MECHANISM: Decrease in arteriolar resistance via vasodilation. This arterial vasodilation goes unmatched by the venous circulation, which CCB do not effect. This is a disproportionate change in resistance increasing hydrostatic pressure in the capillary circulation and causing fluid to shift into the interstitium. Hence, edema!

REFERENCES

  1. Domenic A. Sica. Calcium channel blocker-related periperal edema: can it be resolved? J Clin Hypertens (Greenwich) 2003 Jul-Aug; 5(4): 291-4, 297.

Dihydropyridine: Think Amlodipine and Nifedipine (-dipine)

They act through systemic vascular vasodilation of arteries. Can be used to treat angina. NOTE: can cause hypotension and cause reflex tachycardia (this is bad for patients with ischemic symptoms)

Non-Dihydropyridine: Think Verapamil and Diltiazem

They act selectively on the myocardium. This will reduce oxygen demand of myocardial tissue. They have minimal systemic effect and are less likely to cause reflex tachycardia.

REFERENCES

1. Hockerman, G.H.; Peterson, B.Z.; Johnson, B.D.; Catterall, W.A. (1997). “Molecular Determinants of Drug Binding and Action on L-Type Calcium Channels”. Annual Review of Pharmacology and Toxicology 37: 361–396

  1. Rifampin is the antibiotic that is classically stated to be avoided in women taking OCPs

HOW? Rifampin is a potent inducer of cytochrome P450 3A4 and accelerates the elimination of ethinyl estradiol and some progestin components, resulting in an increased risk of OCP failure

OTHER DRUGS TO AVOID: Griseofulvin (an antifungal), Phenytoin, St. John’s Wort and Chronic Alcohol use (can all induce CYP 3A4)

References

1. Barditch-Crovo P, Trapnell CB, Ette E et al (1999) The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive. Clin Pharmacol Ther 65:428–438

2. Pelkonen, Olavi et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol. October 2008, Volume 82, Issue 10, pp 667-715

It is often stated to patients and even on the product monograph to avoid the use of alcohol when taking Metronidazole systemically or vaginally (and for at least 48 hours afterwards).

WHY? There are been reports of individuals experiencing disulfiram-like reactions (build up of blood acetaldehyde levels) after drinking while on Metronidazole. Mechanism is currently unknown.

References

  1.  Cina SJ, Russell RA, Conradi SE. Sudden death due to metronidazole/ethanol interaction. Am J Forensic Med Pathol 1996; 17:343. 
  2.  Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother 2000; 34:255. 
  3.  Alexander I. ‘Alcohol-antabuse’ syndrome in patients receiving metronidazole during gynaecological treatment. Br J Clin Pract 1985; 39:292. 

Allopurinol => enzyme xanthine oxidase inhibitorallopurinol-mechanism

Therefore blocks the conversion of the purine metabolites (hypoxanthine and xanthine) into uric acid.

NOTE: Allopurinol is used to prevent gout attacks, not to treat them once they occur.

Indications for use:

  1. Recurrent gouty attacks (>3 within 1 year)
  2. Presentation of Gouty tophi
  3. Renal insufficiency or recurrent nephrolithiasis with hyperuricemia
  4. Tumour lysis syndrome

References

1. Pacher et. al. Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol. Pharmacol Rev. 2006 Mar; 58(1): 87–114.doi:  10.1124/pr.58.1.6

Vancomycin is a glycopeptide antibiotic, typically used for treatment of MRSA. Traditionally it is recommended to get trough doses to assess efficiency.steady-state

Typically, we aim for Vancomycin trough levels between 10-20µg/mL (15-20 µg/mL for more severe infections).

WHY NOT MEASURE PEAKS?  Vancomycin displays time-dependent bactericidal activity when above the minimum inhibitory concentration (MIC), not dose-dependent. Hence, there is little evidence to support the measurement of target peak concentrations. It is actually the trough levels that are better correlated with therapeutic efficacy and potential side affects such as nephrotoxicity.

WHEN TO MEASURE? Typically measured in patients with invasive disease (i.e bactermia) or at increased risk of nephrotoxicity (i.e CKD or concurrent aminoglycoside use).

HOW TO MEASURE? Trough concentrations should be measured within 30 minutes prior to infusion of the fourth dose or fifth dose. Why? This is when the drug (in fact all drugs) will reach steady state. NOTE: Can be measured before 3rd dose in patients which renal impairment and risk of toxicity may be greater.

*Patient on oral Vancomycin do not require trough measurements!

REFERENCES

  1. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.AULiu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF, Infectious Diseases Society of America. Clin Infect Dis. 2011;52(3):e18.
  2. Jennifer H Martin, Ross Norris, Michael Barras, Jason Roberts, Ray Morris, Matthew Doogue, and Graham RD Jones. Therapeutic Monitoring of Vancomycin in Adult Patients: A Consensus Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Clin Biochem Rev. 2010 Feb; 31(1): 21–24. 

non-steroidal anti-inflammatory drugs (NSAIDs) irritate gastroduodenal mucosa, suppress prostaglandin production, impair the ability of NSAID-cox-inhibitor-ulcersthe mucosa to repair (reduction in gastric mucosa blood flood), inhibiting platelets function

HOW? Will block COX-2 to reduce inflammation [GOOD] but also block COX-1 [BAD]

Arachidonic Acid —> [COX] –> Prostaglandin

  • COX 1: constitutively expressed in most cells and plays an important role in the GI mucosal protection, renal blood flow regulation and normal platelet function
  • COX 2: largely inducible by inflammation and is thought to generate prostaglandins that are responsible for pain and inflammation

PGE2, remains a critical factor in gastric homeostasis. Prostaglandin E2 inhibits acid secretion through the EP3 receptor and the fluctuation of its levels as a result of NSAID therapy remains a major concern in preserving the integrity of the gastric mucosa

References

1. Wallace JL. How do NSAIDs cause ulcer disease? Baillieres Best Pract Res Clin Gastroenterol. 2000 Feb;14(1):147-59.

Both are minimally absorbed oral antibiotics with broad-spectrum coverage for gram-positive and gram-negative aerobes and anaerobes. They can reduce or eliminate ammonia-producing bacteria as well as blood and brain ammonia levels.

NOTE: long term Neomycin use can lead to renal, auditory, and neurological toxicities, as well as antibiotic-induced microfloral resistances.

*Hence Rifaximin is the agent of choice for long term use. Far fewer complications, with a very low risk of inducing bacterial resistance.

References

  1. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin Treatment in Hepatic Encephalopathy. N Engl J Med. 2010;362:1071-1081

Lactulose (want to achieve 2-3 soft bowel movements per day)

  • Lactulose prevents ammonia (NH3) from diffusing out of the colon and into the blood. Thus reducing the amount of ammonia in blood
  • HOW? Intestinal flora metabolizes lactulose producing organic acids and lowering pH => converting NH3 to NH4 (ammonium)

*It also acts as a laxative to eliminate nitrogen-producing bacteria

References

1. Weber FL Jr. Lactulose and combination therapy of hepatic encephalopathy: the role of the intestinal microflora. Dig Dis. 1996;14 Suppl 1:53-63.

  • Thiamine 100mg IV before 50% glucosewernickes
  • Thiamine is an important co-enzyme for carbohydrate utilization as (thiamine pyrophosphate- TPP)
  • Therefore TTP is required to convert pyruvate to Acetyl-CoA. To put it another way, if you’re thiamine deficient, any glucose you get will tend to form lactate, rather than being fully metabolized in the Krebs Cycle [1]

References

  1. Hoyumpa AM, Jr. Mechanisms of thiamin deficiency in chronic alcoholism.  Am J Clin Nutr  1980;33:2750-2761.