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when blood
volume is great
compared to the
HYPERTENSION
space available
inside blood
vessels
Malfunctions
when the electrical
conduction
pathways ARRHYTHMIA
malfunction
when oxygen-
starved areas of MYOCARDIAL
the heart begin INFARCTION
dying
• Hydraulic Equation:
BP = CO x TPR
Factors that alter the Blood Pressure Equation
Sympathetic Adrenergic
System
vasoconstriction
Na+& H2O
Reabsorption
Heart Blood
Stroke Venous
Volume
Rate x Volume Return Rises
Pituitary
Gland Angiotensin II
Renin –
ACE
Angiotensin
System Angiotensin I
Low Blood Pressure
Low Blood Volume Kidney
Na+ depletion
Renin
Determinants of Blood
Pressure
• Cardiac Output (CO)
– volume of blood pumped out by the
heart in 1 minute
– approximately 2.2 – 3.5 L / min / m2 BSA
– determined by Stroke Volume (SV) and
Heart Rate (HR)
Determinants of Blood
Pressure
• Stroke Volume (SV)
– volume of blood pumped out by the
heart in every contraction
– determined by:
• Inotropic activity –strength of cardiac
contraction
• Venous return – cardiac preload; amount of
blood delivered to the heart from the veins;
affected by the tone of the veins
Determinants of Blood
Pressure
• Heart Rate (HR)
– speed of heart contraction
– chronotropism
• Fluid Content of the Blood
• Total Peripheral Resistance (TPR)
– resistance or pressure encountered by
the heart as it pumps out blood into the
peripheral circulation (cardiac afterload)
– determined by the arterioles
Mechanisms of BP
Regulation
• Baroreceptor Reflex Arch Mechanism
– aka: Postural Reflex Mechanism
– moment-to-moment BP regulation
• Baroreceptor – a type of sensory nerve
ending found in the walls of the atria of the
heart, the vena cava, the aortic arch, and
the carotid sinus that is stimulated by
changes in pressure
Angiotensin I (inactive)
Angiotensin II (active)
-direct vasoconstriction
-stimulates synthesis & release of Epi & NE
-stimulates the synthesis & release of
aldosterone
Hypertension
Hypertension
• persistent or recurrent elevation of BP
defined as having a:
– Systolic reading > 140 mmHg
– Diastolic reading > 90 mmHg
– BP > 140/90
• most common cardiovascular
disorder
Hypertension
• Systole
– the period during which the ventricles
are contracting
• Diastole
– the period during which the ventricles
are relaxed and filling with blood
Hypertension
• Essential (Primary, Idiopathic)
– hypertension with no identifiable cause
– accounts for > 90% of HTNsive cases
• Secondary
– resulting from identifiable causes
• kidney diseases
• adrenal cortical disorders
• pheochromocytoma (adrenal medulla tumor)
• coarctation of the aorta
• drugs such as steroids, sympathomimetics, contraceptives
– treat the underlying cause
– accounts for ~ 10% of HTNsive cases
Classification of BP based on the 7th Report of the
Joint National Committee on Detection, Evaluation
and Treatment of High Blood Pressure (JNC VII)
• Monitor:
– blood pressure routinely
– observe adverse effects
• Patient Counseling:
– Importance of compliance make px realize seriousness
of noncompliance
Anti-hypertensives
• Diuretics
• Sympathoplegics
• Vasodilators
• Calcium Channel Blockers (CCBs)
• ACE Inhibitors
• Angiotensin II Receptor Blockers
(ARBs)
Diuretics
• agents that cause urinary loss of Na+
and H2O
• Furosemide
• Bumetanide
• Torsemide
• Ethacrynic acid
Loop Diuretics
• for px who cannot tolerate thiazides,
have renal impairment, or
ineffectiveness of thiazides
• Chlorothiazide
• Hydrochlorothiazide
• Chlorthalidone
• Indapamide
Thiazide Diuretics
• first-line drug for uncomplicated
hypertension as recommended by
JNC 7
• Spironolactone
• Eprenolone
• Amiloride
• Triamterene
Potassium-Sparing Diuretics
• for patients where potassium loss is
significant and supplementation is not
feasible
• often combined with thiazides
potentiation
– Amiloride, Spirinolactone, Triamterene
• precautions
– Avoid in px with acute renal failure; use
with caution px with impaired renal
function
Potassium Rich Foods
TOPP PNBB’S
• T- Tomatoes
• O-Oranges
• P- Peaches
• P-potatoes
• P-Prunes
• N-Nuts
• B-Banana
• B-Broccoli
• S-Spinatch
Potassium-Sparing Diuretics
• not associated with hypokalemia
• Mannitol
• Sorbitol
• Urea
Osmotic Diuretics
• used to induce forced diuresis
• mostly used to reduce intracranial
pressure
• Clonidine
• Methyldopa
• Guanfacine
• Guanabenz
Clonidine
• MOA: agonist at alpha-2 receptors
(leading to vasodilation)
• Trimethaphan
• Reserpine
• Guanethidine
• Guanadrel
Trimethaphan
• ganglionic receptor blocker
• Prazosin
• Doxazosin
• Alfazosin
• Terazosin
Alpha-1 Blockers
• alternative drugs for the management
of HTN esp among patients with BPH
• First-Dose Phenomenon:
– orthostatic hypotension
– syncope
– remedy: take the drug at bedtime, slow
increase in dose
Beta Blockers
Beta Blockers
• used for the initial therapy of HTN;
effective for patients with rapid resting
HR or concomitant IHD
• MOA
– Block stimulation of renin secretion
– Decrease contractility decrease CO
– Decrease sympathetic output centrally
– Reduction in HR reduced CO
– Combination of all
Beta Blockers
• SE/Precautions/Contraindications:
– can mask hypoglycemia
– CI to patients with bronchospastic
disease: COPD, Bronchial Asthma
– rebound tachycardia and HTN
– easy fatigability
– severe bradycardia and heartblock
(seen esp with concomitant use of
verapamil and diltiazem)
Beta Blockers
• Selective • Membrane Stabilizing
B – Betaxolol Activity
– Anesthetic-like effect
B – Bisoprolol
– Cannot be given as
E – Esmolol ophthalmic drops
A – Acebutolol P – Propranolol
A – Atenolol P – Pindolol
M – Metoprolol A – Acebutolol
L – Labetalol
M – Metoprolol
Beta Blockers
• Mixed alpha and • Intrinsic
beta blocking sympathomimetic
effect activity
– partial agonist effect
– not usually associated
L – Labetalol with rebound
C – Carvedilol hypertension
A – Acebutolol
B – Bisoprolol
C – Carteolol
P – Pindolol
P - Penbutolol
Nematodes (Roundworms)
Nematodes (Roundworms)
Vasodilators
Vasodilators
• second-line agents
• MOA
– Inhibit influx of Ca through the slow
channels in vascular smooth muscle
and cause relaxation
Classification
• Dihydropyridine (DHP)
– block Ca channels in the blood vessels
– Nifedipine, Nicardipine, Felodipine,
Amlodipine
• Non-dihydropyridine (Non-DHP)
– block Ca channels both in the heart and blood
vessels
– Verapamil – heart > blood vessels
– Diltiazem – heart = blood vessels
Calcium Channel Blockers
(CCBs)
• SE:
– peripheral edema
– reflex tachycardia (DHP)
– bradycardia (Non-DHP)
– heart block (Non-DHP + Beta Blocker)
ACE Inhibitors
Angiotensin Converting Enzyme
Inhibitors
• MOA: inhibit ACE, thereby preventing the
conversion of angiotensin I into the active
form angiotensin II
• Short-acting
– Captopril
Generally, long acting ACE
• Long-acting Inhibitors are prodrugs:
– Perindopril
Angiotensin Converting Enzyme
Inhibitors
• SE:
– idiosyncratic dry cough
ACE
Bradykinin inactive
fragments
(causes cough)
– angioedema
– hyperkalemia
Angiotensin II Receptor
Blockers
Angiotensin II Receptor
Blockers (ARBs)
A. Clonidine
B. Guanethidine
C. Hydralazine
D. Propanolol
E. Reserpine
3. Which one of the following is characteristic of
enalapril treatment in patients with essential
hypertension?
A. ACE inhibitors
B. Alpha receptor blockers
C. Arteriolar dilators
D. Beta-selective receptor blockers
E. Nonselective B-blockers
Congestive Heart Failure
Heart Failure
• is the failure of
the heart as a
pump
• inability of the
heart to pump
sufficient
amount of
blood to the
body
Congestive Heart Failure
• pumping ability of the heart becomes
impaired
• accompanied by congestion of body
tissues
• etiology
– acute MI, HPN, cardiomyopathies
– excessive work demands on the heart
Forms of CHF
• High-output • Low-output
– uncommon – caused by disorders
– caused by excessive that impair the
need for cardiac pumping ability of the
output heart (IHD)
– high metabolic – normal metabolic
demands demands, heart
unable to meet them
Forms of CHF
• Right sided • Left-sided
– fatigue – exertional dyspnea
– jugular vein – paroxysmal nocturnal
distension dyspnea
– liver engorgement – cough
– blood-tinged sputum
– anorexia, GI distress
– cyanosis
– cyanosis
– pulmonary edema
– elevation in
peripheral venous
pressure
– peripheral edema
Treatment Goals
• To remove or mitigate the underlying
cause
• To relieve the symptoms and improve
pump
function by:
– Reducing metabolic demands (rest,
relaxation, pharm’l controls)
– Reduce fluid volume excess (food intake,
meds)
– Administer digitalis and other inotropic
agents
– Promote px compliance and self-regulation
through education
– Select appropriate px for cardiac transplants
Compensatory Mechanism
• Myocardial Hypertrophy
– long-term compensatory mechanism
– increase in the number of contractile
elements in myocardial cells as a means
of increasing their myocardial
performance
– ventricular remodeling
Compensatory Mechanism
• Frank-Starling Mechanism
– is the intrinsic ability of the heart to
adapt to changing volumes of inflowing
blood
– the greater the heart muscle is stretched
during filling, the greater the force of
contraction and the greater the quantity
of blood pumped into the aorta
– within physiologic limits, the heart
pumps all the blood that comes to it
without allowing excessive damming of
blood in the veins
Drugs for CHF
Drugs for CHF
• Inotropic Agents
– Cardiac glycosides
– Beta Agonists
– Phosphodiesterase Inhibitors
• Unloaders
– ACE Inhibitors & ARBs
– Beta Blockers
– Diuretics
– Vasodilators
Cardiac Glycosides
• from Digitalis species
• Digoxin, Digitoxin
• Extra-cardiac Manifestations
– GI disturbances (nausea & vomiting)
– visual disturbances (blurred vision,
alteration of color perception, haloes on
dark objects)
Management of Toxicity
• give potassium supplement
• Amrinone
• Milrinone
Unloaders
• ACE Inhibitors & ARBs
– preload and afterload unloaders
– vasodilating effect
– Captopril, Enalapril
• Beta Blockers
– vasodilating effect
– Carvedilol,labetalol
• Diuretics
– preload unloaders
– Spironolactone
• Vasodilators
– Hydralazine, Nitroprusside
1. Drugs that have been found to be useful in one
or more types of heart failure include all of the
following EXCEPT
A. Na+/K+ ATPase inhibitors
B. Alpha-adrenoceptor agonists
C. Beta-adrenoceptor agonists
D. ACE inhibitors
2. The mechanism of action of digitalis is
associated with
A. Digoxin
B. Furosemide
C. Minoxidil
D. Propanolol
E. Spironolactone
4. Drugs associated with clinically useful or
physiologically important positive inotropic effects
include all of the following EXCEPT
A. Amrinone
B. Captopril
C. Digoxin
D. Dobutamine
E. Norepinphrine
6. Successful therapy of heart failure with digoxin
will result in which one of the following?
A. Carvedilol
B. Digoxin
C. Dobutamine
D. Enalapril
E. Furosemide
7. Which of the following is the drug of choice in
treating suicidal overdose of digitoxin?
A. Digoxin antibodies
B. Lidocaine
C. Magnesium
D. Phenytoin
E. Potassium
Coronary Artery Diseases
(CAD)
or
Ischemic Heart Diseases
(IHD)
Coronary Artery Diseases
Coronary Artery Diseases
• occur when the
coronary arteries
become so narrowed
by atherosclerosis
that they are unable
to deliver sufficient
blood to the heart
muscle
– Localized areas of
thickened tunica
intima associated with
accumulation of
smooth muscle cells
and lipids, principally
cholesterol
Coronary Artery Diseases
• Angina Pectoris
– episodic, reversible oxygen insufficiency
– severe chest pains generally radiating to the left
shoulder and down the inner side of the arm
– usually precipitated by physical exertion or emotional
stress
• Myocardial Ischemia
– deprivation of oxygen to a portion of the myocardium
(reversible)
• Myocardial Infarction
– severe, prolonged deprivation of oxygen to a portion
of the myocardium that leads to myocardial tissue
necrosis (reversible)
Risks Factors
• Smoking
• Hypertension
• Diabetes Mellitus
• Males >45 yo; Females >55 yo
• Dyslipidemia
• Obesity
• Family history of CAD
• Others:
– sedentary lifestyle, hx of chronic inflammation
Etiology
• Decreased blood flow
– Atherosclerosis – most common cause
– Coronary artery spasm – sustained
contraction of 1 or more coronary arteries
Prinzmetal’s angina or MI
– Traumatic injury – that interferes with blood
flow in the heart
– Embolic events – can abruptly restrict oxygen
supply
• Increased oxygen demand
– Exertion and emotional stress sympathetic
stimulation increase HR
• Reduced blood oxygenation
– Reduced O2-carrying capacity (anemia)
Angina Pectoris
• chest pain
– Unstable Angina
• can be experienced at rest, or with increasing
severity for the last 1-2 months or a new chest pain
for < 1 month
• mechanism: thrombosis
Angina Pectoris
• Types:
– Angina Decubitus
• nocturnal angina
• occurs in recumbent position
– Prinzmetal Angina
• aka: Variant Angina
• precipitated by coronary artery spasm
Drugs for Angina Pectoris
• Nitrates
• Beta Blockers
• Calcium Channel Blockers
Nitrates
• MOA: metabolized into NO in the
body, leading to peripheral
vasodilation
• examples
– amyl nitrite
– nitroglycerin
– isosorbide dinitrate (ISDN)
– isosorbide mononitrate (ISMN)
• SE:
– throbbing headache, tolerance
Nitrates
• MOA
– Decrease oxygen demand and facilitate
coronary blood flow
– converted to nitric oxide intracellularly which
activates guanylate cyclase increase
cGMP dephosphorylation of myosin
light chain relaxation of vascular smooth
muscle vasodilation
• Important SE
– HEADACHE – most common side effect
– Tolerance (“Nitrate-free interval”)
– Postural hypotension, facial flushing, reflex
tachycardia
Beta Blockers
• drug of choice for stable angina
M MORPHINE
OXYGEN
O
NITROGLYCERINE
N ASA
Drugs for MI
Drugs for MI
• Nitrates
• Oxygen
• Morphine
• Thrombolytic Agents
Oxygen
• for patients who have chest pain and
who may be ischemic
• improve oxygenation of myocardium
Morphine
• MOA
– causes venous pooling and reduces preload,
cardiac workload, and oxygen consumption
– IV until pain is relieved
• Indication
– DOC for MI pain and anxiety
• Precautions
– can produce orthostatic hypotension and
fainting
– monitor for hypotension & signs of resp
depression
– GI SE: nausea and vomiting; constipation
Thrombolytic Agents
• MOA:
– Lysis of thrombus clot
• The following are given IV within 12 h to
restore normal blood flow in an acute MI:
– Recombinant t-PA (recombinant tissue-type
plasminogen activator
– alteplase
– Streptokinase
– Anisoylated plasminogen streptokinase
activator complex (APSAC)
– Reteplase
– Tenecteplase
Post thrombolysis adjunctive
therapy
• Aspirin
– prevents platelet aggregation; shown to
reduce post-infarct mortality
– also: dipyridamole, ticlopidine, clopidogrel
• Heparin
– prevent re-occlusion once a coronary artery
has been opened
– not used with streptokinase increased risk
of hemorrhage
• Warfarin
– reduce mortality, prevent recurrent MI
Post thrombolysis adjunctive
therapy
• Beta Blockers
– if administered early reduce ischemia,
reduce potential zone of infarction, decrease
oxygen demands, preserve left ventricular
function, decrease cardiac workload
• ACE Inhibitors
– improve exercise capacity and reduce
mortality in px with CHF; aid in the prevention
of progressive ventricular remodelling
• “Statins”
– reduced mortality due to MI when used by px
to aggressively lower cholesterol
Post thrombolysis adjunctive
therapy
• Lidocaine
– used for px who develop ventricular
arrhythmia
• Calcium Channel Blockers
– decrease incidence of reinfarction in px
with non-Q-wave infarcts; not for acute
mgt.
Items 1-3. Mr. Green, 60 years old, has
severe chest pain when he attempts to carry
parcels upstairs to his apartment. The pain
rapidly disappears when he rest. A decision
is made to treat him with nitroglycerin.
2. In advising Mr. Green about the adverse effects
he may notice, you point out that nitroglycerin in
moderate doses often produces certain symptoms.
These toxicities result from all of the following
EXCEPT
A. Meningeal vasodilation
B. Reflex tachycardia
C. Hypotension
D. Methemoglobinemia
3. 2 years later, Mr. Green returns complaining
that his nitroglycerin works well when he takes it
for an acute attack but that he is having frequent
attacks now and would like something to prevent
them. Useful drugs for the prophylaxis of angina of
effort include which one of the following?
A. Amyl nitrite
B. Diltiazem
C. Sublingual isosorbide dinitrate
D. Sublingual nitroglycerin
4. The antianginal effect of propanolol may be
attributed to which one of the following?
A. Blood volume
B. Cardiac output
C. Diastolic blood pressure
D. Heart rate
E. Myocardial fiber tension
6. You are considering therapeutic options for a
new patient who presents with hypertension and
angina. In considering adverse effects, you note
that an adverse effect which nitroglycerin,
prazosin, and ganglion blockers have in common
is
A. Bradycardia
B. Impaired sexual function
C. Lupus erythematosus syndrome
D. Orthostatic hypotension
E. Throbbing headache
7. A patient is admitted to the emergency
department following a drug overdose. He is noted
to have severe tachycardia. He has been receiving
therapy for hypertension and angina. A drug that
often causes tachycardia is
A. Diltiazem
B. Guanethidine
C. Isosorbide dinitrate
D. Propanolol
E. Verapamil
Arrhythmias
Arrhythmias
– Ventricular arrhythmia
• Occur when an ectopic pacemaker triggers
a ventricular contraction before the SA
node fires
Normal ECG Pattern
ECG Patterns of Arrhythmias
Anti-arrhythmic Agents
•Quinidine
Antiarrhythmics Class IA •Procainamide
•Disopyramide
•Amiodarone
Potassium Channel Blockers Class III •Sotalol
•Bretylium
•Verapamil
Calcium Channel Blockers Class IV •Diltiazem
CLASS 1A
• Slows phase 0 depolarization
• Prolong action potential
• Slow conduction
CLASS 1B
• Shortens phase 3 repolarization
• Decrease duration of action potential
CLASS 1C
• Markedly slow phase 0 depolarization
CLASS II
• Suppresses phase 4 depolarization
CLASS III
• Prolongs phase 3 repolarization
CLASS IV
• Slows phase 4 spontaneous
depolarization
• Shorten action potential
Miscellaneous Agents
• Adenosine
• MgSO4
TYPE OF ARRHYTHMIA
AND DRUGS
• Atrial flutter
• Class 1 – quinidine
• Class II - propranolol
• Class IV – verapamil
• Others - digoxin
• Atrial fibrillation
• 1- quinidine
• 2- propranolol
• 3- amniodarone
• 4 – anticoagulant
• AV –NODAL REENTRY
• PROPRANOLOL
• VERAPAMIL
• DIGOXIN
• ACUTE SUPRAVENTRICULAR
TACHYCARDIA
• Verapamil
• adenosine
• ACUTE VENTRICULAR TACHYCARDIA
• Lidocaine
• Sotalol
• Amniodarone
• VENTRICULAR FIBBRILLATION
• Lidocaine
• Bretylium
• Amnidarone
• epinephrine
Procainamide
• can cause SLE (Systemic Lupus
Erythematosus)
Quinidine
• drug interaction with digoxin
• can increase serum levels of digoxin
by at least 2x
Lidocaine
• anesthetic
• DOC for digitalis-induced arrhythmias
Propafenone
• for acute atrial fibrillation
Amiodarone
• iodine-containing molecule
• first-line treatment for almost all types
of Ventricular Tachycardia and Atrial
Fibrillation
Verapamil
• alternative for acute SVT
(Supraventricular Tachycardia)
Adenosine
• first-line drug for acute SVT
Drugs for Coagulation
Disorders
Clotting Mechanism
• inciting event: epithelial vascular injury
• followed by:
– migration of platelets to the site of injury
– platelet aggregation
• aka: primary hemostasis
• white thrombus
• platelet plug
• unstable clot
– deposition of fibrin over the plug
– attachment of other blood cells
• aka: secondary hemostasis
• red thrombus
• stable clot
Clotting Mechanism
• thrombus
– clot that adheres to a blood vessel wall
• embolus
– detached thrombus
Clotting Mechanism
• the coagulation process that
generates thrombin that is essential in
the formation of fibrin used in clot
formation involves coagulation
cascade
Coagulation Cascade
Drugs for Coagulation
Disorders
Anticoagulants
Anti-Platelet Drugs
Fibrinolytic Agents
Pro-coagulant Drugs
Anticoagulants
Anticoagulants
• Site of action
– synthesis of or directly against clotting factors
(II, IIa)
• Types:
– Parenteral
• Hirudin, Heparin
– Oral
• Dicumarol, Warfarin
Parenteral Anticoagulants
Hirudin
• obtained from medicinal leeches
(Hirudo medicinalis)
• Aspirin
– primary prophylaxis for MI
– secondary prophylaxis for MI and stroke
Phosphodiesterase Inhibitors
• Dypiridamole
– given together with antiplatelet;
ineffective when alone
– Inc CAMP
– SE: coronary steal phenomenon
ADP Inhibitors -
Thienopyridines
• Ticlopidine
– SE: thrombocytopenia
purpura,neutropenia,
– n/v,diarrhea
• Clopidogrel
– safer than ticlopidine
Glycoprotein Inhibitors
• Abciximab
• Eptifibatide
• Tirofiban
Fibrinolytic Agents
Fibrinolytic Agents /
Thrombolytics
• MOA
– catalyse activation of plasminogen to
plasmin(serine protease)
• Use
– mgt of severe pulmonary embolism
– heart attack, acute MI,DVT
• Ex
– Streptokinase – destroy fibrin that is either
bound to clots or is in the unbound form
– Tissue plasminogen activator – binds to fibrin
bound to a clot
– Anistreplase (APSAC)
Pro-coagulant Drugs
Pro-coagulant Drugs
• Mgt of bleeding disorders
– Vitamin K
• K1 – phytonadione (in plants, useful
clinically)
• K2 – menaquinone (intestinal bacteria)
• K3 – menadione (synthetic)
• used for Vit. K deficiency; hemorrhagic
disorders in newborns
– Aminocaproic Acid
• prevents activation of plasminogen
– Tranexamic Acid (analogue)
Drugs for Dyslipidemia
Dyslipidemia
• Hypercholesterolemia (inc LDL, dec
HDL)
• Hypertriglyceridemia (inc TG, ~ inc
VLDL, chylomicrons)
• Liver
– Only organ in the body that efficiently
uses cholesterol
• Converts it to bile salts
Cholesterol Synthesis
HMG-CoA
Reductase
HMG-CoA Mevalonate Cholesterol
Cholesterol Source
hydroxymethylglutaryl-
Coenzyme A (HMG-CoA) –Diet (exogenous)
–Endogenous
Atherosclerosis
Condition
associated with
cholesterol
deposition in
vascular smooth
muscles (arthroma)
with consequent
narrowing of the
lumen of the
affected blood
Atherosclerosis
• Could lead to…
– CAD
– Cerebrovascular disease
– Aortic disease
– Renal artery disease
Atherosclerosis
• Major Risk factors
• Minor Risk Factors
– Age (males: > 45;
– Chronic infection
females: > 55)
– Sedentary lifestyle
– Smoking
– DM • Modifiable Risk
– HPN Factors
– Dyslipidemia – By therapy
– Obesity – By lifestyle change
– Family history of
premature heart
attack
Drugs for Dyslipidemia
• HMG-CoA Reductase Inhibitors
• Nicotinic Acid
• Bile Acid Sequesterants
• Fibric Acid Derivatives
• Probucol
HMG-CoA Reductase
Inhibitors
• “-statins”
• SE:
– constipation
– impaired absorption of certain drugs
– may increase incidence / risk of biliary
stone formation
Fibric Acid Derivatives
• MOA: stimulate lipoprotein lipase
which decreases triglycerides
• Gemfibrozil
• Fenofibrate
• Clofibrate (withdrawn)
Mechanism of action:
• Fibrates stimulate Peroxisome proliferator
activated receptor alpha (PPAR)-α which
controls the expression of gene products
that mediate the metabolism of TG & HDL
Mechanism of action:
• As a result synthesis of FA , TG & VLDL is
reduced while lipoprotein lipase activity
which catabolizes TG is enhanced, in
addition the promoter regions of genes
such as apolipoprotein I and ATP binding
cassette A1, are up regulated leading to
↑HDL, consequently
• Fibrates reduce TG up to 50%, and ↑HDL
by 20% but LDL changes are variable.
Fibric Acid Derivatives
• SE:
– myositis
– rhabdomyolysis
– increase risk of bile stone formation
– hepatobiliary cancer (Clofibrate)
Cholesterol absorption inhibitors
• Ezetimibe
• These inhibit the intestinal mucosa
transporter NPC1L1 that absorbs dietary
and biliary cholesterol. The resultant
depletion of hepatic cholesterol up
regulates hepatic LDL receptor activity.
Cholesterol absorption inhibitors
• This mechanism is synergistic with statins,
LDL is reduced by 17%, TG is reduced by
6% While HDL is increased by 1.3%
Highly poly unsaturated long chain (n=3)
fatty acids (Fish oil)(omega fatty acids)
• Eicosapentanoic acid (EPA) and
Docosahexanoic acid (DHA) comprise
30% of the fatty acids in fish oil. EPA &
DHA are potent inhibitors of VLDL TG
formation
Highly poly unsaturated long chain (n=3)
fatty acids (Fish oil)(omega fatty acids
• Intake of 2gm of n3 fatty acid (equal to
6gm of most forms of fish oil) per day
lower TG in a dose dependant manner. Up
to 50% reduction of TG can be achieved
with 15gm fish oil per day. Changes in
LDL & HDL are variable.Fish oil also
inhibit platelet aggregation and have been
shown to decrease mortality from
CHD(coronary heart disease).Fish oil is
safe and well tolerated.
Probucol
• MOA: anti-oxidant
• SE:
– increase risk of arrhythmia
– produces fetid odor
How much can you recall…
Question 1:
• Which enzyme is responsible for the
conversion of Angiotensin I into the
active form Angiotensin II?
A. Renin
B. ACE
C. HMG-CoA
D. Streptokinase
Question 2:
• A 55 y/o male patient was
diagnosed to have uncomplicated
HTN. Which of the following drugs
would most likely be given to him?
A. Thiazide diuretic + Beta Blocker
B. ACE Inhibitor
C. CCB + ACE Inhibitor
D. ACEi + ARB
Question 3:
• From the list of anti-hypertensive
drugs below, select the one most
likely to lower blood sugar:
A. Prazosin
B. Nifedipine
C. Propranolol
D. Hydralazine
E. Labetalol
Question 4:
• Which of the following conditions
predisposes a patient taking digitalis
into arrhythmia?
A. hypocalcemia
B. decreased heart rate
C. hyponatremia
D. hypokalemia
Question 5:
• All of the following mechanisms of
action correctly match a drug,
EXCEPT:
A.Minoxidil
B. Verapamil
C. Clonidine
D. Enalapril
12. Which of the following
antihyperthensives more likely to
cause reflex tachycardia?
A. Propranolol
B. Nifedipine
C. Prazosin
D. Hydralazine
13. From the list of antihypertensive
drugs below, select the one most
likely to lower blood sugar.
A. Prazosin
B. Propranolol
C. Nifedipine
D. Captopril
14. The mechanism of actions of felodipine include
which of the following?
A. I only
B. II only
C. I and II only
D. II and III only
E. I,II and III
18.A 50 year old , female patient arrives to
the Emergency Department due to the
severe chest pain. Electrocardiogram
revealed that she has an acute myocardial
infarction . The medical resident-on-duty
gave Streptokinase as her dose . What is the
mechanism of actions of Streptokinase ?
A. It inhibits the conversion of fibrinogen to fibrin
B. It promotes the conversion of fibrin to fibrin-split
products
C. It activates the conversion of plasminogen to
plasmin
D. It inhibits the conversion of prothrombin to thrombin
19. A 70 year old , male patient post
coronary angiography bypass graft
(CABG) with elevated LDL is managed
with Simvastatin ?
A. Magnesium
B. Potassium
C. Calcium
D. Chloride
23.The drug blocks the
sodium/potassium/chloride cotransporter in
the thick ascending loop of Henle:
a) Acetazolamide (Diamox)
b) Furosemide (Lasix)
c) Hydrochlorothiazide (Hydrodiuril)
d) Amiloride (Midamor
24. The drug can cause ototoxicity:
a) Acetazolamide (Diamox)
b) Furosemide (Lasix)
c) Hydrochlorothiazide (Hydrodiuril)
d) Amiloride (Midamor)
25. The drug decreases calcium excretion in
urine:
a) Hydrochlorothiazide (HydroDiuril)
b) Amiloride (Midamor)
c) Furosemide (Lasix)
d) Acetazolamide (Diamox)
26. The drug can be used to treat
nephrogenic diabetes insipidus:
a) Hydrochlorothiazide (HydroDiuril)
b) Amiloride (Midamor)
c) Both of the above
d) Neither of the above
27. Among the diuretic agents, which of the
following would decrease the body pH?
I. Potassium-sparing diuretics
II. Carbonic anhydrase inhibitors
III. Loop diuretics
A. I only
B. II only
C. I and II only
D. II and III only
E. I,II and III
28. Which of the following diuretics
caused hyperglycemia, hypomagnesemia
and hyperuricemia?
A. Spironolactone C. Acetazolamide
B. Furosemide D. Hydrochlorothiazide
28.) The following statements are true for the carbonic
anhydrase inhibitors?
a) I only
b)II only
c)I and II only
d)II and III only
e) I, II and III
“The only thing greater than the power
of the mind is the courage of the
heart.”
- from the movie, A Beautiful Mind