ITE CA-2 pharm

Question 1

what syndrome can methylene blue cause?

Answer 1

Methylene blue can increase plasma serotonin concentrations and precipitate serotonin syndrome.

Question 2

list serotonergic drugs

Answer 2

SSRIs, TCAs, MAO inhibitors, or even St. John’s Wort

Question 3

symptoms of serotonin syndrome

Answer 3

High CNS concentrations of serotonin can produce mental status changes (confusion, hyperactivity, memory problems), muscle twitching, excessive sweating, shivering, and fever.

Question 4

Neuroleptic malignant syndrome

Answer 4

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).

Question 5

Greatest decrease in BP: midaz or diaz

Answer 5

Midazolam produces a greater decrease in systemic blood pressure than diazepam.

Question 6

What receptors do volatiles act on

Answer 6

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.

Question 7

Aminocaproic acid and TXA mechanism of action

Answer 7

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.

Question 8

what does thrombin do

Answer 8

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.

Question 9

Other effects of opiods

Answer 9

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.

Question 10

Phase 1 metabolism

Answer 10

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.

Question 11

Phase II metabolism

Answer 11

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.

Question 12

Phase I or Phase II faster?

Answer 12

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.

Question 13

Effects of volatile anesthetics on circulatory system

Answer 13

The effects of volatile anesthetics on the circulatory system include decreased systemic vascular resistance, decreased myocardial contractility, coronary vasodilatation (especially isoflurane), and ischemic preconditioning.

Question 14

How do volatiles do ischemic preconditioning

Answer 14

Although multifactorial, much of the ischemic preconditioning effects of volatile anesthetics are related to reduced loading of calcium into myocardial cells.

Question 15

How does N2O affect BP when mixed with volatile

Answer 15

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.

Question 16

Levodopa on day of surgery?

Answer 16

For patients with Parkinson disease, levodopa should be continued on the day of surgery.

Question 17

What can you give IV if you can’t give levodopa

Answer 17

Apomorphine is a dopamine agonist that can be administered subcutaneously or intravenously if oral levodopa cannot be given.

Question 18

Meds to avoid in Parkinsons

Answer 18

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).

Question 19

Why give carbidopa

Answer 19

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.

Question 20

Benzos
protein bound?
hydro/lipo philic?
Metabolism?
Which channel?
frequency or duration of channel opening?

Answer 20

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.

Question 21

Benzos in obesity

Answer 21

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.

Question 22

Propofol cardiovascular effects

Answer 22

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.

Question 23

Propofol and heart rate

Answer 23

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.

Question 24

Ketamine effect on potentials

Answer 24

Ketamine increases the amplitude of somatosensory evoked potentials. Auditory and visual evoked responses are decreased by ketamine.

Question 25

Ketamine and secretions

Answer 25

Ketamine use may result in increased salivation and secretions. This effect can be modulated by an anticholinergic drug such as atropine and glycopyrrolate.

Question 26

Ketamine mechanisms and effects

Answer 26

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.

Question 27

CV effects of ketamine

Answer 27

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.

Question 28

Ketamine in bronchi

Answer 28

Ketamine has bronchodilatory activity, which is effective in attenuating bronchospasm.

Question 29

Time constants and | How much per each

Answer 29

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.

Question 30

Succ mech

Answer 30

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.

Question 31

Where does pseudocholinesterase act on succ

Answer 31

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.

Question 32

What conditions change required dose of non-depolarizing NMBDs

Answer 32

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.

Question 33

Termination of action for small, non-protein-bound and hydrophilic drugs

Answer 33

Renal elimination will terminate drug action for small, non-protein-bound and hydrophilic drugs

Question 34

_______ is the most important mechanism of drug action termination for most drugs.

Answer 34

Metabolism is the most important mechanism of drug action termination for most drugs.

Question 35

``` CO2 Response Curve Changes Benzos Prop Opioids Volatiles Hypoxemia ```

Answer 35

``` 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 ```

Question 36

``` Diuretic Electrolyte Changes Urine sodium Urine potassium Urine calcium Blood pH ```

Answer 36

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

Question 37

Where do diuretics act

Answer 37

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.

Question 38

increased drug ionization = increased or decreased vol of dist

Answer 38

decreased

Question 39

increased lipid solubility = increased or decreased vol of dist

Answer 39

increased

Question 40

increased protein binding = increased or decreased vol of dist

Answer 40

decreased

Question 41

skin receives __% of cardiac output

Answer 41

20

Question 42

bone receives __% of cardiac output

Answer 42

1

Question 43

heart receives __% of cardiac output

Answer 43

75

Question 44

kidneys receive __% of cardiac output

Answer 44

75

Question 45

opioid heart rate

Answer 45

decreased

Question 46

increased incidence of delayed resp depression caused by lipophilic or hydrophilic opioids

Answer 46

hydrophilic

Question 47

receptor associated with stiff chest syndrome

Answer 47

mu-receptor and gaba-nergic inhibition

Question 48

lipid solubility fent compared to morphine

Answer 48

fent is more lipid soluble and therefore crosses blood brain barrier faster

Question 49

opioid and urine

Answer 49

retention

Question 50

lipo/hydrophilic for increased diffusion accross vasc membranes

Answer 50

lipophilic

Question 51

buprenorphine

Answer 51

partial mu agonist, weak kappa antag

Question 52

opioid with tachycardia risk and why

Answer 52

meperidine bc atropine like structure

Question 53

opioid pre-load

Answer 53

decreased

Question 54

mu or kappa? | decreased visceral & somatic pain (GABA-mediated)

Answer 54

mu

Question 55

increased diffusion accross spinal membranes

Answer 55

lipophilic

Question 56

histamine release

Answer 56

meperidine, morphine, codeine

Question 57

increased cephalo-caudal spread (epidural and subarachnoid space)

Answer 57

hydrophilic

Question 58

opioid with least pulm uptake

Answer 58

remi

Question 59

how many half-lives required to consider a drug eliminated from the body

Answer 59

5

Question 60

Adenosine Diphosphate Analogues

Answer 60

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.

Question 61

Acetylsalicylic acid -

Answer 61

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.

Question 62

Platelet Receptor Inhibitors –

Answer 62

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.

Question 63

Purinoreceptor antagonist -

Answer 63

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.

Question 64

Glycoprotein Iib/IIIa Antagonists –

Answer 64

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.

Question 65

Barbiturates

Answer 65

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.

Question 66

The context-sensitive half-time is

Answer 66

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

Question 67

Context-sensitive half-times for propofol in obese

Answer 67

Context-sensitive half-times for propofol are not significantly different between obese and lean subjects

Question 68

Etomidate

Answer 68

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.

Question 69

Risk factors for QT prolongation

Answer 69

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

Question 70

Perioperative QT prolongation management

Answer 70

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.

Question 71

Anesthetic meds QT effects

Answer 71

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.

Question 72

Methohexitol CV effects

Answer 72

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

Question 73

Why hypotension more common with propofol

Answer 73

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.

Question 74

Methohexital

Answer 74

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.

Question 75

Barbiturates CV effects and mech

Answer 75

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.

Question 76

Reverse acupuncture analgesia

Answer 76

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.

Question 77

Acupuncture mech

Answer 77

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.

Question 78

Indications for barbiturates

Answer 78

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

Question 79

Contraindications for barbiturates

Answer 79

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

Question 80

Absorption of a drug depends on

Answer 80

Absorption of a drug directly depends on its lipid solubility and inversely on its polarity, or degree of ionization

Question 81

Phase II block

Answer 81

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.

Question 82

Phase I block

Answer 82

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.

Question 83

propofol onset of effect hypnosis vs cardiovascular

Answer 83

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).

Question 84

propofol effect on CYP

Answer 84

inhibits 3A4

Question 85

age effect on central compartment

Answer 85

Older individuals have decreased clearance rates and a smaller central compartment volume.

Question 86

Organophosphates are

Answer 86

Organophosphates are acetylcholinesterase inhibitors that cause an excess supply of the neurotransmitter acetylcholine (ACh).

Question 87

prophylaxis for organophosphate poisoining

Answer 87

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.

Question 88

organophosphate poisoning symptoms

Answer 88

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.

Question 89

organophosphate poisoning treatment

Answer 89

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.

Question 90

Muscarinic agonists

Answer 90

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)

Question 91

Mexiletine

Answer 91

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.

Question 92

Hypercalcemia effect on non-depolarizing neuromuscular blockers

Answer 92

Hypercalcemia antagonizes the effects of non-depolarizing neuromuscular blockers and higher doses may be required to obtain the desired effect.

Question 93

Which of the following neuromuscular blocking drugs has an active metabolite that is nearly as potent as its parent drug?

Answer 93

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.

Question 94

Cisatracurium metabolite

Answer 94

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.

Question 95

Biggest risk for bradycardia with sux admin and why | How prevent?

Answer 95

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.

Question 96

How does phenytoin affect neuromusc blockade of

Answer 96

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.

Question 97

In hypovolemic shock, fentanyl dosing should be

Answer 97

In hypovolemic shock, fentanyl dosing should be cut in half.

Question 98

delta receptor

Answer 98

Delta receptor: analgesia, antidepressant, physical dependence delta airlines: not depressed because high in the sky but you depend on the plane

Question 99

mu receptor

Answer 99

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

Question 100

kappa receptor

Answer 100

Kappa receptor: analgesia, dysphoria, miosis, sedation you get capped: pupils shrink, you feel crappy, you pass out

Question 101

some common GA drugs that lower the seizure threshold

Answer 101

However, if general anesthesia is necessary it is recommended to avoid drugs which lower the seizure threshold such as lidocaine, ketamine, enflurane, and meperidine.

Question 102

Nicardipine metabolism

Answer 102

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.

Question 103

Indomethacin

Answer 103

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.

Question 104

Pathophysiology of PRIS

Answer 104

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.

Question 105

MH Dantrolene dosing

Answer 105

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.

Question 106

Sux increase K by how much for how long

Answer 106

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.

Question 107

Furosemide acid base disturbance

Answer 107

Furosemide administration can cause a hypokalemic-hypochloremic metabolic alkalosis secondary to potassium excretion and a contraction alkalosis.

Question 108

Acetazolamide

Answer 108

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.

Question 109

K sparing diuretics Site of action and mechanism Acid base disturbance

Answer 109

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.

Question 110

Name a immunosuppressant that can prolong NDNBD

Answer 110

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.

Question 111

what type of receptor is NMDA

Answer 111

glutamate

Question 112

Fenoldopam

Answer 112

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

Question 113

Sodium nitroprusside

Answer 113

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

Question 114

Adenosine vasodilate or constrict

Answer 114

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.

Question 115

Fenoldopam | receptor and action

Answer 115

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.