DEPRESSION

DEPRESSION
• Depression (major depressive disorder) is a
common and serious medical illness that
negatively affects how you feel, the way you
think and how you act. Fortunately, it is also
treatable. Depression causes feelings of
sadness and/or a loss of interest in activities
once enjoyed. It can lead to a variety of
emotional and physical problems and can
decrease a person’s ability to function at
work and at home.
 Depression symptoms can vary from
mild to severe and can include:
• Feeling sad or having a depressed mood
• Loss of interest or pleasure in activities once enjoyed
• Changes in appetite — weight loss or gain unrelated to dieting
• Trouble sleeping or sleeping too much
• Loss of energy or increased fatigue
• Increase in purposeless physical activity (e.g., hand-wringing or
pacing) or slowed movements and speech (actions observable by
others)
• Feeling worthless or guilty
• Difficulty thinking, concentrating or making decisions
• Thoughts of death or suicide
NOTE: Symptoms must last at least two weeks for a diagnosis of
depression.
• Depression affects an estimated one in 15
adults (6.7%) in any given year. And one in six
people (16.6%) will experience depression at
some time in their life. Depression can strike
at any time, but on average, first appears
during the late teens to mid-20s. Women are
more likely than men to experience
depression. Some studies show that one-
third of women will experience a major
depressive episode in their lifetime.
 How Is Depression Treated?

• Medication
• Psychotherapy
• Electroconvulsive Therapy (ECT)
 ANTIDEPRESSANT DRUG
(MEDICATION)
TRICYCLIC ANTIDEPRESSANTS
• Amitriptyline
• Imipramine(TOFRANIL)
• Clomipramine(ANAFRANIL) Also desipramine(NORPRAMIN),and
nortriptyline(PAMELOR)
 ANTIDEPRESSANT DRUG
(MEDICATION)
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
• Fluoxetine(PROZAC)
• Fluvoxamine(LUVOX)
• Paroxetine(PAXIL)
• Sertraline(ZOLOFT)Also citalopram(CELEXA), and escitalopram(LEXAPRO)
 ANTIDEPRESSANT DRUG
(MEDICATION)
SEROTONIN AND NOREPINEPHRINE REUPTAKE
INHIBITORS
• Venlafaxine(EFFEXOR)
• Desvenlafaxine(PRISTIQ)
• Duloxetine(CYMBALTA)
 ANTIDEPRESSANT DRUG
(MEDICATION)
MONOAMINE OXIDASE INHIBITORS
• Isocarboxazid(MARPLAN)
• Phenelzine(NARDIL)
• Tranylcypromine(PARNATE)
• Selegiline(ELDEPRYL)
 ANTIDEPRESSANT DRUG
(MEDICATION)
OTHER ANTIDEPRESSANT DRUGS
• Blupropion (WELLBUTRIN)
• Mortazapine(REMERON)
• Trazodone
• Vilazodone(VIIBRYD)
INDICATIONS:
• Antidepressants have been used to treat all
forms of depression and treat several other
conditions. The antidepressant are also
effective in the treatment of certain anxiety
disorders, such as panic disorder, phobic
disorders and obsessive-compulsive
disorder.
INDICATIONS:
• Antidepressants repress excessive eye
movement(REM), sleep and dreaming which
are conditions that contribute to
somnambulism and night terrors.
• In patients with enuresis, antidepressants
appear to increase the awareness of the
need to urinate and thereby facilitate
waking up for this purpose.
INDICATIONS:
• Other antidepressants also have a role in the
treatment of chronic pain syndromes
because of their mood elevating effect and
their analgesic activity.
 TRICYCLIC ANTIDEPRESSANTS
• The TCAs include amitriptyline,clomipramine,
desipramine, imipramine and nortriptyline.
- these agents are highly effective but are
also associated with a high incidence of
adverse effects. They can cause severe toxicity
when taken excessive doses.
 MECHANISM OF ACTION
• The TCAs block the neuronal reuptake of
norepinephrine and serotonin.
• The blockade occurs as soon as a drug
administration begins and causes immediate
increase in synaptic concentrations of
serotonin and norepinephrine.
ADVERSE EFFECT
• As with many of the antipsychotic drugs, the
TCA produce autonomic side effects by
blocking the muscarinic and alpha-1
adrenoreceptors.
• Some of the TCAs also produced marked
sedation. It is often administered at bedtime
when there sedative effects can have the added
benefits of promoting sleep.
• It also lowers the seizure threshold and can
induce seizures at therapeutic as well as toxic
serum concentration.
 SELECTIVE SEROTONIN
REUPTAKE INHIBITORS
MECHANISM OF ACTION:
- The SSRIs selectively block the neuronal
reuptake of serotonin and have much less
effect on the reuptake of norepinephrine.
- Their efficacy in the treatment of
depression support the hypothesis that
serotonin dysfunction plays a significant
role in the pathophysiology of depression.
ADVERSE EFFECTS
• The SSRIs are usually administered in the
morning, because they tend to increase
alertness in the patients.
• Their most common adverse effects are
nervousness, dizziness and insomnia.
• They occasionally cause male sexual
dysfunction in the forms of priapism and
impotence.
NOTE: The SSRIs should be used with caution in
patients with seizure disorders, hepatic
disorders, diabetes or bipolar disorder.
SPECIFIC DRUGS
• Fluoxetine(PROZAC)
-is one of the most popular drugs for
treatment of depression, and the first drug
approved for treatment of bulimia nervosa,
management of anorexia nervosa and OCD.
-it causes more drug interaction than do
other SSRIs. It can impair the regulation of blood
glucose levels in diabetic patients. It can also
cause a syndrome of inappropriate antidiuretic
hormone secretion, characterize by persistent
hypotremia and elevated urine osmolality.
 SPECIFIC DRUGS

• Fluvoxamine
-is approvedfor the treatment of OCD but
has also been used to treat depression and
panic disorder.
-has a half-life of abot 15 hours can
associated with sedative effects.
SPECIFIC DRUGS
• Paroxetine and Sertraline
-have a half-lives of 21 and 26 hours
respectively. Sertraline may be preferred in
elderly patients because its elimination is
not affected substantially by aging.
- Paroxetine is somewhat more sedating
than either fluoxetine or sertraline.
MECHANISM OF ACTION:
• The MAOIs bind irreversibly to an enzyme,
monoamine oxidase (MAO), responsible for
the degradation of the biogenic amine
neurotransmitters, norepinephrine,
dopamine, and serotonin.
• The binding of MAOI prevents the substrate
from reaching the active site on the enzyme.
MECHANISM OF ACTION:
• 2 MAIN TYPES OF MAO:
MAO-A oxidizes serotonin but will also metabolize
norepinephrine and dopamine.
MAO-B metabolizes dopamine
PHARMACOLOGIC EFFECTS:
• MAOIs increase the concentration of
dopamine, norepinephrine, and serotonin in
storage sites throughout the nervous
system.
ADVERSE EFFECTS:
• The occurrence of hypertensive crisis, which
is sometimes fatal.
» SYMPTOMS:
- occipital headache that may radiate frontally
- palpitations
- neck stiffness or soreness
- nausea or vomiting
- sweating
- photophobia
SPECIFIC DRUGS
• First generation MAOIs for treating
depression includes: (irreversible inhibitors
of both MOA-A and MOA-B.)
• isocarboxazid
• phenelzine
• tranylcypromine
SPECIFIC DRUGS
• Second-generation of MAOIs include:
• moclobemide- are reversible inhibitors of MAO-A
(RIMAs). RIMAS are used in many countries to treat
depression but are not yet available in the United
States
• Third-generation of MAOIs include:
• Selegiline- selectively inhibits MAO-B and is also used
in the treatment of Parkinson disease. It was recently
approved for the treatment of depression in a
transdermal patch formulation called EMSAM.
 OTHER ANTIDEPRESSANT
DRUGS
• Bupropion – produces few anticholinergic side
effects, causes very little sedation, and rarely
produces cardiovascular effects or sexual
dysfunction. It can cause agitation, insomnia,
nausea and weight loss.
• Mirtazapine – has both antidepressant and anti-
anxiety effects. It is better tolerated and causes
fewer adverse reactions than do the TCAs. It
can significantly elevate hepatic enzyme levels,
however, and it has been associated with a few
cases of agranulocytosis.
 OTHER ANTIDEPRESSANT
DRUGS
• Trazadone – it causes considerable sedation and
orthostatic hypotention, but it does not produce
anticholinergic side effects and has minimal effects
on cardiac conduction.
• Vilazodone – newest antidepressant
• Hypericin – extracts of the St. John’s wort
(Hypericum perforatum) exhibit antidepressant
activity and products containing these extracts are
available in health food stores. Its extracts appear to
cause fewer adverse effects than other
antidepressants but are not as effective as
prescription antidepressants.
 MONOAMINE OXIDASE
IHIBITORS
• Because the MAOIs have many potentially
serious interactions with other drugs and
with food, they are not considered drugs of
choice in the treatment of depression. They
are generally used as alternatively therapy
when patients have failed to respond
adequately to other drugs.
ANTIMICROBIAL DRUGS
BACTERICIDAL & BACTERIOSTATIC
ANTIBIOTICS

Bactericidal antibiotics works by

killing the bacteria.

Bacteriostatic antibiotics works by

stopping bacteria multiplying.
 MAIN CLASSES OF ANTIBIOTICS

• Beta – Lactams
– Penicillins
– Cephalosphorins
• Macrolides
• Fluoroquinolones
• Tetracyclines
• Aminoglycosides
MECHANISMS OF ACTION OF
ANTIMICROBIAL DRUGS
Mechanism of action
include:
• Inhibition of Cell Wall Synthesis
• Inhibition of Protein Synthesis
• Inhibition of Nucleic Acid Synthesis
• Inhibition of Metabolic Pathways
• Interference with Cell Membrane
Integrity
 Inhibition of Cell wall
synthesis:
• Bacteria cell wall unique in construction
Contains peptidoglycan

• Antimicrobials that interfere with the

synthesis of cell wall do not interfere with
eukaryotic cell
Due to lack of cell wall in animal cells and
differences in cell wall in plant cells

• These drugs have very high therapeutic index

Low toxicity with high effectiveness
Antimicrobials of this class
includes…

– Penicillins
– Cephalosporins
– Bacitracin
– Vancomycin
 Penicillin and
Cephalosporins

• Part of group of drugs called β –

lactams
• Competitively inhibits function of
penicillin-binding proteins
• Considered bactericidal

Penicillin are more effective against Gram+

bacteria. This is because Gram+ bacteria have
penicillin binding proteins on their walls.
 Cephalosporins
• Chemical structures make them
resistant to inactivation by certain β-
lactamases
• Tend to have low affinity to penicillin-
binding proteins of Gram+ bacteria,
therefore are most effective against
Gram- bacteria.
• Chemically modified to produce family
of related compounds
 Vancomycin
• Inhibits formation of glycan chains
• Important in treating infections caused
by penicillin resistant Gram +
organisms
• Must be given intravenously due to
poor absorption from intestinal tract
• Acquired resistance most often due to
alterations in side chain of NAM
molecule
 Bacitracin
• Interferes with transport of
peptidoglycan precursors across
cytoplasmic membrane
• Toxicity limits use to topical
application
• Common ingredient in non-prescription
first-aid ointments
 Inhibition of Protein
Synthesis:

Structure of prokaryotic ribosome

acts as target for many antimicrobials
of this class
– Differences in prokaryotic and
eukaryotic ribosomes responsible for
selective toxicity
Antimicrobials of this class
includes…
– Aminoglycosides
– Tetracyclins
– Macrolids
– Chloramphenicol
 Aminoglycosides
• Irreversibly binds to 30S ribosomal
subunit
• Not effective against anaerobes,
enterococci and streptococci
• Often used in synergistic
• Examples of aminoglycosides include
– Gentamycin, Streptomycin and Tobramycin
• Side effects with extended use include
-Otto toxicity
-Nephrotoxicity
 Tetracyclines
• Reversibly binds 30S ribosomal subunit
• Effective against certain Gram + and
Gram –
• Newer tetracyclines such as doxycycline
have longer half-life
• Resistance due to decreased
accumulation by bacterial cells
• Can cause discoloration of teeth if taken
as young child
 Macrolids
• Reversibly binds to 50S ribosome
• Effective against variety of Gram +
organisms and those responsible for
atypical pneumonia
• Often drug of choice for patients allergic
to penicillin
• Resistance can occur via modification of
RNA target
• Macrolids include
– Erythromycin, Clarithromycin and Azithromycin
 Chloramphenicol
• Binds to 50S ribosomal subunit
• Effective against a wide variety of
organisms
• Generally used as drug of last resort for
life-threatening infections
• Rare but lethal side effect is aplastic
anemia
 Inhibition of Nucleic Acid
Synthesis

These includes
• Fluoroquinolones
• Rifamycins
 Fluoroquinolones
• Inhibit action of topoisomerase DNA
gyrase
• Effective against Gram + and Gram –
• Resistance due to alteration of DNA
gyrase
• Examples include
– Ciprofloxacin and ofloxacin
 Rifamycins
• Block prokaryotic RNA polymerase
• Rifampin most widely used rifamycins
• Effective against many Gram + and some
Gram - as well as members of genus
Mycobacterium
• Primarily used to treat tuberculosis and
Hansen’s disease as well as preventing
meningitis after exposure to N.
meningitidis
• Resistance due to mutation coding RNA
polymerase
 Inhibition of Metabolic
Pathways
• Relatively few
• Most useful are folate inhibitors
– Mode of actions to inhibit the production of folic
acid

Antimicrobials of this class includes…

- Sulfonamides
- Trimethoprim
 Sulfonamides
• Group of related compounds
• Inhibit growth of Gram + and Gram –
organisms
• Structurally similar to para-aminobenzoic
acid
• Human cells lack specific enzyme in folic
acid pathway
• Resistance due to plasmid
 Trimethoprim
• Inhibits folic acid production
• Often used synergistically with
sulfonamide
• Most common mechanism of resistance is
plasmid encoded alternative enzyme
– Genes encoding resistant to sulfonamide and
trimethoprim are often carried on same plasmid
 Interference with cell
membrane integrity
• Binds membrane of Gram – cells
– Alters permeability
– Also bind eukaryotic cells but to lesser extent
• Few damage cell membrane
– Polymyxin B most common
– Common ingredient in first-aid skin ointments
 MICROBIAL
RESISTANCE
 ANTIBIOTICS RESISTANCE
• NATURAL RESISTANCE – Bacteria
may be inherently resistant to an antibiotic
• ACQUIRED RESISTANCE – Bacteria
can develop resistance to antibiotics due to :
– Mutations
– Mobile genetic elements (e.g.,
plasmids or transporons carrying antibiotic
resistance genes)
 PROCESSES OF
ANTIMICROBIAL RESISTANCE
1. Drug inactivation (enzyme
inactivation)
2. Cellular access (decreased
permeability)
3. Site modification (altered target
site)
4. Biochemical feedback (by pass)
WHEN TO USE
ANTIBIOTICS?
Antibiotics are specific for the
type of bacteria being treated
and, in general, cannot be
interchanged from one infection
to another. When antibiotics are
used correctly, they are usually
safe with few side effects.
WHEN NOT TO USE
ANTIBIOTICS?
Antibiotics are not the correct choice
for all infections. For example, more
sore throats, cough and colds, flu or
acute sinusitis are viral in origin and
do not need an antibiotic. These viral
infections are “self-limiting”. Using
antibiotics for viral infections can
increase the risk for antibiotic
resistance, lower the options for future
treatments if an antibiotic is needed,
and put the patient at risk for side
effects and extra cost due to
unnecessary drug treatment.
 ANTIMICROBIAL
SUSCEPTIBILITY
TESTING

• Probably the most widely used testing method is the

disk-diffusion method, also known as the Kirby-Bauer
test.
 Conventional disc
diffusion method
• Kirby-Bauer disc diffusion routinely used
to qualitatively determine susceptibility
• Standard concentration of strain
uniformly spread of standard media
• Discs impregnated with specific
concentration of antibiotic placed on
plate and incubated
• Clear zone of inhibition around disc
reflects susceptibility
– Based on size of zone organism can be described as
susceptible or resistant
 EFFECTS OF
COMBINATION OF
DRUGS
• Sometimes the chemotherapeutic effects
of two drugs given simultaneously is
greater than the effect of either given
alone.
• This is called synergism. For examples,
penicillin and streptomycin in the
treatment of bacterial endocarditis.
Damage to bacterial cell walls by
penicillin makes it easier for streptomycin
to enter
• Other combinations of drugs can be
antagonistic
• For example, the simultaneous use of
penicillin and tetracycline is often less
effective than when wither drugs is used
alone. By stopping the growth of the
bacteria, the bacteriostatic drug
tetracycline interferes with the action of
penicillin, which requires bacterial
growth.
 Combinations of antimicrobial
drugs should be used only for:
1. To prevent or minimize the emergence of
resistant strains.
2. To take advantage of the synergistic
effect.
3. To lessen the toxicity of individual drugs.
ANTIHYPERTENSIVE DRUGS

HYPERTENSION
 Hypertension
• Normal blood pressure is 120 over 80 mm of
mercury (mmHg), but hypertension is higher
than 130 over 80 mmHg.
• Acute causes of high blood pressure
include stress, but it can happen on its own, or it
can result from an underlying condition, such as
kidney disease.
• Unmanaged hypertension can lead to a heart
attack, stroke, and other problems.
• Lifestyle factors are the best way to address high
blood pressure.
 Symptoms
• Severe headache.
• Fatigue or confusion.
• Vision problems.
• Chest pain.
• Difficulty breathing.
• Irregular heartbeat.
• Blood in the urine.
• Pounding in your chest, neck, or ears.
 Treatment
• Regular physical exercise
• Stress reduction
• Medication
 Antihypertensive
• are a class of drugs that are used to
treat hypertension (high blood pressure).Antihypertensive
therapy seeks to prevent the complications of high blood
pressure, such as stroke and myocardial infarction.
Evidence suggests that reduction of the blood pressure by
5 mmHg can decrease the risk of stroke by 34%,
of ischaemic heart disease by 21%, and reduce the
likelihood of dementia, heart failure,
and mortality from cardiovascular disease.There are many
classes of antihypertensives, which lower blood pressure
by different means. Among the most important and most
widely used drugs are thiazide diuretics, calcium channel
blockers, ACE inhibitors, angiotensin II receptor
antagonists (ARBs), and beta blockers.
 Diuretics

• Diuretics help the kidneys eliminate

excess salt and water from the body's
tissues and blood.
• Loop diuretics:
– bumetanide
– ethacrynic acid
– furosemide
– Torsemide
Thiazide diuretics:
– epitizide
– hydrochlorothiazide and chlorothiazide
– bendroflumethiazide
– methyclothiazide
– polythiazide
• Thiazide-like diuretics:
– indapamide
– chlorthalidone
– metolazone
• Potassium-sparing diuretics:
– amiloride
– triamterene
– spironolactone
– eplerenone
 Mechanism of action
• Diuretics are tools of considerable therapeutic
importance. First, they effectively reduce blood
pressure. Loop and thiazide diuretics are secreted
from the proximal tubule via the organic anion
transporter-1 and exert their diuretic action by
binding to the Na(+)-K(+)-2Cl(-) co-transporter
type 2 in the thick ascending limb and the Na(+)-
Cl(-) co-transporter in the distal convoluted
tubule, respectively.[ Classification of common
diuretics and their mechanisms of action.
 Examples Mechanism Location (numbered in distance along nephron)

– ethanol, water Inhibits vasopressin secretion

Acidifying salts CaCl2, NH4Cl 1.

Arginine vasopressin
amphotericin B, lithium citrate Inhibits vasopressin's action 5. collecting duct
receptor 2 antagonists

Competitive vasopressin antagonism leads to decreased number of aquaporin channels

in the apical membrane of the renal collecting ducts in kidneys, causing decreased
Selective vasopressin V2 antagonist (sometimes called aquaretics) Tolvaptan[12]Conivaptan, water reabsorption. This causes an increase in renal free water excretion (aquaresis), 5. collecting duct
an increase in serum sodium concentration, a decrease in urine osmolality, and an
increase in urine output. [13]

Na-H exchanger antagonists dopamine[14] Promotes Na+ excretion 2. proximal tubule[14]

Carbonic anhydrase inhibitors acetazolamide,[14]dorzolamide Inhibits H+ secretion, resultant promotion of Na+and K+ excretion 2: proximal tubule

Loop diuretics bumetanide,[14]ethacrynic acid,[14]furosemide,[14]torsemide Inhibits the Na-K-2Cl symporter 3. medullary thick ascending limb

Osmotic diuretics glucose (especially in uncontrolled diabetes), mannitol Promotes osmotic diuresis 2. proximal tubule, descending limb

Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride

Potassium-sparing diuretics amiloride, spironolactone, eplerenone, triamterene, potassium canrenoate. 5. cortical collecting ducts
inhibits epithelial sodium channels[14]

Thiazides bendroflumethiazide, hydrochlorothiazide Inhibits reabsorption by Na+/Cl− symporter 4. distal convoluted tubules

Xanthines caffeine, theophylline, theobromine Inhibits reabsorption of Na+, increase glomerular filtration rate 1. tubules
 Adverse effect
• The main adverse effects of diuretics
are hypovolemia, hypokalemia, hyperkalemia
, hyponatremia, metabolic
alkalosis, metabolic acidosis,
and hyperuricemia.
 Calcium channel blockers
• Calcium channel blockers block the entry of
calcium into muscle cells in artery walls.
• Dihydropyridines:
– amlodipine
– cilnidipine
– clevidipine
– felodipine
– isradipine
• non-dihydropyridines:
– diltiazem
– lercanidipine
– levamlodipine
– nicardipine
– nifedipine
– nimodipine
– nisoldipine
– nitrendipine
• non-dihydropyridines:
– diltiazem
– verapamil
 Mechanism of action
• In the body's tissues, the concentration of
calcium ions (Ca2+
) outside of cells is normally about 10000-fold
higher than the concentration inside of cells.
Embedded in the membrane of some cells
are calcium channels. When these cells receive a
certain signal, the channels open, letting calcium
rush into the cell. The resulting increase in
intracellular calcium has different effects in
different types of cells. Calcium channel blockers
prevent or reduce the opening of these channels
and thereby reduce these effects.
 Side effect
• Constipation
• Dizziness, headache, redness in the face
• Fluid buildup in the legs and ankle edema
• Gingival overgrowth
• Rapid heart rate
• Slow heart rate
 ACE inhibitors
• ACE inhibitors inhibit the activity of angiotensin-converting enzyme (ACE), an enzyme responsible for the
conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.
• captopril
• enalapril
• fosinopril
• lisinopril
• moexipril
• perindopril
• quinapril
• ramipril
• trandolapril
• benazepril
 Mechanism of action
• ACE inhibitors reduce the activity of the renin-
angiotensin-aldosterone system (RAAS) as the
primary etiologic (causal) event in the
development of hypertension in people with
diabetes mellitus, as part of the insulin-
resistance syndrome or as a manifestation of
renal disease.
 Adverse effects
• Common adverse drug reactions include:
hypotension, cough, hyperkalemia, headache, dizziness, fatigue, nause
a, and renalimpairment. ACE inhibitors might increase inflammation-
related pain, perhaps mediated by the buildup of bradykinin that
accompanies ACE inhibition
 Adverse hematologic effects

• Hematologic effects, such as

neutropenia, agranulocytosis and other
blood dyscrasias, have occurred during
therapy with ACE inhibitors, especially
in patients with additional risk factors
(see Warnings). Patients should be
advised to report symptoms such as
sore throat or fever to their physician
Angiotensin II receptor antagonists

• Angiotensin II receptor antagonists work

by antagonizing the activation of angiotensin receptors.
• azilsartan
• candesartan
• eprosartan
• irbesartan
• losartan
• olmesartan
• telmisartan
• valsartan
• Fimasartan
 Mechanism of action

• These substances are AT1-receptor antagonists; that is, they block the activation
of angiotensin II AT1 receptors. Blockage of AT1 receptors directly causes vasodilation,
reduces secretion of vasopressin, and reduces production and secretion
of aldosterone, among other actions. The combined effect reduces blood pressure.
• The specific efficacy of each ARB within this class depends upon a combination of
three pharmacodynamic and pharmacokinetic parameters. Efficacy requires three key
PD/PK areas at an effective level; the parameters of the three characteristics will need
to be compiled into a table similar to one below, eliminating duplications and arriving
at consensus values; the latter are at variance now.
 Biological half- Protein binding Bioavailability Renal/hepatic cle Daily dosage
Drug Trade Name Food effect
life [h] [%] [%] arance [%] [mg]

Losartan Cozaar 6-9 h 98.7% 33% 10%/90% Minimal 50–100 mg

EXP 3174 6–9 h 99.8% – 50%/50% – –

Candesartan Atacand 9h >99% 15% 60%/40% No 4–32 mg

Valsartan Diovan 6h 95% 25% 30%/70% No 80–320 mg

Irbesartan Avapro 11–15 h 90–95% 70% 20%/80% No 150–300 mg

Telmisartan Micardis 24 h >99% 42–58% 1%/99% No 40–80 mg

Eprosartan Teveten 5h 98% 13% 30%/70% No 400–800 mg

Olmesartan Benicar/Olmetec 14–16 h >99% 29% 40%/60% No 10–40 mg

Azilsartan Edarbi 11 h >99% 60% 55%/42% No 40–80 mg

Fimasartan Kanarb 7-11 h >97% 30-40% - - 30–120 mg

 Adverse effects
• This class of drugs is usually well tolerated.
Common adverse drug reactions (ADRs) include: dizziness,
headache, and/or hyperkalemia. Infrequent ADRs
associated with therapy include: first dose orthostatic
hypotension, rash, diarrhea, dyspepsia, abnormal liver
function, muscle cramp, myalgia, back pain, insomnia,
decreased hemoglobin levels, renal
impairment, pharyngitis, and/or nasal congestion.
• While one of the main rationales for the use of this class is
the avoidance of dry cough and/or angioedema associated
with ACE inhibitor therapy, rarely they may still occur. In
addition, there is also a small risk of cross-reactivity in
patients having experienced angioedema with ACE
inhibitor therapy.
 Adrenergic receptor antagonists
• Beta blockers
– atenolol
– bisoprolol
– betaxolol
– carteolol
– carvedilol
– labetalol
– metoprolol
– nadolol
– nebivolol
– oxprenolol
– penbutolol
– pindolol
– propranolol
– timolol
• Blockers:
– doxazosin
– phentolamine
– indoramin
– phenoxybenzamine
– prazosin
– terazosin
– tolazoline
• Mixed Alpha + Beta blockers:
– bucindolol
– carvedilol
– labetalol
 Beta blocker
• Beta blockers, also written β-blockers, are a
class of medications that are particularly used
to manage abnormal heart rhythms, and to
protect the heart from a second heart attack
(myocardial infarction) after a first heart
attack (secondary prevention). They are also
widely used to treat high blood pressure
(hypertension), although they are no longer
the first choice for initial treatment of most
patient
 Adverse effects
• Adverse drug reactions associated with the use of beta blockers
include: nausea, diarrhea, bronchospasm, dyspnea, cold
extremities, exacerbation of Raynaud's
syndrome, bradycardia, hypotension, heart failure, heart
block, fatigue, dizziness, alopecia (hair loss), abnormal
vision, hallucinations, insomnia, nightmares, sexual
dysfunction, erectile dysfunction and/or alteration
of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is
also commonly associated with orthostatic
hypotension. Carvedilol therapy is commonly associated
with edema.[31] Due to the high penetration across the blood–brain
barrier, lipophilic beta blockers, such
as propranolol and metoprolol, are more likely than other less
lipophilic beta blockers to cause sleep disturbances, such as
insomnia, vivid dreams and nightmares
 Alpha blocker
• alpha blockers have significantly poorer
endpoint outcomes than other
antihypertensives, and are no longer
recommended as a first-line choice in the
treatment of hypertension. However, they
may be useful for some men with symptoms
of prostate disease.
 Adverse Effects
• Although alpha blockers have the ability to
reduce some disease pathology, there are some
side effects that come with these alpha
blockers.] However, because there are several
structural compositions that make each alpha
blocker different, the side effects are different for
each drug. Side effects that arise when taking
alpha blockers can include the First Dose Effect,
cardiovascular side effects, genitourinary side
effects, as well as other side effects.
 Vasodilators
• Vasodilation refers to the widening of blood vessels. It results from
relaxation of smooth muscle cells within the vessel walls, in particular in
the large veins (called venodilators), large arteries, and smaller arterioles.
The process is the opposite of vasoconstriction, which is the narrowing of
blood vessels.
• When blood vessels dilate, the flow of blood is increased due to a
decrease in vascular resistance. Therefore, dilation of arterial blood
vessels (mainly the arterioles) decreases blood pressure. The response
may be intrinsic (due to local processes in the surrounding tissue) or
extrinsic (due to hormones or the nervous system). In addition, the
response may be localized to a specific organ (depending on
the metabolic needs of a particular tissue, as during strenuous exercise),
or it may be systemic (seen throughout the entire systemic circulation).
• Endogenous substances and drugs that cause vasodilation are
termed vasodilators. Such vasoactivity is necessary for homeostasis
(keeping the body running normally).
 Class Description Example

Changes in the resting membrane

Hyperpolarization-mediated (Calcium
channel blocker)
potential of the cell affects the level of
intracellular calcium through
adenosine
modulation of voltage-sensitive
calcium channels in the plasma
membrane.

Adrenergic stimulation results in

elevated levels of cAMP and protein
cAMP-mediated Prostacyclin
kinase A, which results in increasing
calcium removal from the cytoplasm.

Through stimulation of protein kinase

cGMP-mediated (Nitrovasodilator) nitric oxide
G.
 Renin Inhibitors
• Renin comes one level higher than
angiotensin converting enzyme (ACE) in
the renin-angiotensin system. Inhibitors of
renin can therefore effectively reduce
hyptertension. Aliskiren (developed by
Novartis) is a renin inhibitor which has been
approved by the U.S. FDA for the treatment of
hypertension
 Mechanism of action
• Renin inhibitors bind to the active site of renin and inhibit the binding of renin to
angiotensinogen, which is the rate-determining step of the RAAS
cascade. Consequently, renin inhibitors prevent the formation of Ang I and Ang II.
Renin inhibitors may also prevent Ang-(1-7), Ang-(1-9) and Ang-(1-5)
formation, although it is not known if this is clinically important. Renin is highly
selective for its only naturally occurring substrate which is angiotensinogen, and the
incidence of unwanted side effects with a renin inhibitor is infrequent. and similar
to angiotensin II receptor antagonists. Ang II also functions within the RAAS as a
negative feedback to suppress further release of renin. A reduction in Ang II levels or
blockade of angiotensin receptors will suppress the feedback loop and lead to
increased plasma renin concentrations (PRC) and plasma renin activity (PRA). This
can be problematic for ACE inhibitor and angiotensin II receptor antagonist therapy
since increased PRA could partially overcome the pharmacologic inhibition of the
RAAS cascade. Because renin inhibitors directly affect renin activity, decrease of PRA
despite the increased PRC (from loss of the negative feedback) may be clinically
advantageous.
 Adverse effects
• were fatigue, headache, dizziness and
diarrhea
Aldosterone receptor antagonists
• Aldosterone receptor antagonists are not
recommended as first-line agents for blood
pressure, but spironolactone and eplerenone
are both used in the treatment of heart
failure and resistant hypertension.

• Aldosterone receptor antagonists:

• eplerenone
• spironolactone
 Mechanism of action
• Aldosterone antagonists are, as the name
suggests, receptor antagonists at the mineralocorticoid
receptor. Antagonism of these receptors
inhibits sodium resorption in the collecting duct of
the nephron in the kidneys. This interferes with
sodium/potassium exchange, reducing urinary
potassium excretion and weakly increasing water
excretion (diuresis).
• In congestive heart failure, they are used in addition to
other drugs for additive diuretic effect, which
reduces edema and the cardiac workload.
 Adverse side effects
• Eplerenone. Eplerenone is a
selective aldosterone receptor
antagonist derived from spironolactone but
with limited affinity for the progesterone and
androgenreceptors and, therefore, a lack of
sex-related adverse side effects
Alpha-2 adrenergic receptor agonists
• Central alpha agonists lower blood pressure by
stimulating alpha-receptors in the brain which
open peripheral arteries easing blood flow.
These alpha 2 receptors are known
as autoreceptors which provide a negative
feedback in neurotransmission (in this case, the
vasoconstriction effects of adrenaline). Central
alpha agonists, such as clonidine, are usually
prescribed when all other anti-hypertensive
medications have failed. For treating
hypertension, these drugs are usually
administered in combination with a diuretic.
 Examples
• clonidine
• guanabenz
• guanfacine
• methyldopa
• moxonidine
 Adverse effects
• sedation, drying of the nasal mucosa and
rebound hypertension.
 Indirect anti-adrenergics
• guanethidine - replaces norepinephrine in
vesicles, decreasing its tonic release
• mecamylamine - antinicotinic and ganglion
blocker
• reserpine- indirect via
irreversible VMAT inhibition
 Endothelin receptor blockers
• Bosentan belongs to a new class of drug and
works by blocking the receptors of
the hormone endothelin. It is specifically
indicated only for the treatment of pulmonary
artery hypertension in patients with moderate
to severe heart failure.
 Therapeutic Indications
• Because of its powerful vasoconstrictor
properties, and its effects on intracellular
calcium, ET-1 has been implicated in the
pathogenesis of hypertension, coronary
vasospasm, and heart failure. A number of
studies suggest a role for ET-1 in pulmonary
hypertension, as well as in systemic hypertension.
ET-1 has been shown to be released by the failing
myocardium where it can contribute to cardiac
calcium overload and hypertrophy.
Side Effects and Contraindications
• Some of endothelin antagonist side effects are
common to most vasodilators; namely,
headache, cutaneous flushing, and edema
formation. This class of drug may cause birth
defects and therefore is contraindicated in
pregnancy. These drugs can also can cause
liver injury.
 REFERENCE:
• http://www.cvpharmacology.com
• https://www.ncbi.nlm.nih.gov
• https://www.nps.org.au/australian-prescriber
• https://en.wikipedia.org
• https://emedicine.medscape.com
• https://www.medicalnewstoday.com
 DRUGS FOR
GASTROINTESTINAL
TRACT DISORDERS
 Peptic ulcer
 Characterized by epigastric pain, loss of appetite and weight
loss caused by inflammed excavations (ulcers) of the mucosa
and underlying tissue of the upper gastrointestinal tract
 The ulcer results from damage to the mucous membrane that
normally protects the esophagus, stomach and duodenum
from gastric acid and pepsin
 Helicobacter pylori infection
 Drugs that Reduce Gastric Acidity

 Gastrin, acetylcholine and histamine

 The level of gastric acidity can be reduced
either by neutralizing gastric acid with
antacids or by inhibiting gastric acid
secretion with histamine H₂ receptor
antagonist or a proton pump inhibitor
(PPI)
 • Histamine H ₂ Receptor Antagonist
- Includes cimetidine, famotidine,
DURATION OF
DRUGS CLASS ADVANTAGES DISADVANTAGES
ranitidine, and nizatidine
Antimicrobial agents
ACTION
Heal Helicobacter pylori infection and
Microbial resistance increasing (e.g.,
Varies peptic ulcer when used with acid
clarithomycin resistance)
secretion inhibitor
Cytoprotective drugs Limited utility for H. pylori – induced
Few adverse effects; useful when other
(sucralfate)* 6-12 hr ulcers; can impair absorption of ther
drugs not tolerated
drugs
Gastric antacids 3-4 hr Few adverse effects; rapid acting Only used for symptomatic relief

Histamine H ₂
12 hr Few adverse effects; well tolerated Not as effective as PPIs
receptor antagonist
Proton pump
24-48 hr Most efficacious acid inhibitors More adverse effects than other drugs
inhibitors (PPIs)*
• Proton Pump Inhibitors
- Includes esomeprazole, omeprazole,
pantroprazole, and rabeprazole
- Administred orally
• Gastric Antacids
- Chemically neutralizes stomach acids
- Acid indigestion and dyspepsia
 Cytoprotective Drugs
• Sucralfate
- Viscous polymer of sucrose octasulfate and
aluminum
- Stimulates prostaglandin synthesis in mucosal
cells
- Administered orally
• Misoprostol
- A prostaglandin E₁ analogue
Drugs for inflammatory bowel
diseases
• Glucocorticoids
- Ulcerative colitis and Crohn Diseases
• Aminosalicylates
• Infliximab
Gastrointestinal Motility Disorders
• Constipation
• Diarrhea
• GERD
• Gastroparesis
• Irritable Bowel Syndrome (IBS)
 Drugs for Constipation
• Metoclopramide
• Antipasmodic Agents
– Muscarinic Receptor Antagonists
• Laxatives
– Bulk Performing Laxatives
– Surfactant Laxatives
– Osmotic Laxatives
– Stimulant (Secretory) Laxatives
• Lubiprostone and Tegaserode
 Antidiarrheal Agents
• Opoid Drugs
• Locally Acting Drugs
• Alosetron
 Antiemetics
• Serotonin 5-HT₃ Receptor Antagonists
– Ondansetron
• Dopamine D₂ Receptor Antagonist
• Neurokinin-1 Receptor Antagonists
– Aprepitant