Frietzyl Mae S.

Generalao BS – Pharmacy 2A

KINDLY ANSWER THE FOLLOWING:

1.What is cardiovascular system?

Cardiovascular system, sometimes called blood-vascular or circulatory system. This system in

human body consist of heart, which is a pumping device and different kind of vessel such as arteries,
veins and capillaries. This system contained blood that is pumped by the heart around a closed circuit of
vessel.

2.What are the drugs affecting the cardiovascular system (renal drugs)?
(Subclass, MOA, effects)

A. Pharmacologic management of chronic heart failure

Subclass Mechanism of Action Effect

Diuretics

• Furosemide • Loop diuretic: Decreases • Increase excretion of

NaCl and KCl reabsorption
in thick ascending limb of
the loop of Henle in the
nephron
• Decreases NaCl
• Hydrochlorothiazide reabsorption in the distal
convoluted tubule
salt and water
• Reduces cardiac preload
and afterload
• Reduces pulmonary and
peripheral edema
• Same effect with the
Furosemide but less
efficacious

Aldosterone receptor
antagonist

• Spironolactone • Blocks cytoplasmic • Increased salt and water

aldosterone receptors in
collecting tubules of
nephron
• possible membrane effect
Angiotensin Antagonist
excretion
• Reduces remodeling
• Reduces mortality

Angiotensin-Converting
Enzyme (ACE) Inhibitors:
• Captopril
• Inhibits ACE • Arteriolar and venous
• reduces AII formation by dilation
inhibiting conversion of AI • reduces aldosterone
to All secretion

Angiotensin Receptor
Blockers (ARBs):
• Losartan • Antagonize AII effects at
AT1 receptors
Beta Blockers
• Carvedilol • Competitively blocks β1
receptors
Cardiac glycosides
• Digoxin • Na+ /K+ -ATPase inhibition
results in reduced Ca2+
expulsion and increased
Ca2+ stored in sarcoplasmic
reticulum
B. Antiarrhythmic drugs
Subclass Mechanism of Action
Class A1
• Procainamide • INa (primary) and IKr
(secondary) blockade
• reduces cardiac
remodeling
• Arteriolar and venous
dilation
• reduces aldosterone
secretion
• reduces cardiac
remodeling
• Slows heart rate
• Reduces blood pressure
• Poorly understood
effects
• Reduces heart failure
mortality
• Increases cardiac
contractility
• cardiac
parasympathomimetic
effect (slowed sinus
heart rate, slowed
atrioventricular
conduction)
Effect
• Slows conduction
velocity and pacemaker
rate
• Prolongs action
potential duration and
dissociates from INa
channel with
intermediate kinetics
• Direct depressant
effects on sinoatrial (SA)
 and atrioventricular (AV)
nodes
Class 1B

• Lidocaine • Sodium channel (INa) • Blocks activated and

blockade inactivated channels
with fast kinetics
• Does not prolong and
may shorten action
potential
Class 1C

• Flecainide • Sodium channel (INa) • Dissociates from

blockade channel with slow
kinetics
• No change in action
potential duration
Class 2

• Propranolol • β-Adrenoceptor blockade • Direct membrane

effects (sodium channel
block) and prolongation
of action potential
duration
• Slows SA node
automaticity and AV
nodal conduction
velocity
Class 3

• Amiodarone • Blocks IKr, INa, ICa-L channels, • Prolongs action

β adrenoceptors potential duration and
QT interval
• Slows heart rate and AV
node conduction
• Low incidence of
torsades de pointes
• Dofetilide • IKr block • Prolongs action
potential, effective
refractory period

Class 4

• Verapamil • Calcium channel (ICa-L type) • Slows SA node

blockade automaticity and AV
 nodal conduction
velocity
• Decreases cardiac
contractility
• Reduces blood pressure
Miscellaneous

• Adenosine • Activates inward rectifier Ik • Very brief, usually

• blocks ICa complete AV blockade

• Magnesium • interacts with Na+ / K+ - • Normalizes or increases

ATPase, K+ , and Ca2+ plasma Mg2+
channels
• Potassium • Increases K+ perme ability, • Slows ectopic
K+ currents pacemakers
• Slows conduction
velocity in heart

C. Antianginal drugs

Subclass Mechanism of Action Effect

Nitrates

• Nitroglycerin • Releases nitric oxide in • Smooth muscle

smooth muscle, which
acti vates guanylyl cyclase
and increases cGMP
Beta Blockers
relaxation, especially in
vessels
• Other smooth muscle is
relaxed but not as
markedly
• vasodilation decreases
venous return and
heart size
• May increase coronary
flow in some areas and
in variant angina

• Propranolol • Nonselective competitive • Decreased heart rate,

antagonist at β cardiac output, and
adrenoceptors blood pressure
 • Decreases myocardial
oxygen demand
Calcium Channel Blockers

• Verapamil, • Nonselective block of L- • Reduced vascular

Diltiazem type calcium channels in
vessels and heart
• Nifedipine • Block of vascular L-type
calcium channels > cardiac
(dihydropyridine)
channels
resistance, cardiac rate,
and cardiac force
results in decreased
oxygen demand
• Like verapamil and
diltiazem; less cardiac
effect

Miscellaneous

• Ranolazine • Block of vascular L-type • Like verapamil and

calcium channels > cardiac diltiazem; less cardiac
channels effect

D. Antihypertensive drugs

Subclass Mechanism of Action Effect

Diuretics

• Thiazides: • Block Na/Cl transporter in • Reduce blood volume

Hydrochlorothiazide renal distal convoluted and poorly understood
tubule vascular effects
• Loop Diuretics: • Block Na/K/2Cl transporter Like thiazides (greater
Furosemide in renal loop of Henle efficacy)

• Spironolactone, • Block aldosterone receptor • Increase Na and

in renal collecting tubule decrease K excretion
Eplerenone
Sympathoplegics, Central
Acting

• Clonidine, • Activate α2 adrenoceptors • Reduce central

Methyldopa sympathetic outflow
• Rreduce
norepinephrine release
from noradrenergic
nerve endings
Sympathetic Nerve
Terminal Blockers

• Reserpine • Blocks vesicular amine • Reduce all sympathetic

transporter in effects, especially
noradrenergic nerves and cardiovascular, and
depletes transmitter stores reduce blood pressure
• Guanethidine • Interferes with amine • Reduce all sympathetic
release and replaces effects, especially
norepinephrine in vesicles cardiovascular, and
reduce blood pressure
α Blockers
• Prevent sympathetic
Selectively block α1 vasoconstriction
• Prazosin
adrenoceptors • reduce prostatic
• Terazosin
smooth muscle tone
• Doxazosin
β Blockers
• Prevent sympathetic
Block β1 receptors; carvedilol
cardiac stimulation
• Metoprolol, others also blocks α receptors
• Reduce renin secretion
• Carvedilol
Vasodilation

• Verapamil • Nonselective block of L- • Reduce cardiac rate

• Diltiazem type calcium channels and output
• Reduce vascular
resistance
• Nifedipine, • Block vascular calcium • Reduce vascular
amlodipine, other channels > cardiac calcium resistance
dihydropyridines channels

• Hydralazine • Causes nitric oxide release • Vasodilation

• Reduce vascular
resistance
• Metabolite opens K • Arterioles more
• Minoxidil
channels in vascular sensitive than veins
smooth muscle • Reflex tachycardia
Parenterals Agents
Releases nitric oxide Activates
• Nitroprusside
D1 receptors Opens K channels Powerful vasodilation
• Fenoldopam α, β blocker
• Diazoxide
• Labetalol
Angiotensin-Converting
Enzyme (ACE) Inhibitors
 • Captopril • Inhibit • Reduce angiotensin II
angiotensin converting levels
enzyme • Reduce
vasoconstriction and
aldosterone secretion
• Increase bradykinin
Angiotensin Receptor
Blockers Block AT1 angiotensin Same as ACE inhibitors but
receptors no increase in bradykinin
• Losartan
Renin Inhibitor
Inhibits enzyme activity of Reduces angiotensin I and II
renin and aldosterone
• Aliskiren

E. Diuretic drugs

Subclass Mechanism of Action Effect

Carbonic Anhydrase
Inhibitors

• Acetazolamide • Inhibition of the enzyme • Reduces reabsorption

prevents dehydration of of HCO3-, causing self-
H2CO3 and hydration of limited diuresis
CO2 in the proximal • Hyperchloremic
convoluted tubule metabolic acidosis
reduces body pH,
reduces intraocular
pressure
Loop Diuretics

• Furosemide • Inhibition of the Na/K/2Cl • Increased NaCl

transporter in the excretion, some K
ascending limb of Henle’s wasting, hypokalemic
loop metabolic alkalosis,
increased urine Ca and
Mg
Thiazide

• Hydrochlorothiazide • Modest increase in

NaCl excretion
 • Inhibition of the Na/Cl
transporter in the distal
convoluted tubule
Potassium-Sparing
Diuretics
• Spironolactone • Pharmacologic antagonist
of aldosterone in collecting
tubules
• Weak antagonism of
androgen receptors
• Amiloride • Blocks epithelial sodium
channels in collecting
tubules
Osmotic Diuretics
• Mannitol • Physical osmotic effect on
tissue water distribution
because it is retained in
the vascular compartment
Vasopressin (ADH)
Antagonist
• Conivaptan • Antagonist at V1a and V2
ADH receptors
• Tolvaptan
• Selective antagonist at V2
ADH receptors
3. Give the adverse effects of antihypertensive drugs
A. Diuretics
• Hyponatremia
• Hypokalemia
• Some K wasting
• Hypokalemic metabolic
alkalosis
• Decreased urine Ca
• Reduces Na retention
and K wasting in kidney
• Poorly understood
antagonism of
aldosterone in heart
and vessels
• Reduces Na retention
and K wasting
• Increases lithium
clearance
• Marked increase in
urine flow, reduced
brain volume,
decreased intraocular
pressure, initial
hyponatremia, then
hypernatremia
• Reduces water
reabsorption, increases
plasma Na
concentration,
vasodilation
• Reduces water
reabsorption, increases
plasma Na
concentration
 • Hypomagnesaemia
• Hyperuricaemia
• Hyperglycaemia
• Hypocholesterolaemia
• Erectile dysfunction
• Increase plasma renin,
• Idiosyncratic reactions

B. Beta-blockers

• Intolerance – fatigue, cold extremities, erectile dysfunction

• Airways obstruction
• Decompensated heart failure
• Peripheral vascular diseases and vasospasm
• Hypoglycemia
• Heart block
• Metabolic disturbance

C. Vasodilators

• 1st dose hypotension and postural hypotension

• Nasal stuffiness, headache, dry mouth and pruritus
• Urinary incontinence

D. Angiotensin antagonists (ACE inhibitors & Angiotensin II Receptor Blockers)

Angiotensin Converting Enzyme Inhibitors (Adverse Effect)

• 1st dose hypotension
• Dry cough (most frequent symptoms)
• Functional renal failure
• Hyperkalemia
• Fetal injury
• Urticaria and angio-oedema
• Sulphhydryl group-related effects (high dose of captopril) – causes heavy
proteinuria, neutropenia, rash and taste disturbance

Angiotensin Receptor Blockers (Adverse Effect)

• Hyperkalemia
• Fetal renal toxicity
• Angio-oedema
4.What are adverse effects of antihypertensive drugs (class and drug, adverse effects)

Subclass Drug Adverse Effect

• Thiazides: • Hyponatremia
Hydrochlorothiazide • Hypokalemia
• Loop Diuretics: • Hypomagnesaemia
Furosemide • Hyperuricaemia
Diuretics
• Spironolactone, • Hyperglycaemia
Eplerenone • Hypocholesterolaemia
• Erectile dysfunction
• Increase plasma renin,
• Idiosyncratic reactions
• Methyldopa • Sedation
• persistent mental
lassitude and impaired
mental concentration
Sympathoplegics, • lactation (both men
Central Acting and women)
• Coombs positive

• Dry mouth
• Clonidine • Sedation
• Guanethidine • Sympatomatic postural
hypotension
• Diarrhea
• Reserpine • Little postural
hypotension
• Sedation, lassitude,
Sympathetic nightmares and severe
Nerve Terminal mental depression (at
Blockers high doses)
• Extrapyramidal effects
(at low doses)
• Mild diarrhea and
gastrointestinal cramps
and increase gastric
acid secretion
• Prazosin
• Orthostatic
α Blockers • Terazosin
hypotension
• Doxazosin
• Intolerance – fatigue, cold
• Metoprolol, others
β Blockers extremities, erectile
• Carvedilol dysfunction
 • Airways obstruction
• Decompensated heart
failure
• Peripheral vascular
diseases and vasospasm
• Hypoglycemia
• Heart block
• Metabolic disturbance

• Verapamil • 1st dose hypotension and

• Diltiazem postural hypotension
• Nifedipine, amlodipine, • Nasal stuffiness,
Vasodilation other dihydropyridines headache, dry mouth and
pruritus
• Hydralazine
• Urinary incontinence
• Minoxidil

• Nitroprusside
• Fenoldopam • Excessive hypotension
Parenterals Agents
• Diazoxide • Shock
• Labetalol
• Captopril • 1st dose hypotension
• Dry cough (most frequent
symptoms)
• Functional renal failure
• Hyperkalemia
Angiotensin- • Fetal injury
Converting • Urticaria and angio-
Enzyme (ACE) oedema
Inhibitors • Sulphhydryl group-related
effects (high dose of
captopril) – causes heavy
proteinuria, neutropenia,
rash and taste
disturbance
• Hyperkalemia
Angiotensin
• Losartan • Fetal renal toxicity
Receptor Blockers
• Angio-oedema
• Hyperkalemia
Renin Inhibitor • Aliskiren • Renal impairment
• Potential teratogen
5. What are the determinants of Cardiac oxygen requirements
• Wall stress
o Intraventricular pressure
o Ventricular radius (volume)
• Heart rate
• Contractility
6. Drugs use in angina pectoris (subclass, MOA, Effects)
Subclass
Nitrates
• Nitroglycerin
Beta Blockers
• Propranolol
Calcium Channel Blockers
• Verapamil,
Diltiazem
• Nifedipine
(dihydropyridine)
Mechanism of Action
• Releases nitric oxide in
smooth muscle, which
acti vates guanylyl cyclase
and increases cGMP
• Nonselective competitive
antagonist at β
adrenoceptors
• Nonselective block of L-
type calcium channels in
vessels and heart
• Block of vascular L-type
calcium channels > cardiac
channels
Effect
• Smooth muscle
relaxation, especially in
vessels
• Other smooth muscle is
relaxed but not as
markedly
• vasodilation decreases
venous return and
heart size
• May increase coronary
flow in some areas and
in variant angina
• Decreased heart rate,
cardiac output, and
blood pressure
• Decreases myocardial
oxygen demand
• Reduced vascular
resistance, cardiac rate,
and cardiac force
results in decreased
oxygen demand
• Like verapamil and
diltiazem; less cardiac
effect
 Miscellaneous

• Ranolazine • Block of vascular L-type • Like verapamil and

calcium channels > cardiac diltiazem; less cardiac
channels effect

References:
KATZUNG AND Trevor’s Pharmacology 8th edition
Mc GRAW Hill Lange Basic and clinical Pharmacology 11 th edition