Gastrointestinal Pharmacology

Gastrointestinal Pharmacology

• Hepatocytes absorb nutrients, store/release carbs, proteins, and lipids, synthesize cholesterol, glucose, coagulation factors, and bile salts, and detoxify/excrete drugs, while Kupffer cells act as macrophages in the liver.
• Inhalational anesthetics decrease hepatic blood flow.
• Parasympathetic nervous system enhances GI tract activity while the sympathetic inhibits it.
• The lower esophageal sphincter (LES) prevents gastric contents from entering the esophagus.
• The gastric mucosa stores and processes food and secretes H+.
• Mechanisms of delayed gastric emptying include diabetic gastroparesis, GERD, acute viral gastroenteritis, and drug-induced causes (GLP-1 agonists, beta agonists, tricyclic antidepressants, increased EtOH).
• Therapeutic goals of antacids and GI motility drugs are to decrease the volume and increase the pH of gastric contents.
• Oral antacids change gastric fluid pH by removing H+ ions, decreasing H+ secretion, increasing LES tone, and increasing motility.
• Sodium Citrate (15-30 mL PO) can be given to pregnant patients at high risk for aspiration.
• Oral antacids can cause metabolic alkalosis.
• H1 receptors are involved in allergic reactions and targeted by drugs like diphenhydramine and promethazine, which antagonize muscarinic, cholinergic, serotonin, & alpha-adrenergic receptors.
• Perioperative uses of these drugs include sedation, antiemesis, opioid sparing effects, and local anesthetic properties in dentistry.
• H2 receptors are involved in gastric acid secretion and immune cell differentiation and targeted by drugs like famotidine, which blocks cAMP and activation of H+/K+ ATPase.
• The IV dose of famotidine is 20 mg.
• Proton pump inhibitors (PPIs) directly inhibit the H+/K+/ATPase (proton) pump.
• Examples of PPIs are omeprazole and pantoprazole.
• Side effects of PPIs include headache, agitation, confusion, abdominal pain, N/V, and GI tract bacterial overgrowth.
• Metoclopramide increases LES tone and peristaltic contractions.
• Dopamine inhibition in the CNS can cause dystonia, restlessness, sedation, and dysphoria.
• CNS structures involved in nausea include the vestibular apparatus, nucleus tractus solitarius, and CRTZ.
• Neurotransmitters involved in nausea and vomiting include dopamine (D2), acetylcholine (M), serotonin (5HT3), histamine (H1), and substance P (NK1).
• PONV risk factors include patient-related (age, gender, smoking, history of motion sickness/PONV), anesthesia-related (volatile anesthetics, N2O, opioids, neostigmine), and surgery-related factors (duration, laparoscopic technique, gynecologic, ENT, breast/plastic surgery, orthopedics, ophthalmic).
• Granisetron's mechanism of action is as a 5-HT3 receptor antagonist.
• Side effects of ondansetron include headache and diarrhea.
• Side effects of transdermal scopolamine include dry mouth, blurred vision, rash, hyperthermia, tachycardia, restlessness, hallucinations, seizures, coma, and respiratory failure.
• Dexamethasone is a highly effective corticosteroid antiemetic.
• Droperidol, a dopamine antagonist, has a black box warning for QT prolongation in high doses.
• Aprepitant's mechanism of action is as a neurokinin-1 receptor antagonist.
• Propofol and midazolam are effective antiemetic anesthetics.

Dietary Supplements

• Indications for nutritional support include major surgery, trauma, burns, malnourished patients or those taking chemotherapy, and hepatic/renal dysfunction.
• Surgical placement of a feeding tube is indicated when unable to take or absorb PO nutrition, as well as the duration of requirement.
• Dumping syndrome can occur following rapid introduction of hyperosmolar tube feeds into the gut.
• Anesthetic considerations for patients receiving enteral nutrition include the risk of aspiration, location of the feeding tube, and whether a cuffed ETT or tracheostomy is present.
• Side effects of parenteral nutrition assessed by the CRNA include hypervolemia, hypercarbia, alterations in blood sugar, and sepsis/infection risks.
• Fat-soluble vitamins: A, D, E, K.
• Echinacea may cause immune suppression, hepatitis, allergic reaction/anaphylaxis.
• Cardiovascular adverse effects associated with ephedra use include increased HR/BP, Vasoconstriction, arrhythmias, catecholamine depletion, sensitized myocardium.
• Garlic should be held for 1-2 weeks prior to regional anesthesia.
• Ginger interacts with anticoagulants (5HT-3 antagonists) & NSAIDs.
• Ginkgo inhibits platelet-activating factor.
• Ginseng can cause decreased blood sugar and agitation, along with increased bleeding, increased BP, and increased HR.
• Kava potentiates GABA-mediated effects, but does not bind to GABA.
• St. John's Wort is commonly used for depression, psych disorders, and neuropathy.
• Abrupt discontinuation of Valerian can cause withdrawal symptoms similar to benzodiazepines.

Pharmacodynamics & Populations

• Pharmacodynamics is the study of what drugs do to the body, or the relationship between effect site concentration and clinical effects.
• Three phases of the neuronal action potential are depolarization, repolarization, and hyperpolarization.
• The sodium-potassium pump helps restore resting membrane potential.
• Voltage-gated calcium channels are responsible for neurotransmitter release by synaptic vesicles.
• Chirality refers to molecules with 3-D asymmetry that are mirror images. A racemic mixture is a solution with equal amounts of both enantiomers
• An example of an inhibitory ligand-gated ion channel is the glycine receptor.
• Efficacy is the degree at which a ligand can effect a response when coupled to a receptor or the ability of a drug to cause a maximum response or clinical effect.
• Potency is the amount of a drug required to create a response; concentration or amount of drug to cause a specific clinical response.
• The ED50 is the effective dose to produce a response in 50% of the population and is a measure of potency.
• Therapeutic index is a ratio of blood concentration at which a drug causes therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies)
• Competitive antagonists block agonists from binding to a receptor, but can be reversed with more agonist while non-competitive antagonists cannot.
• Additive drug interaction happens when the effect of two drugs given in combination equals the mathematical summation of their effects when given alone.
• Older adult patients are not at higher risk of postoperative nausea and vomiting with anesthesia than younger patients.
• Neurophysiologic changes in older adults affecting pharmacology include: decreased albumin levels (more free drug) and risks of toxicity due to decreased liver/kidney function, polypharmacy, increased CNS sensitivity-delirium.
• Hepatic differences in pediatric/neonatal patients that may affect their ability to metabolize drugs; older children have increased GFR and clearance and increased liver blood flow equals to increased hepatic drug clearance and production of metabolites.
• Renal differences in pediatric/neonatal patients include immature renal function that reduces urine pH which results in reduced renal excretion.
• Cardiovascular parameter increases on average 35 – 50% in obstetric patients depending on the trimester; up to 300% immediately post-delivery.
• Sensitivity of obstetric patients to anesthetics change (increase) due to increased circulating progesterone decreasing requirements, decreased CSF effects distribution, decreased plasma protein, increased total body water resulting in dilutional effect; increased adipose tissue resulting in larger volume of distribution of drugs, increased blood volume, dilutional anemia, and decreased SVR, increase sensitivity to vasoactive drugs, increased MV & O2 consumption = faster induction & emergence; increased renal blood flow & GFR = dose adjustments for renally eliminated drugs. Increased 2D6 & 3A4 enzymes & decreased cholinesterase from alterations in liver activity; delayed gastric emptying = increased risk for PONV & pulmonary aspiration.

Pharmacokinetics & Medication Safety

Pharmacokinetics

• Pharmacokinetics studies the relationship between drug dose and plasma concentration.
• Four major components of pharmacokinetics are absorption, distribution, metabolism, and elimination (ADME).
• Acids are proton donors while bases are proton acceptors.
• The dissociation constant (pKa) measures the strength of the interaction of compounds with a proton and the lower the pKa, the stronger the acid.
• The pH at which ½ the molecules of acid are likely to be deprotonated is at the pKa and in its conjugate base form. The HIGHER the pKa, the GREEDIER the molecule and WEAKER the acid.
• Acids dissolve/diffuse into acidic solutions with pH LOWER than their pKa while bases dissolve/diffuse into basic solutions with pH greater than their pKa.
• A nonionized drug (typically) is its pharmacologically active form.
• Bioavailability is the fraction of chemically unchanged drug that reaches systemic circulation.
• The bioavailability of an intravenous drug is 100%.
• Factors influencing drug distribution include route of administration, first-pass hepatic metabolism, and drug solubility/chemical stability.
• Most drugs are bound to albumin.
• A central compartment includes the heart, lungs, liver, kidneys, and blood whereas peripheral compartments include the brain, skin, muscle, and fat.
• Primary site of drug metabolism is the liver.
• Active metabolites result of drug metabolism that retains similar therapeutic and side effects as parent drug.
• Enzyme induction increases clearance, decreasing plasma level (dose increase may be required); example inducers: Barbiturates, Ethanol, Dilantin, Rifampin.
• Enzyme inhibition decreases clearance, increasing plasma level (dose decrease may be required); example inhibitors: Grapefruit juice, SSRIs, Omeprazole, Erythromycin.
• Renal insufficiency/failure reduces elimination of unchanged drugs and active metabolites, increasing toxicity risks.
• Drug clearance is indirectly related to its half-life.
• Conditions that increase a drug's half-life: Decreased renal blood flow, cardiac output, extraction ratio, & metabolism, displacement of drug from albumin.
• Steady state is the time at which the amount of a drug entering the body is equal to the amount of the drug being eliminated.

Medication Safety

• Common medication errors include errors relating to administration, substitution, and incorrect labeling.
• Strategies to prevent medication errors include barcode scanning, standardization, smart pumps, unique connections, prefilled syringes, premixed solutions, and avoiding multi-use vials and look-alike meds.

Renal (Diuretics)

• The kidneys produce renin and erythropoietin.
• The kidneys receive approximately 20%-25% of the cardiac output.
• Aldosterone causes distal reabsorption of Na+ and water and excretion of K+.
• Hypotension and hypovolemia activate the renin-angiotensin-aldosterone system, not hypertension and hypervolemia.
• Juxtaglomerular cells in the macula densa release renin.
• Angiotensin II causes vasoconstriction.
• Salt and water are reabsorbed by the kidneys.
• Release of arginine vasopressin and aldosterone accompanies increased blood volume from water reabsorption.
• Atrial natriuretic peptide (factor) senses stretch in the heart to increase excretion of salt and water as a result of fluid volume overload.
• Kidneys maintain acid-base balance by reabsorbing bicarbonate ions into plasma and secreting hydrogen ions into the lumen filtrate.
• Filtration is the passive movement of water and small dissolved molecules, which is the first step of urine making.
• Decreased afferent arteriole tone increases GFR while increased efferent arteriole tone does the same.
• Water tends to follow sodium movement.
• The sodium-potassium pump is an example of an active mechanism of reabsorption.
• Osmosis is an example of a passive mechanism of reabsorption.
• Diuretics are commonly used to treat hypertension and congestive heart failure.
• Carbonic anhydrase inhibitors like acetazolamide primarily decrease the reabsorption of sodium, bicarbonate, and water.
• Osmotic diuretics move through glomeruli unmetabolized and freely filtered.
• Osmotics increase the osmolarity of blood and renal tubule fluid.
• IV dose of mannitol: 0.25-1 g/kg up to 2g/kg
• Loop diuretics inhibit the sodium-potassium-2 chloride co-transporter in the thick ascending limb of the loop of Henle.
• Loop diuretics increase the production of prostaglandins and lead to hypokalemia.
• Hypokalemia increases the risk of metabolic alkalosis and potentiation of non-depolarizing neuromuscular blocking drugs.
• Ototoxicity is associated with loop diuretics.
• Thiazide diuretics inhibit the sodium-chloride co-transporter in the ascending Loop of Henle and distal convoluted tubule.
• Thiazides inhibit reabsorption of sodium and increase excretion of potassium.
• Thiazides increase reabsorption of calcium and are associated with hyperglycemia.
• Spironolactone is an aldosterone receptor blocker and affects the sodium-potassium ATPase pump.
• Triamterene prevents sodium reabsorption independently of aldosterone.
• Potassium-sparing diuretics primarily work in the cortical collecting duct.
• Activation of D1 receptors by dopamine increases the formation of cyclic adenosine monophosphate as a cellular 2nd messenger.
• Higher doses of dopamine agonists activate beta adrenergic receptors increasing inotropy and cardiac output and alpha adrenergic receptors causing vasoconstriction.
• Electrolyte Level Changes*

• Patient risk factors for perioperative kidney injury include hypovolemia, decreased cardiac output and systemic vascular resistance, and increased sympathetic nervous system stimulation.
• Common nephrotoxic drug classes include NSAIDs and aminoglycosides.

Fluids/Electrolytes/Blood

• Potassium is the major cation & phosphate is the major anion in the intracellular body fluid compartment.
• Sodium is the major cation and chloride is the major anion in the extracellular body fluid compartment.
• Structures that prevent free movement of proteins and large macromolecules between body fluid compartments are phospholipid bilayer, glycocalyx, capillary permeability, and the blood-brain barrier.
• Examples of "static parameters" for monitoring intravascular volume status include Central Venous Pressure (CVP), urinary output, and mean arterial pressure (MAP).
• Greater than 10-12% variation in dynamic parameters (e.g., pulse pressure variation with respiration) indicates fluid responsiveness or dehydration.
• Lactated Ringers is a balanced crystalloid solution.
• Strong Ion Difference (SID) refers to the difference between fully dissociated strong cations and strong anions in plasma and the formula is: SID = (Na+K+Ca2+Mg2)−(Cl−+other strong anions).
• Excessive infusion of 0.9% Normal Saline (NS) can cause a decrease in SID due to its high chloride content, leading to hyperchloremic metabolic acidosis.
• Approximately 20-25% of infused crystalloids remain intravascular in healthy patients.
• Hypotonic crystalloids: 0.45% NS & D5W
• Water moves towards area with greatest solute concentration; into the cell.
• Hypertonic crystalloid examples: 3% NS & D5NS.
• Water moves towards area with greatest solute concentration; out of the cell.
• Fluid solutions containing large molecular weight particles suspended in a crystalloid solution are known as colloids.
• Anaphylactoid reactions to albumin infusions are not common.
• Populations under black box warning associated with hydroxyethyl starches: CPB/CABG, renal issues, and critically ill.
• Colloids are not superior to balanced crystalloids for maintenance of intravascular fluid volume status.
• Sodium's important physiologic functions, besides water balance & osmolality: neuronal action and secondary transport of other ions.
• Potassium is important in cell membrane excitability, vasodilation, clot formation, and renal function.
• Loops diuretics, beta agonists (albuterol, dopamine), insulin, ABX, and catecholamines decrease serum Potassium levels.
• Magnesium's physiologic functions include protein synthesis, neuromuscular FX, muscle relaxation, antiarrhythmics, vasodilation (OB), and stabilization of blood brain barrier.
• Magnesium may be used to treat preeclampsia with a 4g loading dose and 1g/hr x 24 hours.
• Calcium chloride contains 3 times more elemental calcium per ml than calcium gluconate.
• Risk of giving calcium chloride in small, peripheral IVs: extravasation.
• Main source of blood cell production in the body: bone marrow.
• Agglutinogen is the portion of an RBC that causes an immune response when in contact with incompatible blood causes clots.
• Agglutinin is an antibody that causes the clumping (agglutination) of cells or particles, typically in response to specific antigens.
• Ultimate risk of agglutination: clumping; blood clotting.
• Often depleted as RBCs age from blood storage: ATP & 2,3 DPG.
• IV fluids to avoid as carrier fluid for transfusion of RBCs: Lactated Ringers & D5W.
• Thawed plasma should be transfused within 24 hours.
• Cryoprecipitate: rich in Fibrinogen (Factor 1), Factor VIII & Factor XIII and should not be administered with platelets.
• Leukoreduction: the removal of white blood cells from platelets and RBCs.
• Minimizes: immunomodulatory responses, sensitization, antibody formation, febrile transfusion reactions, postoperative infections, and tumor metastasis formation.
• Cardiogenic volume overload from blood product transfusion: TACO.
• Pulmonary vascular injury and (non-cardiogenic) edema within 6 hrs of transfusion: TRALI.
• Coagulopathies from massive trauma are worsened by hypothermia and sepsis.
• Lab test that provides information on clot strength and formation and promotes goal-directed management of coagulopathies: TEG Thromboelastogram.
• Electrolytes to replace & monitor with massive transfusion: Calcium & Magnesium.
• Massive transfusion generally characterized by the administration of greater than 10 units of RBCs within 24 hours.
• 1:1:1 ratio: RBC: FFP: Platelets
• Risks of excessive crystalloid use (vs. blood products) for volume expansion during massive hemorrhage/trauma: Lack of clotting constituents, increased bleeding, hypoperfusion, decreased nutrient delivery and waste removal ability.

Anticoagulants & Procoagulants

• Mechanisms of primary hemostasis: adhesion, activation, and aggregation.
• Platelet adhesion requires exposure of the subendothelial vascular basement layer and the attachment factor von Willebrand Factor to collagen receptors.
• Mediators synthesized and released during platelet activation: ADP & Thromboxane 2.
• Fibrinogen via GP IIb & GP IIIa links platelets together during aggregation.
• Formation of a cross-linked and water insoluble fibrin clot is called Temporary hemostasis.
• Vitamin K dependent clotting factors: II, VII, IX & X.
• Tissue Factor is the primary initiator of coagulation in the extrinsic coagulation pathway, also known as Thromboplastin, Factor III.
• Extrinsic coagulation pathway: Tissue Factor III is released by traumatized vessels, activates VII, which activates IX and X (common pathway). Platelet factor 3 and calcium are required.
• Intrinsic coagulation pathway: Damage to the endothelium of blood vessel or blood itself, vascular spasm, and platelet activation triggers a cascade starting with Factor XII, activates XI, which activates IX, which activates VIII. VIIIa combines with IXa and platelet factor 3 and calcium to form a complex that then activates Factor X (Common Pathway.)
• Clot stabilization = Common Pathway. Factor X, once activated, combines with V +calcium and activates Prothrombin Activator. PTA reacts with prothrombin (factor II) and converts to thrombin; Thrombin tells fibrinogen to make fibrin fibers. Factor 2 also activates Factor 13, which combines with calcium to create mesh over the surface of the platelet plug.
• Prothrombin time (PT) measures coagulation along the extrinsic pathway and has a normal PT value of 11-14 seconds.
• Activated partial thromboplastin time (aPTT) measures coagulation along the intrinsic pathway and has a normal aPTT value of 25-35 seconds.
• Activated clotting time (ACT) measures the activity of Heparinization & Protamine Antagonization along the intrinsic & final common pathway's.
• Mechanism of action of unfractionated heparin: Binds with Antithrombin III, increasing its effects 100-1000x; AT3 prevents activation of II, IX, X.
• Unfractionated Heparin should be held prior to neuraxial anesthesia for 4-24 hours depending on formulation."
• Heparin-induced thrombocytopenia (HIT) pathophysiology: Type 1 activates platelets inducing aggregation (non-immune) and Type 2 is immune-mediated causing release of IgG which then promotes formation of thrombus.
• Use of low molecular weight heparin (LMWH) places the anesthetic patient at risk for spinal and epidural hematoma.
• Warfarin mechanism of action: Vitamin K epoxide reductase inhibitor (prevents activation of Vitamin K, which is required for Factors II, VII, IX, and X to become activated.).
• International normalized ratio (INR) target value for warfarin therapy: 2.0-3.0.
• Recommended number of days to hold warfarin prior to surgery: 3-5 days.
• Bivalirudin and argatroban binds inhibits Factor II Prothrombin which prevents the shift to Thrombin.
• Xarelto and Apixaban binds inhibits Factor Xa.
• They reduce the risk of stroke in patients with atrial fibrillation.
• Aspirin mechanism of action: COX 2 inhibitor preventing formation of Thromboxane 2 from platelets which prevents aggregation.
• Time to discontinue clopidogrel before surgery and regional anesthesia: 5-7 days.
• Plasminogen activator thrombolytics are contraindicated within 2 days surrounding neuraxial and regional anesthesia.
• Antithrombin III prevents blood clotting by preventing activation of Factors IIa, Xa, IX, XI, and XII.
• Antithrombin III is a co-factor for Heparin.
• Plasminogen activators (e.g., tPA, uPA Urokinase/Streptokinase) increase the formation of Plasmin leading to breakdown of the fibrin clot.
• Epsilon aminocaproic acid (Amicar) mechanism of action: Synthetic anti-fibrinolytic via competitive inhibition of plasminogen to plasmin.
• Tranexamic acid (TXA) mechanism of action: Synthetic anti-fibrinolytic, competitive inhibition of plasminogen to plasmin; high dose =direct inhibition
• Protamine inactivates acidic heparin molecules and not effective against LMWH however some of the side effects include hypotension, anaphylaxis, RV Failure, Acute Pulmonary Vasoconstriction.
• Desmopressin should be given in a dose of 0.3 mcg/kg over 15-30 minutes.
• It releases endogenous stores of Factor VII: vWF.
• Cryoprecipitate is given to treat low fibrinogen levels, or FFP but 1 unit/10 kg can increase fibrinogen levels by approximately 50-70 mg/dL.

NEURO PHARMACOLOGY

ANTI-PARKINSONIAN

• Parkinson's Disease characteristics: resting tremor and stiffness/rigidity.
• Pathophysiology involves depletion of dopamine, leading to an imbalance and excess of excitatory activity from acetylcholine.
• Anesthetic considerations include bradykinesia and rigidity of respiratory and pharyngeal muscles.
• Avoid cardiac drugs (beta blockers) with deep brain stimulation testing for tremors.
• Levodopa is a physiologic precursor to dopamine and a primary treatment for Parkinson's, with cardiovascular side effects including tachycardia and orthostatic hypotension.
• Treat parkinsonism-hyperpyrexia syndrome with Levodopa PO or NGT.
• Bromocriptine mimics dopamine at the receptor, regulating motor functions and prolactin release.
• Monoamine oxidase B breaks down dopamine in the CNS.
• Anticholinergics are given to correct the balance between dopamine and Ach, control tremors, and decrease excess salivation.
• Give droperidol, metoclopramide & ondansetron as the antiemetic for patients with PD.

ANTI-EPILEPTIC

• Symptoms seen with a seizure include altered awareness, convulsions, and loss of consciousness.
• Perioperative factors associated with increased seizure risk are electrolyte abnormalities, sleep-wake pattern changes, hypoglycemia.
• Patients taking antiepileptic drugs may require higher doses of propofol.
• Uses/indications for benzodiazepines in seizure disorder: reducing neuronal excitability during acute seizures and ETHO withdrawal.
• BZ mechanism of action: positive allosteric modulator of GABA.
• Phenobarbital: a long-acting barbiturate and is effective for most types of seizures.
• Gabapentin does not decrease GABA binding and metabolism.
• Levetiracetam (Keppra) can increase blood pressure and has a side effect of sedation.
• Phenytoin increases metabolism of NDMRs; mild blocking effects at NMJ, upregulation of ACH receptors=increase dose requirements

CNS STIMULANTS

• Chronic amphetamine use causes depletion of catecholamines.
• Give epinephrine, vasopressin & phenylephrine to treat.
• Doxapram stimulates medullary respiratory centers via carotid chemoreceptors.
• Methylxanthines act by antagonism at the adenosine receptor and as phosphodiesterase inhibitors.
• Methylxanthines used for the epidural patient who experiences postdural puncture headache.

Psychopharmacology

• Serotonin regulation affects platelet aggregation, vascular tone, hematopoiesis, inflammatory response, and genital arousal outside the CNS.
• Serotonin regulation affects mood, memory, sleep, sex, aggression, and appetite inside the CNS.
• SSRIs like fluoxetine block the 5-HT reuptake transporter, increasing serotonin levels in the synapse.
• SSRIs has a black box warning: suicidal thoughts in children & teens.
• Serotonin syndrome is precipitated by phenylpiperidine opioids (Fentanyl, meperidine), methadone, reglan, erythromycin, metronidazole, and drugs that inhibit CYP 450 enzymes.
• Serotonin Syndrome – Autonomic changes: tachycardia, HTN, tachypnea, diaphoresis, Changes in body Temperature; Neuromuscular abnormalities: Muscle rigidity, tremors, myoclonus, trismus; Mental status changes: Confusion, agitation.
• SNRIs like venlafaxine work by blocking 5-HT and norepinephrine reuptake transporters.
• They may cause hypertension and tachycardia as a side effect.
• Tricyclic antidepressants (TCAs) work by blocking 5-HT and norepinephrine reuptake transporters.
• TCAs antagonize alpha-1, NMDA, H1, H2, and mACh receptors.
• TCAs may cause an increase in HR but also orthostatic hypotension.
• MAOIs block the breakdown of NE, 5-HT, DA, and E.
• Neurological and ventilatory depression are associated with Type 2 depressive adverse reaction when taking MAOIs.
• What type of sympathomimetic drugs are contraindicated in the patient taking MAOIs?: Ephedrine, phenylephrine, and pseudoephedrine.
• Lithium inhibits the excitatory effects of dopamine and glutamate while it increases the inhibitory effects of GABA.
• Signs of lithium toxicity include dysrhythmias, seizures, and weakness.
• Haloperidol is a typical/first-generation antipsychotic drug.
• Haloperidol antagonizes D2 receptors.
• Emergence delirium risk factors: age, gender, substance use, ETOH/Benzodiazepine use, prolonged surgery, temp & BP changes, and hypoxemia.
• Excessive dopamine blockade may cause extrapyramidal symptoms.
• Tardive dyskinesia causes involuntary movements in the tongue, face/neck, and extremities while Akathisia causes restlessness and trouble standing still or tolerating activity, Acute Dystonia causes muscle rigidity/spasms and may lead to laryngeal spasm with respiratory distress.
• Neuroleptic malignant syndrome (NMS) causes flaccid paralysis in NMS compared to Malignant Hyperthermia where Non-depolarizing muscle relaxants are ineffective.
• Metabolic changes common with both types of antipsychotic drugs are extrapyramidal effects-tardive dyskinesia and Neuroleptic malignant syndrome.
• Methylphenidate and mixed amphetamine salts block the reuptake of norepinephrine and dopamine.
• Clonidine is FDA approved to treat ADHD.

Immunologic Worksheet

ANTIMICROBIALS

• Types of surgical site infections (SSI): Incision (superficial incisional), Deep Soft Tissue (deep incisional), Anatomy opened or manipulated (organ/space).
• Endogenous risk factors for SSI development: extreme age, PVD, poor nutritional status, obesity, current infection, altered immunity, ETOH, and tobacco.
• Wound classification Class II: Clean-Contaminated typically in sites such as Respiratory, GI, and GU.
• SCIP-1 measure: vancomycin should be infused within 2 hours before incision however Vancomycin is NOT recommended in the absence of documented or highly suspected MRSA for surgical prophylaxis.
• SCIP-2 state: antibiotics should be discontinued within 24 hours after surgery.
• Bacterial synthesis of enzymes that breakdown antibiotics is known as bacterial resistance.
• Types of beta lactams: penicillins, cephalosporins & carbapenems.
• Patients with a family history of penicillin allergy will not inherit the allergy.
• Cephalosporins (such as Cefazolin) combat skin flora and normal flora in GI & GU tracts which makes it the drug of choice
• This drug (Cefazolin) belongs to the first generation of cephalosporins and the dose required for a patient is 450 g and up for adults q 4 h who is 135 kgs.
• Gentamicin: belongs to which class of antibiotics and its belongs to the Aminoglycosides.
• Aminoglycosides Mechanism of action: interferes with protein synthesis during mRNA translation and toxicity causes Ototoxicity & Nephrotoxicity.
• The common perioperative antibiotic that belongs to the lincosamide class is clindamycin, and should be infused over 10-60 minutes.
• Red Man Syndrome symptoms: Histamine release, erythema, pruritis, HOTN d/t venodilation, dyspnea, Rare cardio toxicity & arrest.
• Metronidazole side effects when combined with alcohol: abdominal disturbances, N/V, headaches, and flushing.
• Topical antiseptics used perioperatively: Chlorhexidine, Povidone Iodine and Iodine.

Respiratory Worksheet

• Functional residual capacity contains the amount of air in the lung at the end of normal exhalation, serving as an O2 reservoir and can be improved with ventilator settings such as PEEP.
• Compliance is a change in lung volume for a given change in airway pressure.
• Turbulent air flow and decreases in lung volumes increase airway resistance.
• Dead space is inspired air that does not enter (or participate in) gas exchanging alveoli.
• Shunt is venous blood that returns to the heart without exposure to ventilated alveoli.
• An oxyhemoglobin dissociation curve shift to the right indicates more O2 is offloaded to tissues (decreased affinity) and is seen in Acidosis, Hyperthermia & Increased 2,3 DPG
• An oxyhemoglobin dissociation curve shift to the LEFT indicates an increased affinity for oxygen binding by hemoglobin. and is seen in Alkalosis, Fetal hemoglobin, Hypothermia & Decreased 2,3 DPG
• General anesthesia can cause atelectasis (partial alveolar closure or collapse).
• Moderate and severe COPD patients experience elevations in Pa CO2 levels.
• Obstructive airway disease is characterized by a low FEV1/FVC ratio and decreased forced expiratory volume.
• Restrictive airway disease is characterized by a normal FEV1/FVC ratio and decreased forced expiratory volume.
• Asthma is an inflammatory airway disease with bronchospasm, edema, mucus secretion and proliferation of smooth muscle cells.
• Pre-oxygenation with 100% O2 helps remove & replace Nitrogen in the alveoli.
• Parasympathetic nervous system releases Acetylcholine via Vagus nerve which Activates M3 receptors which results in smooth muscle contraction-bronchoconstriction.
• Sympathetic nervous system has little direct influence on airways but can cause airway smooth muscle dilation through stimulation of the beta-2 receptor.
• Direct Airway smooth muscle relaxation comes from Non Adrenergic Non Cholinergic.
• Capnographic waveform change with bronchospasm: "Shark fin". (Loss of the alpha angle)
• Beta-2 agonists increase intracellular cAMP levels in smooth muscle and also causes bronchodilation, vasodilation, pancreatic release of glucagon and uterine relaxation.
• Side effects of beta-2 agonists: tremors, tachycardia, hyperglycemia & hypokalemia.
• Initial Inhaled dose of albuterol MDI for acute bronchospasm in puffs: 8 puffs.
• Muscarinic antagonists block the M3 receptor which is attached to what G protein (Gq) which decreases intracellular calcium and are seen in inhaled Ipratropium.
• Theophylline's mechanism of action includes Inhibition of the phosphodiesterase enzyme and blockade of adenosine receptors and toxic plasma level is > 20 mcg/mL.
• Side effects of taking corticosteroids: Oral infection, Adrenal Suppression, Hypertension & Hyperglycemia.
• IV anesthetics that cause bronchodilation: ketamine, midazolam & propofol.
• The receptors and how they affect: Alpha-2= Bronchoconstriction, IP (prostacyclin) receptors= Bronchodilation, Endothelin (ET-A) receptors= Vasoconstriction.
• Mechanisms for cGMP mediated smooth muscle relaxation: Inhibits entry of Calcium, Activates Potassium channels hyperpolarizing membrane & Activates MLC-Phosphatase which breaks down Myosin Light Chains.
• Pulmonary hypertension is defined by a mean pulmonary artery pressure > 20 mmHG.
• Phosphodiesterase Inhibitor example used to treat pulmonary hypertension= Sildenafil.
• Epoprostenol increases hormone which targets IP receptors: cAMP.

ENDOCRINE PHARMACOLOGY

• Paracrine hormones affect adjacent sites, autocrine hormones affect the origin site, and endocrine hormones affect distant sites.

• The hypothalamus regulates homeostasis and sends releasing hormones to the pituitary gland.

• Hormones released by the anterior pituitary gland along with its releases includes; Growth Hormone which releases Growth Hormone-Releasing Hormone (GHRH), Luteinizing Hormone- Gonadotropin-Releasing Hormone (GnRH), Follicle Stimulating Hormone- Gonadotropin-Releasing Hormone/GnRH, Adrenocorticotropic Hormone- Corticotropin-Releasing Hormone/CRH and Thyroid-Stimulating Hormone- Thyrotropin-Releasing Hormone/TRH.

• Posterior pituitary hormones include Vasopressin and Oxytocin.

• Conditions that stimulate ACTH release: Stress, Sleep-wake transition, Hypoglycemia, Alpha Agonists & Beta Antagonists while things that inhibit it: Increased cortisol levels, opioids, etomidate"

• Conditions that stimulate vasopressin release: Increased plasma osmolality, hypotension, pain, stress, hyperthermia, nausea/vomiting, and opioids while things that inhibit: Hypothermia, ethanol, alpha agonists, and decreased plasma osmolarity.

• Octreotide is often used in the treatment of acute upper gastrointestinal bleed and works by inhibition of the release of Growth hormone.

• Treatment choice for central diabetes insipidus: is Vasopressin due to its MOA V2 Agonist while releasing Von Willebrand Factor.

• Mechanism of action of vasopressin for the treatment of refractory hypotension: V1 receptor activation stimulates Gq protein→activates phospholipase C→increases IP3→increases intracellular Calcium release.

• Hormone given to stimulate uterine smooth muscle contraction: oxytocin, mechanism of action: direct vascular smooth muscle relaxation.

• Conditions that stimulate the release of glucagon: Hypoglycemia, stress, trauma, beta agonists, acetylcholine, cortisol while conditions that inhibit its release include Hyperglycemia, free fatty acids, insulin, somatostatin, alpha agonists.

• Conditions that stimulate the release of insulin: Hyperglycemia, Beta Agonists, acetylcholine, glucagon while Insulin Inhibition: Hypoglycemia, Beta Antagonists, Alpha Agonists, somatostatin, volatile anesthetics, thiazide diuretics.

• Insulin effects:*

• Glucose: Increases uptake and use.

• Fat: Increases storage while inhibiting lipolysis.

• Protein: Increases uptake and change into amino acids.

• Anesthetic considerations/risks to diabetic autonomic neuropathy: Resting tachycardia, post-induction hypotension, delayed gastric emptying, nausea/vomiting & GERD.

• Patients who continue insulin pump therapy perioperatively should have Q1hr blood glucose monitored during anesthesia.

• Symptoms/signs of hypoglycemia: Diaphoresis, tachycardia, hypertension, altered mental status and seizures.

• To treat intraoperative hypoglycemia you can give Dextrose & Glucagon

• Administration of Insulin causes Potassium to shift intracellularly.

• Oral biguanide hypoglycemic drug that is 1st line therapy for type 2 diabetes: Metformin and does not always cause hypoglycemia.

• Sulfonylureas inhibit K+-ATP channels in beta cells causing calcium ions to enter the cell which leads to exocytosis of insulin.

• GLP-1 agonists increase beta cell secretion of insulin and decrease alpha cell production of glucagon.

• SGLT2 inhibitors work in the proximal tubule of the kidney