Drugs Week 2 Flashcards
Amoxicillin
Resistance is around 1%, possibly increasing.
More than twice as acid stabile as ampicillin, thus twice the blood levels are achieved w/ the same oral dose –> never substitute.
MOA: Cell wall inhibitor –> binds to PBP –> inhibits transpeptidases
A.E. = Hypersensitivity reactions
Bismuth Subsalicylate
AKA petpo bismol
MOA:
- ) Antimicrobial: disrupt cell wall, prevents adhesion, inhbits urease
- ) Protects surface –> coat, increase secretion of mucus and increase HCO3-
Bismuth is active ingredient in stomach
Drug dissociates in stomach into Bismuth and Salicylate
A.E. Black tongue and stool (benign), salicylate toxicity (vomting, tinnitus, confusion, hypothermia, resp. alkalosis –> metabolic acidosis)
Clarithromycin
Resistance is 10-15%
Has the lowest MIC50 of the macrolides and is the most acid stabile.
MOA: It binds to 23S rRNA, a component of the 50S subunit of the bacterial ribosome, thus inhibiting the translation of peptides.
A.E. - GI effects (stimulates MMC). Drug interactions (CYP 3A4). Increased risk of miscarriage in 1st trimester.
Bacteriostatic
Rifabutin
MOA: Inhibits DNA dependent RNA polymerase blocking transcription.
Bacteriocidal
A.E. HS rxn, hepatotoxicity, inhbitis CYP450, Orange/Red fluids
Tetracycline
Antacids will chelate tetracyclines and render them less efficacious.
Incomplete absorbtion –> give w/ food.
MOA: Binds 30s subunit inhibiting protein synthesis.
A.E. - GI Irritation, Photosensitivity, Discoloration of growing teeth, Don’t give to pregnant women or kids.
Bacteriostatic
Metronidozole
Resistance is 25-35%
MOA: Electron sink
A.E. GI/CNS toxicity, disulfiram reaction, teratogenic
Inhibits CYP2C9 ( increase Warfarin and affects H2 blocker)
Tinidazole has decreased A.E. and dosing
Triple Therapy
Regimens to treat H. pylori ulcers always have 3 key components:
- ) Multiple ABs for eradication of the bacteria
- ) A mechanism for treating pain (usually a PPI) and facilitating healing
- ) Long duration (10-14 days), which can cause problems w/ compliance
Current standard = PPI + Clarithro + Amox or Tinidazole)
Alternatives if resistance = Quadruple therapy:
PPI + Bismuth + Tetracycline + Metronidazole
Or
PPI + Amox + Rifabutin + Cipro
Sucralfate
Requires an acid environment to be activated, thus can’t be given w/ PPIs, H2 blockers or antacids
MOA: H+ converts to paste –> sticks to ulcer.
Use: Stress induced ulcers in ICU “band-aid”
A.E. Constipation, binds drug
Aluminum Hydroxide
MOA: Weak base used to buffer stomach acid.
Rapid onset, but short duration of action, no prevention of ulcer recurrence –> useful for intermittent dyspepsia.
Not systemically absorbed (good)
Significant for constipation (often given w/ Mg(OH)2)
Drug interactions:
- Increase gastric PH
- Bind drugs (tetracycline)
- Increase gastric emptying
- ) Alkalinize urine (changes drug elimination)
Calcium Carbonate
MOA: Weak base used to buffer stomach acid.
Rapid onset, but short duration of action, no prevention of ulcer recurrence –> useful for intermittent dyspepsia.
Rapid onset, long duration.
A.E. Mild systemic alkalosis, hypercalcemia (milk-alkali syndrome)
Drug interactions:
- Increase gastric PH
- Bind drugs (tetracycline)
- Increase gastric emptying
- ) Alkalinize urine (changes drug elimination)
Magnesium Hyroxide
MOA: Weak base used to buffer stomach acid.
Rapid onset, but short duration of action, no prevention of ulcer recurrence –> useful for intermittent dyspepsia.
Not systemically absorbed (good)
Significant for diarrhea (often given w/ Al(OH)3.
Drug interactions:
- Increase gastric PH
- Bind drugs (tetracycline)
- Increase gastric emptying
- ) Alkalinize urine (changes drug elimination)
Sodium Bicarbonate
MOA: Weak base used to buffer stomach acid.
Rapid onset, but short duration of action, no prevention of ulcer recurrence –> useful for intermittent dyspepsia.
Extremely rapid onset.
A.E’s severe metabolic alkalosis, alkalinizes urine.
Drug interactions:
- Increase gastric PH
- Bind drugs (tetracycline)
- Increase gastric emptying
- ) Alkalinize urine (changes drug elimination)
Misoprostol
MOA: PGE1 is the drug of choice for treatment of ulcers induced by NSAIDs.
Adverse effects and frequent dosing lead to limited use.
A.E.’s: Abortifacient, Uterine contractions, diarrhea, severe nausea, cramping, abdominal pain in 25%.
PK: Rapid absorbtion and metabolism. Excreted in urine.
Simethicone
MOA: Antifoaming agent –> decreases gas pain.
-prazoles
MOA: Irreversibly block the final common pathway in acid secretion, the H/K ATPase. AKA PPI.
OTC
Slow onset of action, very long duration of action, excellent prevention. Drugs of choice for ZE syndrome, GERD, and ulcer treatment
PK: Prodrugs (acid labile) –> pass through stomach and absorbed in small intestine before being distributed to the entire body. Then selective for acidic compartments.
Timing is critical –> give in fasting state (don’t want to crush drug) approximately 1/2 hr. before meal –> concentration of drug is highest when pumps turn on.
Short half life, but are irreversibly –> once a day dosing. Full inhibition in 3-4 days; recovery in 3-4 days. High initial dose –> taper off.
A.E.’s - no significant in healthy people. 1-5%: HA, diarrhea, nausea, rash.
Rebound acid secretion when stopped
Concerns:
- Decreased B12, iron, Ca, and Zn –> increase incidence of hip fracture.
- Increased respiratory and enteric infections (from increased pH)
- ECL hyperplasia –> increase carcinoid tumors (only in animals so far).
-tidine
MOA: Highly selective H2 receptor antagonist. (decreases intracellular cAMP –> Effectively decrease all forms of gastric acid secretion (esp. nocturnal) w/ few side effects (except cimetidine)
OTC
Relatively rapid onset, intermediate duration, some prevention –> many uses
t1/2: 1-4hrs
Metabolized by CYP450 (Cimetidine inhibits)and Renally excreted (competes for tubular secretion w/ weak bases –> metronidazole reacts w/ H2 blockers.
A.E.: Very safe when oral (some liver and kidney toxicity); Rapid IV infusion –> Bradycardia, hypotension.
Cimetidine only - 3% - decrease estrogen metabolism and increase prolactin causing gynecomastia/impotence in males and galactorrhea in females
Unsure safety in pregnancy
Tinidazole
Resistance is 25-35%
MOA: Electron sink
A.E. GI/CNS toxicity, disulfiram reaction, teratogenic
Inhibits CYP2C9 ( increase Warfarin and affects H2 blocker)
Metronidazole has increased A.E. and dosing
Atropine
MOA: Competitive inhibitor of all muscarinic receptors (M3 and M1 in this case–> decrease acid production
Very rarely used to treat ulcers because they slow gatric emptying and prolong exposure of ulcer to acid (and have more severe A.E.’s than H2 blockers)
Adverse effects: ABCD’S (Anorexia, Blurred vision, Constipation/Confusion, Dry Mouth, Sedation/Stasis of urine)
Pirenzipine
MOA: Competitive inhibitor of M1 muscarinic (on ECL cells) receptors –> decrease acid production
Very rarely used to treat ulcers because they slow gatric emptying and prolong exposure of ulcer to acid (and have more severe A.E.’s than H2 blockers)
Adverse effects: ABCD’S (Anorexia, Blurred vision, Constipation/Confusion, Dry Mouth, Sedation/Stasis of urine)
