Marion Aleah Moreno BS PHARM 3-V3A DISPENSING 2

Assignment

10 examples of drug-drug interaction

1. One example is the interaction between warfarin (Coumadin), an anticoagulant (blood
thinner), and fluconazole (Diflucan), an antifungal medication. Taking these two drugs
together can lead to a potentially dangerous increase in bleeding.
2. For example, mixing a drug you take to help you sleep (a sedative) and a drug you take
for allergies (an antihistamine) can slow your reactions and make driving a car or
operating machinery dangerous.
3. Digoxin and Quinidine. This significant drug interaction has been known for a long time,
yet it continues to be a problem, often with devastating results. The interaction can lead
to a marked increase in plasma concentration levels of digoxin in more than 90% of
patients.
4. Sildenafil and Isosorbide Mononitrate. Sildenafil may markedly increase the hypotensive
effects of isosorbide mononitrate. More than 123 deaths have been reported since 1998
when sildenafil was made available in the United States. Most deaths were among
patients with 1 or more risk factors, including obesity, hypertension, and cigarette
smoking. Sildenafil was developed as a phosphodiesterase-5 (PDE5) inhibitor.
5. Angiotensin Converting Enzymes (ACE) inhibitors and Potassium Supplements. ACE
inhibitors increase the levels of potassium in the body. Thus, if potassium supplements
are co-administered with ACE inhibitors, there is a potential for elevated potassium
levels in blood (known as hyperkalemia)
6. Digoxin and Amiodarone. Amiodarone may lead to increased levels of digoxin in the
body and potential toxicity.
7. Digoxin and Verapamil. Verapamil may decrease the clearance of digoxin, leading to
increased levels of digoxin in the body and potential toxicity. Intake of digoxin and
verapamil together may result in excessive slowing down of the heart
8. Theophylline and Quinolones. Quinolones inhibit the metabolism of theophylline, thereby
increasing its blood levels and leading to potential theophylline toxicity and increased
likelihood of seizures
9. Warfarin and Macrolides. Macrolides reduce the metabolism and clearance of warfarin,
resulting in increased levels and effects of warfarin like bleeding.
10 example drug with toxic metabolites and ADR
1. Isoniazid. Acetylhydrazine (AcHz), hydrazine (Hz), and acetylisoniazid (AcINH) are the
major metabolites of INH. Studies of INH hepatotoxicity in rats showed that AcINH and
AcHz can cause hepatic necrosis; however, treatment with INH directly even at high
dose and long term did not cause toxicity.
2. NSAIDs. NSAID toxicity should be suspected in the case of any overdose that is
accompanied by a symptom constellation of gastroenteritis, CNS depression, metabolic
acidosis, and renal insufficiency.
3. Paracetamol. In case of overdose the majority of paracetamol is metabolized to
N-acetyl-p-benzoquinone imine (NAPQI), which is responsible for the severe toxic
effects
4. Acetaminophen. Consumption of a single dose greater than 7 g in an adult and 150
mg/kg in a child is considered potentially toxic to the liver and kidneys due to the highly
active metabolite, N-acetyl-p-benzoquinone imine (NAPQI)[5]. Acetaminophen overdose
is one of the most common drug-related toxicities reported to poison centers.
5. Methanol. Methanol is metabolized to its toxic metabolite, formic acid/formate. Formic
acid is responsible for metabolic acidosis and end-organ toxicity. End-organ toxicity
includes primarily retinal damage, and possibly basal ganglia damage. Methanol is
osmotically active.
6. Ethylene glycol. Although ethylene glycol itself is not particularly damaging, its highly
toxic metabolites include glyoxylate, glycolate, oxalic acid, and ketoaldehydes. Glycolic
acid appears to be primarily responsible for the metabolic acidosis observed in this
condition.
7. Cyclophosphamide. Acrolein is the only metabolite of cyclophosphamide that is known to
be both reactive and cytotoxic. Collectively, these data indicate that acrolein is the likely
causative agent in cyclophosphamide-induced cystitis.
8. Valproic acid. The hepatotoxicity of the anticonvulsant drug valproic acid may be
associated with the formation of potentially reactive metabolites, one of which is
(E)-2-propyl-2,4-pentadienoic acid.
9. Carbamazepine. Carbamazepine undergoes oxidation via CYP 3A4 and to a lesser
extent CYP 2C8 to carbamazepine-lO,ll-epoxide, which is the active metabolite that is
thought to cause toxic effects.
10. Acetanilide. Acetanilide is converted to a phenolic metabolite in the human body which
gives it an analgesic effect, but some is converted to aniline (aminobenzene) which is
toxic.