Pharmacogncy

• Quinoline alkaloids


  Alkaloids containing the 'quinoline' nucleus

  
• Major quinoline alkaloids from cinchona bark

  • quinine
  • quinidine
  • cinchonine
  • cinchonidine

  
• More than twenty-five alkaloids have been isolated and characterized either from the Yellow Cinchona (Cinchona calisaya and Cinchona ledgeriana) or from the Red Cinchona (Cinchona succirubra)

  
• Cinchona alkaloids


  • Usually possess two rings: quinolone (benzene ring + pyridine) and bicyclic quinuclidine
  • Possess the basic skeleton of 9'-rubanol derived from the parent compound Ruban

  
• Ruban


  Obtained from the combination of 4-methyl quinoline nucleus and quinuclidine nucleus

  
• Stereoisomers


  Isomeric molecules that have the same molecular formula and sequence of bonded atoms, but differ in the three-dimensional orientations of their atoms in space
• Quinine & quinidine are stereoisomers, Cinchonine & cinchonidine are stereoisomers

  
• For cinchonine & quinidine C8= R , C9 = S, For cinchonidine & quinine C8 = S , C9 = R

  
• Biosynthetic pathway of quinine

  Derived from the monoterpenoid-tryptophan pathway

  
• Quinidine is found as salts (sulfate & gluconate)
• Quinidine


  Depresses myocardial excitability, conduction velocity & contractility
• Totaquine


  A mixture of total alkaloids, containing 7-12% anhydrous quinine, 70-80% total alkaloids, used as anti-malarial and for cold but not as cardiac depressant

  
• Cinchonism or quinism


  Symptoms from continuous use of cinchona or quinine including flushed and sweaty skin, ringing of the ears, blurred vision, impaired hearing, confusion, reversible high-frequency hearing loss, head ache, abdominal pain, rashes, dysphoria, nausea, vomiting and diarrhea
• The roots are used as a tonic and stimulant.
• The leaves are used to treat fever, headache, and inflammation.
• Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes
• Pharmacodynamic processes


  The actions of the drug on the body
• Pharmacokinetic processes


  The actions of the body on the drug
• Pharmacokinetics


  1. Absorption

  2. Distribution

  3. Metabolism

  4. Elimination

  
• Using knowledge of pharmacokinetic parameters, clinicians can design optimal drug regimens, including the route of administration, the dose, the frequency, and the duration of treatment

  
• Routes of drugs administration

  The route of administration is determined by properties of the drug and by the therapeutic objectives

  
• Major routes of drug administration

  • Enteral
  • Parenteral
  • Topical
• Enteral administration


  Administering a drug by mouth, the safest and most common, convenient, and economical method of drug administration

  
• Oral administration


  Oral drugs are easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal
• Oral drug absorption


  • The pathways involved are the most complicated, and the low gastric pH inactivates some drugs
  • A wide range of oral preparations is available including enteric-coated and extended-release preparations

  
• Enteric-coated preparations


  An enteric coating is a chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine, where the coating dissolves and releases the drug
• Extended-release preparations


  Have special coatings or ingredients that control drug release, thereby allowing for slower absorption and prolonged duration of action
• Extended-release (ER) formulations


  Contain components or layers that control the drug release, allowing slower absorption and longer duration of action. May allow lower peak emergency doses and can improve patient compliance. Maintain concentrations within the therapeutic range over a longer duration, as opposed to immediate release dosage forms which may result in larger peaks and troughs in plasma concentration.

  
• ER formulations

  • Advantageous for drugs with short half-lives
  • Example: Oral morphine has a half-life of 2-4 hours and must be administered 6 times daily, but only 2 doses are needed with extended-release tablets
• Sublingual/buccal absorption


  1. Placement of drug under the tongue

  2. Placement of drug between the cheek and gum

  3. Advantages include ease of administration, rapid absorption, bypass of the harsh gastrointestinal environment, and avoidance of first-pass metabolism
• Parenteral administration


  Introduces drugs directly into the body by injection
• Parenteral routes


  • Highest bioavailability
  • Not subject to first-pass metabolism or harsh GI environment
  • Provide most control over actual dose delivered
  • Irreversible and may cause pain, fear, local tissue damage, and infections
• Major parenteral routes


  • Intravascular (intravenous or intra-arterial)
  • Intramuscular
  • Subcutaneous
• Intravenous (IV) injection


  • Most common parenteral route
  • Useful for drugs not absorbed orally
  • Permits rapid effect and maximum control over drug amount delivered
  • When given as bolus, full amount reaches systemic circulation immediately
  • When given as infusion, lower peak plasma concentrations and increased drug duration

  
• Intramuscular (IM) injection


  Drugs can be in aqueous solutions (rapidly absorbed) or specialized depot preparations (slowly absorbed)

  
• Subcutaneous (SC) injection


  • Provides absorption via simple diffusion, slower than IV
  • Minimizes risks of hemolysis or thrombosis associated with IV
  • May provide constant, slow, and sustained effects
  • Should not be used with drugs causing tissue irritation

  
• Intradermal (ID) injection


  • Injection into the dermis, the more vascular layer of skin under the epidermis
  • Used for diagnostic determination and desensitization

  
• Oral inhalation and nasal preparations

  • Provide rapid delivery of drug across large surface area of respiratory tract and pulmonary epithelium
  • Effects almost as rapid as IV bolus
  • Used for gases, aerosols, and respiratory disorders to minimize systemic side effects
• Inhalation and nasal routes of administration

  Provide rapid delivery of drug across the large surface area of mucous membranes of the respiratory tract and pulmonary epithelium
• Drug effects via inhalation

  Almost as rapid as IV bolus