CARDIOACTIVE DRUGS

Many cardiac conditions are treated with drugs. Of

these drugs, only a few require TDM. The cardiac
glycosides and antiarrhythmic are two glasses of
drugs for which assessment of serum
concentration aids in decisions regarding their
dosage regimen.
 DIGOXIN

- It is cardiac glycoside used in the treatment of congestive

heart failure. It functions by inhibiting membrane Na+, K+-
ATPase. ,
- Obtained from Digitalis plants such as foxglove
- Active metabolite of digitoxin
- The nonbound (free) form of serum digoxin is sequestered
into muscle cells
- At equilibrium, the tissue concentration is 15-30 times
greater than that of plasma
- Elimination occurs by renal filtration of the plasma free form
- The half life of plasma digoxin is 38 hours
- Therapeutic range: 0.8 – 2.0 ng/mL
- Thyroid status may also influence the actions of digoxin
- Hyperthyroid patients display a resistance to digoxin actions
- Hypothyroid patients are more sensitive
- Peak level: 8 hours after an orally administered dose
- If samples are collected at the appropriate time, high serum
digoxin correlates with toxicity.
- HOWEVER: Newborns, pregnant women, & patients with
uremia or late stage liver disease produce an endogenous
substance that cross-reacts w/ the Ab used to measure serum
digoxin (falsely elevated)
- Herbal products not only af fect digoxin therapy but can also
interfere w/ common analytical method used to detect digoxin
(falsely elevated)
 QUINIDINE

 Naturally occurring treatment of Cardiac arrhythmic

situation.
 70 – 80% is protein bound
 Oral Administration is most common route of delivery.
 GIT adsorption is complete and rapid for the sulfate.
 Elimination: Hepatic metabolism
 Most common formulation: Quinidine Sulfate and
Quinidine Gluconate
 Through level: drawn 1 hour after the last dose
 Peak serum level:
 Quinidine Sulfate: 2 hrs after oral dose
 Quinidine Gluconate: 4-5 hrs after oral dose
 Most predominant Toxic adverse: nausea, vomiting and
abdominal discomfort
 Barbiturates – increases the clearance rate
 Late stage liver disease may extend the half-life of this drug.
 Plasma concentration determined by: Chromatography and
Immunoassay
 Production of quinidine may contain active contaminants:
Dihydroquinidine
 PROCAINAMIDE

 Quinidine like  for treating cardiac arrhythmia

 Common administration: ORAL
 GIT absorption is rapid and complete
 PEAK PLASMA LEVEL: 1 hour after the dose
 ELIMINATION: combination of renal filtration and hepatic
metabolism
 Hepatic metabolite: N -acetylprocainamide
 Increased concentrations  myocardial depression and
arrhthymia
 Measured by IMMUNOASSAY
 DISOPYRAMIDE

 commonly used as a quinidine substitute

 peaking at about 1–2 hours
 total serum concentrations in the range of 3 –7.5 g/mL
ef fective and nontoxic
 primarily eliminated by renal filtration
 low GFR, the half-life is prolonged and serum concentrations
rise
 Plasma concentration can be determined by chromatography
or immunoassay.
primary toxicities is dose dependent
greater than 4.5 g/mL
 Anticholinergic ef fects, such as dry mouth
 Constipation
greater than 10 g/mL.
 Cardiac ef fects,
 bradycardia
 atrioventricular node blockage
 VANCOMYCIN (GLYCOPEPTIDE)

• Glycopeptide antibiotic
• effective against gram-positive cocci and bacilli
shows activity against antibiotic-resistant
bacteria, such as methicillin-resistant S. aureus.
• Poor oral absorption, administered through IV
• Major toxicities:
 Red man syndrome- erythemic flushing of the
extremities
 Nephrotoxicity- occur frequently in trough concentration
 Ototoxicity- occur frequently in peak serum
concentration
• TDM shows improved therapy and reduced risk of toxicity
 Long distribution phase
 Many of the toxic ef fects occur in the therapeutic range 5-10
ug/mL
 AUC/MIC ratio for optimal therapy is >400
 Primarily eliminated by:
 Renal filtration
 secretion
 Assayed by:
 Immunoassay
 Chromatographic methods
 TEICOPLANIN (GLYCOPEPTIDES)

 Used against gram-positive bacteria, a semi -synthetic drug

which shows similar spectrum of activity with Vancomycin.
 Have minimal toxicity at therapeutic concentrations
 TDM is not routinely necessary unless the patient has renal
dysfunction
 AMINOGLYCOSIDES

 amikacin, gentamicin, tobramycin.. etc.

 aerobic, gram-negative bacterias
 administered intravenously or intramuscularly and elimination
by renal
 MOst common concentration-related adverse ef fects:
Nephrotoxicity (renal tubular necrosis) and irreversible
ototoxicity ( auditory nerve degeneration)
 postantibiotic ef fect: continue to enhance bactericidal activity
after drug has been cleared from the body
 peak (1hr post infusion), trough ( predose, or 10-12 hrs post
infusion)
 ANTIRETROVIRAL AGENTS

• Several classes of drugs which target Human

Immunodeficiency Virus (HIV)
• highly reactive antiretroviral therapy (HART) -generally
involves the use of 2 NRTIs + 1 or more agents from the other
categories (PIs/NNRTI)
 Major Categories:
1) Protease Inhibitors/PIs - interfere with the process of HIV
polypeptide precursor; highly protein bound; oral
administration
 Most commonly used PIs: indinavir, saquinavir, atazanavir,
lopinavir, nelfinavir & retinavir
2) Non-nucleoside Reverse Transcriptase Inhibitors/ NNRTI -
target reverse transcriptase enzyme that transcribes viral RNA
into DNA
Common NNRTIs : efavirenz (CNS toxicity) , nevirapine (liver
enzyme elevation& rash)
3) Nucleoside Reverse Transcriptase Inhibitors/ NRTI- include
both nucleoside and nucleotide analogs; include some of the
1 st anti-HIV therapies devised ( zidovudine, didanosine &
stavudine)