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
