Introduction to Pharmacology

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Outline
— Introduction

— Pharmacokinetic

— Absorption
— Distribution
— Metabolism
— Elimination

— pharmacodynamic
Introduction
Pharmacology: is the branch of medicine that studies the
interactions between drugs and living organisms.

— It encompasses the understanding of the chemical properties,

biological effects, mechanisms of action, therapeutic uses,

and potential side effects of pharmaceutical compounds.

— study of the biochemical and physiological effects of drugs on

organisms.
Introduction
Pharmacology is essential for:

— The development of new medications

— The optimization of drug therapy, and the

— assessment of drug safety and efficacy in clinical practice.

— Decrease possible side effect.

— Avoid drug-drug Interaction.

Absorption
Absorption
— The first stage for the drugs to reach to their target organs is
known as “absorption”.
— In fact, the absorption is the transportation of the drug across
the biological membranes
— There are different mechanisms for a drug to be transported
across a biological membrane for GI tract:
v Passive (simple) diffusion
v Active transport
v Pinocytosis
v Facilitated diffusion
Absorption
1- Passive (simple) diffusion
— The major role for the transportation of the drugs across the
cell membrane is simple (passive) diffusion.
— The substances move across a membrane according to a
concentration gradient.
— The concentration gradient is the factor that determines the
route and rate of the diffusion.
— No energy is required.
— There is no special transport (carrier) protein.
— No saturation.
Absorption
2- Facilitated diffusion

— Occurs by the carrier proteins.

— Net flux of drug molecules is from the high concentration to

low concentration.

— No energy is required.

— Saturable.
Absorption
3- Active transport
— The transportation of the drug molecules across the cell
membrane against a concentration or an electrochemical
gradient.
— It requires energy (ATP) and a special transporter (carrier)
protein.
— There is «transport maximum» for the substances (the rate of
active transport depends on the drug concentration in the
environment).
Absorption
4- Pinocytosis
— The drugs which have MW over 900 can be transported by

pinocytosis.

— It requires energy.

— The drug molecule holds on the cell membrane and then

surrounded with plasma membrane and inserted into the cell

within small vesicles.
Distribution
Drug distribution: is the process by
which a drug reversibly leaves the
bloodstream and enters the extracellular
fluid and tissues.
 Distribution
• The distribution of drugs can occur in 4 patterns throughout the
body:
Ø Distribution only in plasma: HMW-Dextran.

Ø Distribution to all body fluids homogenously: Small and non-ionized few

molecules like alcohol, some sulfonamides.

Ø Concentration in specific tissues: iodine in thyroid; chloroquine in liver;

tetracyclines in bones and teeth; high lipophilic drugs in fat tissue

Ø Non-homogenous (non-uniform) distribution pattern: Most of the drugs

are distributed in this pattern according to their abilities to pass through the cell
membranes or affinities to the different tissues.
Factors Affecting the Distribution of Drugs
— Blood flow

— Capillary permeability

— Binding of drugs to plasma proteins and tissues

— Lipophilicity
Factors Affecting the Distribution of Drugs
1. Blood flow:
— There is a positive correlation between the blood flow in the

tissue and the distribution of the drugs.

— Kidney, liver, brain and heart have a high perfusion rate,

which the drugs distribute higher.

— Skin, resting skeletal muscle and bone have a low perfusion

rate.
Factors Affecting the Distribution of Drugs
2. Capillary permeability:
— Capillary permeability is determined by

v Capillary structure

v Chemical nature of the drug

— In the liver and spleen, a significant portion of the

molecules can pass.

— In the brain, few portion of the molecules can pass.

Factors Affecting the Distribution of Drugs
3- Binding of drugs to plasma proteins and tissues:
— The most important protein that binds the drugs in blood is
albumin for most of the drugs.
— Many drugs bind to albumin, which affects their distribution,
bioavailability, and elimination.
— Acidic drugs (salicylates, vitamin C, sulfonamides,
barbiturates, penicillin, tetracyclines, warfarin, probenecid) are
bound to albumin.
— Basic drugs (streptomycin, chloramphenicol, digitoxin,
coumarin etc.) are bound to alpha-1 and alpha-2 acid
glycoproteins, globulins, and alpha and beta lipoproteins.
Factors Affecting the Distribution of Drugs
Properties of plasma protein-drug binding
— Saturable:
— Bind to limited number of drug molecules
— Non-selective:
— Several drugs with various properties can bind to plasma
protein
— Reversible:
— binding of drugs to albumin is typically reversible

Bound Fraction Unbound Fraction

Factors Affecting the Distribution of Drugs
4- Lipophilicity:

— Lipophilic drugs readily move across most biologic

membranes.

— These drugs dissolve in the lipid membranes and penetrate

the entire cell surface.

— The major factor influencing the distribution of lipophilic

drugs is blood flow to the area.

Metabolism
Metabolism
— The process of alterations in the drug structure by the
enzymes in the body is called “biotransformation (drug
metabolism)” and the products form after these reactions
are called “drug metabolites”.
— Drug examples that is transformed to less active
compounds after biotransformation:

DRUG LESS ACTIVE METABOLITE

Aspirin Salicylic acid
Meperidine Normeperidine
Lidocaine De-ethyl lidocaine
Metabolism
— Drug examples that is transformed to more active
compounds after biotransformation:
DRUG MORE ACTIVE METABOLITE
Imipramine Desmethylimipramine
Codeine Morphine
Nitroglycerin Nitric oxide
Losartan EXP 3174 (5-carboxylic acid metabolite)

— Drug examples that is transformed to inactive

metabolites after biotransformation
DRUGS INACTIVE METABOLITE

Most of the drugs Conjugated compounds

Barbiturates Oxidation products
Metabolism
The enzymatic reactions which the drugs are exposed to:
1. Oxidation

2. Reduction PHASE I

3. Hydrolysis

4. Conjugation PHASE II
Metabolism
— Gene amplification leads to increased expression of the
mRNA for an enzyme and subsequently a greater amount of
the enzyme. This can result in a patient population resistant
to the drug because the drug is eliminated very rapidly.
— Gene deletion leads to a deficiency in enzyme activity. This
gives rise to a patient population that is a slow metabolizer of
a particular drug. plasma drug concentrations can quickly
reach toxic levels
EXCRETION
Excretion
— Renal excretion

— Biliary excretion

— Excretion from the Lungs

— Excretion into breast milk

— Artificial excretion way

ANY QUESTION ???
Pharmacology

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Outline
— Administration routes

— Bioavailability

— Factors that influence bioavailability

— Clearance

— Half-Life
Administration Routes
Drug administration routes:
— Enteral
Ø Oral
Ø Sublingual
— Parenteral
Ø IM
Ø IV
Ø SC
Ø ID
— Topical
— Inhalation
— Rectal
— Transdermal
 Administration Routes
LOCAL ADMINISTRATION
Conjunctival:
üOphthalmic solutions or
ophthalmic ointments are
applied locally for some eye
or eyelid diseases.
Intranasal:
üNasal sprays or solutions can
be used for nasal mucosa or
paranasal sinus diseases (i.e.
allergic rhinitis in spring).
Administration Routes
SYSTEMIC ADMINISTRATION
Oral Route
• This is the most often used administration route of the
drugs.
• This route is known to be the safest, easiest and the most
economic way of administering drugs.
• Drug molecules are mostly absorbed from duodenum,
jejunum and upper ileum.
• Disintegration and Dissolution are the two main processes for
the oral administered drugs before the absorption process.
• The absorption rate and absorption ratio of the orally
administered drugs are closely related with the above two
parameters.
Administration Routes
Inhalation

These drugs should be small particle sized with high lipid-

water partition coefficient.
Administration Routes
Transdermal:
• Transdermal therapeutic systems (patch) is used generally
for transdermal drug application.
• These are absorbed from the skin to circulation to obtain a
systemic effect.
• These are generally high lipophilic drugs.
Bioavailability
Bioavailability is the rate and extent to which an administered
drug reaches the systemic circulation.

— For example, if 100 mg of a drug is administered orally and 70

mg is absorbed unchanged, the bioavailability is 0.7 or 70%.

— Determining bioavailability is important for calculating drug

dosages for non-intravenous routes of administration.

Bioavailability
Factors that influence bioavailability

1- Drug Related Factors That Affect Bioavailability

— First-pass hepatic metabolism
— Solubility of the drug
— Chemical instability
— Nature of the drug formulation
2- Patient Related Factors That Affect Bioavailability
Bioavailability
1- First-pass hepatic metabolism
When a drug is absorbed from the Gl tract, it enters the portal
circulation before entering the systemic circulation.
— If the drug is rapidly metabolized in the liver or gut wall
during this initial passage, the amount of unchanged drug
entering the systemic circulation is decreased.
Factors that influence bioavailability
2- Solubility of the drug:
— Very hydrophilic drugs are poorly absorbed because of the
inability to cross lipid-rich cell mem- branes.
3- Chemical instability:
— Some drugs, such as penicillin G, are unstable in the pH of
gastric contents.
— Others, such as insulin, are destroyed in the Gl tract by
degradative enzymes.
Factors that influence bioavailability
4- Nature of the drug formulation:
Drug absorption may be altered by factors unrelated to the
chemistry of the drug. For example:
— Particle size
— Salt form
— Crystal polymorphism
— Enteric coatings
— Presence of excipients (such as binders and dispersing agents)
can influence the ease of dis- solution and, therefore, alter
the rate of absorption.
 Bioavailability
Patient Related Factors That Affect Bioavailability:
Ø Differences in first-pass metabolism,
Ø drug metabolism differences between
individuals (pharmacogenomics)
Ø Diseases that affect the GI motility
Ø Age
Ø Gender
Ø body weight
Ø drug-drug or drug-food interactions
 HIGH BIOAVAILABILITY LOW BIOAVAILABILITY

Solutions…Suspensions…Capsule…Tablet…Coated tablet…Sustained Release (SR) tablets

Clearance
— It can be described as the volume of plasma cleared

from the drug per unit time (ml/min).

— Total Body Clearance: It is the plasma volume cleared

from the drug per unit time via the elimination of the
drug from all biotransformation and excretion
mechanisms in the body.
Clearance
— Renal Clearance: It can be described as the rate of
the excretion of a drug from kidneys. So in other
words, renal clearance is the volume of plasma cleared
from the non-metabolized (unchanged) drug via the
excretion by kidneys per minute.
Clearance
• There are four important factors that affect the renal

clearance of the drugs:

üTubular reabsorption ratio of the drug.

üTubular secretion ratio of the drug.

üGlomerular filtration ratio of the drug.

üPlasma protein binding of the drug.

 Clearance
BILIARY EXCRETION
• These substances are generally
secreted into the biliary ducts
from the hepatocytes by active
transport and finally they are
drained into the intestines.
• Especially, highly ionized polar
compounds (conjugation
products) can be secreted into
the bile in remarkable amounts.
 Clearance
• After biotransformation, metabolites
are drained into the small intestine
by biliary duct.
• Drug metabolites in the small
intestine are broken down again in
the small intestine and reabsorbed
back reaching the liver by portal
vein again.
• This cycle between the liver and
small intestine is called the
enterohepatic cycle.
Clearance
— This is important, because enterohepatic cycle prolongs
the duration of stay of the drugs in our body which
leads an increase in the duration of their effect.
— Drug examples that go under the enterohepatic cycle in
remarkable amounts.
Ø Chlorpromazine
Ø Digitoxin
Ø Indomethacin
Ø Chloramphenicol
Elimination Half-Life (t½)
Half-Life of the drug (t½)?
It is the time it takes for the plasma concentration or the
amount of drug in the body to be reduced by 50% via different
elimination mechanisms.
— For example, if a drug has a concentration of 100 mg/L,

after one half-life, it would be 50 mg/L.

 Vd
t1/2 = 0,693 x
Clearance

According to the above formulation

1. Elimination half-life is inversely (negatively) proportional with the
clearance.
2. How high the apparent volume of distribution of a drug, that high is
the duration of stay of that drug in the body (Positive correlation
between the half-life and the volume of distribution).
3. If the apparent volume of distribution of the two different drugs is not
the same; having the same clearance does not mean that the rate of
elimination of these two drugs is equal to each other.
Half-Life (t½)
TIME DRUG LEFT % RATIO OF THE DRUG LEFT

0 x t1/2 100 1
1 x t1/2 50 1/2
2 x t1/2 25 1/4
3 x t1/2 12,5 1/8
4 x t1/2 6,25 1/16
5 x t1/2 3,125 1/32
ANY QUESTION ???
Drugs Affecting the Cardiovascular
System (Antihypertensives )

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
 Hypertension
Hypertension: is a chronic
medical condition characterized
by consistently elevated blood
pressure levels in the arteries.

— Blood pressure is measured in

millimeters of mercury
(mmHg)
Effects of Blood Pressure on Arteries
— Narrowing of arteries
— Increased shear stress
— Thickening of arteries walls
— Loss of elasticity
— Endothelial dysfunction
— Atherosclerosis
— Increased risk of cardiovascular events
Blood pressure is expressed with two numbers:
— Systolic blood pressure: is the pressure in the arteries when
the heart beats and pumps blood into the circulation. It is the
higher number in a blood pressure reading.
— Diastolic blood pressure: is the pressure in the arteries when
the heart is at rest between beats. It is the lower number in a
blood pressure reading.
Hypertension
Signs and Symptoms of Hypertension
Hypertension is often referred to as a "silent killer" because it
usually does not present noticeable symptoms until it reaches a
severe stage. However, some individuals may experience:
— Headaches
— Shortness of breath
— Nosebleeds
— Flushing
— Dizziness
— Chest pain
— Visual changes
Etiology of Hypertension
Primary Hypertension: This type has no identifiable cause
and develops gradually over many years. Factors contributing to
primary hypertension include:
— Genetics and family history
— Age
— Obesity
— lifestyle
— High salt intake
— Excessive alcohol consumption
— Chronic stress
Etiology of Hypertension
Secondary Hypertension: This type is caused by an
underlying condition and can develop suddenly. Causes include:
— Kidney disease
— Hormonal disorders (e.g., hyperaldosteronism, Cushing's
syndrome)
— Certain medications (e.g., NSAIDs, corticosteroids)
— Sleep apnea
— Thyroid problems
— Congenital heart defects
Treatment
 Treatment
Goals of Treatment: The overall goal is to reduce cardiovascular and
renal morbidity and mortality. Reduce morbidity and mortality by the
least intrusive means possible.
— The goal for patients with chronic kidney disease CKD is less than

130/80 mm Hg.

— The goal BP for most patients, including those with diabetes or CKD

(non-dialysis), is less than 140/90 mm Hg

— The goal for patients 80 years of age or older without diabetes or

CKD is less than 150/90 mm Hg.

Treatment
Non-pharmacological treatment
— Lifestyle modifications
Ø Weight loss if overweight or obese
Ø Dietary sodium restriction ideally to 1.5 g/day (3.8 g/day
sodium chloride).
Ø Moderation of alcohol consumption
Ø Smoking cessation
Lifestyle modification alone is sufficient for most patients with
prehypertension but inadequate for patients with hypertension
and additional CV risk factors or target- organ damage.
Treatment
Pharmacological Treatment

— Diuretics

— ACE-Inhibitors

— ARB

— CCB
 Treatment
Diuretics
— Initial mechanism of action is based upon decreasing blood volume,
which ultimately leads to decreased blood pressure.
1. Thiazide diuretics (hydrochlorothiazide, chlorthalidone)
Ø Mainly in the distal convoluted tubule to decrease the reabsorption of
Na+ by inhibition of a Na+/CI- cotransporter.
Ø Side effects
ü Hypokalemia (K)
ü Hypomagnesemia (Mg)
ü Hyperuricemia (Uric acid)
ü Hypercalcemia (Ca)
ü Hyperglycemia (glucose)
 Treatment
2. Loop Diuretics (Furosemide)
— Loop diuretics inhibit the cotransport of Na+/K+/2CI- in the
luminal membrane in the ascending limb of the loop of Henle.
— Side effect (Hypokalemia, Hypomagnesemia, Acute hypovolemia,
Ototoxicity).
3. Potassium-sparing diuretics (Spironolactone)
— Act in the collecting tubule to inhibit Na+ reabsorption and K+
excretion.
— Side effects (Hyperkalemia, Gynecomastia).
Angiotensin Converting enzyme Inhibitor (Captopril,
enalapril, lisinopril)
— The ACE inhibitors lower blood pressure by reducing peripheral
vascular resistance without reflexively increasing cardiac output, heart
rate, or contractility.
— These drugs block the enzyme ACE, which cleaves angiotensin I to
form the potent vasoconstrictor angiotensin II.
— Slow progression of diabetic nephropathy.
— Side effects (Dry cough, angioedema, volume depletion).
Angiotensin II Receptor Blocker (Losartan, Candesartan)
— Their pharmacologic effects are similar to those of ACE inhibitors
— ARBs should not be combined with an ACE inhibitor for the
treatment of hypertension due to similar mechanisms and adverse
effects.
— Less side effects than ACE-I
— These agents are also teratogenic and should not be used by pregnant
women
Calcium channel blockers CCBs
are a recommended first-line treatment option in black patients. They
may also be useful in hypertensive patients with diabetes or stable
ischemic heart disease.
— Dihydropyridines (amlodipine, felodipine, nifedipine)
— Binding to L-type calcium channels in smooth muscle of the peripheral
arteriolar vasculature. This causes vascular smooth muscle to relax.
— Used as an initial therapy or as add-on therapy
— Use in patient with asthma and diabetes.
— Side effect (gingival hyperplasia, dizziness, fatigue, headache)
Assignment
Write list for different class members of Anti-hypertensive
drugs groups with their available doses, sides effects, drug-drug
interaction and contraindication.
ANY QUESTION ???
Drugs Affecting the Cardiovascular
System (Heart Failure)

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Introduction
Heart failure (HF): is a complex, progressive disorder in
which the heart is unable to pump sufficient blood to meet the
needs of the body.
— Insufficient blood flow to organs and/or fluid accumulation
in the lungs and body tissues.
Etiologies
— Ischemic Heart Disease

— Cardiomyopathies

— Valvular Heart Disease

— Arrhythmias

— Congenital Heart Defects

Pathophysiology
— Myocardial Dysfunction
Ø Systolic Dysfunction: reduced ejection fraction, damage to the
myocardium reduces its ability to contract effectively,
lower stroke volume (SV) — the amount of blood ejected per
heartbeat.
Ø Diastolic Dysfunction: problem in the filling of ventricles,
filling of the ventricles during diastole is reduced
— Neurohormonal Activation: activation of the renin-
angiotensin-aldosterone system (RAAS) and sympathetic
nervous system (SNS).
— Increase Preload: Is the degree of stretch of the cardiac muscle
fibers at the end of diastole (volume of blood in the ventricles at the
end of filling).
— Increase Afterload: Is the resistance the heart must work against to
eject blood. Increased systemic vascular resistance (SVR), often seen
in hypertension or from neurohormonal activation (angiotensin II).
Signs and Symptoms
— Dyspnea

— Orthopnea

— Fatigue

— Fluid Retention

— ankles edema

— Palpitations

— Cyanosis
Investigations
1- Echocardiogram
— An echocardiogram uses ultrasound waves to create images
of the heart's structures and assess its function.
Ø Ejection fraction (EF) (55% and 70%)
Ø Left ventricular diameter is < 4 cm.
2- Chest X-ray
— Useful for detection of cardiac enlargement, pulmonary edema
— Pulmonary Edema: Presence of Kerley B lines
— cardiothoracic ratio should be less than 0.50
3- ECG: To assesses the presence of any other cardiac problems, such
as arrhythmias
Treatment
— ACE – Inhibitors

— ARB

— Diuretics

— Beta Blockers

— Aldosterone Anta-agonist

— Inotropic Agents
Treatment
ACE inhibitors

Actions: ACE inhibitors decrease vascular resistance (afterload)

and venous tone (preload).

— increased cardiac output.

— Used in patients who have had a recent myocardial infarction

— also used in the treatment of hypertension

— indicated for patients with all stages of left ventricular failure

 Treatment
Beta-Blockers (Metoprolol, Bisoprolol)
— Reduction in Heart Rate: Beta blockers primarily block beta-1
adrenergic receptors in the heart, reducing heart rate and
myocardial oxygen demand.
— Beta blockers block the effects of excessive catecholamines (like
norepinephrine), which can be harmful in heart failure by causing
increased heart rate, vasoconstriction, and further myocardial
stress.
— Control heart rhythm
 Treatment
Aldosterone Anta-agonist (eplerenone, Spironolactone)
— Patients with HF have elevated levels of aldosterone due to
angiotensin II stimulation and reduced hepatic clearance of the
hormone
— Antagonists of aldosterone at the mineralocorticoid receptor
— preventing salt retention, myocardial hypertrophy, and hypokalemia
— Side effects (Gynecomastia and dysmenorrhea)
Inotropic Agents (Digoxin)
— Inhibition of Na+/K+ ATPase
— Enhance the contractility of the cardiac muscle during subsequent
cardiac cycles, which leads to improved cardiac output.
— Reduces heart rate (negative chronotropic effect). This is beneficial
for heart failure patients as it helps to slow down rapid heart rates,
especially in cases of atrial fibrillation.
— Digoxin should also be used with caution with other drugs that slow
AV conduction, such as B-blockers, verapamil, and diltiazem.
ANY QUESTION ???
Endocrine System (DM)

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Introduction
Diabetes Mellitus (DM) is a group of metabolic disorders
characterized by high blood glucose levels (hyperglycemia)
resulting from defects in insulin secretion, insulin action, or
both. It can lead to serious complications if not managed
properly.
Introduction
— The incidence of diabetes is growing rapidly in the United

States and worldwide.

— An estimated 30.3 million people in the United States.

— 422 million people worldwide are afflicted with diabetes.

 Etiologies
Type 1 Diabetes:
— Genetic predisposition: Certain genes increase the risk.
— Autoimmunity: The immune system mistakenly attacks pancreatic beta
cells.
Type 2 Diabetes:
— Genetics: Family history increases risk.
— Lifestyle factors: Sedentary lifestyle, obesity, unhealthy diet.
— Insulin resistance: Cells fail to respond properly to insulin.
— Other factors: Age, certain health conditions, and hormonal changes.
Gestational Diabetes:
— Hormonal changes during pregnancy can affect insulin function.
— Risk factors include obesity, age, and family history.
 Pathophysiology
— Insulin Deficiency: In type 1, there is an absolute deficiency

due to beta cell destruction. In type 2, there is a combination of

resistance to insulin's effects and insufficient insulin production.

— Hyperglycemia: Elevated blood glucose levels result from

increased hepatic glucose production and decreased uptake in

peripheral tissues.

— Metabolic Dysregulation: Leads to disturbances in

carbohydrate, fat, and protein metabolism.
 Signs and Symptoms
— Frequent urination (polyuria)

— Increased thirst (polydipsia)

— Increased hunger (polyphagia)

— Fatigue

— Blurred vision
Complications of Diabetes Mellitus

— Diabetic Retinopathy

— Nephropathy

— Diabetic Neuropathy

— CVD

— Diabetic Foot Ulcers

— Poor Wound Healing

Diagnosis
— FPG (126 mg/dL or greater )

— Random plasma glucose (200 mg/dL or higher)

— OGTT (200 mg/dL or greater)

— HA1c (6.5 %)
Treatment
Goal of Treatment

— symptoms, reduce risk of microvascular and macrovascular

complications, reduce mortality, and improve quality of life.

Treatment
Non-Pharmacological treatment
— The meal plan should be moderate in carbohydrates, with all
of the essential vitamins and minerals
— Weight loss
— Physical activity (150 min/week)
— Ongoing diabetes education should emphasize self-care
behaviors
— Lifestyle modifications
 Treatment
Pharmacological treatment
1- Biguanides
Metformin
— slows intestinal absorption of sugars
— It increases glucose uptake
— Weight loss may occur because metformin causes loss of appetite
— The ADA recommends metformin as the initial drug of choice for
type 2 diabetes.
— Eliminated renally
Treatment
— Metformin may be used alone or in combination with other

oral agents.

— No weight gain or hypoglycemia occurs when take it alone

— Adverse effects: These are largely gastrointestinal, including

diarrhea, nausea, and vomiting.

— Metformin is contraindicated in renal dysfunction due to the

risk of lactic acidosis

— Vitamin deficiency
Treatment
2- Sulfonylureas (glimepiride, glipizide, glyburide)
— These agents are classified as insulin secretagogues, because
they promote insulin release from the Beta cells of the
pancreas.
— Reduce hepatic glucose production.
— Increase peripheral insulin sensitivity.
— The duration of action ranges from 12 to 24 hours.
Treatment
— Adverse effects of the sulfonylureas include hypo- glycemia,

hyperinsulinemia, and weight gain.

— They should be used with caution in hepatic or renal

insufficiency.

— Renal impairment is a particular problem for glyburide,

increase the duration of action

— Glipizide or glimepiride are safer options in renal

dysfunction and in elderly patients.

Treatment
3- Thiazolidinediones (pioglitazone, rosiglitazone)
— The thiazolidinediones (TZDs) are also insulin sensitizers.
— Although insulin is required for their action, the TZDs do not
promote its release from the Beta cells, so hyperinsulinemia
is not a risk.
— lower insulin resistance by acting as agonists for the
peroxisome proliferator-activated receptor-y (PPAR'Y), a
nuclear hormone receptor
Treatment
— Activation of PPARy regulates the transcription of several
insulin responsive genes, resulting in increased insulin
sensitivity in adipose tissue, liver, and skeletal muscle.
— The TZDs can be used as monotherapy or in combination
with other glucose-lowering agents or insulin.
— Rosiglitazone is less utilized due to concerns regarding
cardiovascular adverse effects.
— Weight gain can occur because TZDs may increase
subcutaneous fat and cause fluid retention.
Treatment
— These drugs should be avoided in patients with severe heart
failure.
— TZDs have been associated with osteopenia and increased
fracture risk in women.
— rosiglitazone carries a boxed warning about the potential
increased risk of myocardial infarction and angina with
the use of this agent.
ANY QUESTION ???
 Endocrine System
(Diabetes Mellitus Medication)

Dr. Zeyad A. B. Qwlmany

M. Sc. Clinical Pharmacy
Cihan University - Duhok
 Introduction
Insulin

is a vital hormone that plays a crucial role in glucose metabolism and energy

regulation in the body.

• Insulin is a peptide hormone composed of 51 amino acids arranged in two chains

(A and B) linked by disulfide bonds.

• Management both Type 1 and Type 2 DM

Insulin Structure and Components

1- A Chain:

• Comprises 21 amino acids.

• Contains an amino terminus with the NH2 group (amino group) and
terminates with a carboxyl end with the COOH group (carboxyl group).

2- B Chain:

• Comprises 30 amino acids.

• Begins with an NH2 group and ends with a COOH group.

3- Disulfide Bonds:

• There are two inter-chain disulfide bridges between the A and B chains and
one intra-chain disulfide bond within the A chain.

• These bonds contribute to the molecule's three-dimensional structure, which

is critical for its biological activity.

4- C-Peptide:

• C-peptide, or connecting peptide, is a 31-amino acid fragment that links the A

and B chains in proinsulin.

• It is released into circulation alongside insulin during cleavage and is used

clinically as a marker for insulin production in the body.
Location:

• Insulin is synthesized in the beta cells of the pancreatic islets (Islets of

Langerhans).

Packaging:

• Insulin and C-peptide are packaged into secretory granules for storage until
release.

Mechanism of Release of Insulin

• When blood glucose levels rise (e.g., after a meal), glucose enters the beta
cells via GLUT2 transporters.
Reasons for Insulin Release
1- Increased Blood Glucose Levels:.
2- Hormonal Triggers:
• GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitory polypeptide)
3- Amino Acids:
• Certain amino acids (e.g., leucine and arginine) can also stimulate insulin release.
4- Fatty Acids:
5- Autonomic Nervous System Activation:
• The parasympathetic nervous system (such as through the vagus nerve)
6- Incretin Effect:
• Hormones secreted from the intestine (incretins) in response to nutrient intake
enhance insulin release
Mechanism of Insulin

Insulin binds to the insulin receptor (tyrosine kinase receptors) on the surface of
target cells (such as muscle, liver, and adipose tissue).

1. Increased Glucose Uptake

2. Inhibition of Hepatic Glucose Production

3. Promotion of Glycogenesis

4. Inhibition of Lipolysis

5. Insulin has an inhibitory effect on glucagon secretion

 Insulin Classification
1- Rapid-Acting Insulin
– Insulin Lispro

– Insulin Aspart

– Insulin Glulisine
Properties:
Onset: 10-30 minutes
• Peak: 30 minutes to 3 hours
• Duration: 3-5 hours
• Use: Often taken before meals to control postprandial blood sugar spikes.
2- Short-Acting Insulin
• Regular Insulin (Humulin R, Novolin R)

Properties:

• Onset: 30 minutes to 1 hour

• Peak: 2-5 hours

• Duration: 5-8 hours

• Use: Can be used for mealtime coverage and as a basal insulin.

3- Intermediate-Acting Insulin
Example:

• Insulin NPH (Neutral Protamine Hagedorn)

Properties:

• Onset: 1-3 hours

• Peak: 4-12 hours

• Duration: 10-16 hours

• Use: Provides sustained glucose control, often used twice daily.

4- Long-Acting Insulin
Examples:
• Insulin Glargine
• Insulin Detemir
Properties:
• Onset: 1-2 hours

• Peak: Minimal peak (steady release)

• Duration: Up to 24 hours (Glargine) or 18-24 hours (Detemir)

• Use: Provides a baseline level of insulin and is often administered once daily.
5- Ultra Long-Acting Insulin

• Example:

• Insulin Degludec

Properties:

• Onset: 30-90 minutes

• Peak: No significant peak

• Duration: Over 24 hours (up to 42 hours)

• Use: Offers flexibility in dosing and provides extended glucose control.

Side Effects of Insulin

• Hypoglycemia: The most common and dangerous side effect, characterized by

symptoms such as shaking, sweating, confusion, and in severe cases, seizures
or loss of consciousness.

• Weight Gain: Patients may experience weight gain with insulin therapy.

• Injection Site Reactions: Pain, redness, or swelling at the injection site.

• Allergic Reactions: Although rare, some individuals may develop an allergy to

insulin.

• Lipodystrophy: Changes in subcutaneous fat at the injection site can occur

from repeated injections in the same area.
GLP-1 (glucagon-like peptide-1) is incretin hormones that are secreted in
response to food intake and play significant roles in glucose metabolism.

• gut releases incretin hormones in response to a meal.

– Insulin Secretion

– Glucagon Inhibition

– Gastric Emptying

– Appetite Regulation
Changes of GLP-1 in Diabetes

• Decreased Secretion: Individuals with type 2 diabetes often exhibit reduced

levels of GLP-1 post-meal (postprandial).

• Reduced Sensitivity: Even if GLP-1 is present, the pancreatic beta cells may
become less responsive.

• Shorter Half-Life: GLP-1 has a short half-life due to rapid inactivation by the
enzyme dipeptidyl peptidase-4 (DPP-4).
GLP-1 (glucagon-like peptide-1) receptor agonist
• Albiglutlde
• Dulaglutide
• Exenatide
• Liraglutide
• Lixisenatide
• Semaglutide
These agents are analogs of GLP-1 that exert their activity by:
• Improving glucose-dependent insulin secretion
• Slowing gastric emptying time
• Reducing food intake by enhancing satiety (a feeling of fullness)
• Decreasing postprandial glucagon secretion, and promoting Beta cell
proliferation.
Side effects

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Pancreatitis

Contraindicated in patients with a history of medullary thyroid carcinoma or

multiple endocrine neoplasia type 2.
Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)
• Alogliptin
• Linagliptin
• Saxagliptin
• Sitagliptin
These drugs inhibit the enzyme DPP- 4, which is
responsible for the inactivation of incretin hormones
• Prolonging the activity of incretin hormones
increases release of insulin in response to meals
and reduces inappropriate secretion of glucagon
• used as monotherapy or in combination with
sulfonylureas, metformin, TZDs, or insulin
Side effects

• Nasopharyngitis

• Increase the risk of severe, disabling joint pain

• Alogliptin and Saxagliptin have also been shown to increase the risk of heart
failure hospitalizations and should be used with caution in patients with or at
risk for heart failure.
Sodium-glucose cotransporter 2 inhibitors (SGLT2)
• Canagliflozin
• Dapagliflozin
• Empagliflozin
• Ertugliflozin
are oral agents for the treatment of type 2
diabetes.
• Empagliflozin is also indicated to reduce the risk
of cardiovascular death in patients with type 2
diabetes and cardiovascular disease.
• The sodium-glucose cotransporter 2 (SGLT2) is responsible for reabsorbing
filtered glucose in the tubular lumen of the kidney.
• By inhibiting SGLT2, these agents decrease reabsorption of glucose, increase
urinary glucose excretion, and lower blood glucose.
• Inhibition of SGLT2 also decreases reabsorption of sodium and causes osmotic
diuresis.
Adverse effects
• Female genital mycotic infections
• UTI
• Hypotension
• Ketoacidosis
Any Question?
Drug for Disorders of the Respiratory
System (Asthma)

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Introduction
Asthma:
Is a chronic inflammatory disease of the airways characterized by
episodes of acute bronchoconstriction that cause shortness of
breath, cough, chest tightness, wheezing, and rapid respiration.
Pathophysiology
Airflow obstruction in asthma is due to bronchoconstriction

that results from:

— Contraction of bronchial smooth muscle

— Inflammation of the bronchial wall

— Increased secretion of mucus

Pathophysiology
Asthma attacks may be triggered by exposure to:
— Allergens
— Exercise
— Stress
— Respiratory infections
 Signs and Symptoms
Common signs and symptoms of asthma include:

— Wheezing: A high-pitched whistling sound during breathing,

especially on expiration.

— Shortness of Breath: Breathlessness during normal activities.

— Chest Tightness: A feeling of pressure or constriction in the

chest.

— Coughing: Often worse at night or early morning, frequently

dry and may be productive during the night.

 Diagnostic Criteria
Spirometry: is a medical device used to measure lung function,
specifically the volume and flow of air that can be inhaled and
exhaled.
— ForcedVital Capacity (FVC) : Normal: ≥80%
— Forced Expiratory Volume in 1 second (FEV1): Normal: ≥80%
 Diagnostic Criteria
Peak Expiratory Flow Rate (PEFR): is a measure of how fast a
person can forcibly exhale air from their lungs. It is a valuable
parameter used in the assessment and management of asthma and
other respiratory conditions.
— Approximately 600-700 L/min (Normal)

— Mild Asthma 80-100%

— Moderate Asthma 50-79%

— Severe Asthma <50%

Classification
Treatment
Goals of therapy

— Drug therapy for long-term control of asthma is designed to

reverse and prevent airway inflammation. The goals of asthma

therapy are to decrease the intensity and frequency of asthma

symptoms, prevent future exacerbations, and minimize

limitations in activity related to asthma symptoms.

Treatment
— Short acting B2 Adrenergic agonist (SABA)

— Long acting B2 Adrenergic agonist (LABA)

— Inhaled Corticosteroid

— Short acting anti-cholinergic

— Long acting anti-cholinergic

— Leukotriene Modifiers
 Treatment
Short acting B2 Adrenergic agonist (SABA) [Albuterol, Levalbuterol]
— Directly relax airway smooth muscle.
— They are used for the quick relief of asthma symptoms,
— As well as adjunctive therapy for long-term control of the disease.
Treatment
— Rapid onset of action (5 to 30 minutes) and provide relief for
4 to 6 hours
— All patients with asthma should receive a SABA inhaler for
use as needed
— For patients with mild, intermittent asthma or exercise-
induced bronchospasm
Side effects
— Tachycardia
— Hyperglycemia
— Hypokalemia
— Hypomagnesemia
— Tremor
 Treatment
Long acting B2 Adrenergic agonist (LABA) [Salmeterol and formoterol]
— Providing Long-term control as a monitor
— Have a long duration of action, providing bronchodilation for at least
12 hours.
— Use of LABA monotherapy is contraindicated, and LABAs should be
used only in combination with an asthma controller medication, such
as an inhaled corticosteroid (ICS) in moderate to severe asthma.
— Adverse effects of LABAs are similar to quick-acting ~2 agonists.
 Treatment
Corticosteroids (Mometasone, Fluticasone, Beclomethasone, Budesonide)
— ICS are the drugs of choice for long-term control in patients
with persistent asthma.
— inhibit the release of arachidonic acid through inhibition of
phospholipase A2. thereby producing direct anti-inflammatory
properties in the air- ways.
 Treatment
Leukotriene Modifiers (Montelukast, Zafirlukast)
— Leukotrienes (LT) are inflammatory products
— Cysteinyl leukotrienes constrict bronchiolar smooth muscle, increase
endothelial permeability, and promote mucus secretion.
— Zafirlukast and montelukast are selective antagonists of the cysteinyl
leukotriene-1 receptor.
— Not be used in situations where immediate bronchodilation is
required.
— Side effects (Elevations in serum hepatic enzymes, headache and
dyspepsia)
ANY QUESTION ???
CNS Drugs (Depression)

Zeyad A. B. Qwlmany
M. Sc. Clinical Pharmacy
Cihan University - Duhok
Introduction
Depression
Is a common mental health disorder characterized by persistent
feelings of sadness, hopelessness, and a lack of interest or
pleasure in activities. It can affect daily functioning and may
lead to emotional and physical issues.
 Etiologies
1. Biological Factors:
— Genetics
— Neurotransmitter Imbalances: Alterations in serotonin,
norepinephrine, and dopamine levels are associated with depression.
— Hormonal Changes: Changes in hormone levels, such as during
pregnancy or menopause, can contribute (estrogen and progesterone).
2. Medical Conditions:
Chronic illnesses (e.g., diabetes, heart disease) and certain neurological
conditions (e.g., Parkinson’s disease, stroke) can lead to or worsen
depression.
 Etiologies
3. Psychological Factors:
— Negative Thinking Patterns: Cognitive distortions like black-and-
white thinking may contribute to depression.
— Stressful Life Events: Trauma, loss, or significant life changes (e.g.,
divorce, job loss) can trigger depressive episodes.

4. Social Factors:
— Isolation: Lack of social support and meaningful relationships can
increase vulnerability.
— Cultural Influences: Societal pressures and stigma regarding mental
health can exacerbate feelings of worthlessness.
 Pathophysiology
— Neurotransmitter Systems: Dysregulation of serotonin,
norepinephrine, and dopamine pathways can disrupt mood regulation.

— HPA Axis Dysfunction: Hyperactivity of the hypothalamic-

pituitary-adrenal (HPA) axis leads to chronic stress, resulting in

elevated cortisol levels, which are associated with mood disorders.

— Inflammation: Increased levels of pro-inflammatory cytokines have

been linked to depression, suggesting that inflammation may play a

role in its development.
 Signs and Symptoms
— Emotional Symptoms:

a) Persistent sadness, anxiety, or "empty" mood

b) Feelings of hopelessness, helplessness, or worthlessness
c) Irritability or frustration, even over small matters

— Cognitive Symptoms:

a) Difficulty concentrating, making decisions, or remembering things

b) Pessimism about the future
Signs and Symptoms
— Physical Symptoms:

a) Changes in appetite or weight (increased or decreased)

b) Sleep disturbances (insomnia or hypersomnia)
c) Fatigue or loss of energy

— Behavioral Symptoms:

a) Loss of interest or pleasure in most activities (anhedonia)

b) Withdrawal from social interactions
c) Decreased performance at work or in daily responsibilities
Diagnosis
— Clinical Interview: A comprehensive assessment of the

patient’s history, symptoms, and how these affect daily life.

— Screening Tools: Utilization of standardized questionnaires

(e.g., PHQ-9) to help assess the severity of symptoms and

monitor treatment progress.

— Diagnostic Criteria: The DSM-5 (Diagnostic and Statistical
Manual of Mental Disorders) criteria are commonly used,
requiring at least five of the following symptoms to be present
for a minimum of two weeks:
v Depressed mood
v Anhedonia
v Significant weight changes
v Sleep disturbances
v Psychomotor agitation or retardation Fatigue
v Feelings of worthlessness or excessive guilt
v Diminished ability to think or concentrate
v Recurrent thoughts of death or suicide
Treatment
1- Selective serotonin reuptake inhibitors (SSRIs)
Are a group of antidepressant drugs that specifically inhibit serotonin
reuptake
— (Sertraline , Escitalopram, Fluoxetine)
— Selectivity for the serotonin transporter blocking, leading to
increased concentrations of the neurotransmitter in the synaptic cleft.
— Typically take at least 2 weeks to produce significant improvement in
mood, and maximum benefit may require up to 12 weeks or more.
— First-line treatment for moderate depression and anxiety disorders
due to their safety and tolerability.
— All of the SSRIs are well absorbed after oral administration. Peak
levels are seen in approximately 2 to 8 hours on average.
— The majority of SSRIs have plasma half- lives that range between 16
and 36 hours.
— Fluoxetine differs from the other members of the class by having a
much longer half-life (50 hours)
— Food has little effect on absorption (except with sertraline, for
which food increases its absorption).
— Side effects : (headache, sweating, anxiety and agitation,
hyponatremia, gastrointestinal (GI) effects, weakness and fatigue,
sexual dysfunction, changes in weight, sleep disturbances (insomnia
and somnolence)
— Discontinuation syndrome (Malaise and flu-like symptoms,
nervousness, and changes in sleep pattern).
 Treatment
2- Selective serotonin-Norepinephrine reuptake inhibitors (SNRIs)
— (Venlafaxine, desvenlafaxine, duloxetine)
— Inhibit the reuptake of both serotonin and norepinephrine
— Depression is often accompanied by chronic pain, such as backache
and muscle aches
— Considered when there is a coexisting pain condition or if SSRIs are
ineffective
— The most common side effects of venlafaxine and desvenlafaxine are
— Increase in blood pressure and heart rate
— nausea, headache
— sexual dysfunction
— insomnia
— sedation, and constipation
3- Tricyclic Antidepressants
— The TCAs inhibit norepinephrine and serotonin reuptake into the
presynaptic neuron
— (imipramine, amitriptyline, nortriptyline)
— They also have interactions with various other receptors, including
histamine, acetylcholine, and alpha-adrenergic receptors.
— Considered for patients who have not responded to
SSRIs/SNRIs, particularly in cases of chronic pain or sleep
disturbances.
— The onset of the mood elevation is slow, requiring 2 weeks or longer
 Treatment
— The TCAs are effective in treating moderate to severe
depression.
— Imipramine use in enuresis alarms in the treatment of bed-
wetting in children
— Amitriptyline, have been used to help prevent migraine headache
— Blockade of muscarinic receptors leads to:
— Blurred vision
— Xerostomia
— Urinary retention
— Tachycardia
— constipation
— Angle-closure glaucoma
4- Monoamine oxidase inhibitors (MAOIs)
— (Phenelzine, Selegiline)
— are a class of antidepressants that work by inhibiting the action of
monoamine oxidase, an enzyme responsible for breaking down
monoamines (serotonin, norepinephrine, and dopamine)
— Reserved for severe depression or situations where other
antidepressants have not worked.
— Severe and often unpredictable side effects, due to drug-food and
drug-drug interactions, limit the widespread use of MAOIs.
ANY QUESTION ???