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138 Cards in this Set
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Mannitol
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Mechanism: Osmotic diuretic, T tubular fluid osmolarity, producing increased urine flow.
Clinical Use: Shock, drug overdose, t intracranial/intraocular pressure. Toxicity: Pulmonary edema, dehydration. Contraindicated inanuria, CHF. |
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Acetazolamide
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Mechanism Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total-body
HCO3 stores. Clinical use: Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness. Toxicity: Hyperchloremic metabolic acidosis, neuropathy, ACIDazolamide causes NH3 toxicity, sulfa allergy |
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Furosemide
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Mechanism: Sulfonamide loop diuretic. Inhibits cotransport
edema), hypertension, system (Nat, K+, 2 Cl-) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla, preventing concentration of urine. increased Ca2+ excretion. Clinical use: Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary hypercalcemia. Toxicity: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout. |
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Ethacrynic acid
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Mechanism: Phenoxyacetic acid derivative (NOT a sulfonamide).
Essentially same action as furosemide. Clinical use: Diuresis in patients allergic to sulfa drugs. Toxicity: Similar to furosemide; can be used in hyperuricemia, acute gout (never used to treat gout). |
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Hydrochlorothiazide
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Mechanism: Thiazide diuretic. Inhibits NaC1 reabsorption in
early distal tubule, reducing diluting capacity of the nephron. Ca2+ excretion. Clinical use: Hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus. Toxicity: Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, and hyperCalcemia. Sulfa allergy. |
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K + sparing diuretics
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Spironolactone, Triamterene, Amiloride, eplerenone
Mechanism: Spironolactone is a competitive aldosterone receptor antagonist in the cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT. Clinical use Hyperaldosteronism, K+ depletion, CHF. Toxicity: Hyperkalemia (can lead to arrhythmias), endocrine effects with aldosterone antagonists (e.g., spironolactone causes gynecomastia, antiandrogen effects). |
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ACE Inhibitors
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Captopril, enalapril, lisinopril.
Mechanism:Inhibit angiotensin-converting enzyme, reducing levels of angiotensin II and preventing inactivation of bradykinin, a potent vasodilator. Renin release is increased due to loss of feedback inhibition. Clinical use: Hypertension, CHF, diabetic renal disease. Toxicity: Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems (fetal renal damage), Rash, Increased renin, Lower angiotensin II. Also hyperkalemia. Avoid with bilateral renal artery stenosis because ACE inhibitors significantly GFR by preventing constriction of efferent arterioles. |
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Losartan
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angiotensin II receptor antagonist.
--It is not an ACE inhibitor and does NOT cause cough. |
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H2 blockers
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Pg. 337
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Proton Pump Inhibitors
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Mechanism: Irreversibly inhibit H+/K+-ATPase in stomach parietal cells.
Clinical use: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome. |
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Bismuth, sucralfate
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Mechanism: Bind to ulcer base, providing physical protection,and allow HCO3 secretion to reestablish pH
gradient in the mucous layer. Clinical use:increased ulcer healing, traveler's diarrhea. NOTES: Triple therapy of H. pylori ulcers — Metronidazole, Amoxicillin (or Tetracycline), Bismuth. Can also use PPI —Please MAke Tummy Better. |
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Misoprostol
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Mechanism: A PGE1 analog. Increased production and secretion of gastric mucous barrier, acid production.
Clinical use: Prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used to induce labor. Toxicity: Diarrhea. Contraindicated in women of childbearing potential (abortifacient). |
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Muscarinic antagonists
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Pirenzepine, propantheline.
Mechanism: Block M1 receptors on ECL cells (decreased histamine secretion) and M3 receptors on parietal cells (decreased H+ secretion). Clinical use: Peptic ulcer (rarely used). Toxicity: Tachycardia, dry mouth, difficulty focusing eyes. |
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Octreotide
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Mechanism: Somatostatin analog
Clinical use: Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors. Toxicity: Nausea, cramps, steatorrhea. |
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Antacid use
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Can affect absorption, bioavailability, or urinary
excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. Overuse can also cause the following problems: 1. Aluminum hydroxide—constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures 2. Magnesium hydroxide—diarrhea, hyporeflexia, hypotension, cardiac arrest 3. Calcium carbonate — hypercalcemia, rebound acid increased All can cause hypokalemia. |
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Infliximab
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Mechanism: A monoclonal antibody to TNF, proinflammatory
cytokine. Clinical use: Crohn's disease, rheumatoid arthritis. Toxicity: Respiratory infection (including reactivation of latent TB), fever, hypotension. |
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Sulfasalazine
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Mechanism: A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.
Clinical use: Ulcerative colitis, Crohn's disease. Toxicity: Malaise, nausea, sulfonamide toxicity, reversible oligospermia. |
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Ondansetron
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Mechanism: 5-HT3 antagonist. Powerful central-acting antiemetic.
Clinical use: Control vomiting postoperatively and in patients so you can undergoing cancer chemotherapy. Toxicity: Headache, constipation. |
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Metoclopramide
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Mechanism: D2 receptor antagonist. "increased resting tone, contractility, LES tone, motility. Does not
influence colon transport time. Clinical use: Diabetic and post-surgery gastroparesis. Toxicity: increased parkinsonian effects. Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction. |
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Insulin:
Lispro (rapid-acting) Aspart (rapid-acting) Regular (rapid-acting) NPH (intermediate) Glargine (long-acting) Detemir (long-acting) |
Action: Bind insulin receptor (tyrosine kinase activity).
Liver: increase glucose stored as glycogen. Muscle: increase glycogen and protein synthesis, K+ uptake. Fat: aids TG storage. Clinical Use: Type 1 DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stress-induced hyperglycemia. Toxicities: Hypoglycemia, hypersensitivity reaction (very rare). |
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Sulfonylureas:
First generation: Tolbutamide Chlorpropamide Second generation: Glyburide Glimepiride Glipizide |
Action: Close K+ channel in
(3-cell membrane, so cell depolarizes --> triggering of insulin. release via increase Ca2+ influx. Clinical Use: Stimulate release of endogenous insulin in type 2 DM. Require some islet function, so useless in type 1 DM. Toxicities: First generation: disulfiram-like effects. Second generation: hypoglycemia. |
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Biguanides:
Metformin |
Action: Exact mechanism is
unknown. DECREASES gluconeogenesis, incraeses glycolysis, increases peripheral glucose uptake (insulin sensitivity). Clinical use: Oral. Can be used in patients without islet function. Toxicities: Most grave adverse effect is lactic acidosis (contraindicated in renal failure) |
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Glitazones/
thiazolidinediones: Pioglitazone Rosiglitazone |
Action: Increased insulin sensitivity in
peripheral tissue. Binds to PPAR -gamma nuclear transcription regulator. Clinical use: Used as monotherapy in type 2 DM or combined with other agents. Toxicities: Weight gain, edema, hepatotoxicity, CV toxicity. |
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a-glucosidase inhibitors:
Acarbose Miglitol |
Action: Inhibit intestinal brushborder
a-glucosidases. Delayed sugar hydrolysis and glucose absorption lead to .1. postprandial hyperglycemia. Clinical Use: Used as monotherapy in type 2 DM or in combination with above agents. Toxicity: GI disturbances |
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Mimetics:
Pramlintide |
Action: Decrease glucagon
Clinical use: Type II DM Toxicity: Hypoglycemia, nausea, diarrhea |
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GLP-1 analogs:
Exenatide |
Action: Increase insulin, decrease glucagon release.
Clinical use: Type II DM Toxicity: Nausea, vomiting, and pancreatitis. |
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Propylthiouracil, methimazole
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Mechanism: Inhibit organification of iodide and coupling of thyroid hormone synthesis.
Propylthiouracil also decreases peripheral conversion of T4 to T3. Clinical use: Hyperthyroidism. Toxicity: Skin rash, agranulocytosis (rare), aplastic anemia. Methimazole is a possible teratogen. |
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Levothyroxine, triiodothyronine
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Mechanism: Thyroxine replacement.
Clinical use: Hypothyroidism, myxedema. Toxicity: Tachycardia, heat intolerance, tremors, arrhythmias. |
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Hypothalamic/pituitary drugs
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Drug:
GH use: GH deficiency, Turner syndrome Somatostatin(octreotide) Use: Acromegaly, carcinoid, gastrinoma, glucagonoma Oxytocin use: stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage ADH (desmopressin): use: Pituitary (central, NOT nephrogenic) DI |
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Demeclocycline
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Mechanism: ADH antagonist (member of the tetracycline family).
Clinical use: SIADH. Toxicity: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth. |
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Glucocorticoids
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Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone.
Mechanism: the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2. Clinical use: Addison's disease, inflammation, immune suppression, asthma. Toxicity: Iatrogenic Cushing's syndrome—buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when drug stopped after chronic use. |
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Bethanechol
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Direct Cholinergic agonists
Clinical use: Postoperative and neurogenic ileus and urinary retention Actions: Activates Bowel and Bladder smooth muscle; resistant to AChE. Beth Anne, call (bethanechol) me if you want to activate your Bowels and Bladder. |
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Carbachol
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Direct Cholinergic agonists
Clinical use: Glaucoma, pupillary contraction, and relief of intraocular pressure Action: CARBon copy of acetylcholine |
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Pilocarpine
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Direct Cholinergic Agonists
Clinical use: Potent stimulator of sweat, tears, saliva Action: Contracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle); resistant to AChE. PILE on the sweat and tears. |
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Methacholine
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Direct Cholinergic Agonists:
Clinical use: Challenge test for diagnosis of asthma Actions: Stimulates muscarinic receptors in airway when inhaled |
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Neostigmine
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Indirect cholinergic agonists (anti-cholinesterase)
Clinical app: Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative). NOTES: increases endogenous ACh; no CNS penetration. NEO CNS = NO CNS penetration. |
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Pyridostigmine
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Indirect Cholinergic agonists (anti-cholinesterase)
Clinical app: Myasthenia gravis (long acting); does not penetrate CNS Action: Increase endogenous ACh; Increase strength. |
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Edrophonium
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Indirect Cholinergic Agonists
Clinical app: Diagnosis of myasthenia gravis (extremely short acting) Notes: Increases endogenous ACh. |
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Physostigmine
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Indirect Cholinergic Agonists
Clinical App: Glaucoma (crosses blood-brain barrier CNS) and atropine overdose Actions: Increased endogenous ACh. PHYS is for EYES. |
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Echothiophate
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Indirect Cholinergic Agonists
Clinical App: Glaucoma Action: Increase endogenous ACH |
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Cholinesterase
inhibitor poisoning |
Often due to organophosphates, such as parathion, that irreversibly inhibit AchE. Causes Diarrhea,
Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, and Salivation. Antidote—atropine + pralidoxime (regenerates active AchE). USE: Organophosphates are components of insecticides; poisoning usually seen in farmers. |
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Atropine,
homatropine, tropicamide |
Class: Muscarinic ANtagonists
Organ system: eye Application: Produce mydriasis and cycloplegia |
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Benztropine
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Class: Muscarinic ANtagonists
Organ: CNS Application: Parkinson's disease |
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Scopalamine
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Class: Muscarinic ANtagonists
Organ: CNS Application: Motion sickness |
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Ipratropium
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Class: Muscarinic ANtagonists
Organ: Respiratory Use: Asthma, COPD (I pray I can breathe soon!) |
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Oxybutynin, Glycopyrrolate
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Class: Muscarinic Antagonists
Organ: Genitourinary Use: Reduce urgency in mild cystitis and reduce bladder spasms. |
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Methscopolamine, pirenzepine, propantheline
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Class: Muscarinist ANtagonists
Organ: Gastrointestinal Application: Peptic ulcer treatment |
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Hexamethonium
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Nicotinic antagonist.
Clinical use: Ganglionic blocker. Used in experimental models to prevent vagal reflex responses to changes in blood pressure—e.g., prevents reflex bradycardia caused by NE. Toxicity: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction. |
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Isoproterenol
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Class: Direct Sympathomimetics
Mechanism: Beta1=Beta2 (isolated to beta) Applications: AV block (rare) |
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Dopamine
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Class: Direct sympathomimetics
Mechanism: D1=D2>beta>alpha, inotropic and chronotropic Applications: Heart failure, cardiac stress testing |
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Dobutamine
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Class: Direct sympathomimetics
Mechanism: Beta1>Beta2, inotropic but not chronotropic Applications: Heart failure, cardiac stress testing |
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Phenylephrine
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Class: Direct sympathomimetics
Mechanism: alpha 1 > alpha 2 Applications: Pupillary dilation, vasoconstriction, nasal decongestion. |
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Metaproterenol, Albulterol, salmeterol, terbutaline
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Class: Direct sympathomimetics
Mechanism: Selective bete2-agonists (beta2>beta 1) Application: MAST--Metaproterenol and Albuterol for acute asthma; salmeterol for long-term treatment; Terbutaline to reduce premature uterine contractions. |
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Ritodrine
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Class: Direct sympathomimetics
Mechanism: Beta2 Applications: Reduces premature uterine contractions |
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Amphetamine
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Class: Indirect sympathomimetics
Mechanism: Indirect general agonist, releases stored catecholamines Applications: Narcolepsy, obesity, Attention deficit disorder |
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Ephedrine
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Class: INdirect sympathomimetics
Mechanism: Indirect general agonist, releases stored catecholamines Application: Nasal decongestion, urinary incontinence, hypotension |
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Cocaine
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Class: INdirect sympathomimetics
Mechanism: Indirect general agonist, uptake inhibitor Use: Causes vasoconstriction and local anesthesia. |
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Clonidine, alpha-methyldopa
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Class: Sympathoplegics
Mechanism: Centrally acting alpha-2 agonists, decrease central adrenergic outflow Use: Hypertension, especially with renal disease (no decrease in blood flow to kidney) NOTES: Clonidine--orthostatic hypotension. |
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Phenoxybenzamine (irreversible) and phentolamine (reversible)
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Class: NON-selective alpha blockers
Applications: Pheochromocytoma (use phenoxybenzamine before removing tumor, since high levels of released catecholamines will not be able to overcome blockage) Toxicity: Orthostatic hypotension, reflex tachycardia |
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Prazosin, terazosin, doxazosin
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Class: alpha1 selective antagonist (-zosin ending)
Application: HTN, urinary retention in BPH Toxicity: 1st-dose orthostatic hypotension, dizziness, headache. |
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Mirtazapine
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Class: Alpha2 selective blockers
Application: Depression Toxicity: Sedation, increased serum cholesterol, increased appetite. |
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Antidote
Acetaminophen |
N-acetylcysteine
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Antidote
Salicylates |
NaHCO3 (alkalinize urine),
dialysis |
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Antidote
Amphetamines (basic) |
NH4CL (acidify urine)
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Antidote
Acetylcholinesterase inhibitors, organophosphates |
Atropine, pralidoxime
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Antidote
Antimuscarinic, anticholinergic agents |
Physostigmine salicylate
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Antidote
beta-blockers |
Glucagon
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Antidote
Digitalis |
Stop dig, normalize K+,
lidocaine, anti-dig Fab fragments, Mg2+ |
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Antidote
Iron |
Deferoxamine
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Antidote
Lead |
CaEDTA, dimercaprol,
succimer, penicillamine |
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Antidote
Mercury, arsenic, gold |
Dimercaprol (BAL),
succimer |
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Antidote
Cyanide |
Nitrite, hydroxocobalamin,
thiosulfate |
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Antidote
Methemoglobin |
Methylene blue, vitamin C
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Antidote
Carbon monoxide |
100% 02, hyperbaric 02
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Antidote
Methanol, ethylene glycol (antifreeze) |
Ethanol, dialysis, fomepizole
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Antidote
Opioids |
Naloxone/naltrexone
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Antidote
Benzodiazepines |
Flumazenil
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Antidote
Heparin |
Protamine
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Antidote
Warfarin |
Vitamin K, fresh frozen
plasma |
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Antidote
tPA, streptokinase |
Aminocaproic acid
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Antidote
Theophylline |
beta-blocker
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Cyclosporine
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Mechanism: Binds to cyclophilins. Complex blocks the differentiation and activation of T cells
by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor. Clinical use: Suppresses organ rejection after transplantation; selected autoimmune disorders. Toxicity: Predisposes patients to viral infections and lymphoma; nephrotoxic (preventable with mannitol diuresis). |
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Tacrolimus (FK506)
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Mechanism: Similar to cyclosporine; binds to FK-binding protein, inhibiting secretion of IL-2 and
other cytokines. Clinical use: Potent immunosuppressive used in organ transplant recipients. Toxicity: Significant—nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia. |
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Sirolimus (rapamycin)
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Mechanism: Binds to mTOR. Inhibits T-cell proliferation in response to IL-2.
Clinical use: Immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids. Toxicity: Hyperlipidemia, thrombocytopenia, leukopenia. |
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Daclizumab
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Mechanism Monoclonal antibody with high affinity for the IL-2 receptor on activated T cells.
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Azathioprine
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Mechanism: Antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes.
Clinical use: Kidney transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia). Toxicity: Bone marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase; thus, toxic effects may be increased by allopurinol. |
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Muromonab-CD3 (OKT3)
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Mechanism: Monoclonal antibody that binds to CD3 (epsilon chain) on the surface of T cells. Blocks cellular interaction with CD3 protein responsible for T-cell signal transduction.
Clinical use: Immunosuppression after kidney transplantation. Toxicity: Cytokine release syndrome, hypersensitivity reaction. |
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Penicillin
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Pen G--IV Pen V (Oral) Prototype beta lactam
Mechanism 1. Bind penicillin-binding proteins 2. Block transpeptidase cross-linking of cell wall 3. Activate autolytic enzymes Clinical use Mostly used for gram-positive organisms (S. pneumoniae, S.pyogenes, Actinomyces) and syphilis. Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes. Not penicillinase resistant. Toxicity Hypersensitivity reactions, hemolytic anemia. |
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Methicillin, nafcillin, dicloxacillin (penicillinase-resistant penicillins)
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Mechanism: Same as penicillin. Narrow spectrum; penicillinase
resistant because of bulkier R group. Clinical use: S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site). Toxicity Hypersensitivity reactions; methicillin— interstitial nephritis. |
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Ampicillin, amoxicillin (aminopenicillins)
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Same as penicillin. Wider spectrum; penicillinase
sensitive. Also combine with clavulanic acid to enhance spectrum. AmOxicillin has greater Oral bioavailability than ampicillin. Extended-spectrum penicillin—certain gram-positive bacteria and gram-negative rods (Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, enterococci). Hypersensitivity reactions; ampicillin rash; pseudomembranous colitis. |
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Ticarcillin, carbenicillin, piperacillin (antipseudomonals)
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Mechanism Same as penicillin. Extended spectrum.
Clinical use Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with clavulanic acid. Toxicity Hypersensitivity reactions. |
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3-lactamase inhibitors
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Include clavulanic acid, sulbactam, tazobactam. CAST.
Often added to penicillin antibiotics to protect the antibiotic from destruction by 13-lactamase (penicillinase). |
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Cephalosporins
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Pg. 186
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Aztreonam
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Mechanism A monobactam resistant to P-lactamases. Inhibits cell wall synthesis (binds to PBP3).
Synergistic with aminoglycosides. No cross-allergenicity with penicillins. Clinical use Gram-negative rods only—No activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides. Toxicity Usually nontoxic; occasional GI upset. No cross-sensitivity with penicillins or cephalosporins. |
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Imipenem/cilastatin, meropenem
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Imipenem is a broad-spectrum, P-lactamase-resistant
carbapenem. Always administered with cilastatin (inhibitor of renal dihydropeptidase I) to inactivation of drug in renal tubules. Gram-positive cocci, gram-negative rods, and anaerobes. Wide spectrum, but the significant side effects limit use to life-threatening infections, or after other drugs have failed. Meropenem, however, has a reduced risk of seizures and is stable to dihydropeptidase I. GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels. |
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Vancomycin
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Mechanism Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall
precursors. Bactericidal. Clinical use Gram positive only—serious, multidrug-resistant organisms, including S. aureus, enterococci and Clostridium difficile (pseudomembranous colitis). Toxicity Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing—"red man syndrome" (can largely prevent by pretreatment with antihistamines and slow infusion rate). Well tolerated in general—does NOT have many problems. Resistance Occurs with amino acid change of D-ala D-ala to D-ala D-lac. |
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Aminoglycosides
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Bactericidal; inhibit formation of initiation complex
and cause misreading of mRNA. Require 02 for uptake; therefore ineffective against anaerobes. Severe gram-negative rod infections. Synergistic with 13-lactam antibiotics. Neomycin for bowel surgery. Nephrotoxicity (especially when used with cephalosporins), Ototoxicity (especially when used with loop diuretics). Teratogen. Transferase enzymes that inactivate the drug by acetylation, phosphorylation, or adenylation. Aminoglycosides |
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Tetracyclines
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Pg. 188
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Macrolides
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Erythromycin, azithromycin, clarithromycin.
Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic. Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), URIs, STDs, gram-positive cocci (streptococcal infections in patients allergic to penicillin), and Neisseria. Prolonged QT interval (especially erythromycin), GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes. Increases serum concentration of theophyllines, oral anticoagulants. Methylation of 23S rRNA binding site |
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Chloramphenicol
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Mechanism
Clinical use Toxicity Resistance Inhibits 50S peptidyltransferase activity. Bacteriostatic. Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae). Conservative use owing to toxicities but often still used in developing countries due to low cost. Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase). Plasmid-encoded acetyltransferase that inactivates drug. |
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Clindamycin
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Mechanism
Clinical use Toxicity Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic. Anaerobic infections (e.g., Bacteroides fragilis, Clostridium perfringens) in aspiration pneumonia or lung abscesses. Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea. |
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Sulfonamides
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Pg. 189
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Trimethoprim
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Mechanism Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
Clinical use Used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), causing sequential block of folate synthesis. Combination used for recurrent UTIs, Shigella, Salmonella, Pneumocystis jiroveci pneumonia. Toxicity Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid [leucovorin rescue].) |
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Sulfa drug allergies
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Patients who do not tolerate sulfa drugs should not be given sulfonamides or other sulfa
drugs, such as sulfasalazine, sulfonylureas, thiazide diuretics, acetazolamide, furosemide, celecoxib, or probenecid. |
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Fluoroquinolones
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Mechanism Inhibit DNA gyrase (topoisomerase II). Bactericidal.
Must not be taken with antacids. attachments to your Clinical use Gram-negative rods of urinary and GI tracts . (including Pseudomonas), Neisseria, some grampositive organisms. Toxicity GI upset, superinfections, skin rashes, headache, dizziness. Contraindicated in pregnant women and in children because animal studies show damage to cartilage. Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids. Resistance Chromosome-encoded mutation in DNA gyrase. |
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Metronidazole
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Mechanism Forms free radical toxic metabolites in the bacterial
cell that damage DNA. Bactericidal, antiprotozoal. Clinical use Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, Clostridium). Used with bismuth and the diaphragm. amoxicillin (or tetracycline) for "triple therapy" against H. Pylori. Toxicity Disulfiram-like reaction with alcohol; headache, metallic taste. |
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Polymyxins
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Mechanism Bind to cell membranes of bacteria and disrupt
their osmotic properties. Polymyxins are cationic, basic proteins that act like detergents. Clinical use Resistant gram-negative infections. Toxicity Neurotoxicity, acute renal tubular necrosis. |
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Antimycobacterial drugs
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Bacterium Prophylaxis Treatment
M. tuberculosis Isoniazid Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE for treatment) M. avium— Azithromycin Azithromycin, rifampin, intracellulare ethambutol, streptomycin M. leprae N/A Dapsone, rifampin, clofazimine |
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Anti-TB drugs
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Streptomycin, Pyrazinamide, Isoniazid (INH),
Rifampin, Ethambutol. Cycloserine (2nd-line therapy). Important side effect of ethambutol is optic neuropathy (red-green color blindness). For other drugs, hepatotoxicity. NOTES: Pyrazinamide— effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found. Ethambutol—si, carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase. |
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Isoniazid
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Decreases synthesis of mycolic acids. Bacteria catalaseperoxidase
needed to convert INH to active metabolite. Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB. Neurotoxicity, hepatotoxicity, lupus. Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus. |
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Rifampin
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Inhibits DNA-dependent RNA polymerase.
Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B. Minor hepatotoxicity and drug interactions ( r P-450); orange body fluids (nonhazardous side effect). |
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Amphotericin B
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Binds ergosterol (unique to fungi); forms membrane
pores that allow leakage of electrolytes. Serious, systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier. Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (f "a mphoterrible"). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity. |
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Nystatin
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Mechanism Same as amphotericin B. Topical form because too toxic for systemic use.
Clinical use "Swish and swallow" for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis. |
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Azoles
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Mechanism Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts
lanosterol to ergosterol. Clinical use Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients (because it can cross blood-brain barrier) and candidal infections of all types. Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans; hypercortisolism. Clotrimazole and miconazole for topical fungal infections. Toxicity Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills. |
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Flucytosine
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Mechanism Inhibits DNA synthesis by conversion to 5-fluorouracil.
Clinical use Used in systemic fungal infections (e.g., Candida, Cryptococcus) in combination with amphotericin B. Toxicity Nausea, vomiting, diarrhea, bone marrow suppression. |
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Caspofungin
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Mechanism Inhibits cell wall synthesis by inhibiting synthesis of 13-glucan.
Clinical use Invasive aspergillosis. Toxicity GI upset, flushing. |
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Terbinafine
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Mechanism Inhibits the fungal enzyme squalene epoxidase.
Clinical use Used to treat dermatophytoses (especially onychomycosis —fungal infection of finger or toe nails). |
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Griseofulvin
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Mechanism Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing
tissues (e.g., nails). Clinical use Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm). Toxicity Teratogenic, carcinogenic, confusion, headaches, T P-450 and warfarin metabolism. |
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Pyrimethamine
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Selectively inhibits plasmodial dihydrofolate reductase (best for P. falciparum).
Drug of choice for toxoplasmosis when combined with sulfadiazine. |
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Nifurtimox
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Forms intracellular oxygen radicals, which are toxic to the organism.
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Sodium stibogluconate
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Inhibits glycolysis at PFK reaction.
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Chloroquine
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Blocks plasmodium heme polymerase, leading to accumulation of toxic
hemoglobin breakdown products that destroy the organism. |
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Quinine
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For chloroquine-resistant species when used in combination with
pyrimethamine/sulfonamide. |
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Mebendazole
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Inhibits glucose uptake and microtubule synthesis.
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Pyrantel pamoate
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Stimulates nicotinic receptors at neuromuscular junctions. Contraction occurs,
followed by depolarization-induced paralysis. No effect on tapeworms or flukes. |
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Ivermectin
|
Intensifies GABA-mediated neurotransmission and causes immobilization. Does
not cross the blood-brain barrier; therefore, no effect on humans. |
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Praziquantel
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Increases membrane permeability to calcium, causing contraction and paralysis
of tapeworms and flukes. |
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Amantadine
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Blocks viral penetration/uncoating (M2 protein).
Also causes the release of dopamine from intact nerve terminals. Prophylaxis and treatment for influenza A only; Parkinson's disease. Ataxia, dizziness, slurred speech. Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so not used. |
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Zanamivir, oseltamivir
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Mechanism Inhibit influenza neuraminidase, decreasing the release of progeny virus.
Clinical use Both influenza A and B. |
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Ribavirin
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Mechanism Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.
Clinical use RSV, chronic hepatitis C. Toxicity Hemolytic anemia. Severe teratogen. |
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Acyclovir
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Monophosphorylated by HSVNZV thymidine kinase. Guanosine analog. Triphosphate
formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. HSV, VZV, EBV. Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised patients. For herpes zoster, use a related agent, famciclovir. No effect on latent forms of HSV and VZV. Generally well tolerated. Lack of viral thymidine kinase. |
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Ganciclovir
|
5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase.
Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. CMV, especially in immunocompromised patients. Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir. Mutated CMV DNA polymerase or lack of viral kinase. |
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Foscarnet
|
Mechanism Viral DNA polymerase inhibitor that binds to the
pyrophosphate-binding site of the enzyme. Does analog. not require activation by viral kinase. Clinical use CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSV. Toxicity Nephrotoxicity. Mechanism of Mutated DNA polymerase. resistance |
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Saquinavir
Ritonavir Indinavir Nelfinavir Amprenavir |
Assembly of virions depends on HIV-1 protease
(pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. All protease inhibitors end in -navir. NAVIR (never) TEASE a proTEASE. Toxicity: Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy, thrombocytopenia (indinavir). |
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Zidovudine (ZDV,
formerly AZT) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) |
Competitively inhibit nucleotide binding
to reverse transcriptase and terminate the DNA chain (lack a 3'-OH group). Must be phosphorylated by thymidine kinase to be active. ZDV is used for general prophylaxis and during pregnancy to reduce risk of fetal transmission. Have you dined (vudine) with my nuclear (nucleosides) family? Toxicity: Bone marrow suppression (can be reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (nonnucleosides), megaloblastic anemia (ZDV). |
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Nevirapine
Efavirenz Declaviridine |
Bind to reverse transcriptase at site different from
NRTIs. Do not require phosphorylation to be active or compete with nucleotides. Never Ever Deliver nucleosides. |
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Enfuvirtide
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Bind viral gp41 subunit; inhibit conformational
change required for fusion with CD4 cells, blocking entry and replication. Used in patients with persistent viral replication despite antiretroviral therapy. Toxicity: Hypersensitivity reactions, reactions at subcutaneous injection site, T risk of bacterial pneumonia. |
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Antibiotics to avoid
in pregnancy |
Aminoglycosides—ototoxicity.
Fluoroquinolones— cartilage damage. Erythromycin—acute cholestatic heptatitis in mom (and clarithromycin—embryotoxic). Metronidazole—mutagenesis. Tetracyclines—discolored teeth, inhibition of bone growth. Ribavirin (antiviral) — teratogenic. Griseofulvin (antifungal) — teratogenic. Chloramphenicol—"gray baby." |
