DRUG STUDY

Name of Drug: METFORMIN

Therapeutic Class: Antihyperglycemic
Pharmacological Class: Non-sulfonylureas/Biguanides
Controlled substance schedule:

Pharmacodynamics: Drug Action

Metformin decreases blood glucose levels by decreasing hepatic glucose
production (gluconeogenesis), decreasing the intestinal absorption of glucose, and
increasing insulin sensitivity by increasing peripheral glucose uptake and utilization. It is
well established that metformin inhibits mitochondrial complex I activity, and it has since
been generally postulated that its potent antidiabetic effects occur through this
mechanism. The above processes lead to a decrease in blood glucose, managing type II
diabetes and exerting positive effects on glycemic control.
After ingestion, the organic cation transporter-1 (OCT1) is responsible for the
uptake of metformin into hepatocytes (liver cells). As this drug is positively charged, it
accumulates in cells and in the mitochondria because of the membrane potentials across
the plasma membrane as well as the mitochondrial inner membrane. Metformin inhibits
mitochondrial complex I, preventing the production of mitochondrial ATP leading to
increased cytoplasmic ADP: ATP and AMP:ATP ratios. These changes activate AMP-
activated protein kinase (AMPK), an enzyme that plays an important role in the
regulation of glucose metabolism. Aside from this mechanism, AMPK can be activated
by a lysosomal mechanism involving other activators. Following this process, increases
in AMP:ATP ratio also inhibit fructose-1,6-bisphosphatase enzyme, resulting in the
inhibition of gluconeogenesis, while also inhibiting adenylate cyclase and decreasing the
production of cyclic adenosine monophosphate (cAMP), a derivative of ATP used for
cell signaling. Activated AMPK phosphorylates two isoforms of acetyl-CoA carboxylase
enzyme, thereby inhibiting fat synthesis and leading to fat oxidation, reducing hepatic
lipid stores and increasing liver sensitivity to insulin.
In the intestines, metformin increases anaerobic glucose metabolism in
enterocytes (intestinal cells), leading to reduced net glucose uptake and increased
delivery of lactate to the liver. Recent studies have also implicated the gut as a primary
site of action of metformin and suggest that the liver may not be as important for
metformin action in patients with type 2 diabetes. Some of the ways metformin may play
a role on the intestines is by promoting the metabolism of glucose by increasing
glucagon-like peptide I (GLP-1) as well as increasing gut utilization of glucose.
In addition to the above pathway, the mechanism of action of metformin may be
explained by other ways, and its exact mechanism of action has been under extensive
study in recent years.
Therapeutic Use:
 Metformin is used alone or with other medications, including insulin, to treat type
2 diabetes (condition in which the body does not use insulin normally and, therefore,
cannot control the amount of sugar in the blood). Metformin helps to control the amount
of glucose (sugar) in blood. It decreases the amount of glucose absorb from food and the
amount of glucose made by the liver. Metformin also increases the body's response to
insulin, a natural substance that controls the amount of glucose in the blood. Metformin is
not used to treat type 1 diabetes (condition in which the body does not produce insulin
and therefore cannot control the amount of sugar in the blood).

Precaution and Contraindications:

 Hypersensitivity to amlodipine; pregnancy (category C).
Dynamics – Side Effects/ Adverse Effects
 CNS: Headache, dizziness, agitation, fatigue.
 Metabolic: Lactic acidosis.
 GI: Nausea, vomiting, abdominal pain, bitter or metallic taste, diarrhea, bloatedness,
anorexia; malabsorption of amino acids, vitamin B12, and folic acid possible.

Drug-Drug Interactions:
 CAPTOPRIL, FUROSEMIDE, NIFEDIPINE may increase risk of hypoglycemia. 

 CIMETIDINE reduces clearance of metformin.

 CONCOMITANT THERAPY WITH AZOLEANTIFUNGAL AGENTS

(FLUCONAZOLE, KETOCONAZOLE, ITRACONAZOLE) AND ORAL
HYPOGLYCEMIC DRUGS has been reported in severe hypoglycemia.

  IODINATED RADIOCONTRAST DYES can cause lactic acidosis and acute kidney

failure. 

 AMILORIDE, CIMETIDINE, DIGOXIN, DOFETILIDE, MIDODRINE,

MORPHINE, PROCAINAMIDE, QUINIDINE, QUININE, RANITIDINE,
TRIAMTERENE, TRIMETHOPRIM, OR VANCOMYCIN may decrease metformin
elimination by competing for common renal tubular transport systems.

 ACARBOSE may decrease metformin levels. 

 IODINATED CONTRAST DYES may cause lactic acidosis or acute kidney failure. 

Nursing Considerations:
Assessment
 History: Allergy to metformin; diabetes complicated by fever, severe infections,
severe trauma, major surgery, ketosis, acidosis, coma; type 1 diabetes, serious
hepatic or renal impairment, uremia, thyroid or endocrine impairment, glycosuria,
hyperglycemia associated with primary renal disease, CHF, pregnancy, lactation
 Physical: Skin color, lesions; T, orientation, reflexes, peripheral sensation; R,
adventitious sounds; liver evaluation, bowel sounds; urinalysis, BUN, serum
creatinine, LFTs, blood glucose, CBC

Interventions
 Monitor urine or serum glucose levels frequently to determine effectiveness of drug
and dosage.
 WARNING: Arrange for transfer to insulin therapy during periods of high stress
(infections, surgery, trauma).
 WARNING: Use IV glucose if severe hypoglycemia occurs as a result of overdose.

Teaching points
 Do not discontinue this medication without consulting your health care provider.
 Monitor urine or blood for glucose and ketones as prescribed.
 Swallow extended-release tablets whole; do not cut, crush, or chew.
 Do not use this drug during pregnancy; if you become pregnant, consult with your
health care provider for appropriate therapy.
 Avoid using alcohol while taking this drug.
 Report fever, sore throat, unusual bleeding or bruising, rash, dark urine, light-
colored stools, hypo- or hyperglycemic reactions.

Name of Drug: AMLODIPINE

 Therapeutic Class: Antianginal Agents, Antihypertensive
Pharmacological Class: Calcium Channel Blockers
Controlled substance schedule:

Pharmacodynamics: Drug Action

Action on Blood Pressure
Amlodipine is considered a peripheral arterial vasodilator that exerts its action
directly on vascular smooth muscle to lead to a reduction in peripheral vascular
resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine
calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the
influx of calcium ions into both vascular smooth muscle and cardiac muscle.
Experimental studies imply that amlodipine binds to both dihydropyridine and non-
dihydropyridine binding sites, located on cell membranes. The contraction of cardiac
muscle and vascular smooth muscle are dependent on the movement of extracellular
calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion
influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted
on vascular smooth muscle cells than on cardiac muscle cells Label. Direct actions of
amlodipine on vascular smooth muscle result in reduced blood pressure.
Action in Angina
The exact mechanism by which amlodipine relieves the symptoms of angina have
not been fully elucidated to this date, however, the mechanism of action is likely twofold:
Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral
resistance (afterload) against which the cardiac muscle functions. Since the heart rate
remains stable during amlodipine administration, the reduced work of the heart reduces
both myocardial energy use and oxygen requirements. Dilatation of the main coronary
arteries and coronary arterioles, both in healthy and ischemic areas, is another possible
mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase
in myocardial oxygen delivery in patients experiencing coronary artery spasm
(Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by
smoking.

Therapeutic Use:
Inhibits the movement of calcium ions across the membranes of cardiac and
arterial muscle cells; inhibits transmembrane calcium flow, which results in the
depression of impulse formation in specialized cardiac pacemaker cells, slowing of the
velocity of conduction of the cardiac impulse, depression of myocardial contractility, and
dilation of coronary arteries and arterioles and peripheral arterioles; these effects lead to
 decreased cardiac work, decreased cardiac oxygen consumption, and in patients with
vasospastic (Prinzmetal’s) angina, increased delivery of oxygen to cardiac cells.
Precaution and Contraindications:
 Hypersensitivity to amlodipine
 Congestive heart failure (CHF).
 Persistent progressive dermatologic reactions.
 Symptomatic hypotension with or without syncope possible, particularly with
severe aortic stenosis; because of gradual onset of action, acute hypotension unlikely.
 Worsening of angina and acute myocardial infarction (MI) can develop after dose
is started or increased, particularly with severe obstructive CAD.
 Peripheral edema may develop within 2-3 weeks of starting therapy.
 Use with caution in patients with hypertrophic cardiomyopathy; reduction in
afterload may worsen symptoms associated with this condition.
 May reduce coronary perfusion and result in ischemia in patients with severe
aortic stenosis; use caution.
 Extensively metabolized by liver; titrate dose slowly with severe hepatic
impairment.
 Initiate at lower dose in the elderly.
 Titrate dose every 7-14 days on a given dose; peak antihypertensive effect is
delayed.
 Co-administration with CYP3A inhibitors (moderate and strong) results in
increased systemic exposure to amlodipine and may require dose reduction; monitor
for symptoms of hypotension and edema when amlodipine is co-administered with
CYP3A inhibitors to determine the need for dose adjustment.
 Amlodipine may increase systemic exposure of cyclosporine or tacrolimus when
co-administered; frequent monitoring of trough blood levels of cyclosporine and
tacrolimus recommended; adjust dose when appropriate Pregnancy and Lactation
Use amlodipine with caution during pregnancy if benefits outweigh risks.
 Animal studies show risk and human studies not available or neither animal nor
human studies done. It is unknown whether amlodipine is excreted in milk; use of
amlodipine while breastfeeding is not recommended.
Dynamics – Side Effects/ Adverse Effects
 CV: Palpitations, flushing tachycardia, peripheral or facial edema, bradycardia, chest
pain, syncope, postural hypotension. 
 CNS: Light-headedness, fatigue, headache. 
 GI: Abdominal pain, nausea, anorexia, constipation, dyspepsia, dysphagia, diarrhea,
flatulence, vomiting. 
 Urogenital: Sexual dysfunction, frequency, nocturia. 
 Respiratory: Dyspnea.
  Skin: Flushing, rash. 
  Other: Arthralgia, cramps, myalgia.
Drug-Drug Interactions:
 ADENOSINE may increase the risk of bradycardia.

 BOSENTAN may decrease efficacy of amlodipine

 Additive hypotensive effects with other ANTIHYPERTENSIVE AGENTS.

 AZOLE ANTIFUNGALS (E.G., FLUCONAZOLE, ITRACONAZOLE) may inhibit

metabolism of amlodipine.

 ITRACONAZOLE may increase edema. 

Nursing Considerations:

 Monitor BP for therapeutic effectiveness. BP reduction is greatest after peak levels of

amlodipine are achieved 6–9 h following oral doses.

 Monitor for S&S of dose-related peripheral or facial edema that may not be accompanied
by weight gain; rarely, severe edema may cause discontinuation of drug.

 Monitor BP with postural changes. Report postural hypotension. Monitor more frequently
when additional antihypertensives or diuretics are added.

 Monitor heart rate; dose-related palpitations (more common in women) may occur.

 Report significant swelling of face or extremities.

 Take care to have support when standing & walking due to possible dose-related light-
headedness/dizziness.

 Report shortness of breath, palpitations, irregular heartbeat, nausea, or constipation to

physician.

 Do not breast feed while taking this drug without consulting physician.
Name of Drug: LOSARTAN
Therapeutic Class: Cardiovascular Agents, Antihypertensive
Pharmacological Class: Angiotensin II Receptor Antagonist
Controlled substance schedule:

Pharmacodynamics: Drug Action

Losartan reversibly and competitively prevents angiotensin II binding to the
AT1 receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and
its active metabolite bind the AT1 receptor with 1000 times more affinity than they bind
to the AT2 receptor. The active metabolite of losartan is 10-40 times more potent by
weight than unmetabolized losartan as an inhibitor of AT1 and is a non-competitive
inhibitor. Losartan's prevention of angiotensin II binding causes vascular smooth muscle
relaxation, lowering blood pressure.
Angiotensin II would otherwise bind to the AT1 receptor and induce
vasoconstriction, raising blood pressure.
Therapeutic Use:
Selectively blocks the binding of angiotensin II to the AT1 receptors found in
many tissues (e.g., vascular smooth muscle, adrenal glands). Antihypertensive effect
results from blocking the vasoconstricting and aldosterone-secreting effects of
angiotensin II.

Precaution and Contraindications:

 Hypersensitivity to losartan
 Pregnancy [category C (first trimester) category D (second and third trimesters)]
 Lactation.
 Patients on diuretics
 Renal or Hepatic impairment.
Dynamics – Side Effects/ Adverse Effects
 CNS: Dizziness, insomnia, headache. 
 GI: Diarrhea, dyspepsia. 
 Musculoskeletal: Muscle cramps, myalgia, back or leg pain. 
 Respiratory: Nasal congestion, cough, upper respiratory infection, sinusitis.
Drug-Drug Interactions:
 Phenobarbital decreases serum levels of losartan and its metabolite
Nursing Considerations:

 Monitor BP at drug trough (prior to a scheduled dose).

 Monitor drug effectiveness, especially in African-Americans when losartan is used as
monotherapy.
 Inadequate response may be improved by splitting the daily dose into twice-daily dose.
 Lab tests: Monitor CBC, electrolytes, liver & kidney function with long-term therapy.
 Notify physician of symptoms of hypotension (e.g., dizziness, fainting).
 Notify physician immediately of pregnancy.
 Do not breast feed while taking this drug.
Name of Drug: AZITHROMYCIN
Therapeutic Class: Macrolide Antibiotic
Pharmacological Class: Azalides
Controlled substance schedule:

Pharmacodynamics: Drug Action

Azithromycin is a macrolide antibiotic under the azalide group. It inhibits RNA-
dependent protein synthesis by binding to the 50s ribosomal subunit, preventing the
translocation of peptide chains.
Therapeutic Use:
Azithromycin is used to treat certain bacterial infections, such as bronchitis;
pneumonia; sexually transmitted diseases (STD); and infections of the ears, lungs,
sinuses, skin, throat, and reproductive organs.
Precaution and Contraindications:
 Hypersensitivity to macrolide antibiotics.
 History of hepatic dysfunction/cholestatic jaundice following previous antibiotic
use.
 Patients with myasthenia gravis, electrolyte disturbance particularly hypokalaemia
and hypomagnesaemia; bradycardia, cardiac arrhythmia, severe cardiac
insufficiency, congenital or documented QT prolongation, history of torsades de
pointes.
 Severe renal (GFR <10 mL/min) and hepatic impairment. Children. Pregnancy and
lactation.
 Azithromycin should not be given long-term to prevent bronchiolitis obliterans
syndrome in patients with cancers of the blood or lymph nodes who undergo a
hematopoietic stem cell transplant.

Dynamics – Side Effects/ Adverse Effects

 Significant: Myasthenia gravis.
 Ear and labyrinth disorders: Deafness.
 Eye disorders: Pruritus, burning, stinging of the eye or ocular discomfort, sticky eye
sensation, foreign body sensation (ophthalmic).
 Gastrointestinal disorders: Diarrhoea, vomiting, abdominal pain, nausea, flatulence,
dyspepsia, dysgeusia.
 General disorders and admin site conditions: Injection site pain, fatigue.
 Investigations: Decreased lymphocyte count and blood bicarbonate; increased
eosinophil count, basophils, monocytes and neutrophils.
  Metabolism and nutrition disorders: Anorexia.
 Musculoskeletal and connective tissue disorders: Arthralgia.
 Nervous system disorders: Headache, dizziness, paraesthesia.
 Skin and subcutaneous tissue disorders: Pruritus, rash.
 Potentially Fatal: Rarely, serious hypersensitivity reactions (e.g. anaphylaxis,
angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute
generalised exanthematous pustulosis drug reaction with eosinophilia and systemic
symptoms), fulminant hepatitis leading to liver failure, prolonged cardiac
repolarisation and QT interval, cardiac arrhythmia, torsades de pointes, Clostridium
difficile associated diarrhea (CDAD).

Drug-Drug Interactions:
 Increased risk of prolonged QT interval with class IA (e.g. quinidine, procainamide)
and class III (e.g. dofetilide, amiodarone, sotalol) antiarrhythmics; pimozide
cisapride and terfenadine.
 Increased serum concentrations of digoxin, colchicine, and ciclosporin. May
potentiate the effects of oral anticoagulants (e.g. warfarin).
Nursing Considerations:
 Monitor for and report loose stools or diarrhea, since pseudomembranous colitis (see
Appendix F) must be ruled out.

 Monitor PT and INR closely with concurrent warfarin use.

 Direct sunlight (UV) exposure should be minimized during therapy with drug.

 Take aluminum or magnesium antacids 2 h before or after drug.

 Report onset of loose stools or diarrhea.

 Do not breast feed while taking this drug without consulting physician.
Name of Drug: AMPICILLIN SULBACTAM
Therapeutic Class: Antibiotic
Pharmacological Class: Penicillin-like Antibiotics, Beta-Lactamase Inhibitors
Controlled substance schedule:

Pharmacodynamics: Drug Action

Ampicillin prevents bacterial cell wall synthesis by binding to 1 or more of the
penicillin-binding proteins resulting in the inhibition of the final transpeptidation step of
peptidoglycan synthesis in the bacterial cell walls. Sulbactam extends the spectrum of
ampicillin activity due to its irreversible inhibition of β-lactamases that are found in
penicillin-resistant organisms. It has limited antibacterial activity to Neisseriaceae.
Therapeutic Use:
This combination medication is used to treat a wide variety of bacterial infections.
It is known as a penicillin-type antibiotic. It works by stopping the growth of bacteria.
Precaution and Contraindications:
 Hypersensitivity (e.g. anaphylaxis, Stevens Johnson syndrome [SJS]) to
ampicillin, sulbactam, or β-lactam antibiotics (e.g. penicillins, cephalosporins).

 History of cholestatic jaundice or hepatic dysfunction associated with

ampicillin/sulbactam combination use.

 Special Precautions: Patient with history of atopic allergy (e.g. asthma, eczema,
urticaria).

 Not recommended for use in patients with infectious mononucleosis. Renal and
hepatic impairment. Neonates, infants and children. Pregnancy and lactation.

Dynamics – Side Effects/ Adverse Effects

 Significant: Fungal or bacterial superinfection, including Clostridium difficile-
associated diarrhoea (CDAD) and pseudomembranous colitis (prolonged use);
rash or severe cutaneous reactions (e.g. toxic epidermal necrolysis, SJS, dermatitis
exfoliative, erythema multiforme, acute generalised exanthematous pustulosis).

 Blood and lymphatic system disorders: Anaemia, thrombocytopenia, eosinophilia,

leucopenia, neutropenia.
  Cardiac disorders: Chest pain.

 Gastrointestinal disorders: Diarrhoea, vomiting, nausea, flatulence, abdominal

distension, glossitis, mucosal bleeding.

 General disorders and administration site conditions: Inj site pain, fatigue,
malaise, chills, oedema.

 Hepatobiliary disorders: Hyperbilirubinaemia.

 Investigations: Increased ALT, AST; decreased plasma concentration of total

conjugated estriol, conjugated estrone, estradiol, and estriol-glucuronide (in
pregnant women).

 Nervous system disorders: Headache.

 Renal and urinary disorders: Urine retention, dysuria.

 Respiratory, thoracic and mediastinal disorders: Epistaxis, throat tightness.

 Skin and subcutaneous tissue disorders: Pruritus.

 Vascular disorders: Phlebitis, thrombophlebitis.

 Potentially Fatal: Hypersensitivity reaction (e.g. anaphylaxis), hepatotoxicity (e.g.

hepatitis, cholestatic jaundice).

Drug-Drug Interactions:
 Increased and prolonged serum concentrations with probenecid.
 Ampicillin: Increased incidence of rashes with allopurinol.
 May enhance the effect of anticoagulants. May inactivate the effect of
aminoglycosides.
 Bacteriostatic drugs (e.g. chloramphenicol, erythromycin, sulfonamides,
tetracyclines) may interfere with the bactericidal effect of ampicillin.
 Diminished therapeutic efficacy of estrogen-containing oral contraceptives.
 Decreased clearance of methotrexate thus increase the risk of toxicity.
Nursing Considerations:
Assessment & Drug Effects
 Determine previous hypersensitivity reactions to penicillins, cephalosporins, and
other allergens prior to therapy.
 Lab tests: Baseline C&S tests prior to initiation of therapy; start drug pending
results.
 Report promptly unexplained bleeding (e.g., epistaxis, purpura, ecchymoses).
 Monitor patient carefully during the first 30 min after initiation of IV therapy for
signs of hypersensitivity and anaphylactoid reaction (see Appendix F). Serious
anaphylactoid reactions require immediate use of emergency drugs and airway
management.
 Observe for and report symptoms of superinfections (see Appendix F). Withhold
drug and notify physician.
 Monitor I&O ratio and pattern. Report dysuria, urine retention, and hematuria.
 Patient & Family Education: Report chills, wheezing, pruritus (itching),
respiratory distress, or palpitations to physician immediately. Do not breast feed
while taking this drug without consulting physician.