PHCA 201 ☆ Competency Enhancement & Evaluation 1

RX Medications, HPN Anti-Diabetics ☆ DOM 1

Lecturer: Tesoro, Fatima Mae
Summer ☆ S.Y. 2021-2022

If there’s no insulin, there’s no cascade of secondary

01. Physio-Pathophysio messengers, the cell cannot use the glucose and the glucose
will just stay in the bloodstream.
on Diabetes &
Great concentration of glucose, causes the kidney to filter the
Dispensing Of blood from glucose, meaning more peeing and and then ants
are more attractive to the urine.
Hypoglycemics

Lesson Outline:
● Knowledge On Endocrine System Particularly
Hormones Related To Diabetes
● Pathophysio On Diabetes
● Hypoglycemics - agents used to treat Diabetes

What is diabetes?
● Diabetes mellitus (DM) is a group of diseases
characterized by high levels of blood glucose resulting
from defects in insulin production, insulin action, or
both.
● The term diabetes mellitus describes a metabolic
disorder of multiple aetiology characterized by chronic
hyperglycemia with disturbances of carbohydrate, fat
and protein metabolism resulting from defects in insulin
secretion, insulin action, or both.
● The effects of diabetes mellitus include long-term
damage, dysfunction and failure of various organs.
● Consistent high levels of blood glucose*
Hyperglycemia - “high sugar”
● Diabetes mellitus may present with characteristic
symptoms such as thirst, polyuria (constant peeing),
blurring of vision, and weight loss.
● In its most severe forms, ketoacidosis or a non-ketotic
hyperosmolar state may develop and lead to stupor,
coma and, in absence of effective treatment, death.
● Often symptoms are not severe, or may be absent, and In the 2nd picture,
consequently hyperglycaemia sufficient to cause 1. insulin binds to the alpha insulin receptor and triggers
pathological and functional changes may be present the beta receptor..
for a long time before the diagnosis is made. 2. series of secondary messengers
● Ketotic hyperosmolar state - too much ketone bodies in 3. GLUT-4 undergoes translocation (GLUT4 will go up).
blood

Glycogen Synthesis (Glycogenesis) - sugar is stored

Diabetes - thirst - cell is starved , no insulin

Sige sige sige Gang- Sige gutom, Sige uhaw, Sige ihi
Sige filter

Pancreas releases digestive enzymes like insulin and

glucagon, which control the amount of glucose in the blood.
1. Food goes to the small intestine, villi and microvilli,
glucose go to the bloodstream, redistributed into
different organs/tissues/cells.
2. Cascade of release of secondary messengers in the
cell to trigger GLUT-4.
3. GLUT4 - transporter of glucose into the cell so that
the cell can use it.

Rx Meds CEE ☆ 01. Diabetes


Pancreas releases digestive enzymes and hormones like
insulin and glucagon
Glucose is taken in the bloodstream to be distributed all
around the body as a fuel (converted to ATP for energy)
Insulin – allows uptake of glucose to the cells
- Leaves bloodstream and into the cell, there will be a
release of secondary messengers
- Triggers GLUT-4, a transporter for glucose to enter
the cell so that the cell can use
- If capacity of insulin production is impaired, glucose
cannot enter the cell and stay in thebloodstream
- Cell is then starved even though someone has
enough glucose
- Because of great glucose concentration, kidney is
overworked will filter glucose, which explains why
diabetes patients tend to urinate frequently
Ligands – allows entry of molecules (macromolecules)
- Insulin binds to a-receptors and triggers breceptors
and trigger a cascade of reactions/messengers for
GLUT-4 to undergo translocation (more glucose
inside the cell)
- Glucose will then be used for other processes
Insulin binds to TKinase and signals molecules, which will
trigger GLUT-4 to go up for glucose to go in.
Glucose can be used for glycolysis, lipogenesis or
glycogenesis (storage).
Diabetes Long-term Effects
● Progressive development of the specific complications
of retinopathy (eyes) with potential blindness
● Nephropathy (deterioration of kidney function) that
may lead to renal failure
● Neuropathy with risk of foot ulcers, amputation
● Charcot joints
● Features of autonomic dysfunction (sexual
dysfunction)
Rx Meds CEE ☆ 01. Diabetes
● Increased risk of cardiovascular, peripheral vascular
and cerebrovascular disease
● If glucose stays in the blood, it will alter the viscosity
of blood, more pressure will be applied to move
viscous blood around
● Retinopathy - so much glucose in the blood,
insufficient insulin, glucose stays in the blood (viscous),
movement of blood is slower & cells in the body are not
receiving enough glucose.
● Renal failure because there’s not enough food for the
cells.
Burden of Diabetes
● The development of diabetes is projected to reach
pandemic proportions over the next 10-20 years.
● International Diabetes Federation (IF) data indicate
that by the year 2025, the number of people affected
will reach 333 million -90% of these people will have
Type 2 diabetes.
● In most Western societies, the overall prevalence has
reached 4-6%, and is as high as 10-12% among
60-70-year-old people.
● The annual health costs caused by diabetes and its
complications account for around 6-12% of all
health-care expenditure.
Types of Diabetes
● Type 1 Diabetes Mellitus
● Type 2 Diabetes Mellitus
● Gestational Diabetes (caused by pregnancy)
● Other types:
○ LADA
○ MODY (maturity-onset diabetes of youth)
○ Secondary Diabetes Mellitus
Type 1 Diabetes
● Was previously called insulin-dependent diabetes
mellitus (IDDM) or juvenile-onset diabetes
○ IDDM because their insulin gene is impaired
and they rely on insulin injection
○ aka Juvenile DM because it happens to young
people/genetic
● Type 1 diabetes develops when the body's immune
system destroys pancreatic beta cells, the only cells
in the body that make the hormone insulin that
regulates blood glucose.
● This form of diabetes usually strikes children and
young adults, although disease onset can occur at any
age.
● Type 1 diabetes may account for 5% to 10% of all
diagnosed cases of diabetes (meaning it is not the
common one but Type 2 DM).
● Risk factors for type 1 diabetes may include
autoimmune, genetic, and environmental factors.
● From birth, pancreas cannot produce enough insulin
● No capacity to produce sufficient insulin (are given
insulin injections)
● Pancreatic beta cells – create insulin
Type 2 Diabetes
● was previously called non-insulin-dependent diabetes
mellitus
● The commont type of Diabetes
● Type 2 diabetes may account for about 90% to 95% of
all diagnosed cases of diabetes.
● It usually begins as insulin resistance, a disorder in
which the cells do not use insulin properly. As the
need for insulin rises, the pancreas gradually loses its
ability to produce insulin.
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 ● Type 2 diabetes is associated with older age, obesity,
family history of diabetes, history of gestational
diabetes, impaired glucose metabolism, physical
inactivity, and race/ethnicity.
● African Americans, Hispanic/Latino Americans,
American Indians, and some Asian Americans and
Native Hawaiians or Other Pacific Islanders are at
particularly high risk for type 2 diabetes.
● Type 2 diabetes is increasingly being diagnosed in
children and adolescents.
○ Children are adopting a sedentary lifestyle
(i.e. video games that does not promote
physical activities, hence, glucose is not used,
causing a buildup of glucose in the body).
● Insulin Resistance - because insulin is not used well
(becomes waste), pancreas will produce more insulin
and gets overworked and eventually loses it ability to
create insulin.
Gestational Diabetes
● A form of glucose intolerance that is diagnosed in
some women during pregnancy
● Occurs more frequently among African
● Americans, Hispanic/Latino Americans,
● American Indians
● More common among obese women and women with
a family history of diabetes
● During pregnancy, gestational diabetes requires
treatment to normalize maternal blood glucose levels
to avoid complications in the infant
● After pregnancy, 5% to 10% of women with gestational
diabetes are found to have type 2 diabetes
● Women who have had gestational diabetes have 20%
to 50% chance of developing diabetes in the next 5-10
years
Secondary DM
Secondary causes of Diabetes mellitus include:
● Acromegaly,
● Cushing syndrome,
● Thyrotoxicosis,
● Pheochromocytoma
● Chronic pancreatitis,
● Cancer
● Drug induced hyperglycemia:
○ Atypical Antipsychotics - Alter receptor
binding characteristics,leading to increased
insulin resistance.
○ Beta-blockers - Inhibit insulin secretion.
○ Calcium Channel Blockers - Inhibits
secretion of insulin by interfering with
cytosolic calcium release.
○ Corticosteroids - Cause peripheral insulin
resistance and gluconeogensis.
○ Fluoroquinolones - Inhibits insulin secretion
by blocking ATP sensitive potassium
channels.
Rx Meds CEE ☆ 01. Diabetes
○ Naicin - They cause increased insulin
resistance due to increased free fatty acid
mobilization.
○ Phenothiazines - Inhibit insulin secretion.
○ Protease Inhibitors - Inhibit the conversion
of proinsulin to insulin.
○ Thiazide Diuretics - Inhibit insulin secretion
due to hypokalemia.They also cause
increased insulin resistance due to increased
free fatty acid mobilization.
Prediabetes: Impaired glucose tolerance and impaired
fasting glucose
● Prediabetes is a term used to distinguish people who
are at increased risk of developing diabetes. People
with prediabetes have impaired fasting glucose (IFG)
or impaired glucose tolerance (IGT). Some people
may have both IFG and IGT.
● IFG is a condition in which the fasting blood sugar level
is elevated (100 to 125 milligrams per decilitre or
mg/dL) after an overnight fast but is not high enough to
be classified as diabetes.
● IGT is a condition in which the blood sugar level is
elevated (140 to 199 mg/dL after a 2-hour oral glucose
tolerance test), but is not high enough to be classified
as diabetes.
● Blood sugar level indications:
○ Normal blood sugar level: < 140 mg/dL
○ Diabetes: > 200 mg/dL
○ Prediabetes: 140 to 199 mg/dL
● Progression to diabetes among those with prediabetes
is not inevitable. Studies suggest that weight loss and
increased physical activity among people with
prediabetes prevent or delay diabetes and may return
blood glucose levels to normal.
● People with prediabetes are already at increased risk
for other adverse health outcomes such as heart
disease and stroke.
Symptoms and Complications
● Always tired - glucose just stays in the blood, meaning
it did not reach the cells.
● Amputations - Wounds will heal slowly, blood clotting is
affected (thrombin will be affected by the diabetes)
● Sexual problems - penal organ is engorged with blood
vessels, brain causes the vasodilation, erects the
muscles in penis, copulation, if the person has
diabetes then the penis will not erect.
● Gangrene - no blood but full of bacteria, if not
amputated, then it will lead to sepsis
Other Important Hormones
● There are other hormones other than insulin that affect
the blood sugar levels in your body. It is important to
know about glucagon, amylin, GIP, GLP-1,
epinephrine, cortisol, and growth hormone.
● GLP-1 (glucagon-like peptide-1), GIP
(glucose-dependent insulinotropic polypeptide) and
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 amylin are other hormones that also regulate mealtime
insulin.
● Glucagon is released islet alpha cell overnight and
in-between meals.
○ Also fuels ketones in the liver
○ Released overnight and in between meals
○ Maintain sugar (balance)
○ Signals the liver to breakdown stored starch
or glycogen stores to create glucose and
ketone units
○ Both units promote breakdown of fat in the
fat cells.
○ This happens in fasted state, does not occur
if glucose is taken up through food
consumption
● For diabetic people, both in fed and fasted states, the
glucagon levels are too high.
● Incretin hormones:
1. GLP-1; and
○ GLP-1 slows down the rate at how
the food in the stomach empties,
acts on the brain to make it think that
it is full
○ So that no glycogen stores will be
used in fed state
2. GIP
- stimulate beta cells to release
insulin, and alpha cells to decrease
release of glucagon, so that
glycogen stores will NOT be used.
● Type 1 Diabetes - no beta cells to produce insulin = no
GLUT-4, GLP-1 is mulfunctioning, will keep using the
glycogen stores
● Amylin is released by the beta cell along with insulin in
the cell
○ has the same effect of GLP-1 (incretin)
○ Reduce production of glucagon in the liver
● Glucose Counterregulatory hormones
○ Epinephrine, Cortisol, Growth Hormones -
cause the blood sugar levels to rise
○ Maintain blood sugar levels
○ Epinephrine (adrenaline) - released on the
nerve endings
○ Promotes breakdown of fat nutrients which
can be converted to sugars and ketones
○ Cortisol (from Adrenal glands)– steroid, stress
hormone, adrenal gland makes the cell
resistant to insulin = increases sugar level
Rx Meds CEE ☆ 01. Diabetes
Values of Diagnosis of DM
If you exceed the values, you have Diabetes.
Prevention or delay of diabetes:
1. Life style modification
● Research studies have found that lifestyle
changes can prevent or delay the onset of
type2diabetes among high-risk adults.
● These studies included people with IGT and
other high-risk characteristics for developing
diabetes.
● Lifestyle interventions included diet and
moderate-intensity physical activity(such as
walking for 2 1/2 hours each week).
● In the Diabetes Prevention Program, a large
prevention study of people at high risk for
diabetes,the development of diabetes was
reduced 58% over 3 years.
2. Medications
● Studies have shown that medications have
been successful in preventing diabetes in
some population groups.
● In the Diabetes Prevention Program,people
treated with the drug metformin reduced their
risk of developing diabetes by 31% over 3
years.
● Treatment with metformin was most effective
among younger, heavier people (those 25–40
years of age who were 50 to 80 pounds
overweight) and less effective among older
people and people who were not as
overweight.
● Similarly,in the STOP-NIDDM Trial,treatment
of people with IGT with the drug acarbose
reduced the risk of developing diabetes by
25% over 3 years.
● Other medication studies are ongoing.In
addition to preventing progression from IGT to
diabetes, both lifestyle changes and
medication have also been shown to increase
the probability of reverting from IGT to normal
glucose tolerance.
● Initial treatment for pre-diabetic and young
diabetic people - metformin
Management of Diabetes
A. Diet and Exercise
Diet
● Diet is a basic part of management in every
case.Treatment cannot be effective unless adequate
attention is given to ensuring appropriate nutrition.
● Dietary treatment should aim at:
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 ○ ensuring weight control in those who are intolerant to
○ providing nutritional requirements metformin.
○ allowing good glycaemic control with blood 4. If monotherapy fails, acombination of
glucose levels as close to normal as possible TZDs, acarbose and metformin is
○ correcting any associated blood lipid recommended.
abnormalities 5. If targets are still not achieved,insulin
secretagogues may be added.
The following principles are recommended as dietary guidelines
for people with diabetes: Acarbose - absorption of sugar is small
● Dietary fat should provide 25-35%of total intake of Metformin - has dual purposes:
calories but saturated fat intake should not exceed 1. reduces the sugar
10%of total energy. 2. manages the weight
● Cholesterol consumption should be restricted and
limited to 300mg or less daily. B.2 Combination Oral Agents
● Protein intake can range between 10-15%total energy ● Combination oral agents is indicated in:
(0.8-1g/kg of desirable body weight). Requirements 1. Newly diagnosed symptomatic
increase for children and during pregnancy.Protein patients with HbA1c>10
should be derived from both animal and vegetable 2. Patients who are not reaching
sources. targets after 3 months on
● Carbohydrates provide 50-60% of total caloric content monotherapy
of the diet. Carbohydrates should be complex and high
in fibre. B.3 Combination Oral Agents and Insulin
● Excessive salt intake is to be avoided.It should be ● If targets have not been reached after optimal
particularly restricted in people with hypertension and dose of combination therapy for 3 months,
those with nephropathy. consider adding intermediate-acting/long
acting insulin (BIDS).
Exercise ● Combination of insulin+oral anti-diabetic
● Physical activity promotes weight reduction and agents(BIDS)has been shown to improve
improves insulin sensitivity, thus lowering blood glycaemic control in those not achieving
glucose levels. target despite maximal combination oral
● Together with dietary treatment,aprogramme of regular anti-diabetic agents.
physical activity and exercise should be considered for ● Combining insulin and the following oral
each person.Suchaprogramme must be tailored to the anti-diabetic agents has been shown to be
individual's health status and fitness. effective in people with type2diabetes:
● People should,however,be educated about the 1. Biguanide (metformin)
potential risk of hypoglycaemia and how to avoid it. 2. Insulin secretagogues
(sulphonylureas)
B. Oral Anti-Diabetic Agents 3. Insulin sensitizers(TZDs) (the
● There are currently four classes of oral anti-diabetic combination of a TZD plus insulin is
agents: not an approved indication)
1. Biguanides 4. α-glucosidase inhibitor (acarbose)
2. Insulin Secretagogues- Sulphonylureas ● Insulin dose can be increased until target
3. Insulin Secretagogues - Non-sulphonylureas FPG is achieved.
4. a-glucosidase inhibitors
5. Thiazolidinediones (TZDs) Diabetes Management Algorithm

B.1 Oral Agent Monotherapy

● If glycaemic control is not
achieved(HbA1c>6.5% and/or;FPG>7.0
mmol/Lor;RPG>11.0mmol/L) with lifestyle
modification within 1-3 months,ORAL
ANTI-DIABETIC AGENT should be initiated.
● In the presence of marked hyperglycaemia in
newly diagnosed symptomatic
type2diabetes(HbA1c>8%,FPG>11.1
mmol/L,or RPG>14 mmol/L),oral anti-diabetic
agents can be considered at the outset
together with lifestyle modification.
Monotherapy - 1 drug therapy (usually for pre-diabetic)
● As first line therapy:
1. Obese type2 patients,consider use
of metformin, acarbose or TZD.
2. Non-obese type2 patients, consider
the use of metformin or insulin
secretagogues.
3. Metformin is the drug of choice in
overweight/obese patients.TZDs and
acarbose are acceptable alternatives

Rx Meds CEE ☆ 01. Diabetes 5

Oral Hypoglycaemic Medications ● In some cases,amixture of short- and
intermediate-acting insulin may be given in the
morning.Further doses of short-acting insulin are given
before lunch and the evening meal and an evening
dose of intermediate-acting insulin is given at bedtime.
● Other regimens based on the same principles may be
used.
● A regimen of multiple injections of short-acting insulin
before the main meals, with an appropriate dose of an
intermediate-acting insulin given at bedtime, may be
used,particularly when strict glycaemic control is
mandatory.

Overview of Insulin and Action

General Guidelines for Use of Oral Anti-Diabetic Agent in

Diabetes
● In elderly non-obese patients,short acting insulin
secretagogues can be started but long acting
Sulphonylureas are to be avoided. Renal function
should be monitored.
● Oral anti-diabetic agentsare not recommended for
diabetes in pregnancy.
● Oral anti-diabetic agents are usually not the first line
therapy in diabetes diagnosed during stress,such as
infections. Insulin therapy is recommended for both the
above
● Targets for control are applicable for all age groups.
However, in patients with co-morbidities, targets are
individualized.
● When indicated,start withaminimal dose of oral
anti-diabetic agent, while reemphasizing diet and
physical activity. An appropriate duration of time (2-16
weeks depending on agents used) between increments
should be given to allow achievement of steady state
blood glucose control
● Elderly - have deteriorating kidneys, sulfonylureas
might cause complications for their kidneys

C. Insulin therapy
1. Short-term use:
● Acute Illness, surgery,stress and emergencies
● Pregnancy
● Breast-feeding
● Insulin may be used as initial therapy in type 2
diabetes
● in marked hyperglycaemia
● Severe metabolic decompensation (diabetic
ketoacidosis, hyperosmolar nonketotic coma,
lactic acidosis, severe hypertriglyceridaemia)
2. Long-term use:
● If targets have not been reached after optimal
dose of combination therapy or BIDS,consider
change to multi-dose insulin therapy.When
initiating this,insulin secretagogues should be
stopped and insulin sensitisers e.g. Metformin
or TZDs, can be continued.
● Long-term insulin therapy if the combination
therapy does NOT work.
Insulin regimens
● The majority of patients will require more than one
daily injection if good glycaemic control is to be
achieved. However, a once-daily injection of an
intermediate acting preparation may be effectively used
in some patients.
● Twice-daily mixtures of short- and intermediate-acting
insulin is a commonly used regimen.
D. Self-Care
● Patients should be educated to practice self-care. This
allows the patient to assume responsibility and control
of his/her own diabetes management. Self-care should
include:
- Blood glucose monitoring
- Body weight monitoring
- Foot-care
- Personal hygiene
- Healthy lifestyle/diet or physical activity
- Identify targets for control
- Stopping smoking
● Twin study:
"Non-identical twins generally share 50 per
cent of their DNA and it is usually said that identical
twins share 100 per cent of theirs. Despite this, we
found 1400 places on the identical twins' DNA
where there was a difference in DNA methylation
between the diabetic and the non-diabetic. It is
believed that these differences are due to

Rx Meds CEE ☆ 01. Diabetes 6

 differences in lifestyle and this confirms the theory
that type2 diabetes is strongly linked to lifestyle."
Identical twins are proof that genes alone
are not enough. However, identical twins have
identical genes; therefore, they should have the
same genetic risk foradisease-right? Not
necessarily. Research has found that if one identical
twin has type1 diabetes, the other twin will get the
disease about 50 percent of the time. For type2
diabetes, that risk rises to as much as 4 in 5. In both
type1 and type2, identical twins havea much higher
risk of both developing diabetes than non-identical
(fraternal) twins,which further supports the fact that
genetics is involved.

The Future of Diabetes Treatment:

Regenerating Human Beta Cells

Nathalie Fiaschi-Taesch, PhD |Icahn School of Medicine at

Mount Sinai |BasicScience Award (Funded for 3 years at
$345,000)

Both type 1 and type 2 diabetes result from a

complete or partial loss of beta cell number and function.
Thus, from a therapeutic standpoint, activating the Multiple
approaches to beta cell replacement have been developed,
including: regeneration of an individual's own beta
cells,induction of human beta cells from stem cells,
reprogramming of beta cells from other differentiated cell
types,use of nonhuman beta cell sources (pig or non-human
primate islets), and,finally,expansion of human beta cells
from deceased donors. Regardless of the origins,there is a
clear need for more beta cells for cell replacement therapies
for diabetes.

Rx Meds CEE ☆ 01. Diabetes 7

 PHCA 201 ☆ Competency Enhancement & Evaluation 1
RX Medications, HPN Anti-Diabetics ☆ DOM 1
Lecturer: Tesoro, Fatima Mae
Summer ☆ S.Y. 2021-2022

02. Hypertension

1. Know mechanisms of blood pressure regulation and

cardiovascular pathophysiology which chronically
increase blood pressure(Review).
1. Understand types and etiologies of major forms of
clinical hypertension
2. General treatment strategy for hypertension.
3. Know major classes of anti-hypertensive agents,their
general sites and mechanisms of action.
4. Identify specific,widely used,antihypertensive
agents,sites of action,mechanisms of action,indications
and contraindications.
5. Understand strategies for hypertension management
Mechanisms Controlling CO and TPR
associated with other pathologies.
1. These organ systems and mechanisms control physical
factors of CO and TPR
Blood Pressure > 140/90 mm Hg (Mercuric millimeters)
2. Therefore, they are the targets of antihypertensive therapy.
volume that pump in the blood = stroke volume
1. Primary or Essential Hypertension
- cause of hypertension is unknown
Heart is controlled by heart rate and stroke volume
2. Secondary Hypertension
TPR is the pressure.
- hypertension that results from an identifiable cause
- renal disease (Renin-Angiotension System is already
damaged) Physiological Factors Controlling Hypertension
- adrenal hyperfunction(Sympathetic Adrenergic A. Cardiac Output is the amount of blood that is pumped
System) out of the heart per minute.
CO is determined by the heart rate and
stroke volume.
B. Peripheral Resistance is the resistance or friction
generated by the flow of blood through the arteries.
This resistance is commonly increased by
vasoconstriction.
Vasoconstriction and rise in blood pressure
are results of sympathetic NS activity.

Hypertension: The Silent Killer

Hypertension- asymptomatic
Morbidity and mortality due to end organ damage

Determinants of Arterial Pressure

(blood pressure you are measuring in hypertension)
Change any physical factors
controlling Cardiac Output (CO) and/or
Total Peripheral Resistance (TPR) and MAP can be
altered.
Determinants: Stroke volume and Blood Pressure
RENIN - ANGIOTENSIN SYSTEM
Brain (sympathetic system) influence
1. Calcium influx triggers the release of norepinephrine.
2. Beta-1 receptors and norepinephrine combine.
3. Kidneys will release renin.
4. Renin is released in the blood/juxtaglomerular cells.
5. Renin circulates the Angiotensinogen in the blood
Rx Meds CEE ☆ 02. Hypertension
8
 6. Angitensinogen undergo PC or proteolytic cleavage - weight gain
(split) to form decapeptide (angiotensin 1 which is a - Tachycardia
mild vasoconstrictor = causes Vasco Epithelium - hirsutism
constriction = increase TPR slightly), - hyperthyroid symptoms menstrual
7. Angiotensin1 will release Angiotensin Converting irregularities
Enzyme (ACE). - skin changes or depression for
8. ACE converts angiotensin1 to angiotensin 2. From Cushings
Decapeptide to Octopeptide. Angiotensin 2 is an
intensive vasoconstrictor = effect is an increase in the ● Past medical history of
TPR, release hormone aldosterone [adrenal glands] - cardiac disease
which asks for sodium [Na+] and water [H2O] - neurological disease
reabsorption) - renal disease
9. Blood volume rises - Diabetes Milletus
10. Venous return
11. Stroke volume and heart rate increase, thus increasing ● Current meds (prescription and OTC)
Cardiac Output ● Social history(smoking, alcohol, exercise)
● Diet (lipids, sodium)
Increase in aldosterone will lead to sodium and water ● Psychosocial/environmental
reabsorption = blood volume rises. Because there will then be ● Family history (of Htn, CVA, high lipids or DM)
an increase in venous return, increase in stroke volume, will ● High lipids
make heart pump faster or increase in heart rate, it will ● Weight change
eventually lead to an increase in cardiac output. ● Gout

Secondary Hypertension These may be used as pharmaceutical care

Underlying Causes of Hypertension: protocol parameters.
1. Cushing's Syndrome
2. Renal damage/disease General Treatment Strategy of Hypertension
3. Renal Stenosis 1. Diagnosis - 3-6 independent measurements.
4. Pheochromocytoma 2. Determination of primary vs. secondary hypertension.
5. ischemia 3. If secondary, treat underlying pathology.
6. Hypersecretion of aldosterone 4. If primary, initiate lifestyle changes:
7. Eclampsia a. smoking cessation
8. Drug-Induced b. weight loss
● NSAIDs c. diet
● steroids d. stress reduction
● appetite suppresants e. less alcohol
● MAO inhibitors f. etc.
● nasal decongestants 5. Pharmacological treatment.
● oral contraceptives
● cyclosporine Goal - normalize pressure- decrease CO and/or TPR
● tricyclic anti-depressants Strategy- alter volume,cardiac and/or VSM function

Treatment: Treat the underlying cause

Pharmacological Treatment
Essential Hypertension Classes of Antihypertensive Agents
Predisposing factors: 1. Diuretics
1. Age-40 years old&above;increases with age 2. Peripheral α-1 Adrenergic Antagonists
2. Sex-male;post menopausal women 3. Central Sympatholytics (α-2 agonists)
3. Family History of 4. β-Adrenergic Antagonists
- essential hypertension 5. Anti-angiotensin II Drugs
- Stroke 6. Ca ++ Channel Blockers
- cardiac disease 7. Vasodilators
- Dyslipidemia, hyperlipidemia
4. Patient History 1. Each designed for specific control system
- intermittent elevation in blood pressure 2. Often used in combination
- diabetes mellitus
5. High dietary intake of saturated fats
6. High dietary intake of sodium 1. Diuretics
7. Obesity - increases urine output
8. Sedentary lifestyle
9. Smoking a. Thiazides
10. Stress hydrochlorothiazide (HydroDIURIL, Esidrix);
chlorthalidone(Hygroton)
Pharmacologic Treatment: aims to lower blood pressure to b. Loop diuretics
prevent life-threatening complications furosemide (Lasix);
bumetadine (Burmex);
ethacrynic acid (Edecrin)
Initial Evaluation of a Patient with Hypertension c. K+Sparing
A. History: amiloride (Midamor);
● Past history of hypertension spironolactone (Aldactone);
- how long triamterene (Dyrenium)
- how high d. Osmotic
- how treated mannitol (Osmitrol);
urea (Ureaphil)
● Drugs used e. Others
- success Combination - HCTH + triamterene (Dyazide)
- side effects acetazolamide (Diamox)
● Symptoms suggesting 2⁰ Hypertension: Diuretics only increase urination.
- sweating attacks

Rx Meds CEE ☆ 02. Hypertension 9

 Increase water and sodium secretion. a. Thiazide and Thiazide-like Diuretics

(-azide & -azone)

Examples:
- Hydrochlorothiazide
- Bendroflumethiazide
- Benzthiazide
- Chlorothiazide
- Cyclothiazide
- Metolazone
- Quinethazone
- Chlorthalidone

Special Precautions:
1. Monitor K+ depletion(decreases along with
Na+and Mg ++)
- increase dietary intake or use
K*-sparing diuretics
2. Monitor state of hydration
3. May enhance uric acid retention (significant in
patient w/gout)
4. May increase blood glucose (significant in
patient w/ diabetes)
5. May cause allergy to patients w/ known
allergy to sulfa drugs
6. May cause fatigue, headache, palpitations,
rash, vertigo & transitory impotence
7. Ineffective if Cr>2.5

Site of Action Contraindications:

Renal Nephron 1. Patients taking digoxin
2. Patients with chronic arrythmias, acute
Mechanism of Action myocardial infarction or left ventricular
↑Urinary Na+excretion dysfunction
↑Urinary water excretion 3. Diabetes mellitus because diuretics may
impair glucose tolerance
↓Extracellular Fluid and/or Plasma Volume 4. Patients with gout because diuretics increase
uric acid levels
Effect on Cardiovascular System 5. May increase serum lipid concentrations
↓Acute decrease in CO 6. May cause magnesium depletion

↓Chronic decrease in TPR, normal CO May be taken in lower doses

↓Mechanism(s) unknown to reduce adverse effects.

Adverse Reactions b. Loop Diuretics

dizziness,
Special Precautions:
electrolyte imbalance/depletion,
1. Monitor K+depletion
hypokalemia,
- increase dietary intake or use
hyperlipidemia,
K+-sparing diuretics
hyperglycemia (Thiazides)
2. Monitor state of hydration
gout
3. May enhance uric acid retention
- significant in patient w/gout
Contraindications
4. May increase blood glucose
hypersensitivity,
- significant in patient w/ diabetes
compromised kidney function
5. May cause allergy to patients w/ known
cardiac glycosides (K+effects)
allergy to sulfa drugs
hypovolemia,
6. May cause fatigue, headache, palpitations,
hyponatremia
rash, vertigo & transitory impotence
7. Ineffective if Cr>2.5
Electrolyte depletion because potassium goes out with
sodium during drug action.
c. Potassium-sparing Diuretics
Should NOT be given to people with prior kidney
malfunctions because diuretics overwork the kidneys.
Specific Action:
- enhance Na+ excretion while retaining K+ in
Therapeutic Considerations
the distal tubule
Thiazides (most common diuretics for HTN)
Generally start with lower potency diuretics
Examples:
Generally used to treat mild to moderate HTN
- Spironolactone
Use with lower dietary Na+intake,
- Amiloride
and K+supplement or highK+food
- Triamterene
K+Sparing(combination with other agent)
Used in combination with hydrochlorothiazide;
Loop diuretics (severe HTN, or with CHF)
Prevents cardiac risks of Hetz.
Osmotic (HTN emergencies)
They reabsorb potassium, however the secretion of
Maximum antihypertensive effect reached before
sodium is not much, hence they are paired with
maximum diuresis - 2nd agent indicated.
thiazide diuretics.

Rx Meds CEE ☆ 02. Hypertension 10

 Special Precautions: they do NOT bind with the alpha-1 receptors.
1) Retention of K+ may aggravate acute renal
failure. It should be avoided or used with
caution in patients with acute renal failure or
impaired renal function. Adverse effects
2) Monitor serum electrolytes, blood urea Nausea; drowsiness;
nitrogen (BUN) and serum creatinine to postural hypotension
assess renal function. 1st dose syncope
These signal incipient hyperkalemia.
3) Triamterene should not be used in patients Contraindications
with a history of liver disease or kidney Hypersensitivity
stones.
4) Salt substitutes should be used with caution Therapeutic Considerations
no reflex tachycardia; small 1st dose;
Thiazide Loop K-sparing does not impair exercise tolerance
Diuretic Diuretics Diuretics useful with diabetes, asthma, and/or
hypercholesterolemia
Drug of choice For patients who used in
use in mild to moderate hypertension
for mild to •are unable to tolerate thiazide combination with often used with diuretic,ß antagonist
moderate • have hypertension due to renal thiazides to
Hypertension insufficiency or low glomerular minimize K+ loss
and normal renal filtration rate or to maintain K+ 3. Central Sympatholytics (a-2 Agonists)
and cardiac • have pulmonary edema in balance (Drugs: clonidine [Catapres], methyldopa [Aldomet])
function congestive heart failure

2. Peripheral α-1 Adrenergic Antagonist

(Drugs: prazosin [Minipres]; terazosin [Hytrin])

Site of Action
peripheral arterioles,smooth muscle

Site of Action
CNS medullary
cardiovascular centers

Clonidine: direct a-2 agonist

Methyldopa: "false neurotrans"

Mechanism of Action
CNSa-2 adrenergic stimulation
Peripheral sympathoinhibition
Major mechanism/site of Sympathetic Nervous
Decreased norepinephrine release
System control of blood pressure.
Effects on Cardiovascular System
Mechanism of Action
Decreased NE → vasodilation → Decreased
Competitive antagonist ata-lreceptors on
TPR
vascular smooth muscle.
Stimulation of a-2 receptors in the medulla decreases peripheral
sympathetic activity, reduces tone,
vasodilation and decreases TPR.

They directly cause sympathoinhibition.

They block the release of norepinephrine.
Causing vasodilation.
Emergency Hypertensive Crisis ONLY = Clonidine (Catapres)
Pregnant and Hypertensive = Methyldopa

Adverse Effects
dry mouth;sedation;impotence;

Contraindications
Effects on Cardiovascular System Therapeutic Considerations
Vasodilation, reduces peripheral resistance generally not 1st line drugs;
methyldopa drug of choice for pregnancy
Blocking a-receptors on vascular smooth muscle prolonged use -- salt/water retention, add
allows muscle relaxation, dilation of vessel, diuretic
and reduced resistance. Rebound increase in blood pressure
They control the constriction.
They block the norepinephrine so that

Rx Meds CEE ☆ 02. Hypertension 11

4. ß-Adrenergic Antagonists (Beta Blockers) 2. Do not stop B-blocker therapy abruptly.It may
(Drugs: propranolol [Inderal]; metoprolol cause withdrawal syndrome that may
[Lopressor]; atenolol [Tenormin]; nadolol produce:
[Corgard]; pindolol [Visken]) a) anginal attacks
Sites of Action b) MI
c) increase in blood pressure
3. Should be used with caution in patients with:
a) diabetes because it can mask
hypoglycemic symptoms
b) neurologic disorders because it can
aggravate fatigue,weakness or
mental depression
Mechanism of Action c) asthma and COPD
competitive antagonist at ß-adrenergic
4. May cause impotence and decreased libido
receptors
5. Monitor serum lipids because the drug can
alter lipid levels
Effects on Cardiovascular System
Cardiac -- ↓HR, ↓SV = ↓CO
Renal-- ↓Renin→ ↓Angiotensin = ↓ TPR b. Postganglionic Adrenergic Neuron Blockers

Adverse Effects Special Precautions:

impotence; bradycardia; 1. Must not be used in patients with a history of
fatigue; exercise intolerance depression
2. Must not be used in patients with peptic ulcer
Contraindications because of possible increase in gastric acid
asthma; diabetes; bradycardia; secretion
hypersensitivity 3. Warn patient about possible drowsiness,
dizziness, weakness, sleep disturbances,
Therapeutic Considerations nasal congestion
Selectivity
a. Nadolol (Corgard) non selective, but
20 hr 1/2 life 5. Anti-Angiotensin II Drugs
b. Metoprol (Lopresor) B-1selective, - Inhibits Angiotensin II Formation
3-4 hr 1/2 life
Risky in pulmonary disease even selective
B-1,
Available as mixed a/ß blocker
Available - labetalol (Trandate, Normodyne)
Use post myocardial infarction- protective
Use with diuretic- prevent reflex tachycardia

a. Beta-adrenergic blockers

(-olol)

Examples:
Atenolol *Tenormin start at 25-50 mg
Propanolol *Inderal qd, may increase up
Labetalol to 100 mg qd
Penbutolol
Metoprotol
Succinate *Lopressor, Betazok
Tartrate *Betaloc, Cardiosel,
Acebutolol Neobloc
Bisoprolol
Nadolol *Concore
Esinolol *Corgard
Carvedilol
Betaxolol *Dilatrend
Timolol *Kerlone
Carteolol
Effects on Cardiovascular System
Pindolol *Visken
↓ Volume (Aldosterone, Vasopressin)
↓ Cardiac Output

Indications: ↓ Heart Rate / SV (Angiotensin II,

1. For patients with rapid resting heart rates or Norepinephrine)
angina ↓ Sympathetic Nervous System
2. For post-MI patients ↓ Cardiac Output

Special Precautions:
↓ Angiotensin II (Vasoconstriction)
1. Monitor for signs of increasingly reduced
cardiac output w/e may lead to congestive ↓ Sympathetic Nervous System
heart failure ↓ Total Peripheral Resistance

Rx Meds CEE ☆ 02. Hypertension 12

 a. ACE Inhibitors Indications:
- Same as ACE inhibitors but especially for
(-pril) patients who can not tolerate the coughing
effect of ACE inhibitors.
Examples:
-Captopril *Capoten 25 and 50 General Mechanism of Action:
*Primace mg-requires bid - prevents the activation of the angiotension II
dosing receptor by blocking the receptor site,in effect:
-Perindopril *Coversyl a) it blocks the vasoconstrictor effect of
-Enalapril *Renitec angiotensin II
-Quinapril b) it prevents the secretion of
-Accupril aldosterone from the adrenal glands
-Imidapril *Norten *Vascor
-Ramipril *Tritace
Lisinopril *Zestril 6. Ca ++ Channel Blockers
-Trandolapril Drugs: verapamil (Calan);
-Cilazapril *Vascase nifedipine (Procardia); diltiazem (Cardizem);
-Moexipril amlodipine (Norvasc)
-Fosinopril
-Benazepine Examples:
-Diltiazem *Cardize 180&240 mg tabs,up to 360 mg qd
Indications: -Nicardipine m
1. For Type 1 diabetics with renal damage. ACE
inhibitors decrease BP but do not affect -Isradipine
glucose levels. -Nisoldipine
2. For hypertension that result from increased -Dihydropyridines
renin level
Amlodipine 2.5,5,and 10 mg tabs given qd)
3. For patients with left ventricular dysfunction
Felodipines *Norvasc 2.5,5&10 mg tabs,usual dose 5-10
4. For patients with chronic renal disease
5. For patients with CHF and proteinuria mg qd
Nifedipine(Procardia 30&60 mg tabs,up to 90 mg qd
Special Precautions: ) 420-240 mg qd up to 240
1. Close monitoring if given to patients with renal -Verapamil
insufficiency or autoimmune disease
a. Neutropenia may occur
b. Proteinuria may occur
c. Hyperkalemia may occur
2. Dry cough is experienced by patient
3. Rashes, GI disturbances, headache, fatigue
4. Women of child bearing age

ACE inhibitors = dry coughing (induce stress) = suggest going

back to their doctor, switch to angiotensin2 receptor blockers
because they are uncomfortable with ACE inhibitors.
ACE inhibitors should NOT be given to pregnant women.

Additional Pharmacare Note

● Discontinue or reduce dose of diuretic before
starting ACE inhibitors.
● Drug of choice: Lisinopril Site of Action
- start at 5-10 mg QD Vascular smooth muscle
- generally up to 20 mg QD although
some will need up to 20 mg bid. Mechanism of Action
Blocks Ca ++ channel
decreases/prevents contraction
b. Angiotensin II Receptor Antagonist
Effect on Cardiovascular system
(-sartan) Vascular relaxation
Decreased TPR
Examples:
-Losartan *Cozaar 25-100 mg OD
-Eprosartan 7. Vasodilators
-Telmisartan *Micardis, Pritor Drugs: hydralazine (Apresoline); minoxidil(Loniten)
Irbesartan = also used for hair growth;
-Valsartan Nitroprusside (Nipride); diazoxide (Hyperstat I.V.);
Candesartan cilexetil Fenoldopam (Corlopam)

ACE + NSAID = Diminished antihypertensive Site of Action

Inhibitors effect vascular smooth muscle

Mechanism of action
+
ACE + K sparing = increased K level
Inhibitors diuretic

These mean that we should NOT partner NSAIDs

and K-sparing diuretics with ACE Inhibitors.

Rx Meds CEE ☆ 02. Hypertension 13

 3. May develop thiocyanate and /or cyanide
toxicity with long term use

d. Diazoxide

Specific Action:
- relaxes vascular smooth muscles decreasing
peripheral resistance

Special Precautions:
1. Use with caution in patient with diabetes
because it produces transient hyperglycemia
2. Start with low dose
General Mode of Action: 3. Do not use in patients with impaired cerebral
- act directly on vascular smooth muscles to or cardiac function
cause relaxation resulting in vasodilation and
decrease in blood pressure

Examples: Indication:
● Hydralazine Vasodilators should be used
● Minoxidil only in hypertensive
● Nitroprusside emergencies!
● Diazoxide

a. Hydralazine

Special Precautions:
1. Should not be used alone because it can
increase plasma renin activity, cardiac output
& heart rate as compensatory reactions.

Use in combination with a

● beta-blocker
● central alpha-agonist or SUMMARY OF ANTIHYPERTENSIVE AGENTS
● diuretic
Sites and Mechanisms of Action
2. May cause angina
3. May induced systemic lupus erythematosus Brain / CNS Medullary
and rheumatoid arthritis with long term use ● alpha-2 agonists

Heart
● Beta-blockers
b. Minoxidil Artery / Peripheral arterioles
● Alpha-antagonist
Specific Action: ● Angiotensin 2 - antagonist
1. Relaxes vascular smooth muscles decreasing ● Vasodilators
peripheral resistance ● Ca ++ antagonist
2. Decreases renal vascular resistance
Kidney
Special Precaution: ● Diuretics
1. Should not be used alonc because it can ● beta-blockers
increase plasma renin activity, cardiac output
& heart rate as compensatory reactions.
Other - ACE inhibitors Lungs, VSM, Kidney, CNS
Use in combination with a
● beta-blocker 1. Can alter CO/TPR at number of sites
● central alpha-agonist or and/or mechanisms.
● Diuretic 2. Anthypertensives mechanistically
specific, and alter blood pressure
2. Wam patient of hypertrichosis through psychologically diverse
3. May produce myocardial ischemia and effects on CO/TPR.
pericardial effusion 3. All organ systems and/or effector are
_______ of targets.
c. Nitroprusside
Hypertension Treatment Strategy With Some Common
Specific action: Co-Existing Conditons
1. Relaxes wascular smooth muscles deseasing
peripheral resistance Heart Falure
● ACE inhibitors
Special Precautions: ● Diuretics
1. Start with low dose gradually imcreasing dose
until desired effect is achieved to prevent Myocardial Intarction
abrupt lowering of BP ● Beta-blockers
2. Protect from light, Discard discolored ● ACE inhibitors
solutions

Rx Meds CEE ☆ 02. Hypertension 14

Diabetes
● ACE Inhibitors
● AVOID-beta-bleckers

Isolated systolic hypertension (Older persons)

● Diuretics preferred
● Calcium channel antagonist

Renal insufficiency
● ACE Inhibitors

Angina
● B-blocker
● Calcium channel antagonists

Asthma
● Calcium channel blockers
● AVOID-beta-blockers

Hypertensive Agents

Each class of antihypertensive agent:

1. has as specific mechanism of action,
2. acts at one or more major organ systems,
3. on a major physiological regulator of blood pressure
4. reduces CO and/or TPR to lower blood pressure,
5. has specifio indications, contraindications, and
therapeutic advantages and disadvantages associated
with the mechanism of action

Baroreflexes

1. MAP = set point

2. Reflexes defend set point
a. Arterial Baroreflexes
b. Pressure/Natriuresis
3. Change in MAP opposed by reflex response to
maintain set pressure
4. Hypertension- pressure resets to higher level-defended
by reflex systems.

Multiple therapies often needed

to block reflex compensation.

Rx Meds CEE ☆ 02. Hypertension 15

Rx Meds CEE ☆ 02. Hypertension 16