PHARMACOLOGY

Anti-Inflammatory

  • Immune and inflammatory responses protect the body from invading foreign substances.

  • Certain drug classes can modify these responses:

    • Antihistamines block the effects of histamine on target tissues.

    • Corticosteroids suppress immune responses and reduce inflammation.

    • Uricosurics control the occurrence of gouty arthritis attacks.

Anti-Histamines

  • Antihistamines primarily block histamine effects in immediate (type I) hypersensitivity reactions (allergic reactions).

  • Availability: alone or in combination products; prescription or over-the-counter.

  • H1 receptor antagonists: drugs that act as histamine-1 (H1) receptor antagonists; they compete with histamine for H1-receptor sites throughout the body but do not displace histamines already bound to receptors.

  • Pharmacokinetics (PK): H1-receptor antagonists are absorbed well after oral or parenteral administration; some can be given rectally.

  • Distribution: with the exception of loratadine and desloratadine, antihistamines are distributed widely throughout the body and CNS.

  • Non-sedating antihistamines: fexofenadine, desloratadine, and loratadine; because they minimally penetrate the blood–brain barrier, they are not widely distributed in the CNS and produce fewer sedative effects.

  • Pharmacodynamics (PD): H1 antagonists compete with histamine for H1 receptors on effector cells, blocking histamine from producing its effects.

  • Pharmacotherapeutics: used to treat signs and symptoms of type I hypersensitivity reactions, such as:

    • allergic rhinitis (runny nose and itchy eyes)

    • vasomotor rhinitis (rhinitis not caused by allergy or infection)

    • allergic conjunctivitis (eye membranes)

    • urticaria (hives)

    • angioedema (submucosal swelling in hands, face, feet)

  • Drug interactions:

    • May block/reverse vasopressor effects of epinephrine, causing vasodilation, increased HR, and dangerously low BP at certain doses.

    • May mask toxic signs of ototoxicity with aminoglycosides or with high doses of salicylates.

    • May increase sedative and respiratory depressant effects of CNS depressants (tranquilizers, alcohol).

    • Loratadine may cause serious cardiac effects when taken with macrolide antibiotics (e.g., erythromycin), fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ciprofloxacin, and clarithromycin.

  • Adverse reactions:

    • Most common adverse reaction (except for fexofenadine, loratadine, desloratadine) is CNS depression.

    • Other CNS effects: dizziness, fatigue, disturbed coordination, muscle weakness.

    • GI effects: epigastric distress, loss of appetite, nausea/vomiting, constipation, diarrhea, dry mouth/nose/throat.

  • Nursing considerations (highlights):

    • Take with meals or snacks to prevent GI upset.

    • Avoid caffeine, nicotine, and alcohol.

    • Use warm water rinses, artificial saliva, ice chips, or sugarless gum/candy for dry mouth.

    • If used for motion sickness, take 30 minutes before travel.

    • Avoid hazardous activities until CNS effects are known.

    • Seek medical approval before using alcohol, tranquilizers, sedatives, pain relievers, or sleeping medications.

    • Stop taking antihistamines 4 days before diagnostic skin tests to preserve accuracy.

    • Notify prescriber if tolerance develops (a different antihistamine may be needed).

    • Photosensitivity risk; use sunblock or protective clothing.

    • Avoid using other products containing diphenhydramine (OTC or topical) during breast-feeding due to risk of adverse reactions.

    • For insomnia, administer 20 minutes before typical sleep hours.

Corticosteroids

  • Corticosteroids suppress immune responses and reduce inflammation. They are available as natural or synthetic steroids.

  • Classifications:

    • Natural corticosteroids are hormones produced by the adrenal cortex.

    • Most corticosteroid drugs are synthetic analogues.

    • Classified by biological activities:

    • Glucocorticoids (affect carbohydrate, fat, and protein metabolism).

    • Mineralocorticoids (regulate electrolyte and water balance).

  • Glucocorticoids:

    • Most glucocorticoids are synthetic analogues; exert anti-inflammatory, metabolic, and immunosuppressant effects.

    • Examples include: \text{beclomethasone}, \text{betamethasone}, \text{cortisone}, \text{dexamethasone}, \text{hydrocortisone}, \text{methylprednisolone}, \text{prednisolone}, \text{prednisone}, \text{triamcinolone}

  • Pharmacokinetics (PK) of glucocorticoids:

    • Well absorbed orally; after intramuscular (IM) administration, completely absorbed.

    • Bound to plasma proteins; distributed via blood.

    • Metabolized in the liver; excreted by the kidneys.

  • Pharmacodynamics (PD):

    • Suppress hypersensitivity and immune responses through mechanisms not fully understood.

    • Suspected actions:

    • Inhibit cell-mediated immune reactions; reduce leukocytes, monocytes, eosinophils.

    • Decrease binding of immunoglobulins to cell-surface receptors.

    • Inhibit interleukin synthesis.

  • Drug interactions with glucocorticoids:

    • Barbiturates, phenytoin, rifampin, and aminoglutethimide may reduce glucocorticoid effects.

    • Amphotericin B, chlorthalidone, ethacrynic acid, furosemide, and thiazide diuretics may enhance potassium-wasting effects.

    • Erythromycin and troleandomycin may increase effects by reducing metabolism.

    • Glucocorticoids reduce serum concentrations and effects of salicylates.

    • NSAIDs and salicylates increase peptic ulcer risk when taken with corticosteroids.

    • Vaccines may have reduced response in patients taking glucocorticoids.

    • Estrogen-containing birth control increases corticosteroid effects.

    • Antidiabetic drug effects may be reduced, causing higher blood glucose.

  • Adverse reactions (systemic effects, esp. long-term/high-dose):

    • Insomnia, sodium and water retention, increased potassium excretion, immunosuppression, osteoporosis, gut ulcers, impaired wound healing, cataracts, hypertension, personality changes, increased infection risk.

    • Endocrine: diabetes mellitus, hyperlipidemia, adrenal atrophy, hypothalamic-pituitary axis suppression, Cushingoid signs (buffalo hump, moon face), hyperglycemia.

  • Nursing considerations:

    • Give early in the day to mimic circadian rhythm; with food to prevent GI irritation.

    • Prevent infection; monitor for adverse reactions; adjust dose during physiologic stress (surgery, trauma, infection).

    • Do not stop abruptly; avoid prolonged use in children; notify prescriber of severe adverse reactions.

Mineralocorticoids

  • Mineralocorticoids affect electrolyte and water balance.

  • Example: fludrocortisone acetate, a synthetic analogue of adrenal cortex hormones.

  • Pharmacokinetics:

    • Absorbed well; distributed broadly.

    • Metabolized in the liver; excreted by the kidneys.

  • Pharmacodynamics:

    • Increase sodium reabsorption and increase potassium and hydrogen secretion in the distal renal tubule.

  • Pharmacotherapeutics:

    • Replacement therapy for adrenocortical insufficiency (reduced glucocorticoids, mineralocorticoids, and androgens).

    • Drug interactions similar to glucocorticoids.

Uricosurics

  • Uricosurics and other antigout drugs act on uric acid metabolism.

  • Hyperuricemia leads to gout (increased uric acid in blood) due to overproduction or decreased renal excretion.

  • Major uricosurics: probenecid and sulfinpyrazone (two first-line NSAIDs for gout in this context).

  • Pharmacokinetics:

    • Absorbed from GI tract.

    • 75–95% of probenecid and 98% of sulfinpyrazone are protein-bound.

    • Metabolized in the liver; excreted primarily by the kidneys; small amounts excreted in feces.

  • Pharmacodynamics:

    • Probenecid and sulfinpyrazone reduce reabsorption of uric acid at the proximal convoluted tubule, promoting uric acid excretion in urine and lowering serum urate.

  • Pharmacotherapeutics:

    • Indicated for symptoms of gout, gouty arthritis (joint inflammation due to urate crystals), and abarticular gout (under-skin urate deposits).

    • Note: Should not be given during an acute gout attack; can prolong inflammation if started during an attack. Colchicine is used during the first 3–6 months of therapy to prevent attacks when initiating uricosurics.

  • Drug interactions:

    • Probenecid can significantly increase and prolong effects of cephalosporins, penicillins, and sulfonamides.

    • Serum urate levels may rise when probenecid is used with antineoplastic drugs.

  • Adverse reactions:

    • Uricosurics can cause uric acid stone formation and blood abnormalities.

    • Probenecid: headache, anorexia, nausea/vomiting, hypersensitivity.

    • Sulfinpyrazone: nausea, indigestion, GI pain, GI bleeding.

  • Nursing considerations:

    • Encourage fluid intake to maintain at least 2 L/day; urine alkalinization with sodium bicarbonate or potassium citrate as needed to prevent hematuria, renal colic, uric acid stones.

    • Begin therapy after an acute attack subsides; not useful during an acute attack.

    • Expect increased frequency, severity, and duration of acute attacks during the first 12 months; prophylactic colchicine or another anti-inflammatory is given during the first 3–6 months.

Other antigout drugs

  • Allopurinol and colchicine are also used in gout management.

  • Allopurinol reduces uric acid production and can be used with uricosurics at lower dosages.

  • Colchicine reduces inflammation by affecting white blood cells’ (WBCs) role in inflammation.

  • Allopurinol pharmacokinetics:

    • Oral absorption; allopurinol and its metabolite oxypurinol widely distributed except in brain

    • Metabolized in liver; excreted in urine.

  • Colchicine pharmacokinetics:

    • Oral absorption; partially metabolized in the liver; biliary resecretions; reabsorption from intestines; distributed to tissues; excreted mainly in feces; some in urine.

  • Pharmacodynamics:

    • Allopurinol inhibits xanthine oxidase, the enzyme responsible for uric acid production.

  • Pharmacotherapeutics:

    • Allopurinol treats primary gout, hyperuricemia with blood abnormalities or during tumor treatment; treats primary/secondary uric acid nephropathy; prevents recurrent uric acid stone formation; can be used with uricosurics for lower dosages.

  • Drug interactions:

    • Colchicine has minimal interactions with many drugs, but allopurinol interactions can be serious:

    • Potentiates effects of oral anticoagulants.

    • Increases mercaptopurine and azathioprine levels, increasing toxicity risk.

    • ACE inhibitors increase hypersensitivity risk with allopurinol.

    • Allopurinol can raise theophylline levels.

    • Bone marrow suppression risk increases when cyclophosphamide is used with allopurinol.

  • Adverse reactions:

    • Allopurinol commonly causes a rash.

    • Colchicine long-term may cause bone marrow suppression.

    • Common across allopurinol/colchicine: nausea, vomiting, diarrhea, abdominal pain.

  • Salicylates (for context):

    • Salicylates (e.g., aspirin and related compounds) inhibit prostaglandin synthesis; have antipyretic effects via prostaglandin mediation at the hypothalamus; low-dose aspirin reduces platelet aggregation via thromboxane A2; high-dose inhibition of prostacyclin reduces anti-platelet effects.

    • Indications: mild-to-moderate pain, fever, various inflammatory conditions; mesalamine/balsalazide for ulcerative colitis; sodium thiosalicylate for arthritis/pain.

    • Contraindications and cautions: allergy to salicylates/NSAIDs; bleeding abnormalities; renal impairment; risk of Reye Syndrome in children with influenza or chickenpox; perioperative risk; pregnancy/lactation cautions.

    • Adverse effects: GI upset; hematologic abnormalities; salicylism (dizziness, tinnitus, hearing loss, nausea, vomiting, confusion, lassitude); acute toxicity at doses of about 20-25\,\text{g} in adults or 4\,\text{g} in children.

    • Interactions: anticoagulants; NSAIDs; activated charcoal; antacids; carbonic anhydrase inhibitors.

    • Nursing considerations: take with food; check all medicines for salicylate ingredients; monitor for severe reactions; provide supportive care; ensure hydration; educate about adverse effects and warning signs.

Vaccines and Sera (Immunization)

  • Immunization is the process of artificially stimulating active immunity by exposing the body to weakened or less toxic proteins from disease-causing organisms.

  • Goal: to provoke an immune response without causing disease.

  • Types of immunity:

    • Active Immunization: stimulates host to produce antibodies or cellular responses to protect against/eliminate disease.

    • Passive Immunization: administration of antibodies to neutralize a pathogen around exposure.

  • Vaccines provide an antigenic stimulus that does not cause disease but can produce long-lasting protective immunity.

  • Types of vaccines and their characteristics: 1) Live (attenuated) vaccines: include viral vaccines (polio oral Sabin, mumps, measles, rubella, varicella) and some bacterial (BCG for TB).

    • Advantages: induce both humoral (Abs) and cellular (CTLs) responses; long-lasting immunity often with one or two doses.

    • Limitations: risk for immunocompromised persons; thermolabile/instability.
      2) Inactivated (killed) vaccines: include pertussis, typhoid, polio (Salk), influenza.

    • Advantages: greater stability; safety (no infection risk).

    • Limitations: shorter-lasting immunity; require boosters; lower immunogenicity (often need adjuvant).
      3) Subunit (antigenic) vaccines: use structural antigens (proteins or polysaccharides) or toxoids.

    • Examples: pertussis (acellular), tetanus/diphtheria toxoids, influenza (Hemagglutinin/Neuraminidase), hepatitis B (HBsAg), HPV (L1 protein/virus-like particles), pneumococcal and meningococcal polysaccharide vaccines.

    • Advantages: safety; same general benefits as inactivated.

    • Limitations: sometimes lower immunogenicity (similar to inactivated vaccines).

      • Toxoids: inactivated toxins used as vaccines (e.g., tetanus and diphtheria toxoids) requiring booster injections every ~10 years.

  • Serum preparations (passive antibodies):

    • Types include homogeneous serum (from immunized human donors) and heterogeneous serum (animal sources, e.g., horse antisera such as tetanus antitoxin, diphtheria antitoxin, rabies immune globulin).

    • Immune globulins (human) and various immune globulins (e.g., hepatitis B immune globulin, rabies immune globulin).

    • Hypersensitivity reactions to heterogeneous serum can occur (type I/anaphylactic reactions within 2–30 minutes).

  • Anaphylaxis: systemic reactions causing shock and breathing difficulties; can be fatal; localized reactions include hay fever, asthma, hives.

  • Serum sickness: systemic hypersensitivity occurring 7–12 days after a high-concentration foreign serum injection.

Psychopharmacology: Neurotransmitters, Drugs, and Concepts

  • Neurotransmitters are chemical messengers that can be excitatory or inhibitory; after release into the synapse and receptor activation, they are removed by reuptake or breakdown by enzymes (primarily MAO).

  • Dopamine: located mainly in brainstem; generally excitatory; synthesized from tyrosine.

    • Antipsychotics work by blocking dopamine receptors (D1–D5; D2 most linked to psychosis and EPS).

  • Norepinephrine (noradrenaline) and Epinephrine (adrenaline):

    • Norepinephrine is the most prevalent CNS neurotransmitter; involved in mood regulation.

    • Epinephrine has limited CNS distribution; controls fight-or-flight responses in the periphery.

  • Serotonin (5-HT): in brain; derived from tryptophan; mostly inhibitory; involved in sleep, mood, appetite, pain control, sexual behavior, temperature regulation, etc.

    • Some antidepressants block serotonin reuptake, increasing serotonin in the synapse.

  • Acetylcholine: in brain, spinal cord, PNS; excitatory or inhibitory; involved in sleep-wake cycle and muscle activation; decreased acetylcholine noted in Alzheimer's disease.

  • Glutamate: excitatory amino acid; high levels can be neurotoxic.

  • GABA (gamma-aminobutyric acid): major inhibitory neurotransmitter; modulates other neurotransmitters; benzodiazepines increase GABA function to treat anxiety and aid sleep.

  • Pharmacodynamics and clinical notes:

    • Efficacy: maximal therapeutic effect a drug can achieve.

    • Potency: amount of drug needed to achieve maximal effect; low-potency requires higher doses; high-potency achieves efficacy at lower doses.

    • Half-life: the time it takes for half of the drug to be removed from the bloodstream; denoted as t_{1/2}.

    • The FDA may issue a black-box warning when a drug has serious or life-threatening side effects; boxed warnings appear prominently in package inserts.

Antipsychotic Drugs

  • Also known as neuroleptics; used to treat psychosis (e.g., schizophrenia, schizoaffective disorder, manic phase of bipolar).

  • Mechanism: primarily block dopamine receptors (D2, D3, D4).

  • Generations: 1) First Generation (Conventional): strong D2 blockade; high risk of extrapyramidal symptoms (EPS).

    • Examples: chlorpromazine, thioridazine, fluphenazine, haloperidol.

    • High-potency agents often used for positive symptoms (e.g., hallucinations); associated with EPS; contraindicated in older adults (>65 years) in some contexts.
      2) Second Generation (Atypical): lower D2 blockade with greater effects on serotonin receptors; more effective for negative symptoms; lower EPS but risk of metabolic side effects.

    • Examples: olanzapine, quetiapine, clozapine, risperidone, ziprasidone, lurasidone, molindone.
      3) Third Generation: dopamine system stabilizers; partial agonists that balance dopamine activity.

    • Examples: aripiprazole, brexpiprazole.

  • Depot therapy: long-acting injectable formulations for noncompliance.

  • Extrapyramidal side effects (EPS): major adverse effects include:

    • Acute dystonia (prolonged involuntary muscle contractions), pseudoparkinsonism, akathisia (restlessness).

    • D2 receptor blockade in midbrain causes EPS; features include torticollis, opisthotonus, and oculogyric crisis; acute treatment with anticholinergic drugs.

    • Pseudoparkinsonism features: rigid/stiff posture, mask-like face, reduced arm swing, shuffling gait, tremor, drooling, bradykinesia; managed with anticholinergics or amantadine (dopamine agonist).

  • Neuroleptic Malignant Syndrome (NMS): potentially fatal idiosyncratic reaction; 10–20% mortality; symptoms include rigidity, high fever, autonomic instability, delirium, elevated CK; treat with stopping antipsychotic and supportive care.

  • Tardive Dyskinesia (TD): irreversible syndrome of involuntary movements, especially of tongue and facial muscles; no definitive cure; risk increases with long-term use.

  • Agranulocytosis risk with certain antipsychotics (e.g., clozapine); requires monitoring of WBC; discontinuation if severe leukopenia.

Antidepressants

  • Mechanism: interact with monoamine neurotransmitters (norepinephrine, serotonin, dopamine).

  • Groups:

    • MAO Inhibitors (MAOIs): e.g., tranylcypromine, isocarboxazid, phenelzine, selegiline.

    • Note: MAOIs carry high risk of hypertensive crisis if tyramine-containing foods are ingested (aged cheeses, aged meats, tofu, beer, sauerkraut, soy sauce, yogurt, etc.).

    • MAOIs require caution or avoidance with other antidepressants and CNS depressants; overdose risk is high.

    • Selective Serotonin Reuptake Inhibitors (SSRIs): e.g., fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, paroxetine, etc.

    • Often preferred when suicide risk is a concern due to lower overdose risk than cyclic antidepressants or MAOIs; effective for mild-to-moderate depression.

    • Tricyclic Antidepressants (TCAs) and related cyclics: e.g., imipramine, amitriptyline, nortriptyline, clomipramine, desipramine, etc.

    • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): e.g., venlafaxine, duloxetine, desvenlafaxine (and others).

    • Other antidepressants: venlafaxine, bupropion, duloxetine, trazodone, nefazodone.

  • Quickest antidepressants effects: roughly 1 week; examples reported as effective: \text{Zoloft} (sertraline), \text{Lexapro} (escitalopram), \text{Paxil} (paroxetine), \text{Luvox} (fluvoxamine), \text{Prozac} (fluoxetine).

  • Antidepressants act on monoamine systems; reuptake inhibitors increase synaptic serotonin or norepinephrine depending on class:

    • SSRIs block serotonin reuptake (primary action to improve mood and anxiety symptoms).

    • TCAs and SNRIs block reuptake of norepinephrine to varying degrees and also affect serotonin.

    • MAOIs inhibit enzyme monoamine oxidase, affecting breakdown of monoamines.

  • Memory trick (mnemonics):

    • MAOIs: insomnia; morning dosing.

    • TCAs: sedation; evening dosing.

    • SSRIs/SNRIs: anorexia; take with food.

  • Antidepressants are hepatotoxic; monitor AST/ALT whether indicated.

  • St. John’s wort should not be combined with antidepressants due to risk of seizures and serotonin syndrome.

Mood Stabilizers

  • Mood stabilizers are used to treat bipolar disorder to stabilize mood and prevent manic/depressive episodes.

  • Lithium:

    • First-line agent.

    • Normalizes reuptake of serotonin, norepinephrine, acetylcholine, and dopamine; reduces norepinephrine release via calcium competition.

    • Mechanism of action largely intracellular.

    • Therapeutic serum level: 1.0\ \text{mEq/L}.

    • Therapeutic range: typically 0.6-1.2\ \text{mEq/L}; toxicity concerns begin above ~3.0\ \text{mEq/L} where dialysis may be indicated.

    • Effects may take weeks to manifest.

  • Anticonvulsants used as mood stabilizers: valproic acid, topiramate; gabapentin; pregabalin; lamotrigine; lithium.

    • Valproic acid and topiramate increase GABA activity, thought to stabilize mood by inhibiting kindling (recurrent seizures or subclinical activity that could contribute to mania).

    • Kindling concept: snowball effect where minor seizures lead to more severe episodes; mood stabilization may raise seizure threshold similarly.

  • Nursing considerations for lithium:

    • Therapeutic level typically 0.6-1.2\ \text{mEq/L}; common side effect is fine tremor.

    • Polyuria and polydipsia may indicate toxicity.

    • Severe toxicity signs require management with mannitol (osmotic diuretic) and careful sodium management; monitor sodium levels because low sodium can precipitate lithium toxicity.

    • Normal sodium range: 135-145\ \text{mmol/L}.

    • Diet: moderate sodium intake; avoid excessive sweating; monitor hydration.

  • Anticonvulsants for mood stabilization:

    • Carbamazepine (Tegretol), valproic acid (divalproex), etc.

  • Benzodiazepines as anxiolytics and sedatives are often used adjunctively:

    • They act on GABA to provide CNS inhibition; examples: alprazolam, chlordiazepoxide, clonazepam, diazepam, lorazepam, oxazepam, triazolam.

    • Note: benzodiazepines can be used for anxiety, seizures, sedation; caution about dependence and withdrawal.

    • Pharmacokinetics: rapidly absorbed; high protein binding (~85–90%); liver metabolism; renal excretion; cross placenta and present in breast milk.

    • Pharmacodynamics: anticonvulsants, anti-anxiety, sedative-hypnotics, muscle relaxants.

    • Special notes: avoid long-term daily use; abrupt withdrawal may cause seizures; monitor for CNS depression when coadministered with other CNS depressants; ensure safety when giving IV benzodiazepines.

Stimulants

  • Primary use today: ADHD in children/adolescents; residual adult ADHD; narcolepsy.

  • Mechanism: indirectly acting amines; increase norepinephrine, dopamine, and serotonin by releasing them from presynaptic terminals and/or blocking reuptake.

  • Common stimulants: dextroamphetamine, methylphenidate, mixed amphetamine salts.

  • PK/PD:

    • Well absorbed from GI tract; methylphenidate undergoes significant first-pass metabolism.

    • Metabolized in liver; excreted mainly in urine.

    • Effects include increased synaptic norepinephrine and dopamine; improved attention, reduced impulsivity and hyperactivity.

  • Nursing considerations:

    • Give at least 6 hours before bedtime to avoid sleep interference.

    • Long-term use may cause psychological dependence or habituation, especially in those with prior drug history.

    • After prolonged use, taper to prevent rebound depression.

    • Avoid hazardous activities until CNS effects are known.

    • Avoid caffeine-containing drinks as they increase stimulant effects.

    • Report adverse effects (excess stimulation, tolerance) to prescriber.

Anesthesia

  • General anesthesia aims: analgesia, unconsciousness, amnesia.

  • Risk factors: cardiovascular (CV) and respiratory risk, renal and hepatic considerations; also potential for CNS depression.

  • Balanced anesthesia: combine several agents to achieve required effects while minimizing adverse effects (e.g., NMJ blockers, sedatives, antiemetics, antihistamines, narcotics).

  • Phases of anesthesia:
    1) Induction: start of anesthesia to stage 3.
    2) Maintenance: stage 3 until completed.
    3) Recovery: emergence from anesthesia.

  • General anesthetic agents:

    • Barbiturate and non-barbiturate IV anesthetics, gas anesthetics, and IV liquids.

    • Barbiturate class example: Thiopental (Pentothal) – most widely used IV anesthetic; no analgesic properties; may require additional analgesia after surgery.

    • Methohexital (Brevital) – lacks analgesic property; rapid onset; recovery 3–4 minutes; lipophilic; diffuses rapidly to brain.

    • Contraindications/precautions: Methohexital should not contact silicone; ensure readiness for intubation; rapid onset may cause respiratory depression.

    • Pregnancy and lactation: avoid unless benefits clearly outweigh fetal risk; CNS depressant risk to fetus.

    • Adverse effects: decreased pulse, hypotension, suppressed respiration, decreased GI activity, nausea/vomiting.

    • Drug interactions: barbiturates can affect theophylline, oral anticoagulants, beta blockers, corticosteroids, hormonal contraceptives, etc.; barbiturate anesthesia plus narcotics can cause apnea more commonly.

  • Non-barbiturate IV anesthetics:

    • Midazolam (Versed); Droperidol (Inapsine); Etomidate (Amidate); Fospropofol (Lusedra); Ketamine; Propofol (Diprivan).

    • Pharmacokinetics: varies by agent; e.g., midazolam onset rapid but peak effectiveness around 30–60 minutes; etomidate ~1 minute onset; propofol rapid onset; ketamine ~30 seconds onset.

    • Pharmacodynamics: sedative, amnestic, anticonvulsant, anxiolytic, etc.

    • Indications: premedication, induction, sedation for intubated patients, continuous sedation.

    • Contraindications/precautions: midazolam can cause nausea/vomiting and respiratory depression; monitor; droperidol caution with renal/hepatic failure and prolonged QT risk; etomidate not recommended for children under 10; etc.

    • Adverse effects: various CNS, respiratory, GI, and cardiovascular effects depending on agent.

    • Drug interactions: CNS depressants increase toxicity; cimetidine and hormonal contraceptives increase CNS depression with benzodiazepines; etc.

  • Inhaled gas anesthetics (gas):

    • Nitrous oxide: potent analgesic; fast onset and offset; usually combined with other agents; does not cause muscle relaxation; watch for hypoxia risk due to reuptake-blocking effects; avoid in pregnancy unless benefits outweigh risks; nursing mothers should wait 4 hours before nursing after administration.

    • Halogenated volatile liquids (inhaled anesthetics): Halothane, Desflurane, Enflurane, Isoflurane, Sevoflurane.

    • Prototypes and characteristics:

      • Halothane: rapid onset; maintenance; rare hepatic toxicity (recovery syndrome); avoid repeated use beyond 3 weeks.

      • Desflurane: may cause respiratory irritation; avoid in some patients with respiratory problems.

      • Enflurane: caution with known cardiac/respiratory disease or renal dysfunction.

      • Isoflurane: may cause hypotension, hypercapnia, sour taste; use with caution in respiratory depression.

      • Sevoflurane: minimal adverse effects; rapidly cleared; commonly used for induction.

    • Pharmacokinetics: onset and recovery times vary; Halothane 1–2 minute onset, ~20 minutes recovery; Desflurane/Enflurane/Isoflurane 1–2 minute onset, 5–20 minute recovery; Sevoflurane ~30 second onset, ~10 minute clearance. All are eliminated via the lungs.

    • Contraindications/precautions: hepatic impairment with Halothane; respiratory/cardiac risks with Desflurane/Enflurane; caution with respiratory depression for Isoflurane/Sevoflurane; potential malignant hyperthermia risk; have dantrolene available.

    • Adverse effects: Halothane recovery syndrome; Desflurane respiratory reactions; Isoflurane hypotension and dysgeusia; Enflurane renal impairment; Sevoflurane minimal effects.

    • Drug interactions: caution with other CNS depressants.

  • Local anesthesia

    • Topical: lotion, cream, ointment, eye drops for mucous membranes.

    • Infiltration: injection into tissues to be treated.

    • Field block: injection around the area to be affected; more intense than infiltration.

    • Nerve blocks: peripheral sensory/motor block; central nerve blocks along spinal roots; includes:

    • Epidural: from the word epidural (space around spinal nerves) used in obstetrics.

    • Caudal epidural.

    • Spinal: injection into the subarachnoid space.

    • IV regional anesthesia: tourniquet to isolate limb circulation; inject anesthetic into a limb vein.

    • Local anesthetic agents: esters or amides.

    • Pharmacokinetics:

    • Ester-type locally: rapidly hydrolyzed in plasma by esterases.

    • Amide-type locally: slower metabolism in the liver; potential toxicity if accumulated.

    • Therapeutic actions/indications: to prevent pain during procedures; can be used for infiltration, nerve block, spinal anesthesia, and local pain relief.

    • Contraindications: allergy history, decreased plasma esterases, pregnancy/lactation (balance risk vs benefit).

    • Adverse effects: local numbness, loss of temperature, touch, proprioception, muscle tone; CNS effects (headache, dizziness, tremors); GI effects (nausea, vomiting); cardiovascular effects (vasodilation, myocardial depression, arrhythmias); potential fatal cardiac or respiratory arrest in severe cases.

    • Drug interactions:

    • Local anesthetics + succinylcholine: increased neuromuscular blockade.

    • Local anesthetics + epinephrine: reduced systemic absorption, increased local effect.

    • Heart block risk with certain combinations.

Reminders on Practice and Safety

  • Many drug interactions require careful review of all medications the patient is taking.

  • For anesthesia, ensure monitoring systems and resuscitation equipment are ready; avoid rapid changes in drug administration without confirming airway/ventilation support.

  • For antipsychotics, monitor for EPS, TD, NMS, and agranulocytosis; Clozapine requires regular WBC monitoring.

  • For corticosteroids, consider the physiologic stress response and potential HPA axis suppression; taper rather than abrupt withdrawal.

  • For salicylates, monitor for signs of salicylism and toxicity; exercise caution in populations at risk (children, overweight, comorbidities).

  • For vaccines, be aware of hypersensitivity risks and the difference between live attenuated and inactivated products as described above.

  • For mood stabilizers and antidepressants, monitor therapeutic levels, liver function, and potential suicidal risk if using certain agents; avoid drug interactions that raise toxicity risk.

LaTeX notes used where applicable:

  • Lithium