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PHARMACOLOGY
The science which deals with drugs Origin, structure, preparation, administration, actions, ADME . DRUG: Any molecule used to alter body functions thereby preventing, diagnosing or treating disease (PDT)
Drug Names
1. Chemical name : According to the chemical structure, it is long and rarely used. 2. Official (Approved or Generic) name: The name which is given by the international organization of drug nomenclature. 3. Trade (Proprietary or brand) name: The name which is given by owner (the drug company). Example: 7- Chloro, 3-dihydro benzodiazepine 2- one (Diazepam) Valium, Stesolid, Valipam
Sources of Drugs
1. Plant Alkaloids: Atropine, Pilocarpine and Morphine Glycosides: Digoxin. 2. Mineral: Fe, Ca. 3. Animal: Insulin. 4. Microorganisms: Antibiotics. 5. Synthetic: Aspirin and sulphonamides. 6. Semisynthetic : Ampicillin. 7. Genetic engineering: Recombinant DNA technology, r-insulin, r- erythropoeitin
Oral Routes
Tablets, Capsules, Solution, Syrup, Suspension, Elexir. Advantages: Convenient- portable no pain easy to take Cheap no sterilization no expert.
Oral Routes
Disadvantages: Variable bioavailability First pass effect Food can affect absorption Local effect, taste, irritation Effect on flora Unconscious pts.
Buccal/ Sublingual
Advantages: No first pass effect Rapid absorption and effect Drug stability Disadvantages: Inconvenient Small doses only.
Rectal
Suppository or enema. Advantages: Reduced first pass effect - Useful in patients unable to take drugs orally or young children Disadvantages: - Erratic absorption. - Not well accepted
Injections
Intravenous (IV) Bolous and infusion Advantages: Rapid Total dose and large dose Suitable for irritant drugs Disadvantages: Difficulty in finding suitable vein Need expert Risk of toxicity & non recall Expensive
Subcutaneous (SC)
Advantages Self administration insulin - Complete but slow absorption - Absorption delayed and duration of action prolonged by adding vasoconstrictor. Disadvantages Pain - Irritation - Small dose
Intramuscular (IM)
Advantages Larger volume than SC - Depot or sustained release preparation are possible. Disadvantages Pain - Need expert -Erratic absorption as Phenytoin and diazepam.
Inhalation
Local effect Bronchodilator Systemic effect General anesthesia Advantages: - Rapid - No first pass effect Disadvantages: - Irritation - Some particles may be precipitated in mouth or throat
Topical
Local effect Eye drops, Antiseptic solution, Ointment, cream, Lotion, Gargle Systemic effect- Nitroglycerine ointment or patches. High local conc. and effect. Absorption increased by cuts, abrasions and intact skin of infants.
Pharmacokinetics
What the body does to the drug. It deals with: Absorption Distribution
ADME
Metabolism and Excretion of the drug and the mathematical relationships of these parameters
Pharmacodynamics
It is what the drug does to the body. It deals with the pharmacological actions and the mechanisms by which these actions are performed.
Absorption
The passage of drug from site of administration (from out side) to the blood stream. To do so the drug has to pass through cell membranes. Cell membranes are of lipid bilayer and pores. Most drugs are absorbed by Passive diffusion or simple diffusion.
Absorption(cont.)
Absorption by passive diffusion depends on: 1. Concentration gradient Direct proportion 2. Lipid solubility Direct proportion 3. Degree of ionization Indirect proportion
For acids pKa = pH + log M/I For bases pKb = pH + log I/M Example 1: Aspirin is an acidic drug pKa = 3.4 in the stomach pH = 1.4, so 3.4 = 1.4 + log M/I , log M/I = 2 , M/I = 100 M = 100 I In the duodenum pH 7.4, so 3.4 = 7.4 + log M/I , log M/I = - 4 , M/I = 1/10000 I= 10000 M How does aspirin behave in urine pH = 6.4?
Question
What is the effect of acidification or alkalinization of urine on excretion of aspirin and ephedrine?
Absorption (cont.)
Facilitated difusion Minority of drugs require carrier mediated transport e.g. Levodopa and Iron
Bioavailability (F)
The fraction of the unchanged unmetabolized drug, which reaches the systemic circulation following administration. IV, F = 100% of the dose i.e. F = 1. F = AUC oral/ AUC IV Different routes and different brands give different bioavailabilities
Distribution
Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues. It is the process by which a drug reversibly leaves the blood stream and enters the extracellular fluid and then the cells of the tissues.
Protein Binding
P+D PD P = Plasma protein, D = Free unbound drug PD = Bound drug to protein. Only the the free unbound drug fraction can pass membranes and producing effect, metabolized and excreted. Acid drugs usually bound to albumin. Basic drugs usually bound to 1 acid glycoprotein
Protein Binding(cont.)
Drugs which are highly protein bound: Warfarin Phenylbutazone Diazepam.
Selective distribution
Iodide Thyroid gland. Thyopentone fat act as a reservior Blood brain barrier (BBB) Keeps some drugs from entering CNS - tight junction in the endothelium, and to pentrate the CNS the drug : Low ionization, Low protein binding, High lipid solubility and of Small molecular size The placental barrier: Protects the fetus, more tight at early monts, same criteria as in BBB
Drug Metabolism
Aims: (Usually) 1. Reducing lipid solubility. 2. Alteration of biological activity. Sites: 1. Liver Most drugs 2. Plasma Succinylcholine 3. GIT mucosa - Contraceptives 4. Synaptic neurones Sympathetic amines.
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Microsomal Enzymes
03-12-2010
KLECOP, Nipani
56
Microsomal Enzymes
Found predominately in the smooth Endoplasmic Reticulum of liver Other areas:
Kidney Lungs Intestinal mucosa
Non-microsomal enzymes
Found in the cytoplasm and mitochondria of hepatic cells Other tissues including plasma
03-12-2010
KLECOP, Nipani
57
Microsomal Enzymes
Non-synthetic/ Phase I reactions
Most oxidation and reduction Some hydrolysis
Non-microsomal enzymes
Non-synthetic/ Phase I reactions Most hydrolysis Some oxidation and reduction Synthetic/ Phase II reactions ALL except Glucuronide conjugation
03-12-2010
KLECOP, Nipani
58
Microsomal Enzymes
1. Inducible
Drugs, diet, etc.
Non-microsomal enzymes
Not inducible
03-12-2010 KLECOP, Nipani 59