Final; All units

penicillin G benzathine

• natural penicillin (beta lactam cell wall inhibitor)

• target peptidoglycan layer of bacteria

• treats syphilis

• not stable in gastric acid

  • ROA: intramuscularly

• long-acting

• susceptible to degradation via beta-lactamases

• also for group A strep, group B strep, tooth infections

penicillin V

• natural penicillin (beta lactam cell wall inhibitor)

• works mostly on gram positives

• target peptidoglycan layer of bacteria

• stable in acidic environment

  • ROA: oral

• susceptible to degradation via beta-lactamases

• also for group A strep, group B strep, tooth infections

tazobactam, clavulanic acid

• beta lactamase inhibitors

• given alongside beta lactam antibiotic

• Combinations:

  • clavulanic acid + amoxicillin = clavulin

  • tazobactam + piperacillin = tazocin (pip-tazo)

ampicillin, amoxicillin, amoxicillin + clavulanic acid

• broad spectrum penicillins (beta lactam cell wall inhibitor)

• PO, IV; PO; PO

• add gram negative coverage

cloxacillin, methicillin

beta-lactamase resistant penicillins (beta lactam cell wall inhibitor)

piperacillin + tazobactam

• extended spectrum penicillins (beta lactam cell wall inhibitor)

• cover pseudomonas microorganisms

cefazolin (Ancef), cephalexin (Keflex)

• first-generation cephalosporins (beta lactam cell wall inhibitor)

• IV; PO

• Adverse:

  • hypersensitivity: low cross-reactivity with penicillins

  • nausea, vomiting, diarrhea

  • disulfiram-like effect

    • headaches, flushing, nausea

cefprozil, cefuroxime

• second generation cephalosporins (beta lactam cell wall inhibitor)

• Adverse:

  • hypersensitivity: low cross-reactivity with penicillins

  • nausea, vomiting, diarrhea

  • disulfiram-like effect

    • headaches, flushing, nausea

ceftriaxone, ceftazidime, cefixime

• third generation cephalosporins (beta lactam cell wall inhibitor)

• Adverse:

  • hypersensitivity: low cross-reactivity with penicillins

  • nausea, vomiting, diarrhea

  • disulfiram-like effect

    • headaches, flushing, nausea

cefepime

• fourth generation cephalosporin (beta lactam cell wall inhibitor)

• Adverse:

  • hypersensitivity: low cross-reactivity with penicillins

  • nausea, vomiting, diarrhea

  • disulfiram-like effect

    • headaches, flushing, nausea

ceftobiprole

• fifth generation cephalosporin (beta lactam cell wall inhibitor)

• Adverse:

  • hypersensitivity: low cross-reactivity with penicillins

  • nausea, vomiting, diarrhea

  • disulfiram-like effect

    • headaches, flushing, nausea

meropenem

• carbapenem (beta lactam cell wall inhibitor)

• resistant to beta-lactamase

• CRE due to production of inactivating enzyme New Delhi metallo-beta-lactamase/carbapenemase

aztreonam

• monobactam (beta lactam cell wall inhibitor)

• acts on gram negative aerobic

  • P.aeruginosa, Neisseria, H.influenzae and enterobacteria (E. coli, Klebsiella, Proteus, Serratia, Salmonella and Shigella)

• ROA: inhalation (28 days) for P. aeruginosa in cystic fibrosis patients

• few cross reactions if patient are hypersensitive to other beta-lactams

bacitracin

• non beta-lactam cell wall inhibitor

• ROA: topically

• found in polysporin

  • 500 U bacitracin + Polymyxin B 10 000 units

vancomycin

• non beta-lactam cell wall inhibitor

• used for resistant microorganisms like MRSA and C. diff

• ROA: IV

  • bad availability when given orally so can be useful for C. diff

• Adverse:

  • infusion-related flushing

  • rash

  • hypotension

  • nephrotoxicity

• VRE

gentamicin, tobramycin

• aminoglycosides

• inhibitor of protein synthesis; inhibits 30S ribosomal subunit

• useful against gram-negative aerobic

• charged; not absorbed well orally => IV or IM

• Adverse:

  • nephrotoxicity

  • ototoxicity

clarithromycin

• macrolides

• inhibitor of protein synthesis; inhibits 50S ribosomal subunit

• useful against gram positive bacteria

• treats respiratory infections

• used as a substitute for patients with hypersensitivity to penicillin

• Adverse:

  • nausea, vomiting, diarrhea

  • inhibits hepatic enzymes; risk for toxicity of drug that is normally metabolized/inactivated by the liver

azithromycin

• macrolides

• inhibitor of protein synthesis; inhibits 50S ribosomal subunit

• useful against gram positive bacteria

• treats respiratory infections, chlamydia/gonorrhea

• used as a substitute for patients with hypersensitivity to penicillin

• Adverse:

  • nausea, vomiting, diarrhea

clindamycin

• lincoside (acts like macrolides)

• inhibitor of protein synthesis; inhibit 50S ribosomal subunit

• treats soft tissue infections (cellulitis, bites) and bacterial vaginosis

• used when patient is hypersensitive to beta-lactams

linezolid

• oxazolidinones

• inhibitor of protein synthesis; inhibits the 50S ribosomal subunit

• limited to treating MRSA and VRE to prevent resistance development

tetracycline

• tetracyclines

• inhibitor of protein synthesis; inhibit 30S ribosomal unit

• broad spectrum, widespread resistance

• treats acne and H. pylori induced ulcers

• interactions with milk, antacids, Ca++ and Fe+++

• high affinity for bone and teeth

  • cause discoloration in those aged 4mo - 8yo

• risk for superinfections

• avoid during pregnancy

• causes photosensitivity

doxycycline

• tetracyclines

• inhibitor of protein synthesis; inhibit 30S ribosomal unit

• broad spectrum, widespread resistance

• treats chlamydia

• interactions with milk, antacids, Ca++ and Fe+++

• high affinity for bone and teeth

  • cause discoloration in those aged 4mo - 8yo

• risk for superinfections

• avoid during pregnancy

• causes photosensitivity

minocycline

• tetracyclines

• inhibitor of protein synthesis; inhibit 30S ribosomal unit

• broad spectrum, widespread resistance

• interactions with milk, antacids, Ca++ and Fe+++

• high affinity for bone and teeth

  • cause discoloration in those aged 4mo - 8yo

• risk for superinfections

• avoid during pregnancy

• causes photosensitivity

chloramphenicol

• broad spectrum

• inhibitor of protein synthesis; inhibits 50S ribosomal subunit

• overused => widespread resistance

• good distribution to the brain

• treats rickettsial disease, meningitis, typhoid fever, cholera

• Adverse:

  • bone marrow suppression

    • anema

    • agranulocytosis

    • thrombocytopenia

  • newborns cannot eliminate due to low ability to conjugate enzyme activity (phase 2)

    • can lead to cyanotic “gray baby syndrome”

ciprofloxacin, levofloxacin, moxifloxacin

• fluoroquinolones

• inhibitors of DNA synthesis

• very active against gram negative aerobic and newer drugs also active against gram positive

• treat Bacillus anthracis (anthrax), pneumonia, intra-abdominal infection

• decrease absorption due to binding with Ca++, Fe++, Al+++, Mg++

• Adverse:

  • avoid during pregnancy to prevent poor cartilage development

  • generally well-tolerated

  • nausea

  • tendinopathies

metronidazole (Flagyl)

• inhibitor of DNA synthesis

• affects gram negative anaerobic bacteria

• treats:

  • intra-abdominal infections

  • trichomoniasis

  • bacterial vaginosis

  • aquatic protozoa

    • Giardiasis “beaver fever”

• Adverse: nausea, metallic taste, dizziness/vertigo, disulfiram effect

nitrofurantoin (Macrobid)

• inhibitor of DNA synthesis

• treats UTIs

polymyxins

• disruptors of plasma membranes

• act like detergents to disrupt phospholipid membranes

• affect gram negative bacteria

• ROA: topically/injected into body cavity

• ingredient in Polysporin

  • 10 000 Units polymyxin B, 500 Units bactracin

rifampin

• antimycobacterial drugs

• treats tuberculosis

• used in combination

• inducer of cytochrome P450s

• Adverse:

  • discoloration of body fluids

  • epigastric pain

  • flu-like syndrome

isoniazid

• antimycobacterial drugs

• treats tuberculosis

• Adverse:

  • peripheral neuropathy (tingling, numbness, burning, pain)

  • reduced with vitamin B6 (pyrioxidine)

ethambutol

• antimycobacterial drugs

• treats tuberculosis

• Adverse:

  • optic neuritis

amphotericin B

• Polyenes

• antifungals; target ergosterol (important component of fungus cell membranes)

• ROA: IV

  • poor oral absorption

• Adverse:

  • nephrotoxicity

  • anemia

  • infusion-related reaction (fever, chills)

  • phlebitis

nystatin

• Polyenes

• antifungals; target ergosterol (important component of fungus cell membranes)

• ROA: topical

• poor oral absorption

clotrimazole, miconazole (topical), fluconazole (PO)

• ergosterol synthesis inhibitors

• azoles

• inhibit CYP450s

terbinafine

• ergosterol synthesis inhibitors

• allylamines

• inhibit a reaction upstream from the action of azoles

What is an ulcer? What is it caused by?

• area of erosion passing through the lining of the gastrointestinal wall

• imbalance btwn aggressive and defensive factors

  • ex. acid, pepsin, bile, H. pylori, NSAIDs vs. mucus, prostaglandins, bicarb., circulation

What is the last line of defense for epithelial cells? How?

• gastric circulation

  • allowing cells to dump acid instead of being excessively exposed to the acidity

What percentage of gastric ulcers are caused by H. pylori?

70% by H. pylori and 25% by NSAIDs

What percentage of duodenal ulcers are caused by H. pylori?

92% by H. pylori and 5% by NSAIDs

What is the topical action of NSAIDs?

gastric epithelial cells are damaged by the absorption of acids (NSAIDs are weak acids)

What is the systemic action of NSAIDs?

reduce the synthesis of protective prostaglandins in the gastric mucosa

A reduction in prostaglandins causes what?

• decreased mucus

• decreased circulation

• decreased bicarbonate

• increased secretion of HCl

Name the 5 categories of drugs used in the treatment of peptic ulcers and hypersecretion of gastric acid.

• antacids

• mucosal defenses

• histamine-2 receptors antagonists

• proton pump inhibitors

• antibacterial drugs

What are the 4 goals of drug therapy in peptic ulcer + hypersecretion fo gastic acid treatment?

1. alleviate symptoms

2. promote healing

3. prevent complications (ex. hemorrhage, perforation, obstruction)

4. prevent recurrence

What are antacids?

alkaline compounds that neutralize gastric acid

Name 3 examples of antacids.

Mg(OH)2, Al(OH)3, CaCO3

What is the mechanism of action of antacids?

• make gastric pH more alkaline

• neutralize HCl

• reduces the activity of pepsin

• short duration of action

What are the adverse effects of Al(OH)3?

• constipation

• reduce the absorption of certain drugs (ex. cipro, tetracycline)

What are the adverse effects of Mg(OH)2?

• diarrhea

• reduce the absorption of certain drugs (ex. cipro, tetracycline)

Name 2 examples of mucosal protectant defenses (coating agents)?

sucralfate, bismuth subsalicylate

What is the mechanism of action of sucralfate?

forms protective barrier on the ulcer

What is the mechanism of action of bismuth subsalicylate?

• forms a protective barrier over a gastric mucosa

• bacteriostatic!!!!

• antisecretory and anti inflammatory activities

Adverse effects of sucralfate?

constipation

Adverse effect of bismuth subsalicylate?

black tongue and black feces

Name an example of an enhancer of mucosal defenses.

misoprostol

What is the mechanism of actions of misoprostol?

• prostaglandin PGE1 analogue

• stimulates submucosal blood flow as well as production fo HCO3- and mucus

• attenuates histamine-induced gastric acid production

Adverse effects of misoprostol?

diarrhea, cramps, contraction of the uterus

Off label use for misoprostol?

cervical ripening, induction of labour

What is the mechanism of action of histamine H2 receptor antagonists?

decreased the secretion of gastric acid by parietal cells, particularly at night

Name 4 examples of histamine receptor antagonists.

cimetidine, ranitidine, famotidine, nizatidine

Adverse effects of cimetidine?

• inhibits hepatic metabolism (CYPs)

• anti-androgenic effects

  • gynecomastia, erectile dysfunction, reduced libido

• possible rebound effect of gastric acid secretion after discontinuation

Name 4 examples of proton pump inhibitors.

esomeprazole, pantoprazole, rabeprazole, dexlansoprazole

What is the mechanism of action of proton pump inhibitors?

inhibit the gastric H+/K+ ATPase pump

Adverse effects of proton pump inhibitors?

• headache

• diarrhea

• increase the risk of osteoporosis/related fractures

• increased risk of C. diff and other GI infections

• decreased absorption of vitamin B12 and iron

What is the triple therapy antibiotic regimen for H. pylori?

• proton pump inhibitor (lanzoprazole)

• antibiotic (amoxicillin)

• antibiotic (clarithromycin)

• antibiotic (metronidazole)

What is the quadruple therapy antibiotic regimen for H. pylori?

• proton pump inhibitor

• tetracycline

• bismuth salts

• metronidazole

What are the mechanisms of action of laxatives?

ease of stimulate defecation

Name 2 examples of stimulant laxatives. What is their mechanism of action?

bisacodyl, sennosides

• stimulate peristalsis

• increase water and electrolytes in colon

Name 2 examples of bulk-forming laxatives. What is their mechanism of action?

psyllium, inulin

• stimulate water retention with the stool

Name an examples of surfactant laxatives. What is their mechanism of action?

docusate

• alter stool consistency

• facilitate penetration of water into the feces

Name 3 examples of osmotic laxatives. What is their mechanism of action?

lactulose, polyethylene glycol, Mg(OH)2

• poorly absorbed molecules that draw water by osmosis in to the intestine

Name an examples of lubrification laxatives. What is their mechanism of action?

mineral oil

• decrease the absorption of fat-soluble vitamin (A, D, E, K) and oral contraceptives

Name 2 examples of anti-opioid laxatives. What is their mechanism of action?

methylnaltrexone, naloxegol

• used to treat refractory opioid-induced constipation

Name 5 examples of antidiarrheal agents.

loperamide, anticholinergic drugs, verapamil, Al salts, diphemnoxylate+atropine

What is loperamide? What is its mechanism of action?

• morphine derivative

  • crosses blood-brain barrier poorly

• decreases intestinal motility, slows intestinal transit => allows for more time to absorb fluid and electrolytes

What are the factors that stimulate contraction of vascular smooth muscle?

• increased intracellular calcium in vascular smooth muscle cells

• increased angiotensin II or increased plasma NA

• stimulation of alpha 1 receptors via alpha 1 agonists

What are the factors that stimulate relaxation of vascular smooth muscle?

• decreased intracellular calcium in vascular smooth muscle cells

• stimulation of beta 2 receptors via adrenaline or beta agonists

• increased intracellular cAMP in smooth muscle

• increased nitric oxide

• increased cGMP

What does an increase in cAMP do to the heart?

increased intracellular Ca++ via voltage gated calcium channels => increased force of contraction and HR

What is ischemia?

• inadequate coronary blood flow

• often precipitated by exertion, exposure to cold/emotional excitement

• retrosternal pain

What are the 3 types of angina? Define them.

Stable angina: pain or discomfort with exertion, emotional stress; predictable; symptoms relieved with rest

Prinzmetal angina: unpredictable, occurs at rest/minimal exertion; rest may not relieve the symptoms

Unstable angina: occurs more frequently, lasts longer, often not relieved by rest

What are 2 solutions to solve an imbalance between oxygen delivery and usage?

1. increase O2 supply to the heart

2. reduce oxygen utilization by the heart

What are 3 strategies to increase O2 supply to the heart?

• removal of blockage (angioplasty)

• bypass of blocked coronary vessels

• reversal of vasospasm (drugs)

What are the variables that control oxygen utilization by the heart?

contractility, heart rate, afterload, preload

What is afterload?

• tension on the walls of the ventricle during systole (contraction/ejection)

• influenced by resistance to ejection which is influenced by peripheral resistance which influenced by the diameters of arterioles

What is preload?

• tension on the ventricular walls during diastole (ventricular filling)

• influenced by EDV, venous pressure, and volume of blood returning to the heart

What are the 3 classes of anti-anginal drugs?

• nitrates

• beta blockers

• voltage sensitive calcium channel blockers

From which compound are nitrates derived from?

nitroglycerin

Name the different routes of administration of nitroglycerin.

• sublingual

  • rapid absorption and avoids 1st pass metabolism

• transdermal

  • slow and continuous release of drug

• injectable

  • IV

• oral

  • would need sufficient quantity to overcome hepatic enzymes

What is the form of nitrate given orally?

isosorbide mononitrate

What are the physiological mechanisms of nitrates?

Vasodilation

• veins

  • reduced venous return; decreased preload

• arterioles

  • drop in BP; decreased resistance and afterload

• coronaries

  • increased coronary blood flow

In summary, what are the effects of nitrates on determinants of cardiac O2 requirements?

• decreased preload

• decreased afterload

• increased O2 delivery

What are the adverse effects of nitrates?

• orthostatic hypotension

• frequent headaches

• reflex tachycardia

• tachyphylaxis (tolerance)

What are the effects of beta blockers on the heart?

• negative chronotropic (HR)

• negative inotropic (force of contraction)

• negative dromotrope (conduction velocity)

• decreased renin release by juxtaglomerular cells

  • less Ang II

  • decrease in BP

• decreased afterload

Which beta blocker tends to demonstrate more side effects?

propranolol; less selective

What are the beta 1 cardioselective beta blockers? Which one has ISA?

bisoprolol, metoprolol, atenolol, acebutolol (ISA)

What is intrinsic sympathomimetic activity?

a beta blocker with a little bit of receptor stimulating activity

What are the non-cardioselective antagonists for beta 1 and beta 2 receptors? Which one has ISA?

propranolol, timolol, pindolol (ISA)

What are the non-cardioselective antagonists for beta 1, beta 2, and alpha 1 receptors? Which one can be used for HTN in pregnant patients?

labetalol (HTN), carvedilol

Why can propranolol act on the brain?

lipid soluble, can cross the blood brain barrier

What are the therapeutic uses of beta blockers?

• angina, HTN, arrhythmias, heart failure

• migraines

• anxiety

• hyperthyroidism