Adjunct Pharmacology 2024 PDF

Misc. Adjunct Pharmacology: ROSE PICCOLO 2023 Topics Psych drugs Antibiotics Disinfectants GI/motility drugs Herbals/supplements Anti & pro coagulants 12/08/2024 SAMPLE FOOTER TEXT 2 Psychopharmacologic Therapy Includes:  Antidepressants  An...

Misc. Adjunct Pharmacology: ROSE PICCOLO 2023 Topics Psych drugs Antibiotics Disinfectants GI/motility drugs Herbals/supplements Anti & pro coagulants 12/08/2024 SAMPLE FOOTER TEXT 2 Psychopharmacologic Therapy Includes:  Antidepressants  Anxiolytics (benzodiazepines)  Antipsychotics  Lithium  Anticonvulsants Generally accepted that anesthesia can be safely given to patients receiving drugs for mental illness Psychotropic meds are no longer routinely discontinued preoperatively Stay alert for potential drug interactions! –esp. in elderly pts!  Antidepressants ~10% of the popn. is treated for depressive illness at some time in life Most drugs classified as “antidepressants” have impacts on either serotonergic neurotransmission or on both serotonergic and noradrenergic neurotransmission. Antidepressants can treat a wide range of disorders—including different manifestations of depressive, anxiety, and chronic pain disorders—so, the term “antidepressant” has become a misnomer The “broad spectrum” of the antidepressant drugs does not imply a common pathophysiology, but rather reflects the diverse roles of monoamine neurotransmitters in the human nervous system We don’t know exactly how they work, but we know that they likely increase the amount of serotonin &/or NE in CNS synapses We know that blockade of NT reuptake and inhibition of monoamine oxidase happens soon after starting these drugs…but clinical improvement usually takes 2- 4 weeks Types of antidepressants: SSRIs  selective serotonin reuptake inhibitors (first line Rx) TCAs  tricyclic antidepressants MOAi  monoamine oxidase inhibitors 12/08/2024 SAMPLE FOOTER TEXT 4 SSRIs comprise several classes of medications which bind and inhibit the serotonin transporter protein (SERT), thus enhancing the amt of serotonin in the cleft and increasing serotonergic neurotransmission Drug of choice for treatment of mild to moderate depression, panic d/o, OCD etc. Considered to be very safe In general SSRIs, lack anticholinergic properties, and don’t cause postural hypotension / arrythmias, nor do they alter the seizure threshold Common side effects: insomnia, H/A, agitation, nausea, diarrhea and sexual dysfunction Most have little effect on NE reuptake Newer drugs (SNRIs) like venlafaxine (Effexor) block both NE & serotonin reuptake 12/08/2024 SAMPLE FOOTER TEXT 5  SSRIs/SNRIs 12/08/2024 SAMPLE FOOTER TEXT 6 Other Adverse Effects of SSRIs/SNRIs Suicidality In 2004, the FDA recommended a “black box” warning for newer antidepressant drugs—primarily SSRIs. It was a controversial warning bc it was based on evidence that suicidal thoughts and behaviors—although not completed suicides—occurred in children and adolescents at higher rates during treatment with SRIs compared to placebo. Bleeding risk Serotonin plays a role in platelet aggregation. However, the combination of SRI medications with anticoagulant therapies is common and not specifically contraindicated, Studies find no significant increase in major bleeding events for anticoagulated outpatients taking SSRIs. In surgical settings, the risks of increased bleeding are real and should be weighed in context against the risks of medication discontinuation, including risks of symptom relapse or SRI discontinuation syndrome Serotonin Syndrome attributed to toxic levels of synaptic and extracellular serotonin rare but serious complication of SRI use presents with the triad of neuromuscular excitability, autonomic nervous system excitability, and mental status changes neuromuscular excitability may include hyperreflexia, clonus, myoclonus, opsoclonus, or rigidity autonomic changes may include diarrhea, tachycardia, hypertension, fever, diaphoresis, flushing, and mydriasis mental status changes may range from insomnia, agitation, and anxiety through to confusion or coma In severe cases  life-threatening hyperpyrexia and rigidity may lead to rhabdomyolysis, multiorgan failure, and disseminated intravascular coagulation 12/08/2024 SAMPLE FOOTER TEXT 7  Serotonin Syndrome Differential Diagnosis & Treatment Watch out for SS in the PACU & ICU as serotonergic agonists—known or unknown—may have been administered during surgery typically results from the combination of different classes of serotonergic medications— and most dangerously, the combination of an SRI with a monoamine oxidase inhibitor (MAOI) But nonpsychiatric or nonserotonergic medications may trigger serotonin syndrome in conjunction with SRI or other Treatment for SS: serotonergic medication use. discontinuation of serotonergic medications Including linezolid; methylene blue; prompt initiation of supportive care: lithium; opioids ( e.g. tramadol, fentanyl); stimulants such as including benzodiazepines or other amphetamine, methamphetamine; neuromuscular sedatives, muscle relaxants including intravenous (IV) fluids cyclobenzaprine; and recreational drugs in life-threatening cases, cooling, paralysis, including ecstasy. and ventilation Drugs that cause rapid elevations in serum level of SRI medications via 12/08/2024 8 Tricyclic Antidepressants TCAs were replaced by SSRI’s as 1st line therapy in treatment for depression Highly effective, but narrow therapeutic index (potentially lethal in OD) & many unfavorable side effects TCAs possess anticholinergic, antiadrenergic & antihistamine properties May still be used for in-patient therapy & when SSRIs alone fail Currently used as adjunct therapy in the Rx of chronic pain syndromes in doses lower than those used to Rx depression Include Amitriptyline (Elavil), Doxepin (Sinequan), Imipramine (Tofranil), Nortriptyline (Aventyl) and Desipramine (Norpramine) Mechanism of Action:  Potentiate the actions of NE and/or serotonin in the CNS by inhibiting reuptake of these amines into postganglionic SNS nerve endings  INCREASES NEUROTRANSMITTERS AVAILABILITY  They also antagonize H1 & H2 (antihistamine) as well as as muscarinic acetylcholine receptors (anticholinergic)  More sedative (d/t antihistamine properties) than the SRIs 12/08/2024 SAMPLE FOOTER TEXT 9 Tricyclic Antidepressants Induction of Anesthesia May be associated w/ an increased rate of cardiac dysrhythmias Side Effects:  Anticholinergic Effects:  Prominent especially at high doses  Include dry mouth, blurred vision, tachycardia, urinary retention, delayed gastric emptying & ileus  Cardiovascular effects:  Orthostatic hypotension and modest increases in HR  Depression of AV cardiac conduction  Prolonged P-R interval, widened QRS complex, flattening/inversion T wave (responsive to atropine)  CNS effects:  Sedation  Lowers the seizure threshold (raises transmembrane potential). Caution in patients with seizure disorders  In combination with MAO inhibitors may result in CNS toxicity-hyperthermia, seizures, coma 12/08/2024 SAMPLE FOOTER TEXT 10 MAOs (enzymes) & MAOIs (drugs that block the enzyme) Monoamine oxidase-A (MAO-A) is an enzyme involved in the metabolism of the monoamines (eg 5-HT, NE, dopamine) MAO-A regulates both the free intraneuronal concentration and the releasable stores of 5-HT and NE MAO-A inhibitors bind to and inhibit MAOA, preventing monoamine breakdown This results in greater stores of monoamines available for release MAO-A inhibitors are used in the treatment of depression by preventing 12/08/2024 monoamine S A Mmetabolism PLE FOOTER TEXT 11 and delaying  MAO (2 types, A & B) The MAOs are divided into two subtypes (MAO-A and MAO-B) based on different substrate specificities Monoamines  MAO-A is present in the brain at > concentrations than MAO-B Most MAOIs *form an irreversible complex with BOTH types of MAO enzyme drug effects are prolonged bc synthesis of new enzyme is a Metabolites  slow As a result, the amount of neurotransmitter (e.g.: serotonin, NE, and dopamine) available for release from CNS neurons increases. 12/08/2024 *the monoamine concentration12 SAMPLE FOOTER TEXT MAOIs – monoamine oxidase inhibitors The MAOIs constitute a heterogeneous group of drugs, which block the enzyme that metabolizes biogenic amines, increasing the availability of these neurotransmitters in the CNS and peripheral autonomic nervous system Rx e.g. phenelzine, isocarboxazid, moclobemide, selegiline, tranylcypromine Many patients with MDD who do not respond to other antidepressants improve with MAOIs (more of a last resort Rx though) Historically, MAOIs have been one of the most potent psychopharmacologic interventions for depressive disorders, but they are used much less commonly now because of their side effects Orthostatic hypotension, insomnia, lethality in overdose, and lack of simplicity in dosing most patients treated with MAOIs must follow specific diet guidelines because of the potential for pharmacodynamic interactions with tyramine found in food that can result in systemic hypertension 12/08/2024 SAMPLE FOOTER TEXT 13 MAOI Side Effects cont’d Most common side effect = Orthostatic Hypotension (esp. in elderly) Likely d/t the build of a “false neurotransmitter” called octopamine in sympathetic nerve endings When octopamine is released (instead of NE etc.) it causes less vasoconstriction  leading to orthostatic hypotension Additionally…. Use of MAOIs also blocks the function of the MAO enzymes in the the GI tract, liver, kidneys and lungs Normally MAO in these places breaks down monoamines in our food (e.g. tyramine and beta-phenylethanolamine) and prevents these substances from causing a sympathomimetic effect (e.g precipitous hypertension) Pts on MAOi can’t metabolize tyramine and other monoamines  these compounds can enter the bloodstream and be absorbed by the SNS nerve endings Can cause a massive release of endogenous catecholamines and cause hyperadrenergic crisis (HTN, hyperpyrexia and CVA) This is why pts on MAOis are placed on strict dietary & pharmacologic restrictions (see table) 12/08/2024 14 MAOI Drug Interactions MAOIs can interact adversely with opioids, ephedrine, tricyclic antidepressants, and SSRIs Can lead to hypertensive crises or serotonin syndrome MAOIs are rarely used, yet they have significant interactions with sympathomimetics and opioids that we commonly use in anesthesia,  important for the anesthesia provider to identify them in the patient’s medication list. Opioids and Monoamine Oxidase Inhibitors Administration of meperidine (Demerol) to a patient treated with MAOIs may result in an excitatory (type I) response (agitation, headache, skeletal muscle rigidity) or a depressive (type II) response characterized by hypotension, depression of ventilation, and coma Enhanced serotonin activity in the brain (ie, serotonin syndrome) is presumed to be responsible for excitatory reactions evoked by meperidine. Other opioids that are synthetic phenylpiperidines (fentanyl, sufentanil, alfentanil) have been associated with adverse reactions in patients treated with MAOIs, although the incidence seems to be less than with meperidine the FDA has warned about the risk of serotonin syndrome for all opioid medications when administered in conjunction with serotonergic drugs Sympathomimetics and Monoamine Oxidase Inhibitors Evidence does NOT support avoiding all sympathomimetic drugs in patients treated with MAOIs Occasionally, patients experience an exaggerated BP response after the administration of an indirect-acting vasopressor such as ephedrine … let’s think about why this could be… 12/08/2024 SAMPLE FOOTER TEXT 15 Reminder— Ephedrine MOA: - Why might ephedrine adversely interact with MAOi Rxs? The hypertensive response is presumed to reflect an exaggerated release of norepinephrine from neuronal nerve endings. *If needed, the use of a direct-acting sympathomimetic (phenylephrine) is preferable to an indirect-acting drug *keep in mind that receptor hypersensitivity may enhance the systemic blood pressure response to these drugs as well. *Regardless of the drug selected, the recommendation is to decrease the dose to about one-third of normal, with additional titration of doses based on cardiovascular responses 12/08/2024 SAMPLE FOOTER TEXT 16 MAOI Drug Interactions MAOi Overdose Signs: excessive SNS activity (tachycardia, hyperthermia, mydriasis), seizures, and coma Tx: is supportive in addition to gastric lavage. Consider as a treatment for skeletal muscle rigidity and associated symptoms of hypermetabolism Managing Anesthesia for pts on MAOis Previously we recommended that pts discontinue MAOIs 2-3 weeks before elective surgery (based on the concern that life-threatening cardiovascular and CNS instability could occur during anesthesia and surgery. This was based on anecdotes and put pts at risk for increased psych disturbances Nowadays: general consensus is that anesthesia can be safely given to most patients being chronically treated with MAOIs. but we must consider certain drug interactions, and avoid certain drugs, especially meperidine Selection of Drugs Used During Anesthesia The anesthetic should minimize SNS stimulation & drug-induced hypotension. Regional anesthesia is acceptable, recognizing that ephedrine should be avoided in the treatment of resulting hypotension. 12/08/2024 SAMPLE FOOTER TEXT 17 Antipsychotic Drugs Phenothiazines and Thioxanthenes  Mechanism of action: blockade of dopamine receptors (especially dopamine2) in the basal ganglia & limbic system  Blockade of dopamine receptors is responsible for the extrapyramidal effects (which are d/t unopposed cholinergic activity)  Blockade of dopamine receptors in the CTZ is responsible for the antiemetic effects  Produce sedation, orthostatic hypotension, extrapyramidal and anticholinergic effects in varying degrees. *CTZ = chemoreceptor trigger zone Antipsychotic Drugs Phenothiazines & Thioxanthenes  Include:  Chlorpromazine (Thorazine)  Triflupromazine (Vesprin)  Fluphenazine (Prolixin)  Prochlorperazine (Compazine)  Promethazine (Phenergan)  Known to produce an array of side effects including sedation, anticholinergic effects, orthostatic hypotension & extrapyramidal effects (Table 43-8, p.869) Phenothiazines & Thioxanthenes Side Effects  Extrapyramidal effects:  Tardive Dyskinesia occurs in 20% pts treated with these drugs for >1yr  Manifestations= abnormal involuntary movements of the tongue, facial & neck muscles, upper & lower extremities, truncal muscles & muscles involved in breathing and swallowing  Acute Dystonic reactions:  Occur in 2% of pts within the first 72hrs  Acute skeletal muscle rigidity including muscles of the tongue, neck, face and back  Sudden onset respiratory distress d/t laryngeal dyskinesia (laryngospasm)  Responds to Benadryl 25-50mg IV. Also Rx symptomatically Phenothiazines & Thioxanthenes Side Effects:  CV effects:  Depression of vasomotor reflexes mediated in the hypothalamus  Peripheral alpha blockade, unresponsive to epi  Direct relaxant effects on vascular smooth muscle  Direct cardiac depression  Prolonged Q-T interval and potential for VT (torsades de pointes) Phenothiazines & Thioxanthenes Side Effects:  Neuroleptic Malignant Syndrome:  Occurs in 0.5-1% of pts, associated with dehydration and concurrent illness  Characterized by Hyperthermia, generalized hypertonicity, ANS instability, arrhythmias and decreased LOC  Skeletal muscle rigidity can cause myonecrosis  Mortality is 20-30% d/t multisystem organ failure  Cause unknown & treatment empirical; supportive measures & the administration of dantrolene, and dopamine agonists-bromocriptine or amantidine  NDMR will produce flaccid paralysis--*distinguishes it from MH*  Antiemetic Effects:  D/t interaction with dopamine receptors in the CTZ Phenothiazines & Patients with Pakinson’s Disease Parkinson’s is caused by a deficiency of dopamine in the basal ganglia  Dopamine acts as an inhibitory neurotransmitter & Ach as an excitatory neurotransmitter in the Extrapyramidal system.  Balance of dopamine vs Ach is required for proper functioning  Symptoms occur d/t excess excitatory neurotransmitter  manifested as progressive tremor, skeletal muscle rigidity, bradykinesia Phenothiazines can antagonize the effects of dopamine & should not be administered to patients with Parkinson’s disease Lithium Used in the treatment of bipolar disorder Exact mechanism of action unknown May stabilize neurons by depleting intracellular second messengers & dampening signal transduction Narrow therapeutic window; 1.0-1.2 mEq/L Side Effects: Most serious effects at the kidneys >20% of patients demonstrate polyuria (> 3L/day u/o) Impaired renal concentrating ability d/t inhibitory effects of lithium on intracellular cAMP in the renal tubules Renal function should be evaluated q6 months ECG changes including T-wave flattening or inversion, reversible within 2 weeks of discontinuation Sedation Lithium-Drug Interactions Drug Interaction Thiazide Increased plasma lithium concentrations as a result of diuretics decreased renal clearance NSAIDs Increased plasma lithium concentrations as a result of decreased renal clearance (exception aspirin) ACE inhibitors Increased plasma lithium concentrations Neuroleptic May exacerbate extrapyramidal symptoms or increase drugs the risk of neuroleptic malignant syndrome Beta blockers Decrease lithium-induced tremor NMBDs Prolonged duration of action Lithium Toxicity Diuretic therapy, sodium restriction & sodium wasting will increase reabsorption of lithium  increasing plasma Li concentrations  Lithium is a positive ion replaces sodium Signs and symptoms of Li toxicity closely correlated with the plasma lithium concentration Cardiac changes include widening QRS complex, ventricular dysrhythmias, heart block, hypotension at plasma concentrations > 2.0 mEq/L  Cannabinoids Cannabis is an alkaloid mixture of more than 400 compounds that come from the cannabis sativa plant. The most abundant cannabinoids are D9THC, cannabidiol, and cannabinol. The D9THC is the main psychotropically active cannabinoid D9THC is increasingly used for the long-term treatment of N/V, cachexia, and management of chronic pain There are 2 principal endogenous cannabis receptors (CB1 and CB2 The CB1 receptors are present in the CNS (especially spinal cord) CB2 receptors are located peripherally and linked with cells in the immune system The role of the endogenous cannabinoid system is not fully understood, but evidence suggests it is involved with analgesia, cognition, appetite, vomiting, bronchodilation, inflammation, and immune control Euphoria and feelings of relaxation occur at plasma cannabinoid concentrations of about 3 ng/mL Acute intoxication  perceptual alterations, distortion of time, intensification of normal sensory experiences, decreased reaction A study of patients having major orthopedic surgery found that those times, poor motor skills, increased appetite, impairment of skilled on preoperative cannabinoids had higher pain scores at rest and with activities, tachycardia, and hypotension. movement in the early postoperative period. There was also more sleep interruption in patients who were taking cannabinoids Concerns: long-term toxicity, development of physical dependence, preoperatively. cannabis smoke is carcinogenic & chronic inhalation is linked with As with any retrospective study, causality cannot be inferred. increased risk of COPD and carcinoma of the lung and larynx 12/08/2024 SAMPLE FOOTER TEXT 27 Antimicrobials Antibiotic Prophylaxis: Surgical site infections (SSIs) are a significant burden to the patient and the health care system. SSIs are the most common perioperative infection and the most frequent cause of hospital readmission after surgery, causing ~20% of unplanned readmissions Antibiotic(s) given prior to surgical incision have proven to help decrease surgery-related infections 1990s-2000s: The Surgical Care Improvement Project (SCIP) was designed to combat a perceived national crisis of preventable surgical site infections which were associated with doubled risk of mortality, 60% higher likelihood of spending time in an intensive care unit, and fivefold risk of readmission In the OR, we give antibiotics as “per surgeon request” We review pt allergies & adverse rxns / previous & current abx use The antibiotic chosen depends on pt factors, surgical factors and availability of drugs Nonetheless, there are things beyond abx that contribute to mitigation of SSIs 12/08/2024 SAMPLE FOOTER TEXT 29 Risk Factors for Surgical Site Infection (SSI) P A T I E N T- R E L A T E D V A R I A B L E S I N S T I T U T I O N A L VA R I A B L E S extremes of age (younger than 5 and older than 65 surgical team’s experience years), Surgical team’s technique (e.g. open vs higher American Society of Anesthesiologists physical status score, laparoscopic), poor nutritional status, surgery specific risks, such as the creation of obesity, an ostomy in bowel surgery diabetes mellitus and perioperative glycemic control, duration of procedure, peripheral vascular disease, quantity of blood loss, tobacco use, coexistent infections, hospital environment including sterilization altered immune response /corticosteroid therapy, preoperative skin preparation (surgical scrub and hair of instruments, removal), maintenance of perioperative normothermia length of preoperative hospitalization. 12/08/2024 30  Modifiable Risk Factors for SSI: Perioperative glucose control Perioperative glucose control has been studied in a variety of surgeries. In the cardiothoracic surgery population, it is associated with about a 50% decrease in deep sternal infection Smoking cessation Perioperative education on smoking cessation by the team is important. Even short-lived smoking cessation can reduce infection risk. A meta-analysis of four studies that have assessed the effect of 4 to 8 weeks of preoperative smoking cessation demonstrates a risk reduction of approximately Although electronic cigarettes do not contain tobacco, they do contain nicotine and other chemicals that have thus far shown to decrease wound healing and cutaneous blood flow Maintenance of perioperative normothermia. hypothermia will result in peripheral vasoconstriction, decreased wound oxygen tension, and recruitment of leukocytes, favoring infection and impaired healing In a meta-analysis of trials, warming was associated with a 64% decrease in surgical site infections. Immunosuppression via long-term use of corticosteroid use/ chemotherapy is considered a risk factor for surgical site infection 20 In a study of surgical site infection following lumbar fusion surgery, chronic oral steroid use in patients older than 65 years of age was found to significantly increase the risk of surgical site infections at 90 days and 1 year. Similarly, preoperative chemotherapy and corticosteroid use were independent predictors of cranial surgical site infections even when the data was controlled for leukopenia However, There is clear evidence that a single dose of corticosteroid given to prevent nausea and vomiting and reduce pain does not promote infection. Dexamethasone 4 mg for n/v prophylaxis is safe. 12/08/2024 31 Surgical Wound Classification 12/08/2024 SAMPLE FOOTER TEXT 32 Antimicrobials (Abx) Choice of an antimicrobial is determined by both the properties of the drug and the nature of the infecting organism. Remember, normal flora help prevent colonization by pathogens because they compete for nutrients and produce their own antimicrobial substances. Over treatment of infections where little or no benefit is gained from antimicrobial Rx (URIs) development of bacterial resistance. Narrow spectrum antibiotics should be considered before broad spectrum antibiotics to preserve the normal flora of the patient. SCIP Measures track: Antibiotics administered with 1 hr of surgery appropriate antibiotic given Abx chosen based on the organism that is most likely to cause an infection …. e.g. S. aureus or epidermidis in clean procedures, whereas in clean-contaminated procedures the most common organisms are gram(-) rods & enterococcus) Antibiotic prophylaxis is dependent upon the operative procedure & must coincide with the likely period of inoculation (before incision). First-generation cephalosporins are drug of choice for most procedures because of wide therapeutic index & low cost Typically, abx are not continued beyond the first postoperative day Classification of ABX Restrict bacteria growth and Kill bacteria cells reproduction 12/08/2024 SAMPLE FOOTER TEXT 34 Developme nt of Abx through the years… 12/08/2024 35 MOA: 12/08/2024 SAMPLE FOOTER TEXT 36 MOA: Table 14.3 from Nagelhout 12/08/2024 SAMPLE FOOTER TEXT 37 Common Antimicrobials Used for Prophylaxis by Procedure Type of Recommended Alternative Procedure Agents Agents in Patients with B-Lactam Allergy Cardiac Cefazolin, Clindamycin, Cefuroxime Vancomycin Thoracic Cefazolin, Clindamycin, Ampicillin- Vancomycin sulbactam (Unasyn) Gastrointestinal Cefazolin, Clindamycin or & cefotetan, cefazolin vancomycin + GYN + aminoglycoside or metronidazole aztreonam or fluroquinolone Head & Neck Cefazolin Clindamycin + metronidazole Neurosurgery/ Cefazolin Clindamycin, Vascular vancomycin Orthopedic Cefazolin Clindamycin, vancomycin Urologic Cefazolin, Clindamycin, aminoglycoside vancomycin +/- aminoglycoside or aztreonam Redosing Abx During Long Cases: important to maintain therapeutic serum and tissue levels throughout the surgery Procedures lasting > 2 half-lives of the antimicrobial agent require additional intra-op doses of the antimicrobial agent Institution-specific guidelines (see YNHH below) Antimicrobials & Anesthetic Implications Most Common Abx Risks: Aminoglycosides Aminoglycosides:  Include Streptomycin, Kanamycin, Gentamycin, Tobramycin, Amikacin and Neomycin.  Poorly lipid soluble antimicrobials that are bactericidal for aerobic gram (-) bacteria. Side Effects:  Ototoxicity  Nephrotoxicity  Skeletal muscle weakness  --> Potentiation of neuromuscular blockade Skeletal Muscle Weakness  Inhibit prejunctional release of acetylcholine.  Also decrease postsynaptic sensitivity to Ach  IV administration of calcium overcomes the effect of aminoglycosides at the neuromuscular junction.  Patients with MG are uniquely susceptible to skeletal muscle weakness if treated with an aminoglycoside.  Reappearance of neuromuscular blockade is possible if aminoglycosides given in the early postop period. Macrolids Include Erythromycin, clarithromycin & Azithromycin  Bacterial spectrum of activity includes most gram-positive bacteria  Strep pneuminiae, S. aureus, H. influenzae, & Chlamydia  Erythromycin prolongs cardiac repolarization & is associated with Torsades de pointes  Azithromycin has an extraordinarily long E t1/2 (68hrs) allowing once a day treatment for 5 days, with therapeutic levels 4-7 days after last dose Clindamycin Resembles Erythromycin but more active against many anaerobes Used to Rx infections of the GI & GU tracts  Severe complication pseudomembranous colitis  Its use should be reserved for infections that cannot be treated with less toxic drugs. Side Effects:  Pre- & postjunctional effects at the neuromuscular junction.  Effects CANT be antagonized with Ca++ or anticholinesterase drugs.  Large doses can produce profound and long-lasting neuromuscular blockade. Vancomycin Impairs cell wall synthesis of gram (+) bacteria. Used IV for treatment of severe staph and strep infections in pts allergic to Penicillin and/or cephalosporins. Drug of choice in the Rx of MRSA. May be used for prophylaxis in pts undergoing joint or valve replacement.  Insertion of a foreign body increases risk of SSI Dose is 10-15 mg/kg over 60 minutes to minimize drug-induced histamine release & hypotension. Usually started in preop –must be given w/in 2 hours of incision Vancomycin Side Effects: Rapid infusion ( 120 Kg = 3 g IVP Pediatrics = 25 mg/kg (max of 3 g) *these guidelines may be different at other institutions* 12/08/2024 SAMPLE FOOTER TEXT 49 Antibiotic Allergy Antibiotics account for approximately 15% of anesthesia-related anaphylactic reactions penicillins and cephalosporins are responsible for 70% of these Penicillin allergy is the most reported drug allergy in the United States. (prevalence is ~10% in the general population) However, >90% of these patients are found not allergic to penicillin after skin testing. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other β-lactams. Cross-sensitivity occurs when the R1 side chains of the penicillins and cephalosporins are similar. This is not the case with cefazolin, which is why many clinicians consider it safe in patients with a penicillin allergy. 12/08/2024 SAMPLE FOOTER TEXT 50  Antiseptic and Disinfectant Prophylaxis Decontamination of the skin with antiseptic preparations reduces the burden of skin flora and reduces the incidence of surgical site infection. Practice guidelines from the NIH recommend: bathing or showering with soap, use of an iodine-impregnated drape, and immediate preparation with an antiseptic solution The main types of topical antiseptics are alcohols, chlorhexidine, and iodine-containing preparations, used alone or in combination 12/08/2024 51 Alcohols On the skin, 70% ethyl alcohol kills nearly 90% of the cutaneous bacteria within 2 minutes, provided the area is kept moist. Isopropyl alcohol has a slightly greater bactericidal activity than ethyl alcohol Alcohols reduce bacterial contamination and are not generally fungicidal or virucidal. Alcohol-based preparations are flammable until all the liquid has evaporated 12/08/2024 SAMPLE FOOTER TEXT 52 Chlorhexidine Chlorhexidine is a colorless solution that disrupts bacterial cell membranes and is effective against both gram-positive and gram-negative bacteria. It persists on the skin to provide continued antibacterial protection. As an antiseptic, chlorhexidine is rapid acting, has considerable residual adherence to the skin, has a low potential for producing contact sensitivity, and is poorly absorbed even after many daily hand washings. Chlorhexidine solutions in an alcohol base are not appropriate for instillation into the eye (corneal injury) or middle ear (deafness). 12/08/2024 SAMPLE FOOTER TEXT 53  Iodine-Preparations Iodine is a rapid-acting antiseptic that kills bacteria, viruses, and spores. The most important use of iodine is disinfection of the skin. In rare instances, an individual may be allergic to iodine and react to topical application. usually manifests as fever and generalized skin eruption. A standard surgical scrub with 10% povidone-iodine solutions (Betadine) will decrease the usual cutaneous bacterial population by greater than 90%, with a return to normal in about 6 to 8 hours. An iodophor in isopropyl alcohol (DuraPrep) is more effective than povidone-iodine in decreasing the number of positive skin cultures immediately after disinfection as well as in bacterial regrowth and colonization of epidural catheters Chemical burns to the cornea may follow exposure (accidental splashes) to a variety of disinfectant solutions (chlorhexidine, hexachlorophene, iodine, alcohol, detergents containing iodine-based solutions). 12/08/2024 SAMPLE FOOTER TEXT 54  Alternative Medications/Supplements A N E S T H E T I C I M P L I C AT I O N S Herbal Preparations Many individuals (22-32%) are currently using herbal preparations to improve their health and treat illness Associated with documented adverse outcomes in the perioperative period Plants are the principal source of most currently prescribed drugs and alternative remedies Have both positive and negative effects  Classified as dietary supplements & NOT subject to regulation  FDA must prove unsafe BEFORE can be removed from the market Patients should be evaluated for the use of herbal preparations including possible drug interactions and undesirable side effects Chromium Indications:  Glycemic control NIDDM & gestational DM  Increases insulin sensitivity  Rx hyperlipidemia  Obesity, body building Improves glucose tolerance, increases insulin sensitivity and decreases serum triglycerides Potential exists for nephrotoxicity, hypoglycemia Creatine Indications:  Used to lower cholesterol  Increase muscle mass and enhance physical performance Creatine is removed from the body by renal excretion as creatinine; may cause problems in patients with renal dysfunction- consider avoiding NSAIDs Can cause hypovolemia. Pt’s may be HD unstable intraop Echinacea Indications:  Immune stimulant: activation cell-mediated immunity  Anti-inflammatory  Rx of bacterial, fungal and viral UTI’s & URI’s  Promotes tissue granulation and healing when used topically May block the production of phagocytes if used chronically- immunosuppressant  Use should be limited to 2 weeks  Contraindicated for use in pt’s with HIV, Tb, MS or other autoimmune disorders  Associated with decreased effectiveness Ephedra (Ma-Huang) Ephedra is a plant that contains a variety of ephedrine alkaloids including ephedrine & pseudoephedrine (adrenergic Agonists) Indications:  Rx asthma, bronchitis, allergic rhinitis  Promote weight loss as a dietary supplement Naturally occurring, indirect acting sympathomimetic which stimulates release of NE Banned by the FDA in 2004 but still available via the internet Should be discontinued 24 hours prior to surgery Ephedra Adverse Effects: Contraindications:  Lethal cardiac  Narrow-angle glaucoma arrhythmias, HTN,  Pt’s taking MAOIs, tricyclic tachycardia, Angina, MI antidepressants  Anxiety, insomnia, H/A,  Pts with CAD, HTN stroke, seizures,  Ephedra can induce cardiac subarachnoid hemorrhage  Acute hepatitis arrhythmias in the presence of volatile anesthetics,  Preterm labor especially halothane.  With chronic use, receptor  Ephedra + oxytocin = down-regulation severe hypertension  Hyperglycemia Garlic (Allium Sativum) Extensively researched medical plant Indications:  Rx hypercholesterolemia and hyperlipidemia  Rx HTN  Antiplatelet - Irreversible platelet inhibition  Antidiabetic Should not be used preoperatively because of the increased risk of bleeding Discontinued 7 days prior to surgery Major drug interactions:  Anticoagulants-increased risk bleeding. Garlic inhibits platelet aggregation  ASA, NSAID’s, antiplatelet drugs (plavix)-increased risk bleeding  Ginger, ginko biloba- also inhibit platelet aggregation  Antidiabetic agents-increased risk hypoglycemia Ginger Indications:  Motion sickness  Morning sickness  Nausea and vomiting  Arthritis Interactions:  Inhibits platelet aggregation by inhibiting thromboxane synthetase and stimulating prostacyclin  No data on when to d/c prior to surgery  May potentiate anticoagulants and antiplatelet drugs; increased risk of bleeding perioperatively Ginko Biloba Indications:  Used to treat cognitive disorders and decrease disturbances of cerebral functioning and peripheral vascular insufficiency  Rx of depression, H/A, tinnitus, vertigo, dementia, Alzheimers disease  Intermittent Claudication Mechanism of Action:  Alters vasoregulation, acts as an antioxidant, modulates neurotransmitter & receptor activity and inhibits platelet-activating-factor (PAF)  Increased uptake and utilization oxygen and glucose  Vasodilates blood vessels (capacitance and resistance vessels  Inhibits thromboxane and therefore, inhibits platelet aggregation  d/c 36 hours prior to surgery Ginkgo Biloba Interactions/Contraindications:  Increased risk of bleeding:  should not be taken with anticoagulants or antiplatelet drugs such as ASA, NSAIDs, Plavix  Ginko should be d/c’d 2-3 weeks before surgery  Inhibits MAO & can potentiate the action of MAO inhibitors & SSRIs. Should not be taken concurrently  May potentiate CNS depressants & the hypotensive effects general anesthetics  May potentiate effects of epi or NE d/t MAO inhibition Ginseng Reported to protect the body against stress and is able to restore homeostasis Indications:  Combats mental and physical exhaustion  Combats stress  Enhances immune function  Improved capacity for work and concentration  May lower cholesterol Acts as a stimulant, reversibly inhibits platelet function & lowers blood glucose levels d/c 7 days prior to surgery Ginseng Interactions/Contraindications:  Increased risk of bleeding; d/c 2 weeks prior to surgery  Can inhibit effect of warfarin  May cause hypoglycemia, potentiates oral hypoglycemics  At high doses HTN, tachycardia. Potentiates the action of all catecholamines  Possible decreased analgesic effects opioids Green Tea Contains polyphenoic compounds including catechins, which inhibit platelet aggregation d/t inhibition of thromboxane A2 formation Effects for the life of the platelet Should be d/c’d 7 days prior to surgery Glucosamine Sulfate Used in the Rx of osteoarthritis to alleviate pain, improve mobility and aid in cartilage repair Inhibits platelet adhesion; increased risk of bleeding during the perioperative period. Similar profile to NSAIDs Goldenseal Indications: Interactions/Contraindications:  Treatment gastritis, PUD, colitis Contraindicated for use during pregnancy; uterine stimulant  Diuretic Contraindicated in patients with CV  Antiinflammatory disease; acts as a vasoconstrictor  Hemostatic agent causing HTN, bradycardia, angina  Used externally to aid in wound Increased response to insulin- healing hypoglycemia CNS stimulation, seizures, respiratory failure Can oppose heparin/coumadin anticoagulation Kava Anxiolytic & Sedative  Kavalactones active component  Produce dose-dependent effects on the CNS  Possesses antiepileptic, neuroprotective & local anesthetic properties  Believed to potentiate GABA  Interacts with other sedative/hypnotics & should be d/c’d 24 hours prior to surgery and anesthesia Licorice (Glycyrrhiza) Indications: Pseudoaldosteronism  can  Rx PUD cause HD unstable pt  Consider invasive monitoring  Immune stimulant (a-line)  Expectorant; Rx cough/bronchitis  d/t Water retention,  Stimulates the adrenal cortex; Rx hypernatremia, hypokalemia, Addisons disease HTN Considered to be unsafe HTN Hypokalemia induced muscle because of multiple drug weakness interactions and side effects Paresthesias  One of the “top ten” herbal Arrhythmias meds in the US Vasospasm H/A St. John’s Wort Used in the Rx Depression; may be as effective as tricyclic antidepressants Mechanism of Action:  Nonspecific reuptake inhibitor of serotonin, NE and dopamine  Mild inhibition of MAO  Should be d/c’d 5 days prior to surgery St. John’s Wort Interactions/ Interactions/Contraindications: Contraindications:  **Inducer of the Cytochrome P-450  May produce a serotonin-like enzymes- increased metabolism & syndrome, especially in decreased effect of drugs dependent on combination with SSRI’s and MAO P450 system* inhibitors  Including: warfarin,  HTN, tachycardia, benzodiazepines,β blockers, agitation, restlessness Calcium channel blockers,  Avoid the use of indirect acting steroids sympathomimetics. Response to  Avoid foods high in tyramine direct acting unpredictable Saw Palmetto Used to treat symptoms of BPH Possesses anti-inflammatory effects and its use has been associated with excessive perioperative bleeding  Inhibits cyclooxygenase & causes platelet dysfunction Valerian Indications:  Insomnia  Anxiety  Muscle spasm  Seizures  Benzodiazepine withdrawal CNS depressant Chronic use associated with cardiac failure & delirium during emergence from GA Interactions:  May act synergistically with other CNS depressants- prolonged emergence from GA  Potentiates the effects of opioids  May negate the therapeutic effects of MAO inhibitors, phenytoin and warfarin; do not take concurrently Chronic high dose use associated with cardiac failure and tachycardia Withdrawal reactions with chronic, high dose use Supplement Summary: 12/08/2024 SAMPLE FOOTER TEXT 77 Supplement Summary: 12/08/2024 SAMPLE FOOTER TEXT 78 Supplement Summary: 12/08/2024 SAMPLE FOOTER TEXT 79  Common GI Drugs 12/08/2024 SAMPLE FOOTER TEXT 80 Drugs that Modify Gastric Barrier Pressure 12/08/2024 SAMPLE FOOTER TEXT 81 Histamine Receptor Antagonists Three subtypes of histamine receptors; H1, H2, H3  Nonspecific antihistamines include Dimenhydrinate (Dramamine)  Antiemetic effects related to central anticholinergic effects  May also act directly on the CTZ mediated through H 1 antagonism  Dose: 20 mg IV  H1- Receptor Antagonists  Classified as first and second-generation  First generation produce sedation & have antagonistic properties at muscarinic, cholinergic, serotonin & alpha-adrenergic receptors  Second-generation selective for H1, limiting CNS toxicity  Used to Rx allergy symptoms Histamine Receptor Antagonists H2-Receptor Antagonists  Include cimetidine, ranitidine, famotidine and nizatidine  Produce selective, reversible inhibition of H2-receptor mediated secretion of H+ (acid) by parietal cells in the stomach  Used in the treatment of peptic ulcer disease and to decrease gastric volume, but have no influence on the pH of acid already present in the stomach at time of administration, so NOT effective against aspiration prophylaxis  NOT effective in the treatment of PONV  Multiple drug interactions, especially in the presence of cimetidine  Usually impaired hepatic metabolism of the new drug Side Effects of H2-Receptor Antagonists Interaction with cerebral H2 receptors-H/A, somnolence, confusion Interaction with cardiac H2 receptors-bradycardia, hypotension, heart block  H2 receptor activation mediates inotropic & chronotropic effects, coronary vasodilitaion Increased hepatic transaminase levels Thrombocytopenia Agranulocytosis Interference with drug metabolism by cytochrome p-450 Proton Pump Inhibitors Most effective drugs available for controlling gastric acidity & volume Inhibit the hydrogen-potassium-ATPase pump responsible for moving H + ions across parietal cell membranes Omeprazole prototype  Several days for maximal inhibition of proton pump  As a premedication effectively increases gastric pH and decreases gastric volume  Requires 2-6 hours for effect, therefore should be administered > 3 hrs before induction  Side effects include H/A, agitation and confusion GLP-1 Receptor Agonists (Glucagon-like- peptide-1 Receptor Agonists) 12/08/2024 SAMPLE FOOTER TEXT 86  GLP-1  glucagon-like peptide-1 Is a naturally secreted polypeptide Works on the GLP-1 Receptors, found in the pancreas, brain, heart, kidneys, intestines and stomach In the GI tract, GLP-1s work to slow digestion, causing DELAYED gastric emptying this a safety concern for us in the anesthesia world, b/c we prefer our pts to be NPO in order to decrease the likelihood of pulmonary aspiration of gastric contents while under anesthesia So, if pts on GLP-1R agonists have delayed gastric emptying, we need to be aware that they may have residual gastric contents on the day of surgery (if they follow traditional NPO guidelines) 12/08/2024 SAMPLE FOOTER TEXT 87 GLP-1RA  glucagon-like peptide-1 receptor agonist drugs There have been cases of pulmonary aspiration of gastric contents in pts who are on GLP- 1RAs undergoing procedural sedation and/or GA GLP-1RAs also have side effects including: n/v, abdominal pain, constipation (not great for us!) So, we need special practice guidelines for pts on these drugs…but unfortunately little evidence exists to guide the best approach to managing pts on these drugs perioperatively We are about to discuss the most current guidelines, but these will likely change as we garner more information The following guidelines are not truly “evidence-based guidelines” bc we don’t have enough data yet 12/08/2024 SAMPLE FOOTER TEXT 88 GLP-1RA  glucagon-like peptide-1 receptor agonist drugs Multi-society guidance for safely managing patients on GLP-1RA therapy regardless of indication (type 2 diabetes, overweight and obesity, and heart failure) during the periprocedural period. Pts with elevated risk of delayed gastric emptying and aspiration: GLP-1RA therapy may be continued preoperatively in patients without elevated risk of delayed gastric emptying and aspiration 1. Escalation phase: The escalation phase, vs. the maintenance phase, (left side of slide) is associated with a higher risk of delayed gastric emptying with GLP- 1RA usage When an elevated risk of delayed gastric emptying and aspiration exist, withholding of GLP- 1RAs should be balanced with the 2. Higher dose: The higher the dose of GLP-1RA, the more likely the risk surgical and medical risk of inducing the potential for a hazardous, of gastrointestinal side effects metabolic disease state, like hyperglycemia. 3. Weekly dosing: Gastrointestinal side effects are more common with note: bridging therapy off a GLP-1RA may be resource- intensive, cost weekly compared to daily formulation compounds or insurance prohibitive, and risk other adverse side effects like hypoglycemia. 4. Presence of gastrointestinal symptoms: Symptoms suggestive of delayed gastric emptying and intestinal transit times may include If the decision to hold GLP-1RAs is indicated given an nausea, vomiting, abdominal pain, dyspepsia, and constipation unacceptable safety profile in the preoperative period, the duration to hold therapy is unknown. 5. Medical conditions beyond GLP-1RA usage which may also delay gastric emptying: such as but not limited to bowel dys- It is suggested to hold the day of surgery for daily motility, gastroparesis, and Parkinson’s disease. formulations, and a week prior to surgery for weekly formulations The assessment for these risk factors should occur with enough advance All patients should still be assessed on the day of procedure time prior to surgery to allow adjustments in preoperative care if indicated. for symptoms suggestive of delayed gastric emptying. (e.g. diet modification and evaluation of the feasibility of medication bridging if GLP-1RA discontinuation is indicated) ( 12/08/2024 SAMPLE FOOTER TEXT 89 GLP-1RA  glucagon-like peptide-1 receptor agonist drugs Multi-society guidance for safely managing patients on GLP-1RA therapy regardless of indication (type 2 diabetes, overweight and obesity, and heart failure) during the periprocedural period. The safe use of GLP-1RAs in the perioperative period should include efforts to minimize the aspiration risk of delayed gastric emptying. 3. When clinical concern for retained gastric contents 1.Preoperative diet modification exists or is confirmed on the day of the procedure, 1. preoperative liquid diet for at least 24 providers should engage patients in a shared decision-making model and consider the benefits and hours, can be utilized in patients when risks of rapid sequence induction of general there is concern for delayed gastric anesthesia for tracheal intubation to minimize emptying based on clinical symptom aspiration risk vs. procedure cancellation review Talk to the pt, let them know of the added risk, let them know it may be safer to intubate or to postpone 2. When clinical concern for retained the case gastric contents exists on the day of the procedure, point-of-care gastric ultrasound could be used to assess 12/08/2024 SAMPLE FOOTER TEXT 90 aspiration risk. Anticoagulants & Procoagulants A N E S T H E T I C I M P L I C AT I O N S 12/08/2024 SAMPLE FOOTER TEXT 92 Hemostasis – forming a clot to prevent blood loss 12/08/2024 SAMPLE FOOTER TEXT 93 12/08/2024 SAMPLE FOOTER TEXT 94 Very Helpful Videos! 1. https://www.youtube.com/watch?v=W7n6l2fyggU&t=76s 2. https://www.youtube.com/watch?v=fanjoG9nslc 3. https://www.youtube.com/watch?v=eLXr4yklwDI 4. https://www.youtube.com/watch?v=f4SJokgbp4Q 5. Watch these 4 videos in order (~45 mins) and pause to absorb info and take notes! 6. These videos are presented by a cardiac pharmacist –she explains the clotting cascade and how platelets are involved in clotting. She also does a great job of showing how common drugs impact the cascade (mostly in the last video) 12/08/2024 SAMPLE FOOTER TEXT 95  Classic Model Hemostasis Following vessel injury, vWF binds to damaged blood vessels, stimulating platelet adherence. Thrombin further activates platelets & amplifies clot formation via activation intrinsic pathway Cell-Based Model of Hemostasis 1st Initiation- Tissue factor is expressed. TF and F7a activate F10, which helps generate a small amount of thrombin (FIIa) 2nd Amplification- platelets and cofactors work to generate a lot of thrombin (FIIa) 3rd Propagation- the large burst of FIIa (thrombin) needed to clot the vessel is generated now. Much of this thrombin is produced on the surface of platelets. The thrombin created is enough to activate fibrin. Summary of Prohemostatic Agents: 12/08/2024 SAMPLE FOOTER TEXT 98 Antifibrinolytic Agents: Lysine Analogs Aminocaproic acid (EACA) & Tranexamic acid (TXA)  Competitively inhibit activation of plasminogen to plasmin,  TXA inhibits plasmin directly at high doses  Recall, plasmin is what degrades fibrin (fibrin  FDPs in the presence of plasmin)  TXA has been shown to directly decrease transfusion requirements during surgery, trauma, massive transfusion  Antifibrinolytic agents are “not prothrombotic” per se, rather they are clot stabilizers and prevent the compensatory responses of inflammatory injury and clot lysis.  Potential complication  TXA-seizures  Usual dose: 1 g over 10 minutes, in trauma / open-heart surgery may be followed by an infusion of 1 g over 10 hours  Protamine The only drug used to reverse the anticoagulant effects of unfractionated heparin Protamin is a basic protein that inactivates the acidic heparin molecule via an acid- base interaction (chemical neutralization) Note: Giving too much protamine can cause coagulopathy! b/c it inhibits platelets & serine proteases  Dosing should be based upon the amount of circulating heparin left at the time of reversal  Dose: 1mg protamine per 100 U heparin circulating  *heparin E1/2 is ~1 hour  You gave 6,000 U of heparin one hour ago….how much protamine should you give?  ~3,000 U of heparin remain bc 1 half-life has elapsed.  3,000 / 100 = give 30 mg protamine  Side effects  Histamine release & hypotension, anaphylaxis, acute pulmonary vasoconstriction & RV failure  Systemic vasodilation and pulmonary vasoconstriction!  Patients at increased risk are those treated with NPH insulin and pts with fish allergy (it’s made from salmon sperm) Protamine Side Effects Summary Desmopressin (DDAVP) Stimulates the release of vWF from endothelial cells  vWF mediates platelet adherence (sticky-ness) to vascular subendothelium  this decreases bleeding time in patients with hemophilia A and von Willebrand’s disease  Dose: 0.3 mg/kg over 15-30 minutes to avoid hypotension DDAVP is a synthetic analogue of the antidiuretic hormone arginine vasopressin. Desmopressin: decreases urine volume and increased urine osmolality; increases plasma levels of von Willebrand factor, factor VIII, and t-PA contributing to a shortened activated partial thromboplastin time (aPTT) and bleeding time Recombinant Coagulation Factors Factor VIIa (7a) produces a prohemostatic effect by multiple mechanisms: Forms complexes with TF expressed at the site of injury Leads to activation of factor 10  10a …which leads to thrombin…then fibrin.. & ultimately increased clotting  Traditionally used for the RX of hemophilia but has an off-label use in cardiac surgery patients when severe bleeding is present Factor XIII (13) -important in the final step in clot formation  Stabilization of the fibrin complex  Has been used following CPB when demonstrated deficiencies exist Prothrombin Complex Concentrates (PCCs) The PCCs are concentrates of coagulation factors that include factors II, VII, IX, and X in variable concentrations. Two agents (eg, Kcentra and Octaplex are used worldwide for vitamin K antagonist–induced (ie, warfarin) reversal. Patients on Vitamin K antagonists (e.g. warfarin) may need to reverse their anti-coagulated state during periods of bleeding/surgery Warfin inhibits vitamin k Vitamin k is need to activate factors 2, 7, 9 and 10 (II, VII, IX, X) 12/08/2024 SAMPLE FOOTER TEXT 104  Anticoagulants & Platelet Inhibitors 12/08/2024 SAMPLE FOOTER TEXT 105 Unfractionated Heparin Mixture of sulfated glycosaminoglycans with molecular weights ranging from 3,000-30,000 daltons  Extract of porcine or bovine intestine Produce anticoagulant effects by binding to antithrombin (AT), enhancing the rate of thrombin-AT complex formation by 1,000-10,000 times. We must maintain a balance of clot formation and clot breakdown Think of AT as a protein that sops up major coagulation factors  thereby preventing an excess of clotting Pts with a deficiency of AT are at increased risk of clotting  strokes! So,the heparin-AT complex neutralizes thrombin as well as factors 9a, 10a, 11a and 12a. Hepain also inhibits platelet function Possesses an anti-Xa to anti-IIa activity of 1:1 Heparin dependent upon adequate concentrations of AT for its anticoagulant effects Can give FFP or AT concentrate Unfractionated Heparin When administered IV, onset of action is immediate & elimination half-time ~ 1 hr. After subq administration onset of action 1-2 hours Laboratory Evaluation of Coagulation  Activated Partial Thromboplastin Time (aPTT)  Therapy monitored to maintain range 1.5-2.5X normal values (30-35 sec)  Activated Clotting Time (ACT)  Used when higher concentrations of heparin are used such as during CPB  Normal ACT values: 100-150 seconds  Target for anticoagulation during bypass is >350 sec  We don’t want blood to clot when on bypass!  Contraindications:  Neurosurgery  HIT –heparin induced thrombocytopenia  Regional anesthesia 12/08/2024 SAMPLE FOOTER TEXT 107 Low-Molecular-Weight-Heparins Enoxaparin (Lovenox) & dalteparin Derived from UFH by chemical depolymerization to yield fragments with a mean molecular weight of 4,000-5,000 daltons Depolymerization changes the anticoagulant profile, pharmacokinetics and effect on platelets Possesses an anti-Xa to anti-IIa activity of between 4:1 & 2:1 Also possesses better bioavailability at lower doses Surgery & regional anesthesia should be delayed for 12 hours after last dose of LMWH Not reversed by protamine 12/08/2024 SAMPLE FOOTER TEXT 108 Warfarin Vitamin K Antagonist Initial dose 5-10 mg, average maintenance dose 5 mg  Onset delayed for 8-10 hours, peak effects in 36 -72 hours, must be d/c’d 5 days before surgery  Elimination half-time: 24-36 hrs  Crosses the placenta Mechanism of Action: Prevents the conversion of Vitamin K dependent factors (II, VII, IX, X) to their active form  Inhibits Vitamin K epoxide reductase Warfarin Laboratory Evaluation  Guided my measurement of the Prothrombin time (PT)  Standardized between labs and reported as the INR (international normalized ratio)  Normal