PHARMACOKINETICS

 Pharmacokinetics: Greek word,Pharmacon means: drug, kinein means: to move.

The study of drug absorption, distribution, Biotransformation and elimination is called Pharmacokinetics.

PHARMACOKINETICS

1. Drug administration (various routes) 2.Drug absorption (input) (from the site of administration) 

3Distribution of drug (Plasma = Tissue) (Bioavailability, Plasma ½ life) 

4. Biotransformation

 5.Drug elimination.

DRUG ADMINISTRATION

A) For treatment/cure: e.g.

★ Antibiotics for infections (bacterial) ★Antipyretics for pyrexia (fever). ★Diuretics for oedema

B) For symptomatic relief: e.g. ★Propranolol for cardiac arrhythmia ★Analgesics for pain. 

★Sedatives for pain.

★ Salbutamol for bronchial asthma. ★Insulin for diabetes. 

★Anti-hypertensive drug for hypertension.

 ★Anticoagulant drugs for blood disorders.

C) For prophylactic (preventive) use: e.g.

★ Primaquine for malaria. ★Contraceptives for contraception.

D) For diagnosis: e.g. 

★Barium sulphate for peptic ulcer. ★Endrophonium for myasthenia gravis.

The main Routes of Drug administration are

A) Systemic route:

1.Enteral or alimentary routes:

a.Sublingual 

b.Oral

c.Rectal

2.Parenteral routes (extra-intestinal):

 a) Injection: 

•Subcutaneous (SC) 

•Intracutaneous (IC) 

•Intraarterial (IA) 

•Intravenous (IV) 

•Intramuscular(IM) 

•Intraarticular (IArt)

 •Intraperitoneal (IP)

 •Intraventricular 

•Intrathecal 

•Intracardiac

• Intrapleural

 •Intramedullary 

•Intralesional

b) Inhalation: 

•As a gas: e.g. Volatile anaesthetic: N2O, chloroform.

•As an aerosol: e.g. B2 adrenoceptor agonist: Salbutamol (Bronchodilator) 

•As a powder: e.g. Sodium chromoglycate.

B).Local routes: 

Applied to the localised area and action is confined to that particular area. 

1.Topical application: Ointment, paste, drops, powder, lotion etc.

 a) Skin inunction (by rubbing of drug on skin)

 b) To eye and ear. 

c) To mucous membrane of nose, urethra, rectum, anal canal, vagina.

2.lontophoresis: In this process the drug is applied to the particular area of skin and Galvanic current is used to increase absorption through skin.

 SUBLINGUAL ROUTE 

Commonest use of sublingual drugs.

a) Nitroglycerine (tablet): in angina pectoris for coronary vasodilatation.

 b) Isoprenaline sulphate: in bronchial asthma for broncho- dilatation. 

c) Nifedipine: in severe hypertension for vasodilatation.

Advantages of sublingual route 

a) Lipid soluble drugs are rapidly absorbed, So, onset of action is very quick due to high vascularity of buccal mucosa. 

b) Once the desired effect is obtained rest of the drug can be discarded. 

c) Drugs with high first pass metabolism enter the general circulation without passing through liver.

Disadvantage of sublingual route

 a) Large dose can not be given. 

b) Irritant dose can not be given. 

c) Can not be given to unconscious patients. 

d) Lipid insoluble drugs can not be given.

   

Some drugs and their particular route are

•Sublingual: Nitroglycerine in angina pectoris. 

•Subcutaneous: Insulin in diabetes mellitus.

 •Intramuscular: Vit-B complex. •Intravenous: Blood, Heparin. Intraarterial: Inj. Neostigmine in myasthenia gravis 

•Intrathecal: Spinal anaesthesia. •Intraarticular: Hydrocortisone acetate in Rh. arthritis

 •Intracardiac: Adrenaline in sudden heart failure. 

•Intracutaneous: Tuberculin test, BCG vaccine. 

•Inhalation: Adrenaline spray in asthma. •Orally: Ampicillin, Cotrimoxazole.

              ORAL ROUTE

Advantages of oral route

1.Oral route is cheap, safe and painless route. 

2.Convenient route because drug can be given in the form of tablet or capsule which contain an exact dose. 

3.Self-medication is possible.

4.Prolong action can be obtained by delaying absorption.

5. Drugs need not sterile and highly purified.

6.Free from fear and anxiety for pricking needle & associated with pain. 

7.This route has psychological effect on the patient that he has taken medicine. 

8.It is easy and patient can take the drug without interrupting his activity. 

9.Hypersensitivity reaction in many cases is less.

Disadvantages of oral Route

1. Onset of drug action is slow due to delayed absorption. So not suitable for emergency cases. 

2.Irritant, unpleasant and hypertonic drugs can not be administered. 

3.This route may not be useful in presence of vomiting or diarrhoea. 

4.This route can not be employed in an unconscious or non- co-operative patient.

5.Drugs that are destroyed by digestive juice are not administered orally, e.g. insulin, heparin.

6.Drugs having high first pass metabolism are not given orally, e.g. Testosterone. 

7.Absorption of certain drugs are irregular and negligible, e.g. Streptomycin, Neomycin. 

Some orally used drugs 

* Ampicillin

 * Amoxacillin 

* Acetaminophen

 * Ciprofloxacin 

* Cimetidine

 * Digoxin

 * Loperamide

            RECTAL ROUTE 

Advantages of rectal route

1.Drugs that are irritant to the stomach can be given by suppository.

 2 Suitable route in vomiting, motion sickness, migraine, non-co-operative patient. 

3.Avoid first pass metabolism. 

Disadvantages of rectal route

1.Patient may be embarrassed.

 2 Rectal inflammation may occur with repeated use. 

3 Absorption may be unreliable. 

                      ENEMA 

Administration of liquid drugs into the rectum is called enema. 

TTypes of enema

1).Evacuant enema: Soap water to remove the faecal matter and the flatus. The quantity of fluid administered at a time about 600 ml.

 Indications of evacuant enema: 

a) Before surgical operation. 

b) Before delivery.

 c) Before radiological examination of GIT.

2).Retention enema: The fluid containing the drugs is retained in the rectum so that the drug may act locally or systematically. 

a) Acts locally: For enemä & bowel wash. e.g. In constipation: Glycerine vegetable oil In ulcerative colitis: Prednisolone. 

b) Acts after absorption into systemic circulation: 

•For basal anaesthesia: Paraldehyde. 

•For nutrition: Glucose or normal saline. 

3).Diagnostic enema: BaSO4 suspension or, emulsion is injected into the rectum for X-ray examination of the colon.

INTRAVENOUS ROUTE

 Advantages of I.V route

 1.LV route is used in emergency cases to obtain immediate effectland highly predictable blood level. 

2.Large volume, unpleasant & irritant solution can be given. 

3.Suitable for unconscious and non-co-opèration patients.

4.Drugs can be given through I.V route in case of Diarrhoea, vomiting or where the patient is unable to swallow.

5. This route avoids drug modification by the digestive juice or hepatic enzymes, e.g. oxytocin.

 6.Rapid action and accuracy of dose are ensured. 

Disadvantage of I.V route 

1.It is invasive painful procedure. 2.Self-medication is difficult.

3.Strict aseptic measures, special techniques are essential. 

4.Risks: like infection, hypersensitivity reaction, pyrogenic reaction, local venous thrombosis & haemolysis may occur. 

5. Leakage of drug outside vein can produce severe irritation. 

6.Overdose may have effects so immediate that it is impossible to reverse them. 

7.Chance of injury to surrounding nerves and vessels.

8.Drug must be water-soluble.

9. Short duration of action, as excretion is rapid. 

10.Expensive.

  INTRAMUSCULAR ROUTE

 

Advantages of I.M route 

1. Absorption of drug is more rapid and uniform than subcutaneous injection due to rich blood supply to the muscle. 2.Slightly irritant drugs can be given that is too irritant for subcutaneous route. 

3.Moderately large volume can be given (but not above 5ml).

4. Depot preparation can be administered, e.g. penicillin medroxyprogesterone (site: deltoid, gluteal region, thigh). 

5.The rate of absorption is slower for females because of more subcutaneous fat (fat is relatively poorly vascularised). 

Disadvantages of I.M route

1. It is invasive and painful route. 

2.Self-medication is difficult.

3. Large volume of drug can not be given (max: 7-10 ml). 

4.Chance of local inflammation, infection, abscess formation, irritation and haematoma formation. 

5.Chance of nerve injury, which may cause severe pain, paresis and even paralysis of the muscles.