ComplianceCompliance

• Degree of , “patient following doctors advice”

• When the patient is following the doctor’s advice strictly , then the compliance is very good;

• When the doctor’s advice is not followed properly, then the compliance is poor.

Empirical drugsEmpirical drugs

• Drug that is used only on the basis of experience , without any scientific pharmacological basis.

Empirical therapyEmpirical therapy

• When a treatment module is focused on broad spectrum rather than an exact etiology.

• E.g Broad spectrum being prescribed as antibiotic without confirming the etiological diagnosis.

Prescription writingPrescription writing Dr. ……… MBBS (TMU), china Registration number: - 2347

Date : ……………Name : ----------Age : ……… Sex : ………Address : …….. Weight : …….Occupation :…….. Religion : ……

• Chief complain (C/C) 1. Burning sensation in upper abdomen 2. Nausea • Diagnosis : GERD

• Rx. : - 1. Omeprazole 20mg two times a day for 7 days before meal Cap. Omeprazole - 20 mg X q12h X 7d

Doctor’s signature:------------

Two Main Areas In Pharmacology Two Main Areas In Pharmacology

Pharmacodynamics

Pharmacokinetics

Scope of pharmacology ?

PharmacodynamicsPharmacodynamics

Study of the biochemical and physiological effects of drugs and the mechanisms of drug action and the relationship between drug concentration and effect.

PharmacokineticsPharmacokinetics

Pharmacokinetics is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism.

PharmacokineticsPharmacokinetics

PharmacodynamicsPharmacodynamics

Pharmacodynamic is the study of :“What a drug does to the body”

Pharmacokinetics is the study of :“What the body does to a drug”

Pharmacokinetics

What the body does to

the drug

(movement of the drug)

Absorption

Distribution

Biotransformation

Excretion

Pharmacodynamics

What the drug does to

the body

Mechanism of action

Pharmacological

actions

Adverse effects

Drug interactions

PharmacokineticsPharmacokinetics

Drug at site of administratio

n

Drug in plasma Drug /

metabolites in tissues

Drug / metabolites in

urine, feces, bile

AbsorptionDistribution

Elimination

Metabolism

Kidney

Liver

Pharmacokinetics Pharmacokinetics

Pharmacokinetics Pharmacokinetics

Knowledge of pharmacokinetics helps the doctor to determine:

How much drug is present in the body at any given time?

How long does it take to reach a constant level of drug in the body during chronic drug administration?

How long does it take for the body to get rid of drug once intake of drug has stopped?

PharmacokineticsPharmacokinetics

Absorption Absorption

Absorption of drugsAbsorption of drugs

• Whatever the route of administration, a drug must reach its site of action.

• Drugs can cross cell membranes by :– Simple diffusion– Facilitated diffusion– Active transport

AbsorptionAbsorption by Simple diffusion

• Depends on lipid solubility.

• Lipid-soluble substances diffuse easily through the lipid bilayer like O2, CO2, fatty acids, steroids and fat-soluble vitamins.

• lipid solubility of a drug depends on its state of ionization.

• Only non ionized form can cross the membrane.

• Ionized is better eliminated since they are water soluble.

AbsorptionAbsorption by Simple diffusion

• The extent to which a drug is ionized depends on the pH of the local environment and the pKa of the drug.

• pH is a measure of hydrogen ion concentration.

• The lower the pH, the higher the hydrogen ion concentration and the greater the acidity of a solution.

AbsorptionAbsorption by Simple diffusion

• The pKa of a drug molecule is the pH at which the drug is 50% ionized and is different for different drugs.

AbsorptionAbsorption by Simple diffusion• Chemically, most drugs are either weak acids or weak bases.

• In an acidic environment, acidic drugs are unionized according to the following simple equation:

• Where A− is an acidic drug and the excess hydrogen ions (H+) drive the equation to the left.

• In an alkaline environment, as in the small intestine and the majority of body fluids, basic drugs are unionized according to the following simple equation:

• where B is a basic drug and the deficit of hydrogen ions drives the equation to the right.

AbsorptionAbsorption by Simple diffusion

• Thus, acidic drugs are preferentially absorbed in the stomach and basic drugs are preferentially absorbed in the intestine.

• In practice however, because of the large surface area of the small intestine, the majority of drug absorption takes place there.

AbsorptionAbsorption by fascialiated diffusion• Many nutrients and a few drugs can pass across the

cell membrane by facilitated diffusion.

• In this case, in addition to the concentration gradient, a carrier protein acts to transport a substance from one side of the membrane to the other.

• Carrier proteins are specific and only transport molecules that they ‘recognize’.

• Glucose, amino acids and vitamins enters many body cells by facilitated diffusion, and the same carrier can transport drugs that are structurally similar to them.

AbsorptionAbsorption by Active transport• Active transport :

– Involves a carrier protein – ATP is required – Transport goes against the concentration gradient.

• Active transport mechanisms are particularly important in the transport of ions, nutrients and neurotransmitters.

• They may be involved in the transport of some drugs.

• Many drugs have been developed that interfere with the active transport of neurotransmitters.

Absorption from the gastrointestinal tract

• Drugs taken orally goes through the processes of mechanical degradation and liquefaction and the action of enzymes.

• The stomach produces acid and pepsinogen to begin protein digestion. It can take 2–4 hours before food is passed onto the small intestine.

• Stomach acid and enzymes can destroy some drugs so they need to be protected by an enteric coat (capsule) so they pass unharmed into the small intestine.

Absorption from the gastrointestinal tract

• Drugs absorbed pass directly to the liver in the hepatic portal system before going to other parts of the body.

• The liver excretes some drugs into the intestine via bile. Once back in the small intestine the original drug can be reabsorbed.

PharmacokineticsPharmacokinetics

Distribution Distribution

Distribution of drugsDistribution of drugs• When a drug is administered, it does not achieve an

equal concentration throughout the body.

• The body can be considered to be made up of aqueous and lipid compartments.

• Lipid compartments include all cell membranes and adipose tissue.

• Aqueous compartments include tissue fluid, cellular fluid, blood plasma and fluid in places like the central nervous system, the lymphatic system, joints and the gastrointestinal tract.

• The distribution of a drug into these different compartments depends on many factors.

Factors affecting drug distribution Factors affecting drug distribution

• Aqueous solubility– Water-soluble drugs have difficulty crossing cell

membranes and therefore tend to remain in the circulation.

– Thus ,water-soluble drugs are not well distributed throughout the body. They exist in large amounts in the plasma or tissue fluid.

– They are rapidly cleared by the liver or kidney.

– In practice, such drugs have little therapeutic use.

Factors affecting drug distributionFactors affecting drug distribution• Blood flow

– At equilibrium, drugs are partitioned between plasma, plasma proteins and the different tissues.

– The rate of distribution to different tissues depends largely on the rate of blood flow through them.

– Well perfused organs receive a relatively high concentration of a drug whereas it can be difficult to get drugs into less well-perfused areas.

Although the brain has a very good blood supply, distribution of drugs into the central nervous system is restricted. This is because of the so-called ‘blood-brain barrier’.

Blood-Brain BarrierBlood-Brain Barrier• This is not an anatomical barrier as such,

rather a combination of the tight junctions between endothelial cells of brain capillaries and the close association of glial cells with the outside of the capillaries.

• This arrangement makes diffusion of lipid-soluble drugs into the brain difficult and diffusion of water-soluble drugs almost impossible.

Factors affecting drug distributionFactors affecting drug distribution• Plasma protein binding

– A large number of drugs have a high affinity for albumin and other plasma proteins.

– Plasma protein binding reduces active drug concentration and ultimate response to the drug.

– Drugs can compete for the same protein binding sites and this is a form of drug interaction.

Example - warfarin and aspirin. • Warfarin is an anticoagulant, which binds extensively to plasma

proteins, and this is taken into account when dosages are worked out. Aspirin taken with warfarin competes for the same protein binding sites, which means that they each displace the other and the amount of free drug in the plasma is increased for both drugs. Patients stabilized on warfarin should never take aspirin because the effect of increased free plasma concentration of warfarin can be severe haemorrhaging. Coincidental increased activity of aspirin is not as serious.

Factors affecting drug distributionFactors affecting drug distribution

• Lipid solubility– Lipid-soluble drugs enter cells readily.

– Distribution of such drugs is widespread unless plasma protein binding is extensive.

– Elimination of lipid-soluble drugs is usually slow because clearance from plasma via the kidneys removes only a small proportion of the drug in any given time.

Factors affecting drug distributionFactors affecting drug distribution• Tissue sequestration

– Considerable amounts of drug may be stored in certain tissues, particularly fat and muscle.

– Sequestration in this way gives an apparent large volume of distribution but also means that only a small proportion of total drug concentration will reach its site of action. This can create difficulties with the usage of certain drugs.

For example,

– General anaesthetics are highly lipid-soluble drugs. Sequestration into adipose tissue can make anaesthetizing obese people hazardous because it is difficult to control the amount of free drug in the circulation.

– Benzodiazepines (antianxiety drugs) can be difficult to clear from the body because they are stored in large amounts in adipose tissue. This can complicate withdrawal.

– Griseofulvin has an affinity for keratin. Since this drug can be used to treat fungal infections of the skin and nails its sequestration into keratin is something of an advantage.

– Tetracycline has an affinity for bones and teeth. It should never be used in children as its accumulation can damage teeth and stunt growth.

Factors affecting drug distributionFactors affecting drug distribution• Metabolism and excretion

– The rate at which a drug is metabolized will affect its distribution.

– Similarly the rate of elimination or excretion also affects distribution and vice versa.

Factors affecting drug distributionFactors affecting drug distribution• Volume of distribution

– Volume of distribution is a concept that describes the body compartments into which a drug could be distributed.

– If a drug is water soluble it is likely to remain in the blood stream and its volume of distribution will be relatively small and equal blood volume.

– Similarly, acidic drugs tend to bind to plasma albumin and therefore also remain in the blood stream and have a small volume of distribution.

– If a drug is highly lipid soluble, then it will be distributed to many parts of the body and have a large volume of distribution.

– In addition, basic drugs tend to bind to tissue proteins and as a result have a large volume of distribution.

To be continued……..To be continued……..