Chronic kidney disease is a broad term that includes subtle called azotemia, which can cause general symptoms
neral symptoms like It
decreases in kidney function that develop over a minimum of 3
months.
acute kidney injury (AKI) refers to any deterioration in kidney
function that happens in <3 months.
Kidney’s job
● regulate what’s in the blood
● remove waste
● make sure electrolyte levels are steady
● regulate the overall amount of water,
● and even make hormones
Blood gets into the kidney through the renal artery, and once
inside it goes into tiny clumps of arterioles called glomeruli where
it’s initially filtered, and the filtrate which is the stuff that gets
filtered out, moves into the renal tubule. The rate at which this
filtration takes place is known as glomerular filtration rate or
GFR.
NORMAL RATE: 100-120 mL/min/1.73m^2
Note:
● The value is slightly less in women than
men
● the value decreases slowly in all of us as
we grow older.
Common causes of chronic kidney disease
● Hypertension. In hypertension, the walls of arteries
supplying the kidney begin to thicken in order to
withstand the pressure, and that results in a
narrow lumen(less blood & oxygen -> kidney =
ischemic injury to the nephron’s glomerulus)
Immune cells like macrophages and fat-laden
macrophages(foam cells) slip into the damage
glomerulus and start secreting growth factors like
Transforming Growth Factor ß1 or TGF-ß1. These
growth factors cause the mesangial cells to regress
back to their more immature stem cell state
known as mesangioblasts(secrete extracellular
structural matrix). This excessive extracellular matrix
leads to glomerulosclerosis, hardening and scarr,
and diminishes the nephron’s ability to filter the
blood - over time leading to chronic kidney
disease.
● Diabetes, excess glucose in the blood starts
sticking to proteins in the blood — a process called
non-enzymatic glycation. Affects the efferent
arteriole and causes it to get stiff and more
narrow - a process called hyaline arteriosclerosis.
This creates an obstruction that makes it difficult for
blood to leave the glomerulus, and increases
pressure within the glomerulus leading to
hyperfiltration. In response to this high-pressure state,
the supportive mesangial cells secrete more and
more structural matrix expanding the size of the
glomerulus. Over many years, this process of
glomerulosclerosis, diminishes the nephron’s
ability to filter the blood and leads to chronic
kidney disease.
Other systemic diseases
● Lupus
● Rheumatoid arthritis
● HIV
● Long-term use NSAIDs
● Toxins (tobacco)
Now, normally urea in the body gets excreted in the urine, but
when there’s a decreased glomerular filtration rate, less urea get
filtered out, and therefore it accumulates in the blood, a condition
nausea and a loss of appetite. As the toxin levels really build up,
they can affect the functioning of the central nervous system -
causing encephalopathy. This results in asterixis, a tremor of the
hand that kind of resembles a bird flapping its wings and is best
seen when the person attempts to extend their wrists. Further
accumulation of these toxins in the brain can even progress to
coma and death. The buildup of toxins can also cause
pericarditis which is inflammation of the lining of the
heart. In addition, there can be increased tendency for bleeding,
since excess urea in the blood makes platelets less likely to stick
to each other, and so there’s less clot formation.
Uremic frost, urea crystals can deposit in the skin and they
look like powdery snowflakes.
In addition to getting rid of waste, the kidneys play an important
role in electrolyte balance. Potassium levels are particularly
important, and normally the kidney helps with potassium
excretion. In chronic kidney disease, just like with urea, less
potassium is excreted and more builds up in the blood, and it
leads to hyperkalemia, which is worrisome because it can cause
cardiac arrhythmias. Another key role of the kidneys relates to
balancing calcium levels. Normally, the kidney helps to activate
vitamin D which helps to increase absorption of calcium from the
diet. In chronic kidney disease, there’s less activated vitamin D,
so less calcium is absorbed into the blood, resulting in
hypocalcemia - low calcium levels. As calcium levels in the blood
falls, parathyroid hormone is released, causing the bones to lose
calcium. Over time, this resorption of calcium from the bones
leaves them weak and brittle, a condition known as renal
osteodystrophy. The kidneys also release key hormones. For
example, normally when the kidneys start sensing a lower than
normal amount of fluid getting filtered, they respond by releasing
the hormone renin to increase the blood pressure. In chronic
kidney disease, the falling glomerular filtration rate leads to more
and more renin secretion which leads to hypertension. Now,
remember that hypertension is a cause of chronic kidney disease
itself, so this creates quite the vicious cycle. The kidney also
secretes the hormone erythropoietin which stimulates the
production of red blood cells from the bone marrow. In chronic
kidney disease, erythropoietin levels fall and this leads to
lowered production of red blood cells, and ultimately
anemia. Ultimately the diagnosis of chronic kidney disease
comes down to looking at changes in the glomerular filtration
rate over time.
Chronic kidney disease might be suspected
● GFR of less than 90 ml/min/1.73 m2
● irreversible kidney damage might happen with a
GFR below 60 ml/min/1.73 m2.
To confirm the diagnosis
● Kidney biopsy can be done to look for changes like
glomerulosclerosis.
Treatment for chronic kidney disease
● dialysis
● kidney transplant
KEY POINTS:
Chronic kidney disease is when the glomerular filtration rate
(GFR) <90 ml/min/1.73 m2 over at least 3 months.
Mainly caused
● Diabetes
● Hypertension
Complications
● electrolyte abnormalities
● accumulation of toxins in the body
● hypertension
● bone abnormalities.
Chronic Kidney Disease
CLINICAL PHARMACY LECTURE
Presented by: Marielle Lianne B. Agustin
Marie Rose P. Badoc
Archie Ryan Jay A. Bonghanoy
Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Objectives
Describe the primary etiological factors contributing to the
1 development of CKD, including hypertension, metabolic,
glomerular and lower urinary tract diseases.

Identify common clinical manifestations of CKD, including fluid

2 retention, electrolyte imbalances, and uremia.

Discuss the importance of routine screening for CKD using

3 laboratory tests.

Determine comprehensive patient education and supportive care

4 strategies to enhance patient understanding of CKD
 ROAD MAP

Etiology
Pathophysiology

CHRONIC Clinical
Manifestations
KIDNEY
DISEASE Diagnosis
Treatment
Patient Care

Case Study
Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Introduction
C hronic kidney disease (CKD) is defined by
a reduction in the glomerular filtration
rate (GFR) and/or urinary abnormalities or
structural abnormalities of the renal tract. The
severity of CKD is classified from G1 to G5
depending upon the level of GFR.

The prevalence of chronic kidney disease (CKD) increases

with age and is greater in females and some ethnic
populations.
Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Introduction The GFR is defined as the volume

of filtrate produced by the glomeruli of
both kidneys each minute and is a
reliable indicator of renal function.
GFR = 100-120 ml/min/ 1.73 m2
slightly less in women
Normal Average
GFR = 125 ml/min
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Classification
of Chronic
Kidney
Disease
(CKD)

Stage G1–G3
CKD is common
and may not cause
symptoms.
As CKD becomes
more advanced
(stage G4 and G5),
virtually all body
systems are
adversely affected.
Chronic Kidney Disease Acute Kidney Disease
the presence of kidney damage or sudden decline in glomerular
decreased GFR for greater than 3 filtration rate (GFR) (less than 3
months (months to years) months)

common causes are diabetic common causes are acute tubular

nephropathy, hypertension, necrosis, pre-renal disease, and
glomerulonephritis, polycystic kidney urinary tract obstruction
disease, and nephrotoxin exposure

clinical signs are DO NOT APPEAR UNTIL

clinical signs are IMMEDIATE
LATER STAGES of the disease

treament DEPENDS on the severity of the requires EMERGENCY treatment

disease

has NO CURE may disappear completely

 CKD EPI equation was
first published in 2009 and
is now recommended in
the UK and elsewhere for
reporting eGFR. This
equation is the most
accurate equation.

Some laboratories are

still reporting this
equation.

Creatinine Clearance is time-consuming, The Cockroft–Gault equation uses weight,

inconvenient, prone to inaccuracy and sex and age to estimate ClCr and was
now is rarely used in clinical practice. derived using average population data.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

The reduction in renal function observed in CKD is often a

Etiology patchy process, resulting from damage to the infrastructure of the
kidney in discrete areas rather than throughout the kidney.

A renal
damage can
Etiology occur due to
Ischaemic/hypertensive various underlying
renal disease causes.
Metabolic diseases This causes
Chronic ‘bystander’
glomerulonephritis damage with
Lower urinary tract secondary
disease nephron loss.
Hereditary/congenital
diseases
Unknown cause MECHANISM OF PROGRESSIVE RENAL DAMAGE
 Objectives Introduction Etiology Pathophysiology
Manifestations
Ischaemic/Hypertensive
Renal Disease
Ischaemic nephropathy was traditionally
referred to as under-per fusion of the kidneys
caused by renal artery stenosis. This term is now
used for impairment of renal function caused by
vascular disease distal to occlusion of the main
renal arteries.
Metabolic Diseases
Diabetes mellitus (1/3 of patients) is the most
common metabolic disease that causes CKD. The
predominant lesion is glomerular and is referred to
as diabetic nephropathy or diabetic kidney
disease, but a kidney biopsy hasn’t performed to
confirm the diagnosis.
Clinical Diagnosis Treatment Patient Care Case Study
Chronic Glomerulonephritis
Glomerulonephritis is a term that is used to
describe the process of inflammation of the
glomerulus. Chronic glomerulonephritis causes
around 15% of cases of advanced CKD in which
the most common is IgA nephropathy.
IgA nephropathy is by the deposition of
polymeric IgA in the glomerulus with subsequent
immune activation.
Lower Urinary Tract Disease
Represents 5–10% of all cases of CKD. They
include the following conditions: reflux disease,
renal stone disease, chronic pyelonephritis and
extrinsic renal tract obstruction.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Hereditary/Congenital Diseases Uknown Cause

Represents 5% of CKD cases. They make up a The cause of CKD is unknown in around 30% of
higher proportion of cases of ESRD. The more patients, who typically present with small kidneys
common inherited conditions are APKD and and unremarkable immunological investigations.
Alport’s syndrome.

Autosomal dominant polycystic kidney disease

is an inherited condition which results in the
formation of multiple cysts in both kidneys
throughout life. The kidneys become enlarged and
frequently fail in middle age.
Alport’s syndrome is a disorder of glomerular
basement membranes caused by a mutation
affecting type IV collagen; X-linked, autosomal
dominant and autosomal recessive forms of
inheritance are all seen.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Pathophysiology
I. Electrolyte Abnormalities May not effectively remove excess electrolytes.

II. Water Imbalance It may result to fluid volume overload or edema

III. Uremia Inability to maintain to remove waste products

IV. Hormone Imbalances Hormone production and regulation may be

disrupted
V. Metabolic Acidosis Buildup of acid in the body and metabolic acidosis

VI. Albumin Regulation The kidneys may leak albumin into the urine due to
damage to the glomeruli, leading to a condition
called albuminuria.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Pathophysiology
RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM (RAAS)

It has a critical role in the progression of CKD, and an

awareness of this system is important for understanding the
pathophysiology of CKD and the targets for therapeutic
intervention.
Renin is an enzyme which is formed and stored in the
juxtaglomerular apparatus.

In patients with CKD, intra-renal pressures are often low,

and sympathetic overactivity is common.

ATII has two major physiological functions: (1) promote

production of the mineralocorticoid hormone aldosterone;
(2) vasoconstrictor
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Clinical Manifestation

Polyuria and Nocturia Haematuria

Polyuria in CKD is linked to medullary damage, ADH
insensitivity, and high serum urea (>40 mmol/L). Impaired
urine concentration and modified physiological
nocturnal antidiuresis in advanced CKD lead to nocturia,
causing patients to wake overnight to urinate.
Haematuria, blood in urine, indicates renal or lower urinary
tract issues. Active urinary sediment may include
blood/protein. Use a near-patient dip test promptly to avoid
red cell lysis. Consider and exclude infection through white
cell quantification.

Proteinuria and Albuminuria Hypertension

Proteinuria, primarily albuminuria, is diagnosed when
urine protein levels exceed a set threshold. About 70% of
proteinuria is albuminuria, a crucial marker for classifying
chronic kidney disease.
Hypertension is common in CKD, accelerating renal
damage. Sodium retention causes volume-dependent
hypertension, often salt-sensitive. RAAS is activated in
reduced kidney perfusion. Treating hypertension slows CKD
progression.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Clinical Manifestation

Uremia Bone Disease (Renal Osteodystrophy)

Uraemia refers to the clinical manifestation of the
accumulation of small molecules in CKD. In patients with
ESRD, some of the molecules responsible for the toxicity of
uraemia are intermediate in size between small, readily
dialysed molecules and large, non-dialysable proteins.
•Secondary hyperparathyroidism
•Osteomalacia (reduced mineralisation)
•Mixed renal osteodystrophy (both hyperparathyroidism
and osteomalacia)
• Adynamic bone disease (reduced bone formation and
resorption)

Anemia Neurological Changes

Anemia is common in stages G4 and G5 CKD, developing
gradually with declining renal function. Hemoglobin levels
drop to around 80 g/L by ESRD, showing a normochromic,
normocytic pattern. The primary cause is peritubular cell
damage, leading to inadequate erythropoietin secretion.
The most common neurological changes are nonspecific
and probably caused by uraemic toxins; they include
poor concentration, memory impairment, irritability and
stupor
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Clinical Manifestation

Electrolyte Disturbances
The kidneys play such a crucial role in the
maintenance of volume, extracellular fluid
composition and acid–base balance,
disturbances of electrolyte levels are common in
CKD.

Sodium, Potassium, and Hydrogen ions

Muscle Function
Muscle symptoms are probably caused by
general nutritional deficiencies and electrolyte
disturbances, notably of divalent cations and
especially by hypocalcaemia.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Diagnosis
Blood test
Urinalysis
Abdominal ultrasound
X-Rays
Kidney Biopsy
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Diagnosis Changes in GFR overtime

Less than 90 mL / min / 1.73 m²

Irreversible kidney damage

Less than 60mL/ min / 1.73m²

Biopsy
Look for GLOMERULOSCLEROSIS
Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

INDICATION DRUG MOA

ACE inhibittor reduce circulating ATII, and ARBs block binding to the ATII receptor.

Calcium Channel blocker:

reduce Ca2+ influx into vascular muscle cells, causing vasodilation.
Nifedipine Amlodipine

Diuretics: Furosemide inhibit the Na+/K+/2Cl- co-transporter

reduction in renin production, leading to decreased levels of

β-Blockers:Atenolol Metropolol
HYPERTENSION
angiotensin II and aldosterone.

Centrally Acting Drugs

Methyldopa stimulates the central inhibitory α-adrenergic receptors .

Selective α1-
blockers:Vasodilators opening adenosine triphosphate‐sensitive potassium channels in
Hydralazine, Minoxidil vascular smooth muscle cells.
 INDICATION DRUG MOA

Metoclopramide ,Prochlorperazine inhibition of D2 receptors, stimulation of presynaptic

GASTRO-INTESTINAL
Ondansetron excitatory 5-HT4 receptors

bind to the alpha-2-delta subunit of voltage-gated calcium

PRURITUS Gabapentin and Pregabalin
channels in neurons.

IV Iron supplementation interacts directly with the EPO receptor on the red blood cell
ANEMIA
Erthropoetin (RBC) .

Sodium Bicarbonate(1-6 g/day)

ACIDOSIS increasing plasma bicarbonate levels.

facilitating the binding of the inhibitory neurotransmitter GABA

NEUROLOGICAL PROBLEMS Clonazepam
.

Calcium acetate, Sevelamer,

OSTEODYSTROPHY
Lanthanum, Desferrioxamine (4–6 g binding with the phosphate in the food you eat.
:HYPERPHOSPHATAEMIA
in 500 mL of saline 0.9% per week)

VITAMIN D DEFICIENCY AND stimulates intestinal calcium (Ca) absorption, increases urinary
Alfacalcidol, Calcitriol
HYPERPARATHYROIDISM Ca excretion and serum Ca levels.
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Non-Drug
Therapies
Dietary
Modification
LOW-PROTEIN
DIETS
SODIUM
RESTRICTION
POTASSIUM
RESTRICTION

Common
therapeutic
problems in
chronic renal
failure
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Immunosuppres-
sants commonly
used following
renal
transplantation
Drug
 Objecti es Introduction Etiolog Pathoph siolog Clinical Diagnosis Treatment Patient Care Case Stud
Manifestations
IMPLEMENTATION OF REGULAR
DIALYSIS TREATMENT 2 Main Types: Haemodialysis and Peritoneal dialysis

Peritoneal dial sis Haemodial sis

P eritoneal dial sis offers

continuous treatment ith
H emodial sis is
another crucial
options like continuous modalit in the
ambulator peritoneal dial sis treatment of in CKD.
(CAPD) and automated It in ol es the use of a
peritoneal dial sis (APD). machine, kno n as a
hemodial zer.
In CAPD, a fle ible catheter is Controls blood
placed in the abdominal ca it . pressure and maintain
Maintains dial sate in the abdomen the proper balance of
24 hours a da . On the other hand, fluid and arious
minerals — such
APD emplo s a c cler machine for as potassium and
o ernight e changes. sodium .
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Patient care
5 Stages of CKD
Stage 1 - with normal or high GFR (GFR > 90 mL/min)
Stage 2 - Mild CKD (GFR = 60-89 mL/min)
Stage 3A - Moderate CKD (GFR = 45-59 mL/min)
Stage 3B - Moderate CKD (GFR = 30-44 mL/min)
Stage 4 - Severe CKD (GFR = 15-29 mL/min)
Stage 5 - End Stage CKD (GFR <15 mL/min)
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Patient care
Stage 1
and Adequate fluid balance
Stage 2
Slowing down the
decline in kidney
function
Prevent complications
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Patient care

Stage 3 Blood abnormalities

corrected
Calcium
supplementation
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Patient care

Stage 4
Prepare for Renal
replacement therapy
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Patient care

Stage 5
Prepare for Renal
replacement therapy
Consider kidney
transplantation
Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations
 Objectives Introduction Etiology Pathophysiology Clinical Diagnosis Treatment Patient Care Case Study
Manifestations

Case Study
Mr D, a 19-year-old undergraduate student, visited his university
health centre describing a 3-month history of fatigue, weakness, nausea
and vomiting that he had attributed to ‘examination stress’. His medical
history indicated an ongoing history of bed wetting from an early age.
Laboratory results from a routine blood screen showed the following:
CLINICAL PHARMACY: HTN NOTES
HYPERTENSION: Pathophysiology
Hypertension
- Defined as either a sustained systolic
blood pressure of greater than 140
mmHg or a sustained diastolic blood
pressure of greater than 90 mmHg
- Hypertension results from increased
peripheral vascular arteriolar smooth
muscle tone.
- In other words, hypertension is a state of
elevated blood pressure which is the
pressure exerted on the walls of arteries.
Systolic blood pressure
- The blood pressure during systole or
myocardium contraction.
Diastolic blood pressure
- The blood pressure during diastole or
myocardium relaxation
Classification of the blood pressure
1. Normal blood pressure
- Lesser than 120 for the systolic
and lesser than 80 for the
diastolic
2. Prehypertension
- 120 to 139 for the systolic or
from 80 to 89 for the diastolic
3. Stage 1 hypertension
- 140 to 159 for the systolic or
from 90 to 99 for the diastolic
4. Stage 2 hypertension
- Equals to or greater than 160
for the systolic or equals to or
greater than 100 for the
diastolic
Chronic hypertension
- can lead to heart disease and stroke
- It is also an important risk factor in the
development of chronic kidney disease
and heart failure.
Hypertension may occur secondary to other
diseases but more than 90% of patients have
essential hypertension that happens with no
identifiable cause.
There are some risk factors, family history of
hypertension increases the chance to develop
hypertension:
a. Older ages diabetes
b. Obesity
c. Smoking
d. Alcohol consumption
e. Stressful lifestyle
f. High dietary intake of sodium
Organs that control blood pressure
- Heart
- Blood vessels
- Kidney
- Lungs
- Liver
Two major processes control these organs to
work in harmony and control blood pressure:
- the borrow receptors in the sympathetic
nervous system
- the arena angiotensin aldosterone
system.
Three processes increase the blood pressure:
1. increasing cardiac output
2. increasing peripheral resistance
3. increasing blood volume
A fall in blood pressure causes pressure
sensitive neurons in the aortic arch and carotid
sinuses that are called baroreceptors to send
fewer impulses to cardiovascular centers in the
spinal cord.
- This prompts a reflex response of
increased sympathetic and decreased
parasympathetic output to the heart and
vasculature resulting in:
CLINICAL PHARMACY: HTN NOTES

- Activation of beta-1 adrenoceptors in the increased renal sodium

heart = increasing cardiac output reabsorption and
increased blood volume
- Activation of alpha-1 adrenoceptors in which contribute to a
the blood vessels = vasoconstriction further increase in
leading to a compensatory rise in blood blood pressure
pressure
- These effects of
- The kidneys control the blood volume angiotensin II are
- Simply when blood pressure mediated by stimulation
falls the kidneys release the of angiotensin II type 1
enzyme renin leading to a at1 receptors
series of events that increase - Categories of the drugs
blood pressure. that are used for
hypertension either they
- There are also baroreceptors in work as
the kidneys they respond to: - sympatholytics
- Reduced arterial to decrease the
pressure; and sympathetic
- To sympathetic activity
stimulation of beta-1 - interfere with
adrenoceptors in the renin-angiotensi
kidneys by releasing the n system
enzyme renin - diuretics to
- Low sodium decrease blood
intake and volume.
greater sodium
loss HYPERTENSION: Causes, symptoms,
- Increase renin diagnosis, etc.
release
Most of the time blood pressure is taken in the
- Renin converts angiotensinogen brachial artery in your upper arm because of
which is synthesized in the liver the pressure's high there it's probably high
and secreted in plasma to throughout all of the arteries
angiotensin 1 which is
converted to angiotensin 2 in the High blood pressures can significantly increase
lungs in the presence of your risk for developing heart disease
angiotensin converting enzyme
ace
- Angiotensin II is a potent
circulating vasoconstrictor
constricting both arteries and
veins increasing peripheral
resistance and blood pressure
- angiotensin II also
stimulates aldosterone
secretion leading to
CLINICAL PHARMACY: HTN NOTES
Typically both systolic and diastolic pressures
tend to climb or fall together.
Sometimes you can have systolic or diastolic
hypertension when one number's normal and the
other is really high this is referred to as:
- Isolated systolic hypertension
- Isolated diastolic hypertension
high blood pressure is a serious problem for the
blood vessels because it causes wear and tear on
the endothelial cells that line the inside of the
blood vessels that can lead to serious problems;
- Myocardial infarctions
- Aneurysms
- Strokes
90% percent of the time hypertension happens
without a clearly identifiable underlying reason
and we call this primary hypertension or
essential hypertension
Risk Factors:
- Old age
- Obesity
- Salt heavy diets
- Sedentary lifestyles
Note: With the exception of age all of these can
be improved with lifestyle changes and those
changes can help reduce hypertension.
10% of the time though there is a specific
identifiable underlying condition that's the cause
of hypertension and we call this secondary
hypertension.
Causes of Hypertension:
- Low renal blood flow
- Atherosclerosis
- Vasculitis
- Aortic dissection
Kidneys play a super important role in blood
pressure regulation when not enough blood flows
to the kidney the kidney secretes the hormone
renin which ultimately helps the kidneys retain
more water that water contributes to more blood
in the arteries making them more full which leads
to higher pressures.
Other diseases can also cause secondary
hypertension:
- Fibromuscular dysplasia which affects;
- Young women can cause the
walls of the large and
medium-sized arteries to thicken.
If it involves the renal artery and limits blood
flow to the kidneys it triggers more renin.
Another example:
- Tumor that produces excess aldosterone
and just like renin this leads to fluid
retention
Hypertensive crisis
- It involves a systolic pressure greater
than 180 millimeters of mercury or a
diastolic pressure greater than 120
millimeters of mercury
- hypertensive crisis can be further split
into:
- hypertensive urgency - there
hasn't yet been damage to end
organs like the brain, kidneys,
heart, and lungs
- hypertensive emergency -
there has been shown to be
evidence of damage to end
organs
Symptoms:
- Primary hypertension isn't actually
accompanied by any symptoms which is
why it's sometimes referred to as a silent
killer
- Secondary hypertension might involve a
variety of symptoms associated with the
underlying cause
CLINICAL PHARMACY: HTN NOTES

- Hypertensive emergency might involve

symptoms like confusion, drowsiness,
chest pain, and breathlessness.

Treatment:
1. Lifestyle changes (first choice)
- diet
- exercise
- stress reduction

2. Anti-hypertensive medications
HYPERTENSION
Clinical Pharmacy Lecture
Group 2: Baisac, Canada, Cirera
 LEARNING OBJECTIVES

To understand the To recognize the risk To implement

etiology and factors, complications effective
pathophysiology of and clinical management and
hypertension manifestations of treatment
hypertension strategies
 HYPERTENSION
- a condition in which blood pressure
(BP) is elevated to a level likely to lead to
adverse consequences.

- particularly above 140/90 mmHg.

- leading risk factor for death worldwide

(WHO).
 ETIOLOGY, PATHOPHYSIOLOGY,
CLINICAL MANIFESTATION AND DIAGNOSIS
 ETIOLOGY, PATHOPHYSIOLOGY,
CLINICAL MANIFESTATION AND DIAGNOSIS
 ETIOLOGY
Essential hypertension precise etiology = currently
unknown.

Genetic factors account for about 1/3 of the BP

variation between individuals.

Common in black people of African or Caribbean

family origin.

Other factors: ↑ salt / ↑ alcohol intake / obesity

 PATHOPHYSIOLOGY

Hypertension:
-chronic ↑ BP → end-organ damage
-↑ morbidity and mortality
- CO x SVR = BP
CLINICAL MANIFESTATION
 DIAGNOSIS OF HYPERTENSION

Validated manual or automated sphygmomanometer

 TREATMENT
Non-pharmacologic approaches for HTN
Important aspect of treatment
First-line strategy in people with stage 1
hypertension at low risk of cardiovascular events

Lifestyle advice:
- weight loss discussion - diet & physical activity
- salt, alcohol, smoking cessation
 TREATMENT
Non-pharmacologic approaches for HTN
Dietary Approaches to Stop Hypertension (DASH)
Regular physical activity should be encouraged
↓ Alcohol intake, ↓ smoking or smoking cessation

Low-risk S1: lifestyle approaches (recommended)

S2 & severe: non-pharmacological interventions
should be parallel with drug therapy initiation
 TREATMENT
Non-pharmacologic approaches for HTN
 TREATMENT
Drug Treatment
Treatment thresholds for HTN
- guide healthcare decisions in managing BP effectively.
 TREATMENT
Target blood pressure
TREATMENT
TREATMENT
TREATMENT
 PATIENT CARE
1. Medication Adherence
2. Healthy lifestyle
a. lessen salty foods, and fatty foods
3. Weight management
a. excercise regularly
4. Reduce stress
5. Monitor BP and regular doctor visits
6. Avoid tobacco and limit alcohol
7. Know emergency signs
CASE STUDY 1
Mr PT, a 35-year-old man, is overweight and has a
blood pressure of 178/108 mmHg. He smokes 25
cigarettes daily and drinks 28 units of alcohol per
week. He has a sedentary occupation. He eats
excessive quantities of saturated fat and salt. Mr
PT subsequently stopped smoking and lost some
weight but remained hypertensive. He was treated
with atenolol 50 mg daily. His blood pressure fell to
136/84 mmHg, but he developed tiredness and
bradycardia and complained of erectile impotence
QUESTIONS:
1. What is the likely diagnosis?

- Mr. PT is experiencing hypertension, or high blood

pressure, along with related problems and risk
factors such as cardiovascular illnesses. He further
suffered from bradycardia, erectile dysfunction,
and fatigue as adverse effects of the medicine
atenolol.
QUESTIONS:
2. What complications does Mr. PT’s high blood
pressure place him at increased risk of?

- Mr. PT's high blood pressure increases his risk of

cardiovascular diseases, kidney disease, peripheral
artery disease, vision loss, and erectile dysfunction. It
strains his heart and arteries, leading to heart attack
and stroke. It can also cause kidney failure, peripheral
artery disease, vision loss, and genital dysfunction.
QUESTIONS:
3. Should he receive drug treatment? If so, with which drug,
and if not, how should he be managed?

- Given Mr. PT's medical history and the side effects of

atenolol, losartan, an angiotensin II receptor blocker (ARB),
would be the most appropriate course of treatment. ARBs
decrease the progression of renal disease in people with
hypertension by lowering blood pressure, having fewer
adverse effects, and having renoprotective benefits. ARBs
also lower the chance of cardiovascular events and death in
people with hypertension.
CASE STUDY 2
Mrs KB, a 23-year-old woman, has a normal blood
pressure (118/82 mmHg) when reviewed at 8 weeks
of pregnancy. In the 24th week of pregnancy, she is
reviewed by her midwife and found to have a blood
pressure of 148/96 mmHg. Urinalysis is normal.
QUESTIONS:
1. What is the likely diagnosis?

- Mrs KB may have gestation-induced

hypertension or chronic hypertension that had
previously been masked by the fall in blood
pressure that happens in early pregnancy.
QUESTIONS:
2. What complications does Mrs. KB’s high
blood pressure place her at increased risk of?

- She is at increased risk of pre-eclampsia

and intrauterine growth retardation.
QUESTIONS:
3. Should she receive drug treatment? If so, with which drug, and if not,
how should she be managed?

- There are differences of opinion between specialists as to whether

blood pressure should be treated at this level during pregnancy. In
favour of treatment is the substantial rise over the earlier blood
pressure recording. Some specialists would not treat unless the blood
pressure was greater than 170/110 mmHg or other compli- cations
were present, but NICE (2010) recommends intervention if the BP is
greater than 150/100 mmHg. If Mrs KB was treated, methyldopa would
be a suitable choice. In any event, Mrs KB requires close monitoring of
her blood pressure, urinalysis and fetal growth.
CONGESTIVE HEART FAILURE VIDEO REVIEWER
BY: CIRERA
CONGESTIVE HEART FAILURE
 A point at which the heart can’t supply
enough blood to meet the bodies
demand.
2 WAYS
SYSTOLIC HEART FAILURE
 Ventricles can’t pump hard enough
DIASTOLIC HEART FAILURE
 Can’t fill enough blood
In both cases blood backs up into the lungs
causing CONGESTION or Fluid buildup
CONGESTIVE HEART FAILURE
 Affects millions of people
 May lead to death
 ISCHEMIA + VALVULAR DISEASE
SYSTOLIC HEART FAILURE
 Can’t pump hard enough
 (vol. blood/minute) = cardiac output
(heart rate) = number of beats per
minute x stroke volume per beat
Stroke volume is only a fraction of the total
volume
Stroke volume/ Total volume = ejection
fraction
EJECTION FRACTION
Normal: 50% - 70%
Borderline: 40% - 50%
Systolic heart failure: < 40%
DIASTOLIC HEART FAILURE
 Heart is squeezing hard enough but not
filling enough
ABNORMAL FILLING
 Reduced “preload”
o Is the volume of blood in the
ventricle right before the
ventricle muscle contracts
FRANK-STARLING MECHANISM
 It is the important relationship between
systolic and diastolic function.
Heart failure can affect the right ventricle
(Right-sided HR) or the left ventricle (Left-sided
HR) or even both
BIVENTRICULAR HEART FAILURE
 It is when both left and right ventricle is
affected.
CONGESTIVE HEART FAILURE VIDEO REVIEWER
BY: CIRERA
LEFT-SIDED HEART FAILURE (Blood to Lungs) so thinned out that it causes systolic
left-sided heart failure.
 Usually systolic (pumping) dysfunction
 Due to the damage to MYOCARDIUM
o Can’t contract forcefully and
4. DIASTOLIC HEART FAILURE OR FILLING
pump blood efficiently
DYSFUNCTION
CAUSES
Concentric hypertrophy (sarcomere) less
1. ISCHEMIC HEART DISEASE room for filling  Diastolic heart failure
 caused by coronary artery
5. AORTIC STENOSIS
atherosclerosis or plaque buildup is the
 Narrowing of the aortic valve opening
most common cause

6. HYPERTROPHIC CARDIOMYOPATHY
 Abnormal ventricular wall thickening
2. LONG –STANDING HYPERTENSION often from a GENETIC cause
 is another common cause of heart
failure 7. RESTRICTED CARDIOMYOPATHY
 Arterial pressure increases in the  Heart muscle gets stiffer and less
systemic circulation it gets harder for compliant  left ventricle can’t stretch
the left ventricle to pump blood out out and fill  Diastolic Heart Failure
into that hypertensive systemic
circulation, to compensate the left
ventricle bulks up (MUSCLE
Decreased blood flow to the Kidneys 
HYPERTROPHY) or grows so that the
activates the renin-angiotensin aldosterone
ventricle can contract more force. The
system (RAAS)  fluid retention  filling &
increasing muscle mass also means
increases preload  increases contraction
there is greater demand for oxygen and
strength
the coronary gets squeezed down by
the extra muscle that leads to WEAKER
CONTRACTIONS. PULMONARY EDEMA (CONGESTION)

 MAJOR SIGN OF THE HEART NOT BEING

ABLE TO PUMP ENOUGH BLOOD
3. DILATED CARDIOMYOPATHY
FORWARD TO THE BODY
 Heart chamber dilates or grows in size
 Dyspnea (trouble breathing)
in attempt to fill-up the ventricles with
larger volumes of blood (preload) and  Orthopnea (difficulty in breathing while
stretches the muscle walls increased lying down)
contraction strength via the frank-  Crackles (Rales)
starling mechanism. Over time the
muscle walls get thinner and weaker
eventually leading the muscles that are
CONGESTIVE HEART FAILURE VIDEO REVIEWER
BY: CIRERA
HEMOSIDERIN-LADEN MACHROPHAGES CHRONIC KUNG DISEASE

 HEART FAILURE CELLS  Hard to exchange O2

 Alveolar macrophages ear up these red
blood cells causing “Brownish color”
from iron buildup

MEDICATIONS FOR L-S HF

 ACE inhibitors – dilate blood vessels

 Diuretics – reduce the overall fluid
build-up

RIGHT-SIDED HEART FAILURE (Blood to Body)

 Often caused by left-sided HR

 Inc. in pulmonary artery  harder for
 COR PULMOLANE – enlarged right
the right ventricle to pump blood
ventricle
 BIVENTRICULAR

ISOLATED RIGHT-SIDED HR
Right sided Failure
 e. left to right cardiac shunt like:
o atrial septal defect  Blood backs up to the body therefore
o ventricular septal defect patients have congestion in the veins of
 allow blood to flow from the high systemic circulation
pressure left side to the lower pressure o Jugular venous distention –
right side which increases fluid vol. on common manifestation
the right side
HEPATOSPLENOMEGALY

 ENLARGMENT of the LIVER and SPLEEN

CARDIAC CIRRHOSIS & LIVER FAILURE

 If the congestion is prolonged in the

liver

PERITONEAL SPACE

 Can take a lot of fluid

 Ascites

Kayo na bahala mag intindi

CONGESTIVE HEART FAILURE VIDEO REVIEWER
BY: CIRERA
PITTING EDEMA

It is where the fluid backs up into the interstitial

space of the soft tissue of the legs (yang pag
tinusok mo yung part ng pang yun matagal siya
mag balik)

GRAVITY causes the majority of fluid to pool in

the dependent parts of the body:

 LEGS –when standing up

 SACRUM (lower back) – when lying
down
- assists or help pump
TREATMENT blood

 ACE inhibitors
 Diuretics

SUMMARY OR CLOSING REMARKS NIYA EWAN

KAYO NA BAHALA MAG INTINDI KASI ANTOK NA
AKO

Pacemakers - Stimulate the ventricles to

contract
CORONARY HEART DISEASE
& CHRONIC HEART FAILURE
(CHD/CHF)
by
BSPH4-A GROUP 2
CUIZON, ENONG, GABILAGON
 CONTENT ROADMAP
INTRODUCTION CLINICAL TREATMENT
NYHA Class I
NYHA Class II
ETIOLOGY MANIFESTATION
ACEIs / ARBs
Beta Blockers
Diuretics
Digoxin
Hydralazine/Nitrate
Sacubitril/Valsartan
Ivabradine
CONCLUSION
NYHA Class III MRA
NYHA Class IV

1 3 5 7 9
CHD/F END

2 4 6 8

PATHO- DIAGNOSIS PATIENT CARE

EPIDEMIOLOGY PHYSIOLOGY
Blood Test
ECG
Echocardiography
Px Education & Self-Monitoring
Monitoring of Drug Tx Effectiveness
Chest X-ray Monitoring of Drug Tx Safety
 1. INTRODUCTION
CORONARY HEART CHRONIC HEART
DISEASE FAILURE
aka Coronary Artery Disease (CAD); a condition where the heart is
characterized by the narrowing or unable to pump blood effectively,
blockage of coronary arteries due to due to underlying conditions
buildup of plaque/cholesterol including CHD

CHD can lead to damage and weakening of the heart, eventually

progressing to CHF, where the heart's pumping ability progressively
deteriorates. Understanding their relationship and management
strategies is crucial for improving patient outcomes.
1. INTRODUCTION
NYHA CLASSIFICATION OF HEART FAILURE
 2. EPIDEMIOLOGY
Increases with age, affecting < 2% of people
Prevalence younger than 60 to > 10% of those aged 75
or older

Varies, with a median survival of 5 years after

Prognosis
diagnosis

6-7% for stable heart failure, up to 25% or

Mortality rate more for acute heart failure

Progressive pump failure, sudden cardiac

Main causes of death death, recurrent myocardial infarction (MI)
 3. AETIOLOGY
may be a consequence of MI
Type of Heart Failure
often gradual in onset with symptoms
arising insidiously and without any
specific cause over a number of years
COMMON UNDERLYING AETIOLOGIES:
*MOST COMMON*
Coronary Heart/Artery Disease
Hypertension
OTHER IDENTIFIABLE CAUSES:
aortic stenosis, cardiomyopathy,
mechanical defects such as cardiac
valvular dysfunction, hyperthyroidism,
severe anemia
Description
Systolic Failure (HFrEF)
left ventricle weakens and
cannot pump blood effectively
Left-Sided Heart reduced ejection fraction
Failure Diastolic Failure (HFpEF)
normal left ventricle, but heart
muscle is stiff and doesn't fill
properly
preserved ejection fraction
Right-Sided Heart develops as a consequence of
Failure left-sided failure
blood returning to the heart through
Congestive Heart
the veins accumulates, causing
Failure (CHF)
congestion in the body’s tissues
3. AETIOLOGY
 4. PATHOPHYSIOLOGY: CHD

1 formation of a "fatty streak” in the vessel wall

monocytes migrate into the vessel wall, then

2 become macrophages and take up oxidized
LDL particles, forming foam cells
T cells activate, release cytokines and growth
3 factors, promoting further plaque
development
Over time, plaque grows and calcifies,
4 eventually leading to CHD = insufficient blood
flow and supply
As heart tries to pump harder to compensate
5 for insufficient blood flow, heart weakens and
eventually leads to CHF.
 4. PATHOPHYSIOLOGY: CHF
Normal heart:
1 Pumps 5 liters of blood per minute at rest.
Cardiac output at rest: approximately 5
L/min.
Mean heart rate: 70 beats/min.
Stroke volume: 70 mL.
Left ventricular ejection fraction (EF) >
50%.
Residual volume: approximately 60 mL.

LVSD:
2 Weak left ventricle pumps less blood.
EF is below 45%, and symptoms are
common if below 35%.
increased risk of blood clots in the
ventricle (EF falls below 10%).
Can result from cardiac injury (e.g., MI)
or mechanical stress (e.g., long standing
hypertension).
 5-6. CHD:
CLINICAL MANIFESTATIONS & DIAGNOSIS
Let’s examine how blood flows through the heart.
 5-6. CHD:
CLINICAL MANIFESTATIONS & DIAGNOSIS
Let’s examine how blood flows through the heart.

Coronary Angiography - gold

standard
Chest pain or discomfort ECG or EKG (Electrocardiogram)
(Angina) Echocardiogram (Ultrasound)
Weakness Exercise Stress Test
Chest X-ray
Light headedness
Magnetic Resonance Imaging (MRI)
Feeling sick to your stomach
and Multi-Slice Computerized
Cold sweating Tomography (CT) Scanning - non-
Pain or discomfort in the arms invasive, alternatives to angiography
or shoulder Cardiac Catheterization
Shortness of breath Coronary Artery Calcium Scan
Myocardial Scintigraphy (isotope
scanning)
 5. CHF:
CLINICAL MANIFESTATIONS
6. CHF: DIAGNOSIS
 7. TREATMENT
Foundation of Treatment:
ACE inhibitors (in the absence of
contraindication or intolerance)
Alternative: ARBs
Optimum Therapy:
ACE inhibitor
Beta- Blockers
Mineralocorticoid Receptor Antagonist
Diuretics (for symptomatic control)
Adjunctive Therapy:
Diuretics
Sacubitril/Valsartan
Ivabradine
Hydralazine/Nitrates combination
Digoxin
7. TREATMENT
 7. TREATMENT

Mineralocorticoid Receptor Antagonists Inotropic/Vasopressor Agents

(MRA) almost exclusively limited to
Adjunct to standard treatment (w/ACE or hospital practice, where
ARB) acute heart failure with
Spironolactone 25mg daily + ACE (C/I: px potentially reversible
with >5.5 mmol/L serum K or >200 mmol/L cardiogenic shock may
serum creatinine) require the use of these
Eplerenone (same C/I with Spironolactone) agents
Currently has no evidence available on Generally only be used
effectiveness and safety of combining an where there is hypotension
ACE inhibitor, ARB and a mineralocorticoid or hypoperfusion.
receptor antagonist, and therefore it is Risk of tolerance
recommended that this combination is development and
avoided until more information about this precipitating arrhythmias
particular combination becomes available.
 7. TREATMENT
Digoxin
add-on therapy at low doses in patients with moderate to severe heart failure who remain
symptomatic despite adequate doses of ACE inhibitor, β-blocker and diuretic treatment.
Potentially toxic due to NTI
 8. PATIENT CARE
PATIENT EDUCATION and
1
SELF-MONITORING
To achieve treatment
concordance, patients must
understand the need for
treatment, benefits, and risks of
prescribed medication.
Appropriate education is essential
to encourage understanding of
the condition, medication effects
on daily life, and active
participation in care.
Specific advice should cover
dosing timing, administration, and
troublesome symptoms.
 8. PATIENT CARE
MONITORING
2 EFFECTIVENESS OF DRUG
TREATMENT
To assess therapeutic
effectiveness in heart failure,
monitor patients for
improvements in symptoms (e.g.
shortness of breath, oedema),
exercise tolerance, and body
weight.
Consider other factors that may
affect symptoms, such as
comorbidities, dietary habits, and
medication adherence.
8. PATIENT CARE

MONITORING
3
SAFETY OF DRUG
TREATMENT
Drug-Drug interactions
Drug-Disease interactions
8. PATIENT CARE

MONITORING
3
SAFETY OF DRUG
TREATMENT
Drug-Drug interactions
Drug-Disease interactions
9. CONCLUSION
Coronary Heart Disease is a major global health issue that
affects millions of people worldwide. It is caused by the
buildup of plaque in the coronary arteries, leading to a
decrease in blood flow to the heart muscle. CHD can lead
to chronic heart failure if the heart muscle is damaged due
to a heart attack or prolonged ischemia. The diagnosis and
treatment of CHD involve a combination of medical history,
physical examination, and diagnostic tests, and may include
lifestyle changes, medications, and procedures or surgeries.
Ongoing management and patient care of CHD/CHF is
essential to prevent further progression of the disease and
to improve the patient's quality of life.
 REFERENCES:
Clinical Pharmacy and Therapeutics 5th Edition by
R. Walker, C. Whittlesea

Clinical Pharmacy and Therapeutics 6th Edition by

C. Whittlesea, K. Hodson

Types of Heart Failure. (2017, May 8).

www.heart.org. https://www.heart.org/en/health-
topics/heart-failure/what-is-heart-failure/types-
of-heart-failure
 CHF:
CASE DESCRIPTION
Mr. HS, 72-year-old, is admitted to hospital with increasing
shortness of breath at rest. He has a previous medical
history of severe left ventricular systolic dysfunction,
confirmed by echocardiography, and angina. Before
admission he had been taking the following medication:
lisinopril 10 mg daily, furosemide 80 mg each morning and 40
mg at 2 pm, digoxin 62.5 micrograms each morning, ISMN SR
60 mg daily, glyceryl trinitrate spray 1–2 doses as required,
aspirin 75 mg dispersible each morning. His chest X-ray
shows severe pulmonary oedema, his blood pressure is
110/70 mmHg and serum urea, and electrolytes are within
normal range. During the admission, carvedilol 3.125 mg
twice daily is started.
 CHF:
CASE QUESTIONS
1. What therapeutic options would you choose to treat the acute
symptoms presented by Mr. HS at the beginning of his admission?

Oxygen therapy: Administer supplemental oxygen to improve

oxygenation and alleviate dyspnea.
Intravenous diuretics: Increase the dose of furosemide or administer
intravenous loop diuretics such as furosemide to reduce fluid overload
and relieve pulmonary congestion.
Vasodilators: Administer nitroglycerin or nitroprusside to reduce
preload and afterload, thus improving cardiac output and relieving
symptoms of pulmonary edema.
Morphine: Consider administering morphine for its analgesic and
anxiolytic effects, which can help reduce preload and dyspnea.
Non-invasive positive pressure ventilation (NIPPV): Initiate NIPPV if the
patient fails to respond adequately to initial medical therapy, as it can
improve oxygenation and ventilation by reducing the work of breathing.
 2. Was the addition of carvedilol appropriate for this patient?

Yes, the addition of carvedilol was appropriate for this

patient. Carvedilol is a beta-blocker with proven efficacy in
improving outcomes in heart failure patients with reduced
ejection fraction. It exerts its effects by blocking beta-
adrenergic receptors, resulting in decreased heart rate,
myocardial contractility, and systemic vascular resistance. By
adding carvedilol to Mr. HS's medication regimen, there is a
potential for long-term benefits such as improved cardiac
function, reduced hospitalizations, and increased survival.
3. What other drug treatment options might be considered for this
patient in the longer-term?

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers

(ARBs): These medications have shown benefits in reducing mortality and
hospitalizations in heart failure patients by blocking the renin-angiotensin-aldosterone
system, leading to vasodilation and inhibition of adverse cardiac remodeling.
Mineralocorticoid receptor antagonists (MRAs): Drugs such as spironolactone or
eplerenone can be considered to further reduce morbidity and mortality in patients
with heart failure and reduced ejection fraction by blocking the harmful effects of
aldosterone on the heart and vasculature.
SGLT2 inhibitors: Recent evidence has shown that sodium-glucose cotransporter 2
(SGLT2) inhibitors, such as empagliflozin or dapagliflozin, provide additional benefits in
reducing heart failure hospitalizations and cardiovascular mortality in patients with
heart failure and reduced ejection fraction, irrespective of the presence of diabetes
mellitus.
Neprilysin Inhibitor: If ACE inhibitors or ARBs are not tolerated, an ARNI such as
sacubitril/valsartan can be considered as an alternative therapy. ARNIs have shown
superiority over ACE inhibitors in reducing cardiovascular mortality and heart failure
hospitalizations in patients with heart failure and reduced ejection fraction.
DRUG INTERACTIONS

By: Mariabe P. Quinco RPh, MS Pharm

LEARNING OBJECTIVES:
1. Define drug interaction.
2. Identify the types of drug interactions which include
drug-drug, drug-herbal and food-drug
3. Classify drug interactions
4. Discuss the management of drug interactions
5. Realize the role of Pharmacist in drug identification and
prevention
6. Participate in class discussion
 DRUG INTERACTION
 An interaction that occur when the effects of one drug are
altered by the co administration of another drug, herbal
medicine ,food, drink or other chemical agents
 Net effect:
 Additive or enhanced effect ; ex. Combination of different
antihypertensive drugs
 Antagonism effect of one or more drug; ex. Opioid to reverse
the overdose effect of morphine
 Any other alteration in the effect of one or more drug
Precipitant Drug
- is one which is taken concurrently with another drug and
changes,alters,modifies or nullifies the action of that drug

Object Drug
-The drug whose action is changed,altered,modified or
nullified.
EVENTS / EXAMPLES
 Withdrawal from the market:(ADR)
 CCB: mibefradil
 Terfenadine,grepafloxacin, cisapride + thiorizadine = QT
Prolongation: inc. VA – “ Torsade de pointes”
 Prescription and non prescription + herbal medicines:
 St. John Wort – depression ;enzyme inducer
 Drug-food interaction
 MAOIs + tyramine containing food = HYPERTENSIVE CRISIS
 Grapefruit juice + simvastatin, atorvastatin = statin induced
ADR: myopathy and myositis
SUSCEPTIBLE PATIENTS
 Polypharmacy patient groups
 Patients with hepatic or renal disease
 Patients on long term therapy ex HIV infection, epilepsy,DM
 Patients in intensive care
 Transplant patients
 Patients undergoing complicated procedures
 Critically ill elderly

 Box 4.1 Examples of drugs with high risk of interaction

 Require careful attention
MECHANISM OF DI
 PHARMACOKINETIC INTERACTION
 PHARMACODYNAMIC INTERACTION
 DRUG-FOOD INTERACTION
 DRUG-HERB INTERACTION
Pharmacokinetic Drug Interactions
-occurs when one drug enhances or interferes with the ADME
of another drug resulting in a change in drug concentration in
the body or the duration of the drug's availability at receptor
sites.
PHARMACOKINETIC INTERACTION 1
 Absorption
 Changes in GIT pH
 Adsorption, chelation and other complexing mechanism
 Effects on GIT motility
 Induction or inhibition of drug transport proteins
 malabsoprtion
 Drug distribution
 Drug metabolism
 Elimination interaction
 Drug metabolism
 CYP450 isoenzymes
 Enzyme induction
 Enzyme inhibition

 Elimination interaction
 Changes in urinary pH
 Changes in active renal tubule excretion
 Changes in renal blood flow
 Biliary excretion and enterohepatic shunt
 Drug transporter proteins
DRUG INTERACTION PHARMACOKINETIC:
Absorption
Changes in the GIT pH

1. Mechanism Due to: antacids, histamine, H2 agonist, PPI = dec other

drug rate absorption

Example Object drug:ketoconazole, itraconazole

Precipitant Drug: Antacids,histamine, H2 agonists,
omeprazole
Effect: siginificantly dec bioavailability of ketoconazole,
itraconazole
Severity level Level IV CAUTION
Intervention Leave a 2-3 hour interval
DRUG PHARMACOKINETICS
INTERACTIO metabolism
N ENZYME INDUCTION

Mechanism Results in a decreased pharmacological effect of the

Drug affected + inducing agent = decreased pharmacological effect of drug affected.

Examples 1. Oral contraceptive + rifampicin = therapeutic failure of oral contraceptives

2. Oral contraceptive + rifabutin = additional contraceptive precautions
required,
3. Oral contraceptive + modafinil =
Intervention Shift to other birth control or contraceptives. increased estrogen dose required.

Ciclosporin + Phenytoin, carbamazepine, St. john’s wort = decreased

ciclosporin levels with possibility of transplant rejection.

Intervention Possible serious or life-threatening interaction. Monitor closely. Use alternatives if

available.

Paracetamol + alcohol (chronic alcoholism) = hepatotoxicity at lower dose

 DRUG PHARMACOKINETICS
INTERACTION metabolism
ENZYME INDUCTION

Intervention If possible, do not take excessive quantity of alcohol.

Examples Corticosteroids + phenytoin, rifampicin =

increased metabolism with possibility of therapeutic
failure.
Intervention Monitor hydantoin blood level.
DRUG INTERACTION PHARMACOKINETICS
metabolism
ENZYME INHIBITION

MECHANISM Concurrent administration of an enzyme inhibitor = reduced metabolism of the

drug and an increase in the steady state drug concentration.

Examples Anticoagulants + ciprofloxacin, clarithromycin = anticoagulant effect

increased and risk of bleeding

intervention Check bleeding time more often. Adjust the dose of blood thinning medicine.

Example Azathioprine + allopurinol = enhancement of effect with increased

toxicity.

intervention Concomitant use should be done with caution and close monitoring.
 DRUG PHARMACOKINETICS
INTERACTION metabolism
///INHIBITION

Example Clopidogrel + Lansoprazole = reduced antiplatelet effect.

intervention Lower the dose of lansoprazole.

Example Carbamazepine, Phenytoin, Sodium Valproate + Cimetidine =

antiepileptic levels increased with risk of toxicity

intervention dose adjustment.

Example Sildenafil + Ritonavir = enhancement of sildenafil, effect with risk of

hypotension.

intervention Close monitoring.

 DRUG PHARMACOKINETICS
INTERACTION metabolism
CYP450 ISOENZYME

Mechanism Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in

clinically significant drug-drug interactions that can cause unanticipated adverse
reactions or therapeutic failures.

Example Amiodarone + Warfarin =

Increased risk of bleeding caused by increased warfarin level

Intervention dose of warfarin should be decreased and more frequent monitoring of INR should
occur.

Example Carbamazepine, phenobarbital, phenytoin +Ethinyl estradiol-

containing contraceptives =
Unplanned pregnancy caused by reduced estradiol level

Intervention Increase the dose of contraceptive.

 DRUG PHARMACOKINETICS
INTERACTION metabolism
CYP450 ISOENZYME

Example Diltiazem, verapamil + Prednisone=

Immunosuppression caused by increased prednisolone serum levels

Intervention Dose adjustment for both drugs.

Example Fluoxetine,paroxetine + Risperidone, tramadol =

Increased risk of extrapyramidal adverse effects caused by increased risperidone level;
decrease in analgesic effect caused by low level of active metabolite.

Intervention Dose adjustment.

Example Grapefruit juice + Buspirone =

Dizziness and serotonin syndrome caused by increased buspirone level.

Intervention Alternative citrus beverages.

 DRUG PHARMACOKINETICS
INTERACTION metabolism
CYP450 ISOENZYME

Example Metronidazole +Warfarin =

Increased risk of bleeding caused by increased warfarin level.

Intervention Dose reduced by third to half of warfarin

Example Terbinafine + Amitriptyline =

Dry mouth, dizziness, and cardiac toxicity caused by prolonged increase in
amitriptyline and nortriptyline levels

Intervention Dose adjustment and let your doctor know when you stop taking terbunafine. It may
be necessary to increase the dose of tricyclic medicine few weeks after stopping.

Example Clarithromycin,erythromycin, telithromycin +Verapamil , Simvastatin

= Myopathy or rhabdomyolysis caused by increased simvastatin level. Hypotension
and QT interval prolongation caused by increased verapamil level.
Regular monitoring may be required or alternate medication will be
required.
 DRUG METABOLISM
PREDICTING INTERACTION INVOLVING
METABOLISM

May be involved in many of the drug

Mechanism interaction previously thought to be due
to effects on CYP3A4

Ciprofloxacin and Norfloxacin= Increase

Example
plasma theophylline levels

Continue therapy for 2 days after signs

Intervention
and symptoms of infections are gone.
 ELIMINATION INTERACTIONS
CHANGES IN URINARY PH

Very minor clinical significance

Mechanism becausemost weak acids and bases are
inactivated by hepatic metabolism.

Urine alkalinisation or acidification +

Example salicylates and amphetamines =
Increasing drug elimination

Observations of vital signs and patient

status should occur continously in 1st 10
minutes after parenteral sedation and
Intervention
every 10 min for 1st 30 min, then every
15 min for 60 min, then hourly for 4
hours after last dose or until awake.
 ELIMINATION INTERACTIONS
CHANGES IN ACTIVE RENAL TUBULE
EXCRETION

May be multifactorial but competitive

Mechanism inhibition of methotrexate's renal tubular
secretion

Methotrexate + Salicylates or NSAIDS =

Example Dose of methotrexate should be closely
monitored.

Intervention Should be avoided

 ELIMINATION INTERACTIONS
CHANGES IN RENAL BLOOD FLOW
ELIMINATION
INTERACTIONS
Underlying this interaction is not entirely
CHANGES IN URINARY PH
Mechanism
clear.

NSAIDS +LITHIUM = Plasma levels

should closely monitored.
Example
NSAID impairs renal synthesis of
bronchodilator prostaglandin

Lithium levels should be checked every

Intervention
4-5 days after starting an NSAID.
 ELIMINATION INTERACTIONS
BILIARY EXCREATION AND THE
ENTEROHEPATIC SHUNT

Prolongs the stay of the drug within the

body but if the gut flora are diminished
Mechanism by the presence of an antibacterial, the
drug is not recycled and is lost more
quickly

ANTIBIOTICS + ORAL CONTRACEPTIVES=

Antibiotics may reduce the enterohepatic
Example
ciculation of ethinyloestradiol
conjugates.

Woman using non-enzyme antibiotics for

short courses (more than 3 weeks)
Intervention should be advised to use additional
contraception during the course and for
7 days afterwards.
 ELIMINATION INTERACTIONS
DRUG TRANSPORTER PROTEINS

May be involved in many of the drug

Mechanism interaction initially thought to be due to
changes CYP3A4

DIGOXIN+VERAPAMIL =increased digoxin

Example levels with the potential for digoxin
toxicity

Reduced when verapamil is

Intervention
administered.
PHARMACODYNAMIC INTERACTIONS
 Antagonistic interactions
 Additive or synergistic interactions
 Serotonin syndrome
 Drug or neurotransmitter uptake interactions
 Antagonistic
DRUG
INTERACTION
Interaction
PHARMACODYNAMIC

S
Mechanism Due to: Antagonism
Example Object: Opioid
Precipitant: Naloxone
Effect: Reverse and block the effects of other opioids, such as
heroin, morphine, and oxycodone.
Severity level Level IV – CAUTION
Intervention Be alert for increased or decreased effect, depending on the
combination of drugs
 Antagonistic Interaction
DRUG PHARMACODYNAMIC
INTERACTIO
NS
Mechanism Due to: Antagonism
Example Object: Benzodiazepine
Precipitant: Flumazenil
Effect: Potential to precipitate convulsions and/or
arrhythmias.
Severity level Level III – MINOR
Intervention Px monitoring for possible manifestation of interaction
 Antagonistic Interaction
DRUG PHARMACODYNAMIC
INTERACTI
ONS
Mechanism Due to: Pharmacodynamic synergism
Example Object: Alpha adrenergic
Precipitant: Metaraminol
Effect: Consequently increasing systemic blood pressure
(both systolic & diastolic).
Severity Level 0 - NOT ESTABLISHED
level
Intervention Proper monitoring
 Additive or Synergistic
Interaction
DRUG PHARMACODYNAMIC
INTERACTIONS
Mechanism Due to: the combined effect of two or more
chemicals
Example Object drug: Warfarin, Clopidogrel
Precipitant Drug: Non-steroidal anti-inflammatory
drugs
Effect: Increased risk of bleeding
Severity level Level II - MODERATE
Intervention Patients should be closely monitored for
anticoagulant control and bleeding complications.
 Additive or Synergistic Interaction
DRUG PHARMACODYNAMIC
INTERACTIONS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Angiotensin-converting enzyme
inhibitors
Precipitant Drug: K+ sparing diuretic
Effect: Increased risk of hyperkalemia
Severity level Level 1 - MAJOR
Intervention It is not impossible to combine an ACE inhibitor with
a potassium-sparing diuretic, as long as renal function
is normal and serum potassium concentration is
monitored closely.
 Additive or Synergistic Interaction
DRUG PHARMACODYNAMIC
INTERACTI
ONS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Verapamil
Precipitant Drug: β-adrenergic antagonists
Effect: Bradycardia and asystole
Severity Level 1 – SEVERE/MAJOR
level
Intervention Use alternative drugs
 Additive or Synergistic
Interaction
DRUG PHARMACODYNAMIC
INTERACTIO
NS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Neuromuscular blockers
Precipitant Drug: Aminoglycosides
Effect: Increased neuromuscular blockade
Severity Level 1 – SEVERE/MAJOR
level
Intervention Use alternative drugs
 Additive or Synergistic Interaction
DRUG PHARMACODYNAMIC
INTERACTI
ONS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Alcohol
Precipitant Drug: Benzodiazepines
Effect: Increased sedation
Severity Level V – NOT CLINICALLY SIGNIFICANT
level
Intervention Do not use drugs with similar pharmacological effects
Additive or Synergistic Interaction
DRUG PHARMACODYNAMIC
INTERACTIO
NS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Pimozide
Precipitant Drug: Sotalol
Effect: Increased risk of QT interval prolongation
Severity Level 1 – SEVER/MAJOR
level
Intervention Regular monitoring by the doctor or alternate medication
may be needed
Additive or Synergistic Interaction
DRUG PHARMACODYNAMIC
INTERACTI
ONS
Mechanism Due to: the combined effect of two or more chemicals
Example Object drug: Clozapine
Precipitant Drug: Co-trimoxazole
Effect: Increased risk of bone marrow suppression
Severity Level II - MODERATE
level
Intervention Avoid or use alternative drug
DUG-FOOD INTERACTIONS (7)
DRUG-HERB INTERACTIONS 8
 HERB MECHANISM/EFFECT DRUGS AFFECTED

• Glycyrrhizin glabra (liquorice) ▪ May exacerbate hypokalaemia. o Diuretics

* Used for treating digestive ▪ Precipitate digoxin toxicity

disorders o Digoxin

* Contains coumarin-like ▪ May increase the risk of oWarfarin

constituents: bleeding.
• Alfafa (Medicago sativa), o Aspirin
Angelica (Angelica archangelica),
Dong Quai, Chamomile, Horse
Chestnut, Red Clover (Trifolium
pratense)
* With anti-platelet
properties:
• Borage (Borago officinalis),
Bromelain (Ananas comosus),
Capsicum, Feverfew, Garlic,
Ginkgo biloba
 HERB MECHANISM/EFFECT DRUGS AFFECTED
• Asian Ginseng ▪ May cause hypoglycemia o Hypoglycemic agents
➢ Sympathetic (tachycardia,
palpitations, sweating)
* Can enhance hypoglycemic ➢ Parasympathetic (nausea,
effects hunger)
➢ Convulsion

• Hawthorn ▪ May cause hypotension o Anti-hypertensives

➢ Beta-adrenergic
antagonists/ Beta-blockers
* Can enhance hypotensive
effects
HERB MECHANISM/EFFECTS DRUGS AFFECTED
• St. John’s Wort (Hypericum ▪ Enzymatic Inhibition oWarfarin
perforatum) o Digoxin
oTheophylline
o Phenytoin
* Used for depression

Medicinal plants or herbs modify the individual’s response to the drug resulting to a change in the
effects. There is only very little data available regarding interactions involving medicinal plants for
various reasons but what is important to note is the fact that they cause change in the drug’s
effect. It is therefore very necessary for anyone taking medications to consult a
pharmacist on the possible interactions that may happen if these medicinal plants
are taken.
Tables to memorize
 Table 4.2 examples of interactions due to enzyme induction
 Table 4.3 examples of interactions due to enzyme inhibition
 Table 4.5 examples of additive or synergistic interactions
POSSIBLE INTERVENTIONS TO AVOID/
MINIMISE THE RISK OF DI:
 Switching one of the potential interacting drugs
 Allowing an interval of 2-3 h between administration of the
interacting drugs
 Altering the dose of one of the interacting drugs
 Advising patient to seek guidance about their medication
DRUG INTERACTION SEVERITY LEVEL
 LEVELS SEVERITY LEVEL
1 SEVERE/ MAJOR
2 MODERATE
3 MINOR
4 CAUTION
5 NOT CLINICALLY SIGNIFICANT
0 NOT ESTABLISHED
 DRUG INTERACTION SEVERITY LEVEL
LEVE SEVERITY EFFETCS INTERVENTIONS EXAMPLES
LS LEVEL
1 SEVERE/ -life threatening -Not usually used -AMIKACIN +
MAJOR -caused concurrently FUROSEMIDE
permanent --required medical (OTOTOXICITY,NEP
damage intervention HROTOXICITY)
AZITHROMYCIN
+QUINOLONES
(TORSADE
POINTES
2 MODERATE - Potential -pt. monitoring for Amlodipine + aspirin
deterioration of possible = Inc blood pressure
patient’s condition manifestation of Atorvastatin + PPI =
interaction Inc Adv effect of
-medical intervention statins(musculo -
or change in therapy skeletal toxicity)
is required
 DRUG INTERACTION SEVERITY LEVEL
LEV SEVERIT EFFECTS INTERVENTIONS EXAMPLES
ELS Y LEVEL
3 MINOR -clinical effects -pt. monitoring for Aluminum OH +
may be possible Bisacodyl = early
bothersome but manifestation of release of enteric
would not require interaction coated Bisacodyl tab in
major change in the stomach
therapy
4 CAUTION -interaction may - Be alert for Atorvastatin +
occur based on increased or Clopidogrel = Dec
MOA of co- decreased effect, efficay of clopidogrel
administered depending on the Azithromycin + Divalent
drug combination of or tirvalent cations =
drugs diminshed antibac effect
DRUG INTERACTION SEVERITY LEVEL
LE SEVERITY EFFETCS INTERVENTI EXAMPLES
VE LEVEL ONS
LS
5 NOT -interaction may
CLINICALLY occur, but the
SIGNIFICNAT outcome may not
be clinically
significant
0 NOT Interaction may
ESTABLISHED theoretically occur
due to its
pharmacokinetics
and
pharmacodynamics
but there have been
no any established
reports on the
interaction
MEDICATION SAFETY THROUGH
PHARMACY INTERVENTIONS
 DRUG INFORMATION SERVICES
 MANAGEMENT OF ADE
 ADMISSION DRUG HISTORIES
 DRUG PROTOCOL MANAGEMENT

 Note: From here , these are not included anymore!

DRUG INFORMATION SERVICES
 DIS of the Hospital Pharmacy should :
 be able to answer requests and inquiries on drugs and DRP
from all hosp staff (physicians, nurses, pharmacy tech, etc.)
 Provide support to PTC for drug information and evaluation
 Take an active role in the hosp formulary formulation and
training
MANAGEMENT OF ADE
 Drug therapy monitoring – is a process which includes all
functions necessary to ensure appropriate, safe, effective and
economical drug therapy for the patient. It includes:
 Recognizing the presence or lack of adequate therapeutic
response
 Assessing the potential for and occurrence of ADE
 Recommending changes or alternatives in therapy
 ADR MONITORING COMMITTEE – should be created
and well represented by all members of the health care team
with the PTC
ADMISSION DRUG HISTORIES
 Done by nurses and medical residents however it more
beneficial if RPh joins the medical admission team
 Intervention by RPh regarding re-use of medicines brought in
by patients
 Support from pharmacists to physicians prescribing for older
patients and fro antibiotic prescribing
 Advice regarding administration
 Allergy status of patients
 Patient counseling
 Cost of medications
DRUG PROTOCOL MANAGEMENT
 Is important for standardization of treatment in hospitals,
RPh should take part.
 The key elements in ADE management include:
 Detection – watch for:
 Prescribing error dispensing errors
 Prescribing omissions administration error
 Transcribing errors ADE
 Monitoring
 Assessment and correlation
 Treatment
 Documentation
 Reporting
 Prevention
Assignment
 Study all examples of DI for group activity
UNIT 3: CONCEPTS OF
PHARMACOTHERAPY
CARE PLANNING
By: MARIABE P. QUINCO,RPh, Clin
Pharm, MS Pharm
LEARNING OBJECTIVES:
◦ Differentiate between traditional pharmacy /
Clinical Pharmacy & Pharmaceutical Care
◦ Discuss process of Pharmaceutical care
• PWDT
• CORE
• PRIME
• FARM
◦ Documentation of Pharmaceutical care process
◦ Participate actively in class discussion
PWDT SAMPLE
THANK YOU!
ANY QUESTION?
ADVERSE DRUG REACTIONS
(ADR)

BY:
MARIABE P. QUINCO, RPH MSPHARM
 LEARNING OBJECTIVES

At the end of the lesson, the students will be able to:

1. Define the following terms: adverse drug event and

adverse drug reaction and side effect
2. State the types of adverse drug reactions give examples
of each.
3. Discuss the active role pharmacists as well as all
healthcare professionals should take in monitoring,
reporting, and trending ADR information.
4. Describe pharmacovigilance.
5. Participate in class discussion
 ADR

 All medicines-produced therapeutic effect

- Cause unwanted adverse effects
 Health Professionals – aware
 : for continued drug safety
 -identification

 Avoidance
 Post-marketing surveillance
 history

 Digitalis (William Withering-1785)

 Thalidomide (1957)
 serious birth defects (withdrawn December 1961)
 8,000-12,000 deformed children and number of deaths

 Practolol a cardioselective beta-adrenergic receptor

blocker (June 1970)
 Severe rashes: psoriasis(dry eyes, scarring of cornea, corneal
ulceration, blindness)
 Sclerosing peritonitis-death
 4 years- over 100,000 affected
 COX II
 Digitalis toxicity
 Confusion

 Irregular pulse

 Loss of appetite

 Nausea, vomiting, diarrhea

 Palpitations

 Vision changes
 COX II SELECTIVE(NSAIDS): Celecoxib (1998) &
Rofecoxib (1999)
 Reduced GIT ADR
 Cardiovascular events
 Rofecoxib – withdrawn
 Celecoxib – dose related

COX II NON SELECTIVE NSAIDS:DICLOFENAC

-THROMBOTIC RISK
 DRUG SAFETY ISSUES

 MMR Vaccine : does not cause AUTISM

 ASSESSING THE SAFETY OF THE DRUG

 Safety profile( complete safety profile is impossible)

 Premarketing trials – average 2500 patients

 Pharmacologically predictable ADRs

 Patients’ condition on trial

 Rare and potentially serious adverse effects often remain

undetected until a wider population is exposed to the drug

IMPORTANT PART :
- Vigilance of health care professionals
-Rational prescribing
-Careful monitoring of drug therapy
 Definitions

 ADR - (WHO, 1972)) a response to a drug that is

noxious and unintended and occurs at doses
normally used in man for the prophylaxis, diagnosis
or therapy of disease or for modification of
physiological function.
 - an appreciably harmful or unpleasant reaction,
resulting from an intervention related to the use of a
medicinal product which predicts hazard for the
future administration and warrants prevention or
specific treatment, or alterations of the dosage
regimen or the withdrawal of the product
Adverse drug reaction vs. adverse drug event
 Adverse reaction – applies to the patient’s point of view
 Adverse effect – applies to the drug
 Side effect – an unintended effect of a drug related to its
pharmacological properties and can include unexpected
benefits of treatment

 ADR – in a patient is an adverse outcome that is

attributed to the a suspected action of a drug
 ADE – adverse outcome that occurs after the use of drug,
but which may or may not be linked to use of drug

 All ADRs are ADE but not all ADEs are ADRS
 There are several ADE which is directly related to
formulations of active drug and excipients. These
effects are most likely due to any of the ff reasons:
 Wrong formulation
 Sensitivities to formulation of ingredients
 Reactions to impurities and breakdown products (presence of
impurities may degrade active drug)
 Aggregation of protein drugs in devices
 Nature of formulations (ex. Adhesion to mucous membrane,
precipitation from injection)
 CLASSIFICATION
 Rawlins-Thompson system
 2 main groups: type A, type B

 DoTS system
 Based on DOSE RELATEDNESS, TIMING and PATIENT
SUSCEPTIBILITY
 Table 5.2 p. 65 (pls study! Included in the exam)
 CLASSIFICATION
 Rawlins-Thompson system
 2 main groups: type A, type B
 Type A – normal but quantitatively exaggerated, pharmacological
effects of drugs.
 Ex. ADR caused by antimuscarinic activity of tricyclic
antidepressants
 Type B – qualitatively abnormal effects, which appear unrelated to
the drug’s normal pharmacology; more serious, cause deaths &
often discovered after drug has marketed ex. Hepatoxicity from
INH
 Extended ADR classification (Table 5.1 p. 64)-
(Pls study! Included in the exam)
 Antimuscarinic activities:
 dry mouth, dry nose, blurry vision, lowered gastrointestinal
motility or constipation, urinary retention, cognitive and/or
memory impairment, and increased body temperature.
 FACTORS AFFECTING SUSCEPTIBILITY TO
ADRS

 Age
 Gender
 Co-morbidities and concomitant medicines use
 Ethnicity
 Pharmacogenetics
 Erythrocyte G6PD deficiency
 Porphyrias
 AGE

 ELDERLY
 Prone to ADRs:
 Decline in both the metabolism and elimination of drugs
 Multiple co-morbidities: more drugs exposure
 CHILDREN
 Neonatal: Inc ADR:
 differences in body composition, metabolism & other physiological parameters
First weeks of Life : CLORAMPHENICOL, DIGOXIN & OTOTOXIC drugs
(STREPTOMYCIN) – higher risk of toxicity
 OLDER CHILDREN & YOUNG ADULTS
 May be susceptible to ADR: dosing error; lack of safety and efficacy
 Ex:
 METOCLOPRAMIDE: extrapyrimidal effects
 ASPRIN : Reye’s Syndrome (under age 12)
 REYES SYNDROME (ASPIRIN)
 As liver damage and brain damage get worse, other
symptoms may develop, including:
 Confusion. ...

 Fast, deep breathing (hyperventilation).

 Violent behavior, such as hitting others without reason.

 Seizures and coma.

 GENDER

 Women : more susceptible

 Psychiatric Adverse events : MEFLOQUINE (anti-malarial)

 Torsade de Pointes : SOTALOL (CV drug) and

ERYTHROMYCIN
 A ventricular arrythmia linked to ventricular fibrillation and death
 Co-morbidities and concomitant medicines use

 Reduction in hepatic and renal functions : Inc ADR

 Co-morbidites:
 Congestive cardiac failure, DM, peripheral vascular dx, chronic
pulmonary dx, rheumatologocal dx, hepatic dx, renal dx, and
malignant diseases
 Reasons:
 Pharmacokinetic and pharmacodynamic changes
 DI of multiple therapy
 ETHNICITY

 WHITE individuals: cytochrome P450 genotype

 CYP2C9 alleles: poor metabolism: affect warfarin metabolism
= inc warfarin toxicity
 BLACK patients
 ACE INHIBITORS: angioedema

 WHITE & BLACK patients vs Chinese or Japanese

 MEFLOQUINE: CNS ADRs

 ASIAN
 ROSUVASTATIN : myopathy
 Pharmacogenetics

 Is the study of genetic variations that influence an

individual’s response to drugs and examines
polymorphisms that code for drug transporters, drug
metabolising enzymes and drug receptors
 WARFARIN : CYP2C9
 ABACAVIR (nucleoside analogue reverse
transcriptase inhibitor – NRTI)
 HIV inf : hypersensitivity rxn
 CARBMAZEPINE & PHENYTOIN, LAMOTRIGINE
 SJS & TEN : HLA allele HLA-B 1502 : china, thailand,
malaysia indonesia, philippines and taiwan vs india & japan
 Erythrocyte G6PD deficiency

 Sex linked inherited enzyme deficiency leading to

susceptibility to hemolytic anemia
 PRIMAQUINE, SULFONAMIDES AND
NITRUFURANTOIN
 PORPHYRIAS

 - are heterogenous group of inherited disorders of

haem biosynthesis
 Effects:
 May precipitate life threatening attacks
 Abdominal and neuropsychiatric disturbances

 Other Trigger factors: Alcohol and changes in sex hormone

balance
 Pharmacovigilance and
epidemiological methods in ADR
detection

 Pharmacovigilance - ‘the study of the safety of

marketed
drugs under the practical conditions of clinical use in
large communities’.
Concern: detection, assessment and prevention of
adverse effects or any other possible drug-related
problems,
Goal: ultimate goal of achieving rational and safe
therapeutic decisions in clinical practice.
 Pharmacovigilance

 Spontaneous reporting
 UK, the spontaneous reporting scheme is the Yellow Card scheme
and in some countries reporting is a voluntary activity, in others
reporting is a legal requirement.
 Signal Detection
 A signal can be described as a possible causal relationship between
an adverse event and a drug, which was previously unknown
 Causality assessment
 Direct patient reporting
 Yellow Card Scheme
 Published Case reports
 Roles of health professionals

 Identifying and assessing ADRs in clinical practice

 Preventing ADRs
 Monitoring Therapy
 Explaining risk to the patients
 Example of ADE resulted from use of specific
formulations
DOSAGE ADE POSSIBLE HOW TO AVOID
FORMULATIONS EXPLANATION
Indomethacin, Esophageal Acidity of the conc. solutions The pt should take
alendronate, aspirin, injury of some of the drugs (aspirin, them with sufficient
clindamycin, alendronate, risendronate,; volume of water to
doxycycline, ferous high amount of doxycycline facilitate passage of
salts, KCl, that chelates Ca and thus the drug into the
risendronate, damage epithelial lining esophagus
tetracycline,
thioridazine

Transdermal patch Contact Presence of causative agents ( Sensitivity testing of

dermatitis, nickel SO4, the patient
pain on hydroxymethycellulose) on
removal the patches: strong adhesion

Penicillin oral Sensitivites Impurities such as 2-OH-3 Sensitivity testing of

formulations and pyrazine, 4-OH phenylglycine, the pt., use of quality
allergies 4-OH phenylglycamoxicillin, API by the
amoxilloic acid manufacturer.
 ASSIGNMENT -

 Discuss the epidemiology or ADR in the Philippines

(latest)
 Discuss the methods and actions in detecting ADR of
the DOH
 What is the progress of PHARMACOVIGILANCE
ADR detection in the Philippines conducted by DOH
 Secure ADR form prepared by DOH (filled or empty)
 ACTIVITY

 Search an article about update on ADR (2019-2022)

 Abstract/summary/conclusion
 Insights/Reaction