No, but they are less susceptible than the other Beta lactams
Are Cephalosporins resistant to penicillinase?
Mycobacterium tuberculosis, the only agent used as solo prophylaxis against TB
Clinical use of Isoniazid (INH)?
Pseudomembranous colitis (C. difficile), fever, diarrhea
Common side effects associated with Clindamycin include?
GI upset, Superinfections, Skin rashes, Headache, Dizziness
Common toxicities associated with Fluoroquinolones?
Glycoproteins from leukocytes that block various stages of viral RNA and DNA synthesis
Describe the MOA of Interferons (INF)
AmOxicillin has greater Oral bioavailability
Does Ampicillin or Amoxicillin have a greater oral bioavailability?
Triple Therapy' 2 Nucleoside RT Inhibitors with a Protease Inhibitor
How are the HIV drugs used clinically?
Pretreat with antihistamines and a slow infusion rate
How can Vancomycin-induced 'Red Man Syndrome' be prevented?
As PABA antimetabolites that inhibit Dihydropteroate Synthase, Bacteriostatic
How do Sulfonamides act on bacteria?
Ganciclovir is more toxic to host enzymes
How does Ganciclovir's toxicity relate to that of Acyclovir?
HSV, VZV, EBV, Mucocutaneous and Genital Herpes Lesions, Prophylaxis in Immunocompromised pts
How is Acyclovir used clinically?
Wide spectrum of systemic mycoses: Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor
How is Amphotericin B used clinically?
Meningitis (H. influenza, N. meningitidis, S. pneumoniae), Conserative treatment due to toxicities
How is Chloramphenical used clinically?
1. Mycobacterium tuberculosis 2. Delays resistance to Dapsone when used of Leprosy 3. Used in combination with other drugs
How is Rifampin used clinically?
Used in combination therapy with SMZ to sequentially block folate synthesis
How is Trimethoprim used clinically?
Premature infants, because they lack UDP-glucuronyl transferase
In what population does Gray Baby Syndrome occur? Why?
1)Binds penicillin-binding proteins 2) Blocks transpeptidase cross- linking of cell wall 3) Activates autolytic enzymes
MOA for Penicillin (3 answers)?
Penicillin, Cephalosporins, Vancomycin, Aminoglycosides, Fluoroquinolones, Metronidazole
MOA: Bactericidal antibiotics
Penicillin, Ampicillin, Ticarcillin, Pipercillin, Imipenem, Aztreonam, Cephalosporins
MOA: Block cell wall synthesis by inhib. Peptidoglycan cross-linking (7)
Chloramphenicol, Erythromycin/macrolides, Lincomycin, Clindamycin, Streptogramins (quinupristin, dalfopristin)
MOA: Block protein synthesis at 50s subunit
Sulfamethoxazole (SMZ), Sulfisoxazole, Triple sulfas, Sulfadiazine
Name some common Sulfonamides (4)
Ciprofloxacin, Norfloxacin, Ofloxacin, Grepafloxacin, Enoxacin, Nalidixic acid
Name the common Fluoroquinolones (6)
Zidovudine (AZT), Didanosine (ddI), Zalcitabine (ddC), Stavudine (d4T), Lamivudine (3TC)
Name the common Nucleoside Reverse Transcriptase Inhibitors
Staphlococcus aureus and Clostridium difficile (pseudomembranous colitis)
Name two organisms Vancomycin is commonly used for?
Modification via Acetylation, Adenylation, or Phosphorylation
Resistance mechanisms for Aminoglycosides
Altered bacterial Dihydropteroate Synthetase, Decreased uptake, or Increased PABA synthesis
Resistance mechanisms for Sulfonamides
Terminal D-ala of cell wall replaced with D-lac; Decreased affinity
Resistance mechanisms for Vancomycin
Hemolysis (if G6PD deficient), Neurotoxicity, Hepatotoxicity, SLE-like syndrome
Side effects of Isoniazid (INH)?
Binds to the Pyrophosphate Binding Site of the enzyme
Specifically, how does Foscarnet inhibit viral DNA pol?
Hormone synthesis inhibition (Gynecomastia), Liver dysfunction (Inhibits CYP450), Fever, Chills
Toxic side effects of the Azoles?
Nephrotoxicity (esp. with Cephalosporins), Ototoxicity (esp. with Loop Diuretics)
What are common serious side effects of Aminoglycosides and what are these associated with?
Fever/Chills, Hypotension, Nephrotoxicity, Arrhythmias
What are common side effects of Amphotericin B?
GI intolerance (nausea, diarrhea), Hyperglycemia, Lipid abnormalities, Thrombocytopenia (Indinavir)
What are common side effects of Protease Inhibitors?
BM suppression (neutropenia, anemia), Peripheral neuropathy
What are common side effects of RT Inhibitors?
-Hypersensitivity reactions -Hemolysis -Nephrotoxicity (tubulointerstitial nephritis) -Kernicterus in infants Displace other drugs from albumin (e.g., warfarin)
What are common toxic side effects of Sulfonamides? (5)
GI discomfort, Acute cholestatic hepatitis, Eosinophilia, Skin rashes
What are common toxicities associated with Macrolides? (4)
GI distress, Tooth discoloration and Inhibition of bone growth in children, Fanconi's syndrome, Photosensitivity
What are common toxicities associated with Tetracyclines?
Well tolerated in general but occasionally, Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing='Red Man Syndrome'
What are common toxicities related to Vancomycin therapy?
1.Gram - rods of the Urinary and GI tracts (including Pseudomonas) 2.Neisseria 3. Some Gram + organisms
What are Fluoroquinolones indicated for? (3)
What are major side effects of Methicillin, Nafcillin, and Dicloxacillin?
Gram + cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae (PEcK)
What are the clinical uses for 1st Generation Cephalosporins?
Gram + cocci, Haemophilus influenza, Enterobacter aerogenes, Neisseria species, P. mirabilis, E. coli, K. pneumoniae, Serratia marcescens ( HEN PEcKS )
What are the clinical uses for 2nd Generation Cephalosporins?
1) Serious Gram - infections resistant to other Beta lactams 2) Meningitis (most penetrate the BBB)
What are the clinical uses for 3rd Generation Cephalosporins?
Gram - rods: Klebsiella species, Pseudomonas species, Serratia species
What are the clinical uses for Aztreonam?
-Upper respiratory tract infections -pneumonias -STDs: Gram+ cocci (streptococcal infect in pts allergic to penicillin) -Mycoplasma, Legionella,Chlamydia, Neisseria
What are the Macrolides used for clinically?
Cephalosporin: 1) has a 6 member ring attached to the Beta lactam instead of a 5 member ring 2)has an extra functional group ( attached to the 6 member ring)
What are the major structural differences between Penicillin and Cephalosporin?
GI distress, Skin rash, and Seizures at high plasma levels
What are the major toxic side effects of Imipenem/cilastatin?
1) Hypersensitivity reactions 2) Increased nephrotoxicity of Aminoglycosides 3) Disulfiram-like reaction with ethanol (those with a methylthiotetrazole group, e.g., cefamandole)
What are the major toxic side effects of the Cephalosporins?
Aplastic anemia (dose independent), Gray Baby Syndrome
What are toxicities associated with Chloramphenicol?
Giardiasis, Amoebic dysentery (E. histolytica), Bacterial vaginitis (Gardnerella vaginalis), Trichomonas
What conditions are treated with Metronidazole?
Mebendazole/Thiabendazole, Pyrantel Pamoate
What do you treat Nematode/roundworm (pinworm, whipworm) infections with?
AZT, to reduce risk of Fetal Transmission
What drug is used during the pregnancy of an HIV+ mother?, Why?
What drug is used to treat Trematode/fluke (e.g., Schistosomes, Paragonimus, Clonorchis) or Cysticercosis
Blocks Influenza A and RubellA; causes problems with the cerebellA
What is a mnemonic to remember Amantadine's function?
It must be Phosphorylated by Viral Thymidine Kinase
What is a prerequisite for Acyclovir activation?
Pseudomonas species and Gram - rods
What is clinical use for Carbenicillin, Piperacillin, and Ticarcillin?
Recurrent UTIs, Shigella, Salmonella, Pneumocystis carinii pneumonia
What is combination TMP-SMZ used to treat?
What is combined with Ampicillin, Amoxicillin, Carbenicillin, Piperacillin, and Ticarcillin to enhance their spectrum?
Cryptococcal meningitis in AIDS patients and Candidal infections of all types
What is Fluconazole specifically used for?
Blastomyces, Coccidioides, Histoplasma, C. albicans; Hypercortisolism
What is Ketoconazole specifically used for?
Bismuth and Amoxicillin or Tetracycline; against Helobacter pylori
What is Metronidazole combined with for 'triple therapy'? Against what organism?
Antiprotozoal: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis Anaerobes: Bacteroides, Clostridium
What is Metronidazole used for clinically?
Extended spectrum penicillin: certain Gram + bacteria and Gram - rods
What is the clinical use for Ampicillin and Amoxicillin?
Bactericidal for: Gram + rod and cocci, Gram - cocci, and Spirochetes
What is the clinical use for Penicillin?
What is the major side effect for Carbenicillin, Piperacillin, and Ticarcillin?
1. RNA pol inhibitor 2. Revs up P450 3. Red/orange body fluids 4. Rapid resistance if used alone
What is the memory key involving the '4 R's of Rifampin?'
Same as penicillin. Extended spectrum antibiotics
What is the MOA for Carbenicillin, Piperacillin, and Ticarcillin?
Same as penicillin. Act as narrow spectrum antibiotics
What is the MOA for Methicillin, Nafcillin, and Dicloxacillin?
Inhibits formation of Initiation Complex, causes misreading of mRNA, Bactericidal
What is the MOA for the Aminoglycosides?
Blocks translocation, binds to the 23S rRNA of the 50S subunit, Bacteriostatic
What is the MOA for the Macrolides?
Binds 30S subunit and prevents attachment of aminoacyl-tRNA, Bacteriostatic
What is the MOA for the Tetracyclines?
Blocks viral penetration/uncoating; may act to buffer the pH of the endosome
What is the MOA of Amantadine?
Interferes with microtubule function, disrupts mitosis, inhibits growth
What is the MOA of Griseofulvin?
Bind cell membrane, disrupt osmotic properties, Are Cationc, Basic and act as detergents
What is the MOA of Polymyxins?
Inhibits IMP Dehydrogenase (competitively), and therefore blocks Guanine Nucleotide synthesis
What is the MOA of Ribavirin?
Inhibit RT of HIV and prevent the incorporation of viral genome into the host DNA
What is the MOA of the RT Inhibitors?
Vibrio cholerae Acne Chlamydia Ureaplasma Urealyticum Mycoplasma pneumoniae Borrelia burgdorferi (Lyme's) Rickettsia Tularemia
What microorganisms are clinical indications for Tetracycline therapy?
Tendonitis and Tendon rupture
What musculo-skeletal side effects in Adults are associated with Floroquinolones?
Dopamine; causes its release from intact nerve terminals
What neurotransmitter does Amantadine affect? How does it influence this NT?
Giant Roundworm (Ascaris), Hookworm (Necator/Ancylostoma), Pinworm (Enterobius)
What parasites are treated with Pyrantel Pamoate (more specific)?
Onchocerciasis ('river blindness'--rIVER-mectin)
What parasitic condition is treated with Ivermectin?
Pregnant women, Children; because animal studies show Damage to Cartilage
What populations are Floroquinolones contraindicated in? Why?
Milk or Antacids, because divalent cations inhibit Tetracycline absorption in the gut
What should not be taken with Tetracyclines? / Why?
1. Meningococcal carrier state 2. Chemoprophylaxis in contacts of children with H. influenzae type B
When is Rifampin not used in combination with other drugs?
1) Aminoglycosides = bactericidal 2) Tetracyclines = bacteriostatic
Which antimicrobial classes inhibit protein synthesis at the 30S subunit? (2)
1) Chloramphenical = bacteriostatic 2) Erythromycin = bacteriostatic 3) Lincomycin = bacteriostatic 4)cLindamycin = bacteriostatic
Which antimicrobials inhibit protein synthesis at the 50S subunit? (4)
Doxycycline, because it is fecally eliminated
Which Tetracycline is used in patients with renal failure? / Why?
Due to the presence of a bulkier R group
Why are Methicillin, Nafcillin, and Dicloxacillin penicillinase resistant?
To inhibit renal Dihydropeptidase I and decrease Imipenem inactivation in the renal tubules
Why is Cilastatin administered with Imipenem?
-S-phase anti-metabolite Pyr analogue -Colon, solid tumors, & BCC/ -Irreversible myelosuppression
List the mechanism, clinical use, & toxicity of 5 FU.
-DNA intercalator -testicular & lymphomas -Pulmonary fibrosis mild myelosuppression.
List the mechanism, clinical use, & toxicity of Bleomycin.
-Alkalates DNA -CML -Pulmonary fibrosis hyperpigmentation
List the mechanism, clinical use, & toxicity of Busulfan.
-Alkalating agent -testicular,bladder,ovary,& lung -Nephrotoxicity & CN VIII damage.
List the mechanism, clinical use, & toxicity of Cisplatin.
-Alkalating agent -NHL, Breast, ovary, & lung. - Myelosuppression, & hemorrhagic cystitis.
List the mechanism, clinical use, & toxicity of Cyclophosphamide.
-DNA intercalator -Hodgkin's, myeloma, sarcoma, and solid tumors -Cardiotoxicity & alopecia
List the mechanism, clinical use, & toxicity of Doxorubicin.
-Topo II inhibitor(GII specific) -Oat cell of Lung & prostate, & testicular -Myelosuppression & GI irritation.
List the mechanism, clinical use, & toxicity of Etoposide.
-S-phase anti-metabolite folate analogue -Luk, Lymp, sarc, RA, & psoriasis / -Reversible myelosuppression
List the mechanism, clinical use, & toxicity of Methotrexate.
-Alkalate DNA -Brain tumors -CNS toxicity
List the mechanism, clinical use, & toxicity of Nitrosureas.
-MT polymerization stabilizer -Ovarian & breast CA -Myelosupperession & hypersensitivity.
List the mechanism, clinical use, & toxicity of Paclitaxel.
-Triggers apoptosis -CLL, Hodgkin's in MOPP -Cushing-like syndrome
List the mechanism, clinical use, & toxicity of Prednisone.
-Estrogen receptor antagonist -Breast CA -increased endometrial CA risk
List the mechanism, clinical use, & toxicity of Tamoxifen.
-MT polymerization inhibitor(M phase) -MOPP, lymphoma, Willm's & choriocarcinoma -neurotoxicity and myelosuppression
List the mechanism, clinical use, & toxicity of Vincristine.
-Alkalating agents+cisplatin -Doxorubicin+Dactinomycin -Bleomycin -Etoposide
Which cancer drugs effect nuclear DNA (4)?
reduce levels of Angiotensin II, thereby preventing the inactivation of bradykinin (a potent vasodilator); renin level is increased
ACE inhibitors- mechanism?
fetal renal damage, hyperkalemia, Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems, Rash, Increased renin, Lower Angiotensin II (CAPTOPRIL)
ACE inhibitors- toxicity?
glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness
Acetazolamide- clinical uses?
acts at the proximal convoluted tubule to inhibit carbonic anhydrase. Causes self-limited sodium bicarb diuresis and reduction of total body bicarb stores.
impotence, asthma, CV effects (bradycardia, CHF, AV block), CNS effects (sedation, sleep alterations)
adverse effects of beta-blockers?
fetal renal toxicity, hyperkalemia, Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems, Rash, Increased renin, Lower Angiotensin II (CAPTOPRIL)
adverse effects of Captopril?
severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction
adverse effects of ganglionic blockers?
nausea, headache, lupus-like syndrome, reflex tachycardia, angina, salt retention
adverse effects of Hydralazine?
hypokalemia, slight hyperlipidemia, hyperuricemia, lassitude, hypercalcemia, hyperglycemia
adverse effects of Hydrochlorothiazide?
hypertrichosis, pericardial effusion, reflex tachycardia, angina, salt retention
adverse effects of Minoxidil?
pulmonary fibrosis, corneal deposits, hepatotoxicity, skin deposits resulting in photodermatitis, neurologic effects, consitpation, CV (bradycardia, heart block, CHF), and hypo- or hyperthyroidism.
block voltage dependent L-type Ca2+ channels of cardiac and smooth muscle- decreasing contractility
Ca2+ channel blockers- mechanism?
cardiac depression, peripheral edema, flushing, dizziness, constipation
Ca2+ channel blockers- toxicity?
increased AP duration, increased ERP increased QT interval. Atrial and ventricular.
Antiarrhythmic class IA effects?
decrease AP duration, affects ischemic or depolarized Purkinje and ventricular system
Antiarrhythmic class IB- effects?
NO AP duration effect. useful in V-tach that progresses to V-fib and in intractable SVT LAST RESORT
Antiarrhythmic class IC- effects?
decrease the slope of phase 4, increase PR interval (the AV node is particularly sensitive)
Antiarrhythmic class II- effects?
blocking the beta adrenergic receptor leads to decreased cAMP, and decreased Ca2+ flux
Antiarrhythmic class II- mechanism?
impotence, exacerbation of asthma, CV effects, CNS effects, may mask hypoclycemia
Antiarrhythmic class II- toxicity?
increase AP duration, increase ERP, increase QT interval, for use when other arrhythmics fail
Antiarrhythmic Class III- effects?
constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression), and torsade de pointes (Bepridil)
Antiarrhythmic class IV- toxicity?
diuretics, sympathoplegics, vasodilators, ACE inhibitors, Angiotensin II receptor inhibitors
classes of antihypertensive drugs?
Sulfonamide Loop Diuretic. Inhibits ion co-transport system of thick ascending loop. Abolishes hypertonicity of the medulla, thereby preventing concentration of the urine.
Furosemide- class and mechanism?
edematous states (CHF, cirrhosis, nephrotic syndrome, pulm edema), HTN, hypercalcemia
Furosemide- clinical use?
Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout
Furosemide- toxicity? (OH DANG)
decrease myocardial O2 consumption by: 1-decreasing end diastolic volume 2- decreasing BP 3- decreasing HR 4-decreasing contractility 5-decreasing ejection time
how do we stop angina?
vasodilator- increases cGMP to induce smooth muscle relaxation (arterioles>veins; afterload reduction)
Hydralazine- class and mechanism?
Inhibits NaCl reabsorption in the early distal tubule. Decreases Ca2+ excretion.
Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia, sulfa allergy.
Hydrochlorothiazide- toxicity? (hyperGLUC, plus others)
osmotic diuretic- increase tubular fluid osmolarity, thereby increasing urine flow
cardiac muscle: Verapamil>Diltiazem>Nifedipine
preferential action of the Ca2+ channel blockers at cardiac muscle?
vascular sm. Mus.: Nifedipine>Diltiazem>Verapamil
preferential action of the Ca2+ channel blockers at vascular smooth muscle?
cinchonism: HA, tinnitus, thrombocytopenia, torsade de pointes due to increased QT interval
Hydralazine and Minoxidil
what two vasodilators require simultaneous treatment with beta blockers to prevent reflex tachycardia and diuretics to prevent salt retention?
all except the K+ sparing diuretics Spironolactone, Triamterene, Amiloride
which diuretics increase urine K+?
Acetaminophen has antipyretic and analgesic properties, but lacks anti-inflammatory properties.
Acetaminophen has what two clinical uses and lacks what one clinical use of the NSAIDs?
Impairs the synthesis of vitamin K-dependent clotting factors
For Warfarin what is the Mechanism of action
1. Hydrocortisone 2. Predisone 3. Triamcinolone 4. Dexamethasone 5. Beclomethasone
List five common glucocorticoids.
The COX-2 inhibitors should not have the corrosive effects of other NSAIDs on the gastrointestinal lining.
The COX-2 inhibitors (celecoxib, rofecoxib) have similar side effects to the NSAIDs with what one exception?
Sulfonylureas are oral hypoglycemic agents, they are used to stimulate release of endogenous insulin in NIDDM (type-2).
What are are the Sulfonylureas (general description) and what is their use?
1. Reliable (<1% failure) 2. Lowers risk of endometrial and ovarian cancer 3. Decreased incidence of ectopic pregnancy 4. Lower risk of pelvic infections 5. Regulation of menses
What are five advantages of Oral Contraceptives (synthetic progestins, estrogen)?
1. Taken daily 2. No protection against STDs 3. Raises triglycerides 4. Depression, weight gain, nausea, HTN 5. Hypercoagulable state
What are five disadvantages of Oral Contraceptives (synthetic progestins, estrogen)?
1. Gastric ulceration 2. Bleeding 3. Hyperventilation 4. Reye's syndrome 5. Tinnitus (CN VIII)
What are five possible toxic effects of Aspirin therapy?
1. Significant: nephrotoxicity 2. Peripheral neuropathy 3. Hypertension 4. Pleural effusion 5. Hyperglycemia.
What are five toxicities associated with Tacrolimus (FK506)?
1. Better bioavailability 2. 2 to 4 times longer half life 3. Can be administered subcutaneously 4. Does not require laboratory monitoring
What are four advantages of newer low-molecular-weight heparins (Enoxaparin)?
1. Antipyretic 2. Analgesic 3. Anti-inflammatory 4. Antiplatelet drug.
What are four clinical activities of Aspirin?
1. Addison's disease 2. Inflammation 3. Immune suppression 4. Asthma
What are four clinical uses of glucocorticoids?
1. Peptic ulcer 2. Gastritis 3. Esophageal reflux 4. Zollinger-Ellison syndrome
What are four conditions in which H2 Blockers are used clinically?
1. Hot flashes 2. Ovarian enlargement 3. Multiple simultaneous pregnancies 4. Visual disturbances
What are four unwanted effects of Clomiphene use?
1. Buffalo hump 2. Moon facies 3. Truncal obesity 4. Muscle wasting 5. Thin skin 6. Easy bruisability 7. Osteoporosis 8. Adrenocortical atrophy 9. Peptic ulcers
What are nine findings of Iatrogenic Cushing's syndrome caused by glucocorticoid therapy?
Headache, flushing , dyspepsia, blue-green color vision.
What are signs of Sildenafil (Viagra) toxicity?
Acute coronary syndrome; coronary stenting. Decreases the incidence or recurrence of thrombotic stroke.
What are the clinical uses for Ticlopidine, Clopidogrel?
1. Peptic ulcer 2. Gastritis 3. Esophageal reflux 4. Zollinger-Ellison syndrome
What are the four conditions in which Omeprazole, Lansoprazole is used?
1. Infertility (pulsatile) 2. Prostate cancer (continuous: use with flutamide) 3. Uterine fibroids
What are three clinical uses of the Leuprolide?
1. Bleeding 2. Teratogenicity 3. Drug-drug interactions
What are three complications of Warfarin usage?
1. Bleeding 2. Thrombocytopenia 3. Drug-drug interactions
What are three possible complications of Heparin therapy?
1. Renal damage 2. Aplastic anemia 3. GI distress
What are three possible toxicities of NSAID usage?
1. Skin rash 2. Agranulocytosis (rare) 3. Aplastic anemia
What are three toxicities of Propylthiouracil?
1. Aluminum hydroxide: constipation and hypophosphatemia 2. Magnesium hydroxide: diarrhea 3. Calcium carbonate: Hypercalcemia, rebound acid increase - All may cause hypokalemia
What are three types of antacids and the problems that can result from their overuse?
1. Heavy bleeding 2. GI effects (n/v, anorexia) 3. Abdominal pain
What are three unwanted effects of Mifepristone?
1. Kidney transplantation 2. Autoimmune disorders (including glomerulonephritis and hemolytic anemia)
What are two clinical uses of Azathioprine?
Inhibits organification and coupling of thyroid hormone synthesis. Also decreases peripheral conversion of T4 to T3.
What are two mechanisms of action of Propythiouracil?
1. Phospholipase A2 is prevented from releasing arachidonic acid 2. Decreases protein synthesis thus lowering amount of Cyclooxygenase enzymes
What are two processes Corticosteroids inhibit leading to decreased inflammation?
1. Predisposes to viral infections and lymphoma 2. Nephrotoxic (preventable with mannitol diuresis)
What are two toxicities associated with Cyclosporine?
1. Hypoglycemia (more common with 2nd-generation drugs: glyburide, glipizide) 2. Disulfiram-like effects (not seen with 2nd-generation drugs).
What are two toxicities of the Sulfonylureas?
Sucralfate cannot work in the presence of antacids or H2 blockers because it requires an acidic environment to polymerize.
What are two types of drugs that interfere with the action of Sucralfate and why?
Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.
What can result due to antacid overuse?
Cyclooxygenases (COX I, COX II).
What enzymes are inhibited by NSAIDs, acetaminophen and COX II inhibitors?
GI side effects. (Note: Indomethacin is less toxic, more commonly used.)
What is a common side effect of Colchicine used to treat acute gout, especially when given orally?
Overdose produces hepatic necrosis; acetaminophen metablolite depletes glutathione and forms toxic tissue adducts in liver.
What is a possible result of overdose of Acetaminophen?
What is a possible toxicity of Alpha-glucosidase inhibitors used in type-2 diabetes?
Neutropenia (ticlopidine); reserved for those who cannot tolerate aspirin.
What is a possible toxicity of Ticlopidine, Clopidogrel usage?
1. In liver, increases storage of glucose as glycogen. 2. In muscle, stimulates glycogen and protein synthesis, and K+ uptake. 3. In adipose tissue, facilitates triglyceride storage.
What is action of insulin in the liver, in muscle, and in adipose tissue?
1. Suppresses organ rejection after transplantation 2. Selected autoimmune disorders.
What is are two clinical uses of Cyclosporine?
Antileukotriene; blocks leukotriene receptors.
What is the category and mechanism of action of Zafirlukast in Asthma treatment?
Antileukotriene; blocks synthesis by lipoxygenase.
What is the category and mechanism of action of Zileuton in Asthma treatment?
Phenothiazine (neuroleptic, antiemetic).
What is the category of drug names ending in -azine (e.g. Chlorpromazine)
Antibiotic, protein synthesis inhibitor.
What is the category of drug names ending in -cycline (e.g. Tetracycline)
What is the category of drug names ending in -operidol (e.g. Haloperidol)
Cardiac glycoside (inotropic agent).
What is the category of drug names ending in -oxin (e.g. Digoxin)
What is the category of drug names ending in -triptyline (e.g. Amitriptyline)
Nonspecific beta-agonist; desired effect is the relaxation of bronchial smooth muscle (Beta 2). Adverse effect is tachycardia (Beta 1).
What is the category, desired effect, and adverse effect of Isoproterenol in the treatment of Asthma?
Beta 2 agonist; desired effect is the relaxation of bronchial smooth muscle (Beta 2). Use during acute exacerbation.
What is the category, desired effect, and period of use of albuterol in the treatment of Asthma?
Methylzanthine; desired effect is bronchodilation, may cause bronchodilation by inhibiting phosphodiesterase, enzyme involved in degrading cAMP (controversial).
What is the category, desired effect, and possible mechanism of Theophylline in treating Asthma?
Muscarinic antagonist; competatively blocks muscarinic receptors, preventing bronchoconstriction.
What is the category, mechanism of action, and effect of Ipratroprium in Asthma treatment?
Corticosteroids; prevent production of leukotrienes from arachodonic acid by blocking phospholipase A2. Drugs of choice in a patient with status asthmaticus (in combination with albuterol.)
What is the category, mechanism of action, and particular use of beclomethasone and prednisone in Asthma treatment?
Beta 2 agonist; used as a long-acting agent for prophylaxis. Adverse effects are tremor and arrhythmia.
What is the category, method of use, and adverse effects of Salmeterol in Asthma treatment?
Prevention of NSAID-induced peptic ulcers, maintains a PDA.
What is the clincial use for Misoprostol?
Potent immunosuppressive used in organ transplant recipients.
What is the clinical use of Tacrolimus (FK506)?
Increase target cell response to insulin.
What is the effect of the Glitazones in diabetes treatment?
Finasteride inhibits 5 Alpha-reductase, this decreases the conversion of testosterone to dihydrotestosterone, useful in BPH
What is the enzyme inhibited, the effect of this inhibition, and the clinical use of the antiandrogren Finasteride?
Aluminum sucrose sulfate polymerizes in the acid environment of the stomach and selectively binds necrotic peptic ulcer tissue. Acts as a barrier to acid, pepsin, and bile.
What is the mecanism of action of Sucralfate?
Selectively inhibit cyclooxygenase (COX) isoform 2, which is found in inflammatory cells nad mediates inflammation and pain; spares COX-1 which helps maintain the gastric mucosa.
What is the mecanism of action of the COX-2 inhibitors (celecoxib, rofecoxib)?
Prevents release of mediators from mast cells. Effective only for the prophylaxis of asthma. Not effective during an acute attack.
What is the mecanism of action, effective period, and ineffective period of use for Cromolyn in treating Asthma?
Flutamide is a nonsteroidal competitive inhibitor of androgens at the testosterone receptor, used in prostate carcinoma.
What is the mechanism of action and clinical use of the antiandrogen Flutamide?
Inhibit steroid synthesis, used in the treatment of polycystic ovarian syndrome to prevent hirsutism.
What is the mechanism of action and clinical use of the antiandrogens Ketoconazole and Spironolactone?
Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
What is the mechanism of action of Acetaminophen?
Inhibits xanthine oxidase, decresing conversion of xanthine to uric acid.
What is the mechanism of action of Allopurinol used to treat chronic gout?
Acetylates and irreversibly inhibits cyclooxygenase (COX I and COX II) to prevent the conversion of arachidonic acid to prostaglandins.
What is the mechanism of action of Aspirin?
Clomiphene is a partial agonist at estrogen receptors in the pituitary gland. Prevents normal feedback inhibition and increses release of LH and FSHfrom the pituitary, which stimulates ovulation.
What is the mechanism of action of Clomiphene?
Depolymerizes microtubules, impairing leukocyte chemotaxis and degranulation.
What is the mechanism of action of Colchicine used to treat acute gout?
Binds to cyclophilins (peptidyl proline cis-trans isomerase), blocking the differentiation and activation of T cells mainly by inhibiting the production of IL-2 and its receptor.
What is the mechanism of action of Cyclosporine?
Competitive inibitor of progestins at progesterone receptors.
What is the mechanism of action of Mifepristone (RU486)?
Misoprostol is a PGE1 analog that increases the production and secretion of the gastic mucous barrier.
What is the mechanism of action of Misoprostol?
Reversibly inhibit cyclooxygenase (COX I and COX II). Block prostaglandin synthesis.
What is the mechanism of action of NSAIDs other than Aspirin?
Irreversibly inhibits H+/K+ ATPase in stomach parietal cells.
What is the mechanism of action of Omeprazole, Lansoprazole?
Inhibits reabsorption of uric acid.
What is the mechanism of action of Probenacid used to treat chronic gout?
Inhibits cGMP phosphodiesterase, casuing increased cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, and penile erection.
What is the mechanism of action of Sildenafil (Viagra)?
Inhibit intestinal bursh border Alpha-glucosidases; delayed hydrolysis of sugars and absorption of sugars leading to decresed postprandial hyperglycemia.
What is the mechanism of action of the Alpha-glucosidase inhibitors?
Decrease the production of leukotrienes and protaglandins by inhibiting phospholipase A2 and expression of COX-2.
What is the mechanism of action of the glucocorticoids?
Close K+ channels in Beta-cell membrane leading to cell depolarization causing insulin release triggered by increase in Calcium ion influx.
What is the mechanism of action of the Sulfonylureas?
Directly of indirectly aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots. (It is claimed that tPA specifically converts fibrin-bound plasminogen to plasmin.)
What is the mechanism of action of the thrombolytics?
Inhibits platelet aggregation by irreversibly inhibiting the ADP pathway involved in the binding of fibrinogen.
What is the mechanism of action of Ticlopidine, Clopidogrel
Warfarin interferes with the normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, Protein C and S via vitamin K antagonism.
What is the mechanism of action of Warfarin (Coumadin)?
Antimetabolite derivative of 6-mercaptopurine that interferes with the metablolism and synthesis of nucleic acid.
What is the mechanism of Azathioprine?
GnRH analog with agonist properties when used in pulsatile fashion and antagonist properties when used in continuous fashion, causing a transient initial burst of LH and FSH
What is the mechanism of Leuprolide?
Similar to cyclosporine; binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines.
What is the mechanism of Tacrolimus (FK506)?
WEPT: Warfarin affects the Extrinsic pathway and prolongs the PT.
What is the memory key to remember which pathway (extrinsic vs. intrinsic) and which lab value Warfarin affects?
Mechanism unknown; possibly inhibits gluconeogenesis and increases glycolysis; effect is to decrease serum glucose levels
What is the possible mechanism and effect of Metformin in treating diabetes?
Indomethacin is used to close a patent ductus arteriosus.
What is the specific clinical use of Indomethacin in neonates?
Protamine Sulfate is used for rapid reversal of heparinization (positively charged molecule that binds to negatively charged heparin).
What is used to reverse the action of Heparin?
Those patients who are taking nitrates.
What patients are at risk for life threatening hypotension when taking Sildenafil (Viagra)?
Misoprostol is contraindicated in women of childbearing potential because it is an abortifacient.
What type of patient should not take Misoprostol and why?
Cimetidine is a potent inhibitor of P450; it also has an antiandrogenic effect and decreases renal excretion of creatinine. Other H2 blockers are relatively free of these effects.
Which H2 Blocker has the most toxic effects and what are they?
Because they require some residual islet function.
Why are the Sulfonylureas inactive in IDDM (type-1)?
-Disulfram & also sulfonylureas, metronidazole
Acetaldehyde is metabolized by Acetaldehyde dehydrogenase, which drug inhibs this enzyme?
-Weak Acids>Alkinalize urine(CO3) to remove more -Weak bases>acidify urine to remove more
Explain pH dependent urinary drug elimination?
-Airway -Breathing -Circulation -Dextrose (thiamine & narcan) -ABCD
How do you treat coma in the ER (4)?
-Infections -Trauma -Seizures -CO -Overdose -Metabolic -Alcohol (IT'S COMA)
In coma situations you rule out what (7)?
-A57Blue lines in gingiva & long bones -Encephalopathy & Foot drop -Abdominal colic / -Sideroblastic anemia
List some specifics of lead poisoning(4)?
-Atropine & pralidoxime
List the specific antidote for this toxin: Anticholinesterases (organophosphate.)
List the specific antidote for this toxin: Antimuscarinic (anticholinergic)
-Ethanol, dialysis, & fomepizole
List the specific antidote for this toxin: Methanol & Ethylene glycol
-Acetaldehyde -Nausea, vomiting, headache, & hypotension
What are the products and their toxicities of the metabolism of ethanol by / alcohol dehydrogenase?
-Oxalic acid -Acidosis & nephrotoxicity
What are the products and their toxicities of the metabolism of Ethylene Glycol by / alcohol dehydrogenase?
-Formaldehyde & formic acid -severe acidosis & retinal damage
What are the products and their toxicities of the metabolism of Methanol by / alcohol dehydrogenase?
-Chloramphenicol -benzene -NSAIDS -PTU -phenytoin
Which drug(s) cause this reaction: Aplastic anemia (5)?
-Niacin -Ca++ channel blockers -adenosine -vancomycin
Which drug(s) cause this reaction: Cutaneous flushing (4)?
-Metronidazole -certain cephalosporins -procarbazine -sulfonylureas
Which drug(s) cause this reaction: Disulfram-like reaction (4) ?
-Haloperidol -chlorpromazine -reserpine -MPTP
Which drug(s) cause this reaction: Drug induced Parkinson's (4) ?
-Chlorpromazine -thioridazine -haloperidol
Which drug(s) cause this reaction: Extrapyramidal side effects (3)?
-Halothane -Valproic acid -acetaminophen -Amantia phalloides
Which drug(s) cause this reaction: Focal to massive hepatic necrosis (4)?
-Sulfonamides -INH -ASA -Ibuprofen -primaquine -nitrofurantoin /-pyrimethamine -chloramphenicol
Which drug(s) cause this reaction: G6PD hemolysis(8)?
-Cimetidine -ketoconazole -spironolactone -digitalis -EtOH -estrogens
Which drug(s) cause this reaction: Gynecomastia (6)?
-aminoglycosides -loop diuretics -cisplatin
Which drug(s) cause this reaction: Oto and Nephrotoxicity (3)?
-Barbiturates -phenytoin -carbamazipine -rifampin -griseofulvin -quinidine
Which drug(s) cause this reaction: P450 induction(6)?
-Cimetidine -ketoconazole -grapefruit juice -erythromycin -INH -sulfonamides
Which drug(s) cause this reaction: P450 inhibition(6)?
-Ethosuxamide -sulfonamides -lamotrigine
Which drug(s) cause this reaction: Stevens-Johnson syn. (3)?
-Class III antiarrhythmics (sotalol) -class IA (quinidine)
Which drug(s) cause this reaction: Torsade de pointes (2)?
-Sulfonamides -furosemide -methicillin -rifampin -NSAIDS (ex. ASA)
Which drug(s) cause this reaction: Tubulointerstitial Nephritis (5)?
-reduction, oxy, & hydrolysis -H2O sol. Polar product -P450
Describe Phase I metabolism in liver(3)?
-acetylation, glucuron., & sulfation -Conjugation -Polar product
Describe Phase II metabolism in liver(3)?
- Act on same receptor - Full has greater efficacy
Explain differences between full and partial agonists(2).
- partial agonist can have increased, decreased, /A21or equal potency as full agonist. - Potency is an independent factor.
Explain potency in relation to full and partial agonists(2).
-Phase I (clinical tests) -Phase II -Phase III -PhaseIV (surveillance)
Name the steps in drug approval(4)?
In 4 half-lifes= (94%) T1/2 = (0.7x Vd)/CL
Steady state concentration is reached in __ number of half-lifes
-Constant AMOUNT eliminated per unit time. -Etoh & ASA
What is the definition of zero-order kinetics? Example?
Epinephirine(Alpha1,2 and Beta 1,2)
A 12yo patient was treated for a reaction to a bee sting, what drug provides the best coverage of sympathomimetic receptors?
A 57 yo heart failure pt develops cardiac decompensation, what drug will give you adequate perfusion of his kidneys as well as tx for his Hypotension
A fellow passenger on a Carnival cruise ship looks pale and diaphoretic, what antimuscarinic agent would you give them?
Atropine pts are suffering from Cholinestrase inhibitor poisining (Nerve gas/Organophosphate poisining)
A group of pts are rushed into the ER complaining of excessive sweating, tearing, salivation, HA, N and V, muscle twitching, difficulty breathing and diarrhea. What drug would be the most effective immediate tx
As an Anes you want to use a depolarizing neuromuscular blocking drug on your pt, what do you use
Centrally acting alpha agonist, thus causing a decrease in central adrenergic outflow, spairing renal blood flow
Clonidine is the preferred sym pathomimetic tx of HTN in pts with renal disease, why??
Indirect agonist, uptake inhibitor
Cocaine casues vasoconstriction and local anesthesia by what mechanism
Prevents the release of ACh, which results in muscle paralysis.
How does botulinum toxin result in respiratory arrest?
Prevents the release of calcium from the sarcoplasmic reticulum of skeletal muscle.
How does dantrolene work?
NE acts presynaptically on alpha-2 receptors to inhibit its own release. ACh also acts presynaptically through M1 receptors to inhibit NE release.
How does NE modulate its own release? What other neurotransmitter has this same effect?
Hemicholinium inhibits the transport of choline into the nerve, thus inhibiting formation of ACh.
How would hemicholinium treatment affect cholinergic neurons?
Give an antichloinesterase - neostigmine, edrophonium, etc
How would you reverse the effect of a neuromuscular blocking agent?
It would increase to ~ 100 beats/min. Both sympathetic and vagal stimulation would be knocked out, but the SA node has an intrinsic pace of 100 beats/min, which is normally checked by vagal stimulation.
If a patient is given hexamethonium, what would happen to his/her heart rate?
Stimulates beta adrenergic receptors
Isopoterenol was given to a patient with a developing AV block, why?
Binding to the presynaptic alpha 2 release modulating receptors
Norepi feedbacks and inhibits the presynaptic receptor by what mechanism
Blocks Norepi, but not Dopamine
Reserpine will block the syntheis of this drug and but not its precursor.
Amphetamine and Ephedrine
These drugs acts indirectly by releasing strored catecholamines in the presynaptic terminal
Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, and Salivation = DUMBBELS; also abdominal cramping
What are the classic symptoms of cholinesterase inhibitor poisoning (parathion or other organophosphates)?
Activates cholinergic receptors on bladder and bowel smooth muscle, alleviating post-op and neurogenic ileus and urinary retention.
What are the clinical indications for bethanechol?
Post-op and neurogenic ileus and urinary retention, myasthenia gravis, and reversal of neuromuscular junction blockade (post-op) through anticholinesterase activity.
What are the clinical indications for neostigmine?
narcolepsy, obesity, and attention deficit disorder (I wouldn't recommend this)
What are the indications for using amphetamine?
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rapacuronium
What are the nondepolarizing neuromuscular blocking drugs?
Phase 1 = prolonged depolarization, no antidote, effect potentiated by anticholinesterase; Phase 2 = repolarized but blocked, an anticholinesterase is the antidote for this phase.
What are the phases of succinylcholine neuromuscular blockade?
What cholinergic inhibitor acts by directly inhibiting Ach release at the presynaptic terminal
Carbachol, pilocarpine, physostigmine, echothiophate
What cholinomimetics might your pt be taking for his glaucoma
In treatment of malignant hyperthermia, due to concomitant use of halothane and succinylcholine. Also in neuroleptic malignant syndrome, a toxicity of antipsychotic drugs.
What conditions would you use dantrolene?
edrophonium (extremely short acting anticholinesterase)
What drug is used to diagnose myasthenia gravis?
Neostigmine, pyridostigmine edrophonium, physostigmine echothiophate
What drugs target anticholinesterase
Theoretically it could be used to block the cephalic phase of acid secretion (vagal stimulation).
What effect would atropine have on a patient with peptic ulcer disease?
None. No, because atropine would block the postganglionic muscarinic receptors involved in sweat gland stimulation.
What effect would atropine have on the preganglionic sympathetic activation of sweat glands? Would this person sweat?
Acetylcholinesterase; ACh is broken down into choline and acetate.
What enzyme is responsible for the breakdown of ACh in the synaptic cleft?
What enzyme is responsible for the production of Ach from Acetyl CoA and Choline
Treatment of hypertension, especially with renal disease (lowers bp centrally, so flow is maintained to kidney).
What is the clinical utility of clonidine?
The only local anesthetic with vasoconstrictive properties.
What is the clinical utility of cocaine?
Dobutamine has more of an affintiy for beta-1 than beta-2, and is used for treating heart failure and shock. Albuterol and terbutaline is the reverse, and is used in treatment of acute asthma.
What is the difference between the affinity for beta receptors between albuterol/terbutaline and dantroline?
Prefers beta's at low doses, but at higher doses alpha agonist effects are predominantly seen.
What is the difference in receptor affinity of epinephrine at low doses? High doses?
Increased systolic and pulse pressure, decreased diastolic pressure, and little change in mean pressure.
What is the effect of epinephrine infusion on bp and pulse pressure?
Increases mean, systolic, and diastolic bp, while there is little change in pulse pressure.
What is the effect of norepinephrine on bp and pulse pressure?
They inhibit reuptake of NE at the nerve terminal (as does cocaine).
What is the effect of TCA's on the adrenergic nerve?
It affects beta receptors equally and is used in AV heart block (rare).
What is the receptor affinity and clinical use of isoproterenol?
SLUD (salivation, Lacrimation, urination, Defecation)as well as airway secretion, GI motility, acid secretions
What physiological effects was the Anes using Atropine to tx
Bethanechol, Neostigmine, physostigmine
What reversal agent could a Anes give to reverse the effects of Atropine
Atropine would also block the receptors in the ciliary muscle, causing an impairment in accommodation (cycloplegia).
What side effect of using atropine to induce pupillary dilation would you expect?
Norepinephrine (Alpha1,2 and beta 1)
What sympathomimetic would you not prescribe for hypotension in a pt with renal artery sclerosis.
Hexamethonium is a nicotinic antagonist, and thus is a ganglionic blocker.
What type of neurological blockade would hexamethonium create?
Initially vasoconstriction would increase bp, but then it acts on central alpha-2 receptors to decrease adrenergic outflow resulting in decreased bp.
What would be the effect on blood pressure with infusion of the alpha -2 agonist clonidine?
atropine, homatropine, tropicamide
Which antimuscarinic agents are used in producing mydriasis and cycloplegia?
Dry flushed skin, due to inhibition of sympathetic post-ganglionic blockade on muscarinic receptors of sweat glands. All others are opposite of what would be expected.
Which of the following would atropine administration cause? Hypothermia, bradycardia, excess salivation, dry flushed skin, or diarrhea
Which of these three drugs will cause a reflex bradycardia in your pt (Norepi, Epi, or Isoporterenol)
alpha-1 > alpha-2; used as a pupil dilator, vasoconstrictor, and for nasal decongestion
Which receptors does phenylephrine act upon?
Epinephrine to treat anaphylaxis. Also useful if you have open angle glaucoma, asthma, or hypotension.
While at a tail gait party, you bite into a sandwich that a yellow jacket is also enjoying. Knowing your allergy to this creature, what should you do?
These B-2 agonists cause respiratory smooth muscle to relax.
Why are albuterol and terbutaline effective in tx of acute asthmatic attacks?
Blocking muscarinic receptors in the circular fibers of the eye, results in unopposed action of radial muscles to dilate.
Why does atropine dilate the pupil?
NE increases bp, which stimulates baroreceptors in the carotid sinus and the aorta. The CNS signals through vagal stimulation to decrease heart rate.
Why does NE result in bradycardia?
They activate the ciliary muscle of the eye (open angle) and pupillary sphincter (narrow angle).
Why is carbachol and pilocarpine useful in treatment of glaucoma?
As an anticholinesterase it increases endogenous ACh and thus increases strength.
Why is pyridostigmine effective in the treatment of myasthenia gravis?
Reserpine inhibits dopamine transport into vesicles, attenuating its conversion to NE by dopamine beta-hydroxylase.
Why is reserpine effective in treating HTN?
Stimulating beta receptors stimulates heart rate, but beta receptor induced vasodilation reduces peripheral resistance.
Why is there a drop in systolic, mean, and diastolic bp with infusion of isoproterenol?
Parkinson patients benefit from antimuscarinic agents through its inhibitory action within the indirect pathway.
Why would a patient with cog-wheel rigidity and a shuffling gait be given benztropine?
Receptors = D1=D2>beta>alpha, thus increasing heart rate (beta) and blood pressure (alpha vasoconstriction) while maintaining kidney perfusion (dopamine receptors)
Why would dopamine be useful in treating shock?
Useful in muscle paralysis during surgery or mechanical ventilation.
Why would you give a drug like pancuronium or succinylcholine?
Pralidoxime regenerates active cholinesterase.
Why would you use pralidoxime after exposure to an organophosphate?
No, hemicholinum block the uptake of Choline and thus Ach synthesis
Will Hemicholinum affect the release of stored Ach during Cholinergic Stimulation
No. Atropine is used to reduce urgency in mild cystitis. So it would aggravate the urinary retention.
Would blockade of muscarininc receptors in the bladder be useful in treating urinary retention?