Part I: General Pharmacology

What is Pharmacology?

The word pharmacology derives from the Greek word for drug
“pharmakon”. It is a basic medical science which offers fundamental theories for
rational usage of drugs to prevent and treat diseases.

Pharmacology can be defined as the study of substances that interact with

living systems through chemical processes, especially by binding to regulatory
molecules and activating or inhibiting normal body processes.

What is drug?

Drugs are chemical agents which could be used for treatment, diagnosis,
prevention of diseases, and bring benefit to the patients or the recipients.

In the most general sense, a drug may be defined as any substance that
brings about a change in biologic function through its chemical actions.

In the great majority of cases, the drug molecule interacts with a specific
molecule in the biologic system that plays a regulatory role, i.e. a receptor
molecule.

The chain of events between administration and production of effects in

the body can be divided into two components:

 Pharmacokinetics: deals with the absorption, distribution,

biotransformation, and excretion of drugs in a living organism. the actions
of the body on the drug.
 Pharmacodynamics: is the study of the biochemical and physiological
effects of drugs and their mechanisms of action in living organisms. The
actions of the drug on the body.
Indications For Drug Therapy: Risk Vs. Benefit
Benefits of drug therapy should outweigh the risks. Benefits fall into two
broad categories: those designed to alleviate a symptom and those designed to
prolong useful life.
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 Adverse Effects
Some adverse effects are so common and are identified very early during
clinical use of a drug. Serious adverse drug reactions may be uncommon therefore
escape detection for many years after a drug begins to be widely used.
Poisons and Toxins
Poisons are drugs. Poisons in small doses are the best medicines; and
useful medicines in too large doses are poisonous. (William Withering. ‘discover’
of digitalis, 1789)
Toxins are usually defined as poisons of biological origin, i.e. synthesized by
plants or animals, in contrast to inorganic poisons such as lead and arsenic.
Routes of Drug Administration
The route of administration is determined primarily by
 The properties of the drug (for example, water or lipid solubility, ionization,
etc.)
 The therapeutic objectives (for example, the desirability of a rapid onset of
action or the need for long-term administration or restriction to a local
site).
There are two major routes of drug administration, enteral and parenteral.
1) Enteral Route
The drug is given in the mouth, to be swallowed, allowing oral delivery, or it may
be placed under the tongue, facilitating direct absorption into the bloodstream.
A. Oral
Some drugs are absorbed from the stomach; however, the duodenum is a major
site of entry to the systemic circulation because of its larger absorptive surface.
Most drugs absorbed from the GI tract enter the portal circulation to the liver
"undergo first-pass metabolism" before they are distributed into the general
circulation. Ingestion of drugs with food "delays gastric emptying", or in
combination with other drugs, can influence absorption. Enteric coating of a drug
protects it from the acidic environment; the coating may prevent gastric
irritation, and depending on the formulation, the release of the drug may be
prolonged, producing a sustained release effect.
Advantages
o Easily self-administered.
o Cheap
o Toxicities or overdose by the oral route may be overcome with antidotes.

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Disadvantages
o Sometimes inefficient - only part of the drug may be absorbed
o Limited absorption " First-pass metabolism by the intestine or liver" .
o Irritation to gastric mucosa - nausea and vomiting
o Destruction of drugs by gastric acid and digestive juices
o Effect too slow for emergencies
o Unpleasant taste of some drugs
o Unable to use in unconscious patient
B. Sublingual: Placement under the tongue allows a drug to diffuse into the
capillary network and, therefore, to enter the systemic circulation directly.
Advantages
 Rapid absorption
 Convenience of administration
 Low incidence of infection
 Avoidance of first-pass metabolism.
Disadvantages
o Inconvenient
o Small doses
o Unpleasant taste of some drugs
C. Rectal: administration of drugs into the rectum
Advantages
50% bypasses the portal circulation; thus, the biotransformation of drugs
by the liver is minimized.
Prevents the destruction of the drug by intestinal enzymes or by low ph in
the stomach.
Useful if the drug induces vomiting when given orally, if the patient is
already vomiting, or if the patient is unconscious.
The rectal route is commonly used to administer antiemetic agents.
Good for drugs affecting the bowel such as laxatives
Disadvantages
Some drugs may irritate the rectal mucosa.

2) Parenteral
The parenteral route introduces drugs directly across the body's barrier defenses
into the systemic circulation or other vascular tissue. Parenteral administration is

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used for drugs that are poorly absorbed from the GI tract (heparin) and for agents
that are unstable in the GI tract (insulin).
The three major parenteral routes are intravascular (intravenous or intra-arterial),
intramuscular, and subcutaneous.
A. Intravenous (IV): placing a drug directly into the blood stream. Useful for
drugs that are not absorbed orally. Similar concerns apply to intra-arterially
injected drugs.
Advantages
 Can be used for unconscious patients
 Rapid onset of action.
 100% bioavailability no first-pass metabolism.
Disadvantages
 Pain
 Infections.
 Risk of embolism
 Cannot be recalled by emesis or by antidote.
 Prominent adverse reactions if delivered too-rapidly.
B. Intramuscular (IM): drug is injected into skeletal muscle. Drugs administered
IM can be aqueous solutions (fast) or specialized depot preparations (slow)
e.g. haloperidol decanoate.
Advantages
 Slower absorption than IV route
 No first pass metabolism
Disadvantages
 Local pain
 Introduction of infection
 Damage to the surrounding structures "nerves"
 Maximum injectable volume 4ml
C. Subcutaneous (SubQ): Absorption of drugs from the subcutaneous tissues.
Like IM injection, requires absorption and is somewhat slower than the IV
route.
Advantages
o It minimizes the risks associated with intravascular injection.
o Concurrent administration of vasoconstrictor will slow absorption
o Slow and constant absorption

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 3) Other routes
A. Inhalation: Inhalation provides the rapid delivery of a drug across the large
surface area of the mucous membranes of the respiratory tract and pulmonary
epithelium. This route of administration is used for drugs that are gases
Advantages
 The drug is delivered directly to the site of action and systemic side effects
are minimized.
 Produce an effect almost as rapidly as with IV injection
B. Intranasal: This route involves administration of drugs directly into the nose.
The abused drug, cocaine, is generally taken by intranasal sniffing.
C. Intrathecal/intraventricular: It is sometimes necessary to introduce drugs
directly into the cerebrospinal fluid.
D. Topical: Topical application is used when a local effect of the drug is desired. It
is applied as a cream directly to the skin or instilled (administered drop by
drop) directly into the eye.
E. Transdermal: This route of administration achieves systemic effects by
application of drugs to the skin, usually via a transdermal patch. The rate of
absorption can vary markedly, depending on the physical characteristics of the
skin at the site of application.
Advantages
Stable blood vessels thus, sustained delivery of drugs.
No first pass metabolism
Disadvantages
Drug should be potent or patch becomes larger

Sources of drugs

1. Plants – Atropine, Morphine

2. Animals – Insulin
3. Minerals – Calcium chloride and Sodium bicarbonate
4. Synthetics – Naloxone, Lidocaine

Drug Nomenclature

• Chemical name: -long name, describes the chemical constituents of the

drug.

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 • Generic name: - Original chemical name of drug assigned by the
manufacturer that first develops it.
• Trade/brand/commercial name: - given by the company that sells the drug

Dosage forms of drug

Pharmaceutical dosage forms are classified according to their physical
properties
Gaseous dosage forms
Liquid dosage forms
Semisolid dosage forms
Solid dosage forms

 Gases
– Medicinal gases, inhalation/volatile anaesthetics
– Aerodispersions of solid particles (e.g., inhalation antiasthmatics) or
liquid particles (inhalation antiasthmatics or sprays)
 Liquids
– Solutions –prepared by dissolving one or more solutes in a solvent
– Emulsions
• consisting of two immiscible liquids
• o/w or w/o
• cloudy appearance
– Suspensions
• Solid particles are dispersed in liquid
• Not intended for systemic administration of drugs with high
potency
 Semisolid dosage forms
– Unshaped
• Gels
• Creams
• Ointments
– Shaped
• Suppositories
 Solid dosage forms
– Unshaped
o Powders

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 – Shaped
o Tablets
o Capsules
o Transdermal patches
 Injections (available as ampoules, vials with rubber head)
 Solutions, emulsions or suspensions which MUST BE
– Sterile
– Pyrogen-free
– Isotonic
 lntravenous ( I.V.) injections
 Intramuscular (I.M.) and subcutaneous ( SubQ)
 Infusions

Nursing implications in administration of drugs

• Follow the “six rights”: -
 Right drug
 Right dose
 Right time
 Right route
 Right patient
 Right documentation
Documentation is a language for health workers.
• Right to a “double check”
• Right to proper storage/documentation
• Right to accurate calculation& preparation
• Right to careful checking of transcription of orders
• Patient safety- use of correct administration procedures
• Right to accurate routes of administration
Evaluation of drug therapy: an ongoing part of the nursing process
• Monitor patient responses to the drug
• Monitor expected and unexpected responses
• Monitor therapeutic (intended effects), side effects & toxic effects
• Document !! Very important!!
Drug administration is very important and can be a dangerous duty.
▫ Given correctly – restore patient’s health
▫ Given incorrectly – worsen patient’s condition
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Progress notes
o Administration
o Special problems
 New symptoms
 Patient’s statements
 Patient tolerance
o Be sure to have the right chart
o Be specific and accurate

Medical Prescriptions:

1. Patient name
2. Patient age
3. Patient gender
4. Drug name: generic Vs. brand
5. Dose
6. Route
7. Frequency
8. Duration
9. Quantity
[Link]
[Link]

Chapter One: Pharmacokinetics

The processes of absorption, distribution, metabolism, and excretion
collectively termed drug disposition determine the concentration of drug
delivered to target effector molecules.
Absorption of Drugs
Absorption is the transfer of a drug from its site of administration to the
bloodstream. The rate and efficiency of absorption depend on the route of
administration.
A. Transport of a drug from the GI tract
Drug movement across the membrane of any cell, including enterocytes
and hepatocytes, is a combination of passive diffusion and active transport,
mediated by specific drug uptake and efflux molecules. Depending on their

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chemical properties, drugs may be absorbed from the GI tract by either passive
transport, active transport, Endocytosis and exocytosis.
B. Physical factors influencing absorption
Blood flow to the absorption site
Total surface area available for absorption
Contact time at the absorption surface

Bioavailability
Bioavailability is expressed as the fraction of administered drug that gains access
to the systemic circulation in a chemically unchanged form.
Bioavailability may be <100% for two main reasons:
1) Absorption is reduced.
2) The drug undergoes metabolism or elimination prior to entering the
systemic circulation.
The extent of absorption may be reduced because;
A drug is incompletely released from its dosage form.
Undergoes destruction at its site of administration.
It has physicochemical properties such as insolubility that prevent complete
absorption from its site of administration.
Slow absorption rates are deliberately designed into “slow-release” or
“sustained-release” drug formulations in order to minimize variation in plasma
concentrations during the interval between doses.
“First-Pass” Effect
When a drug is administered orally, it must traverse the intestinal
epithelium, the portal venous system, and the liver prior to entering the systemic
circulation.
The elimination of drugs in intestine and liver, which reduces the amount of
drug delivered to the systemic circulation, is termed pre-systemic elimination,
pre-systemic extraction, or first-pass elimination.
Factors that influence bioavailability
 First-pass hepatic metabolism
 Solubility of the drug
 Chemical instability
 Nature of the drug formulation

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 Drug Distribution
Drug distribution is the process by which a drug reversibly leaves the bloodstream
and enters the interstitium (extracellular fluid) and/or the cells of the tissues. The
delivery of a drug from the plasma to the interstitium primarily depends on:
A. Blood flow
B. Capillary permeability
C. Binding of drugs to plasma proteins
Volume of Distribution
The volume of distribution is a hypothetical volume of fluid into which a drug is
dispersed.
Water compartments in the body
Once a drug enters the body, it has the potential to distribute into the Plasma
compartment, Extracellular fluid or Total body water. Other sites (pregnancy,
the fetus)
Binding of Drugs to Plasma Proteins
Drug molecules may bind to plasma proteins (usually albumin). Bound drugs are
pharmacologically inactive; only the free, unbound drug can act on target sites in
the tissues, elicit a biologic response, and be available to the processes of
elimination.
A. Binding capacity of albumin
The binding of drugs to albumin is reversible and may show;
o Low capacity (one drug molecule per albumin molecule)or
o High capacity (a number of drug molecules binding to a single albumin
molecule).
B. Competition for binding between drugs
When two drugs are given, each with high affinity for albumin, they
compete for the available binding sites. The drugs with high affinity for albumin
can be divided into two classes, depending on whether the dose of drug in the
body is greater than, or less than, the binding capacity of albumin.
Class I drugs: If the dose of drug is less than the binding capacity of
albumin, then the dose/capacity ratio is low. The binding sites are in excess of the
available drug, and the bound-drug fraction is high. This include the majority of
clinically useful agents.

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 Class II drugs: These drugs are given in doses that greatly exceed the
number of albumin binding sites. The dose/capacity ratio is high, and a relatively
high proportion of the drug exists freely not bound to albumin.
Clinical importance of drug displacement: if Class I drug and Class II drug
are administered simultaneously , the former displaces the later, leading to a
rapid increase in the concentration of free Class I drug in plasma, which in turn
may lead to increased therapeutic effects, as well as toxic effects.

Drug Metabolism
Drug metabolism generates compounds that are usually more polar and,
hence, more readily excreted than parent drug. Metabolism takes place
predominantly in the liver but can occur at other sites such as kidney, intestinal
epithelium, lung, and plasma.
Drugs are most often eliminated by biotransformation and/or excretion
into the urine or bile.
Note: Some agents are initially administered as inactive compounds (pro-drugs)
and must be metabolized to their active forms.

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A. Kinetics of metabolism

First-order kinetics: The metabolic transformation of drugs is catalyzed by

enzymes, and the rate of drug metabolism is directly proportional to the
concentration of free drug. This means that a constant fraction of drug is
metabolized per unit of time.
Zero-order kinetics: the doses are very large. Therefore, The enzyme is
saturated by a high free-drug concentration, and the rate of metabolism remains
constant over time. A constant amount of drug is metabolized per unit of time.
B. Reactions of drug metabolism
The kidney cannot efficiently eliminate lipophilic drugs that readily cross
cell membranes and are reabsorbed in the distal tubules. Therefore, lipid-soluble
agents must first be metabolized in the liver using two general sets of reactions,
called Phase I and Phase II.
Phase I: this reactions convert lipophilic molecules into more polar
molecules by introducing or unmasking a polar functional group. The Phase I
reactions most frequently involved in drug metabolism are catalyzed by the
cytochrome (CYP) P450 system primarily found in the liver and GI tract.
Consequences of increased drug metabolism include:
1) Decreased plasma drug concentrations
2) Decreased drug activity if metabolite is inactive
3) Increased drug activity if metabolite is active
4) Decreased therapeutic drug effect.
Inhibition of drug metabolism may lead to increased plasma levels over
time with long-term medications, prolonged pharmacological drug effect, and
increased drug-induced toxicities.
Phase II: This phase consists of conjugation reactions. Many Phase I
metabolites are too lipophilic thus, A subsequent conjugation reaction with an
endogenous substrate, such as glucuronic acid (most common and important),
sulfuric acid, acetic acid, or an amino acid, results in polar and therapeutically
inactive compounds.
Note: some drugs may enter Phase II directly and become conjugated without
prior Phase I metabolism.

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 Half-Life of Drugs
Half-life is the time required for 50% of a first-order process to be
completed. Thus, 50% of drug elimination is achieved after one drug-elimination
half-life, 75% after two, 87.5% after three, etc. In practice, first-order processes
such as elimination are near complete after four–five half-lives.
Drug Elimination
Removal of a drug from the body occurs via a number of routes, the most
important being through the kidney into the urine. Other routes include the bile,
intestine, lung, or milk in nursing mothers and extracorporeal dialysis in a renal
failure patient.
A. Renal elimination of a drug
Glomerular filtration: Drugs enter the kidney through renal arteries, which
divide to form a glomerular capillary plexus. Free drug (not bound to albumin)
flows through the capillary slits into Bowman's space as part of the
glomerular filtrate. The glomerular filtration rate (125 mL/min) is normally about
twenty percent of the renal plasma flow (600 mL/min).
Note: Lipid solubility and pH do not influence the passage of drugs into the
glomerular filtrate.
Role of drug metabolism: lipid soluble drugs without modification would
diffuse out of the tubular lumen when the concentration in the filtrate becomes
greater than that in the perivascular space. Thus, the two Phase reactions.
Clinical situations resulting in changes in drug half-life
When a patient has an abnormality that alters the half-life of a drug, adjustment
in dosage is required.
The half-life of a drug is increased by
1) Diminished renal plasma flow or hepatic blood flow for example, in
cardiogenic shock, heart failure, or hemorrhage
2) Decreased extraction ratio for example, as seen in renal disease
3) Decreased metabolism for example, when another drug inhibits its
biotransformation or in hepatic insufficiency, as with cirrhosis.
On the other hand, the half-life of a drug may decrease by
1) Increased hepatic blood flow
2) Decreased protein binding
3) Increased metabolism.
X. Kinetics of Continuous Administration
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Pharmacokinetics also describes the quantitative, time-dependent changes of
both the plasma drug concentration and the total amount of drug in the body,
following the drug's administration by various routes, with the two most common
being IV infusion and oral fixed-dose/fixed-time interval regimens.
Loading dose: A delay in achieving the desired plasma levels of drug may be
clinically unacceptable. Therefore, a loading dose of drug can be injected as a
single dose to achieve the desired plasma level rapidly, followed by an infusion to
maintain the steady state (maintenance dose).

Chapter Two: Drug Receptor Interactions and

Pharmacodynamics
I. Overview
Most drugs exert their effects, both beneficial and harmful, by interacting with
receptors that is, specialized target macromolecules present on the cell surface or
intracellularly. Receptors bind drugs and initiate events leading to alterations in
biochemical and/or biophysical activity of a cell, and consequently, the function of
an organ.
Most receptors are named to indicate the type of drug/chemical that
interacts best with it; for example, the receptor for histamine is called a histamine
receptor. The magnitude of the response is proportional to the number of drug
receptor complexes. Not all drugs exert their effects by interacting with a
receptor; for example, antacids chemically neutralize excess gastric acid, reducing
the symptoms of heartburn.
Pharmacodynamics deals with the interaction of drugs with receptors, the
molecular consequences of these interactions, and their effects in the patient. A
fundamental principle of pharmacodynamics is that drugs only modify underlying
biochemical and physiological processes; they do not create effects de novo.
II. Major Receptor Families
Pharmacology defines a receptor as any biologic molecule to which a drug binds
and produces a measurable response. Thus, enzymes and structural proteins can
be considered to be pharmacologic receptors.
These receptors may be divided into four families:
1) Ligand-gated ion channels
2) G protein coupled receptors

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 3) Enzyme-linked receptors
4) Intracellular receptors.
III. Some Characteristics of Receptors
A. Spare receptors: A characteristic of many receptors is their ability to amplify
signal duration and intensity.
B. Desensitization of receptors
Repeated or continuous administration of an agonist (or an antagonist) may
lead to changes in the responsiveness of the receptor. When repeated
administration of a drug results in a diminished effect, the phenomenon is called
tachyphylaxis. In this phenomenon, the receptors are still present on the cell
surface but are unresponsive to the ligand.
Other types of desensitization occur when receptors are down-regulated.
Binding of the agonist results in molecular changes in the membrane-bound
receptors, such that the receptor undergoes endocytosis decreasing the total
number of receptors available.
Some receptors, particularly voltage-gated channels, require a finite time
(rest period) following stimulation before they can be activated again. During this
recovery phase they are said to be refractory or unresponsive.
IV. Dose Response Relationships
Agonist is defined as an agent that can bind to a receptor and elicit a
biologic response. The magnitude of the drug effect depends on the drug
concentration at the receptor site.
Potency: a measure of the amount of drug necessary to produce an effect
of a given magnitude.
Efficacy [intrinsic activity]: This is the ability of a drug to illicit a physiologic
response when it interacts with a receptor.
Affinity (Drug receptor binding): describes the strength of the interaction
(binding) between a ligand and its receptor.
Agonists: If a drug binds to a receptor and produces a biologic response
that mimics the response to the endogenous ligand, it is known as an agonist.
Antagonists: Antagonists are drugs that decrease the actions of another
drug or endogenous ligand. Antagonism may occur in several ways. Many
antagonists act on the identical receptor macromolecule as the agonist.
Antagonists, however, have no intrinsic activity and, therefore, produce no effect
by themselves. Antagonists are able to bind to target receptors because they

15
possess strong affinity. If both the antagonist and the agonist bind to the same
site on the receptor, they are said to be competitive.
If the antagonist binds to a site other than where the agonist binds, the
interaction is non-competitive or allosteric.
Functional antagonism: An antagonist may act at a completely separate
receptor, initiating effects that are functionally opposite those of the agonist.
This functional antagonism is also known as physiologic antagonism.
Partial agonists: Partial agonists have efficacies (intrinsic activities) greater
than zero, but less than that of a full agonist. A unique feature of these drugs is
that, under appropriate conditions, a partial agonist may act as an antagonist of a
full agonist. As the number of receptors occupied by the partial agonist increases,
the Emax would decrease until it reached the Emax of the partial agonist.
A. Therapeutic index
The therapeutic index of a drug is the ratio of the dose that produces toxicity to
the dose that produces a clinically desired or effective response in a population of
individuals. The therapeutic index is a measure of a drug's safety. Well-tolerated
drugs demonstrate a wide margin, termed the therapeutic ratio, therapeutic
index, or therapeutic window, between the doses required to produce a
therapeutic effect and those producing toxicity.
 TD50 = the drug dose that produces a toxic effect in half the population
 ED50 = the drug dose that produces a therapeutic or desired response in
half the population.
In humans, the therapeutic index of a drug is determined using drug trials and
accumulated clinical experience. Drugs either have a narrow therapeutic index
(warfarin) or a wide therapeutic index (penicillin).

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 Part II: Systemic Pharmacology
Chapter Three: Epilepsy and Antiepileptic Drugs
Overview
Epilepsy is not a single entity but, instead,
an assortment of different seizure types and
syndromes originating from several
mechanisms that have in common the
sudden, excessive, and synchronous
discharge of cerebral neurons. This
abnormal electrical activity may result in a
variety of events, including loss of
consciousness, abnormal movements,
atypical or odd behavior, or distorted
perceptions that are of limited duration but
recur if untreated. The site of origin of the
abnormal neuronal firing determines the
symptoms that are produced. Drug or vagal
nerve stimulator therapy is the most widely
effective mode for the treatment of
patients with epilepsy.
Idiopathic and Symptomatic Seizures
In most cases, epilepsy has no identifiable cause. It can be triggered by
environmental factors, including alteration in blood gases, pH, electrolytes, blood
glucose level, sleep deprivation, alcohol intake, and stress.
Epilepsy can be labeled idiopathic or symptomatic depending if the etiology is
unknown, or is secondary to an identifiable condition.

Idiopathic epilepsy

When no specific anatomic cause for the seizure, such

as trauma or neoplasm, is evident, a patient may be
diagnosed with idiopathic or cryptogenic (primary)
epilepsy. Patients are treated chronically with

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antiseizure drugs or vagal nerve stimulation. Most
cases of epilepsy are idiopathic.
Classification of Seizures
It is important to correctly classify seizures to determine appropriate treatment.
Seizures have been classified into two broad groups: partial (or focal), and
generalized.
Partial Seizures
Partial seizures involve only a portion of the brain, typically part of one lobe of
one hemisphere. Consciousness is usually preserved. May progress, becoming
generalized tonic-clonic seizures.
Simple partial: These seizures are confined to a single locus in the brain.
The electrical discharge does not spread, and the patient does not lose
consciousness. The patient often exhibits abnormal activity of a single limb or
muscle group.
Complex partial: These seizures exhibit complex sensory hallucinations,
mental distortion, and loss of consciousness. Motor dysfunction may involve
chewing movements, diarrhea, and/or urination. Consciousness is altered. Simple
partial seizure activity may spread and become complex and then spread to a
secondarily generalized convulsion.
Generalized Seizures
Generalized seizures may begin locally, may be convulsive or nonconvulsive, and
the patient usually has an immediate loss of consciousness.
Tonic-clonic: Seizures result in loss of consciousness, followed by tonic
(continuous contraction) and clonic (rapid contraction and relaxation) phases. The
seizure may be followed by a period of confusion and exhaustion due to the
depletion of glucose and energy stores.
Absence: These seizures involve a brief, abrupt, and self-limiting loss of
consciousness. The onset generally occurs in patients at 3 to 5 years of age and
lasts until puberty or beyond. The patient stares and exhibits rapid eye-blinking,
which lasts for 3 to 5 seconds. This seizure has a very distinct three-per-second
spike and wave discharge seen on electroencephalogram.
Myoclonic: These seizures consist of short episodes of muscle contractions
that may reoccur for several minutes. They generally occur after wakening and
exhibit as brief jerks of the limbs. Myoclonic seizures occur at any age but usually
begin around puberty or early adulthood.

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 Febrile seizures: Young children may develop seizures with illness
accompanied by high fever. This may occur in siblings. The febrile seizures consist
of generalized tonic-clonic convulsions of short duration and do not necessarily
lead to a diagnosis of epilepsy.
Status epilepticus: two or more seizures recur without recovery of full
consciousness between them. These may be partial or primary generalized,
convulsive or nonconvulsive. Status epilepticus is life-threatening and requires
emergency treatment.
Mechanism of action of antiepileptic drugs
Drugs that are effective in seizure reduction accomplish this by a variety of
mechanisms, including blockade of voltage-gated channels (Na+ or Ca2+),
enhancement of inhibitory GABAergic impulses, or interference with excitatory
glutamate transmission. Antiepilepsy drugs suppress seizures but do not cure or
prevent epilepsy.
Drug Choice
Choice of drug treatment is based on the
 Classification of the seizures being treated
 Patient specific variables (for example, age, comorbid medical conditions,
lifestyle, and other preferences)
 Characteristics of the drug, including cost, toxicities and interactions with
other medications.
In newly diagnosed patients, monotherapy is instituted with a single agent until
seizures are controlled or toxicity occurs. If seizures are not controlled with the
first drug, monotherapy with an alternate antiepileptic drug(s), or vagal nerve
stimulation should be considered.
Primary Antiepileptic Drugs
 Older antiepileptics: phenobarbital, phenytoin, carbamazepine,
ethosuximide, divalproex and valproic acid.
 Second generation "new drugs": gabapentin, lamotrigine, topiramate,
levetiracetam, oxcarbazepine, zonisamide.
 Second-generation drugs are not significantly better than the older
agents. In addition, an increased risk of suicidal behavior and
suicidal ideation has been observed with many of the antiepileptic
drugs.

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 Adverse effect of Anti-Epileptic Drugs

 Nausea and vomiting

 Drowsiness and sedation
 Ataxia
 Rash
 Hyponateraemia
 Weight gain or weight loss
 Teratogenesity
 Osteoprosis

Benzodiazepines
Benzodiazepines bind to GABA inhibitory receptors to reduce firing rate.
Diazepam, and lorazepam are most often used as an adjunctive therapy for
myoclonic as well as for partial and generalized tonic-clonic seizures.
Carbamazepine
Mechanism of action: reduces the propagation of abnormal impulses in the
brain by blocking sodium channels, thereby inhibiting the generation of repetitive
action potentials in the epileptic focus and preventing their spread.
Clinical uses: it is effective for treatment of partial seizures and secondarily
generalized tonic-clonic seizures. It is also used to treat trigeminal neuralgia and
in bipolar disease.
It is not as well tolerated by the elderly as other available antiseizure
medications. A characteristic rash may develop early in therapy but may not
require a change in treatment. Carbamazepine should not be prescribed for
patients with absence seizures because it may cause an increase in seizures.
Divalproex
Divalproex sodium is a combination of sodium valproate and valproic acid and is
reduced to valproate when it reaches the gastrointestinal tract. It was developed
to improve gastrointestinal tolerance of valproic acid.
Mechanisms of action: include sodium channel blockade, blockade of
GABA transaminase, and action at the T-type calcium channels.
Clinical uses: It is effective for the treatment of partial and primary
generalized epilepsies.

20
 Side effects: Rare hepatic toxicity may cause a rise in hepatic enzymes in
plasma, which should be monitored frequently.
Teratogenicity: it causes neural tube defects.
Ethosuximide
Mechanisms of action: reduces propagation of abnormal electrical activity
in the brain, most likely by inhibiting T-type calcium channels.
Clinical uses: It is effective in treating only primary generalized absence
seizures. Use of ethosuximide is limited because of this very narrow spectrum.
Felbamate
Felbamate has a broad spectrum of anticonvulsant action.
Mechanisms of action: blocking voltage-dependent sodium channels,
blocking calcium channels, and potentiation of GABA actions.
Clinical uses: It is reserved for use in refractory epilepsies (particularly
Lennox-Gastaut syndrome) because of the risk of aplastic anemia and hepatic
failure.
Gabapentin
Gabapentin is an analog of GABA. However, it does not act at GABA receptors nor
enhance GABA actions, nor is it converted to GABA.
Mechanism of action is not known.
Clinical uses: It is approved as adjunct therapy for partial seizures and for
treatment of postherpetic neuralgia.
Pharmacoinetics: Gabapentin does not bind to plasma proteins and is
excreted unchanged through the kidneys. It's well tolerated by the elderly
population with partial seizures with limited drug interactions.
Lamotrigine
Mechanism of action: blocks sodium channels as well as high voltage
dependent calcium channels.
Clinical uses: It's effective in partial seizures, generalized seizures,
typical absence seizures, the Lennox-Gastaut syndrome, and bipolar disorder.

Levetiracetam [lee-ve-tye-RA-se-tam]
Mechanism of action is unknown. It demonstrates high affinity for a
synaptic vesicle protein (SV2A).
Clinical uses: It is approved for adjunct therapy of partial onset seizures,
myoclonic seizures, and primary generalized tonic-clonic seizures in adults and
children.
21
 Side effects: dizziness, sleep disturbances, headache, and weakness.

Phenobarbital
This drug should only be considered for chronic therapy once a patient is found to
be refractory to many other drugs, and the benefits of therapy outweigh the
multiple risks.
Mechanism of action: is the enhancement of inhibitory effects of GABA-
mediated neurons.
Clinical uses: in epilepsy, is in treatment of status epilepticus.
Adverse effects: sedation, cognitive impairment, osteoporosis.
Phenytoin
Mechanism of action: blocks voltage-gated sodium channels by selectively
binding to the channel in the inactive state and slowing its rate of recovery. At
very high concentrations, phenytoin can block voltage-dependent calcium
channels and interfere with the release of monoaminergic neurotransmitters.
Clinical uses: it is effective for treatment of partial seizures and generalized
tonic-clonic seizures and in the treatment of status epilepticus.
Adverse effects: Depression of the CNS occurs particularly in the
cerebellum and vestibular system, causing nystagmus and ataxia. The elderly are
highly susceptible to this effect. Gingival hyperplasia may cause the gums to grow
over the teeth. Long-term use may lead to development of peripheral
neuropathies and osteoporosis.
Primidone
It has two active metabolites, phenobarbital and phenylethylmalonamide, which
have longer half-lives than the parent drug.
Clinical uses: It is used only in those patients with refractory epilepsy Due
to the nature of the long term adverse effects.
Vagal Nerve Stimulation
Vagal nerve stimulation requires surgical implant of a small pulse generator with a
battery and a lead wire for stimulus. The device is implanted and lead wires
wrapped around the patient's vagal nerve. Vagal nerve stimulation requires
invasive procedure and is
expensive.
Mechanism of action is unknown.

22
 Clinical uses: It's effective in treatment of partial onset seizures and has
enabled reduction of drug therapy in some cases. It is an alternative for patients
who have been refractory to multiple drugs, who are sensitive to the many
adverse effects of antiseizure drugs, and who have difficulty adhering to
medication schedules.
Epilepsy in Pregnancy
Planning is the most important component. All women should be on high doses of
folic acid prior to conception. Divalproex and barbiturates should be avoided.
Switching women to other drugs before pregnancy should be accomplished when
possible. When seizures are controlled, maintenance medication should be
reduced, if possible, to the lowest dose that provides control. If seizures are not
controlled, medications and dosages should be adjusted. The frequency and
severity of seizures may change during pregnancy.

Chapter Four: Antimicrobial drugs (antibiotic)

Antimicrobial drugs are drugs used to treat microbial infections such as
• Bacterial infection
• Viral infection
• Fungal infection
• Parasites infection
Empiric Therapy
• The antibiotic selected is one that can best kill the microorganisms known
to be the most common cause of infection
• NO Culture? and NO sensitivity test?
• Broad-spectrum
▫ Treat multiple organisms
▫ More likely to disrupt normal flora..
▫ Used when a specific causative organism is unknown.
Empiric Therapy Selection
• Patient Characteristics
▫ age, immune function, other disease states, pregnancy, renal/hepatic
function
• Site of Infection
• Drug Characteristics
▫ Efficacy, side effects, tissue penetration, cost
23
Antimicrobial drugs are divided into:
 Antibacterial drugs
 Antifungal drugs
 Antiviral drugs
 Antiparasitic drugs
Principles Of Antimicrobial Therapy
• Bateriostatic: inhibit bacterial multiplication.
• Bactericidal: kills bacteria.
• Broad spectrum: covers large number of bacteria.
• Narrow spectrum: covers small number of bacteria.
• Extended spectrum: antibiotics that are effective against gram-positive
organisms and also against a significant number of gram-negative bacteria.
Mechanism of Action of Antibiotics
• Block protein formation
▫ Macrolides
▫ Tetracyclines
▫ Aminoglycosides
• Inhibit cell wall formation
• Prevent folic acid synthesis
▫ Sulfonamides
• Interfere with DNA formation
▫ Nalidixic acid
• Antibacterial drugs are sub grouped into:
▫ Beta-lactams
• Penicillins
• Cephalosporins
• Monobactams
• Carbapenems
▫ Aminoglycosides
▫ Macrolides
▫ Tetracyclines
▫ Fluoroquinolones

Beta-Lactams

Mechanisms of action:

24
 • Inhibitors of cell wall synthesis
• Inhibitors of protein synthesis
• Inhibitors of nucleic acid synthesis

Penicillins

Mechanism of penicillins: Inhibit enzymes involved in cross-linking of

peptidoglycan layer of cell wall.

• Natural Penicillins :
▫ Penicillin G and Penicillin V
• Antistaphylococcal Penicillins :(Specifically resist action of staphylococcal
beta-lactamase)
▫ Flucloxacillin, Cloxacillin, Methicillin, Oxacillin, Nafcillin and
Dicloxacillin
• Amino Penicillins :
▫ Amoxicillin and Ampicillin

Penicillin-Inhibitor Combinations

• Augmentin* (Amoxicillin + Clavulanic Acid)

• Ampiclox [ Ampicillin + Cloxacillin ]
• Timentin (Ticarcillin + Clavulanic Acid)
• Zosyn (Piperacillin + Tazobactam)
• Unasyn (Ampicillin + Sulbactam)

Adverse effects of penicillins

• Allergic reactions:
▫ Pruritis
▫ Rash,
▫ Fever
▫ Anaphylactic shock
▫ Non-allergic effects:
• Diarrhea
• Anemia
• Thrombocytopenia

25
Cephalosporins

• Similar structure to penicillin.

• Less gram positive activity, but more gram negative (compared to
penicillins).
• Resist attack by beta-lactamases.

Classification

• First generation
• Second generation
• Third generation
• Fourth generation

First generation

• Spectrum: gram-positive cocci E. coli, Klebsiella and pneumoniae.

• Common use in surgical prophylaxis.
• Gram +
• Skin infections
• Take with food to decrease GI upset
• Cephadroxil*, Cefazolin, Cephalexin*, Cephaloridine, Cephalothin,
Cephapirin and Cephradine*

Second generation

• Spectrum: gram-negative coverage, including some anaerobes.

▫ gram + and gram -
▫ low cost
▫ broad range of organisms
• Cefaclor*, Cefamandole, Cefmetazole, Cefonicid, Ceforanide, Cefotetan,
Cefotiam, Cefoxitin and Cefuroxime

Third generation
26
 • Spectrum: gram-positive and gram-negative cocci (Neisseria gonorrhea)
plus many gram-negative rods.
▫ Works best against Gram -, +
▫ severe infections and immuno-compromised patients
▫ SE: bleeding, no alcohol
• Ceftriaxone, Cefotaxime, Ceftizoxime, Cefoperazone and Ceftazidime.

Fourth generation

• Even wider spectrum

• Resistant to most beta-lactamases
• Enters CNS
▫ Active against Gram + , -
▫ highly resistant to to destruction by beta-lactamases (both 3rd and
4th)
▫ Vancomycin (Vancocin)

Side effects of Cephalosporins

• Hypersensitivity:
▫ Rashes
▫ Fever- most common
▫ Rarely hemolysis

Carbapenems

• Imipenem
• Meropenem
• Ertapenem

Clinical uses

Active against penicillinaseproducing gram-positive and gram-negative organisms,

anaerobes, and P. aeruginosa

Adverse effects of Carbapenems

 Nausea, vomiting, and diarrhea.

27
  Eosinophilia and neutropenia
 Imipenem may provoke seizures,

Aminoglycosides

• Not given orally due to their poor absorption

• Low dose: bacteriostatic
• High dose: bactericidal
• Use primarily for Gram -
• Monitor peak and trough
• Gentamicin, Tobramycin, Amikacin, Netilmicin, Neomycin, Framycetin,
Streptomycin and Spectinomycin
• Activity and clinical uses:
▫ Bactericidal, accumulated intracellularly in microorganisms.
▫ Useful spectrum includes gram-negative rods;
• Potential for serious AE
▫ ototoxicity, nephrotoxicity, Neuromuscular paralysis and allergic
reaction.

Macrolides

Activity and clinical uses:

• Wide-spectrum antibiotics
• Gram-positive cocci
• Atypical organisms (Chlamydia and Mycoplasma).
• Bacteriostatic and high doses are bactericidal
• Erythromycin, Azithromycin, Telithromycin and Clarithromycin

Side effects

• Gastrointestinal distress and hepatotoxicity are Common

• Reversible Ototoxicity at high doses
• Cholestatic jaundice:

Tetracyclines

• Mechanism of action: Inhibit the growth of bacteria, does not kill them
28
 • Clinical Uses: Gram +, -, broad spectrum
• Contraindication: children under 8, pregnant or nursing women
• Adverse Effect: GI upset, hepatotoxicity, stained teeth, superinfections
• Doxycycline, Tetracycline and Minocycline

Fluoroquinolones

• Very broad-spectrum antibiotic.

• Kill rather than inhibit.
• Clinical uses: active against aerobic gram - organisms.
• Ciprofloxacin, Levofloxacin, Moxifloxacin, Gatifloxacin, Norfloxacin and
Ofloxacin

Mechanism of Action

 Inhibit the replication of bacterial DNA during bacterial growth and

reproduction.

Adverse effects

 Gastrointestinal: nausea, vomiting, and diarrhea.

 Central nervous system: headache and dizziness or light-headedness.
 Phototoxicity: Patients are advised to avoid excessive sunlight and to apply
sunscreens.
 Connective tissue problems: arthropathy can infrequently cause ruptured
tendons.

Contraindications
 Pregnancy
 Nursing mothers
 Children under 18 years of age

Anti-viral drugs
• Viruses have no cell wall and made up of nucleic acid components.
• Viruses containing envelope – antigenic in nature.
• Common antiviral drugs are:

29
 • Acyclovir and Interferons
• Acyclovir:
• Treats herpes-viruses; herpes simplex, herpes zoster, Epstein Barr
virus, CMV
• Effective against actively replicating viruses
• AE: N/V, anorexia, nephrotoxic and headache.

Interferons

Mechanism of action: The antiviral mechanism is incompletely understood. It

appears to involve the induction of host cell enzymes that inhibit viral RNA
translation, ultimately leading to the degradation of viral mRNA and tRNA.

Adverse effects of Interferons

• Acute flu-like syndrome (fever, headache

• Neurotoxicity (confusion, seizures)
• Cardiotoxicity - arrhythmia
• Impairment of fertility

Anti-fungal drugs
• Fungal infections are usually more difficult to treat than bacterial infections,
because fungal organisms grow slowly and because fungal infections often
occur in tissues.
• Therapy of fungal infections usually requires prolonged treatment.

Mechanisms of antifungal drugs

• Antifungals damaging permeability of the cell membrane Imidazoles:

• Clotrimazole
• Ketoconazole
• Miconazole
• Fluconazole
• Antifungals inhibiting chitin synthesis in the cell wall
• Griseofulvin
• Antifungals inhibiting synthesis of nucleic acids

30
 • Flucytosine

Types of fungal infections

• Superficial fungal infections: involve cutaneous surfaces (skin, nails, and

hair), and mucous membrane surfaces (oropharynx and vagina).
• Deepseated or disseminated fungal infections: systemic agents:
amphotericin B, ketoconazole, fluconazole, itraconazole, and voriconazole.

Antifungal Azoles are:

▫ Clotrimazole
▫ Miconazole
▫ Ketoconazole
▫ Fluconazole
▫ Clotrimazole
▫ voriconazole

Polyene antibiotics:

• Amphotericin B
• Nystatin

Anti-parasitic drugs
• A parasite is an organism that lives on or in a host and gets its food.
• Types of antiparasitic drugs are:
▫ Anthelminths
▫ Antimalarials

Anti-helminths

• Mebendazole
• Praziquantel
• Albendazole
• Tinidazole

Mebendazole
31
  Mechanism of action: acts by binding to and interfering with the assembly
of the parasites' microtubules and also by decreasing glucose uptake
 Clinical uses: is effective against a wide spectrum of nematodes.
 Adverse effects: relatively free of toxic effects, patients may complain of
abdominal pain and diarrhea.
 Contraindications: pregnant women

Praziquantel

 Mechanism of action: Increases Permeability of the cell membrane to

calcium, causing contracture and paralysis of the parasite.
 Clinical uses: agent of choice for the treatment of all forms of
schistosomiasis and other trematode infections and for cestode infections
like cysticercosis.
 Adverse effects: drowsiness, dizziness, malaise, and anorexia, as well as
gastrointestinal upsets.
 Contraindications: pregnant women or nursing mothers and for the
treatment of ocular cysticercosis.
 Drug interactions: due to increased metabolism have been reported with
dexamethasone, phenytoin, and carbamazepine. Cimetidine, which inhibits
cytochrome P450 isozymes, causes increased praziquantel levels.

Albendazole
 Mechanism of action: inhibits microtubule synthesis and glucose uptake in
nematodes.
 Clinical uses: treatment of cestodal infestations, and hydatid disease.
 Adverse effects: are mild and transient and include headache and nausea.
o Treatment of hydatid disease (3 months) has a risk of hepatotoxicity
and, rarely, agranulocytosis or pancytopenia.
o Medical treatment of neurocysticercosis is associated with
inflammatory responses to dying parasites in the CNS, including
headache, vomiting, hyperthermia, convulsions, and mental
changes.
 Contraindications:The drug should not be given during pregnancy or to
children under 2 years of age.

32
Metronidazole

 Mechanism of action: The nitro group of metronidazole is able to serve as

an electron acceptor, forming reduced cytotoxic compounds that bind to
proteins and DNA, resulting in cell death.
 Clinical uses: a nitroimidazole, is the mixed amebicide of choice for
 treating amebic infections, Giardia lamblia, Trichomonas vaginalis,
anaerobic cocci, and anaerobic gram-negative bacilli, anaerobic, gram-
positive bacillus Clostridium difficile and also brain abscesses caused by
these organisms.
 Adverse effects: The most common are GI nausea, vomiting, epigastric
distress, and abdominal cramps. An unpleasant, metallic taste. Other
effects include oral moniliasis (yeast infection of the mouth) and, rarely,
dizziness, vertigo, and numbness or paresthesias in the peripheral nervous
system.
 Drug interactions: If taken with alcohol, a disulfiram-like effect occurs.

Tinidazole
 is a second-generation nitroimidazole that is similar to metronidazole in
spectrum of activity, absorption, adverse effects and drug interactions.
 Tinidazole is as effective as metronidazole, with a shorter course of
treatment, yet is more expensive than generic metronidazole.

Anti-malarials

Drugs that are active against the four species of Plasmodia.

• Quinine
• Chloroquine

Chapter Five: Insulin Regimens and Oral Hypoglycemic Agents

33
When should insulin be started?

 All type I diabetic patients

 Any patient who presents with diabetes, HbA1c ≥9%, and have symptoms
of complication
 Patients who fail maximum anti-hyperglycemic therapy

Formulations of insulin

 Rapid acting insulin

o Insulin aspart
o Insulin glulisine
o Insulin lispro
 Short acting insulin
o Regular insulin
o 75/25, 70/30, 50/50 (intermediate/regular) preparation.
 Intermediate acting insulin
o Insulin NPH " Non Proteated Hagedorn"
 Long acting insulin
o Insulin detemir
o Insulin glargine

Insulin regimens

 Basal
o Once daily: in the morning or in the evening with a long acting insulin.
Patient is also on oral anti-hyperglycemic agents. Patient takes 10U of
Insulin detemir or glargine in the morning or in the night.
 Twice daily: in the morning and in the evening with a short acting
insulin. Usually 70/30 in the morning and 50/50 in the evening. Daily
dosage is 0.5U/kg, 2/3 of the daily dosage in units are taken in the
morning and 1/3 of the daily dosage in units are taken in the evening.

 Basal-bolus "prandial"
 Patient takes a long acting insulin in the morning and rapid acting
insulin before break-fast, lunch and dinner.

34
  Daily dosage is 10U of long acting Insulin "detemir or glargine" in the
morning or in the night and 0.1-0.3 U of rapid acting insulin 15 minutes
before each main meal.
 Sliding-scale Protocol
 Used in hospital inpatients, a short acting insulin is given at scheduled
times according to their glucose level.
 Desirable usually when there is inflammation or active infection,
because these may dramatically alter the blood glucose level.
 Blood glucose levels are measured every 2 hours then insulin is given
accordingly.
 If below 150mg/dl no insulin required if above, 2 U are give every
50mg/dl rise in blood glucose.
 If blood glucose rise beyond 450mg/dl, consult a doctor.

Oral Anti-Hyperglycemic Agents

 Begunides
o Metformin
 Sulfonylureas
o Glipizide
o Gliburide
o Chlorpropamide
 Thiazolidinedianose
o Pioglitazone
o rosiglitazone

Begunides

Cornestone of the therapy in type II diabetes mellitus along with dietary

change and exercise
Best initial pharmacological management, unless contraindicated
Mechanism of action: the exact mechanism is not known but, it slows
down glucose absorption of the gut and increases glucose uptake of the
muscles.
Contraindication: renal disease, liver disease and lung disease.

35
 Adverse effects: lactic acidosis and GI upset "anorexia, nausea, vomiting
and diarrhea"

Sulfonylureas

 Fallen out of favor because of increased risk of hypoglycemia

 Used as a second line therapy when meftormin is contraindicated or fails
as monotherapy.
 Can be used in underweight patients
 Mechanism of action: improve insulin release and reduce peripheral
resistance to insulin.
 Adverse effects: hyponatraemia Weight gain, and hypoglycemia.

Thiazolidinediones

 Fallen out of favor

 Used as a second line therapy when meftormin is contraindicated or fails
as monotherapy.
 Adverse effects: Liver disturbances and fluid retention "edema".
 Contraindication: Heart failure and Hypertensive patients.

Chapter Six: Anti-hypertensive drugs (Anti-HTN Drugs)

Blood Pressure Classification according to the JNC 7

• Normal: <120 / <80 range SBP:110 -130 DBP:70 – 80

• Pre hypertension: SBP:130-139 DBP:80-89
• First stage: SBP: 140-159 DBP:90-99
• Second stage: SBP: 160-179 DBP:100-109
• Third stage: SBP:>180 DBP:>110

Types of Hypertension

36
 • Essential or primary: Contributors include: salt sensitivity, insulin
resistance, genetics, environmental factors, and others
• Secondary: renal, adrenal, coarctation of the aorta, steroids, pregnancy etc

Non-pharmacologic Management of Hypertension

• Weight reduction
• Exercise
• Salt restriction in diet
• Stress reduction
• DASH eating plan
• Moderation in alcohol intake
• Manage co-morbidities
• If systolic BP cannot be maintained <140 systolic, treat pharmacologically.

Anti-hypertensive Drugs

1. Angiotensin converting enzyme inhibitors (ACEI)

2. Angiotensin II Receptor Blockers
3. Alpha I antagonists and alpha II agonists
4. Beta blockers
5. Calcium channel blockers
6. Diuretics and Direct vasodilators
7. Renin inhibitors

Angiotensin converting enzyme inhibitors (ACEI)

• Enalapril
• Captopril
• Lisinopril
• Ramipril

Mechanism of Action

• Block the enzymes that convert angiotensin I to angiotensin II (potent

vasoconstrictor)
37
 • Have action of vasodilation and decrease aldosterone production
• Inhibit breakdown of bradykinins (vasodilator) prolonging effect
• Reverse remodeling of heart muscle and blood vessels

Clinical Uses

• Reno-protective
• Excellent for heart failure and hypertension
• Improve post-myocardial infarction survival
• Used alone or in combination

Adverse Effect

 Dry cough
 Hyperkalemia
 Chronic dry mouth
 Skin rash

Contraindication: pregnancy

Angiotensin II Receptor Blockers (ARBs)

• Losartan
• Candesartan
• Valsartan
• Telmisartan

Mechanism of Action

• Block effects of angiotensin II, compete with angiotensin II for tissue

binding sites
• Block the receptors in brain, kidneys, heart, vessels and adrenal tissue
• Similar end results as seen with ACEIs

Clinical Uses

 Used as an alternative therapy when patients can't tolerate ACEIs due to

dry cough
38
Adverse Effect

• Less likely to cause hyperkalemia and cough is rare

• Other side effects, similar to ACEIs

Alpha I Adrenergic Antagonists

• Doxazosin
• Prazosin
• Terazosin

Mechanism of Action

o Dilate vessels and decrease peripheral vascular resistance by block alpha I

receptors

Clinical Uses

 Used when hypertension co-exist with benign prostatic hyperplasia

Adverse Effect

 Orthostatic hypotension
 Dizziness
 Syncope
 Possible sodium and fluid retention

Alpha II Agonists

• Methyldopa
• Clonidine
• Guanfacine

Mechanism of Action

39
  Centrally acting sympatholytics stimulate presynaptic alpha II receptors in
the brain
 Less norepinephrine is released and sympathetic outflow is reduced
 Results in decreased cardiac output, heart rate, peripheral vascular
resistance and blood pressure

Adverse Effect

 Fluid and sodium retention

 Sedation
 Nightmares
 Depression
 Nausea
 Flatulence
 Constipation
 Gynecomastia, lactation
 Hemolytic anemia, leukopenia, thrombocytopenia (rare)

Beta Adrenergic Blockers

Classification

Cardio-selective beta blockers

• Atenolol 25mg
• Metopronolol 50mg

Non-cardioselective beta blockers

• Propranolol
• Labelalol
• Carvedilol

40
Mechanism of Action

• Decrease heart rate, force of myocardial contraction, cardiac output.

• It inhibits renin–angiotensin–aldosterone system (RAAS) is a hormone
system that regulates blood pressure and water (fluid) .

Clinical Uses

• Drugs of choice with patients with tachycardia, angina, MI, left ventricular
hypertrophy and high renin hypertension.

Adverse Effect

 Fatigue
 Impotence
 Insomnia
 Depresion

Contraindication

 COPD and Asthma patients

 Patients with peripheral vascular disease

Calcium Channel Blockers CCBs

Classification

Cardio-selective beta blockers

• Diltiazem
• Verapamil

Non-cardioselective beta blockers

• Amlodipine
• Nifedipine
• Nicardapine

Mechanism of Action
41
  Dilate peripheral arteries and decrease peripheral vascular resistance by
relaxing vascular smooth muscle

Adverse Effect

 Headache
 Bradycardia
 Constipation
 Heart block

Direct Vasodilators

• Hydralazine
• Felodapam
• Minoxidil

Mechanism of Action

o Relax smooth muscle in blood vessels resulting in dilation and decreased

peripheral vascular resistance
o Reduce after load so helpful in heart failure
o May cause sodium and water retention

Hydralazine

• Directly relaxes arterioles, via relaxing smooth muscles

• Little effect on venous tone
• Mechanism of action unclear
• Safe to use in pregnancy
1
• T 2 = 1 hour
• Side Effects: lupus-like syndrome

Minoxidil

• Hemodynamic properties similar to that of hydralazine, but more potent

• More reflexive cardiac effects & fluid retention
• Last resort

42
 • Main side effect:
▫ Hypertrichosis

Nicorandil

• Acts both as a nitrate (activating cGMP) and as a K-channel opener

• Oral administration
• Indicated with angina, and as alternative to nitrates when tolerance is
problem
• Side effects:
▫ Similar to nitrates

Diuretics
Mechanism of Action

• Indicated for the treatment of edematous and nonedematous conditions

• May be useful in preventing renal failure by sustaining urine flow
• A minimum daily urine output of approx. 400ml is required to remove
normal amounts of metabolic end products
• Act on kidneys to decrease absorption of sodium, chloride, water and other
substances such as calcium

Classificaion

 Thiazide duiretics …………............ hydrochlorothiazide

 Loop duiretics ……….. .............furesimade 40mg
 Potasium sparing duiretics ...............Spirolactone 25mg.

Clinical Uses

• Edema and ascites

• Management of heart failure
• Hypertension

Thiazide Diuretics

• Chlorothiazide
43
 • Chlorthalidone
• Hydrochlorothiazide

Loop Diuretics

 Bumetamide and furosemide.

 Inhibit sodium and chloride reabsorption in the ascending limb of the Loop
of Henle
 Potent diuresis
 Need to restrict dietary sodium when taking these meds

Potassium Sparing Diuretics

 Act at distal tubule to decrease reabsorption of sodium and potassium

excretion
 Spironolactone (prototype) blocks the sodium retaining effects of
aldosterone
 Weak diuretics when used alone, often used in combination
 Contraindicated in renal failure

Side effects of Duiretics

 Hypokalemia
 Hyponatremia
 Hyperglycemia
 Impotence
 Skin rash

Chapter Seven: Anti-coagulants

• Thrombosis may occur in both arteries and veins
• Arterial thrombi cause disease by obstructing blood flow which can result in
tissue ischemia or death
• Venous thrombosis is associated with venous stasis.
• Anticoagulant drugs help prevent the development of harmful clots in the
blood vessels.

44
 • Given to prevent formation of new clots; do not dissolve clots already
present
• Prototype is Heparin
• Can cause heparin induced thrombocytopenia
• Aspirin, Heparin and Warfarin

Risk Factors of Thromboembolism

1. Obesity
2. Myocardial Infarction
3. Atrial fibrillation
4. Prosthetic heart valves
5. History of DVT or PE
6. Cigarette smoking
7. Immobility

Side effects of Anticoagulant Drugs

 Excessive bleeding (haemorrhages)

 severe bruising
 Headache
 Pain

Contraindications

• Active or recent bleeding

• History of stroke within 30 days
• Major surgery or severe trauma within past month
• Uncontrolled or severe hypertension ( > 180/120 mmHg)
• History of intracranial hemorhage
• Neoplasm
• AV malformation or aneurysm
• Thrombocytopenia platelet count less than 100,000
• Creatinine greater than 2 mg/dl

45
 Heparin

Mechanism of Action

• Inhibits conversion of prothrombin to thrombin and prevents thrombus

formation.
• Further affects coagulation by preventing conversion of fibrinogen to fibrin,
and platelet aggregation.

Low Molecular Weight Heparins

• Fragmin (dalteparin)
• Lovenox (enoxaparin)

Side effects

○ Bleeding (bruises, epistaxis, bleeding gums, hematuria, GI- bleeding)

Warfarin

• Most commonly used oral anticoagulant

• Anticoagulant of choice for long-term maintenance therapy.
• Anticoagulant effects do not occur for 3-5 days after warfarin is started
• Regulated according to the INR (international normalized ratio) with
Therapeutic values of 2 to 3.

Mechanism of Action

• Drug acts in liver to prevent synthesis of vitamin K-dependent clotting

factors.
• Acts as a competitive antagonist to hepatic use of vitamin K.

Other anticoagulants
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 • Orgaran (danaparoid)—low molecular weight, heparin-like drug. Given
subQ. Used in management of hip surgery, ischemic stroke or in those who
cannot take heparin. Does not contain heparin.
• Refludan (lepirudin)—used as heparin substitutes
• Arixtra (fondaparinux) –binds to clot bound factor Xa, inhibits thrombus
productions.

Thrombolytics

• Given to dissolve thrombi

• Stimulate conversion of plasminogen to plasmin, an enzyme that breaks
down fibrin (the framework of a thrombus)
• Used in severe thromboembolic disease such as MI and PE
• Goal is to re-establish blood flow and prevent tissue damage
• Also used to dissolve clots in arterial or venous canola or catheters
• Must obtain baseline INR, aPTT, platelet count and fibrinogen
• Monitor labs 2-3 hours after thrombolytic treatment is instituted to
determine efficacy

Drugs Used to Control Bleeding

• Amicar (aminocaproic acid) and Cyklokapron (tranexamic acid) are used to

stop bleeding caused by overdoses of thrombolytic agents

Chapter Eight: Anti-inflammatory Drugs

 Inflammation: is a biological response of vascular tissues to harmful stimuli,
such as damaged cells, or irritants.
 Signs of inflammation
 Redness
 Hotness
 Swelling
 Loss of function

 Anti-inflammatory drugs are classified into:

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  Steroid drugs:
 Cortisone
 Hydrocortisone
 Betamethasone
 Dexamethasone
 Prednisalone
 Non steroid drugs:
 Aspirin
 Ibuprofen
 Diclofenac
 Indomethacine

Side effects of anti-inflammatory drug

• Immunosuppression
• Hyperglycemia
• Osteoporosis
• Obesity
• Cancer
• weakness
• Growth failure
• Pubertal delay
• Glaucoma

Chapter Nine: Antacids and Anti-emetics

This chapter describes drugs used to treat three common medical conditions
involving the gastrointestinal tract: peptic ulcers and gastroesophageal reflux
disease (GERD), chemotherapy-induced emesis, and diarrhea and constipation.

Antacids

Treatment approaches include

1) Eradicating H. pylori infection
2) Reducing secretion of gastric acid with the use of H2-receptor antagonists
or PPIs

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 3) Providing agents that protect the gastric mucosa from damage, such as
misoprostol and sucralfate.

Antacids

 Aluminum salts
 Magnesium salts
 Calcium salts
Sodium bicarbonate

Used alone or in combination

Antacids: Side Effects

Minimal, and depend on the compound used

• Hypophosphatemia (bindins of phosphate by aluminum), belching and

flatulence.

• Aluminum and calcium

▫ Constipation
• Magnesium
▫ Diarrhea

Histamine H2-Receptor Antagonists

The use of these agents has decreased with the advent of the PPIs.

Cimetidine "prototype" limited by its adverse effect profile and drug interactions
Ranitidine
Famotidine
Nizatidine

Mechanism of Action

• Block histamine (H2) at the receptors of acid-producing parietal cells

• Production of hydrogen ions is reduced, resulting in decreased production
of HCl

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 • Suppressed acid secretion in the stomach

Therapeutic Uses

• Shown to be effective for:

▫ Gastric ulcer
▫ Gastroesophageal reflux disease (GERD)
▫ Upper GI bleeding
▫ Duodenal ulcer (with or without H. pylori)
• May be effective for:
▫ Stress ulcers
▫ Peptic esophagitis

Side Effects

 Reduced gastric acid production. The most common side effects are
headache, dizziness, diarrhea, and muscular pain. Other central nervous
system effects (confusion, hallucinations) occur in elderly or after IV
administration. Cimetidine "gynecomastia, galactorrhea, and reduced
sperm count.

Drug Interactions

• SMOKING has been shown to decrease the effectiveness of H2 blockers.

• Drugs such as ketoconazole, which depend on an acidic medium for gastric
absorption, may not be efficiently absorbed if taken with one of these
antagonists.

Proton Pump Inhibitors ( PPI)

These agents are prodrugs with an acid-resistant enteric coating to protect them
from premature degradation by gastric acid. For maximum effect, PPIs should be
taken 30 minutes before breakfast or the largest meal of the day.

Omeprazole
Esomeprazole
Lansoprazole

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Pantoprazole
Rabeprazole

Mechanism of Action

 Bind to the H+/K+-ATPase enzyme system (proton pump) of the parietal

cell, thereby suppressing secretion of hydrogen ions into the gastric lumen.
 The membrane-bound proton pump is the final step in the secretion of
gastric acid.

Therapeutic Uses

• GERD maintenance therapy

• Erosive esophagitis
• Short-term treatment of active duodenal and
• Treatment of H. pylori-induced ulcers
• NSAID induced ulcer.

Adverse effects: generally well tolerated, but in long-term There is

increased incidence of gastric carcinoid. Increased concentrations of viable
bacteria in the stomach, low vitamin B12, diarrhea and Clostridium difficile colitis.
Drug interactions: Omeprazole inhibits the metabolism of warfarin,
phenytoin, diazepam, and cyclosporine. Incomplete absorption of calcium
carbonate products (use calcium citrate as a source of calcium).

Prostaglandins
Mechanism of action: Prostaglandin E2, produced by the gastric mucosa,
inhibits secretion of HCl and stimulates secretion of mucus and bicarbonate
(cytoprotective effect).
Clinical uses: Misoprostol a stable analog of prostaglandin E1, is approved
for prevention of gastric ulcers induced by NSAIDs in patients who are
taking NSAIDs and are at high risk of NSAID-induced ulcers, such as the
elderly or patients with ulcer complications.
Contraindications: pregnancy "produces uterine contractions"
Side effects: Dose-related diarrhea and nausea are the most common
adverse effects and limit the use of this agent.
H. Mucosal protective agents
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Sucralfate:
 Mechanism of action: creates a physical barrier that impairs diffusion of
HCl and prevents degradation of mucus by pepsin and acid. It also
stimulates prostaglandin release as well as mucus and bicarbonate output,
and it inhibits
 peptic digestion.
 Clinical uses: effectively heals duodenal ulcers and is used in long-term
maintenance therapy to prevent their recurrence.
 Drug interaction: it should not be administered with H2 antagonists or
antacids.
This agent does not prevent NSAID-induced ulcers, nor does it heal gastric
ulcers.
Bismuth subsalicylate:
Clinical uses: effectively heal peptic ulcers.
Mechanism of action: In addition to their antimicrobial actions, they inhibit
the activity of pepsin, increase secretion of mucus, and coat and protect
the ulcer crater.
Anti-emetics

• Anti-emetics usually taken as therapy against vomiting induced by motion

sickness, cancer chemotherapy, etc.
• Include:
▫ Phenothiazines such as Prochlorperazine
▫ 5-HT3 receptor blockers such as Ondansetron
▫ Anti-dopaminergics such as metoclopramide, domperidone

Phenothiazines
The first group of drugs shown to be effective antiemetic agents, such as
Prochlorperazine.
 Mechanism of action: acts by blocking dopamine receptors.
 Clinical uses: It is effective against low or moderately emetogenic
chemotherapeutic agents
 Side effects: hypotension and restlessness, extrapyramidal symptoms and
sedation.
5-HT3 receptor blockers
Ondansetron

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Granisetron
Palonosetron
Dolasetron
 Mechanism of action: selectively block 5-HT3 receptors in the periphery
(visceral vagal afferent fibers) and in the brain (chemoreceptor trigger
zone).
 Clinical uses: important in treating emesis linked with chemotherapy and
are efficacious against all grades of emetogenic therapy. They have the
advantage of a long duration of action.
 Precautions: doses of these agents should be adjusted in patients with
hepatic insufficiency.
 Side effect: Headache is a common, prolonged of the QT interval.
These drugs are costly.
Substituted benzamides
Metoclopramide
o Mechanism of action

 Acts centrally by blocking dopamine D2 receptors

 Raises tone of lower esophageal sphincter (LES)
 Relaxes pyloric antrum and duodenal cap
 Increases peristalsis & emptying of upper gut

o Clinical uses: highly effective anti-emetic at high doses

o Side effects: sedation, diarrhea, and extrapyramidal symptoms, limit its
high-dose use "Antidopaminergic".

Domperidone

o Selective D2 receptor antagonist

o No Ach-like effect
o Less risk of adverse effects in the CNS, but may cause gynecomastia &
galactorrhea
o Used for nausea and vomiting associated with GI d/o, with cytotoxic drugs

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