcholine, stimulating ACh receptors on the motor nerve, causing repetitive firing and release of neurotransmitter.
propofol onset of effect hypnosis vs cardiovascular
Hypnosis after a usual 2.5 mg/kg bolus of propofol occurs quickly, peaks at 90-100 seconds, and lasts 5-10 minutes. The onset of decreasing arterial blood pressure is much slower (double the time on average).
The onset of EEG effect with propofol seems to be independent of age, but the onset of decreasing arterial blood pressure is delayed with advanced age (up to triple the time required for the hypnotic effect).
propofol effect on CYP
inhibits 3A4
age effect on central compartment
Older individuals have decreased clearance rates and a smaller central compartment volume.
Organophosphates are
Organophosphates are acetylcholinesterase inhibitors that cause an excess supply of the neurotransmitter acetylcholine (ACh).
prophylaxis for organophosphate poisoining
Pyridostigmine is effective for prophylaxis against, not treatment for, organophosphate poisoning. It must be taken >30 minutes prior to organophosphate exposure in order to be effective. For example, it is utilized by those serving in the military who anticipate imminent encounters with organophosphate-containing nerve agents. Pyridostigmine provides protection of cholinesterase from inhibition by the organophosphate.
organophosphate poisoning symptoms
Most symptoms of organophosphate poisoning are the result of excess parasympathetic activation secondary to muscarinic stimulation. These include: diarrhea, urination, miosis, blurred vision, bronchoconstriction, emesis, lacrimation, and salivation (“DUMBBELS”). Excess nicotinic stimulation causes flaccid muscle paralysis, twitching, and muscle fatigue. Heart rate effects are variable because of mixed effects on the muscarinic and nicotinic preganglionic receptors.
organophosphate poisoning treatment
Treatment for organophosphate poisoning includes administration of atropine to reduce the muscarinic-mediated side effects. Pralidoxime chloride (2-PAM) is the more definitive treatment and acts as an “antidote” by removing the organophosphate compound from organophosphate-inactivated acetylcholinesterase. Decontamination protocols are also utilized to minimize continued exposure (e.g. the compounds can continue to be absorbed through the skin by contaminated clothing) and spread. Finally, supportive modalities may be necessary, such as assisted ventilation in the setting of severe respiratory compromise.
Muscarinic agonists
Muscarinic receptor agonists can act through two mechanisms, directly on the muscarinic receptor or indirectly by inhibiting the breakdown of ACh causing more ACh to be available to bind to the muscarinic receptor. The direct acting agents are choline esters (ACh, methacholine, carbachol, bethanechol) or alkaloids (pilocarpine, muscarine, arecoline)
Mexiletine
Mexiletine is a class IB antiarrhythmic often used for sodium channel blockade and is one of the treatments for PC and myotonia congenita. It is unlikely to trigger a myotonic episode.
Hypercalcemia effect on non-depolarizing neuromuscular blockers
Hypercalcemia antagonizes the effects of non-depolarizing neuromuscular blockers and higher doses may be required to obtain the desired effect.
Which of the following neuromuscular blocking drugs has an active metabolite that is nearly as potent as its parent drug?
Vecuronium has an active metabolite, 3-desacetyl-vecuronium, that has 80% of the potency of vecuronium. Accumulation of this renally-cleared metabolite can significantly prolong the duration of action of the drug, particularly when an infusion is used in a patient with renal failure.
Cisatracurium metabolite
Cisatracurium (and atracurium) is primarily metabolized (80%) to laudanosine. This renally-cleared excitatory amine can precipitate seizures, but does not have neuromuscular blocking activity. The clinical significance of laudanosine was more important with atracurium since it is much less potent than cisatracurium, and thus more of the metabolite is produced.
Biggest risk for bradycardia with sux admin and why
How prevent?
Repeat administration (e.g. an additional dose given within five minutes of an initial dose) and young age are the greatest risk factors for bradycardia with succinylcholine use. Bradycardia with repeat administration is a result of myocardium being sensitized by metabolic products of succinylcholine.
Bradycardia may be prevented by the administration of thiopental, atropine, ganglion-blocking drugs, and nondepolarizing neuromuscular blockers.
How does phenytoin affect neuromusc blockade of
Acute phenytoin administration potentiates the neuromuscular blockade of aminosteroid NDNBDs. Chronic phenytoin administration increases a patient’s resistance to the effects of NDNBDs and reduces their duration of action.
1) Increased metabolism via cytochrome P450 enzymes induction (this may explain why there is a clear effect with the aminosteroid NDNBDs, which rely on hepatic metabolism, but not with the benzylisoquinolines which undergo hepatic-independent Hofmann elimination and ester hydrolysis)
2) Increased postjunctional acetylcholine receptor density (the weak neuromuscular blocking properties of phenytoin, see below, results in postjunctional acetylcholine receptor upregulation)
3) Decreased sensitivity at the receptor sites
4) Increased end-plate anticholinesterase activity
By contrast, acute phenytoin administration to a phenytoin-naïve patient enhances the neuromuscular blockade of aminosteroid NDNBDs. The mechanism of action for this effect is not entirely understood, but thought to primarily be the results of an acute reduction of stimulus-induced acetylcholine release from the prejunctional neuron. The plasma concentration or the extent of binding to plasma proteins of the NDNBDs are not altered by phenytoin.
In hypovolemic shock, fentanyl dosing should be
In hypovolemic shock, fentanyl dosing should be cut in half.
delta receptor
Delta receptor: analgesia, antidepressant, physical dependence
delta airlines: not depressed because high in the sky but you depend on the plane
mu receptor
Mu receptor: analgesia, physical dependence, respiratory depression, miosis, euphoria, decreased gastrointestinal motility
Mu (you) make me feel happy and take my breath away and make me hold in farts
kappa receptor
Kappa receptor: analgesia, dysphoria, miosis, sedation
you get capped: pupils shrink, you feel crappy, you pass out
some common GA drugs that lower the seizure threshold
However, if general anesthesia is necessary it is recommended to avoid drugs which lower the seizure threshold such as lidocaine, ketamine, enflurane, and meperidine.
Nicardipine metabolism
Remember: 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.
Indomethacin
Indomethacin is a nonselective cyclooxygenase (COX) inhibitor and therefore inhibits prostaglandin synthesis. Prostaglandins typically aid in smooth muscle relaxation within the ductus arteriosus, thus preventing closure.
Pathophysiology of PRIS
The pathophysiology of PRIS relates to propofol’s ability to impair cellular free fatty acid utilization and mitochondrial activity leading to inadequate aerobic metabolism and increased reliance on anaerobic metabolism. Cardiac and skeletal muscle are particularly susceptible leading to muscle damage or necrosis that can cause cardiac failure and rhabdomyolysis. Additional downstream effects include lactic acidosis, hyperkalemia, and renal failure.
MH Dantrolene dosing
Dantrolene should be administered as a rapid 2.5 mg/kg IV bolus as soon as a diagnosis of MH is suspected. The bolus dose can be repeated every 5-10 minutes until signs of acute MH have abated.
Sux increase K by how much for how long
Serum potassium levels increase approximately 0.5 mEq/L after succinylcholine administration and normalize within 10-15 minutes in normal individuals. The same is seen in patients with chronic renal failure. This rise may be larger, and lethal, in patients with denervation injuries, muscular dystrophies, stroke, burns, or trauma due to diffuse up-regulation of extrajunctional acetylcholine receptors.
Furosemide acid base disturbance
Furosemide administration can cause a hypokalemic-hypochloremic metabolic alkalosis secondary to potassium excretion and a contraction alkalosis.
Acetazolamide
Acetazolamide is a carbonic anhydrase inhibitor. It is a commonly used diuretic that causes noncompetitive inhibition of the carbon anhydrase enzyme. This enzyme usually catalyzes the reaction between water, carbon dioxide, carbonic acid, and bicarbonate. Inhibition of this enzyme causes an increase in renal bicarbonate with a resultant alkalization of the urine. Acetazolamide may cause a mild hyperchloremic metabolic acidosis due to bicarbonate excretion. It is especially important in patients with chronic hypercapnia as alkalemia can further depress ventilation. Acetazolamide may impair carbon dioxide elimination in patients with chronic obstructive pulmonary disease and should be used in caution with that patient population.
K sparing diuretics
Site of action and mechanism
Acid base disturbance
Potassium sparing diuretics act in the collecting ducts where they alter transport of sodium resulting in decreased sodium reabsorption. Additionally, the potassium excretion is inhibited resulting in decreased excretion and potassium sparing. A mild hyperchloremic metabolic acidosis can be observed when administering potassium-sparing diuretics. This is due to the lack of aldosterone effect on hydrogen ion secretion.
Name a immunosuppressant that can prolong NDNBD
Cyclosporine is an immunosuppressant drug that can prolong the action of NDNBDs. In addition, it has potentially neurotoxic effects, including generalized seizures, and is nephrotoxic.
what type of receptor is NMDA
glutamate
Fenoldopam
Fenoldopam is a selective dopamine-1 agonist that increases renal blood flow despite decreased systemic arterial blood pressure. Fenoldopam has little to no alpha, beta, or dopamine-2 receptor agonist activity
Sodium nitroprusside
Sodium nitroprusside relaxes smooth muscle in the veins via the release of nitric oxide. When veins are dilated, arterial blood pressure decreases, which then releases renin and catecholamines. There is a decrease in renal perfusion but renal function is maintained
Adenosine vasodilate or constrict
Adenosine is a vasodilator that affects vessels primarily in afterload. It also causes renal vasoconstriction and as such, there is a decrease in renal perfusion, urinary output, and glomerular filtration rate after administration.
Fenoldopam
receptor and action
Fenoldopam is a selective dopamine D1 receptor agonist with direct natriuretic and diuretic properties. Fenoldopam promotes an increase in creatinine clearance and has been employed as a renal protector when renal vasoconstriction is anticipated.
