Basics of Pharmacology w.s.r to Pharmacokinetics

Guided by: Presentors:Dr. Bhawana Mehra Priyanshi Samadhiya Lecturer Department Bharti Barfa of Dravyaguna

Shubhdeep Ayurved Medical College and Hospital & P.G. Institute , Indore

PharmacologyOrigin of term

Greek Modern Latin (Drug) Pharmacologia Pharmacology (early 18th century)

Pharmacon Logos (Drug/ medicine) (Study)

What is Pharmacology?

Science of Drug

• Deals with interaction of chemical

molecules (Drugs) with living system.

• Includes all aspects of drugs

• Most importantly those that are relevant to

effective and safe use for medicinal

purpose.

Scope of pharmacology• Pharmacokinetics – Movement of drug• Pharmacodynamics – effect of drugs• Pharmacotherapeutics – use of drug • Toxicology – adverse effects of drugs.

Pharmacokinetics• Pharmacon kinesis (Drug ) (Movement ) • This refers to movement of the drug in

and alteration of drug by the body.• How does the drug concentration change

as it moves through the different compartment of body

• “ Time course” of Drug in body.

Simply it is …….

• Study of the basic processes that determine the duration and Intensity of drug effect namely……. ADME i.e.

AbsorptionDistributionMetabolism

Excretion

Absorption

Distribution

ExcretionMetabolism

What body does with drug?

Components of Pharmacokinetics ( In VS. Out)

IN

Absorption Distribution

OUT

Metabolism Excretion

• Absorption – The process of drug entering into systemic circulation.• Distribution – The dispersion of a

substance throughout fluids and tissues of body. • Metabolism - The transformation of

parent compound into structurally similar daughter compounds.• Excretion – The removal of substance

from the body.

The interrelation of the ADME of a drug and its concentration at its site of action

Mechanism of transport of drugs

Passive Transport

Simple Diffusion Filteration Facilitated

diffusion

Active transport Active

Transport

The ADME and action of drug all involve its passage across cell membrane. There are varieties of ways for transport of drug.

Endocytosis and exocytosis

Endocytosis Exocytosis

ABSORPTION Site of Movement of drug Systemic administration circulation

• Occurs by passive or active transport. • Rate & extent – depends on Route of Administration. • Necessary for the production of a therapeutic effect.• IV route – 100% absorption• For all other routes <100%

GIT Liver IVCRt. Side of heart

Lungs

Systemic circulation

Lt. side of heartProcess of Absorption

IVOral Inhalation

So, absorption is everything that happens before a drug enters into systemic circulation.

Absorption of drug by different routes

• IV – 100%• IM/SC / sublingual - >75% (due to local binding of drug)• Oral – low due to (a) incomplete absorption (b) first pass metabolism Chloroquine ~ 80% Bromohexine ~ 20% Carbamezapine ~ 70% Chlortetracycline ~ 30%

Factors affecting rate and extent of absorption of oral dose

• Disintegration and dissolution time • Particle size• Lipid solubility• pH and ionization• Concentration continue……

Continue……

• Area and Vascularity of absorbing surface• GI motility• Presence of food • Diseases • Metabolism

First Pass metabolism• Metabolism of drug during its passage from

the site of absorption into systemic circulation.• “First pass effect” or “ Pre systemic

metabolism” • All orally administered drug –in intestinal wall

and liver.• Transdermally administered drug – in skin• Any other route – in lungs• Important determinant of oral bioavailability.

First pass metabolism of orally administered drug

OralDrug

to systemic

circulation

Destroyed in gut

Not absorbed

Destroyed by gut wall

Destroyed by liver

Extent of first pass metabolism of some important drugs

Low Intermediate High(Not given orally )

High( high oral dose)

PhenobarbitonePhenylbutazoneTolbutamolTheophyline

AspirinQuinidineChlorpromazinePentozocineMetoprolol

InsulineHeparine IsoprenalineLignocaineHydrocortisoneTestosterone

Propanolol progesteroneSalbutamolMorphinePethidineNitroglycerine

Bioavailability• Fraction (F) of administered dose that reaches

the systemic circulation. • IV – 100%• IM/SC / sublingual - >75% (due to local

binding of drug)• Oral – low due to (a) incomplete absorption (b) first pass metabolism

• Dispersion of drug throughout the body.

Movment of drug

• Movement proceed till an equilibrium is established between two spaces.

Extra Vascular space viz.

Interstitial spaceFat

tissuesVascular compartment

Distribution

Factors affecting distribution• Lipid solubility• Blood flow • Ionization • Plasma protein binding• Tissue binding

Plasma protein binding• Drugs bound to plasma protein. Acidic drug to albumin Basic drug to α1- glyacoprotein• Binding is reversible • free fraction - available for action.• Bound form acts as reservoir • Make the drug long acting. e.g. Warfarin – 99% Morphine – 35% Lithium - 0%

Tissue storage • Drugs may bound to tissues.• E.g. – Skeletal muscle, heart & kidney– Digoxin

Liver & Retina - Chloroquine Thyroid - Iodine Bone and teeth – Tetracycline Iris – Ephedrine, Atropin Adipose tissue – Thiopentene , ether, DDT• Act as reservoir • Prolong duration of action.

Apparent volume of distribution • Assumption- 1. body as single homogenous compartment

with volume V. 2. Drugs get uniformly distributed. Amount of drug in body Plasma concentration of drug = 500mg 10mg/liter of plasma Vd = 50liters

Vd=

Importance of Vd

• Highly protein bound drugs largely restricted to vascular space lower Vd

• Distributed in other tissues high Vd

• In liver and renal disease hypoalbuminemia PPB reduced free fraction increased

Tissues , fat , Interstitial space

• Chemical alteration of the drug in the body. • Non Polar( Lipid soluble) to Polar ( Lipid

insoluble) • Hydrophilic drugs are excreted unchanged.• Primary site –

Others are -

Metabolism (Biotransformation)

It may leads to • Inactivation of active drug Phenobarbitone hydroxyphenobarbitone Propanolol 4 hydroxypropanalol• Active drug to active metabolite/metabolites Codeine Morphine Digitoxin Digoxin Diazapam Oxazapam• Inactive (Prodrug) to active drug Levodopa Dopamine Prednisone Prednisolone Bacampicillin Ampicillin

• Passage out of systemically absorbed drug.• Drugs may get excreted after metabolism or

unchanged.• Primarily through–

• Others are – Saliva, Sweat, Milk

Excretion

• Urine – Most important and common channel. e.g. – aspirin, • Faeces /bile – for larger molecule (MW> 300)

e.g. – erythromycin, ampicillin, rifampicin • Intestine – e.g. heavy metals • Exhaled air – for gases and volatile liquids e.g.- general anesthetics, alcohol, salbutamol• Saliva and sweat – e.g. lithium, pot. Iodide,

heavy metals• Milk – e.g. Tetracyclines, Streptomycine,

Theophylline, Vit A & D.

Importance of pharmacokinetics

PK determines the – • Route of administration• Dose• Latency of onset• Duration of action• Frequency of drug administration

Examples Aspirin• Poorly absorbed from stomach and small intestine.• Microfining enhance absorption• Deacetylated in gut wall, liver, plasma and other

tissues.• ~80% bound to plasma protein• Vd ~ 0.17L/kg• Metabolized in – liver • Excreted by urine.

Bromohexine (alkaloid of Adhatoda vasica)

• Poorly absorbed orally • Extensive first pass metabolism • Bioavailability ~ 20%• Plasma protein binding ~ 99%• Vd~ 5.5 to 7 liter/kg• Excretion by urine – 1% unchanged and

rest as metabolites.

Conclusion • Pharmocokinetic is study of what body does

with drug viz. absorption, distribution, metabolism and excretion.

• It is important for determination of route of administration, dose, latency of onset, duration of action & frequency of drug administration

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