1.

ANTIHYPERTENSIVE DRUGS

The antihypertensives are a class of drugs that are used to treat hypertension (high blood
pressure).

A. ACE INHIBITOR

ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of

pharmaceuticals that are used primarily in treatment of hypertension and congestive heart
failure, in some cases as the drugs of first choice. It is very effective in reducing hypertension
caused by renal artery stenosis, renal disease and malignant hypertension (arteriole
inflammation), where excessive levels ofrenin are released, causing high levels of angiotensin
II, a potent vasoconstrictorand releaser of aldosterone. ACE inhibitors lower circulating
angiotensin II andincreases bradykinin, a potent vasodilator. Cardiac output is unaffected in
patientswith normal heart function, but is significantly increased in individuals
withcongestive heart failure.

Example:
Captopril

Therapeutic Actions: Blocks ACE from converting angiotensin I to angiotensin II, a

powerful vasoconstrictor, leading to decreased blood pressure, decreased aldosterone
secretion, a small increase in serum potassium levels, and sodium and fluid loss; increased
prostaglandin synthesis also may be involved in the antihypertensive action

Special Precautions: Patients on diuretics or with sodium depletion should discontinue

diuretics or increase sodium intake prior to initiation of therapy. Renal impairment, SLE and
other autoimmune collagen disorders and during concurrent use of immunosuppressant or
leucopenic drugs, monitor WBC count and urinary protein before and during therapy.
Lactation. Porphyria. Severe CHF.

B. BETA-BLOCKER

Beta-blocker or beta-adrenergic blocking agent , drug that reduces the symptoms connected
with hypertension, cardiac arrhythmias, angina pectoris, migraine headaches, and other
disorders related to the sympathetic nervous system. Beta-blockers also are sometimes given
after heart attacks to stabilize the heartbeat. Within the sympathetic nervous system, beta-
adrenergic receptors are located mainly in the heart, lungs, kidneys, and blood vessels. Beta-
blockers compete with the nerve-stimulating hormone epinephrine for these receptor sites and
thus interfere with the action of epinephrine, lowering blood pressure and heart rate, stopping
arrhythmias, and preventing migraine headaches. Because it is also epinephrine that prepares
the body for “fight or flight” in stressful or fearful situations, beta-blockers are sometimes
used as antianxiety drugs, especially for stage fright and the like.

Example:
Bisoprolol (Concore)

Therapeutic Actions: Bisoprolol is a highly beta1-selective beta-adrenoceptor antagonist

with low beta2-receptor affinity. It has no intrinsic sympathomimetic activity nor membrane-
stabilising properties. It reduces blood pressure, and by blockade of the cardiac beta1-
receptors, it reduces cardiac action, and hence myocardial oxygen demand.

Special Precautions: Abrupt discontinuation of therapy may cause exacerbation of angina

pectoris in patients suffering from ischaemic heart disease. Discontinuation of therapy should
be gradual, and patients should be advised to limit the extent of their physical activity during
the period in which the medicine is being discontinued.

Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other
 chronic pulmonary diseases. Since bisoprolol is a highly selective beta1-adrenoceptor
blocking agent, it may be used with caution in patients with chronic obstructive airway
disease. However, in some asthmatic patients, an increase in airway resistance may occur.
This bronchospasm can usually be reversed by commonly-used bronchodilators. Congestive
cardiac failure and marked bradycardia may occur.
Bisoprolol may mask the symptoms of hyperthyroidism.
It should be used with caution in patients with hypoglycaemia.

C. CALCIUM CHANNEL BLOCKER

Calcium channel blockers prevent calcium from entering cells of the heart and blood vessel
walls, resulting in lower blood pressure. Calcium channel blockers, also called calcium
antagonists, relax and widen blood vessels by affecting the muscle cells in the arterial walls.

Example:
Amlodipine (Norvasc)

Therapeutic Actions: Amlodipine blocks the transport of calcium into the smooth muscle
cells lining the coronary arteries and other arteries of the body. Since calcium is important in
muscle contraction, blocking calcium transport relaxes artery muscles and dilates coronary
arteries and other arteries of the body. By relaxing coronary arteries, amlodipine is useful in
preventing chest pain (angina) resulting from coronary artery spasm. Relaxing the muscles
lining the arteries of the rest of the body lowers the blood pressure, which reduces the burden
on the heart as it pumps blood to the body. Reducing heart burden lessens the heart muscle's
demand for oxygen, and further helps to prevent angina in patients with coronary artery
disease.

Special precautions: Since the vasodilation induced by Amlodipine is gradual in onset,

acute hypotension has rarely been reported after oral administration. Nonetheless, caution as
with any other peripheral vasodilator, should be exercised when administering Amlodipine ,
particularly in patients with severe aortic stenosis.

2. DIURETICS

A diuretic is any drug that elevates the rate of urination and thus provides a means of forced
diuresis. There are several categories of diuretics. All diuretics increase the excretion of water
from bodies, although each class does so in a distinct way.

A. LOOP DIURETICS

Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are
primarily used in medicine to treat hypertension and edema often due to congestive heart
failure or renal insufficiency.

Loop diuretics act on the Na+-K+-2Cl- symporter (cotransporter) in the thick ascending limb
of the loop of Henle to inhibit sodium and chloride reabsorption. This is achieved by
competing for the Cl- binding site. Because magnesium and calcium reabsorption in the thick
ascending limb is dependent on sodium and chloride concentrations (primarily on the
recycling of the potassium due to the lack of the electropostive gradient generation), loop
diuretics also inhibit their reabsorption. By disrupting the reabsorption of these ions, loop
diuretics prevent the urine from becoming concentrated and disrupt the generation of a
hypertonic renal medulla. Without such a concentrated medulla, water has less of an osmotic
driving force to leave the collecting duct system, ultimately

resulting in increased urine production. Loop diuretics cause an increase in the renal blood
flow by this mechanism. This diuresis leaves less water to be reabsorbed into the blood,
resulting in a decrease in blood volume.

Example:
 Furosemide (Lasix)

Threpautic Actions: Inhibits the reabsorption of sodium and chloride from the loop of
Henle and distal renal tubule. Increases renal excretion of water, sodium, chloride,
magnesium, hydrogen, and calcium. May have renal and peripheral vasodilatory effects.
Effectiveness persists in impaired renal function.

Special Precautions: Hypotension, latent or manifest DM, gout, obstruction of urinary

passages; hepatic cirrhosis w/ concomitant renal insufficiency; hypoproteinemia; premature
infant. Pregnancy, lactation.

B. THIAZIDE

Thiazide is a term used to describe a type of molecule [1] and a class of diuretics[2] often used
to treat hypertension (high blood pressure) and edema (such as that caused by heart, liver, or
kidney disease).

The members of this class of diuretics are derived from benzothiadiazine. They work by
inhibiting reabsorption of sodium (Na+) and chloride (Cl-) ions from the distal convoluted
tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl- symporter. Thiazides also
cause loss of potassium and an increase in serum uric acid. The term "thiazide" is also often
used for drugs with a similar action that do not have the thiazide chemical structure, such as
chlortalidone and metolazone. These agents are more properly termed thiazide-like diuretics.

The thiazides and thiazide-like diuretics reduce the risk of death, stroke, heart attack and
heart failure due to hypertension, and, as of 2009, the best available evidence favors them as
the first choice of treatment for high blood pressure when drugs are necessary. In most
countries, the thiazides are also the cheapest antihypertensive drugs available.

Example:
Hydrochlorothiazide (Hytaz)

Therapeutic Actions: Thiazide diuretics increase the excretion of water by inhibiting the
reabsorption of sodium and chloride ions at the distal renal tubule. The natriuretic effects are
accompanied by a secondary loss of potassium and bicarbonate which can cause a mild
hypokalemic, hypochloremic, metabolic alkalosis. Thiazides also decrease the elimination of
calcium and uric acid. Thiazide diuretics usually do not affect normal blood pressure. When
chronically administered, thiazide diuretics decrease peripheral vascular resistance. The exact
mechanism responsible for lowered peripheral resistance is not known. However, excretion of
urinary sodium by the kidneys is required to achieve blood pressure reduction.

Special precautions:

Patients with renal disease resulting in severe renal impairment because HCTZ decreases the
glomerular filtration rate and may precipitate azotemia in these patients.

Patients with hepatic disease since minor alterations of fluid and electrolyte balance may
precipitate hepatic coma.

Patients with gout or hyperuricemia since thiazide diuretics eg, HCTZ have been reported to
reduce the clearance of uric acid.

Patients with history of pancreatitis since thiazide diuretics have been reported to cause
pancreatitis.

C. POTASSIUM-SPARING

Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium
into the urine.
The potassium-sparing diuretics are competitive antagonists that compete with aldosterone
for intracellular cytoplasmic receptor sites, or by directly blocking sodium channels
(specifically ENaC by amiloride (ENaC is Epithelial Sodium Channel)). The former prevents
the production of proteins that are normally synthesized in reaction to aldosterone. These
 mediator proteins are not produced, and so stimulation of sodium-potassium exchange sites in
the collection tubule does not occur. This prevents sodium re-absorption and potassium and
hydrogen ion secretion.[2]

Example:
Amiloride (Midamor)

Therapeutic Actions: Amiloride works by directly blocking the epithelial sodium channel
(ENaC) thereby inhibiting sodium reabsorption in the distal convoluted tubules and collecting
ducts in the kidneys (this mechanism is the same for triamterene). This promotes the loss of
sodium and water from the body, but without depleting potassium.

Special precautions: Electrolyte Imbalance and BUN Increases. Hyponatremia and

hypochloremia may occur when MIDAMOR is used with other diuretics and increases in
BUN levels have been reported. These increases usually have accompanied vigorous fluid
elimination, especially when diuretic therapy was used in seriously ill patients, such as those
who had hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant edema.
Therefore, when MIDAMOR is given with other diuretics to such patients, careful
monitoring of serum electrolytes and BUN levels is important. In patients with pre-existing
severe liver disease, hepatic encephalopathy, manifested by tremors, confusion, and coma,
and increased jaundice, have been reported in association with diuretics, including amiloride
HCl.

D. OSMOTIC DIURETICS

An osmotic diuretic is a type of diuretic that inhibit reabsorption of water and sodium. In the
nephron, osmotic diuretics act at the portions of the nephron that are water-permeable.

Osmotic diuretics works by increasing blood flow to the kidney. This washes out the cortical
medullary gradient in the kidney. This stops the loop of Henle from concentrating urine,
which usually uses the high osmotic and solute gradient to transport solutes and water.

Example:
Mannitol (Osmitrol)

Therapeutic Actions: Increases the osmotic pressure of glomerular filtrate, which inhibits
tubular reabsorption of water and electrolytes and increases urinary output

Special Precautions: In patients being treated for cerebral edema, mannitol may accumulate
in the brain (causing rebound increases in intracranial pressure) if circulating for long periods
of time as with continuous infusion; intermittent boluses preferred. Cardiovascular status
should also be evaluated; do not administer electrolyte-free mannitol solutions with blood. If
hypotension occurs monitor cerebral perfusion pressure to insure adequate.

3. ANTIBIOTICS

A. CEPHALOSPORINS

Therapeutic Actions: Cephalosporins are bactericidal and have the same mode of action as
other beta-lactam antibiotics (such as penicillins) but are less susceptible to

penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial

cell walls. The peptidoglycan layer is important for cell wall structural integrity.
 The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by
transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala
at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-
lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of
peptidoglycan.

1st Generation

Example: Cefalexin ( Keflex)

Special Precautions: Allergic reactions. Marked renal impairment.

Hypersensitivity to penicillins. Positive Coombs' test; false-positive reaction for glucose in
urine. Pregnancy & lactation.

2nd Generation

Example: Cefaclor (Ceclor)

Special Precautions: Penicillin-sensitive patients. Superinfection.

History of GI disease. Renal impairment. Positive Coombs' test. Pregnancy, lactation. Cross-
hypersensitivity.

3rd Generation

Example: Cefixime (Tergecef)

Special Precautions: Hypersensitivity to penicillins. Personal or

familial history of some form of allergy. Serious renal dysfunction. Poor oral nutrition,
patients receiving parenteral nutrition, elderly, debilitated patients. Pregnancy, lactation.
Infants <6 mth.

4th Generation

Example: Cefepime (Cepimax)

Special Precautions: Antibiotics should be administered with caution to

any patient who has demonstrated some form of allergy, particularly to drugs. If an allergic
reaction to Cepimax occurs, discontinue the drug and treat the patient appropriately. Serious
hypersensitivity reactions may require epinephrine and other supportive therapy.

B. MACROLIDES

Action: Inhibition of bacterial protein biosynthesis by binding irreversibly to the subunit 50S
of the bacterial ribosome, thereby inhibiting translocation of peptidyl tRNA.

Example: Clarithromycin (Clariget)

Special Precautions: Impaired hepatic function & moderate to severe renal impairment.

C. TETRACYCLINES

Action: Inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. They

do so mainly by binding to the 30S ribosomal subunit in the mRNA translation complex.

Special Precautions: Renal impairment. Lactation.

Example: Oxytetracycline (Terramycin)

 Special Precautions: Renal impairment. Lactation.

D. QUINOLONES

Action: Inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby
inhibiting DNA replication and transcription.

Example: Ciprofloxacin (Ciprobay)

Special Precautions: Epilepsy, CNS damage. Photosensitivity.