351 PHL

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351 PHL

• Lab 1

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Purpose of Pharmacological Experiments

• Qualitative
• To determine the activity mechanism of
  drugs action e.g. analgesic, effect on blood
  pressure
• Quantitative
• To assay (measure) the activity of drugs e.g.
  toxic level

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Types of pharmacological experiments

• In vivo
• Study the action of drugs on the whole body
  (intact animal)
• There is interference by compensatory mechanisms
  of body
• Easier to study effect of drugs

• In vitro
• Study the action of drugs on pieces of tissue
• There is no interference by compensatory
  mechanisms of body
• Easier to study MOA potency of drugs

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In vitro experiments

• - In vitro experiments involve the use of
  isolated organ or muscle
• - Conditions of the experiment should be kept
  similar to body
• Experiment conditions
• 1- Electrolytes
• 2- Nutrients
• 3- Physiological pH
• 4- Constant temperature
• 5- Aeration

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Electrolytes

• Physiological solution
• Ex. Tyrodes Krebs
• Ingredients
• 1- Nacl ? adjust the tonicity
• 2- Ca2, K, Mg2 ? for normal contraction
• 3- Sodium bicarbonate ? to render the pH similar
  to that of blood
• 4- NaH2PO4 ? to compensate for any change in the
  pH
• 5- Glucose ? nutrient

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Aeration

• Examples
• Pure oxygen ? for heart tissues
• Air ? for intestine
• Carbogen (95 O2, 5 CO2) ? used for uterus

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Temperature

• Temperature should be kept constant during the
  experiment
• Physiological temp. (37C) is needed for
  mammalian tissues e.g. rabbit intestine
• The temp. should be reduced in some experiments
  to decrease spontaneous contraction e.g. isolated
  guinea-pig ileum
• Amphibian tissues can survive in room temp. e.g.
  isolated frog rectus abdominis

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Definitions

• Dose cycle time between different drug additions
  
• Contact time time from addition of drug until
  its removal by washing

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Autonomic nervous system innervations in the
intestine

• Sympathetic
• Transmitter NA, Adrenaline
• Receptors
• (intestine) a1, b2
• Action
• (intestine) inhibitory (?cont.)

• Parasympathetic
• Ach
• Nicotinic (Nn),
• muscarinic (M3)
• excitatory (?cont.)

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The effect of different doses of acetylcholine on
smooth muscle of intestine
N 0.05 0.1 0.2 0.3
0.4
Ach Ach Ach Ach Ach
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? amplitude
? amplitude
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? tone
? tone
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? tone amplitude
? tone amplitude