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pharmacology

General Pharmacology

By “Dr. Shimaa Elshazly”

Faculty of PharmacyDepartment of Pharmacology

3rd year pharmacy students

The term pharmacology comes from the Greek words:•Pharmakon - drug or medicine•Logos - the truth about or a rational discussion

…………Truth about medicine

• Pharmacology is the study of howdrugs exert their effects on livingsystems.• More specifically it is the study ofthe interactions between a livingorganism and drugs that alter normalbiochemical function.

Early pharmacologyfocused on naturalsubstances, mainly plantextracts.

History of Pharmacology

Modern approach

• Pharmacology is a discipline as a bridge, not only to connect pharmacy with medicine, but also to link foundational medicine to clinical medicine

Foundational Medicine

Manufacture of Drugs

Medicine

Research of Drugs

Pharmacy

Clinical Medicine

Pharmacology

……..Subdivisions of Pharmacology

Clinical Pharmacology:application of pharmacodynamics and pharmacokinetics to human.

•Toxicology -Study ofharmful effects of drug

•Posology- How medicines aredosed or calculation of dose

•Pharmacognosy-Development of medicinalsubstances obtained fromplants

The science of pharmacology is divided into TWO important and interrelated areas :

A.Pharmacokinetics: Study of the absorption,distribution, metabolism and excretion of drugs(ADME).……………..what the body does to the drug

B. Pharmacodynamics: Study of the molecular,biochemical and physiology effects of drugs oncellular systems and their mechanisms of action.……………..what the drug does to the body

Division of Pharmacology:

In other meaning:

• Chemical agents used in the diagnosis, treatment, or prevention of disease

What Is a Drug?

• A drug is a substance which when given to a patient can affect his body functions. This effect is useful in the treatment of a disease ( therapeutic ).If given in high dose it may cause a disease due to the toxicity of the drug itself.

What are the sources of a drug?

1- Natural

2- Semisynthetic

3- Purely synthetic

4.Mineral Origin

5.Genetic Engineering

a)Plant Origin: eg.Atropine from belladonna & Morphine from Opium.

b) Animal Origin: eg. Insulin, calcitonin etc.

These are compounds that are obtained from natural source and subjected to chemical modification eg.Penicillins and heroin (prepared by acetylation of morphine).

1- Natural:

2- Semisynthetic:

3- Purely synthetic:

Are purely chemically synthesized. eg. The majority of drugs.

4.Mineral Origin:

eg. Iodine, magnesium sulphate

5.Genetic Engineering:

a) Gene Therapy. b) Recombinant DNA as the production of human insulin from bacterial origin.

(I)Pharmacokinetics of drugs (ADME)

……………..what the body does to the drug

Are studies of: Absorption Distribution or Disposition Metabolism Excretion or Elimination of drugs

Drug Absorption• Absorption is the movement of a drug from its site of application into the blood or lymphatic system without being chemically altered• Mathematically it is define in terms of Bioavailability (Rateand extent of absorption).

BioavailabilityDefinition: Rate and extent of absorption

i.e. Ka (Absorption constant)………. Rate of absorption.

Area under curve (AUC)………. extent of absorption.

• for i.v.: 100%

• for non i.v.: ranges from 0-100%

e.g. lidocaine bioavailability is 35% due to destruction in gastric acid and liver metabolism

Process of Absorption

In order for a drug to be absorbed, it must be able to

pass through cell membranes (which is a lipid

barrier)• Lipid soluble drugs would be ideal to pass

through themembrane easily.• Drugs can be absorbed by 4 main ways : 1. Simple diffusion = passive diffusion. 2. Active transport. 3. Facilitated diffusion. 4. Pinocytosis (Endocytosis).

Water soluble drug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane.

Lipid soluble drug (nonionized or non polar) is readily absorbed via cell membrane itself.

Characters common.Occurs along concentration gradient. Non

selective Not saturable Requires no energy No carrier is neededDepends on lipid solubility.

Drugs exist in two forms ionized (water soluble) & nonionized forms (lipid soluble) in equilibrium. Drug ionized + nonionized

• Only nonionized form is absorbable.

Six things influence the rate of diffusion

Concentration gradient Big concentration difference (Fick’s Law) increase diffusion.

Size of molecule involved

Large molecules slow diffusion

Distance the molecule has to travel Short distance increase diffusion

Temperature High temperatures increase diffusion

Solubility of the molecule

Surface area of the membrane over which the molecule can work. Large surface area increase diffusion

Relatively unusual.Occurs against concentration gradient.Requires carrier and energy.Specific Saturable. Iron absorption.Uptake of levodopa by brain.

Occurs along concentration gradient. Requires carriers Selective. Saturable. No energy is required. Selection is by size; shape; charge. Common molecules entering/leaving

cells this way include glucose and amino-acids.

Carrier-mediated facilitated diffusion

Active transport

along concentration gradient

(From high to low)

Against concentration gradient

(From low to high)

Needs carriers Needs carriers

Selective, saturable Selective, saturable

No energy is required Energy is required

Active transport Passive transport

against concentration gradient

(From low to high)

Along concentration gradient

(From high to low)

Needs carriers No carriers

Selective, saturable Not selectiveNot saturable

energy is required No energy

Endocytosis: uptake of membrane-bound particles.

Exocytosis: expulsion of membrane-bound particles.

High molecular weight drugs or Highly lipid insoluble drugs

Factors which influence the rate of absorption:– Routes of drug administration– The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug

• Enteral via gastrointestinal tract (GIT).

– Oral – Sublingual– Rectal

• Parenteral administration = injections.• Topical application• Inhalation

Disadvantages AdvantagesSlow effectNo complete absorption (Low bioavailability).Destruction by GITFirst pass effectGIT irritationFood–Drug interactionsDrug-Drug interactionsNot suitable for vomiting, unconscious, emergency.

- Easy - Self use - Safe- Convenient- cheap- No need for sterilization- Highly acceptable- Prolongation of the action of drugs could be possible by using slow release tablets

First pass Metabolism

Metabolism of drug in the gut wall or portalcirculation before reaching systemic circulation• So the amount reaching system circulation is less

than the amount absorbedWhere ? Liver Gut wall Gut LumenResult ? Low bioavailability. Short duration of action (t ½).

First pass effect

Dosage forms Capsules Tablets Syrup Suspension

Tablets Hard- gelatin capsule Spansule

Soft- gelatin capsule

Disadvantages Advantages• May be irritant to the mucus membrane

Salivation may produce swallowing so losing the advantage of this route. Not used for irritant drugs Not used for frequent use Only suitable for a small number of drugs

Can produce rapid effect (Emergency) & with smaller doses because: Oral mucosa has a good blood supply.• Not subjected to first pass metabolism.• High bioavailability• Not susceptible to inactivation in the GIT• No food drug interaction•Dosage form: friable tablet

Disadvantages AdvantagesNot for – Irregular absorption & bioavailability.– Irritation of rectal mucosa.– Rectal inflammation may be caused with repeated use.

Suitable for–Vomiting & children. &unconsciousness & pts that cannot swallow. – Irritant & Bad taste drugs.– less first pass metabolism (50%)

Dosage form: suppository or enema

Intradermal (I.D.) (into skin)Subcutaneous (S.C.)Intramuscular (I.M.)Intravenous (I.V.) (into veins)Intra-arterial (I.A.) (into arteries)Intrathecal (I.T.) (cerebrospinal fluids )Intraperitoneal (I.P.) (peritoneal cavity)Intra - articular (Synovial fluids)Intracardial

Disadvantages Advantages– Infection– Sterilization.– Pain– Needs skill– Anaphylaxis– Expensive.

• high bioavailability• Rapid action (emergency)• No first pass metabolismSuitable for–Vomiting &unconsciousness– Irritant & Bad taste drugs.– No gastric irritation– No food-drug interactionDosage form: Vial or ampoule

Ampoule Vial

1- Intravenous ( IV )

The drug is injected right into the venous blood.

Advantages: Immediate effect. Suitable for drugs not absorbed by the gut. Rapidly destroyed drugs, short t½ can be infused

continuously to provide a steady state of plasma concentration

Disadvantages: Dangerous if given rapidly. Prolonged infusion of irritant drugs lead to venous thrombosis. Susceptibility to infection if not using aseptic conditions.

2- Intramuscular

Injection is made into a large muscle

Advantages: Reliable & produces more rapid absorption than SC. Could be used for irritant drugs. Could be used for depot preparations eg. Long acting

penicillins.

Disadvantages: It is painful. Not accepted as self administration. Risk of infection & formation of abscess.

3- Subcutaneous (SC)

Just under the skinAdvantages Can be given by the patient Slow to obtain sustained drug effect eg. Insulin but

generally complete Suitable only for nonirritant drugs.

Disadvantages Large volume may be painful. Tissue damage from irritant drugs Maximum of 2 ml injection Heat, Vasoconstrictors such as adrenaline greatly

decrease the rate of absorption.

Produce local effect to: Skin (percutaneous) e.g. allergy testing,

topical local anesthesia Mucous membrane of respiratory tract

(Inhalation) e.g. asthma Eye drops e.g. conjunctivitis Ear drops e.g. otitis externa Intranasal, e.g. decongestant nasal spray

Disadvantages Advantages Only few drugs

can be used•Needs special apparatus. • Drugs may irritate the mucus membrane. • The presence of mucus plugs in the bronchi hinders treatment, if used in bronchial asthma.

• Easily administered eg. Aerosols. • Rapid absorption (large surface area)•Provide local action• Minor systemic effect• Low bioavailability• Less side effects. • No first pass effect Dosage form: aerosol, nebulizer

Nebulizer Atomizer

TDS is a method by which the drug is releasedand absorbed through the skin for systemicabsorption by a medicated adhesive patchapplied to skin * Slow effect (prolonged drug action) e.g. the nicotine patches

Advantages: Lead to more stable drug level in the blood. Avoid inactivation by first hepatic bypass eg. Nitroglycerine Minimal side effects.

Factors which influence the rate of absorption:– Routes of drug administration– The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug

Factor affecting absorption……Physico-chemical properties of drug• Molecular weight· Drugs with a small M.W. are absorbed well· Drugs which are large (often proteins) are absorbed poorly.• Chemical and enzymatic stability· The drug should be stable in gastric acid and in gut enzymes.e.g. Penicillin G is highly acid labile, or unstable in acid.• Aqueous and lipid solubility· For better absorption a drug must have optimum water and lipid solubility or a optimum partition coefficient. If it is highly lipid soluble it would not dissociate in the circulation i.e. Ion trapping. On the other hand, if it is highly water soluble then it will not cross the biological membrane.

pH and lipid solubility:Most drugs are either weak acids or weak bases and can exist in either the ionised (less lipid soluble) or unionised (more lipid soluble) form depending on the pH of the surrounding environment.

REMEMBER THAT A DRUG IS ABSORBED BETTER IN THEUNIONISED FORM (Lipophillic drug can cross cell membrane)

Factor affecting absorption……

Ion TrappingBody fluids where a pH difference will favor trapping of highlylipophillic drugs: e.g. Breast milk , Aqueous humor (eye) ,Vaginal secretions , Prostatic secretions Aspirin is an acidic drug (pKa=5) and exist in the

unionised form in stomach (pH 2.0) In this form, it can enter the cells of the stomach lining

(pH=7.4) where it is ionized and, in this form, it cannot leave the cell.

The concentration of ionized aspirin inside the cell continues to rise until it saturates and precipitates as crystals, which lead to gastric bleeding.

Factors which influence the rate of absorption:– Routes of drug administration– The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug

Drug dosage forms Different dosage forms have different rate and extent

of absorption.

A syrup has fast rate of absorption as compare to tablet

A capsule has fast rate of absorption than tablet Controlled-release, timed-release, sustained-release

dosage form have a uniform absorption and less side effects