Medical Pharmacology
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Medical Pharmacology


In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being.

What is Pharmacology

It is the science that deals with the study of chemical substances (drugs). The stud of drug, what they are? how they work? what they do?

What is Toxicology

It is brance of pharmacology which deals with the undesirable effects of chemicals and drugs on living system.

What is Drug

Any substance other than food can be used in prevention, diagnosis, or treatment of diseases.

Source of Drugs
  • Natural
    • Plant (eg., Pilocarpine)
    • Animal (eg., Heparin)
    • Micro-organisms (eg., Anibiotics)
    • Mirerals (eg., Ferrous sulfate)
  • Synthetic
    • Chemically (eg., Sulphonamides)
    • Genetic Engineering - rDNA technology (eg., Human insulin)
Classes of Drugs
  • Prescription only medication (POM) drugs: Only for prescription.
  • Over the counter (OTC) drugs: Used by the public without a prescription.

Routes of administration
  • Oral
    - Inactivation or elimination of part or whole of the drug reaching the systemic circulation
    • Sites: Gut first pass effect
      • Gastric acidity -> Benzyl penicillin
      • Digestive enzyme -> Insulin
      • Mucosal enzyme -> Benzyl Tyramine
    • Sites: Hepatic first pass effect
      • Complete -> Nitroglycerine
      • Partial -> Propranolol
      • Minimul -> Atenolol
    • Polar drugs (water soluble drug) not totally absorbed and not pass through Blood Brian Barrier (BBB)
    • Non-polar drugs (Lipid soluble drugs) highly absorbed and pass BBB
  • Parenteral route (Injection)
    • Intravenous (IV) injection
      - Suitable in emergency and acid labile drugs
    • Intramuscular (IM) Injection
      - Suitable for solution, suspension and oily drugs
    • Subcutaneous (SC) Injection
      - Suitable for drugs that are non-irritant in aqueous solution / suspension.
    • Intradermal (ID) Injection
      - Sensitive tests
    • Other injection
      • Intra-cardiac
      • Intra-bone marrow
      • Intrathecal (CSF)
      • Intra-peritoneal
  • Musocal
    • Buccual / Sublingual
    • Ocular
    • Vaginal
    • Nasal
    • Rectal
  • Inhalation
    - Systemic delivery of drugs
    - Highly blood sypply and wide surface area
    - Highly absorbed (high bioavailability)
    - Many drugs make lunk irritants
  • Topical
    - Usually local effect but high lipid soluble drugs can be absorbed
    - Transdermal drug delivery system (TDDS) enhance skin absorption (eg., Skin patches of nicotine)

Pharmacology Classification
  • Pharmacology
    • Phamacokinetics:
      - What the body does to the drug.
      • A-Absorption
      • D-Distribution
      • M-Metabolism
      • E-Elimenation
    • Pharmacodynamics:
      - What the drug does to the body.
      • Mechanism of action (Drug receptor interaction)
    • Pharmacotheraputics:
      - The result of drug and body action.
      • Uses of drug (Theraputic effect)

I. Phamacokinetics

What the body does to the drug (A-D-M-E).

1) Absorption

Transfer of drug from the site of administration to the systemic circulation.

Mechanism of Absorption
  • Passibe Transfer
    • Simple diffusion (Lipid diffusion):
      - From High to Low concetration
      - No needed energy and carrier
      - Drug must be lipid soluble and small in molecular wieght
      - weak acid drugs -> less ionized in acidic medium
      - weak base drugs -> less ionized in basic medium
    • Filtration (Osmosis):
      - No carrier and energy
  • Special Transfer
    • Facilitate Diffusion:
      - From High to Low concetration
      - Need carrier and not need energy
    • Active Transport:
      - From Low to High concetration
      - must need energy and carrier -> eg., Glucose (Na+/K+ Pump)
  • Pinocytosis / Endocytosis:
    - Drug of exceptionallh large size
    - Engulfment of a drug molecule by the cell membrane

2) Distribution

The transfer of drug from the blood stream into the tissue.

Depend on, Increase blood flow -> increase distrubution (Lung > Liver > Brain). Ability of the drug to pass biological membrane (Polarity and size of drug). Degree of binding to plasma protien (PP), Increase pp biding -> decrease distrubution.

  • Total Body Fluid (42 litters / 70kg)
    • Extracellular Body Fluid (14 litters)
      • Intravascular Body Fluid (4 litters)
      • Interstitial Body Fluid (10 litters)
    • Intracellular Body Fluid (28 litters)
  1. Binding to plasma protiens
    When the free drug concentration is decreased -> the binding drug converted to free drug -> to give the same action
    1. Displacement by other drugs -> Replacement of one drug by another
    -> E.g., Aspirin and Wargarin (Anticoagulant) -> Aspirin displaces warfarin due to high affinity to PP -> Increase free active Warfarin -> Increase toxicity of warfarin.
    - Drug with high affinity for PP are Aspirin, Sulfonamides, and Chloramphenical can replace the other drugs e.g., Warfarin.
    2. Decrease in albumin or plasma protien -> LIver disease.
  2. Patterns of distribution
    • Intravascular (Single compartment):
      - Drug (High Mwt) is retained in the blood compartment.
      - Eg., Drug pound to plasma protiens and polysaccharides (Heparin and Dextran)
    • Extracellular (Two compartment) = Intravascular + Interstitial:
      - Drug (Small Mwt) can filtrate but can not pass through cell membrane (Lipid membrane)
      - Eg., Quaternary ammonium compound (Neostigmine) and Mannitol (Osmotic diuretic)
    • All over the body (Multi-compartment) = Intra + Extracellular:
      - Drug (small Mwt) can filtrate but can pass through cell membrane (Lipid membrane)
      - Tetiary amines (Physostigmine), Alcohol and aspirin.
    • Tissue reservoirs:
      * Hair -> Arsenic
      * Liver -> Vitamin B12
      * Thyroid -> Iodine
      * Heart -> Digitalis
      * Fate -> Thiopentone
      * Bone -> Ca2+
    • Blood brain barrier (BBB)
      Lipid cellular barrier -> only lipid soluble (Non-ionized).
      Inflamamation (Meningitis) -> Increase permeability of BBB.
    • Placenta barriers
      Lipid cellular barrier
      - If the drug pass placenta during pregnancy -> Teratogenicity e.g., Tetracyclines.
      - If the drug pass placenta during labor -> Neonatal asphyxia e.g., Morphine and barbi
  3. Volume of distribution
    - The apparent volume of fluid into which an administrated drug is dispersed. Vd (Volumne of distribution) = Q (Total Amount of drug in the body) / Cp (Plasma concetration of the drug)
    - Useful to determine the total amount of drug in the body (Q = Cp X Vd)
    - The additional dosage needed (Vd = C2 X C1)
    - If the drug has high Vd -> the drug has low affinity to binding to PP.
    - If the drug has low Vd -> the drug has high affinity to binding to PP.

3) Metabolism

Metabolism or biotransformation usually conversion of drug from non-polar -> polar -> more polar -> to facilitate excretion.

Sites of Metabolism
  • Hepatic microsomal biotransformation
    • In hepatic smooth endoplasmic reticulum
    • Oxidation (cytochrome P450), reduction, hydrolysis and glucuronidation only.
    • Can be induced and inhibited
    • Activity is unstable
  • Non-hepatic microsomal biotransformation
    • In lung, kidney, skin and plasma
    • Oxidation, reduction, hydrolysis, all conjugation, except glucuronidation.
    • Can't be induced and inhibited
    • Activity is stable

Drug -> Phase I -> Oxidation/Reduction/Hydrolysis -> Phase II -> Conjugation

  • Phase I
    • Oxidation: e.g., Phenacetin -> Acetaminophen
    • Reduction: e.g., Chloral hydrate -> Tri-chloro ethanol
    • Hydrolysis e.g., Acetylcholine -> Choline + Acetic acid
  • Phase II (Conjugation)
    • Acitic acid (Acetylation) -> e.g., Isoniazid
    • Methylation -> (e.g., Nor-addrenaline)
    • Sufate -> Phenols
    • Glycine -> Aspirin
    • Glucuronic acid -> Chloramphenical

4) Excretion

The process which involve cexretion of drug outside of the body

Routes of drug excretion
  • Renal:
    • Glomerular filtration: For water soluble non boud drugs.
    • Proximal (Active) tubular secretion: e.g., Penicillin.
    • Distal (Passive) tubular reasorption: For lipid soluble drugs.
      Reasorption may affected by pH:
      - Acidification of urine (Vitamin C) -> Increase excretion of basic drugs, e.g., Ephedrine
      - Alkalization of urine (NaHCo3) -> Increase excretion of acidic drugs, e.g., Aspirin
  • GIT:
    • Saliva: (Iodine & Morphine)
    • Stomach: (Morphine)
    • Bile: (Feces)
  • Skin:
    • Sweat gland: Rifampicin
    • Breast (milk) Nicotine & Morphine
  • Lung:
    • Gases e.g., Nitrous oxide (N2O) and Halothane

Prolong duration of action
  1. Decrease absorption
    * Add Vasoconstictor (Adreneline + local anesthesia)
    * Use sparingly soluble complex (Protamine zinc insulin)
    * Use of drug in oil (Vasopressin in oil)
    * Use of slow release (SR) tablets
    * Use SC pellet implantation (DOCA in Addision's disease and contraception)
  2. Decrease Metabolism
    - Use HME inhibitors e.g., Omeprazole & Erythromycin
  3. Decrease Excretion
    - Probenecid with Penicillin
  4. Increase protien biniding
    - Add methoxy group to sulfonamide

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