• derived from the Greek word for drug

• A science that studies drug effects within a living system, biochemical and physiological aspects

• Deals with all drugs used in society today, legal or illegal, including street, prescription, and non-prescription or over –the-counter medications

What is Pharmacology?

• A drug is defined as any substance; chemical agent; used in the

• Diagnosis• Cure• Treatment• prevention of a disease or condition

Drug

• Chemical Name• Generic Name• Trade Name

Drug Names

• Describes its molecular structure and distinguishes it from other drugs

Chemical Name

• Determined by the pharmaceutical company along with a special organization known as the U.S. Adopted Names Council (USAN)

Generic name

• Or brand name- the manufacturer selects alone…can become a registered trademark.

• They are the only one who can advertise and market the drug under that name.

Trade Name

• The particular spelling of a brand name drug is proposed by a manufacturer for one of several reasons.

How is the Trade Name Chosen?

• Azmacort- treats asthma

• Rythmol- treats cardiac arrhythmias

1. To indicate the disease process being treated

• Pseudoephedrine to Sudefed

• Haloperidol to Haldol

• Ciprofloxacin to Cipro

2. To simplify the generic name

• Slow-K slow release potassium supplement

3. To indicate the duration

• Or legend drugs• Means in order to obtain drug, you must

have a legal prescription

Prescription Drugs

• Or Over-the-Counter (OTC) drugs• Drug that may be purchased without a

prescription

Non-Prescription Drugs

Drugs have been identified or derived from four main sources:

• Plants• Animals• Minerals and Mineral Products• Synthetic or Chemical Substances Made in

the Laboratory

Sources of Drugs

Routes of drug administration

The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts

Routes of Drug Administration

ImportantInfo

• The main routes of drug entry into the body may be divided into two classes:

–Enteral–Parenteral

• Enteral - drug placed directly in the GI tract:

– sublingual - placed under the tongue

– oral - swallowing (p.o., per os)

– rectum - Absorption through the rectum

Enteral Routes

Some drugs are taken as smaller tablets which are held in the mouth or under the tongue.

• Advantages – rapid absorption– drug stability– avoid first-pass effect

Sublingual/Buccal

• Disadvantages

– inconvenient– small doses– unpleasant taste of some drugs

Sublingual/Buccal

• Disadvantages– Sometimes inefficient - only part of the drug may

be absorbed

– First-pass effect - drugs absorbed orally are initially transported to the liver via the portal vein

– irritation to gastric mucosa - nausea and vomiting

Oral

• Disadvantages

– destruction of drugs by gastric acid and digestive juices

– effect too slow for emergencies

– unpleasant taste of some drugs

– unable to use in unconscious patient

Oral

• The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation.

• The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally

First-pass Effect

First-pass Effect Magnitude of first pass hepatic effect: Extraction ratio (ER)ER = CL liver / Q ; where Q is hepatic blood flow (usually about 90 L per hour. Systemic drug bioavailability (F) may be determined from the extent of absorption (f) and the extraction ratio (ER): F = f x (1 -ER)

First-pass Effect

• Absorption across the rectal mucosa occurs by passive diffusion.

• This route of administration is useful in children, old people and unconscious patients.

• Eg., drugs that administered are: aspirin, acetaminophen, theophylline, indomethacin, promethazine & certain barbiturates.

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RECTAL ADMINISTRATION:

Advantages: 1. Suitable for unconscious patients and

children 2. suitable if patient is nauseous or vomiting 3. easy to terminate exposure 4. good for drugs affecting the bowel such

as laxativesDisadvantages: 2. absorption may be variable 3. irritating drugs contraindicated

Rectal

– Intravascular (IV, IA)- placing a drug directly into the blood stream

– Intramuscular (IM) - drug injected into skeletal muscle– – Subcutaneous - Absorption of drugs from the

subcutaneous tissues

– Intrathecal : into CSF

Parenteral Routes

IntravascularAbsorption phase is bypassed (100% bioavailability)1.precise, accurate and almost immediate onset of

action, 2. large quantities can be given, fairly pain free

Disadvantages a-. greater risk of adverse effects b- high concentration attained rapidly C- risk of embolism

Intramuscular

1. very rapid absorption of drugs in aqueous solution 2. Slow release preparations Disadvantages

pain at injection sites for certain drugs

Subcutaneous

1. slow and constant absorption 2. absorption is limited by blood flow, affected if circulatory problems exist

3. concurrent administration of vasoconstrictor will slow absorption

1. gaseous and volatile agents and aerosols 2. rapid onset of action due to rapid access to circulation a. large surface area b. thin membranes separates alveoli from

circulation c. high blood flow

Inhalation

Topical•Mucosal membranes (eye drops, antiseptic) •Skin a. Dermal - rubbing in of oil or ointment (local action, sun screen, an callus removal) b. Transdermal - absorption of drug through

skin (systemic action) i. stable blood levels ii. no first pass metabolism iii. drug must be potent or patch becomes too large

o Intra nasal administration

• Drugs generally administered by intra nasal route for treatment of local condition such as perennial rhinitis, allergic rhinitis and nasal decongestion etc.

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• intravenous 30-60 seconds• intraosseous 30-60 seconds• endotracheal 2-3 minutes• inhalation 2-3 minutes• sublingual 3-5 minutes• intramuscular 11-30 minutes• subcutaneous 14-30 minutes• rectal 5-30 minutes• ingestion 30-90 minutes• transdermal (topical) variable (minutes to hours)

Route for administration -Time until effect-

Aspects of Drug Pharmacokinetics (ADME)

Drug at site of administration

Drug in plasma

Drug/metabolitesin urine, feces, bile

Drug/metabolites in tissues

Absorption

Distribution

Elimination

Metabolism

• Definition :The process of movement of unchanged drug from the site of administration to systemic circulation.

• The ultimate goal is to have the drug reach the site of action in a concentration which produces a pharmacological effect.

• No matter how the drug is given (other than IV) it must pass through a number of biological membranes before it reaches the site of action.

Absorption

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LIPID BILAYER

the Rate dependent on polarity and size.

Polarity estimates partition coefficient.

The greater the lipid solubility – the faster the rate of diffusion

Smaller molecules penetrate more rapidly.

Highly permeable to O2, CO2, NO and H2O .

Large polar molecules – sugar, amino acids, phosphorylated

intermediates – poor permeability

These are essential for cell function – must be actively transported

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DIFFUSION THR OUGH MEMB RANES

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MOVEMENT OF SUBSTANCES ACROSS CELL MEMBRANES

1) Passive diffusion2) Carrier- mediated transport a) Facilitated diffusion

b) Active transport3) PINOCYTOSIS

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MECHANISMs OF DRUG ABSORPTION

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1) PASSIVE DIFFUSION

• Also known as non-ionic diffusion.

• It depends on the difference in the drug concentration on either side of the membrane.

• Absorption of 90% of drugs.• The driving force for this

process is the concentration or electrochemical gradient.

• Involves a carrier (a component of the membrane) which binds reversibly with the solute molecules to be transported to yield the carrier solute complex which transverses across the membrane to the other side where it dissociates to yield the solute molecule

• The carrier then returns to its original site to accept a fresh molecule of solute.

• There are two types of carrier mediated transport system:

a) facilitated diffusion b) active transport

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2) CARRIER MEDIATED TRANSPORT MECHANISM

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a) Facilitated diffusion

• This mechanism driving force is concentration gradient.

• In this system, no use of energy is involved (down-hill transport), therefore the process is not inhibited by metabolic poisons that interfere with energy production.

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b) Active transport• More important process than

facilitated diffusion.• The driving force is against

the concentration gradient or uphill transport.

• Since the process is uphill, energy is required in the work done by the barrier.

• As the process requires energy, it can be inhibited by metabolic poisons that interfere with energy production.

Drug Absorption Active vs. Passive

• Active transport:• Carrier-mediated• Energy-dependent• Against conc gradient• Shows carrier saturation

kinetics Passive transport• Energy-independent• No carrier involved• Along conc gradient• No saturation kinetics

ATP

ADP + Pi

A-

BH+

Passive diffusion of a water-sol drug via aqueous channel

Carrier-mediated energy-dependent active transport

Passive diffusion of a lipid-sol drug

AHB

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3) Pinocytosis

• This process is important in the absorption of oil soluble vitamins & in the uptake of nutrients.

• Drug transported by passive diffusion depend upon:

dissociation constant, pKa of the drug lipid solubility, K o/w pH at absorption site.• • Most drugs are either weak acids or weak

bases whose degree of ionization is depend upon pH of biological fluid.

P H YS I CO C H E M I C A L FAC TO RS

• For a drug to be absorbed, it should be unionized and the unionized portion should be lipid soluble. Only non-ionized fraction of drugs (acids or bases is absorbed

• The fraction of drug remaining unionized is a function of both

• Dissociation constant (pKa) and pH of solution.

HENDERSON HASSELBATCH EQUATION For acid, pKa - pH = log[ Cu/Ci ]For base, pKa – pH = log[ Ci/Cu ] Eg. Weak acid aspirin (pKa=3.5) in stomach (pH=1) will have > 99%of unionized form so gets absorbed in stomach

Weak base quinine (pKa=8.5) will have very negligible unionization in gastric pH so negligible absorption

Several prodrugs have been developed which are lipid soluble to overcome poor oral absorption of their parent compounds.

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Factors Affecting GIT Absorption• Blood Flow To Absorptive Site:o Greater blood flow raises absorptiono Intestine has greater BF than stomach

• Total Surface Area of Absorptive Site: Intestinal microvilli increases surface area to 1000-fold that of

the stomach favoring intestinal absorption

• Contact Time at Absorptive Site: Diarrhea reduces absorption Accelerated gastric emptying→ faster delivery to intestinal

large surface → increased absorption

Factors Affecting GIT Absorption

• Food: Presence of food in the gut reduces/delays drug absorption from GIT

Increased splanchnic blood flow during eating increases drug absorption

Ionized drugs as tetracycline can form insoluble complexes with Ca2+ in food/milk.

• Formulation Factors: Solid dosage forms dissolution & solubility are essential Aqueous solutions are absorbed more quickly than tablets or

suspensions56

Stomach:

The surface area for absorption of drugs is relatively small in the stomach due to the absence of macrovilli & microvilli.

Extent of drug absorption is affected by variation in the time it takes the stomach to empty, i.e., how long the dosage form is able to reside in stomach.

Drugs which are acid labile must not be in contact with the acidic environment of the stomach

Factors affecting absorption from GIT

PHYSIOLOGICAL FACTORS:Gastrointestinal (Gi) PhysiologyInfluence Of Drug Pka And Gi Ph On Drug

AbsorbtionGit Blood FlowGastric Emptying………………..contact timeDisease StatesTotal surface area

Intestine• Major site for absorption of most drugs due to its large surface

area (0.33 m2 ).• It is 7 meters in length and is approximately 2.5-3 cm in diameter.• These folds possess finger like projections called Villi which

increase the surface area 30 times ( 10 m2).• From the surface of villi protrude several microvilli which increase

the surface area 600 times ( 200 m2).• Blood flow is 6-11 times that of stomach.• PH Range is 5–7.5 , favorable for most drugs to remain

unionized.• Peristaltic movement is slow, while transit time is long.• Permeability is high.

All these factors make intestine the best site for absorption of most drugs.

Large intestine :

The major function of large intestine is to absorb water from ingestible food residues which are delivered to the large intestine in a fluid state, & eliminate them from the body as semi solid feces.

Only a few drugs are absorbed in this region.

Bioavailability• the proportion of the drug in a dosage

form available to the body

i.v injection gives 100% bioavailability.

BIOAVAILABIITY Fraction of a drug reaching

systemic circulation in chemically unchanged form after a particular route

First pass metabolism, i.e., rapid hepatic metabolism, reduces bioav. (lidocaine, propranolol, nitrates)

Drug solubility Chemical instability in gastric

pH (penicillin G, insulin) Drug formulation: Standard &

SR formulations

• Bio = AUC oral/AUC IV x 100

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Seru

m C

once

ntra

tion

Time

Injected Dose

Oral Dose