Pharmacology Nursing final exam

What are the major functions of the α1 receptor? - answer-Increase vascular smooth muscle
contraction, increase pupillary dilator muscle contraction (mydriasis), increase intestinal and bladder
sphincter muscle contraction

What are the major functions of the α2 receptor? - answer-Decrease sympathetic outflow, decrease
insulin release, decrease lipolysis, increase platelet aggregation, decrease aqueous humor production

What are the major functions of the β1 receptor? - answer-Increase heart rate, increase contractility,
increase renin release, increase lipolysis

What are the major functions of the β2 receptor? - answer-Vasodilation, bronchodilation, increase
lipolysis, increase insulin release, decrease uterine tone (tocolysis), ciliary muscle relaxation, increase
aqueous humor production

What are the major functions of the M1 receptor? - answer-CNS, enteric nervous system

What are the major functions of the M2 receptor? - answer-Decrease heart rate and contractility of atria

What are the major functions of the M3 receptor? - answer-Increase exocrine gland secretions (e.g.,
lacrimal, salivary, gastric acid), increase gut peristalsis, increase bladder contraction, increase
bronchoconstriction, pupillary sphincter muscle contraction (miosis), ciliary muscle contraction
(accommodation)

What are the major functions of the D1 receptor? - answer-Relaxes renal vascular smooth muscle

What are the major functions of the D2 receptor? - answer-Modulates transmitter release, especially in
the brain
What are the major functions of the H1 receptor? - answer-Increase nasal and bronchial mucus
production, increase vascular permeability, contraction of bronchioles, pruritis, pain

What are the major functions of the H2 receptor? - answer-Increase gastric acid secretion

What are the major functions of the V1 receptor? - answer-Increase vascular smooth muscle contraction

What are the major functions of the V2 receptor? - answer-Increase H2O permeability and reabsorption
in collecting tubules of kidney (V2 is found in the "2" kidneys)

What receptors are associate with Gq? - answer-H1, α1, V1, M1, and M3

What receptors are associated with Gs? - answer-H2, B1, B2, V2, D1

What receptors are associated with Gi? - answer-M2, α2, D2

Bethanechol - answer--Direct cholinergic agonist

-Activates bowel and bladder smooth muscle

-Used in postoperative and neurogenic ileus

-Resistant to AChE

Carbachol - answer--Direct cholinergic agonist

-Carbon copy of acetylcholine

-Constricts pupils and relieves intraocular pressure in glaucoma

Methacholine - answer--Direct cholinergic agonist

-Stimulates muscarinic receptors in airways when inhaled

-Used as a challenge test for diagnosis of asthma

Pilocarpine - answer--Direct cholinergic agonist

-Contracts ciliary muscle of eye (open angle glaucoma), contracts pupillary sphincter (closed angle
glaucoma)

-Potent stimulator of sweat, tears and saliva

-AChE resistant

Donepezil - answer--Anticholinesterse - increases ACh

-Alzheimer disease

Galantamine - answer--Anticholinesterse - increases ACh

-Alzheimer disease

Rivastigmine - answer--Anticholinesterse - increases ACh

-Alzheimer disease

Edrophonium - answer--Anticholinesterse - increases ACh

-Historically used to diagnose myasthenia gravis (MG is now diagnosed by anti-AChR Ab test.

Neostigmine - answer--Anticholinesterse - increases ACh

-Used in postoperative and neurogenic ileus and urinary retention, myasthenia gravis, and postoperative
reversal of neuromuscular junction blockade

Physostigmine - answer--Anticholinesterse - increases ACh

-Used in anticholinergic toxicity

-Crosses the blood-brain barrier (CNS)

Pyridostigmine - answer--Anticholinesterse - increases ACh

-Increases muscle strength

-Used in myasthenia gravis (long acting)

-Does not penetrate CNS

Atropine - answer--Muscarinic antagonist

-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

Benztropine - answer--Muscarinic antagonist

-Works in CNS

-Used in Parkinson disease and acute dystonia

Glycopyrrolate - answer--Muscarinic antagonist

-Parental use: preoperative use to reduce airway secretions

-Oral use: drooling, peptic ulcer

Hyoscyamine - answer--Muscarinic antagonist

-Antispasmodics for IBS

Dicyclomide - answer--Muscarinic antagonist

-Antispasmodics for IBS

Ipratropium - answer--Muscarinic antagonist

-Used in COPD and asthma

Tiotropium - answer--Muscarinic antagonist

-Used in COPD and asthma

Oxybutynin - answer--Muscarinic antagonist

-Reduced bladder spasms and urge urinary incontinence

Solifenacin - answer--Muscarinic antagonist

-Reduced bladder spasms and urge urinary incontinence

Tolterodine - answer--Muscarinic antagonist

-Reduced bladder spasms and urge urinary incontinence

Scopalamine - answer--Muscarinic antagonist

-Motion sickness

Tetrodotoxin - answer--Poisoning can result from ingestion of poorly prepared puffer fish (exotic sushi)

-Highly potent toxin that binds fast voltage-gated Na+ channels in cardiac and nerve tissue, preventing
depolarization - blocks action potential without changing resting potential (same mechanism as
Lidocaine)

-Causes nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes.

-Treatment is primarily supportive.

Ciguatoxin - answer--Consumption of reef fish (e.g. barracuda, snapper, eel...)

-Causes ciguatera fish poisoning.

-Opens Na+ channels causing depolarization. Symptoms easily confused with cholinergic poisoning.

-Temperature-related dysesthesia (e.g., "cold feels hot; hot feels cold") is regarded as a specific finding
of ciguatera.

-Treatment is primarily supportive.

Scombroid poisoning - answer--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).

Albuterol - answer--β2 > β1 direct agonist

-Acute asthma

Salmterol - answer--β2 > β1 direct agonist

-Long term asthma or COPD control

Dobutamine - answer--β1 > β2, α direct agonist

-Uses: heart failure (HF) (inotropic > chronotropic), cardiac stress testing.

Dopamine - answer--D1 = D2 > β > α direct agonist

-Uses: unstable bradycardia, HF, shock; inotropic and chronotropic α effects predominate at high doses.

Epinephrine - answer--β > α direct agonist

-Uses: anaphylaxis, asthma, open-angle glaucoma;

α effects predominate at high doses. Significantly stronger effect at β2-receptor than norepinephrine.

Isoprterenol - answer--β1 = β2 direct agonist

-Uses: electrophysiologic evaluation of tachyarrhythmias. Can worsen ischemia

Norepinephrine - answer--α1 > α2 > β1 direct agonist

-Hypotension (butrenal perfusion). Significantly weaker effect at β2-receptor than epinephrine.

Phenylephrine - answer--α1 > α2 direct agonist

-Uses: hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)

Amphetamine - answer--Indirect general sympathetic agonist

-reuptake inhibitor; also releases stored catecholamines

-Narcolepsy, obesity, ADHD.

Cocaine - answer--Indirect general sympathetic agonist

-Reuptake inhibitor

-Causes vasoconstriction and local anesthesia.

-Never give β-blockers if cocaine intoxication is

suspected (can lead to unopposed α1 activation and extreme hypertension).

Ephedrine - answer--Indirect general sympathetic agonist

-Releases stored catecholamines

-Nasal decongestion, urinary incontinence, hypotension.

Norepinephrine vs. isoproterenol - answer--Norepinephrine increases systolic and diastolic pressures as

a result of α1-mediated vasoconstriction causing increased in mean arterial pressure and reflex
bradycardia. -However, isoproterenol (no longer commonly used) has little α effect but causes β2-
mediated vasodilation, resulting in decreased mean arterial pressure and increased heart rate through
β1 and reflex activity.

Clonidine - answer--α2-agonist

-Uses: hypertensive urgency (limited situations); does not decrease renal blood flow; ADHD, Tourette
syndrome

-Toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis

α-methyldopa - answer--α2-agonist
-Used for hypertension in pregnancy

-Toxicity: Direct Coombs ⊕ hemolysis, SLE-like syndrome

Phenoxybenzamine - answer--Nonselective α-blocker

-Irreversible

-Used preoperatively for pheochromocytoma to prevent catecholamine (hypertensive) crisis

-Toxicity: orthostatic hypotension, reflex tachycardia

Phentolamine - answer--Nonselective α-blocker

-Give to patients on MAO inhibitors who eat tyramine containing foods

-Toxicity: orthostatic hypotension, reflex tachycardia

Prazosin - answer--Selective α1-blocker

-Uses: urinary symptoms of BPH; PSTD

-Hypertension

-Toxicity: 1st-dose orthostatic hypotension, dizziness, headache

Terazosin - answer--Selective α1-blocker

-Uses: urinary symptoms of BPH;

-Hypertension

-Toxicity: 1st-dose orthostatic hypotension, dizziness, headache

Doxazosin - answer--Selective α1-blocker

-Uses: urinary symptoms of BPH;

-Hypertension

-Toxicity: 1st-dose orthostatic hypotension, dizziness, headache

Tamsulosin - answer--Selective α1-blocker

-Uses: urinary symptoms of BPH;

-Toxicity: 1st-dose orthostatic hypotension, dizziness, headache

Mirtazapine - answer--Selective α2-blocker

-Used in depression

-Toxicity: sedation, increased serum cholesterol, increased appetite

α-blockade of epinephrine vs. phenylephrine - answer-Shown in the picture are the effects of an α-
blocker (e.g., phentolamine) on blood pressure responses to epinephrine and phenylephrine. The
epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the α
response) to a net decrease (the β2 response). The response to phenylephrine is suppressed but not
reversed because phenylephrine is a "pure" α-agonist without β action.

Effects of β-blockers - answer--Angina pectoris—decrease heart rate and contractility, resulting in

decrease O2 consumption

-MI—β-blockers (metoprolol, carvedilol, and bisoprolol) mortality

-SVT (metoprolol, esmolol)—decrease AV conduction velocity (class II antiarrhythmic)

-Hypertension—decrease cardiac output, decrease renin secretion (due to β1-receptor blockade on JGA
cells)

-HF—decrease mortality in chronic HF

-Glaucoma (timolol)—decrease secretion of aqueous humor

Nonselective β-blockers - answer--Nadolol, pindolol (partial agonist), propranolol, timolol

-Mostly go from N to Z

β1-selective antagonist - answer--acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol

-Mostly go from A to M

Nonselective α- and β-antagonists - answer--Carvedilol, labetalol

Nebevolol - answer--Combines cardiac-selective β1-adrenergic blockade with stimulation of β3-

receptors, which activate nitric oxide synthase in the vasculature
Toxicity of β-blockers - answer--Impotence, cardiovascular adverse effects (bradycardia, AV block, HF),
CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthma/COPD
exacerbations

-Avoid in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity

-Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not
contraindicated

Acetaminophen toxicity antidote - answer-N-acetylcysteine (replenishes glutathione)

AChE inhibitor/organophosphate toxicity antidote - answer-Atropine > pralidoxime

Amphetamines toxicity antidote - answer-NH4Cl (acidify urine)

Antimuscarinic, anticholinergic agents toxicity antidote - answer-Physostigmine salicylate, control

hyperthermia

Benzodiasepines toxicity antidote - answer-Flumazenil

β-blocker toxicity antidote - answer-Glucagon

Carbon monoxide toxicity antidote - answer-100% O2, hyperbaric O2 Penicillamine

Cyanide toxicity antidote - answer-Nitrite + thiosulfate, hydroxocobalamin

Digitalis toxicity antidote - answer-Anti-dig Fab fragments

Heparine toxicity antidote - answer-Protamine sulfate

Iron toxicity antidote - answer-Deferoxamine, deferasirox

Lead toxicity antidote - answer-EDTA, dimercaprol, succimer, penicillamine

Mercury, arsenic, gold toxicity antidote - answer-Dimercaprol (BAL), succimer

Copper, arsenic, gold toxicity antidote - answer-Penicillamine

Methanol, ethylene glycol (antifreeze) toxicity antidote - answer-Fomepizole > ethanol, dialysis

Methemoglobin toxicity antidote - answer-Methylene blue, vitamin C

Opioids toxicity antidote - answer-Naloxone, naltrexone

Salicylates toxicity antidote - answer-NaHCO3 (alkalinize urine), dialysis

TCAs toxicity antidote - answer-NaHCO3 (plasma alkalinization)

tPA, streptokinase, urokinase toxicity antidote - answer-Aminocaproic acid

Warfarin toxicity antidote - answer-Vitamin K (delayed effect), fresh frozen plasma (immediate)

Drugs that cause coronary vasospasm - answer-Cocaine, sumatriptan, ergot alkaloids

Drugs that cause cutaneous flushing - answer-Vancomycin, Adenosine, Niacin, Ca2+ channel blockers
(VANC)

Drugs that cause dilated cardiomyopathy - answer-Anthracyclines (e.g., doxorubicin, daunorubicin);

prevent with dexrazoxane
Drugs that cause Torsades de pointes - answer-Class III (e.g., sotalol) and class IA (e.g., quinidine)
antiarrhythmics, macrolide antibiotics, antipsychotics, TCAs

Drugs that cause adrenocortical insufficiency - answer-HPA suppression 2° to glucocorticoid withdrawal

Drugs that cause hot flashes - answer-Tamoxifen, clomiphene

Drugs that cause hyperglycemia - answer-Tacrolimus, Protease inhibitors, Niacin, HCTZ,

Corticosteroids

Drugs that cause hypothyroidism - answer-Lithium, amiodarone, sulfonamides

Drugs that cause acute cholestatic hepatitis, jaundice - answer-Erythromycin

Drugs that cause diarrhea - answer-Metformin, Erythromycin, Colchicine, Orlistat,

Acarbose

Drugs that cause focal to massive hepatic necrosis - answer-Halothane, Amanita phalloides (death cap

mushroom), Valproic acid, Acetaminophen

Drugs that cause hepatitis - answer-Rifampin, isoniazid, pyrazinamide, statins, fibrates

Drugs that cause pancreatitis - answer-Didanosine, Corticosteroids, Alcohol, Valproicacid,

Azathioprine, Diuretics (furosemide, HCTZ)

Drugs that cause pseudomembranous colitis - answer-Clindamycin, ampicillin, cephalosporins

Drugs that cause agranulocytosis - answer-Ganciclovir, Clozapine, Carbamazepine, Colchicine,

Methimazole, Propylthiouracil
Drugs that cause aplastic anemia - answer-Carbamazepine, Methimazole, NSAIDs, Benzene,
Chloramphenicol, Propylthiouracil

Drugs that cause direct Coombs- positive hemolytic anemia - answer-Methyldopa, penicillin

Drugs that cause gray baby syndrome - answer-Chloramphenicol

Drugs that cause hemolysis in G6PD deficiency - answer-Isoniazid, Sulfonamides, Dapsone, Primaquine,
Aspirin, Ibuprofen, Nitrofurantoin

Drugs that cause thrombocytopenia - answer-Heparin

Drugs that cause thrombotic complications - answer-OCPs, hormone replacement therapy

Drugs that cause gingival hyperplasia - answer-Phenytoin, Ca2+ channel blockers, cyclosporine

Drugs that cause gout - answer-Pyrazinamide, Thiazides, Furosemide, Niacin, Cyclosporine

Drugs that cause myopathy - answer-Fibrates, niacin, colchicine, hydroxychloroquine, interferon-α,

penicillamine, statins, glucocorticoids

Drugs that cause osteoporosis - answer-Corticosteroids, heparin

Drugs that cause photosensitivity - answer-Sulfonamides, Amiodarone, Tetracyclines,

5-FU

Drugs that cause Stevens-Johnson syndrome - answer-Anti-epileptic drugs (especially lamotrigine),

allopurinol, sulfa drugs, penicillin

Drugs that cause SLE-like syndrome - answer-Sulfa drugs, Hydralazine, Isoniazid,

Procainamide, Phenytoin, Etanercept

Drugs that cause teeth discoloration - answer-Tetracyclines (TETra=bad TEeTh)

Drugs that cause tendonitis, tendon rupture, and cartilage damage - answer-Fluoroquinolones

Drugs that cause cinchonism (symptoms are tinnitus and slight deafness, photophobia and other visual
disturbances, mental dullness, depression, confusion, headache, and nausea) - answer-Quinidine,
quinine

Drugs that cause Parkinson-like syndrome - answer-Antipsychotics, Reserpine, Metoclopramide

Drugs that cause seizures - answer-Isoniazid (vitamin B6 deficiency), Bupropion, Imipenem/cilastatin,

Enflurane

Drugs that cause tardive dyskinesia - answer-Antipsychotics, metoclopramide

Drugs that cause diabetes insipidus - answer-Lithium, demeclocycline

Drugs that cause fanconi syndrome - answer-Expired tetracycline

Drugs that cause hemorrhagic cystitis - answer-Cyclophosphamide, ifosfamide

Drugs that cause interstitial nephritis - answer-Methicillin, NSAIDs, furosemide

Drugs that cause SIADH - answer-Carbamazepine, Cyclophosphamide, SSRIs

Drugs that cause dry cough - answer-ACE inhibitors

Drugs that cause pulmonary fibrosis - answer-Bleomycin, amiodarone, methotrexate, busulfan

Drugs that cause antimuscarinic reaction - answer-Atropine, TCAs, H1-blockers, antipsychotics

Drugs that cause disulfiram-like reaction - answer-Metronidazole, certain cephalosporins, griseofulvin,

procarbazine, 1st-generation sulfonylureas

Drugs that cause nephrotoxicity/ototoxicity - answer-Aminoglycosides, vancomycin, loop diuretics,

cisplatin. Cisplatin toxicity may respond to amifostine.

Cytochrome P-450 inducers - answer-Chronic alcohol use, St. John's wort, Phenytoin Phenobarbital,
Nevirapine, Rifampin, Griseofulvin, Carbamazepine

Cytochrome P-450 substrates - answer-Anti-epileptics, Theophylline, Warfarin OCPs

Cytochrome P-450 inhibitors - answer-Acute alcohol abuse, Ritonavir, Amiodarone, Cimetidine,

Ketoconazole, Sulfonamides, Isoniazid (INH), Grapefruit juice, Quinidine, Macrolides, (except
azithromycin)

Sulfa drugs - answer-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.

-azole - answer-Ergosterol synthesis inhibitor

-bendazole - answer-Antiparasitic/antihelmintic
-cillin - answer-Peptidoglycan synthesis inhibitor

-cycline - answer-Protein synthesis inhibitor

-ivir - answer-Neuraminidase inhibitor

-navir - answer-Protease inhibitor

-ovir - answer-DNA polymerase inhibitor

-thromycin - answer-Macrolide antibiotic

-ane - answer-Inhalational general anesthetic

-azine - answer-Typical antipsychotic

-barbital - answer-Barbiturate

-caine - answer-Local anesthetic

-etine - answer-SSRI

-ipramine, -triptyline - answer-TCA

-triptan - answer-5-HT1B/1D agonists

-zepam, -zolam - answer-Benzodiazepine

-chol - answer-Cholinergic agonist

-curium, -curonium - answer-Nondepolarizing paralytic

-olol - answer-β-blocker

-stigmine - answer-AChE inhibitor

-terol - answer-β2-agonist

-zosin - answer-α1-antagonist

-afil - answer-PDE-5 inhibitor

-dipine - answer-Dihydropyridine CCB

-pril - answer-ACE inhibitor

-sartan - answer-Angiotensin-II receptor blocker

-statin - answer-HMG-CoA reductase inhibitor

-dronate - answer-Bisphosphonate

-glitazone - answer-PPAR-γ activator

-prazole - answer-Proton pump inhibitor

-prost - answer-Prostaglandin analog

-tidine - answer-H2-antagonist

-tropin - answer-Pituitary hormone

-ximab - answer-Chimeric monoclonal Ab

-zumab - answer-Humanized monoclonal Ab

Penicillin G, V - answer--Prototype β-lactam antibiotics

-G=IV or IM; V=Oral administration

-Bind penicillin-binding proteins (transpeptidases).

-Block transpeptidase cross-linking of peptidoglycan in cell wall. Activate autolytic enzymes.

-Mostly used for gram-positive organisms (S. pneumoniae, S. pyogenes, Actinomyces). Also used for
gram-negative cocci (mainly N. meningitidis) and spirochetes (namely T. pallidum). Bactericidal for gram-
positive cocci, gram-positive rods, gram-negative cocci, and spirochetes.

-Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

-Toxicity: hypersensitivity reactions, hemolytic anemia

Amoxicillin, ampicillin (aminopenicillins) - answer--Penicillinase-sensitive penicillins

-Same mechanism as penicillin (inhibits peptidoglycan cross-linking) with wider spectrum;

-Penicillinase sensitive (ombine with clavulanic acid to protect against destruction by β-lactamase)

-Use: extended-spectrum penicillin—H. influenzae, H. pylori, E. coli, Listeria monocytogenes, Proteus

mirabilis, Salmonella, Shigella, enterococci.

-Toxicity: Hypersensitivity reactions; rash; pseudomembranous colitis.

-Resistance: penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

Dicloxacillin, nafcillin, oxacillin - answer--Penicillinase-resistant penicillins

Same mechanism as penicillin (inhibits peptidoglycan cross-linking)

-Narrow spectrum;

-Penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.
-Use with S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).

-Toxicity: Hypersensitivity reactions, interstitial nephritis.

Piperacillin, ticarcillin - answer--Antipseudomonals

-Same mechanism as penicillin (inhibits peptidoglycan cross-linking); extended spectrum

-Use: Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with β-lactamase
inhibitors.

-Toxicity: hypersensitivity reactions

β-lactamase inhibitors - answer--Clavulanic Acid, Sulbactam, Tazobactam

-Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase
(penicillinase).

Mechanism of action of cephalosporins - answer--β-lactam drugs that inhibit cell wall synthesis but are
less susceptible to penicillinases. Bactericidal.

-Organisms typically not covered by cephalosporins are LAME: Listeria, Atypicals (Chlamydia,
Mycoplasma), MRSA, and Enterococci. Exception: ceftaroline covers MRSA.

1st generation cephalosporins - answer-Cefazolin, cephalexin

Use: Gram- positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to
surgery to prevent S. aureus wound infections

2nd generation cephalosporins - answer--Cefoxitin, cefaclor, cefuroxime

-Use: gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus
mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.

3rd generation cephalosporins - answer--Ceftriaxone, cefotaxime, ceftazidime)

-Use: serious gram-negative infections resistant to other β-lactams. Ceftriaxone—meningitis, gonorrhea,

disseminated lyme disease; ceftazidime—Pseudomonas

4th generation cephalosporins - answer--Cefepime

-Use: gram-negative organisms, with activity against Pseudomonas and gram-positive organisms.

5th generation cephalosporins - answer--Ceftaroline

-Use: broad gram-positive and gram-negative organism coverage, including MRSA; does not cover
Pseudomonas.

Cephalosporin toxicity - answer--Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-

like reaction, vitamin K deficiency.

-Exhibit cross-reactivity with penicillins.

-Increased nephrotoxicity of aminoglycosides.

Mechanism of resistance of cephalosporins - answer-Structural change in penicillin-binding proteins

(transpeptidases)

Carbapenems - answer--Imipenem, meropenem, ertapenem, doripenem

-Imipenem is a broad-spectrum, β-lactamase- resistant carbapenem. Always administered with cilastatin

(inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules

-Use: gram-positive cocci, gram-negative rods, and anaerobes. Wide spectrum, but significant side
effects limit use to life-threatening infections or after other drugs have failed. Meropenem has arisk of
seizures and is stable to dehydropeptidase I

-Toxicity: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels

Aztreonam - answer--Monobactam

-Less susceptible to β-lactamases. Prevents peptidoglycan cross-linking by binding to penicillin- binding

protein 3.

-Synergistic with aminoglycosides. No cross-allergenicity with penicillins.

-Gram-negative rods only—no activity against gram-positives or anaerobes. For penicillin-allergic

patients and those with renal insufficiency who cannot tolerate aminoglycosides.

-Usually nontoxic; occasional GI upset.

Vancomycin - answer--Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell
wall precursors. Bactericidal. Not susceptible to β-lactamases.
-Gram-positive bugs only—serious, multidrug-resistant organisms, including MRSA, S. epidermidis,
sensitive Enteroccocus species, and Clostridium difficile (oral dose for pseudomembranous colitis).

-Well tolerated in general—but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse
flushing—red man syndrome (can largely prevent by pretreatment with antihistamines and slow
infusion rate).

-Resistance occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac. "Pay back 2 D-
alas (dollars) for vandalizing (vancomycin)."

Aminoglycosides - answer--Gentamicin, neomycin, amikacin, tobramycin, streptomycin

-Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit. Can cause
misreading of mRNA. Also block translocation. Require O2 for uptake; therefore ineffective against
anaerobes.

-Severe gram-negative rod infections. Synergistic with β-lactam antibiotics.

-Neomycin for bowel surgery.

-Toxicity: Nephrotoxicity, Neuromuscular blockade, Ototoxicity (especially when used with loop
diuretics). Teratogen.

-Resistance: Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or

adenylation.

Tetracyclines - answer--Tetracycline, doxycycline, minocycline

-Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration.
Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take tetracyclines
with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations
inhibit drugs' absorption in the gut.

-Clinical use: Borrelia burgdorferi, M. pneumoniae. Drugs' ability to accumulate intracellularly makes
them very effective against Rickettsia and Chlamydia. Also used to treat acne.

-Toxicity: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Contraindicated in pregnancy.

-Resistance: decrease uptake or increased efflux out of bacterial cells by plasmid-encoded transport
pumps.

Chloramphenicol - answer--Blocks peptidyltransferase at 50S ribosomal subunit.

-Bacteriostatic.
-Use: Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and
Rocky Mountain spotted fever (Rickettsia rickettsii). Limited use owing to toxicities but often still used in
developing countries because of low cost.

-Toxicity: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in
premature infants because they lack liver UDP-glucuronyl transferase).

-Resistance: plasmid-encoded acetyltransferase inactivates the drug.

Clindamycin - answer--Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.

-Anaerobic infections (e.g., Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung
abscesses, and oral infections. Also effective against invasive group A streptococcal infection.

-Treats anaerobic infections above the diaphragm vs. metronidazole (anaerobic infections below
diaphragm)

-Toxicity: pseudomembranous colitis (C. difficile -overgrowth), fever, diarrhea

Linezolid - answer--Oxazolidinone

-Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

-Gram-positive species including MRSA and VRE.

-Toxicity: Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin

syndrome.

-Resistance: Point mutation of ribosomal RNA.

Macrolides - answer--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.

Trimethoprim - answer--Inhibits bacterial dihydrofolate reductase. Bacteriostatic.

-Used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP- SMX]), causing
sequential block of folate synthesis. Combination used for UTIs, Shigella, Salmonella, Pneumocystis
jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.

-Toxicity: megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic
acid). TMP Treats Marrow Poorly.

Sulfonamides - answer--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.

Fluoroquinolones - answer--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.

Daptomycin - answer--Lipopeptide that disrupts cell membrane of gram-positive cocci.

-S. aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE. Not used for pneumonia
(avidly binds to and is inactivated by surfactant)

-Toxicity: myopathy, rhabdomyolysis.

Metronidazole - answer--Forms toxic free radical metabolites in the bacterial cell that damage DNA.
Bactericidal, antiprotozoal.

-Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile).

Used with a proton pump inhibitor and clarithromycin for "triple therapy" against H. Pylori.

-Treats anaerobic infection below the diaphragm vs. clindamycin (anaerobic infections above
diaphragm).

Toxicity: Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache,
metallic taste.

What is the prophylaxis for M. tuberculosis? - answer-Isoniazid

What is the treatment for M. tuberculosis? - answer-Rifampin, isoniazid, pyrazinamide, ethambutol

(RIPE)

What is the prophylaxis for M. avium-intracellulare? - answer-Azithromycin, rifabutin

What is the treatment for M. avium-intracellulare? - answer-More drug resistant than M. tuberculosis.
Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.

What is the prophylaxis for M. leprae? - answer-None

What is the treatment for M. leprae? - answer-Long-term treatment with dapsone and rifampin for
tuberculoid form. Add clofazimine for lepromatous form.

Rifamycins - answer--Rifampin, rifabutin

-Inhibit DNA-dependent RNA polymerase

-Mycobacterium tuberculosis; delay resistance

to dapsone when used for leprosy. Used

for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus

influenzae type B.
-Toxicity: minor hepatotoxicity and drug interactions (cytochrome P-450); orange body fluids
(nonhazardous side effect). Rifabutin favored over rifampin in patients with HIV infection due to less
cytochrome P-450 stimulation.

-Resistance: mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to
resistance.

Isoniazid - answer--Decrease synthesis of mycolic acids. Bacterial catalase- peroxidase (encoded by

KatG) needed to convert INH to active metabolite.

-Use in Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.

-Toxicity: Neurotoxicity, hepatotoxicity. Pyridoxine (vitamin B6) can prevent neurotoxicity.

-Resistance: mutations leading to underexpression of KatG.

Pyrazinamide - answer--Mechanism uncertain. Pyrazinamide is a prodrug that is converted to the active

compound pyrazinoic acid.

-Use: Mycobacterium tuberculosis.

-Toxicity: Hyperuricemia, hepatotoxicity.

Ethambutol - answer--Reduces carbohydrate polymerization of mycobacterium cell wall by blocking

arabinosyltransferase.

-Use: Mycobacterium tuberculosis.

-Toxicity: optic neuropathy (red-green color blindness).

High risk for endocarditis and undergoing surgical or dental procedures - answer-Amoxicillin

Exposure to gonorrhea - answer-Ceftriaxone

History of recurrent UTIs - answer-TMP-SMX

Exposure to meningococcal infection - answer-Ceftriaxone, ciproflaxacin, or rifampin

Pregnant woman carrying group B strep - answer-Penicillin G

Prevention of gonococcal conjunctivitis in newborn - answer-Erythromycin ointment

Prevention of postsurgical infection due to

S. aureus - answer-Cefazolin

Prophylaxis of strep pharyngitis in child with prior rheumatic fever - answer-Benzanthine penicillin G or
or penicillin V

Exposure to syphili - answer-Benzanthine penicillin G

Prophylaxis in HIV patients - answer-

Treatment of MRSA - answer-Vancomycin, daptomycin, linezolid, tigecycline, ceftaroline

Treatment of Vancomycin-resistant enterococci (VRE) - answer-Linezolid and streptogramins

(quinupristin, dalfopristin).

Treatment of multidrug-resistant P. aeruginosa, multidrug-resistant Acinetobacter baumannii - answer-

Polymyxins B and E (colistin).

Antifungal therapy (general overview) - answer-

Amphotericin B MoA - answer--Binds ergosterol (unique to fungi); forms membrane pores that allow
leakage of electrolytes.

-Amphotericin "tears" holes in the fungal membrane by forming pores

Aphotericin B clinical use - answer--Serious, systemic mycoses. Cryptococcus (amphotericin B

with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida,
Mucor.

-Intrathecally for fungal meningitis.

-Supplement K+ and Mg2+ because of altered renal tubule permeability

Amphotericin B toxicity - answer-Fever/chills ("shake and bake"), hypotension, nephrotoxicity,

arrhythmias, anemia, IV phlebitis ("amphoterrible"). Hydration nephrotoxicity. Liposomal amphotericin
toxicity.

Nystatin MoA - answer-Same as amphotericin B. Topical use only as too toxic for systemic use.

Nystatin clinical use - answer-"Swish and swallow" for oral candidiasis (thrush); topical for diaper rash or
vaginal candidiasis.

Flucytosine MoA - answer-Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine
deaminase.

Flucytosine clinical use - answer-Systemic fungal infections (especially meningitis caused by

Cryptococcus) in combination with amphotericin B.

Flucytosine toxicity - answer-Bone marrow suppression.

Name the -azoles - answer-Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole,

voriconazole.

Azoles MoA - answer-Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450
enzyme that converts lanosterol to ergosterol.

Azoles clinical use - answer-Local and less serious systemic mycoses. Fluconazole for chronic suppression
of cryptococcal meningitis in AIDS patients and candidal infections of all types. Itraconazole for
Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections.

Azoles toxicity - answer-Testosterone synthesis inhibition (gynecomastia, especially with ketoconazole),

liver dysfunction (inhibits cytochrome P-450).
Terbinafine MoA - answer-Inhibits the fungal enzyme squalene epoxidase.

Terbinafine clinical use - answer-Dermatophytoses (especially onychomycosis—fungal infection of finger

or toe nails).

Terbinafine toxicity - answer-GI upset, headaches, hepatotoxicity, taste disturbance.

Name the echinocandins - answer-Anidulafungin, caspofungin, micafungin

Echinocandins MoA - answer-Inhibit cell wall synthesis by inhibiting synthesis of β-glucan.

Echinocandins clinical - answer-Invasive aspergillosis, Candida.

Echinocandins - answer-GI upset, flushing (by histamine release).

Griseofulvin - answer-Interferes with microtubule function; disrupts mitosis. Deposits in keratin-

containing tissues (e.g., nails).

Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).

Teratogenic, carcinogenic, confusion, headaches, cytochrome P-450 and warfarin metabolism.

Toxoplasmosis therapy - answer-Pyrimethamine

Trypanosoma brucei therapy - answer-Suramin and melarsoprol

T. cruzi therapy - answer-Nifurtimox

Leishmaniasis therapy - answer-Sodium stibogluconate

Anti-mite/louse therapy - answer--Permethrin (blocks Na+ channels neurotoxicity), malathion

(acetylcholinesterase inhibitor), lindane (blocks GABA channels neurotoxicity).
-Used to treat scabies (Sarcoptes scabiei) and lice (Pediculus and Pthirus).

Chloroquine MoA - answer-Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic
to plasmodia

Chloroquine clinical use - answer-Treatment of plasmodial species other than P. falciparum (frequency
of resistance in P. falciparum

is too high). Resistance due to membrane pump that intracellular concentration of drug. Treat

P. falciparum with artemether/lumefantrine or atovaquone/proguanil. For life-threatening malaria, use

quinidine in U.S. (quinine elsewhere) or artesunate.

Choroquine toxicty - answer-Retinopathy; pruritus (especially in dark-skinned individuals).

Antihelminthic therapy drug regimen - answer-Mebendazole, pyrantel pamoate, ivermectin,

diethylcarbamazine, praziquantel.

Antiviral therapy general - answer-

Oseltamivir, zanamivir MoA - answer-Inhibit influenza neuraminidase and decrease release of progeny
virus.

Oseltamivir, zanamivir clinical use - answer-Treatment and prevention of both influenza A and B.

Acyclovir, famciclovir, valacyclovir MoA - answer-Guanosine analogs. Monophosphorylated by HSV/VZV

thymidine kinase and not phosphorylated in uninfected cells few adverse effects. Triphosphate formed
by cellular enzymes. Preferentially inhibit viral DNA polymerase by chain termination.

Acyclovir, famciclovir, valacyclovir clinical use - answer--HSV and VZV. Weak activity against EBV. No
activity against CMV. Used for HSV- induced mucocutaneous and genital lesions as well as for
encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV.
Valacyclovir, a prodrug of acyclovir, has better oral bioavailability.

-For herpes zoster, use famciclovir.

Acyclovir, famciclovir, valacyclovir toxicity - answer-Obstructive crystalline nephropathy and acute renal
failure if not adequately hydrated. Mutated viral thymidine kinase.

Acyclovir, famciclovir, valacyclovir mechanism of resistance - answer-Mutated viral thymidine kinase.

Ganciclovir MoA - answer-5′-monophosphate formed by a CMV viral kinase. Guanosine analog.

Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. Preferentially
inhibit viral DNA polymerase by chain termination.

Ganciclovir clinical use - answer-CMV, especially in immunocompromised patients. Valganciclovir, a

prodrug of ganciclovir, has better oral bioavailability.

Ganciclovir toxicity - answer-Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to

host enzymes than acyclovir.

Ganciclovir mechanism of resistance - answer-Mutated viral kinase.

Foscarnet MoA - answer-Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor.
Binds to pyrophosphate-binding site of enzyme. Does not require activation by viral kinase.

Foscarnet = pyrofosphate analog.

Foscarnet clinical use - answer-CMV retinitis in immunocompromised patients when ganciclovir fails;
acyclovir-resistant HSV.

Foscarnet toxicity - answer-Nephrotoxicity, electrolyte abnormalities (hypo- or hypercalcemia, hypo- or

hyperphosphatemia, hypokalemia, hypomagnesemia) can lead to seizures.

Foscarnet mechanism of resistance - answer-Mutated DNA polymerase.

Cidofovir MoA - answer-Preferentially inhibits viral DNA polymerase. Does not require phosphorylation
by viral kinase.

Cidofovir clinical use - answer-CMV retinitis in immunocompromised patients; acyclovir-resistant HSV.

Cidofovir toxicity - answer-Long half-life. Nephrotoxicity (coadminister with probenecid and IV saline to
toxicity).

HIV therapy - answer--Highly active antiretroviral therapy (HAART): often initiated at the time of HIV
diagnosis.

-Strongest indication for patients presenting with AIDS-defining illness, low CD4+ cell counts (< 500
cells/mm3), or high viral load.

-Regimen consists of 3 drugs to prevent resistance: 2 NRTIs and 1 of the following: NNRTI or protease
inhibitor or integrase inhibitor.

List the protease inhibitors - answer-Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Ritonavir
Saquinavir

Protease inhibitor mechanism - answer--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.

-Ritonavir can "boost" other drug concentrations by inhibiting cytochrome P-450.

-All protease inhibitors end in -navir. Navir (never) tease a protease.

Protease inhibitor toxicity - answer--Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy.

-Nephropathy, hematuria (indinavir).

-Rifampin (a potent CYP/UGT inducer) contraindicated with protease inhibitors because it can decrease
protease inhibitor concentration.

List the NRTIs - answer-Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine
(d4T) Tenofovir (TDF) Zidovudine (ZDV, formerly AZT)
NRTI mechanism of action - answer--Competitively inhibit nucleotide binding to reverse transcriptase
and terminate the DNA chain (lack a 3′ OH group). Tenofovir is a nucleoTide; the others are nucleosides
and need to be phosphorylated to be active.

-ZDV is used for general prophylaxis and during pregnancy to risk of fetal transmission.

NNRTIs - answer-Delavirdine Efavirenz Nevirapine

NNRTIs MoA - answer-Bind to reverse transcriptase at site different from NRTIs. Do not require
phosphorylation to be active or compete with nucleotides.

NNRTIs toxicity - answer-Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS
symptoms are common with efavirenz. Delavirdine and efavirenz are contraindicated in pregnancy.

Raltegravir MoA - answer--Integrase inhibitors

-Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.

Raltegavir toxicity - answer-Increased creatine kinase

Enfuvirtide MoA - answer-Binds gp41, inhibiting viral entry

Enfuvirtide toxicity - answer-Skin reaction at injection sites

Maraviroc MoA - answer-Binds CCR-5 on surface of T-cells/monocytes, inhibiting interaction with gp120

Interferons MoA - answer-Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide

range of antiviral and antitumoral properties.

Interferons clinical use - answer-IFN-α: chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia,
condyloma acuminatum, renal cell carcinoma, malignant melanoma.

IFN-β: multiple sclerosis.

IFN-γ: chronic granulomatous disease.

Interferons toxicity - answer-Neutropenia, myopathy.

Ribavirin MoA - answer-Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine

monophosphate dehydrogenase.

Ribavirin clinical use - answer-Chronic HCV, also used in RSV (palivizumab preferred in children)

Ribavirin toxicity - answer-Hemolytic anemia; severe teratogen.

Simeprevir MoA - answer-HCV protease inhibitor; prevents viral replication

Simeprevir clinical use - answer--Chronic HCV in combination with ribavirin and peginterferon alfa.

-Do not use as monotherapy.

Simeprevir toxicity - answer-Photosensitivity reactions, rash

Sofosbuvir MoA - answer-Inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator.

Sofosbuvir clinical use - answer--Chronic HCV in combination with ribavirin, +/- peginterferon alfa.

-Do not use as monotherapy.

Sobosbuvir toxicity - answer-Fatigue, headache, nausea

Goals of infection control techniques - answer-Goals include the reduction of pathogenic organism
counts to safe levels (disinfection) and the inactivation of self-propagating biological entities
(sterilization).

Describing autoclaving - answer-Pressurized steam at > 120°C. May be sporicidal.

Describe the mechanism of alcohols as an infection control technique - answer-Denature proteins and
disrupt cell membranes. Not sporicidal.

Describe the mechanism of chlorhexidine as an infection control technique - answer-Denatures proteins

and disrupts cell membranes. Not sporicidal.

Describe the mechanism of hydrogen peroxide as an infection control technique - answer-Free radical
oxidation. Sporicidal.

Describe the mechanism of iodine and iodophors as an infection control technique - answer-
Halogenation of DNA, RNA, and proteins. May be sporicidal

Antibiotics to avoid during pregnancy - answer--Sulfonamides

-Aminoglycosides

-Fluoroquinolones

-Clarithromycin

-Tetracyclines

-Ribavirin (antiviral)

-Griseofulvin (antifungal)

-Chloramphenicol

(SAFe Children Take Really Good Care)

Adverse effect of sulfonamides during pregnancy - answer-Kernicterus

Adverse effect of aminoglycosides during pregnancy - answer-Ototoxicity

Adverse effect of fluorquinolones during pregnancy - answer-Cartilage damage

Adverse effect of clarithromycin during pregnancy - answer-Embryotoxic

Adverse effect of tetracyclines during pregnancy - answer-Discolored teeth, inhibition of bone growth

Adverse effect of ribavirin during pregnancy - answer-Teratogenic

Adverse effect of griseofulvin during pregnancy - answer-Teratogenic

Adverse effect of chloramphenicol during pregnancy - answer-Gray baby syndrome (vomiting, ashen
gray color of the skin, limp body tone, hypotension, cyanosis of lips and skin, hypothermia,
cardiovascular collapse, within 2-9 days of birth-especially premature)

Cyclosporine MoA - answer-Calcineurin inhibitor; binds cyclophilin. Blocks T-cell activation by preventing
IL-2 transcription.

Cyclosporine clinical use - answer-Transplant rejection prophylaxis, psoriasis, rheumatoid arthritis

Cyclosporine toxicity - answer-Nephrotoxicity, hypertension, hyperlipidemia, neurotoxicity, gingival

hyperplasia, hirsutism.

Tacrolimus MoA - answer--Calcineurin inhibitor; binds FK506 binding protein (FKBP).

-Blocks T-cell activation by preventing IL-2 transcription.

Tacrolimus clinical use - answer-Transplant rejection prophylaxis

Tacrolimus toxicity - answer-Similar to cyclosporine, risk of diabetes and neurotoxicity; no gingival

hyperplasia or hirsutism.

Sirolimus (Rapamycin) MoA - answer--mTOR inhibitor; binds FKBP.

-Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.

Sirolimus (Rapamycin) clinical use - answer--Kidney transplant rejection prophylaxis.

-Synergistic with cyclosporine.

-Also used in drug-

eluting stents

Sirolimus (Rapamycin) toxicity - answer-Anemia, thrombocytopenia, leukopenia, insulin resistance,

hyperlipidemia; not nephrotoxic (kidney "sir-vives")

Daclizumab, basiliximab MoA - answer-Monoclonal antibodies; block IL-2R.

Daclizumab, basiliximab clinical use - answer-Kidney transplant rejection prophylaxis

Daclizumab, basiliximab toxicity - answer-Edema, HTN, tremor

Azathioprine MoA - answer-Antimetabolite precursor of 6-mercaptopurine.

Inhibits lymphocyte proliferation by blocking nucleotide synthesis.

Azathioprine clinical use - answer-Transplant rejection prophylaxis, rheumatoid arthritis, Crohn disease,
glomerulonephritis, other autoimmune conditions.

Azathioprine toxicity - answer--Leukopenia, anemia, thrombocytopenia.

-6-MP degraded by xanthine oxidase; toxicity by allopurinol.

Glucocorticoids MoA - answer-Inhibit NF-κB. Suppress both B- and T-cell function by transcription of
many cytokines.

Glucocorticoids clinical use - answer-Transplant rejection prophylaxis (immunosuppression), many

autoimmune disorders, inflammation
Glucocorticoids toxicity - answer--Hyperglycemia, osteoporosis, central obesity, muscle breakdown,
psychosis, acne, hypertension, cataracts, avascular necrosis.

-Can cause iatrogenic Cushing syndrome.

Immunosuppression targets image - answer-

Clinical use of aldesleukin (IL-2) - answer-Renal cell carcinoma, metastatic melanoma

Clinical use of epoetin alfa (erythropoietin) - answer-Anemias (especially in renal failure)

Clinical use of filgrastim (G-CSF) - answer-Recovery of bone marrow

Clinical use of sargramostim (GM-CSF) - answer-Recovery of bone marrow

Clinical use of IFN-α - answer-Chronic hepatitis B and C, Kaposi sarcoma, malignant melanoma

Clinical use of IFN-β - answer-Multiple sclerosis

Clinical use of IFN-γ - answer-Chronic granulomatous disease

Clinical use of romiplostim, eltrombopag - answer-Thrombocytopenia

Clinical use of oprelvekin (IL-11) - answer-Thrombocytopenia

Alemtuzumab target - answer-CD52

Alemtuzumab clinical use - answer-CLL

"Alymtuzumab"—chronic lymphocytic leukemia

Bevacizumab target - answer-VEGF

Bevacizumab clinical use - answer-Colorectal cancer, renal cell carcinoma

Cetuximab target - answer-EGFR

Cetuximab clinical use - answer-Stage IV colorectal cancer, head and neck cancer

Rituximab target - answer-CD20

Rituximab clinical use - answer-B-cell non-Hodgkin lymphoma, CLL, RA, ITP

Trastuzumab target - answer-HER2/neu (Can't 'trust' HER)

Trastuzumab clinical use - answer-Breast cancer

Adalimumab, infliximab target - answer-Soluble TNF-α

Etanercept is a decoy TNF-α receptor and not a monoclonal antibody

Adalimumab, infliximab clinical use - answer-IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Eculizumab target - answer-Complement protein C5

Eculizumab clinical use - answer-Paroxysmal nocturnal hemoglobinuria

Natalizumab target - answer-α4-integrin

α4-integrin: WBC adhesion Risk of PML in patients with

JC virus

Natalizumab clinical use - answer-Multiple sclerosis, Crohn disease

Abciximab target - answer-Platelet glycoproteins IIb/IIIa

IIb times IIIa equals "absiximab"

Abciximab clinical use - answer-Antiplatelet agent for prevention of ischemic complications in patients
undergoing percutaneous coronary intervention

Denosumab target - answer-RANKL

Denosumab clinical use - answer-Osteoperosis; inhibits osteoclast maturation (mimics osteoprotegerin)

Digoxin immune Fab target - answer-Digoxin

Digoxin immune Fab clinical use - answer-Antidote for digoxin toxicity

Omalizumab target - answer-IgE

Omalizumab clinical use - answer-Allergic asthma, prevents IgE binding to FcεRI

Palivizumab target - answer-RSV F protein

("VI" for VIrus)

Palivizumab clinical use - answer-RSV prophylaxis for high risk infants

Ranibizumab, bevacizumab target - answer-VEGF

Ranibizumab, bevacizumab clinical use - answer-Neovascular age-related macular degeneration

Primary (essential) hypertension therapy - answer-Thiazide diuretics, ACE inhibitors, angiotensin II

receptor blockers (ARBs), dihydropyridine Ca2+ channel blockers.

Hypertension with heart failure therapy - answer--Diuretics, ACE inhibitors/ARBs, β-blockers

(compensated HF), aldosterone antagonists.

-β-blockers must be used cautiously in decompensated HF and are contraindicated in cardiogenic shock.

Hypertension with diabetes mellitus - answer-ACE inhibitors/ARBs, Ca2+ channel blockers, thiazide
diuretics, β-blockers.

ACE inhibitors/ARBs are protective against diabetic nephropathy.

Hypertension in pregnancy - answer-Hydralazine, lebetalol, methyldopa, nifedipine

List the dihydropyridine calcium channel blockers - answer-Amlodipine, clevidipine, nicardipine,

nifedipine, nimodipine

-Act on vascular smooth muscle

List the non-dihydropyridine calcium channel blockers - answer-diltiazem, verapamil

-Act on the heart

Calcium channel blockers mechanism - answer--Block voltage-dependent L-type calcium channels of
cardiac and smooth muscle to decrease muscle contractility.

-Vascular smooth muscle—amlodipine = nifedipine > diltiazem > verapamil.

-Heart—verapamil > diltiazem > amlodipine = nifedipine (verapamil = ventricle).

Dihydropyridine calcium channel blockers clinical use - answer-HTN, angina (including Prinzmetal),
Raynaud phenomenon.

**NOT nimodipine which is used for subarachnoid hemorrhage to prevent cerebral vasospasm)

Nimodipine clinical use - answer-Used in subarachnoid hemorrhage to prevent cerebral vasospasm)

Clevidipine clinical use - answer-HTN urgency or emergency

Non-dihydropyridine calcium channel blockers clinical use - answer-HTN, angina, atrial fib/flutter

Calcium channel blocker toxicity - answer-Cardiac depression, AV block (non-dihydropyridines),

peripheral edema, flushing, dizziness, hyperprolactinemia (verapamil), constipation, gingival hyperplasia.

Hydralazine mechanism - answer-Increase cGMP causing smooth muscle relaxation. Vasodilates

arterioles > veins; afterload reduction.

Hydralazine clinical use - answer--Severe HTN (particularly acute), HF (with organic nitrate).

-Safe to use in pregnancy.

-Frequently coadministered with a β-blocker to prevent reflex tachycardia.

Hydralazine toxicity - answer-Compensatory tachycardia (contraindicated in angina/CAD), fluid

retention, headache, angina.

Lupus-like syndrome!!!!
What drugs can be used in a hypertensive emergency? - answer-Clevidipine, fenoldopam, labetalol,
nicardipine, nitroprusside

Nitroprusside - answer-Short acting; increase cGMP via direct release of NO. Can cause cyanide toxicity
(releases cyanide)

Fenoldopam - answer--Dopamine D1 receptor agonist—coronary, peripheral, renal, and splanchnic

vasodilation.

-Decrease BP, increase natriuresis.

List the nitrates - answer-Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate

Nitrate mechanism of action - answer-Vasodilate by increasing NO in vascular smooth muscle thereby

increasing cGMP and smooth muscle relaxation. Dilate veins >> arteries. Reduces preload

Nitrate clinical use - answer-Angina, acute coronary syndrome, pulmonary edema

Nitrate toxicity - answer-Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache,
"Monday disease" in industrial exposure: development of tolerance for the vasodilating action during
the work week and loss of tolerance over the weekend - tachycardia, dizziness, headache upon
reexposure.

Goal of antianginal therapy - answer-Goal is reduction of myocardial O2 consumption (MVO2) by

decreasing 1 or more of the determinants of MVO2: end-diastolic volume, BP, HR, contractility.

What effect do nitrates have on EDV? - answer-Decreases

What effect do nitrates have on BP? - answer-Decreases

What effect do nitrates have on contractility? - answer-None

What effect do nitrates have on HR? - answer-Increase (reflex response)

What effect do nitrates have on ejection time? - answer-Decrease

What effect do nitrates have on MVO2? - answer-Decreased

What effect do β-blockers have on EDV? - answer-None or decrease

What effect do β-blockers have on BP? - answer-Decrease

What effect do β-blockers have on contractility? - answer-Decrease

What effect do β-blockers have on HR? - answer-Decrease

What effect do β-blockers have on ejection time? - answer-Increase

What effect do β-blockers have on MVO2? - answer-Decrease

What effect does nitrates + β-blockers have on EDV? - answer-No effect or decrease

What effect does nitrates + β-blockers have on BP? - answer-Decrease

What effect does nitrates + β-blockers have on contractility? - answer-Little/no effect

What effect does nitrates + β-blockers have on HR? - answer-No effect or decreased

What effect does nitrates + β-blockers have on ejection time? - answer-little/no effect

What effect does nitrates + β-blockers have on MVO2 - answer-Double decrease

Antianginal therapy summary table - answer-

Lipid lowering agents summary table - answer-

Lipid lowering agents summary schematic - answer-

List the HMG-CoA reductase inhibitors - answer-Lovastatin, pravastatin, simvastatin, atorvastatin,

rosuvastatin

HMG-CoA reductase effect on lipid levels - answer-LDL Δ: big time triple decrease!!!

HDL Δ: increase

TG Δ: decrease

HMG-CoA reductase mechanism of action - answer-Inhibit conversion of HMG- CoA to mevalonate, a

cholesterol precursor;

Decreased mortality in CAD patients

HMG-CoA reductase side effects/problems - answer-Hepatotoxicity ( LFTs), myopathy (esp. when used
with fibrates or niacin)

List the bile acid resins - answer-Cholestyramine, colestipol, colesevelam

Bile acid resins effect on lipid levels - answer-LDL Δ: double decrease

HDL Δ: slight increase

TG Δ: slight increase

Bile acid resin mechanism - answer-Prevents intestinal absorption of bile acids; liver must use
cholesterol to make more
Bile acid resin side effects/problems - answer-GI upset, decrease absorption of other drugs and fat-
soluble vitamins

What effect does ezetimibe have on lipid levels? - answer-LDL Δ: double decrease

HDL Δ: none

TG Δ: none

Ezetimibe mechanism of action - answer-Prevents cholesterol absorption at the small intestine brush
border

Ezetimibe side effects/problems - answer-Rare increase in LFTs, diarrhea

List the fibrates - answer-gemfibrozil, clofibrate, bezafibrate, fenofibrate

Fibrate effect on lipid levels - answer-LDL Δ: down

HDL Δ: up

TG Δ: TRIPLE DOWN!!!

Fibrates mechanism of action - answer--Upregulate LPL causing increase in TG clearance.

-Activates PPAR-α to induce HDL synthesis

Fibrates side effects/problems - answer-Myopathy (increase risk with statins), cholesterol gallstones

Niacin effect on lipid levels - answer-LDL Δ: double down

HDL Δ: double up

TG Δ: down

Niacin mechanism - answer--Inhibits lipolysis (hormone sensitive lipase) in adipose tissue;

-Reduces hepatic VLDL synthesis

Niacin side effects/problems - answer-Red, flushed face, which is decreased by NSAIDs or long term use;
hyperglycemia, hyperuricemia (gout)

Digoxin mechanism - answer-Direct inhibition of Na+/K+ ATPase causing indirect inhibition of Na+/Ca2+
exchanger. Increased [Ca2+]i creates positive inotropy. Stimulates vagus nerve to increase HR.

Digoxin clinical use - answer-HF (increased contractility), atrial fibrillation (decrease conduction at AV
node and depression of the SA node)

Digoxin toxicity - answer--Cholinergic—nausea, vomiting, diarrhea, blurry yellow vision (think van Gogh),
arrhythmias, AV block.

-Can lead to hyperkalemia, which indicates poor prognosis.

Factors predisposing to digoxin toxicity - answer-Renal failure (decreased excretion), hypokalemia

(permissive for digoxin binding at K+-binding site on Na+/K+ ATPase), verapamil, amiodarone, quinidine
(digoxin clearance; displaces digoxin from tissue-binding sites).

Antidote - answer-Slowly normalize K+, cardiac pacer, anti-digoxin Fab, Mg2+

General mechanism of sodium channel blockers (class I antiarrhythmic) - answer--Slow or block

conduction (especially in depolarized cells). -Decrease slope of phase 0 depolarization.

-Are state dependent - selectively depress tissue that is frequently depolarized (e.g., tachycardia)

List the class IA sodium channel blockers - answer-Quinidine, procainamide, disopyramide,

Class IA sodium channel blockers effect on action potential - answer--Decreases slope of phase 0

-Increase action potential duration

-Increase effective refractory period

-Increased QT interval
Class IA sodium channel blocker mechanism - answer-Increase action potential duration, increase
effective refractory period in ventricular action potential, and increase QT

Class IA sodium channel blocker clinical use - answer-Both atrial and ventricular arrhythmias, especially
re-entrant and ectopic SVT and VT

Class IA sodium channel blocker toxicity - answer-Cinchonism (headache, tinnitus with quinidine),
reversible SLE like syndrome (procainamide), heart failure (disopyramide), thrombocytopenia, torsades
de pointes due to increased QT

Procainamide toxicity - answer-SLE like syndrome (reversible)

Quinidine toxicity - answer-Cinchonism (headache, tinnitus)

Disopyramide toxicity - answer-Heart failure

List the class IB sodium channel blockers - answer-Lidocaine, mexiletine

Phenytoin can also fall into this category

Class IB sodium channel blockers effect on action potential - answer--Decreases AP duration

-Decreases slope of phase 0

Class IB sodium channel blockers mechanism - answer-Decrease AP duration. Preferentially affect

ischemic or depolarized Purkinje and ventricular tissue.

Class IB sodium channel blockers clinical use - answer-Acute ventricular arrhythmias (especially post-
MI), digitalis-induced arrhythmias.

(IB is Best post-MI)

Class IB sodium channel blockers toxicity - answer-CNS stimulation/depression, CV depression

List the class IC sodium channel blockers - answer-Flecainide, propafenone

Class IC sodium channel blockers effect on action potential curve - answer--Minimal effect on action
potential duration

-Decreases slope of phase 0

Class IC sodium channel blockers mechanism - answer--Significantly prolongs ERP in AV node and
accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue.

-Minimal effect on AP duration

Class IC sodium channel blockers clinical use - answer-SVTs, including atrial fibrillation. Only as a last
resort in refractory VT.

Class IC sodium channel blockers toxicity - answer--Proarrhythmic, especially post-MI (DO NOT USE POST
MI!)

-Contraindicated in structural and ischemic heart disease

List the key β-blockers (class II antiarrhythmics) - answer-Metoprolol, propranolol, esmolol, atenolol,
timolol, carvedilol

β-blockers (class II antiarrhythmics) mechanism - answer--Decrease SA and AV nodal activity by

decreasing cAMP, and decreasing Ca2+ currents. Suppress abnormal pacemakers by decreasing slope of
phase 4.

-AV node particularly sensitive - increase PR interval. Esmolol very short acting

What is the shortest acting β-blocker - answer-Esmolol

β-blockers (class II antiarrhythmics) clinical use - answer-SVT, ventricular rate control for atrial
fibrillation and atrial flutter
β-blockers (class II antiarrhythmics) toxicity - answer-Impotence, exacerbation of COPD and asthma,
cardiovascular effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask
the signs of hypoglycemia.

β-blockers cause unopposed α1-agonism if given alone for pheochromocytoma or cocaine toxicity.

Metoprolol side effects - answer-Dyslipidemia

Propranolol side effects - answer-May exacerbate vasospasm in Prinzmetal angina

β-blockers overdose treatment - answer-Saline, atropine, glucagon

β-blockers effect on the pacemaker cell action potential curve - answer--Decreased slope of phase 4
depolarization

-Prolonged repolarization (at AV node)

-Increased PR interval

List the potassium channel blockers (class III antiarhythmics) - answer-Amiodarone, ibutilide, dofetilide,
sotalol

Potassium channel blockers mechanism - answer-Increase AP duration, increase ERP, increase QT

interval

Potassium channel blockers clinical use - answer-Atrial fibrillation, atrial flutter; ventricular tachycardia
(amiodarone, sotalol)

Amiodarone toxicity - answer-Pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism, act

as hapten (corneal deposits, blue/gray skin deposits resulting in photodermatitis), neurologic effects,
constipation, CV effects (bradycardia, heart block, HF)

Sotalol toxicity - answer-Torsades de pointes, excessive β blockade.

Ibutilide toxicity - answer-Torsades de pointes

Potassium channel blockers effect on action potential curve - answer--No change in slope of phase 0

-Greatly increased action potential duration

-Greatly increased ERP and QT interval

List the calcium channel blockers (class IV antiarrhythmics) - answer-Verapamil, diltiazem

Calcium channel blockers effect on the pacemaker cell action potential curve - answer--Slow rise of AP
(decrease conduction velocity)

-Increased ERP

-Increased PR interval

-Prolonged repolarization (at AV node)

Calcium channel blockers (class IV antiarrhythmics) mechanism - answer--Decrease conduction velocity

-Increase ERP and PR interval

Calcium channel blockers (class IV antiarrhythmics) clinical use - answer-Prevention of nodal arrhythmias
(e.g. SVT), rate control in atrial fibrillation

Calcium channel blockers (class IV antiarrhythmics) toxicity - answer-Constipation, flushing, edema, CV

effects (HF, AV block, sinus node depression)

Adenosine - answer--Antiarrhythmic

-Increase K+ out of cells hyperpolarizing the cell and increasing intracellular Ca2+.

-Drug of choice in diagnosing/abolishing supraventricular tachycardia. Very short acting (~ 15 sec).

Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists).

What are the adverse effects of adenosine? - answer-Adverse effects include flushing, hypotension,
chest pain, sense of impending doom, bronchospasm.
Mg2+ - answer-Effective in torsades de pointes and digoxin toxicity

Treatment strategy with type 1 DM - answer-Low-carb diet and insulin replacement

Treatment strategy with type 2 DM - answer-Dietary modification and exercise for weight loss; oral
agents, non-insulin injectables, insulin replacement

Treatment strategy for gestational DM - answer-Dietary modification, exercise, insulin replacement if

lifestyle changes fail

Name the rapid acting insulins - answer-Aspart, glulisine, lispro

Rapid acting insulin mechanism - answer--Binds insulin receptor (tyrosine kinase activity)

-Liver: increase glucose stored as glycogen

-Muscle: increase glycogen, protein synthesis; increase K+ uptake

-Fat: increase TG storage

Rapid acting insulin clinical use - answer-Type 1 DM, type 2 DM, GDM (postprandial glucose control)

Rapid acting insulin toxicity - answer-Hypoglycemia, rare hypersensitivity reaction

Short acting insulin (regular) mechanism - answer--Binds insulin receptor (tyrosine kinase activity)

-Liver: increase glucose stored as glycogen

-Muscle: increase glycogen, protein synthesis; increase K+ uptake

-Fat: increase TG storage

Short acting insulin clinical use - answer-Type 1 DM, type 2 DM, GDM, DKA (IV), hyperkalemia (+
glucose), stress hyperglycemia.
Intermediate acting insulin (NPH) clinical use - answer-Type 1 DM, type 2 DM, GDM

Name the long acting insulins - answer-Detemir, Glargine

Long acting insulin clinical use - answer-Type 1 DM, type 2 DM, GDM (basal glucose control)

Metformin mechanism - answer--Exact mechanism unknown.

-Decrease gluconeogenesis, increase glycolysis, increase peripheral glucose uptake (increase insulin
sensitivity).

Metformin clinical use - answer--Oral. First line therapy in type 2 DM, causes modest weight loss.

-Can be used in patients without islet function

Name the Sulfonylureas - answer-First generation: Chlorpropamide, Tolbutamide

Second generation: Glimepiride, Glipizide, Glyburide

Sulfonylureas mechanism - answer-Close K+ channel in β-cell membrane then cell depolarizes causing
insulin release via increased Ca2+ influx.

Sulfonylureas clinical use - answer-Stimulate release of endogenous insulin in type 2 DM. Require some
islet function, so useless in type 1 DM.

Sulfonylureas toxicity - answer-Risk of hypoglycemia in renal failure.

First generation: disulfiram- like effects.

Second generation: hypoglycemia.

List the glitazones/ thiazolidinediones - answer-Pioglitazone, rosiglitazone

Glitazones/ thiazolidinediones mechanism - answer-Increase sensitivity in peripheral tissue. Binds to

PPAR-γ nuclear transcription regulator.
Glitazones/ thiazolidinediones clinical use - answer-Used as monotherapy in type 2 DM or combined
with other agents

Glitazones/ thiazolidinediones toxicity - answer-Weight gain, edema, hepatotoxicity, HF, increased risk if
fractures

List the GLP-1 analogs - answer-Exenatide, liraglutide

GLP-1 analogs action - answer--Increase insulin

-Decrease glucagon release

GLP-1 analogs clinical use - answer-Type 2 DM

GLP-1 analogs toxicity - answer-Nausea, vomiting, pancreatitis

List the DPP-4 inhibitors - answer-Linagliptin, saxagliptin, sitagliptin

DPP-4 inhibitors action - answer--Increase insulin

-Decrease glucagon release

DPP-4 inhibitors - answer-Type 2 DM

DPP-4 inhibitors - answer-Mild urinary or respiratory infections

Pramlintide action - answer--Amylin analog

-Decrease gastric emptying

-Decrease glucagon
Pramlintide clinical use - answer-Type 1 and type 2 DM

Pramlintide toxicity - answer-Hypoglycemia, nausea, diarrhea.

Canagliflozin action - answer--SGLT-2 inhibitor

-Block reabsorption of glucose in PCT

Canagliflozin clinical use - answer-Type 2 DM

Canagliflozin toxicity - answer-Glucosuria, UTIs, vaginal yeast infections.

α-glucosidase inhibitors - answer-Acarbose, miglitol

α-glucosidase inhibitors action - answer--Inhibit intestinal brush-border α-glucosidases.

-Delayed carbohydrate hydrolysis and glucose absorption leading to decreased postprandial

hyperglycemia.

α-glucosidase inhibitors clinical use - answer--Used as monotherapy in type 2 diabetes or in combination

with other agents

PPAR-γ - answer-Genes activated by PPAR-γ regulate fatty acid storage and glucose metabolism.
Activation of PPAR-γ insulin sensitivity and levels of adiponectin.

Propylthiouracil, methimazole mechanism - answer-Block thyroid peroxidase, inhibiting the oxidation of

iodide and the organification (coupling) of iodine -> inhibition of thyroid hormone synthesis.
Propylthiouracil also blocks 5′-deiodinase -> decreased peripheral conversion of T4 to T3.

Levothyroxine (T4), triiodothyronine (T3) mechanism - answer-Hormone replacement

Levothyroxine (T4), triiodothyronine (T3) clinical use - answer-Hypothyroidism, myxedema. Off label use
as weight loss supplements
Levothyroxine (T4), triiodothyronine (T3) toxicity - answer-Tachycardia, heat intolerance, tremors,
arrhythmias

ADH antagonists - answer-Conivaptan, tolvaptan

ADH antagonist clinical use - answer-SIADH, block action of ADH at V2-receptor.

Desmopressin acetate clinical use - answer-Central (not nephrogenic) DI.

GH clinical use - answer-GH deficiency, Turner syndrome

Oxytocin clinical use - answer-Stimulates labor, uterine contractions, milk let-down; controls uterine
hemorrhage

Somatostatin (octeotride) clinical use - answer-Acromegaly, carcinoid syndrome, gastrinoma,

glucagonoma, esophageal varices

Demeclocycline (mechanism, use, and toxicity) - answer--Mechanism: ADH antagonist (member of

tetracycline family).

-Use: SIADH.

-Toxicity: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.

Glucocorticoids (the ridiculist) - answer-Beclomethasone, dexamethasone, fludrocortisone

(mineralocorticoid and glucocorticoid activity), hydrocortisone, methylprednisolone, prednisone,
triamcinolone.

Basically anything ending in -sone/lone

Glucocorticoids mechanism - answer-Metabolic, catabolic, anti-inflammatory, and immunosuppressive

effects mediated by interactions with glucocorticoid response elements, inhibition of phospholipase A2,
and inhibition of transcription factors such as NF-κB.
Glucocorticoids clinical use - answer-Addison disease, inflammation, immunosuppression, asthma

Glucocorticoids toxicity - answer--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.

Cinacalcet (mechanism, use, and toxicity) - answer--Mechanism: Sensitizes Ca2+-sensing receptor (CaSR)
in parathyroid gland to circulating Ca2+ and thus decreases PTH.

-Use: Hypercalcemia due to 1° or 2° hyperparathyroidism.

-Toxicity: Hypocalcemia.

Acid suppression therapy general overview image - answer-

List the H2 blockers - answer--Cimetidine, ranitidine, famotidine, nizatidine.

-Take H2 blockers before you "dine". Think "table for 2" to remember H2.

H2 blocker mechanism - answer-Reversible block of histamine H2 receptors decreasing H+ secretion by

parietal cells

H2 blocker clinical use - answer-Peptic ulcer, gastritis, mild esophageal reflux

H2 blocker toxicity - answer--Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug

interactions); it also has antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased
libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta.

-Both cimetidine and ranitidine increase renal excretion of creatinine. Other H2 blockers are relatively
free of these effects.

Name those proton pump inhibitors - answer-Omeprazole, lansoprazole, esomeprazole, pantoprazole,

dexlansoprazole.
Proton pump inhibitor mechanism - answer-Irreversibly inhibits H+/K+ ATPase in stomach parietal cells

PPI use - answer-Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome

PPI toxicity - answer--Increased risk of C. difficile infection, pneumonia.

-Decreased serum Mg2+ with long term use

Bismuth, sucralfate mechanism - answer-Bind to ulcer base, providing physical protection and allowing
HCO3- secretion to reestablish pH gradient in the mucus layer

Bismuth, sucralfate use - answer-Increased ulcer healing, travelers' diarrhea

Misoprostol (mechanism, use, and toxicity) - answer--Mechanism: A PGE1 analog. Increased production
and secretion of gastric mucous barrier, decreased acid production.

-Use: Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production); maintenance of a

PDA. Also used off-label for induction of labor (ripens cervix).

-Toxicity: Diarrhea. Contraindicated in women of childbearing potential (abortifacient).

Octreotide (mechanism, use, and toxicity) - answer--Mechanism: Long-acting somatostatin analog;

inhibits actions of many splanchnic vasoconstriction hormones.

-Use: Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors.

-Toxicity: Nausea, cramps, steatorrhea.

Overuse of aluminum hydroxide - answer-Causes constipation and hypophosphatemia; proximal muscle

weakness, osteodystrophy, seizures

Overuse of calcium carbonate - answer--Hypercalcemia, rebound acid increase

-Can chelate and decrease effectiveness of other drugs

Overuse of magnesium hydroxide - answer-Diarrhea, hyporeflexia, HoTN, cardiac arrest

Osmotic laxatives (drugs, mechanism, clinical use and toxicity) - answer-Magnesium hydroxide,
magnesium citrate, polyethylene glycol, lactulose.

-Mechanism: provide osmotic load to draw water into the GI lumen.

-Use: Constipation. Lactulose also treats hepatic encephalopathy since gut flora degrade it into
metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+.

-Toxicity: Diarrhea, dehydration; may be abused by bulimics.

Sulfasalazine (mechanism, clinical use and toxicity) - answer--Mechanism: A combination of

sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria.

-Use: Ulcerative colitis, Crohn disease (colitis component).

-Toxicity: Malaise, nausea, sulfonamide toxicity, reversible oligospermia.

Ondansetron (mechanism, clinical use and toxicity) - answer--Mechanism: 5-HT3 antagonist; decrease
vagal stimulation. Powerful central-acting antiemetic.

-Use: Control vomiting postoperatively and in patients undergoing cancer chemotherapy.

-Toxicity: Headache, constipation, QT interval prolongation.

Metoclopramide (mechanism, clinical use and toxicity) - answer--Mechanism: D2 receptor antagonist.

Increase resting tone, contractility, LES tone, motility. Does not influence colon transport time.

-Use: Diabetic and postsurgery gastroparesis, antiemetic.

-Toxicity: Increased parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue,

depression, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with
small bowel obstruction or Parkinson disease (due to D1-receptor blockade).

Orlistat (mechanism, clinical use and toxicity) - answer--Mechanism: Inhibits gastric and pancreatic
lipase breakdown and absorption of dietary fats.

-Use: Weight loss.

-Toxicity: Steatorrhea, decreased absorption of fat-soluble vitamins.

Heparin mechanism - answer-Activator of antithrombin; decrease thrombin and decrease factor Xa.
Short half-life.

Heparin use - answer-Immediate anticoagulation for pulmonary embolism (PE), acute coronary
syndrome, MI, deep venous thrombosis (DVT). Used during pregnancy (does not cross placenta). Follow
PTT.

Heparin toxicity - answer-Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For

rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively
charged heparin).

What is the heparin toxicity antidote, and how does it work? - answer-Protamine sulfate, positively
charged molecule that binds negatively charged heparin

Low molecular weight heparins (e.g., enoxaparin, dalteparin) and fondaparinux - answer-Act more on
factor Xa, have better bioavailability, and 2-4 times longer half-life; can be administered subcutaneously
and without laboratory monitoring. Not easily reversible

Heparin-induced thrombocytopenia (HIT) - answer-Development of IgG antibodies against heparin-

bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets leading to thrombosis
and thrombocytopenia.

Bivalirudin - answer-Related to hirudin, the anticoagulant used by leeches; inhibit thrombin directly.
Alternatives to heparin for anticoagulating patients with HIT

See also argatroban, dabigatran

Warfarin mechanism - answer--Interferes with γ-carboxylation of vitamin K- dependent clotting factors

II, VII, IX, and X, and proteins C and S. -Metabolism affected by polymorphisms in the gene for vitamin K
epoxide reductase complex (VKORC1). In laboratory assay, has effect on EXtrinsic pathway and increase
PT.

-Long half-life.
Warfarin use - answer-Chronic anticoagulation (e.g., venous thromboembolism prophylaxis, and
prevention of stroke in atrial fibrillation). Not used in pregnant women (because warfarin, unlike
heparin, crosses placenta). Follow PT/INR.

Warfarin toxicity - answer-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.

Reversal of warfarin toxicity - answer-Vitamin K; for rapid reversal give fresh frozen plasma

What coagulation pathway is affected by heparin? - answer-PTT (intrinsic pathway)

What coagulation pathway is affected by warfarin? - answer-PT (extrinsic pathway)

Direct factor Xa inhibitors (drugs, mechanism, use, toxicity) - answer-Apixaban, rivaroxaban

-Mechanism: bind to and directly inhibit factor Xa.

-Use: treatment and prophylaxis for DVT and PE (rivaroxaban); stroke prophylaxis in patients with atrial
fibrillation. Oral agents do not usually require coagulation monitoring.

-Toxicity: bleeding (no reversal agent available).

Thrombolytics (drugs, mechanism, use, toxicity) - answer-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.

Aspirin mechanism - answer-Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by
covalent acetylation. Platelets cannot synthesize new enzyme, so effect lasts until new platelets are
produced: increase bleeding time, decrease TXA2 and prostaglandins. No effect on PT or PTT.

Aspirin use - answer-Antipyretic, analgesic, anti-inflammatory, antiplatelet (decreased aggregation).

Aspirin toxicity - answer--Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure,
interstitial nephritis, and upper GI bleeding. Reye syndrome in children with viral infection.

-Overdose initially causes hyperventilation and respiratory alkalosis, but transitions to mixed metabolic
acidosis-respiratory alkalosis.

ADP receptor inhibitors (drugs, mechanism, use, toxicity) - answer-Clopidogrel, prasugrel, ticagrelor
(reversible), ticlopidine.

-Mechanism: inhibit platelet aggregation by irreversibly blocking ADP receptors. Prevent expression of
glycoproteins IIb/IIIa on platelet surface.

-Use: acute coronary syndrome; coronary stenting. Decreased incidence or recurrence of thrombotic
stroke

-Toxicity: neutropenia (ticlopidine). TTP may be seen.

Cilostazol, dipyridamole (mechanism, use, toxicity) - answer--Mechanism: phosphodiesterase III

inhibitor; increase cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators.
-Use: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with
aspirin), angina prophylaxis.

-Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain.

GP IIb/IIIa inhibitors (drugs, mechanism, use, toxicity) - answer-Abciximab, eptifibatide, tirofiban

-Mechanism: bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation.
Abciximab is made from monoclonal antibody Fab fragments.

-Use: unstable angina, percutaneous transluminal coronary angioplasty.

-Toxicity: bleeding, thrombocytopenia.

Cancer drugs - cell cycle - answer--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)

6-mercaptopurine (6-MP), Azathioprine, 6-thioguanine (6-TG) mechanism - answer--Purine (thiol)

analogs leading to decreasedde novo purine synthesis.

-Activated by HGPRT. Azathioprine is metabolized into 6-MP.

6-mercaptopurine (6-MP), Azathioprine, 6-thioguanine (6-TG) clinical use - answer-Preventing organ

rejection, rheumatoid arthritis, IBD, SLE; used to wean patients off steroids in chronic disease and to
treat steroid-refractory chronic disease.

6-mercaptopurine (6-MP), Azathioprine, 6-thioguanine (6-TG) toxicity - answer--Myelosuppression, GI,

liver.

-Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have increase toxicity with
allopurinol or febuxostat.

Cladribine (2-CDA) (mechanism, use, toxicity) - answer--Mechanism: purine analog - multiple

mechanisms (e.g., inhibition of DNA polymerase, DNA strand breaks).
-Use: hairy cell leukemia.

-Toxicity: myelosuppression, nephrotoxicity, and neurotoxicity.

Cytarabine (mechanism, use, toxicity) - answer--Mechanism: pyrimidine analog inhibition of DNA

polymerase.

-Use: leukemias (AML), lymphomas.

-Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia. Cytarabine causes pancytopenia

5-fluorouracil (5-FU) mechanism - answer--Pyrimidine analog bioactivated to 5F-dUMP, which covalently

complexes folic acid.

-This complex inhibits thymidylate synthase decreasing dTMP and decreasing DNA synthesis.

5-fluorouracil (5-FU) use - answer-Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

5-fluorouracil (5-FU) toxicity - answer-Myelosuppression, which is not reversible with leucovorin (folinic
acid)

Methotrexate (MTX) mechanism - answer-Folic acid analog that competitively inhibits dihydrofolate
reductase decreasing dTMP and decreasing DNA synthesis.

Methotrexate (MTX) use - answer--Cancers: leukemias (ALL), lymphomas, choriocarcinoma, sarcomas.

-Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis,
IBD, vasculitis.

Methotrexate (MTX) toxicity - answer--Myelosuppression, which is reversible with leucovorin "rescue."

-Hepatotoxicity.

-Mucositis (e.g., mouth ulcers).

-Pulmonary fibrosis.

Bleomycin (mechanism, use, toxicity) - answer--Mechanism: induces free radical formation causing
breaks in DNA strands.
-Use: testicular cancer, Hodgkin lymphoma.

-Toxicity: Pulmonary fibrosis, skin hyperpigmentation, mucositis, minimal myelosuppression.

Dactinomycin/actinomycin D (mechanism, use, toxicity) - answer--Mechanism: intercalates in DNA.

-Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. **Used for childhood tumors ("children act
out").

-Toxicity: myelosuppression.

Doxorubicin, daunorubicin (mechanism, use, toxicity) - answer--Mechanism: generate free radicals.

Intercalate in DNA causing breaks in DNA decreasing replication.

-Use: solid tumors, leukemias, lymphomas.

-Toxicity: cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following

extravasation.

Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.

What is used to prevent cardiotoxicity with doxorubicin? - answer-Dexrazoxane (iron chelating agent)

Busulfan (mechanism, use, toxicity) - answer--Mechanism: cross-links DNA.

-Use: CML. Also used to ablate patient's bone marrow before bone marrow transplantation.

-Toxicicty: severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation

Cyclophosphamide, ifosfamide (mechanism, use, toxicity) - answer--Mechanism: cross-link DNA at

guanine N-7. Require bioactivation by liver.

-Use: solid tumors, leukemia, lymphomas.

-Toxicity: myelosuppression; hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna
binds toxic metabolites).

Nitrosoureas (drugs, mechanism, use, toxicity) - answer-Carmustine, lomustine, semustine, streptozocin

-Mechanism: require bioactivation. Cross blood-brain barrier into CNS. Cross-link DNA.

-Use: brain tumors (including glioblastoma multiforme).

-Toxicity: CNS toxicity (convulsions, dizziness, ataxia)

Paclitaxel, other taxols (mechanism, use, toxicity) - answer--Mechanism: hyperstabilize polymerized

microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur). "It is
taxing to stay polymerized."

-Use: ovarian and breast carcinomas.

Toxicity: myelosuppression, alopecia, hypersensitivity.

Vincristine, vinblastine (mechanism, use, toxicity) - answer--Mechanism: vinca alkaloids that bind β-
tubulin and inhibit its polymerization into microtubules preventing mitotic spindle formation (M-phase
arrest).

-Use: Solid tumors, leukemias, Hodgkin (vinblastine) and non-Hodgkin (vincristine) lymphomas.

-Toxicity: vincristine: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. Vinblastine blasts bone
marrow (suppression).

Cisplatin, carboplatin (mechanism, use, toxicity) - answer--Mechanism: cross-link DNA.

-Use: testicular, bladder, ovary, and lung carcinomas.

-Toxicity: nephrotoxicity, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and
chloride (saline) diuresis.

How do you prevent nephrotoxicity when taking cisplatin? - answer-With amifostine, a free radical
scavenger, and chloride (saline) diuresis.

Etoposide, teniposide (mechanism, use, toxicity) - answer--Mechanism: etoposide inhibits

topoisomerase II causing increased DNA degradation.

-Use: solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas.

-toxicity: myelosuppression, GI upset, alopecia.

Irinotecan, topotecan (mechanism, use, toxicity) - answer--Mechanism: inhibit topoisomerase I and

prevent DNA unwinding and replication.
-Use: colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).

-Toxicity: severe myelosuppression, diarrhea.

Hydroxyurea (mechanism, use, toxicity) - answer--Mechanism: inhibits ribonucleotide reductase

decreasing DNA Synthesis (S-phase specific).

-Use: melanoma, CML, sickle cell disease ( HbF).

-Toxicity: severe myelosuppression, GI upset.

Prednisone, prednisolone (mechanism, use, toxicity) - answer--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.

Bevacizumab (mechanism, use, toxicity) - answer--Mechanism: monoclonal antibody against VEGF.

Inhibits angiogenesis.

-Use: solid tumors (colorectal cancer, renal cell carcinoma).

-Toxicity: hemorrhage, blood clots, and impaired wound healing.

Erlotinib (mechanism, use, toxicity) - answer--Mechanism: EGFR tyrosine kinase inhibitor.

-Use: non-small cell lung carcinoma.

-Toxicity: rash.

Imatinib (mechanism, use, toxicity) - answer--Mechanism: tyrosine kinase inhibitor of BCR-ABL

(Philadelphia chromosome fusion gene in CML) and c-kit (common in GI stromal tumors).

Use: CML, GI stromal tumors.

-Toxicity: fluid retention.

Rituximab (mechanism, use, toxicity) - answer--Mechanism: monoclonal antibody against CD20, which is
found on most B-cell neoplasms.
-Use: non-Hodgkin lymphoma, CLL, IBD, rheumatoid arthritis.

Toxicity: increased risk of progressive multifocal leukoencephalopathy.

Tamoxifen, raloxifene (mechanism, use, toxicity) - answer--Mechanism: selective estrogen receptor

modulators (SERMs)—receptor antagonists in breast and agonists in bone. Block the binding of estrogen
to ER ⊕ cells.

-Use: breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent
osteoporosis.

-Toxicity: tamoxifen—partial agonist in endometrium, which increases the risk of endometrial cancer;
"hot flashes." Raloxifene—no increased in endometrial carcinoma because it is an estrogen receptor
antagonist in

endometrial tissue.

Difference between tamofixen and raloxifene? - answer-Tamoxifen has increased risk of endometrial
carcinoma whereas raloxifene does not because it is an estrogen receptor antagonist in endometrial
tissue

Trastuzumab (Herceptin) (mechanism, use, toxicity) - answer--Mechanism: monoclonal antibody against

HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill cancer cells that overexpress HER-2, through
inhibition of HER2-initiated cellular signaling and antibody- dependent cytotoxicity.

-Use: HER-2 ⊕ breast cancer and gastric cancer (tras2zumab).

-Toxicity: cardiotoxicity. "Heartceptin" damages the heart.

Vemurafenib (mechanism, use) - answer--Mechanism: small molecule inhibitor of BRAF oncogene ⊕

melanoma

-Use: metastatic melanoma.

Common chemotoxicities (chemo-tox man) - answer--Cisplatin/Carboplatin acoustic nerve damage (and

nephrotoxicity)

-Vincristine peripheral neuropathy

-Bleomycin, Busulfan: pulmonary fibrosis

-Doxorubicin: cardiotoxicity

-Trastuzumab cardiotoxicity
-Cisplatin/Carboplatin: nephrotoxic (and

acoustic nerve damage)

-CYclophosphamide: hemorrhagic cystitis

-5-FU: myelosuppression

-6-M: myelosuppression

-Methotrexate: myelosuppression

Inflammatory mediators image - answer-

Acetaminophen (mechanism, use, toxicity) - answer--Mechanism: reversibly inhibits cyclooxygenase,

mostly in CNS. Inactivated peripherally.

-Use: antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome
in children with viral infection.

-Toxicity: overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione
and forms toxic tissue byproducts in liver. N-acetylcysteine is antidote—regenerates glutathione.

What is the antidote to acetaminophen toxicity? - answer-N-acetylcysteine - regenerates glutathione

Aspirin (mechanism, use, toxicity) - answer--Mechanism: irreversibly inhibits cyclooxygenase (both COX-
1 and COX-2) via acetylation, which synthesis of TXA2 and prostaglandins. bleeding time. No effect on
PT, PTT. A type of NSAID.

-Use: low dose (< 300 mg/day): platelet aggregation. Intermediate dose (300-2400 mg/day): antipyretic
and analgesic. High dose (2400-4000 mg/day): anti-inflammatory.

-Toxicity: gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial
nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Causes
respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis.

Celecoxib (mechanism, use, toxicity) - answer--Mechanism: reversibly inhibits specifically the

cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and vascular endothelium and
mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa. Thus, does not
have the corrosive effects of other NSAIDs on the GI lining. Spares platelet function as TXA2 production
is dependent on COX-1.

-Use: rheumatoid arthritis, osteoarthritis.

-Toxicity: increased risk of thrombosis. Sulfa allergy.

NSAIDs (drugs, mechanism, use, toxicity) - answer-Ibuprofen, naproxen, indomethacin, ketorolac,

diclofenac.

-Mechanism: reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.

-Use: antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.

-Toxicity: interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia
(prostaglandins vasodilate afferent arteriole).

Bisphosphonates (drugs, mechanism, use, toxicity) - answer-Alendronate, other -dronates.

-Mechanism: pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.

-Use: osteoporosis, hypercalcemia, Paget disease of bone.

-Toxicity: corrosive esophagitis (patients are advised to take with water and remain upright for 30
minutes), osteonecrosis of jaw.

Teriparatide (mechanism, use, toxicity) - answer--Mechanism: recombinant PTH analog given

subcutaneously daily. Increases osteoblastic activity.

-Use: osteoporosis. Causes increase bone growth compared to antiresorptive therapies (e.g.,
bisphosphonates). -Toxicity: transient hypercalcemia. May increase risk of osteosarcoma (seen in rodent
studies).

Chronic gout drugs - answer-Allopurinol, febuxostat, pegloticase, probenecid

Allopurinol - answer--Gout

-Inhibits xanthine oxidase after being converted to alloxanthine, decrease conversion of xanthine to uric
acid. Also used in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy.
Increase concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase).

Febuxostat - answer--Gout

-Inhibits xanthine oxidase

Pegloticase - answer--Gout

-Recombinant uricase that catalyze metabolism of uric acid into allantoin (a more water soluble product)

Probenecid - answer-Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits
secretion of penicillin). Can precipitate uric acid calculi.

Gout drugs general diagram - answer-

Acute gout drugs - answer-NSAIDs (naproxen, indomethacin), glucocorticoids, colchicine

Colchicine - answer--Acute gout

-Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and
degranulation.

-Acute and prophylactic value. GI side effects.

TNF-α inhibitors - answer-All TNF-α inhibitors predispose to infection, including reactivation of latent TB,
since TNF is important in granuloma formation and stabilization.

Etanercept - answer--Mechanism: fusion protein (receptor for TNF-α + IgG1 Fc), produced by
recombinant DNA. Etanercept is a TNF decoy receptor.

-Use: rheumatoid arthritis, psoriasis, ankylosing spondylitis

Infliximab, adalimumab - answer--Mechanism: anti-TNF-α monoclonal antibody.

-Use: inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Goal of glaucoma drugs - answer-Decrease IOP via reducing amount of aqueous humor (inhibit
synthesis/secretion or increase drainage)

Epinephrine (α1 agonist) as a glaucoma drug - answer--Mechanism: decrease aqueous humor synthesis
via vasoconstriction
-Side effects: mydriasis (α1); do not use in closed-angle glaucoma. Blurry vision, ocular hyperemia,
foreign body sensation, ocular allergic reactions, ocular pruritus

Brimonidine (α2 agonist) - answer-Decrease aqueous humor synthesis

β-blockers as glaucoma drugs (drugs, mechanism, side-effects) - answer-Timolol, betaxolol, carteolol

-Mechanism: decreased aqueous humor synthesis

-Side effects: No pupillary or vision changes

Acetazolamide as a glaucoma drug - answer--Mechanism: diuretic; decrease aqueous humor synthesis

via inhibition of carbonic anhydrase

-No pupillary or vision changes

Direct cholinomimetics as glaucoma drugs - answer-Pilocarpine, carbachol

-Mechansism: increase outflow of aqueous humor via contraction of ciliary muscle and opening of
trabecular meshwork

-Use pilocarpine in emergencies—very effective at opening meshwork into canal of Schlemm

-Side effects: miosis and cyclospasm (contraction of ciliary muscle)

Indirect cholinomimetics as glaucoma drugs - answer-Physostigmine, echothiophate

-Mechanism: increase outflow of aqueous humor via contraction of ciliary muscle and opening of
trabecular meshwork

-Side effects: miosis and cyclospasm (contraction of ciliary muscle)

Latanoprost (PGF2α) as a glaucoma drug - answer--Decrease outflow of aqueous humor

-Side effect: darkens color of iris (browning)

Morphine mechanism - answer-Act as agonists at opioid receptors (μ = full, κ = full, decreased potency)
to modulate synaptic transmission—open K+ channels, close Ca2+ channels decreasing synaptic
transmission.

Morphine clinical use - answer-Relief of Moderate-Severe Acute & Chronic Pain associated with: Cancer,
MI (vasodilating properties), Relief of Dyspnea (caused by acute LV failure & pulmonary edema),
Preanesthetic Medication

Adverse effects of morphine - answer--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

Methadone mechanism - answer-Full agonist at μ receptor; NMDA receptor antagonist and MAOI

Methadone use - answer--Opioid abuse

-Increasingly Recognized as a useful analgesic (can be used in opioid rotation)

Methadone side effects - answer--CSA Schedule 2 drug

-Same as morphine, plus prolonged QT interval, and cardiac arrhythmia.

-CI: ↓metabolism (by drug-drug interaction or impaired hepatic function) ↑risk of respiratory
depression & cardiac adverse effects. Potential for drug-drug interaction w/ MAOIs & SSRIs (due to weak
inhibition of serotonin reuptake)→ potential for Serotonin Syndrome

Meperidine mechanism - answer-Full agonist at μ receptor with antimuscarinic effects

Meperidine use - answer-No longer first line analgesic due to high adverse effect profile

Meperidine adverse effects - answer--CSA Schedule 2

-Drug-drug interactions w/ MAOIs & SSRIs (due to weak inhibition of serotonin reuptake and/or
inhibition of hepatic CYP enzymes)→ Serotonin Syndrome, Coma, Death

-Use w/ MAOIs (or 2 weeks after) is CI

Fentanyl mechanism - answer-Full agonist at μ receptor

Fentanyl use - answer--One of the Most Used Synthetic Opioids

-Relief of Moderate-Severe Pain

-Anesthetic Adjuvant (Preoperative Analgesia)

-Postoperative or Labor Analgesia (Epidural)

-Chronic Pain (Patch)

-Breakthrough in Cancer pain (Oral Lozenge)

Fentanyl adverse effects - answer--CSA Schedule 2

-As for morphine (except histamine release)

-Chest muscle rigidity if infused IV too fast

-CI: As for morphine

-Use w/ MAOIs (or 2 weeks afterwards)

Partial agonist at μ receptor - answer-codeine and hydrocodone

Codeine (mechanism, use, adverse effects) - answer--Mechanism: partial agonist at μ receptor;

biotransformed into a number of active metabolites: morphine (<10%)

-Use: relief of moderate pain; antitussive in selected patients (at doses much less than needed for
analgesia)

-Adverse effects: same as morphine

Hydrocodone (mechanism, use, adverse effects) - answer--Mechanism: partial agonist at μ receptor;

partially biotransformed to hydromorphone
-Use: in combination w/ acetaminophen for relief of mild-moderate pain (MC prescribed generic drug);
antitussive in selected patients (doses are ↓than needed for analgesia)→ in combination w/
Guaifenesin or other drugs

-Adverse effects: same as morphine

Pentazocine (mechanism, use, adverse effects) - answer--Mechanism: partial agonist at μ receptor and
full agonist at κ receptor

-Use: relief of moderate to severe pain; preoperative sedative and supplement to anesthesia

-Adverse effects: as for morphine (except CVS effects), HTN, tachycardia (opposite to morphine),
injection site reactions (rotate choice of injection site)

-CI: As for morphine; individuals already receiving full agonists (can precipitate opioid withdrawal)

Buprenorphine (mechanism, use, adverse effects) - answer--Mechanism: partial agonist at μ receptor

and full antagonist at κ and δ receptor. Prolonged actions: slow dissociation from μ receptors which also
reduces naloxone antagonism; highly lipophilic

-Use: relief of moderate-severe pain (acute=IM, chronic=transdermal), opioid dependence (sublingual)

-Adverse effects: as for morphine;

-CI: individuals already receiving full agonists (can precipitate opioid withdrawal)

Naloxone (mechanism, use, adverse effects) - answer--Mechanism: antagonist at all opioid receptor sites

-Use: treatment of acute opioid overdose; low dose treatment for adverse effects of opioid agonist
delivered IV or epidural

-Adverse effects: can precipitate withdrawal syndrome in individuals already receiving full agonists
(particularly in dependent users)

-CI: pregnancy→ crosses placenta, can precipitate withdrawal in fetus

Naltrexone (mechanism, use, adverse effects) - answer--Mechanism: antagonist at all opioid receptors

-Use: alcohol dependence treatment; maintenance treatment to prevent relapse in opioid dependent
patients.

-Adverse effects: multiple effects including CNS, hepatic & injection site effects; can precipitate
withdrawal syndrome in individuals already receiving full agonists (particularly in dependent users)

-CI: narcotic dependence or current use of opioid analgesics; compromised liver function
Tramadol (mechanism, use, adverse effects) - answer--Mechanism: inhibition of serotonin & NE
reuptake (main mechanism); μ receptors (partial agonist)→ analgesic effect only partially inhibited by
naloxone

-Use: mild to moderate pain; chronic neuropathic pain (can be insensitive to opioids)

-Adverse effects: as for morphine except - ↓respiratory depression than equivalent doses of morphine,
↓constipation, precipitation of withdrawal on abrupt discontinuation (tapered withdrawal
recommended)

CI: As for morphine; patients w/ Hx of opioid abuse/addiction (can reinitiate dependence). Avoid using
w/ MAOIs & SSRIs (drug-drug interaction)→ Serotonin Syndrome

Butorphanol (mechanism, use, toxicity) - answer--Mechanism: κ-opioid receptor agonist and μ-opioid
receptor partial agonist; produces analgesia.

-Use: severe pain (e.g., migraine, labor). Causes less respiratory depression than full opioid agonists.

-Toxicity: can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition
for opioid receptors). Overdose not easily reversed with naloxone.

Ethosuximide (mechanism, use, side effects) - answer--Mechanism: blocks thalamic T-type Ca2+
channels

-Use: Absence seizures (Sux to have Silent (absence) Seizures)

-Side effects: *Stevens-Johnson syndrome*, GI, fatigue, headache, urticaria,

Benzodiazepines as anti-epileptic (diazepam, lorazepam)(mechanism, use, side effects) - answer--

Mechanism: increase GABA-A action

-Use: first line for acute status epilepticus. Also for eclampsia seizures (1st line is MgSO4)

-Adverse effects: sedation, tolerance, dependence, respiratory depression

Phenytoin (mechanism, use, side effects) - answer--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

Carbamazepine (mechanism, use, side effects) - answer--Mechanism: increase Na+ channel inactivation

-Use: first line for simple, complex, and tonic-clonic seizures. 1st line for trigeminal neuralgia

-Side effects: blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction
of cytochrome P-450, SIADH, *Stevens-Johnson syndrome*

Valproic acid/valproate (mechanism, use, side effects) - answer--Mechanism: increase Na+ channel
inactivation, increase GABA concentration by inhibiting GABA transaminase; action at the T-type Ca2+
channels

-Use: all seizure types except for status epilepticus; first line for tonic-clonic; also used for myoclonic
seizures; bipolar disorder

-Adverse effect: GI, distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects (e.g., spina
bifida), tremor, weight gain, contraindicated in pregnancy

Gabapentin (mechanism, use, side effects) - answer--Mechanism: primarily inhibits high- voltage-
activated Ca2+ channels; designed as GABA analog

-Use: partial (focal) seizures - simple and complex. Also used for peripheral neuropathy, postherpetic
neuralgia

-Adverse effects: sedation and ataxia

Phenobarbital (mechanism, use, side effects) - answer--Mechanism: increased GABA-A receptor action
(keeps receptor open longer)

-Use: simple, complex, and tonic-clonic seizures; 1st line in neonates

-Adverse effects: sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory

depression

Topiramate (mechanism, use, side effects) - answer--Mechanism: blocks Na+ channels, increases GABA
action

-Use: simple, complex, and tonic-clonic seizures; also used for migraine prevention

-Adverse effects: sedation, mental dulling, kidney stones, weight loss

Lamotrigine (mechanism, use, side effects) - answer--Mechanism: blocks voltage gated Na+ channels

-Use: all seizure types except for status epilepticus

-Adverse effects: *Stevens-Johnson syndrome* (titrate slowly)

Levetiracetam (mechanism, use, side effects) - answer--Mechanism: largely unknown; but drug binds to
a synaptic vesicle glycoprotein, SV2A, and inhibits presynaptic calcium channels reducing
neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse
conduction across synapses

-Use: simple, complex, and tonic-clonic seizures

-Side effects: none noted

Tiagabine (mechanism, use, side effects) - answer--Mechanism: increase GABA by inhibiting reuptake

-Use: partial (focal) seizures - simple and complex

-No notable side effects

Vigabatrin (mechanism, use, side effects) - answer--Mechanism: increase GABA by irreversibly inhibiting
GABA transaminase

-Use: partial (focal) seizures - simple and complex

-No notable side effects

What is Stevens-Johnson syndrome and which epilepsy drugs can cause it? - answer--SJ syndrome is a
prodrome of malaise and fever followed by a rapid onset of erythematous/purpuric macules (oral,
ocular, genital). Skin lesions progress to epidermal necrosis and sloughing

-Drugs that can cause this horrific motha ****a: lamotragine, carbamazepine, phenytoin, ethosuximide
(Stephen Johnson's LAMe CAR SUX PHENis)

Drugs for simple seizure - answer--Carbamazepine is 1st choice

-All other epilepsy drugs can be used except for ethosuxamide and the benzodiazepines

Drugs for complex seizure - answer--Carbamazepine is 1st choice

-All other epilepsy drugs can be used except for ethosuxamide and the benzodiazepines

Drugs for tonic-clonic seizure - answer--Carbamazepine, valproate, and phenytoin are 1st choice

-Phenobarbital, lamotragine, topiramate, and levetiracetam can all be used 2nd line

Drugs for absence seizures - answer--Ethosuxamide is 1st line

-Lamotragine and valproate may also be used

Drugs for status epilepticus - answer--Benzodiazepines (diazepam, lorazepam) are first line for acute

-Phenytoin is first line prophylaxis

Barbiturates (drugs, mechanism, use, toxicity) - answer-Phenobarbital, pentobarbital, thiopental,

secobarbital

-Mechanism: facilitate GABA-A action by increasing duration of Cl− channel opening, thus decreasing
neuron firing (barbidurates increase duration). Contraindicated in porphyria.

-Use:sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).

-Toxicity: respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated
by EtOH use); dependence; drug interactions (induces cytochrome P-450). Overdose treatment is
supportive (assist respiration and maintain BP).

Benzodiazepines (drugs, mechanism, use, toxicity) - answer-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)
Nonbenzodiazepine hypnotics (drugs, mechanism, use, toxicity) - answer-Zolpidem, Zaleplon,
esZopiclone. "All ZZZs put you to sleep."

-Mechanism: act at BZI subtype of the GABA receptor;

-Use: insomnia

-Toxicity: ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes.
Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic
effects. Decreased dependence risk than benzodiazepines.

What is the ultra-short acting barbiturate used in IV anesthesia? - answer-Thiopental

Remember "Thio Hucksable had an ultra short acting career"

What are the 4 intermediate acting benzos? - answer-Alprozolam, lorazepam, oxzepam, temazepam

Which benzos are used in the elderly? - answer-Lorazepam, oxazepam, temazepam

"The elderly like Benzos a LOT"

Flumazenil (mechanism, use, toxicity) - answer--Mechanism: : competitive BZ receptor antagonist that

can block the effects of BZ and any drug that binds to the BZ site, including the Z drugs. Does not block
effects of other sedative hypnotics: alcohol, barbiturates or buspirone

-Use: antidote to excessive BZ intake

-Toxicity: none

Buspirone (mechanism, use, toxicity) - answer--Mechanism: partial agonist at 5-HT 1A, acts as agonist
when 5-HT is low and an antagonist when 5-HT is high; may also have effects on D2 receptors; uses P450
enzyme system for elimination; onset of action takes 1-2 weeks; does not work through GABA system;
doesn't produce sedation, confusion, mental clouding; doesn't enhance alcohol or other CNS
depressants
-Use: reduce cognitive aspects of worry and poor concentration; helps in depression with anxiety; useful
with CBT; anxiety in ADHD; alleviates aches, cramps, fatigue, pain, and sexual dysfunction due to GAD

-Toxicity: no abuse liability

-CI: MAOIs

Zaleplon (mechanism, use, toxicity) - answer--Mechanism: agonist at GABA-A α1-subunit (omega 1

receptor); ↑melatonin; shortens sleep latency

-Use: Can be used in middle of the night Tx (4 hours prior to wakening); used for people w/ difficulty
falling asleep but normally stay asleep; effective up to 5 weeks

-Toxicity: tolerance, dependence & rebound insomnia do not occur

Zolpidem (mechanism, use, toxicity) - answer--Mechanism: selective agonist at GABA-A α1-site; shortens
sleep latency, prolongs sleep time; onset w/in 30 minutes; extended release available→ 7 hours of
sleep; T ½: 2-4 hours; greater in hepatic insufficiency & the elderly

-Use: approved for bedtime use to sleep through the night, especially if one has lots of awakenings; can
try to fall asleep & then use after not falling asleep for 30 min. (don't use in the middle of the night b/c
you'll be drowsy if you don't get 7 hours); should taper off for 5 weeks

-Tolerance and dependance rare

Eszopiclone (mechanism, use, toxicity) - answer--Mechanism: agonist at GABA-A α1-subunit (S-isomer of

zopiclone); shortens sleep latency & ↑sleep time; *improves daytime alertness*, gives full night sleep 7-
8 hours, effective for 6-12 months

-Use: only Z drug approved for long-term use

-Can use intermittently w/o fear of withdrawal

Ramelteon (mechanism, use, toxicity) - answer--Mechanism: melatonin agonist (MT1 & 2); shortens
sleep latency

-Use: may be used in the elderly, ICU & those who travel

-No bad side effects, tolerance or dependency

Drugs with solubility in blood = - answer-Rapid induction and recovery times.

Drugs with solubility in lipids = - answer-increased potency = 1 / MAC

MAC - answer--Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of
subjects from moving in response to noxious stimulus (e.g., skin incision).

-Examples: nitrous oxide (N2O) has blood and lipid solubility, and thus fast induction and low potency.
Halothane, in contrast, has lipid and blood solubility, and thus high potency and slow induction.

Inhaled anesthetics (drugs, mechanism, use, toxicity) - answer-Halothane, enflurane, isoflurane,

sevoflurane, methoxyflurane, N2O

-Mechanism: unknown.

-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.

Most common drug used for endoscopy? - answer-Midazolam; used adjunctively with gaseous
anesthetics and narcotics. May cause severe postoperative respiratory depression, BP (treat overdose
with flumazenil), anterograde amnesia.

Arylcyclohexylamines (Ketamine) - answer-PCP analogs that act as dissociative anesthetics. Block NMDA
receptors. Cardiovascular stimulants. Cause disorientation, hallucination, bad dreams. cerebral blood
flow.

Propofol - answer-Used for sedation in ICU, rapid anesthesia induction, short procedures. Less
postoperative nausea than thiopental. Potentiates GABA-A

Esters (local anesthetics) - answer-Procaine, cocaine, tetracaine

Amides (local anesthetics) - answer-Lidocaine, mepIvacaIne, bupIvacaIne

(amIdes have 2 I's in name)

Local anesthetics mechanism - answer-Block Na+ channels by binding to specific receptors on inner
portion of channel. Preferentially bind to activated Na+ channels, so most effective in rapidly firing
neurons. 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels
as charged form

Why give a local anesthetic with vasoconstrictors? - answer-Enhance local action - decrease bleeding,
increase anesthesia by decreasing systemic concentration

Local anesthetic and infected tissue? - answer-Infected tissue is acidic, thus alkaline anesthetics are
charged and cannot penetrate the membrane effectively - need more anesthetic

Order of nerve bockade - answer-small-diameter fibers > large diameter. Myelinated fibers >
unmyelinated fibers. Overall, size factor predominates over myelination such that small myelinated
fibers

> small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers

Order of loss with local anesthetic - answer-1. pain 2. temp 3. touch 4. pressure

Clinical use of local anesthetics - answer-Minor surgical procedures, spinal anesthesia. If allergic to
esters, give amides

Local anesthetic toxicity - answer-CNS excitation, severe cardiovascular toxicity (bupivacaine),

hypertension, hypotension, arrhythmias (cocaine), methemoglobinemia (benzocaine).

Neuromuscular blocking drugs - answer-Muscle paralysis in surgery or mechanical ventilation. Selective

for motor (vs. autonomic) nicotinic receptor.

Depolarizing neuromuscular blocking drugs - answer-Succinylcholine—strong ACh receptor agonist;

produces sustained depolarization and prevents muscle contraction
Reversal of blockade of depolarizing neuromuscular blocking drugs - answer--Phase I (prolonged
depolarization)—no antidote. Block potentiated by cholinesterase inhibitors.

-Phase II (repolarized but blocked; ACh receptors are available, but desensitized)—antidote is
cholinesterase inhibitors.

Complications of depolarizing neuromuscular blocking drugs - answer-Complications include

hypercalcemia, hyperkalemia, malignant hyperthermia.

Nondepolarizing neuromuscular blocking drugs - answer-Tubocurarine, atracurium, mivacurium,

pancuronium, vecuronium, rocuronium—competitive antagonists—compete with ACh for receptors.

Nondepolarizing neuromuscular blocking drugs blockade reversal - answer-Neostigmine (must be given

with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other
cholinesterase inhibitors.

Dantrolene - answer--Mechanism: prevents release of Ca2+ from the sarcoplasmic reticulum of skeletal
muscle.

-Use: malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).

Baclofen - answer--Mechanism: inhibits GABA-B receptors at spinal cord level, inducing skeletal muscle
relaxation.

-Use: muscle spasms (e.g., acute low back pain).

Cyclobenzaprine - answer--Mechanism: centrally acting skeletal muscle relaxant. Structurally related to

TCAs, similar anticholinergic side effects.

-Use: muscle spasms

Dopamine agonists - answer-Ergot—Bromocriptine

Non-ergot (preferred)—pramipexole, ropinirole

Amantadine - answer--Mechanism: increase dopamine release and decrease dopamine reuptake)

-Use: Parkinson disease; also used as an antiviral against influenza A and rubella
-Toxicity: ataxia, livedo reticularis

Levodopa (L-dopa)/carbidopa - answer--Mechanism: carbidopa blocks peripheral conversion of L-DOPA

to dopamine by inhibiting DOPA decarboxylase. Also reduces side effects of peripheral L-dopa
conversion into dopamine (e.g., nausea, vomiting).

-Use: Parkinson disease therapy

Entacapone, tolcapone - answer--Mechanism: prevent peripheral L-dopa degradation to 3-O-

methyldopa (3-OMD) by inhibiting COMT

-Use: Parkinson disease therapy

Selegiline - answer--Mechanism: blocks conversion of dopamine

into 3-MT by selectively inhibiting MAO-B.

-Use: Parkinson disease therapy

Tolcapone - answer--Mechanism: blocks conversion of dopamine to DOPAC by inhibiting central COMT

-Use: Parkinson disease therapy

Benztropine - answer--Mechanism: antimuscarinic; improves tremor and rigidity but has little effect on
bradykinesia

-Use: Parkinson disease therapy

Parkinson disease drugs schematic - answer-

l-dopa (levodopa)/carbidopa - answer--Mechanism: increase level of dopamine in brain. Unlike

dopamine, l-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to
dopamine. Carbidopa, a peripheral DOPA decarboxylase inhibitor, is given with l-dopa to the
bioavailability of l-dopa in the brain and to limit peripheral side effects.

-Use: Parkinson disease.

-Toxicity: arrhythmias from peripheral formation of catecholamines. Long-term use can lead to
dyskinesia following administration ("on-off" phenomenon), akinesia between doses.
Memantine - answer--Mechanism: NMDA receptor antagonist; helps prevent excitotoxicity (mediated
by Ca2+).

-Use: Alzheimer disease

-Toxicity: dizziness, confusion, hallucinations

Donepezil, galantamine, rivastigmine, tacrine - answer--Mechanism: AChE inhibitors

-Use: Alzheimer disease

-Toxicity: nausea, dizziness, insomnia

Treatment of Huntington disease - answer--Neurotransmitter changes in Huntington disease: decrease

GABA, decrease ACh, increase dopamine.

-Treatments: 1. tetrabenazine and reserpine—inhibit vesicular monoamine transporter (VMAT); limit

dopamine vesicle packaging and release; 2. haloperidol—D2 receptor antagonist.

Sumatriptan - answer--Mechanism: 5-HT1B/1D agonists. Inhibit trigeminal nerve activation; prevent

vasoactive peptide release; induce vasoconstriction.

-Use: acute migraine, cluster headache attack

-Toxicity: Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild
paresthesia.

Nonspecific depressant intoxication - answer-Mood elevation, anxiety, sedation, behavioral

disinhibition, respiratory depression.

Nonspecific depressant withdrawal - answer-Anxiety, tremor, seizures, insomnia

Alcohol intoxication - answer-Emotional lability, slurred speech, ataxia, coma, blackouts. Serum γ-
glutamyltransferase (GGT)—sensitive indicator of alcohol use. AST value is twice ALT value.

Alcohol withdrawal - answer-Mild alcohol withdrawal: symptoms similar to other depressants. Severe
alcohol withdrawal can cause autonomic hyperactivity and DTs (5-15% mortality rate). Treatment for
DTs: benzodiazepines.
Opioids (e.g., morphine, heroin, methadone) intoxication - answer-Euphoria, respiratory and CNS
depression,

gag reflex, pupillary constriction (pinpoint pupils), seizures (overdose).

Treatment: naloxone, naltrexone.

Opioids (e.g., morphine, heroin, methadone) withdrawal - answer-Sweating, dilated pupils, piloerection
("cold turkey"), fever, rhinorrhea, yawning, nausea, stomach cramps, diarrhea ("flu-like" symptoms).
Treatment: long-term support, methadone, buprenorphine.

Barbiturates intoxication - answer-Low safety margin, marked respiratory depression. Treatment:

symptom management (e.g., assist respiration, BP).

Barbiturates withdrawal - answer-Delirium, life-threatening cardiovascular collapse.

Benzodiazepines intoxication - answer--Greater safety margin that barbiturates; ataxia, minor

respiratory depression.

-Treatment: flumazenil (benzodiazepine receptor antagonist, but rarely used as it can precipitate
seizures).

Benzodiazepines withdrawal - answer-Sleep disturbance, depression, rebound anxiety, seizure

Nonspecific stimulant intoxication - answer-Mood elevation, psychomotor agitation, insomnia, cardiac

arrhythmias, tachycardia, anxiety.

Nonspecific stimulant withdrawal - answer-post-use "crash," including depression, lethargy, weight gain,
headache

Amphetamines intoxication - answer-Euphoria, grandiosity, pupillary dilation, prolonged wakefulness

and attention, hypertension, tachycardia, anorexia, paranoia, fever. Severe: cardiac arrest, seizure

Amphetamines withdrawal - answer-Anhedonia, appetite, hypersomnolence, existential crisis.

Cocaine intoxication - answer-Impaired judgment, pupillary dilation, hallucinations (including tactile),
paranoid ideations, angina, sudden cardiac death. Treatment: α-blockers, benzodiazepines. β-blockers
not recommended.

Cocaine withdrawal - answer-Hypersomnolence, malaise, severe psychological craving,

depression/suicidality.

Caffeine intoxication - answer-Restlessness, increase diuresis, muscle twitching

Caffeine withdrawal - answer-Lack of concentration, headache

Nicotine intoxication - answer-Restlessness

Nicotine withdrawal - answer-Irritability, anxiety, craving. Treatment: nicotine patch, gum, or lozenges;
bupropion/ varenicline

PCP intoxication - answer-Belligerence, impulsivity, fever, psychomotor agitation, analgesia, vertical and
horizontal nystagmus, tachycardia, homicidality, psychosis, delirium, seizures. Treatment:
benzodiazepines, rapid-acting antipsychotic

PCP withdrawal - answer-Depression, anxiety, irritability, restlessness, anergia, disturbances of thought

and sleep.

LSD intoxication - answer-Perceptual distortion (visual, auditory), depersonalization, anxiety, paranoia,

psychosis, possible flashbacks.

Marijuana intoxication - answer-Euphoria, anxiety, paranoid delusions, perception of slowed time,

impaired judgment, social withdrawal, appetite, dry mouth, conjunctival injection, hallucinations.
Pharmaceutical form is dronabinol (tetrahydrocannabinol isomer): used as antiemetic (chemotherapy)
and appetite stimulant (in AIDS).

Marijuana withdrawal - answer-Irritability, depression, insomnia, nausea, anorexia. Most symptoms

peak in 48 hours and last for 5-7 days. Generally detectable in urine for up to 1 month.
DOC for ADHD - answer-Stimulants (e.g. methylphenidate)

DOC for alcohol withdrawal - answer-Long-acting benzodiazepine (e.g. chlordiazepoxide, lorazepam,

diazepam)

DOC for bipolar disorder - answer-Lithium, valproic acid, atypical antipsychotics

DOC for bulimia - answer-SSRIs

DOC for depression - answer-SSRIs

DOC for generalized anxiety disorder - answer-SSRIs, SNRIs

DOC for OCD - answer-SSRIs, clomipramine

DOC for panic disorder - answer-SSRIs, venlafaxine, benzodiazepines

DOC for PTSD - answer-SSRIs, venlafaxine

DOC for schizophrenia - answer-Atypical antipsychotics

DOC for social phobias - answer-SSRIs, β-blockers

DOC for Tourette syndrome - answer-Antipsychotics(e.g. fluphenazine, pimozide), tetrabenazine,

clonidine

Methylphenidate - answer--Mechanism: ↑dopamine & NE tone by blocking their reuptake & facilitating
their release;

-Use: ADHD; narcolepsy

Amphetamine - answer--Mechanism: ↑dopamine & NE tone by blocking their reuptake & facilitating
their release

-Use: ADHD; improves attention, concentration, execution, wakefulness, hyperactivity

Lisdexamfetamine Demisylate - answer--Mechanism: prodrug (1xDay) for dextroamphetamine; Schedule

II drug; must be absorbed & metabolized in the blood→ once converted to dextroamphetamine, it
↑dopamine & NE tone by blocking their reuptake & facilitating their release

-Use: ADHD

Atomoxetine - answer--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

Bupropion SR - answer--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

Guanfacine - answer--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
List the typical (neuroleptics) antipsychotics - answer-Haloperidol, trifluoperazine, fluphenazine,
thioridazine, chlorpromazine (haloperidol + "-azines")

Typical antipsychotic mechanism - answer-All typical antipsychotics block dopamine D2 receptors (

[cAMP])

Typical antipsychotic use - answer-Schizophrenia (primarily positive symptoms), psychosis, acute mania,
Tourette syndrome

Typical antipsychotic toxicity - answer--Highly lipid soluble and stored in body fat; thus, very slow to be
removed from body.

-Extrapyramidal system side effects (e.g., dyskinesias). Treatment: benztropine or diphenhydramine.

-Endocrine side effects (e.g., dopamine receptor antagonism hyperprolactinemia galactorrhea).

-Side effects arising from blocking muscarinic (dry mouth, constipation), α1 (hypotension), and
histamine (sedation) receptors.

-Can cause QT prolongation.

High potency typical antipsychotics - answer-Trifluoperazine, fluphenazine, haloperidol

"Try to Fly through the Halo"

Side effects of high potency typical antipsychotics - answer--Neurologic side effects (e.g. Huntington
disease, delirium, EPS symptoms)

Low potency typical antipsychotics - answer-Chlorpromazine, thioridazine

Side effects of low potency typical antipsychotics - answer-Non-neurologic side effects (anticholinergic,
antihistamine, and α1-blockade effects).

Side effect of chlorpromazine - answer-Corneal deposits

Side effect of thioridazine - answer-ReTinal deposits

Side effect of haloperidol - answer-NMS, tardive dyskinesia

Evolution of EPS side effects - answer--4 hr acute dystonia (muscle spasm, stiffness,

oculogyric crisis)

-4 day akathisia (restlessness)

-4 wk bradykinesia (parkinsonism)

-4 mo tardive dyskinesia

Neuroleptic malignant syndrome (NMS) - answer-Rigidity, myoglobinuria, autonomic instability,

hyperpyrexia.

Treatment: dantrolene, D2 agonists (e.g., bromocriptine).

For NMS, think FEVER - answer-Fever

Encephalopathy

Vitals unstable

Enzymes up

Rigidity of muscles

Tardive dyskinesia - answer-stereotypic oral- facial movements as a result of long-term antipsychotic

use.

List the atypical antipsychotics - answer-Olanzapine, clozapine, quetiapine, risperidone, aripiprazole,

ziprasidone

Atypical antipsychotics mechanism - answer-Not completely understood. Varied effects on 5-HT2,

dopamine, and α- and H1-receptors
Atypical antipsychotics use - answer-Schizophrenia—both positive and negative symptoms. Also used
for bipolar disorder, OCD, anxiety disorder, depression, mania, Tourette syndrome.

Atypical antipsychotic toxicity - answer--Fewer extrapyramidal and anticholinergic side effects than
traditional antipsychotics.

-Olanzapine/clozapine may cause significant weight gain. --Clozapine may cause agranulocytosis
(requires weekly WBC monitoring) and seizure.

-Risperidone may increase prolactin (causing lactation and gynecomastia) decreasing GnRH, LH, and FSH
(causing irregular menstruation and fertility issues).

-All may prolong QT interval.

Lithium mechanism - answer--Mechanism: not established; possibly related to inhibition of

phosphoinositol cascade.

Lithium use - answer-Mood stabilizer for bipolar disorder; blocks relapse and acute manic events. Also
SIADH.

Lithium toxicity - answer--Tremor, hypothyroidism, polyuria (causes nephrogenic diabetes insipidus),

teratogenesis.

-Causes Ebstein anomaly in newborn if taken by pregnant mother.

-Narrow therapeutic window requires close monitoring of serum levels.

-Almost exclusively excreted by kidneys; most is reabsorbed at PCT with Na+. Thiazide use is implicated
in lithium toxicity in bipolar patients.

Buspirone - answer--Mechanism: stimulates 5-HT1A receptors.

-Use: generalized anxiety disorder. Does not cause sedation, addiction, or tolerance. Takes 1-2 weeks to
take effect. Does not interact with alcohol (vs. barbiturates, benzodiazepines).

Antidepressants schematic - answer-

SSRIs - answer-Fluoxetine, paroxetine, sertraline, citalopram.

SSRIs mechanism - answer-5-HT-specific reuptake inhibitors.

SSRIs use - answer--Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social
phobias, PTSD.

SSRIs toxicity - answer-Fewer than TCAs. GI distress, SIADH, sexual dysfunction (anorgasmia, decreased
libido).

Serotonin syndrome - answer-With any drug that increases 5-HT (e.g., MAO inhibitors, SNRIs, TCAs)
hyperthermia, confusion, myoclonus, cardiovascular instability, flushing, diarrhea, seizures.

-Treatment: cyproheptadine (5-HT2 receptor antagonist).

How long does it take for antidepressants to have an effect? - answer-It normally takes 4-8 weeks for
antidepressants

to have an effect

SNRIs - answer-Venlafaxine, duloxetine

SNRIs mechanism - answer-Inhibit 5-HT and norepinephrine reuptake.

SNRIs use - answer-Depression. Venlafaxine is also used in generalized anxiety disorder, panic disorder,
PTSD. Duloxetine is also indicated for diabetic peripheral neuropathy

SNRIs toxicity - answer-Increase BP most common; also stimulant effects, sedation, nausea.

Tricyclic antidepressants - answer-Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine,

doxepin, amoxapine.

Tricyclic antidepressants mechanism, use, and toxicity - answer--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.

Monoamine oxidase (MAO) inhibitors (drugs, mechanism, use, toxicity) - answer-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).

Bupropion (use, mechanism, toxicity) - answer--Use: Depression; also used for smoking cessation and
ADHD.

-Mechanism: increase norepinephrine and dopamine via unknown mechanism.

-Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in anorexic/bulimic patients. No

sexual side effects.

Mirtazapine (use, mechanism, toxicity) - answer--Use: depression

-Mechanism: α2-antagonist (increase release of norepinephrine and 5-HT) and potent 5-HT2 and 5-HT3
receptor antagonist.

-Toxicity: sedation (which may be desirable in depressed patients with insomnia), increase appetite,
weight gain (which may be desirable in elderly or anorexic patients), dry mouth.

Trazodone - answer--Mechanism: primarily blocks 5-HT2 and α1-adrenergic receptors.

-Used primarily for insomnia, as high doses are needed for antidepressant effects.
-Toxicity: sedation, nausea, priapism, postural hypotension. Called trazobone due to male-specific side
effects.

Diuretics: sites of action schematic - answer-

Mannitol (mechanism, use, toxicity) - answer--Mechanism: osmotic diuretic; increase tubular fluid
osmolarity - increase urine flow, decreasing intracranial/intraocular pressure.

-Use: drug overdose, elevated intracranial/intraocular pressure.

-Toxicity: pulmonary edema, dehydration. Contraindicated in anuria, HF.

Acetazolamide (mechanism, use, toxicity) - answer--Mechanism: carbonic anhydrase inhibitor. Causes

self- limited NaHCO3 diuresis and decreased total body HCO3− stores.

-Use: glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri.

-Toxicity: hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy.

Loop diuretics (drugs, mechanism, use, toxicity) - answer-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.

Ethacrynic acid (mechanism, use, toxicity) - answer--Mechanism: phenoxyacetic acid derivative (not a
sulfonamide). Essentially same action as furosemide.

-Use: diuresis in patients allergic to sulfa drugs.

-Toxicity: similar to furosemide; can cause hyperuricemia; never use to treat gout

Thiazide diuretics (drugs, mechanism, use, toxicity) - answer-Chlorthalidone, hydrochlorothiazide.

-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.

K+-sparing diuretics (drugs, mechanism, use, toxicity) - answer-Spironolactone and eplerenone;

Triamterene, and Amiloride.

-Mechanism: spironolactone and eplerenone are competitive aldosterone receptor antagonists in

cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+
channels in the cortical collecting tubule.

-Use: hyperaldosteronism, K+ depletion, HF.

-Toxicity: hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (e.g.,
gynecomastia, antiandrogen effects).

Urine NaCl changes with diuretic therapy - answer-Increase with all diuretics except acetazolamide.
Serum NaCl may decrease as a result

Urine K+ changes with diuretic therapy - answer-Increase with loop and thiazide diuretics. Serum K+ may
decrease as a result.

Diuretics that decrease blood pH (acidemia) - answer-Carbonic anhydrase inhibitors: decrease HCO3−
reabsorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion. Additionally,
hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.

Diuretics that increase blood pH (alkalemia) - answer-Loop diuretics and thiazides cause alkalemia
through several mechanisms:

-Volume contraction increase AT II increasing Na+/H+ exchange in PCT increasing HCO3− reabsorption
("contraction alkalosis")

-K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells

-In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule causing alkalosis
and "paradoxical aciduria"
Urine Ca2+ changes with diuretic therapy - answer--Increase with loop diuretics: decrease paracellular
Ca2+ reabsorption causing hypocalcemia

-Decreases with thiazides: enhanced Ca2+ reabsorption in DCT

ACE inhibitors (drugs, mechanism, use, toxicity) - answer-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.

Angiotensin II receptor blockers (ARBs) (drugs, mechanism, use, toxicity) - answer-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.

Aliskiren (mechanism, use, toxicity) - answer--Mechanism: direct renin inhibitor, blocks conversion of
angiotensinogen to angiotensin I.

-Use: hypertension

-Toxicity: hyperkalemia, decreased renal function, hypotension.

-Contraindicated in diabetics taking ACE inhibitors or ARBs.

Control of reproductive hormones schematic - answer-

Leuprolide (mechanism, use, toxicity) - answer--Mechanism: GnRH analog with agonist properties

when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates
GnRH receptor in pituitary causing decreased FSH/LH).

-Use: infertility (pulsatile), prostate cancer (continuous use following androgen receptor blockade with
flutamide), uterine fibroids (continuous), precocious puberty (continuous).

-Toxicity: antiandrogen, nausea, vomiting.

Estrogens (ethinyl estradiol, DES, mestranol) (mechanism, use, toxicity) - answer--Mechanism: bind
estrogen receptors.

-Use: hypogonadism or ovarian failure, menstrual abnormalities, hormone replacement therapy in

postmenopausal women; use in men with androgen-dependent prostate cancer.

-Toxicity: increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell
adenocarcinoma of vagina in females exposed to DES in utero, increased risk of thrombi.

-Contraindications—ER ⊕ breast cancer, history of DVTs

Clomiphene (mechanism, use, toxicity) - answer--Mechanism: antagonist at estrogen receptors in

hypothalamus. Prevents normal feedback inhibition and

release of LH and FSH from pituitary, which stimulates ovulation.

-Use: to treat infertility due to anovulation (e.g., PCOS). ----Toxicity: may cause hot flashes, ovarian
enlargement, multiple simultaneous pregnancies, visual disturbances.

Tamoxifen (mechanism, use, toxicity) - answer--Mechanism: antagonist at breast; agonist at bone,

uterus;

-Used to treat and prevent recurrence of ER/PR ⊕ breast cancer;

-Increased risk of thromboembolic events and endometrial cancer (as opposed to raloxifine)

Raloxifene (mechanism, use, toxicity) - answer--Mechanism: antagonist at breast, uterus; agonist at

bone; -Use: primarily to treat osteoporosis

-Increased risk of thromboembolic events but no increased risk of endometrial cancer (vs. tamoxifen);
Hormone replacement therapy - answer--Used for relief or prevention of menopausal symptoms (e.g.,
hot flashes, vaginal atrophy), osteoporosis (increased estrogen, decreased osteoclast activity).

-Unopposed estrogen replacement therapy increases risk of endometrial cancer, so progesterone is

added. Possible increased cardiovascular risk.

Anastrozole/ exemestane - answer-Aromatase inhibitors used in postmenopausal women with ER ⊕

breast cancer.

Progestins (mechanism, use) - answer--Mechanism: bind progesterone receptors, decrease growth and
increase vascularization of the endometrium

-Used in oral contraceptives and to treat endometrial cancer, abnormal uterine bleeding.

Mifepristone (RU-486) (mechanism, use, toxicity) - answer--Mechanism: competitive inhibitor of

progestins at progesterone receptors.

-Use: termination of pregnancy. Administered with misoprostol (PGE1).

Toxicity: heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.

Oral contraception (synthetic progestins, estrogen) - answer--Estrogen and progestins inhibit LH/FSH
and thus prevent estrogen surge. No estrogen surge, then no LH surge then no ovulation.

-Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus. Progestins
also inhibit endometrial proliferation -> endometrium is less suitable to the implantation of an embryo.

-Contraindications: smokers > 35 years old (increased risk of cardiovascular events), patients with
history of thromboembolism and stroke or history of estrogen-dependent tumor.

Terbutaline, ritodrine - answer-β2-agonists that relax the uterus; used to contraction frequency in
women during labor.

Danazol (mechanism, use, toxicity) - answer--Mechanism: synthetic androgen that acts as partial agonist
at androgen receptors.

-Use: endometriosis, hereditary angioedema.

-Toxicity: weight gain, edema, acne, hirsutism, masculinization, decreased HDL levels, hepatotoxicity.
Testosterone, methyltestosterone (mechanism, use, toxicity) - answer--Mechanism: agonists at
androgen receptors.

-Use: treats hypogonadism and promotes development of 2° sex characteristics; stimulation of

anabolism to promote recovery after burn or injury.

-Toxicity: causes masculinization in females; decreased intratesticular testosterone in males by inhibiting

release of LH (via negative feedback) causing gonadal atrophy. Premature closure of epiphyseal plates.
Increased LDL, decreased HDL.

Finasteride - answer--A 5α-reductase inhibitor ( conversion of testosterone to DHT).

-Useful in BPH and male-pattern baldness

Flutamide - answer--A nonsteroidal competitive inhibitor at androgen receptors.

-Used for prostate carcinoma.

Ketoconazole - answer-Inhibits steroid synthesis (inhibits 17,20-desmolase)

Spironolactone - answer-Inhibits steroid binding, 17α-hydroxylase, and 17,20-desmolase.

Use and side effects of ketoconazole and spironolactone - answer-Ketoconazole and spironolactone are
used to treat polycystic ovarian syndrome to reduce androgenic symptoms. Both have side effects of
gynecomastia and amenorrhea

Tamsulosin - answer-α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective
for α1A,D receptors (found on prostate) vs. vascular α1B receptors

Sildenafil, vardenafil, tadalafil (mechanism, use, toxicity) - answer--Mechanism: inhibit PDE-5 increasing
cGMP, smooth muscle relaxation in corpus cavernosum, increase blood flow, penile erection. "Sildenafil,
vardenafil, and tadalafil fill the penis"

-Use: erectile dysfunction.

-Toxicity: headache, flushing, dyspepsia, cyanopsia (blue-tinted vision). Risk of life-threatening

hypotension in patients taking nitrate**
Minoxidil - answer--Mechanism: direct arteriolar vasodilator

-Use: androgenetic alopecia; severe refractory hypertension

1st generation H1 blockers - answer-Diphenhydramine, dimenhydrinate, chlorpheniramine

1st generation H1 blockers mechanism, use, and toxicity - answer--Mechanism: reversible inhibitors of
H1 histamine receptors.

-Use: allergy, motion sickness, sleep aid.

-Toxicity: sedation, antimuscarinic, anti-α-adrenergic.

2nd generation H1 blockers - answer-Loratadine, fexofenadine, desloratadine, cetirizine

2nd generation H1 blockers mechanism, use, and toxicity - answer--Mechanism: reversible inhibitors of
H1 histamine receptors.

-Use: Allergy.

-Toxicity: far less sedating than 1st generation because of decreased entry into CNS.

Guaifenesin - answer-Expectorant—thins respiratory secretions; does not suppress cough reflex.

N-acetylcysteine - answer-Mucolytic—can loosen mucous plugs in CF patients by disrupting disulfide

bonds. Also used as an antidote for acetaminophen overdose.

Dextromethorphan - answer--Antitussive (antagonizes NMDA glutamate receptors).

-Synthetic codeine analog. Has mild opioid effect when used in excess.

-Naloxone can be given for overdose. Mild abuse potential. -May cause serotonin syndrome if combined
with other serotonergic agents

Pseudoephedrine, phenylephrine (mechanism, use, toxicity) - answer--Mechanism: α-adrenergic

agonists, used as nasal decongestants.

-Use: reduce hyperemia, edema, nasal congestion; open obstructed eustachian tubes. Pseudoephedrine
also illicitly used to make methamphetamine.

-Toxicity: hypertension. Can also cause CNS stimulation/anxiety (pseudoephedrine).

Endothelin receptor antagonists - answer--Pulmonary hypertension therapy

-Include bosentan.

-Competitively antagonize endothelin-1 receptors decreasing pulmonary vascular resistance.

-Hepatotoxic (monitor LFTs)

PDE-5 inhibitors - answer--Pulmonary hypertension therapy

-Include sildenafil. Inhibit cGMP PDE5 and prolong vasodilatory effect of nitric oxide. Also used to treat
erectile dysfunction

Prostacyclin analogs - answer--Include epoprostenol, iloprost.

-Prostacyclins (PGI2) with direct vasodilatory effects on pulmonary and systemic arterial vascular beds.

-Inhibit platelet aggregation.

-Side effects: flushing, jaw pain

Bronchoconstriction is mediated by - answer-(1) inflammatory processes and (2) parasympathetic tone;

therapy is directed at these 2 pathways

Albuterol - answer--β2-agonists

-Relaxes bronchial smooth muscle (β2).

-Used during acute exacerbation

Salmeterol, formoterol - answer--β2-agonists

-Long-acting agents for prophylaxis.

-Adverse effects are tremor and arrhythmia.

Fluticasone, budesonide - answer--Corticosteroids

-Inhibit the synthesis of virtually all cytokines. Inactivate NF-κB, the transcription factor that induces
production of TNF-α and other inflammatory agents. 1st-line therapy for chronic asthma.

Ipratropium - answer--Muscarinic antagonist

-Competitively blocks muscarinic receptors, preventing bronchoconstriction. Also used for COPD.
Tiotropium is long acting.

Montelukast, zafirlukast - answer--Antileukotrienes

-Block leukotriene receptors (CysLT1).

-Especially good for aspirin-induced asthma.

Zileuton - answer--Antileukotrienes

-5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes.

-Used for asthma

-Hepatotoxic

Omalizumab - answer--Monoclonal anti-IgE antibody. Binds mostly unbound serum IgE and blocks
binding to FcεRI.

-Used in allergic asthma resistant to inhaled steroids and long-acting β2-agonists.

Theophylline - answer--Methylxanthine

-Likely causes bronchodilation by inhibiting phosphodiesterase increasing cAMP levels due to decreased
cAMP hydrolysis.

-Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by

cytochrome P-450.

-Blocks actions of adenosine.

Methacholine - answer--Muscarinic receptor (M3) agonist.

-Used in bronchial challenge test to help diagnose asthma.