Clarissa Grace O.

Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

WHAT IS PHARMACOLOGY? Determinants of Blood Pressure

- science of pharmakon - “drug” • Cardiac Output (CO)
– volume of blood pumped out by the
I. Cardiovascular, Renal and Haematologic heart in 1 minute
– approximately 2.2 – 3.5 L / min / m2 BSA
Pharmacology
– determined by Stroke Volume (SV) and
Heart Rate (HR)
 The Cardiovascular System
o Heart • Stroke Volume (SV)
o Blood – volume of blood pumped out by the
o Blood Vessels heart in every contraction
– determined by:
 Arteries
• Inotropic activity –strength of cardiac
 Veins contraction
 Capillaries • Venous return – cardiac preload;
amount of blood delivered to the
heart from the veins; affected by the
tone of the veins
o Heart
• Heart Rate (HR)
• The heart is a pump. – speed of heart contraction
• It pumps blood through a system of blood – “chronotropism”
• Fluid Content of the Blood - plasma
vessels that has a limited volume capacity.
• Total Peripheral Resistance (TPR)
• electric conduction system maintains regular – resistance or pressure encountered by
rate and rhythm. the heart as it pumps out blood into the
• Myocardial cells require oxygen. peripheral circulation (cardiac afterload)
– determined by the arterioles
 HEART FAILURE – heart can no longer pump
Mechanisms of BP Regulation
enough blood to meet the metabolic demands of
• Baroreceptor Reflex Arch Mechanism
the body
– aka: Postural Reflex Mechanism
 HYPERTENSION - blood volume is great compared – moment-to-moment BP regulation
to the space available inside blood vessels o Baroreceptor – a type of sensory nerve
 ARRHYTHMIA – when electrical conduction ending found in the walls of the atria of
pathways malfunctions the heart, the vena cava, the aortic arch,
 ANGINA - the heart’s way of signaling that some and the carotid sinus that is stimulated
by changes in pressure
cells are not getting enough oxygen.
 MYOCARDIAL INFARCTION - when oxygen starved • Renin Angiotensin Aldosterone System (RAAS)
areas of the heart begin dying

Cardiovascular Drugs
 Anti-hypertensives
 Drugs for Heart Failure
 Anti-anginal and Drugs for MI
 Anti-arrhythmic Agents

Hydraulic Equation:

BP = CO x TPR

1
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Hypertension • Gender – males

• 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
Systole - the period during which the ventricles are
contracting
Diastole - the period during which the ventricles are
relaxed and filling with blood
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
Joint National Committee on Detection, Evaluation
and Treatment of High Blood Pressure (JNC VII)
• Age > 60
• Postmenopausal women
Treatment Goals
 Rule out uncommon secondary causes of hypertension
 Determine the presence and extent of target organ damage
 Determine the presence of other CV risk factors
 To lower BP with minimal side effects
Treatment
• First line: diuretics (thiazides) and beta blockers
• Alternatives: ACE inhibitors, ARBs, alpha blockers,
calcium- channel blockers à for px who cannot
tolerate first line agent
Monitor: blood pressure routinely & observe adverse effects
Patient Counseling: – Importance of compliance à make px
realize seriousness of noncompliance
Complications
• Cardiac effects - Increased oxygen requirements à
angina pectoris; because of atherosclerosis à
angina, MI, sudden death
• Renal effects - Increased blood volume; renal
parenchymal damage due to atherosclerosis
• Cerebral effects - Transient ischemic attacks,
cerebral thromboses, aneurysms with
hemorrhage

• Retinal effects - Visual defects (blurred vision,

spots, blindness)

 Anti-Hypertensive Drugs
 Diuretics
- agents that cause urinary loss of Na+ and
 Hypertensive Emergency H2O
- aka: Hypertensive Crisis Gen MOA: act on their specific sites in the
- rare, but life-threatening situation renal tubule
- systolic pressure > 210 mm Hg
- diastolic pressure > 150 mm Hg

Risk Factors
• Family history
• Patient history
• Racial predisposition (common in blacks)
• Obesity
• Smoking
• Stress
• High dietary intake
– Saturated fats and sodium
• Sedentary lifestyle
• DM
• Hyperlipidemia

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 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

DI: their efficacy can be reduced by NSAIDs

Five major classes
1. Thiazides and thiazide-like
MOA: inhibit Na-Cl-cotransporter at the distal
convoluted tubule
ex.
Chlorothiazide
Hydrochlorothiazide
Chlorthalidone
Indapamide
• first-line drug for uncomplicated
hypertension as recommended by JNC 7
• effective initial therapy together with beta-
blockers
• also used for Nephrogenic Diabetes Insipidus
SE: hypokalemia, hyponatremia, hyperuricemia,
hyperglycemia, hyperlipidemia, hypercalcemia
DI: their efficacy can be reduced by NSAIDs
3. Potassium-sparing
MOA: act in the collecting tubule by inhibiting
Na+ reabsorption, K+ secretion and H+
secretion
ex.
Spirinolactone
Eprenolone
Amiloride
Triamterene
• for patients where potassium loss is
significant and supplementation is not
feasible
• often combined with thiazides a potentiation
– Amiloride, Spirinolactone, Triamterene
precautions
– Avoid in px with acute renal failure; use with
caution px with impaired renal function
• not associated with hypokalemia
• can be given with other diuretics to lessen
the risk of hypokalemia
• SE: hyperkalemia, gynecomastia, impotence,
sterility
4. Carbonic anhydrase inhibitors
MOA: inhibit carbonic anhydrase (the enzyme
that catalyzes the reaction of CO2 and H2O
leading to H+ and HCO3 ) that can lead to the
spillage of Na+ causing diuresis.

2. Loop diuretics • limited diuretic effect (2 to 3 days)

aka: High Ceiling Diuretics • act on the proximal convoluted tubule (PCT)
ex.
high ceiling (most efficacious) as compared
Acetazolamide
with other diuretics
Brinzolamide
- act on the thick ascending Loop of Henle Dorzolamide
MOA: inhibit the Cl-Na-K- cotransporter at
the thick ascending LOH SE: metabolic acidosis, bone marrow depression
ex. (sulfonamide-like toxicity), allergic reactions
Furosemide (Stevens-Johnson’s Syndrome)
Bumetanide
Torsemide 5. Osmotic diuretics
Ethacrynic acid MOA: increase the osmotic pressure at the
proximal convoluted tubule and Loop of Henle
• for px who cannot tolerate thiazides, have preventing water reabsorption
renal impairment, or ineffectiveness of ex.
thiazides MannitoL
Sorbitol
SE: hypovolemia, ototoxicity, increase serum Urea
creatinine, Hypokalemia, –Bicarbonate is lost in the
urine, –INCREASED calcium excretion, Hypocalcemia, • used to induce forced diuresis
–Ototoxicity due to the electrolyte imbalances • mostly used to reduce intracranial pressure

SE: hypernatremia, hypovolemia

3
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Sympathoplegics - inhibits catecholamine (NE, Epi,

Dopamine, Serotonin) storage
1. Centrally-acting - impairs sympathetic function because of
decreased release of Norepinephrine
MOA: act primarily within the CNS on alpha-2
(NE)
receptors to decrease sympathetic outflow to
the CVS
ex. Guanethidine , Guanadrel
Clonidine - inhibit the response of the adrenergic
- MOA: agonist at alpha-2 receptors nerve to stimulation or to indirectly-
(leading to vasodilation) acting sympathetic amines
- effective in patients with renal - blocks the release of stored
impairment Norepinephrine
- SE: orthostatic hypotension, impaired
SE: transient increase in BP, male sexual function
sedation/depression, rebound hypertension
on abrupt withdrawal
Methyldopa 3. Alpha-1 blockers
- reduce TPR with little effect on CO and MOA: inhibit the alpha-1 receptors,
blood flow to vital organs (such as resulting to vasodilation of arteries and
kidneys) veins
- effective for patients with renal ex.
impairment Prazosin
- used in the management of HTN in Doxazosin
pregnancy (pre-eclampsia) Alfazosin
Terazosin
SE: sedation, depression, hepatotoxicity (at
doses >2g / day), (+) Coomb,s Test* • alternative drugs for the management of HTN
esp among patients with BPH
* Coomb’s Test – indicator of a possible • First-Dose Phenomenon:
immune-mediated hemolytic anemia – orthostatic hypotension
– syncope
– remedy: take the drug at bedtime, slow
Guanfacine increase in dose
- adjunctive therapy to other anti-
HTNsive drugs
- avoided unless necessary to treat 4. Beta blockers
severe refractory HTN that is
used for the initial therapy of HTN;
unresponsive to other meds
effective for patients with rapid resting HR
Guanabenz
MOA
*
o Block stimulation of renin secretion
o Decrease contractility  decrease CO
2. Peripherally-acting o Decrease sympathetic output centrally
ex. o Reduction in HR  reduced CO
Trimethaphan o Combination of all
- ganglionic receptor blocker
- given via IV infusion SE/Precautions/Contraindications:
- used in hypertensive emergencies • can mask hypoglycemia
caused by pulmonary edema or aortic • CI to patients with bronchospastic disease: COPD,
aneurism when other agents cannot be Bronchial Asthma
used • rebound tachycardia and HTN
• easy fatigability
Reserpine • severe bradycardia and heartblock (seen esp with
concomitant use of verapamil and diltiazem)
- plant alkaloid

4
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Selective Sodium Nitroprusside

B – Betaxolol - metabolized in the body into nitric oxide (NO)
B – Bisoprolol also called EDRF or Endothelium-Derived
E – Esmolol Relaxing Factor
A – Acebutolol - 1st line drug for almost all types of HTNsive
A – Atenolol emergencies
M – Metoprolol - Caution: use freshly prepared solutions or
admixtures
 Membrane Stabilizing Activity - protect from light
–
Anesthetic-like effect - SE: thiocyanate or cyanide toxicity, acute
–
Cannot be given as ophthalmic drops psychosis, severe hypotension, coma, death
P – Propranolol
P – Pindolol  Calcium Channel Blockers (CCBs)
A – Acebutolol
• alternative for the mgt of HTN
L – Labetalol
MOA – Inhibit influx of Ca through the slow
M – Metoprolol channels in vascular smooth muscle and cause
relaxation
 Mixed alpha and beta blocking effect
L – Labetalol CLASSIFICATION
C – Carvedilol o Dihydropyridine (DHP)
– block Ca channels in the blood vessels
 Intrinsic sympathomimetic activity – Nifedipine, Nicardipine, Felodipine,
- partial agonist effect not usually associated with Amlodipine
rebound hypertension o Non-dihydropyridine (Non-DHP)
– block Ca channels both in the heart
A – Acebutolol and blood vessels
– Verapamil – heart > blood vessels
B – Bisoprolol
– Diltiazem – heart = blood vessels
C – Carteolol
SE:
P – Pindolol
- peripheral edema
P – Penbutolol
- reflex tachycardia (DHP)
- bradycardia (Non-DHP)
- heart block (Non-DHP + Beta Blocker)

 Vasodilators  ACE Inhibitors

(Angiotensin Converting Enzyme Inhibitors)
common SE: reflex tachycardia, peripheral edema
MOA: inhibit ACE, thereby preventing the
common CI: as single agents, should be avoided in conversion of angiotensin I into the active
patients with Ischemic Heart Disease (IHD) form angiotensin II

ex. o Short-acting
Hydralazine –
Captopril
- used in the management of HTN in pregnancy
- SE: Lupus-like side effect (drug- induced SLE o Long-acting
or Systemic Lupus Erythematosus) –
Enalapril
–
Lisinopril
Diazoxide –
Perindopril
- used in the emergency treatment of SE:
hypertensive crisis –
idiosyncratic dry cough

Minoxidil
- most effective arteriolar vasodilator
- SE: hypertrichosis, hirsutism

5
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Angiotensin II Receptor Blockers (ARBs) 4. A pregnant patient is admitted to the hematology

 direct inhibitors of angiotensin II receptors
 Losartan, Valdesartan, Candesartan
 clinical use: same as ACE Inhibitors
Advantage over ACE inhibitors: less associated with
dry cough
service with moderately severe hemolytic anemia.
After a thorough workup, the only positive finding is a
history of treatment with an antihypertensive drug
since 2 months after beginning the pregnancy. The
most likely cause of the patient’s blood disorder is

A. Atenolol
B. Captopril
Sample Questions: C. Hydralazine
D. Methyldopa
1. A friend has very severe hypertension and asks E. Minoxidil
about a drug her doctor wishes to prescribe. Her
physician has explained that this drug is associated
with tachycardia and fluid retention (w/c may be 5. Postural hypotension is a common adverse effect of
marked) and increased hair growth. Which of the which one of the following types of drugs?
following is most likely to produce the effects that
your friend has described? A. ACE inhibitors
A. Captopril B. Alpha receptor blockers
B. Guanethidine C. Arteriolar dilators
C. Minoxidil D. Beta-selective receptor blockers
D. Prazosin E. Nonselective B-blockers
E. Propanolol

2. A patient is admitted to the emergency department

with severe bradycardia following a drug overdose.
His family reports that he has been depressed about
his hypertension. Each of the following can slow the
heart rate EXCEPT
A. Clonidine
B. Guanethidine
C. C. Hydralazine
D. D. Propanolol
E. E. Reserpine

3. Which one of the following is characteristic of

enalapril treatment in patients with essential
hypertension?
A. Competitively blocks angiotensin II at its
receptor
B. Decreases angiotensin II concentration in the
blood
C. Decreases renin concentration in the blood
D. Increases sodium and decreases potassium in
the blood
E. Decreases sodium and increases potassium in
the urine

6
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Congestive Heart Failure Compensatory Mechanism

- is the failure of the heart as a pump  Myocardial Hypertrophy
- inability of the heart to pump sufficient – long-term compensatory mechanism
amount of blood to the body – increase in the number of contractile
- pumping ability of the heart becomes elements in myocardial cells as a means
impaired of increasing their myocardial
- accompanied by congestion of body tissues performance
Etiology – ventricular remodeling
• acute MI, HPN, cardiomyopathies
• excessive work demands on the heart  Frank-Starling Mechanism
– is the intrinsic ability of the heart to
Forms of CHF adapt to changing volumes of inflowing
blood
o High-output
– the greater the heart muscle is stretched
 uncommon
during filling, the greater the force of
 caused by excessive need for cardiac output
contraction and the greater the quantity
 high metabolic demands
of blood pumped into the aorta
o Low-output
 Drugs for CHF
 caused by disorders that impair the pumping
ability of the heart (IHD)  Inotropic Agents
 normal metabolic demands, heart unable to
meet them  Cardiac glycosides
o from Digitalis species
o Right sided
 fatigue MOA: inhibit the Na-K-ATPase pump leading
 jugular vein distension to an increase in intracellular calcium
 liver engorgement - have low therapeutic indices
 anorexia, GI distress - toxicity can be enhanced by:
 cyanosis  hypokalemia
 elevation in peripheral venous pressure  hypomagnesemia
 peripheral edema  hypercalcemia
ex.
o Left-sided • Digitoxin
 paroxysmal nocturnal dyspnea – >90% Bioavailable
 cough – half-life: 168 hours
 blood-tinged sputum – >90% protein bound
 cyanosis – excreted in the bile
 pulmonary edema • Digoxin
– ~75% Bioavailable
Treatment Goals – half-life: 36-40 hours
• To remove or mitigate the underlying cause – 20-40% protein bound
• To relieve the symptoms and improve pump – excreted in the urine
function by: Toxicity
– Reducing metabolic demands (rest, • Cardiac Manifestations
relaxation, pharm’l controls) – arrhythmias (ventricular tachycardia)
– Reduce fluid volume excess (food – cardiac death
intake, meds) • Extra-cardiac Manifestations
– Administer digitalis and other – GI disturbances (nausea & vomiting)
inotropic agents – visual disturbances (blurred vision,
– Promote px compliance and self- alteration of color perception, haloes on
regulation through education dark objects)
Management of Toxicity
• give potassium supplement
• give digitalis antibodies (FAB fragments)
• for arrhythmias, give lidocaine or amiodarone

7
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Beta Agonists 2. The mechanism of action of digitalis is associated

MOA: increase intracellular cAMP, which results with
in the activation of protein kinase, that leads to A. A decrease in calcium uptake by the sarcoplasmic
an increase in intracellular calcium reticulum
ex. B. An increase in ATP synthesis
Dopamine C. A modification of the actin molecule
Dobutamine D. An increase in systolic intracellular calcium levels
• given as an IV infusion E. A block of cardiac B adrenoceptors
• primarily used in the management of acute
heart failure in the hospital setting 3. A 65-year old woman has been admitted to the
coronary care unit with a left ventricular myocardial
 Phosphodiesterase Inhibitors infarction. If this patient develops acute severe heart
MOA: inhibits the enzyme phosphodiesterase failure with mark pulmonary edema, which one of the
which hydrolyses cAMP , thereby prolonging the
following would be most useful?
action of protein kinase
ex. A. Digoxin
Amrinone B. Furosemide
Milrinone C. Minoxidil
D. Propanolol
 Unloaders E. Spironolactone
 ACE Inhibitors & ARBs
 preload and afterload unloaders
4. Drugs associated with clinically useful or
 vasodilating effect
physiologically important positive inotropic effects
 Captopril, Enalapril
include all of the following EXCEPT:
 Beta Blockers
A. Amrinone
 vasodilating effect
B. Captopril
 Metoprolol, Misoprolol, Carvedilol
C. Digoxin
 Diuretics
D. Dobutamine
 preload unloaders
E. Norepinphrine
 Spironolactone
 Vasodilators
5. Successful therapy of heart failure with digoxin will
Treating Congestive Heart Failure result in which one of the following?
A. Decreased heart rate
U – Upright Position
B. Increased afterload
N – Nitrates (low dose) C. Increased aldosterone
L – Lasix D. Increased renin secretion
O – Oxygen E. Increased sympathetic outflow to the heart
A – Aminophylline
D – Digoxin 6. Which of the following has been shown to prolong
life in patients with chronic congestive failure but has
a negative inotropic effect on cardiac contractility?
F – Fluid (decrease)
A. Carvedilol
A – Afterload (decrease) B. Digoxin
S – Sodium Restriction C. Dobutamine
T – Test (Dig Level, ABGs, Potassium Level) D. Enalapril
E. Furosemide
Sample Questions:
1. Drugs that have been found to be useful in one or 7. Which of the following is the drug of choice in
more types of heart failure include all of the following treating suicidal overdose of digitoxin?
EXCEPT:
A. Digoxin antibodies
A. Na+/K+ ATPase inhibitors
B. Lidocaine
B. Alpha-adrenoceptor agonists
C. Magnesium
C. Beta-adrenoceptor agonists
D. Phenytoin
D. ACE inhibitors
E. Potassium

8
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

• Coronary Artery Diseases (CAD) or Ischemic

Heart Diseases (IHD)
- 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

 Drugs for Angina Pectoris

Nitrates
 Myocardial Ischemia MOA: metabolized into NO in the body,
– deprivation of oxygen to a portion of leading to peripheral vasodilation
the myocardium (reversible) ex.
– amyl nitrite
 Myocardial Infarction – nitroglycerin
– severe, prolonged deprivation of – isosorbide dinitrate (ISDN)
oxygen to a portion – isosorbide mononitrate (ISMN)

SE: throbbing headache, tolerance

 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
– chest pain (px presentation)
– a symptom of myocardial ischemia in
the absence of an infarction
Types:
 Stable Angina
- aka: Classical Angina
- develops on exertion and lasts for < 5 min
- relieved with rest or drugs
- mechanism: imbalance oxygen supply
 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
Beta Blockers
• drug of choice for stable angina
MOA: decreases HR & contractility  reduce
oxygen demand (rest and during exertion) 
reduce arterial BP
Calcium Channel Blockers
MOA
– inhibits calcium influx into vascular smooth
muscle & heart muscles  increased blood
flow  enhance oxygen supply  prevent and
reverse coronary spasm
– dilates peripheral arterioles & reduce
contractility  reduce total peripheral vascular
resistance reduced oxygen demand

 Angina Decubitus Indications

- nocturnal angina – Stable angina not controlled by nitrates & beta
- occurs in recumbent position blockers; px who could not take beta blockers

 Prinzmetal Angina – Prinzmetal’s angina (with or without nitrates)

- aka: Variant Angina
- precipitated by coronary artery spasm

9
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )
Note:
Other Agents Damage on
myocardial tissue
• Morphine is not reversible.
– Unstable angina with no CI; IV doses
given after 3 sublingual nitroglycerin
tabs have failed to relieve pain
• Cellular ischemia
• Aspirin • Tissue injury
– Indefinite in px with stable or • Tissue necrosis
unstable angina
• Heparin, Enoxaparin, Dalteparin Signs and Symptoms of MI
– Together with aspirin  hospitalized • Compared to angina
px with unstable angina until – Pain persists longer
– Not relieved by rest or nitroglycerin
resolved
– Sense of impending doom, sweating, nausea,
vomiting, difficulty in breathing; some px à
Risks Factors fainting and sudden death
- Smoking – Extreme anxiety, restlessness, ashen pallor
- Hypertension
- Diabetes Mellitus • Some px:
- Males >45 yo; Females >55 yo – Mild or indigestion-like pain, manifest in
- Dyslipidemia worsening CHF, loss of consciousness, acute
- Obesity confusion, dyspnea, sudden drop in BP,
- Family history of CAD lethal arrhythmia
- Others:
–
Sedentary lifestyle, hx of chronic inflammation  Drugs for MI
 Nitrates
MOA
Etiology - Decrease oxygen demand and facilitate coronary
 Decreased blood flow blood flow
– Atherosclerosis – most common cause - converted to nitric oxide intracellularly which
– Coronary artery spasm – sustained activates guanylate cyclase  increase cGMP 
contraction of 1 or more coronary arteries dephosphorylation of myosin light chain 
 Prinzmetal’s angina or MI
relaxation of vascular smooth muscle 
– Traumatic injury – that interferes with vasodilation
blood flow in the heart
– Embolic events – can abruptly restrict Important SE
oxygen supply (bloodclot nagstuck - HEADACHE – most common side effect
up>emboli) - Tolerance (“Nitrate-free interval”)
 Increased oxygen demand - Postural hypotension, facial flushing, reflex
– Exertion and emotional stress 
sympathetic stimulation  increase HR
 Reduced blood oxygenation  Morphine
MOA
- causes venous pooling and reduces preload,
cardiac workload, and oxygen consumption
 Myocardial Infarction - IV until pain is relieved
–
Results from prolonged myocardial ischemia, Indication
precipitated in most cases by an occlusive - DOC for MI pain and anxiety
coronary thrombus at the site of a pre-existing
atherosclerotic plaque Precautions
- can produce orthostatic hypotension and fainting
- persistent, severe chest pain or pressure à - monitor for hypotension & signs of respiratory
“crushing”, “squeezing” or heavy “an elephant depression
sitting on the chest”

10
 Clarissa Grace O. Geraldino
BS Pharmacy – 3
 Oxygen
- for patients who have chest pain and who may be
ischemic
- improve oxygenation of myocardium
 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 à increased
risk of hemorrhage
 Warfarin
– reduce mortality, prevent recurrent MI
 Beta Blockers
– if administered early à- 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
 Lidocaine
– used for px who develop ventricular
arrhythmia (anesthetic agent)
 Calcium Channel Blockers
– decrease incidence of reinfarction in
px with non-Q-wave infarcts; not for
acute mgt.
Sample Questions:
11
PCOL 2 ( PhBioSci 8 )
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. Block of exercise-induced tachycardia
B. Decreased end-diastolic ventricular volume
C. Dilation of constricted coronary vessels
D. Increased cardiac force
E. Decreases heart rate
5. The major common determinant of myocardial oxygen
consumption is
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
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Arrhythmias • Five Phases: (Myocardial Action Potential)

- deviations from normal heartbeat pattern Phase 0: Rapid Depolarization
o abnormalities in impulse formation Phase 1: Early Rapid Repolarization
o conduction disturbances Phase 2: Plateau Phase of Repolarization
The heart is endowed with a specialized electrogenic Phase 3: Final Rapid Repolarization
Phase 4: Slow Depolarization
system for:
o Generating rhythmical impulses to cause
rhythmical contraction of the heart muscle
o Conducting these impulses rapidly throughout
the heart

Cardiac Conduction System

• Sinoatrial node
– Pacemaker of the heart
– 60 – 100 beats/min
– Location: posterior wall of the right atrium near
the entrance of the superior vena cava
• Atrioventricular node
– Location: posterior septal wall of the right atrium
immediately behind the tricuspid valve
– Connects the atrial and ventricular conduction
systems

• Bundle of His (AV bundle)

o Delayed transmission
- Delays in transmission provide
mechanical advantage  atria
complete ejection of blood before
initiating ventricular
Purkinje System
- Supplies the ventricles
• Has large fibers that allow for rapid conduction
and almost simultaneous excitation of the
entire left and right ventricles
• Rapid rate of ejection is necessary for the swift
and efficient ejection of blood from the heart
Myocardial Action Potential
• electric current generated by nerve and
muscle cells
Resting Membrane Potential
- membrane is relatively permeable to K+
- charges of opposite polarity become aligned
along the membrane (+) outside (-) inside
Depolarization
- cell membrane suddenly becomes selectively
permeable to current-carrying ions such as Na+
- Na+ enters cell  sharp rise of intracellular
potential to positivity while K+ migrate outside
Repolarization
• re-establishment of the resting potential
• slower process; increased permeability to K+
 K+ ions move outward  removes (+)

• involve movement or flow of electrically charges inside the cell

charged ions at the level of the cell
membrane – The Na-K pump
 helps to preserve the intracellular negativity by
moving 3

Electrocardiography (ECG)
• A recording of the electrical activity of the
heart during depolarization- repolarization
– P wave
• SA node and atrial depolarization
– QRS complex
• Ventricular depolarization
– T wave
• Ventricular repolarization

12
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

Electrocardiography (ECG) Normal ECG Pattern

• Isoelectric line between P wave & Q wave
– Depolarization of the AV node, bundle
branches, Purkinje system
• ST segment
– Absolute refractory period; part of
ventricular repolarization
• Atrial repolarization occurs during ventricular
depolarization and is hidden in the QRS
complex.
ECG Patterns of Arrhythmias
Electrocardiography (ECG)

 Anti-arrhythmic Agents

Action Potential & ECG

Cardiac arrhythmia may cause the heart to: CLASS 1A

- To beat too slowly • Slows phase 0 depolarization
- To beat too rapidly • Prolong action potential
- To respond to impulses originating from sites • Slow conduction
other than the SA node
CLASS 1B
- To respond to impulses travelling along extra
• Shortens phase 3 repolarization
pathways
• Decrease duration of action potential
CAUSES OF ARRHYTHMIA CLASS 1C
• Abnormal automaticity • Markedly slow phase 0 depolarization
• Effect of drug
• Abnormalities in impulse conduction CLASS II
• Suppresses phase 4 depolarization
Classification of Arrhythmias CLASS III
 By origin • Prolongs phase 3 repolarization
– Supraventricular arrhythmia
• Stem from enhanced automaticity of the CLASS IV
SA node or from re-entry conduction • Slows phase 4 spontaneous depolarization
– Ventricular arrhythmia • Shorten action potential
• Occur when an ectopic pacemaker triggers Miscellaneous Agents
a ventricular contraction before the SA • Adenosine
node fires • MgSO4

13
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

TYPE OF ARRHYTHMIA DRUGS Verapamil

Atrial flutter • alternative for acute SVT (Supraventricular
• Class 1 – quinidine Tachycardia) , adenosine
• Class II -propranolol
• Class IV – verapamil Adenosine
• Others - digoxin • first-line drug for acute SVT

Atrial fibrillation  Drugs for Coagulation Disorders

• 1- quinidine  Anticoagulants
• 2- propranolol  Anti-Platelet Drugs
• 3- amniodarone  Fibrinolytic Agents
• 4 – anticoagulant  Pro-coagulant Drugs

AV –NODAL REENTRY
• PROPRANOLOL Clotting Mechanism
• VERAPAMIL • inciting event: epithelial vascular injury
• DIGOXIN • followed by:
– migration of platelets to the site of injury
ACUTE SUPRAVENTRICULAR TACHYCARDIA – platelet aggregation
• Verapamil • aka: primary hemostasis
• adenosine • white thrombus
• platelet plug
ACUTE VENTRICULAR TACHYCARDIA • unstable clot
• Lidocaine – deposition of fibrin over the plug
• Sotalol – attachment of other blood cells
• Amniodarone • aka: secondary hemostasis
• red thrombus
VENTRICULAR FIBBRILLATION • stable clot
• Lidocaine  thrombus
• Bretylium - clot that adheres to a blood vessel wall
• Amnidarone
• Epinephrine  embolus
- detached thrombus

• the coagulation process that generates thrombin

Procainamide (Class IA) that is essential in the formation of fibrin used
• can cause SLE (Systemic Lupus in clot formation involves coagulation cascade
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

14
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Anticoagulants
Warfarin
Site of action MOA: blocks carboxylation of X, IX,VII,II
- synthesis of or directly against clotting • ONSET: 8 – 12 hrs maximum after 1 to 3days
factors (II, IIa) • delay in the anticoagulant effect
Types: Clinical use
 Parenteral Anticoagulants – Chronic anticoagulation (DVT prophylaxis,
cardiac thrombus, prosthetic heart valves)
Hirudin • SE:
- obtained from medicinal leeches (Hirudo • Hemorrhage
medicinalis) - Monitor PT (Prothrombin Time) and INR
- used in the management of HIT (Heparin- (International Normalized Ratio)
Induced Thrombocytopenia) - Goal for INR = 2-3
o Lepirudin – produced by recombinant DNA - <2  insufficient dose
technology - >3  x’sive dose
- With prosthetic heart valves INR goal =
Heparin 3-4
- heterogeneous mixture of sulfated - Hemorrhagic dose of the newborn
mucopolysaccharides - Teratogenic: abnormal bone formation
o Regular or Unfractionated heparin - Cutaneous necrosis
• activates antithrombin III which in turn - Purple toe syndrome
inactivates thrombin (IIa); Ixa, Xa, Xia - Alopecia, urticaria, dermatitis
• SQ/IV

o Low MW Heparin  Anti-Platelet Drugs

• Inactivates IIa and Xa  Thromboxane Synthesis Inhibitors
• Enoxaparin,fraxiparin,dalteparin - Irreversibly acetylates COX- inhibition
• SQ of TXA2 synthesis, lasts for 8 – 10 days

Clinical use Aspirin

– initiation of anticoagulant therapy • primary prophylaxis for MI
– mgt of MI or unstable angina • secondary prophylaxis for MI and
– tx & prevention of pulmonary embolism & stroke
DVT
– anticoagulation in pregnancy (APAS)  Phosphodiesterase Inhibitors
SE:
– hemorrhage (monitor aPTT – activated Dypiridamole
partial thromboplastin time) 2-2.5x or delay - given together with antiplatelet;
of 50 – 80 secs except SQ ineffective when alone
– Thrombocytopenia - Inc CAMP
- SE: coronary steal phenomenon
Contraindications:
– Hypersensitivity  ADP Inhibitors
– Active bleeding
– Thrombocytopenia Ticlopidine
– Severe HPN - SE: thrombocytopenia
– Active TB purpura,neutropenia,
- n/v,diarrhea
- Clopidogrel
 Oral Anticoagulants - safer than ticlopidine
Dicumarol
- aka: bis-hydroxycoumarin  Glycoprotein IIb/IIIa Inhibitors
- high incidence of GI side-effects ex.
- PHENPROCOUMON Abciximab
- INDANEDIONES ex: anisindione,phenindione Eptifibatide
• WARFARIN Tirofiban

15
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Fibrinolytic Agents / Thrombolytics Cholesterol Synthesis

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  Atherosclerosis
- Condition associated with cholesterol deposition
 Tissue plasminogen activator – binds to fibrin
in vascular smooth muscles (arthroma) with
bound to a clot
consequent narrowing of the lumen of the
 Anistreplase (APSAC) affected blood
 Urokinase – from the kidneys Could lead to…
– CAD
 Pro-coagulant Drugs – Cerebrovascular disease
– Mgt of bleeding disorders – Aortic disease
Vitamin K – Renal artery disease
- K1 – phytonadione (in plants, useful
clinically) Minor Risk Factors
- K2 – menaquinone (intestinal bacteria) • Chronic infection
- K3 – menadione (synthetic) • Sedentary lifestyle
- used for Vit. K deficiency; hemorrhagic • Modifiable Risk Factors
disorders in newborns • By therapy
• By lifestyle change
Aminocaproic Acid
Major Risk factors
- prevents activation of plasminogen
• Age (males: > 45; females: > 55)
- Tranexamic Acid (analogue)
• Smoking
• DM
 Dyslipidemia
• HPN
- Hypercholesterolemia (inc LDL, dec HDL)
• Dyslipidemia
- Hypertriglyceridemia (inc TG, ~ inc VLDL,
• Obesity
chylomicrons)
• Family history of premature heart attack
Liver
 Drugs for Dyslipidemia
- Only organ in the body that efficiently uses
cholesterol,  HMG-CoA Reductase Inhibitors ( “-statins” )
- Converts it to bile salts MOA: inhibit the enzyme HMG-CoA
Reductase, thereby inhibiting the first step
(rate-limiting step) in cholesterol synthesis
- first-line drugs for dyslipidemia
o Diurnal Pattern of Cholesterol Synthesis
– means that the biosynthesis of cholesterol
in the body occurs at night
– thus most statins are given at bedtime
(esp the short-acting ones)
 Short-acting
– simvastatin
– lovastatin
– fluvastatin

 Long-acting
– atorvastatin

16
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

SE: 2. A 55 y/o male patient was diagnosed to have

– hepatotoxicity uncomplicated HTN. Which of the following drugs
– myositis would most likely be given to him?
– rhabdomyolysis (muscle wasting) A. Thiazide diuretic + Beta Blocker
B. ACE Inhibitor
C. CCB + ACE Inhibitor
 Nicotinic Acid D. ACEi + ARB
- unknown MOA
3. From the list of anti-hypertensive drugs below,
- used in the management of
select the one most likely to lower blood sugar:
hypertriglyceridemia A. Prazosin
- SE: flushing (due to percutaneous B. Nifedipine
vasodilation), myositis C. Propranolol
D. Hydralazine
 Bile Acid Sequesterants E. Labetalol
- aka: Bile Acid – Binding Resins 4. Which of the following conditions predisposes a
patient taking digitalis into arrhythmia?
MOA: Inhibit reabsorption of bile acid A. hypocalcemia
- since liver must maintain a certain amount B. decreased heart rate
of bile, it will synthesize bile from C. Hyponatremia
endogenous cholesterol when bile levels D. hypokalemia
go low 5. All of the following mechanisms of action
ex. correctly match a drug, EXCEPT:
Cholestyramine A. Quinidine: blocks Na+ channels
Colestipol B. Bretylium: blocks K+ channels
SE: C. Propranolol: blocks β-receptors
- constipation D. Procainamide: Dblocks K+ channels
- impaired absorption of certain drugs 6. Which of the following adverse effects is
- may increase incidence / risk of biliary stone associated with nitrates?
formation A. nausea
B. throbbing headache
 Fibric Acid Derivatives C. sexual dysfunction
MOA: stimulate lipoprotein lipase which D. anemia
decreases triglycerides 7. A patient experienced orthostatic hypotension
after taking the first dose of her drug. She most
- first-line drug in hypertriglyceridemia likely took:
ex. A. Labetalol
Gemfibrozil B. Valdesartan
Fenofibrate C. Prazosin
Clofibrate (withdrawn) D. Digoxin
SE: 8. Mrs. G. R. is a hypertensive patient under therapy.
- myositis After some time, she developed Lupus-like
- rhabdomyolysis symptoms. Which of the ff drugs may have cause
- increase risk of bile stone formation this?
- hepatobiliary cancer (Clofibrate) A. Hydralazine
B. Losartan
C. Furosemide
 Probucol D. D. Metoprolol
MOA: anti-oxidant
9. Which of the following antagonizes the co-factor
SE: functions of Vitamin K?
- increase risk of arrhythmia A. Tranexamic acid
- produces fetid odor B. Heparin
C. Warfarin
Sample Questions:
1. Which enzyme is responsible for the conversion of D. Hirudin
Angiotensin I into the active form Angiotensin II? 10. The following drugs for dyslipidemia can cause
A. Renin rhabdomyolysis, EXCEPT:
B. ACE A. simvastatin
C. HMG-CoA B. atorvastatin
D. Streptokinase C. colestipol
D. fenofibrate

17
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

Pharmacology of the Endocrine System

The Endocrine System

 Controls many body functions
– exerts control by releasing special
chemical substances into the blood
called hormones
– Hormones affect other endocrine
glands or body systems
Endocrine Functions
 Maintain Internal Homeostasis
 Support Cell Growth
 Coordinate Development
 Coordinate Reproduction , fertility, sexual
function
 Facilitate Responses to External Stimuli Location of receptors
- On cell surface (Peptides and proteins
- In cytoplasm (Steroids)
- In nucleus (Thyroid hormones)

Sources of hormones:
Natural
Human (GH; LH & FSH; hCG);
Animal (Insulin, T3 & T4)
Biosynthetic
Insulin (Porcine & Bovine) Synthetic
Most hormones and their antagonists
DNA recombinant technology
Hormone
- A substance that is released in one tissue and Hypothalamic & Pituitary Hormones
travels through the circulation (usually) to the
target tissue.
- Hormones reach all parts of the body, but
only target cells are equipped to respond
- Hormones are secreted in small amounts and
often in bursts (pulsatile secretion)
4 Classes of Hormones
1. Peptide/ Protein (Range from 3 amino acids to
hundreds of amino acids in size. )
2. Steroid
3. Amine (Thyroid hormones and
Catecholamines)
4. Eicosanoid (Fatty acid derivatives )

The hormones fall into two general classes based on

Hypothalamus and Pituitary
their solubility in water.
Ø
The water soluble { amine (epinephrine) and The output of the hypothalamus-pituitary unit
regulates the function of the thyroid, adrenal and
peptide/protein hormones} are secreted by
reproductive glands and also controls somatic growth,
exocytosis, travel freely in the bloodstream, and lactation, milk secretion and water metabolism.
bind to cell-surface receptors.
Ø Hypothalamic Hormones can have effect of stimulating
The lipid soluble hormones { thyroid hormone,
or inhibiting the release of anterior pituitary hormones
steroid hormones and Vitamin D3}. diffuse
Called RELEASING HORMONES “RH” or INHIBITING
across cell membranes, travel in the HORMONES “IH” respectively, reflecting their
bloodstream bound to transport proteins, and influence on ant. Pit. Hs.
diffuse through the membrane of target cells .

18
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

The Pituitary Gland Diagnostic Uses of GHRH (Sermorelin)

The Pituitary Gland is divided into 2 areas, with separate To test pituitary function in patients with GH deficiency.
types of hormone production. o GH deficiency could reflect either a hypothalamic or
The anterior pituitary makes and releases hormones under a pit defect.
regulation of the hypothalamus o If the primary defect is hypothalamic, as is most
 Growth Hormone (GH) common, GHRH will elicit an increase in GH
 Thyroid-stimulating Hormone (TSH) release.
 Adrenocorticotropin (ACTH) o If the defect is at the level of the pituitary, there will
 Follicle-stimulating Hormone (FSH) ), be no increase in GH following GHRH
 Leutinizing Hormone (LH), administration.
 Prolactin
– The posterior pituitarystores and secretes hormones Therapeutic Uses of GHRH to enhance GH secretion
that are made in the hypothalamus: oxytocin and o Pulsatile subcutaneous delivery of GHRH,
antidiuretic hormone (ADH) mimicking
o the normal endogenous patterns (e.g. ~ every 3
hours)
o has been used to stimulate GH release in patients
with GH deficiency that is not of pituitary origin.n
IV, SC, intranasal

2- Somatostatin (Growth hormone-releasing

inhibiting hormone (GHRIH) :
Inhibits GH release and TSH from the ant. pituitary.
Inhibits release of most GI hormones, reduces
gastric acids and pancreatic secretion. (glucagon,
insulin & gastrin),

Therapeutic Uses Somatostatin

Somatostatin is of no clinical value because of its
short half-life (<3 min)

Octreotide, a synthetic somatostatin analogue

with a longer
duration of action

Lanreotide is much longer acting, and is

administered only twice a month.
used to treat: Acromegaly, Gastrinoma,
Glucagonoma & Other Endocrine Tumors , and
esophageal varices bleeding.
(Inhibits Mesenteric vasodilatation induced by
glucagon)
A/E: GI disturb. postprandial hyperglycemia.

3- Thyrotropin-Releasing Hormone(TRH):
Stimulates release of thyrotropin (TSH) from
the ant pit. Is used in diagnostic testing of thyroid
dysfunction e.g. Protirelin: IV

Hypothalamic Hormones: 4- Corticotropin Releasing Hormone(CRH)

1- Growth Hormone- Releasing
Hormone( GHRH):
Together with somatostatin controls release of the GH from
the ant. pit.
It is released from hypothalamus in a pulsatile fashion,
with 5-9 major pulses detected per day.
5- Gonadotropin-Releasing Hormone:(GnRH):
• GHRH release is enhanced by α2-adrenergic
agonists (e.g. clonidine) and opioids.
• GHRH release is increased by vigorous exercise.
It stimulates secretion of both ACTH & beta –
endorphin (a closely related peptide ) from the ant.
pituitary .
CRH can be used in the diagnoses of abnormalities of
ACTH secretion .
Stimulate the gonadotroph cell to produce and release
LH and FSH, Gonadorelin, Buserelin, Nafarelin

19
 Clarissa Grace O. Geraldino
BS Pharmacy – 3
GnRH agonists, SC infusion in pulses mimic
physiological GnRH, stimulates ovulation.
In contrast, steady dosing inhibits gonadotropin
release by causing down –regulation (desensitization)
of GnRH receptors in pituitary cells that normally
release gonadotropins.
GnRH is used in the diagnosis & treatment (by pulsatile
administration) of hypogonadal states in females &
males.
Continuous GnRH agonists are used in sex H-
dependent conditions: prostate & breast
cancers, uterine fibroids, endometriosis or precocious
puberty .
6- Prolactin-Inhibiting Hormone (PIH,dopamine):
Dopamine is the physiologic inhibitor of prolactin release
Because of its peripheral effects & the need for parenteral
administration, dopamine is not useful in the control of
hyperprolactinemia, but bromocrptine & other orally active
ergot –derivatives (eg. Cabergoline, pergoline) are effective
in reducing prolactin secretion from the normal glands as
well as from prolactinomas .
Also used in treatment of acromegaly
A/E: orthostatic hypotension, Psychiatric manifestations
Anterior Pituitary Hormones
 Growth Hormone
• Derived from the somatotroph cells
• Its secretion is controlled by GHRH and
somatostatin;
• GH secretion is high in newborn, deceasing at 4 yr
to an intermediate level, which is then maintained
until puberty, when there is further decline.
• Insulin-like growth factor 1 (IGF-1) released from
the liver inhibits GH secretion by stimulating
somatostatin secretion from the hypothalamus,
Growth Hormone Activity
1. Increases plasma free fatty acids (source of energy
for muscle tissue)
2. Increases hepatic glucose output
3. Decreases insulin sensitivity in muscle
4. Is protein anabolic hormone
20
PCOL 2 ( PhBioSci 8 )
Growth Hormone Deficiency
Can have a genetic basis or can be acquired as a result
of damage to the pituitary or hypothalamus by a
tumor, infection, surgery, or radiation therapy.
In childhood: short stature and adiposity,
hypoglycemia. Adults : generalized obesity, reduced
muscle mass.
GROWTH HORMONE EXCESS
Mainly benign pituitary tumor
In adults causes acromegaly,
If this occurred before the long bone epiphyses close, it
leads to the rare condition, gigantism.
Treatment of excess GH disorders:
- Synthetic Somatostatin (Octreotide)
- DA agonists (Bromocriptine)
- Surgical removal / Radiotherapy of the tumor
- GH Antagonists (Pegvisomant)
An excess of GH can cause gigantism, while a lack of GH
can cause dwarfism
Clinical uses of GH Somatotropin
 GH deficiency in children & adults.
 Children with short stature that is due to factors other
than GH deficiency:
 Idiopathic short stature, Turner syndrome, Chronic
renal failure
A/E:
Hypothyroidism, Pancreatitis, Gynecomastia, Possibilities
of abuse have also arisen, e.g. creation of “super” sports
people.
 Thyroid-stimulating Hormone (TSH)
• Also called thyrotrophin
• Stimulates secretion of thyroid hormone &
growth of thyroid gland.
Diagnostic Uses of TSH
- In patients who have been treated surgically for
thyroid carcinoma, to test for recurrence
 Adrenocorticotropin (ACTH)
• Stimulates cortisol secretion by the adrenal cortex
& promotes growth of adrenal cortex
• Diagnostic use : as a test of the capacity of the
adrenal cortex to produce cortisol;
 Follicle –stimulating hormone (FSH)
• Females: stimulates growth & development of
ovarian follicles, promotes secretion of estrogen
by ovaries.
• Males: required for sperm production
• 3 preparations are available for clinical use:
• Urofollitropin ,purified from of the urine of post
menopausal women,
• 2 recombinant forms, follitropin alpha & follitropin
beta.
• These products are used in combination with
other drugs to treat infertility in women & men.
 Clarissa Grace O. Geraldino
BS Pharmacy – 3 PCOL 2 ( PhBioSci 8 )

 Leutinizing hormone (LH) Clinical uses of oxytocin

• Females: responsible for ovulation, formation of o IV, IM
corpus luteum in the ovary, and regulation of o Induction of labor
ovarian secretion of female sex hormones. o Control of postpartum bleeding
• Males: stimulates cell in the testes to secrete o A/E :
testosterone o fetal distress, placental abruption, or uterine rupture
o excessive fluid retention
• Lutropin alfa, approved for use in combination
with follitropin alfa for stimulation of follicular
 Vasopressin (antidiuretic hormone ADH)
development in infertile women with profound LH - It is synthesized in the hypothalamus &
deficiency. transported to the post. Pit.
• The function of ADH is to increase water
 Prolactin conservation by the kidney.
• Secreted by lactotroph cells of the ant. Pit., which • If there is a high level of ADH secretion, the
increase in number during pregnancy. kidneys reabsorb water.
• Its secretion is stimulated by estrogen • If there is a low level of ADH secretion, the kidneys
• Females: stimulates breast development and milk release water in dilute urine.
production. • ADH release increases if blood pressure falls or
• Males: involved in testicular function blood becomes too salty.
• No preparation of prolactin is available for use in • ADH causes peripheral blood vessel constriction to
prolactin- deficient patients. help elevate blood pressure .
• For patients with symptomatic
Clinical uses
hyperprolactinemia, inhibition of prolactin
secretion can be achieved with dopamine  Diabetes insipidus,
agonists, which act in the pituitary to inhibit  Nocturnal enuresis (by decreasing nocturnal urine
prolactin release. production)
A/E: hyponatremia and seizures
Posterior pituitary Hormones
Synthetic ADH drugs
– Vasopressin: IV, IM
– Desmopressin: IV, IM. PO, intranasal

 Oxytocin
• It is synthesized in the hypothalamus & transported to
the post. Pit.
• It is an effective stimulant of uterine contractions & is
used intravenously to induce or reinforce labor .
• Induces the release of milk
• Suckling sends a message to the hypothalamus via the
nervous system to release oxytocin, which further
stimulates the milk glands

21