-Used in bradycardia and for ophthalmic applications
-Also used as antidote for cholinesterase inhibitor poisoning
-Actions include increase pupil dilation, cycloplegia, decreased airway secretions, decreased acid secretions, decreased gut motility, decreased bladder urgency in cystitis
-Toxicity: increased body temp (due to decreased sweating), rapid pulse, dry mouth, dry and flushed skin, cycloplegia, constipation, disorientation;
-Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants
-See also homatropine and tropicamide
-Caused by consumption of dark-meat fish (e.g., bonito, mackerel, mahi-mahi, tuna) improperly stored at warm temperature.
-Bacterial histidine decarboxylase converts histidine to histamine. Histamine is not degraded by cooking.
-Acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruritus, headache. May cause anaphylaxis-like presentation (i.e., bronchospasm, angioedema, hypotension).
-Frequently misdiagnosed as allergy to fish.
-Treat supportively with antihistamines; if needed, antianaphylactics (e.g., bronchodilators, epinephrine).
Acute alcohol abuse, Ritonavir, Amiodarone, Cimetidine, Ketoconazole, Sulfonamides, Isoniazid (INH), Grapefruit juice, Quinidine, Macrolides, (except azithromycin) Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonamide antibiotics, Sulfasalazine, Sulfonylureas.
Patients with sulfa allergies may develop
fever, urinary tract infection, Stevens-
Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives). Symptoms range from mild to life threatening.
-Azithromycin, clarithromycin, erythromycin
-Inhibit protein synthesis by blocking translocation ("macroslides"); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
-Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram-positive cocci (streptococcal infections in patients allergic to penicillin), and B. pertussis.
Toxicity: MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsinophilia. Increases serum concentration of theophyllines, oral anticoagulants. Clarithromycin and erythromycin inhibit cytochrome P-450.
Resistance: methylation of 23S rRNA-binding site prevents binding of drug.
-Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
-Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic (bactericidal when combined with trimethoprim). (Dapsone, used to treat lepromatous leprosy, is a closely related drug that also inhibits folate synthesis.)
-Gram-positives, gram-negatives, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
-Toxicity: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin).
-Resistance: Altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis.
-Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin.
-Inhibit prokaryotic enzymes topoisomerase
II (DNA gyrase) and topoisomerase IV. Bactericidal. Must not be taken with antacids.
-Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms.
Toxicity: GI upset, superinfections, skin rashes, headache, dizziness. Less commonly, can cause leg cramps and myalgias.
-Contraindicated in pregnant women, nursing mothers, and children < 18 years old due to possible damage to cartilage. Some may prolong QT interval. May cause tendonitis or tendon rupture in people > 60 years old and in patients taking prednisone.
-Resistance: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
-Iatrogenic Cushing syndrome (hypertension, weight gain, moon facies, truncal obesity, buffalo hump, thinning of skin, striae, osteoporosis, hyperglycemia, amenorrhea, immunosuppression), adrenocortical atrophy, peptic ulcers, steroid diabetes, steroid psychosis.
-Adrenal insufficiency when drug stopped abruptly after chronic use.
Bleeding, teratogenic, skin/tissue necrosis
A , drug-drug interactions. Proteins C and S
have shorter half-lives than clotting factors
II, VI, IX, and X, resulting in early transient hypercoagulability with warfarin use. Skin/tissue necrosis believed to be due to small vessel microthromboses.
-For reversal of warfarin, give vitamin K.
-For rapid reversal, give fresh frozen plasma.
-Heparin "bridging": heparin frequently used
when starting warfarin. Heparin's activation of antithrombin enables anticoagulation during initial, transient hypercoagulable state caused by warfarin. Initial heparin therapy reduces risk of recurrent venous thromboembolism and skin/tissue necrosis.
Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA)
-Mechanism: Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increase PT, increase PTT, no change in platelet count.
-Use: Early MI, early ischemic stroke, direct thrombolysis of severe PE.
-Toxicity: Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension. Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis. Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.
-G1: alkylating agents (carmustine, cisplatin, lomustine)
-S: antimetabolites (azanthroprine, cladribine, cytarabine, 5-fluouracil, hydroxyurea, methotrexate, 6-MP, 6-thioguanine), also etoposide, teniposide
-G2: bleomycin, etoposide, teniposide
-M: microtubule inhibitors (paclitaxel), vinca alkaloids (vinblastine, vincristine)
-Mechanism: various; bind intracytoplasmic receptor; alter gene transcription.
-Use: most commonly used glucocorticoids in cancer chemotherapy. Used in CLL, non-Hodgkin lymphoma (part of combination chemotherapy regimen). Also used as immunosuppressants (e.g., in autoimmune diseases).
-Toxicity: Cushing-like symptoms; weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.
-CSA Schedule 2 drug
-Behavioral restlessness, tremulousness, hyperactivity, respiratory depression, N/V, ↑intracranial pressure, postural HoTN accentuated by hypovolemia, constipation, urinary retention, itching around nose, urticaria
-CI: concomitant use of full w/ partial agonists (or antagonists), ↓pulmonary function, head injury, pregnancy, impaired hepatic or renal function, endocrine dysfunction
-Drug Interactions: sedative hypnotics, antipsychotics, MOAIs
-Mechanism: Increase Na+ channel inactivation, zero order kinetics
-Use: all seizure types except for absence; first line tonic-clonic; first line prophylaxis for status epilepticus
-Adverse effects: gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia, teratogenesis (fetal hydantoin syndrome), SLE-like syndrome, induction of cytochrome P-450, lymphadenopathy, Stevens- Johnson syndrome, osteopenia
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
-Mechanism: Facilitate GABA-A action by increasinf the frequency of Cl− channel opening. Decrease REM sleep. Most have long half-lives and active metabolites (exceptions: Alprazolam, Triazolam, Oxazepam, and Midazolam are short acting higher addictive potential)
-Use: anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia)
-Toxicity: dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, N2O
-Use: myocardial depression, respiratory depression, nausea/emesis, cerebral blood flow ( cerebral metabolic demand).
-Toxicity: hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (N2O). *Can cause malignant hyperthermia—rare, life-threatening hereditary condition in which inhaled anesthetics (except N2O) and succinylcholine induce fever and severe muscle contractions. Treatment: dantrolene.
Sweating, dilated pupils, piloerection ("cold turkey"), fever, rhinorrhea, yawning, nausea, stomach cramps, diarrhea ("flu-like" symptoms). Treatment: long-term support, methadone, buprenorphine. Belligerence, impulsivity, fever, psychomotor agitation, analgesia, vertical and horizontal nystagmus, tachycardia, homicidality, psychosis, delirium, seizures. Treatment: benzodiazepines, rapid-acting antipsychotic -Mechanism: selective NE reuptake inhibitor→ boost NT NE & may ↑dopamine (from ↑NE levels) in prefrontal cortex; not a controlled stimulant; metabolized by liver (CYP450 2D6) so inhibitors ↑plasma levels
-Use: ADHD; improves attention, concentration, execution, wakefulness, hyperactivity
-Toxicity: sedation, fatigue, ↓appetite (immediate, then goes away). Rare: ↑HR/HTN, orthostatic HoTN; use caution in patients w/ HTN, diabetes, heart disease; reversible Liver Injury
-CI: Tramadol ↑risk of seizures; don't use w/ MAO inhibitors
-Mechanism: boosts NE & DA, blocks reuptake sites; XL best for ADHD; inhibits CYP450 2D6
-Use: major depression, SAD, smoking cessation, ADHD
-Toxicity: peripheral NE effects: dry mouth, constipation, weight loss, anorexia, nausea; DA: insomnia, headache, agitation, anxiety; most side effects are immediate & go away w/ time
-Mechanism: works like clonidine→ CNS postsynaptic α-2A receptor agonist; ↑noradrenergic effects directly; phenobarbitol & phenytoin may ↓plasma levels
-Use: improves attention, concentration, execution, wakefulness, hyperactivity; often used when too activated or oppositional→ tics, emotional outbursts
-Toxicity: -Somnolence, headache, fatigue, upper abdominal pain, sedation, HoTN, dry mouth & constipation
-CI: don't use w/ other sedative drugs, caution w/ drug inducers & inhibitors
-Mechanism: block reuptake of norepinephrine and 5-HT.
-Use: major depression, OCD (clomipramine), peripheral neuropathy, chronic pain, migraine prophylaxis.
-Toxicity: sedation, α1-blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3° TCAs (amitriptyline) have more anticholinergic effects than 2° TCAs (nortriptyline). Can prolong QT interval.
-Tri-C's: Convulsions, Coma, Cardiotoxicity (arrhythmias); also respiratory depression, hyperpyrexia. Confusion and hallucinations in elderly due to anticholinergic side effects (use nortriptyline). Treatment: NaHCO3 to prevent arrhythmia.
Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline (selective MAO-B inhibitor)
-Mechanism: nonselective MAO inhibition increases levels of amine neurotransmitters (norepinephrine, 5-HT, dopamine).
-Use: atypical depression, anxiety.
-Toxicity: hypertensive crisis (most notably with ingestion of tyramine, which is found in many foods such as wine and cheese); CNS stimulation.
-Contraindicated with SSRIs, TCAs, St. John's wort, meperidine, dextromethorphan (to prevent serotonin syndrome).
Furosemide, bumetanide, torsemide
-Mechanism: sulfonamide loop diuretics. Inhibit cotransport system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle. Abolish hypertonicity of medulla, preventing concentration of urine. Stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs. Increase Ca2+ excretion. Loops Lose Ca2+.
-Use: edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia.
-Toxicity: ototoxicity, hypokalemia, dehydration, allergy (sulfa), nephritis (interstitial), gout.
-Mechanism: inhibit NaCl reabsorption in early DCT decreasing diluting capacity of nephron. Decreased Ca2+ excretion.
-Use: hypertension, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis.
-Toxicity: hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy.
Captopril, enalapril, lisinopril, ramipril
-Mechanism: inhibit ACE -> decrease AT II -> decrease GFR by preventing constriction of efferent arterioles. Levels of renin increase as a result of loss of feedback inhibition. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator.
-Use: hypertension, HF, proteinuria, diabetic nephropathy. Prevent unfavorable heart remodeling as a result of chronic hypertension. In diabetic nephropathy, intraglomerular pressure, slowing GBM thickening
-Toxicity: cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), increased Creatinine (decreased GFR), Hyperkalemia, and Hypotension. Avoid in bilateral renal artery stenosis, because ACE inhibitors will further decrease GFR causing renal failure.
Losartan, candesartan, valsartan
-Mechanism: selectively block binding of angiotensin II to AT1 receptor. Effects similar to ACE inhibitors, but ARBs do not increase bradykinin.
-Use: hypertension, HF, proteinuria, or diabetic nephropathy with intolerance to ACE inhibitors (e.g., cough, angioedema).
-Toxicity: hyperkalemia, decreased renal function, hypotension; teratogen.