Drugs acting in the cardiovascular system. System pharmacology. Pharmacokinetics Akem lazare alain RHIBMS

1. Cardiovascular system
drug classes
 Diuretics
 Beta- adrenergic blockers
 Renin inhibitor
 Angiotensin ii receptor blocker
 ACE inhibitor
 Calcium channel blockers
 Alpha- receptor blockers
 HMG-CoA reductase inhibitor
 Bile acid resins
 Niacin
 Cholesterol absorption
 Nitrates

2. Diuretics; Diuretics decrease BP by causing diuresis, which results
in decreased plasma volume, stroke volume, and cardiac output.
• Thiazide Diuretics; Thiazide diuretics work by increasing the urinary
excretion of sodium and chloride in equal amounts. They inhibit the
reabsorption of sodium and chloride in the thick ascending limb of the loop of
Henle and the early distal tubules. . E.g chlorthalidone (Hygroton),
hydrochlorothiazide, Microzide, indapamide, metolazone (Zaroxolyn)
• Contraindications Diuretics are contraindicated in patients who are anuric,
renal decompensation, in patients hypersensitive to these compounds or to
sulfonylureas,
• Adverse Events/ Side effects include hypokalemia, hypomagnesemia,
hypercalcemia, hyperuricemia, hyperglycemia, and hyperlipidemia. Other side
effects include tinnitus, paresthesias, abdominal cramps, nausea, vomiting,
diarrhea, muscle cramps, weakness, and sexual dysfunction.

3. • Loop Diuretics; Loop diuretics are indicated in the presence of edema
associated with congestive heart failure, hepatic cirrhosis, and renal disease.
E.g bumetanide (Bumex), ethacrynic acid (Edecrin), urosemide (Lasix),
torsemide (Demadex)
• Furosemide and ethacrynic acid inhibit the reabsorption of sodium and chloride,
not only in proximal and distal tubules but also in the loop of Henle.
• Adverse Events Loop diuretics may cause the same side effects as thiazides,
• Potassium-Sparing Diuretics The potassium-sparing diuretics interfere with
sodium reabsorption at the distal tubule, thus decreasing potassium secretion.
Potassium-sparing diuretics have the potential for causing hyperkalemia and
hyponatremia,
• Contraindications; should be avoided in patents with serum potassium levels
of more than 5 mEq/L.
• Adverse Events Side effects of spironolactone include gynecomastia,
hirsutism, and menstrual irregularitie

4. Beta-Adrenergic Blockers
• Beta-1 receptors, are found in the heart and kidney, regulate heart rate,
renin release, and cardiac contractility. Beta-2 receptors, located in the lungs,
liver, pancreas, and arteriolar smooth muscle, regulate bronchodilation and
vasodilation.
• Beta blockers that bind specifically to beta-1 receptors are referred to as
cardioselective e.g. metoprolol (Lopressor), betaxolol (Kerlone), atenolol
(Tenormin), acebutolol (Sectral), etc.
• Blockade of beta-1 receptors on the surface of juxtaglomerular cells located
on the afferent arteriole of the kidney results in reduced renin release and
decreased stimulation of the RAAS.
• Contraindications Beta blockers should be avoided in patients who have
sinus bradycardia, asthma, chronic obstructive pulmonary disease,
• Adverse Events The most common side effects of beta blockers are fatigue,
drowsiness, dizziness, bronchospasm, nausea, and vomiting.

5. • Renin Inhibitors; Renin inhibitors block the conversion of angiotensinogen
to angiotensin I. e.g. aliskiren (Tekturna), fosinopril (Monopril), lisinopril
(Prinivil, Zestril)
• Contraindications There are no contraindications , However, this medication
should be avoided during pregnancy because drugs that act directly on the
renin-angio tensin system can cause fetal and neonatal morbidity.
• Adverse Events Significant adverse events include diarrhea and,
infrequently, angioedema
• Angiotensin II Receptor Blockers ARBs block the vasoconstriction and
aldosterone-secreting effects of angiotensin II by selectively blocking the
binding of angiotensin II to the angiotensin II receptor found in many tissues
• E.g. losartan (Cozaar), valsartan (Diovan), candesartan (Atacand),

6. Cardiovascular drugs
• ACE Inhibitors; ACE inhibitors such as captopril, enalapril, and lisinopril exert an
antihypertensive effect by inhibiting ACE, which is responsible for converting
angiotensin I to angiotensin II
• Contraindications ACE inhibitors should be avoided in patients with bilateral renal
artery stenosis or unilateral stenosis because of the risk of acute renal failure.
• Adverse Events; include chronic dry cough, rashes (most common with captopril
[Capoten]), and dizziness.
• Calcium Channel Blockers CCBs share the ability to inhibit the movement of
calcium ions across the cell membrane. They depress of mechanical contraction of
myocardial and smooth muscle The result is muscle relaxation and vasodilation. E.g.
verapamil (Calan) and diltiazem (Cardizem),
• Contraindications First-generation CCBs such as verapamil and diltiazem may
accelerate the progression of congestive heart failure in a patient with cardiac
dysfunction.
• Adverse Events The most common side effects of CCBs are headache, peripheral
edema, and bradycardia.

7. CVS drugs
• Direct Vasodilators; The direct vasodilators hydralazine (Apresoline) and minoxidil (Loniten)
cause arteriolar smooth muscle relaxation, resulting in reduced BP, indicated for patients with
severe hypertension.
• Contraindications; Hydralazine is contraindicated in patients with coronary artery disease and
mitral valvular rheumatic heart disease, Minoxidil is contraindicated in patients with
pheochromocytoma, acute MI, and dissecting aortic aneurysm.
• Adverse Events Hydralazine is associated with a lupus-like syndrome, Other adverse reactions
include dermatitis, drug fever, and peripheral neuropathy.
• Bile Acid Resins; Bile acid resins decrease cholesterol absorption through the exogenous
pathway. This decreases the cholesterol return to the liver The body responds to this by increasing
LDL receptors on the liver, which in turn increases the amount of LDL cholesterol taken up by the
liver and thus decreases LDL cholesterol levels in the bloodstream. E.g. lestyramine (Questran,
Questran Light, Prevalite), colesevelam (Welchol)
• Adverse Events Bile acid resins are not absorbed, and therefore systemic adverse events are
minimal. The adverse events are GI-related and include flatulence, bloating, abdominal pain,
heartburn, and constipation. As such elderly patients, may not be good candidates
• Interactions; Because bile acid resins block the absorption of cholesterol from the GI tract, they
should be taken with meals to maximize effectiveness.

8. CVS DRUGS
• HMG-CoA Reductase Inhibitors (Statins); the statins block the conversion of
HMG-CoA to mevalonate, which is the rate-limiting step in the production of
cholesterol in the liver. e.g. fluvastatin (Lescol) can lower LDL cholesterol levels up to
approximately 36% with the maximum dose,
• Contraindications Although no studies have been conducted in pregnant women,
lovastatin causes skeletal malformations in rats, so statins are contraindicated during
pregnancy.
• Adverse Events; Gastrointestinal (GI) complaints and headache are the two most
commonly reported adverse events
• Cholesterol Absorption Inhibitors; ezetimibe (Zetia), appears to act at the brush
border of the small intestine and inhibits the absorption of cholesterol, leading to a
decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of
hepatic cholesterol stores and an increase in clearance of cholesterol from the blood;
• Contraindications; Ezetimibe is contraindicated in patients who have a
hypersensitivity to any component of the medication
• Adverse Events; Adverse events with ezetimibe are minimal but headache, diarrhea,
and abdominal pain are common

9. • Anticoagulants; they are use to prevent thrombus formation and hinder the
growth of blood clots that have already formed. They are indicated in; ischemic
stroke, DIC , recurrent venous thromboembolism(VTE). Etc. the most commonly
used are
• Heparin e.g. lovenox e(noxaparin), fragmin (deltaprin), innohep (tinzaparin) they
bind to antiheparin III and inactivate factor IIa and Xa
• Adverse event include; easy bleeding, bruising, pain, redness, warmth, irritation.
• Contraindications include; history of heparin-induced low blood platelets,
uncontrolled, active bleeding except DIC.
• Warfarin; it is a vitamin k antagonist.
• Adverse effect like necrosis, osteoporosis, artery calcification, it can cross the
placenta leading to fetal bleeding, spontaneous abortion, still birth and neonatal
death
• It is contraindicated for patient taking aspirin or aspirin containing products.
Acetaminophen, antacids or laxatives

10. Pharmacotherapy for Endocrine Disorders
• Sulfonylureas Sulfonylureas are a major group of oral hypoglycemic agents used to
treat type 2 diabetes; E.g. tolbutamide (Orinase), chlorpropamide (Diabinese), glyburide
(DiaBeta, Micronase), glyburide,
• Mechanism of Action Sulfonylureas bind to specific receptors on beta cells, causing
ATP dependent potassium channels to close. The calcium channels subsequently open,
leading to increased cytoplasmic calcium, which stimulates the release of insulin.
• Adverse Events/Contraindications/Interactions The most important complication
of the use of sulfonylureas is hypoglycemia
• Biguanides; This class inhibits hepatic glucose production and moderately improves
peripheral sensitivity to insulin. Gluconeogenesis and glycogenolysis are inhibited in the
liver. Glycemic control is achieved without stimulating insulin secretion, so hypoglycemia
does not develop. Metformin (Glucophage) is the only available biguanide.
• Contraindications; Contraindications include renal dysfunction, serum creatinine level
of 1.4 mg/dL or higher, heart failure, and pregnancy.]
• Adverse Events/Interactions; The most common side effect of metformin therapy is
gastrointestinal (GI) upset, which includes diarrhea, nausea, vomiting, abdominal
bloating, flatulence, anorexia, and a metallic taste in the mouth.

11. Endocrine drugs
• Thiazolidinediones. E.g. rosiglitazone (Avandi), pioglitazone (Actos).
• Mechanism of Action; TZDs bind to the nuclear steroid hormone receptor perixosome
proliferator-activated receptor-gamma and increase insulin sensitivity in skeletal muscle
and fat
• Adverse Events/Contraindications Pioglitazone may cause reduced concentrations of
combined oral contraceptives; therefore, patients using oral contraceptives should
consider alternative contraception methods.
• a-Glucosidase Inhibitors; acarbose (Precose), miglitol (Glyset):
• Mechanism of Action; The enzyme a-glucosidase, found on the brush border of the
intestine, is necessary for the absorption of starch and disaccharides. They acts by
slowing the absorption of carbohydrates from the intestines, minimizing the postprandial
rise in blood sugar.
• Contraindications; Acarbose (Precose) is contraindicated in patients with diseases of
the bowel (e.g., inflammatory bowel disease, absorptive disorders, history of bowel
obstruction) or cirrhosis.
• Adverse Events/Interactions The most common side effects involve the GI tract.
Increased fermentation secondary to the delay in carbohydrate absorption increases

12. Endocrine system drug
• Meglitinide Analogs; are rapid-acting insulin secretagogues that stimulate the release of insulin from
the pancreas in response to a meal by binding to sites closes the ATP-dependent K channels in the
membranes of the beta cells. This causes a depolarization of the beta cells and an opening of Ca
channels. The resulting increased influx of calcium causes insulin secretion. E.g. repaglinide (Prandin),
nateglinide (Starlix)
• Adverse Events; Adverse events include hypoglycemia, GI disturbances, upper respiratory infections,
headache, diarrhea, constipation, arthralgias, and back or chest pain
• Interactions; erythromycin, and other cytochrome P450 (CYP450) 3A4 inhibitors may potentiate the
drug as may nonsteroidal anti-inflammatory drugs, aspirin, sulfonamides, and warfarin while Drugs
such as rifampin, barbiturates, may antagonize it.
• Insulin; It causes the rapid transport of glucose and amino acids intracellularly, promotes anabolism,
and inhibits protein catabolism. In the liver, it promotes the uptake and storage of glucose in the form
of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat. .g.
Insulin analog (Humalog), Insulin injection (Novolog), Regular (R) (Novolin R, Velosulin BR)
• Adverse Events Hypoglycemia, hypokalemia, lipodystrophy, and local or systemic allergic reaction
can occur with insulin.
• Interactions Salicylates, beta blockers, monoamine oxidase inhibitors, alcohol, and sulfa drugs
potentiate insulin

13. Endocrine drugs
• Antithyroid Drugs Antithyroid drugs commonly used are methimazole
(Tapazole) and propylthiouracil (PTU [Propyl-Thyracil]; propylthiouracil
(PTU [Propyl-Thyracil]), methimazole (Tapazole).
• Mechanism of Action; These drugs act by inhibiting iodine
organification. They also block the conversion of T4 to T3 in the
periphery, although this mechanism has minimal clinical relevance.
• Adverse Events; Side effects are fairly minimal, with the most common
being rash, arthralgias, itching, and hepatic abnormalities.
• Interactions; Because these drugs decrease iodine uptake and
organification, they can interfere with subsequent radioactive iodine
therapy

14. Genitourinary tract drugs
• Anti-Infectives
Trimethoprim–Sulfamethoxazole; This agent ultimately adversely affects the
production of proteins and nucleic acids of bacteria at the target (prostate) site.
Interaction. Drug–drug interactions can present when the patient is also taking
phenytoin (Dilantin), oral hypoglycemics, or warfarin (Coumadin).
Fluoroquinolones; these agents decrease the growth and replication of bacteria by
inhibiting bacterial deoxyribonucleic acid (DNA) during synthesis.
interaction.; The absorption of fluoroquinolones is reduced by milk, antacids
(aluminum- or magnesium-based), iron or zi.nc salts, and sucralfate.
Tetracycline; e.g. doxycycline (Vibramycin) acts by inhibiting protein synthesis:
binding of peptidyl transfer ribonucleic acid (tRNA) is blocked at ribosomal Mrna
macrolide antibiotics; e.g. Azithromycin and Clarithromycin, they inhibits RNA
dependent protein synthesis by reversibly binding to the 50 S ribosomal subunits of
susceptible microorganisms.

15. Genitourinary tract drugs
• 5-Alpha-Reductase Inhibitors; androgen hormone inhibitors, are used for
managing the symptoms of BPH (benign prostatic hypertrophy). They block 5-a-
reductase enzyme that activates testosterone in the prostate. It impairs prostate
growth by inhibiting the conversion of testosterone to DHT and causes changes in the
epithelial cells of the transition zone. E.g. Finasteride (Proscar) and dutasteride
(Avodart
• Adverse Events Adverse events include decreased libido, impotence, ejaculatory
failure, and gynecomastia. Finasteride can also falsify the PSA level after 6 months of
therapy.
• Anticholinergic/Antimuscarinic Drug; e.g. oxybutynin, tolterodine, trospium,
solifenacin etc. this agents act as antagonist to the muscarinic receptor that is
effective in reducing frequency of micturition, increasing bladder capacity, reducing
frequency and severity of urgency, and reducing the number of episodes of
incontinence
• Contraindications Anticholinergic medications are capable of precipitating or
worsening urinary retention as well as worsening narrow-angle glaucoma.
• Adverse Events The expected adverse event profile includes traditional
anticholinergic effects such as xerostomia, constipation, and urinary retention.

16. Genitourinary tract drugs
• Tricyclic Antidepressants; imipramine (Tofranil) also has anticholinergic activity and
has been used in the treatment of OAB. It Imipramine has established utility in treating
nocturnal enuresis in children with success rates as high as 70%.
• Mechanism of Action Imipramine, a TCA, blocks the reuptake of serotonin and
norepinephrine by the presynaptic neuronal membrane. that support the use of
imipramine in OAB.
• Adverse Events, Contraindications, and Interactions Imipramine may cause
orthostatic hypotension and numerous cardiotoxic effects, The use of monoamine
oxidase (MAO) inhibitors within 14 days of initiation of imipramine is contraindicated
because this increases the risk of serotonin syndrome.
• Serotonin-Norepinephrine Reuptake Inhibitors; Venlafaxine (Effexor) and
duloxetine (Cymbalta), SNRIs, have been evaluated as nontraditional therapies for OAB.
• Contraindications, Adverse Events, and Interactions. Duloxetine is metabolized in
the liver by CYP3A4 and CYP2D6 and therefore is subject to pharmacokinetic interactions
with strong inhibitors of these isoenzymes.

17. Genitourinary tract drugs
• Estrogens; Both the vaginal tablet and the vaginal ring are indicated for urinary urgency and
dysuria.
• Mechanism of Action Topical estradiol exerts a local action that improves tone and
elasticity of female urogenital anatomy by increasing secretion of the cervical mucosa,
thickening vaginal mucosa, and proliferation of the endometrium.
• Contraindications Patients with undiagnosed vaginal bleeding, a history of breast
carcinoma or estrogen-dependent tumors,
• Adverse Events Administration of topical estrogens for OAB and incontinence symptoms is
not without risk.
• Antidiuretic Drugs; reduces urine volume and osmolality
• Contraindications and Adverse Events Patients with hyponatremia or a history of
hyponatremia or moderate to severe renal impairment (CrCl<50ml/min) should avoid
demopressin.
• Interactions There are no significant drug interactions associated with DDAVP. Several
medications (lithium, TCAs, SSRIs, nonsteroidal anti-inflammatory drugs, carbamazepine)
may enhance the toxic effects of DDAVP, but none of the risks are particularly likely.

18. Pharmacotherapy for Respiratory Disorders
• Decongestants;
• that stimulate alpha- and beta-adrenergic receptors, causing vasoconstriction in the
respiratory tract mucosa and thereby improving ventilation.
• Topical agents have little systemic absorption. However, topical decongestants should
not be used for more than 3 days because prolonged use can cause rhinitis
medicamentosa (rebound congestion
• E.g oxymetazoline hydrochloride, phenylephrine hydrochloride, pseudoephedrine
(Sudafed, Benylin decongestant).
• Contraindications; Decongestants are contraindicated in patients with narrow
angle glaucoma, hypertension, and severe coronary artery disease
• Adverse Events; Adverse events include increased blood pressure, increased heart
rate, palpitations, headache, dizziness, gastrointestinal (GI) distress, and tremor.
• Interactions; Decongestants interact with appetite suppressants, monoamine
oxidase (MAO) inhibitors (hypertensive crisis), and beta- adrenergic agents
(bradycardia and hypertension).

19. • Expectorants; One of the most important nondrug considerations in treating coughs
• Mechanism of Action; Expectorants, including water, increase the output of
respiratory tract fluid by decreasing the adhesiveness and surface tension of the
respiratory tract and by facilitating removal of viscous mucous
• Adverse Events; Adverse events include drowsiness, headache, and GI symptoms.
• Antitussives they diminish the cough reflex by direct inhibition of the cough center in
the medulla.
• E.g. There are narcotic antitussives( codeine phosphate, and non-narcotic antitussives
(dextromethorphan hydrobromide
• Antitussives are contraindicated in a patient with a productive cough, a history of
substance abuse, or chronic obstructive pulmonary disease.
• Adverse Events; Adverse events include dizziness, nausea, drowsiness, and sedation
• Interactions; Drug–drug interactions occur with concomitant use of amiodarone
(Cordarone), MAO inhibitors, quinidine (Cardioquin, others),