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Miscellaneous Adjunct Pharmacology

• Topics included: Psych drugs, Antibiotics, Disinfectants, GI/motility drugs, Herbals/supplements, and Anti & pro coagulants.

Psychopharmacologic Therapy

• Includes Antidepressants, Anxiolytics (benzodiazepines), Antipsychotics, and Anticonvulsants.
• Anesthesia can be safely administered to patients taking mental illness psychotropic medications.
• Preoperative discontinuation of psychoactive medications is no longer routine.
• Be aware of potential drug interactions, especially in elderly patients.

Antidepressants

• Approximately 10% of the population is treated for depressive illness.
• Antidepressants impact serotonergic and/or noradrenergic neurotransmission.
• Antidepressant use can treat different disorders, such as depressive, anxiety and chronic disorders—making “antidepressant” a broad term.
• Mechanism of action is unknown, but these medications likely increase serotonin and/or norepinephrine in CNS synapses.
• Improvement takes 2-4 weeks.
• Types include SSRIs (selective serotonin reuptake inhibitors -first line),TCAs (tricyclic antidepressants), and MAOIs (monoamine oxidase inhibitors).

SSRIs

• First-line treatment for mild to moderate depression, panic disorder, and OCD.
• Generally considered safe.
• Common side effects include insomnia, headache, agitation, nausea, diarrhea, and sexual dysfunction.
• Newer drugs (SNRIs) block both norepinephrine and serotonin reuptake.

Other Adverse Effects of SSRIs/SNRIs

• Suicidality: FDA black box warning; increased suicidal thoughts and behaviors in children and adolescents observed in some studies.
• Bleeding risk: serotonin plays a role in platelet aggregation. Combining SSRIs with anticoagulant therapy is common and not contraindicated. Studies have shown that there's no major increase in bleeding events in patients receiving anticoagulants and taking SSRIs.
• Serotonin Syndrome: rare but serious complication of SRI use; characterized by a triad of neuromuscular excitability, autonomic nervous system excitability, and mental status changes.

MAOIs

• Useful for treatment-resistant depression, but more rarely used due to side effects.
• Require a specific dietary regimen to avoid potentially dangerous interactions with some foods, like aged cheese, fermented products, preserved meats, and red wine due to significant interactions with tyramine found in some foods.
• Serious side effects, including orthostatic hypotension, insomnia, and lethality in overdose, make them more of a last resort treatment.

Tricyclic Antidepressants (TCAs)

• Formerly first-line treatment for depression, but surpassed by SSRIs because of side effect burden
• Can be used in patients who do not respond to SSRIs or in the treatment of chronic pain.
• Side effects include anticholinergic effects (prominent at high doses), cardiovascular effects (orthostatic hypotension, tachycardia, prolonged PR, widened QRS, and inverted/flattened T waves), CNS effects (sedation), and induction of anesthesia.

Monoamine Oxidase Inhibitors (MAOIs)

• Also for treatment-resistant depression
• Also have a significant dietary restriction required
• Dangerous interactions with foods and other drugs can occur.
• Less commonly used due to severe side effects and considerable dietary restrictions.

Antipsychotic Drugs

• Phenothiazines & Thioxanthenes
• Include Chlorpromazine (Thorazine), Triflupromazine (Vesprin), Fluphenazine (Prolixin), Prochlorperazine (Compazine), and Promethazine (Phenergan).
• Known to produce side effects, including sedation, anticholinergic effects, orthostatic hypotension, and extrapyramidal effects.

Antipsychotic Drugs-Side Effects

• Extrapyramidal Effects: Tardive Dyskinesia (abnormal involuntary movements) in 20% of patients taking these drugs for a year, and acute dystonic reactions (muscle rigidity).
• Cardiovascular Effects: includes hypotension and depressed vasomotor reflexes, arrhythmias, cardiac depression, prolonged QT interval.

Lithium

• Used in the treatment of bipolar disorder.
• Mechanism of action is unknown, but it may regulate intracellular second messengers and dampens signal transduction, stabilizing neurons.
• Therapeutic range is narrow (1.0-1.2 mEq/L).
• Common side effects include polyuria (>3L/day), impaired renal concentrating ability, ECG changes (T wave flattening or inversion).

Lithium-Drug Interactions

• Thiazide diuretics, NSAIDs, and ACE inhibitors increase plasma lithium concentrations by decreasing renal clearance.
• Neuroleptic drugs can exacerbate extrapyramidal symptoms or increase the risk of neuroleptic malignant syndrome.
• Beta-blockers decrease lithium-induced tremor.
• NMBs prolong duration of action.

Lithium Toxicity

• Diuretic therapy and sodium restriction can increase reabsorption of lithium and lead to increased plasma lithium concentration.
• Symptoms and signs of lithium toxicity correlate closely with plasma lithium concentrations and can include lethargy, irritability, muscle weakness, tremor, slurred speech, nausea, confusion, and coma.
• Cardiac changes that can occur include widening QRS complexes, dysrhythmias, heart block, and hypotension.

Cannabinoids

• Mixture of more than 400 compounds from Cannabis sativa.
• Most abundant include D9THC, cannabidiol, and cannabinol.
• D9THC is the primary psychotropic cannabinoid.
• Used for chronic pain and other conditions.
• Causes changes in perception, time distortion, altered sensory experience etc.

Antimicrobials

• Choice of antimicrobial is determined by drug properties and the infecting organism.
• Normal flora compete for nutrients, and produce their own antimicrobials, and overtreatment can lead to bacterial resistance.

Antibiotic Prophylaxis

• Surgical site infections are a significant burden to the patient and healthcare system, often causing readmission.
• Antibiotics are given before surgery to reduce the risk of surgical site infections.

Risk Factors for Surgical Site Infection (SSI)

• Patient Related: extremes of age, poor nutritional status, obesity, diabetes mellitus, peripheral vascular disease, tobacco use, coexisting infections, altered immune response, preoperative skin preparation (surgical scrub, hair removal, and length of preoperative hospitalization)
• Institutional Related: surgical team's experience, surgical technique, surgery-specific risks, duration of procedure, blood loss, hospital environment, sterilization of instruments, and maintenance of perioperative normothermia.

Modifications for SSI Risk

• Perioperative glucose control: smoking cessation interventions
• Maintenance of normothermia: Maintaining appropriate body temperature during and after surgery.
• Immunosuppression: Patients on chronic oral steroids have a greater risk of surgical site infection as well as those undergoing chemotherapy.

Surgical Wound Classification

• Clean: uninfected operative wound; no inflammation; no entry into respiratory, alimentary, genital or urinary tract.
• Clean-contaminated: Respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions without unusual contamination.
• Contaminated: Open, fresh, and accidental wounds; major break in sterile technique; gross spillage from the GI tract; acute nonpurulent inflammation encountered.
• Dirty-infected: Old traumatic wounds with retained devitalized tissue; existing clinical infection; perforated viscera.

Antimicrobials

• Choice based on infecting organism and drug properties to prevent overtreatment and resistance.
• Broad or Narrow spectrum depending on the type of infection
• Administered within 1 hour of surgical incision, for the likely time of inoculation before the surgical incision.
• Selection based on the procedure in question, known risk of post surgical infections.

Classification of Antibiotics (ABX)

• Based on mode of action (bacteriostatic, bactericidal)
• Based on spectrum of action(broad spectrum, narrow spectrum)

Development of Antibiotics Over Time

• Chronological development and introduction of different antibiotic classes throughout history.

Side Effects of Antibiotics

• Beta-Lactams: Allergic reactions, nephrotoxicity, rarely seizures
• Aminoglycosides: Ototoxicity, nephrotoxicity, neuromuscular blockade.
• Tetracyclines: Hepatotoxicity.
• Fluoroquinolones: GI intolerance, tendonitis, tendon rupture.
• Macrolides: Prolonged QT interval, possible torsades de pointes
• Clindamycin: pseudomembranous colitis (severe complication).
• Vancomycin: Rapid infusion can cause hypotension, red man syndrome, possible renal dysfunction or injury.

General Anaesthetic Considerations for Antibiotics

• Allergies;
• Administration time of antibiotics;
• Any relevant risks considering the drug interactions;
• Renal or other organ functions;
• Drug potency (narrow vs wide spectrum);

Alternative Medications/Supplements

• Many individuals currently use herbal remedies for health improvement and illness treatment
• Potential benefits and risks for these herbal remedies during perioperative periods

Herbal Preparations

• Positive and negative effects on patients.
• Not regulated by FDA so, should be discontinued 2 weeks before surgery.
• Consider drug interactions, adverse risks, etc.

Common GI Drugs

• Modifying Gastric Barrier Pressure impacting GERD, including drugs that decrease/increase gastric tone.
• Anticholinergics, Cricoid pressure, Pregnancies, Metoclopramide, Succinylcholine.

Histamine Receptor Antagonists

• Include Dimenhydrinate, Cimetidine, Ranitidine, Famotidine, Nizatidine.
• H2-receptor antagonists reduce acid secretions in the stomach but do not affect existing stomach pH.
• Used to treat acid-related disorders
• H1-receptor antagonists. Sedative side effects.

Proton Pump Inhibitors (PPIs)

• Omeprazole prototype.
• Used to control gastric acidity effectively.
• May cause adverse side effects, including headache, agitation, and confusion.
• Administration >3 hrs before induction is recommended.

GLP-1 Receptor Agonists

• Delay in gastric emptying can cause potential problems related to pulmonary aspiration during or after surgery.
• Preoperative diet modification (liquid diet for at least 24 hours) and assessment of aspiration risk using point-of-care ultrasound are recommended as part of a protocol in perioperative period.

Anticoagulants & Procoagulants

• Blood exists as a liquid in the absence of injury and injury leads to blood clotting via hemostasis
• Coagulation cascade is a chain of events for blood clot formation and dissolution
• Includes coagulation factors, pathways, cell based model
• Anticoagulants (warfarin, heparin, enoxaparin, rivaroxiban, apixiban, dabigatran)
• Procoagulants (protamine, Desmopressin, recombinant coagulation factors)

Antifibrinolytics

• Drugs that inhibit plasmin, the enzyme that dissolves clots, include aminocaproic acid (EACA) and tranexamic acid (TXA), which can potentially decrease transfusion requirements in surgeries; however, they can also cause complications.

Antiplatelet Drugs

• Drugs that keep platelets from aggregating and forming clots, such as aspirin, clopidogrel, prasugrel, and ticagrelor.

Most Common Antibiotic Risks