Class notes

Fundamentals of pharmacology & therapeutics - complete notes

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Course
PHAR270 (PHAR270)

Institution
Queen’s University (QU )

Covers basic principles of pharmacology & pharmacology of the nervous, cardiovascular, respiratory, endocrine, & gastrointestinal systems. Also covers pharmacology in the context of infections, cancer & special populations.

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Uploaded on July 1, 2024
Number of pages 103
Written in 2019/2020
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Virtual Ileum Lab
Monday, January 27, 2020 11:11 AM

Protocol and materials:
• Rabbit ileum tissue preparation is hung in an organ bath containing physiological concentrations of salts (NACl, KCl, CaCl2, etc.) and glucose, required to
maintain tissue viability
• Tissue sample is attached by string to a force transducer that measures contractions of the longitudinal muscle. Contractionsare viewed and analyzed usin
LabChart software,

• Solution in which the ileum tissue is submerged contains:
○ Tyrode's solution: roughly isotonic solution that contains magnesium, a sugar (usually glucose) as an energy source, and uses bicarbonate as a buffer
○ Carbogen: mixture of carbon dioxide and oxygen gas that is required to aerate these artificial solutions

Analyzing LabChart Data
• y-axis: contractile force of the rabbit ileum tissue in grams
• x-axis: time period of the contraction (minutes:seconds)
• Oscillations: red oscillations represent the change in tension due to contraction or relaxation of the tissue
• Tensile force: display of tension (in grams) measured by the force transducer at the current point in time

Baseline data: Contraction, relaxation, no response

Contraction No response Relaxation

Research on the 6 autonomic drugs
➢ Atenolol
▪ Cardioselective beta blocker
▪ Adrenergic beta-1 receptor antagonist
▪ Blocking beta-1 receptors in the heart reduces heart rate and the force of contraction of the heart, resulting in a decrease in oxygen demand and
blood pressure, thus relieving pain
▪ Result: no effect
➢ Epinephrine
▪ Activates alpha and beta receptors
▪ Drugs that mimic effects of the sympathetic system
▪ Induce relaxation of ileum
➢ Prazosin
▪ Alpha-1 antagonist
▪ Drugs that block effects of the sympathetic system
➢ Isoprenaline (isopropylnorepinephrine)
▪ analog of epinephrine; beta-sympathomimetic
▪ Non-selective beta receptor agonist
▪ Result: relaxation
➢ Norepinephrine
▪ Adrenergic agonist (alpha and beta-1 receptors)
▪ Result: relaxation
➢ Phenylepinephrine
▪ alpha-1 adrenergic receptor agonist
▪ Result: relaxation

Unknown drug
➢ Adrenergic agonist
▪ Want to use antagonists that target the different adrenergic receptors
▪ Atenolol + prazosin = adrenergic antagonists
◊ Administering atenolol would change the effect on rabbit ileum for isoprenaline
- Atenolol = beta-1 adrenergic receptor antagonist
- Since epinephrine, norepinephrine and Phenylepinephrine are all adrenergic receptor agonists that elicit their effects on adrenergic
receptors other than or in addition to the beta-1 receptor, they can still produce a relaxation in the rabbit ileum tissue when co-
administered with atenolol

PHAR270 Page 1

, administered with atenolol
- Since isoprenaline is a non-selective beta-adrenergic receptor agonist, when this drug is administered after atenolol (beta-1 receptor
antagonist), the blocked beta-adrenergic will prevent isoprenaline from eliciting a relaxation effect on the rabbit ileum tissue
- Thus, if you administer ;
→ Atenolol --> unknown autonomic drug and the effect changes from relaxation --> no effect, then the autonomic unknown drug =
isoprenaline
◊ Administering prazosin would change the effect on rabbit ileum for phenylephrine
- Prazosin = selective alpha-1 adrenergic receptor antagonist
- Since epinephrine, norepinephrine and isoprenaline all have effects on beta receptors, they can still produce a relaxation in the rabbit
ileum tissue when prazosin is administered
- Since phenylephrine is a selective alpha-1 adrenergic receptor agonist, when prazosin is administered prior to phenylephrine, the blocke
alpha-1 adrenergic receptors will prevent Phenylepinephrine from eliciting a relaxation effect on the rabbit ileum tissue
- Thus, if you administer;
→ Prazosin--> unknown autonomic drug and the effect changes from relaxation --> no effect, then the autonomic unknown drug is
likely phenylephrine

Blood pressure tracings
• Can be used to differentiate epinephrine from norepinephrine
• Accurate and constant measurement of BP can be conducted through indwelling catheters in the left femoral vein and right femoral artery of an
anesthetized animal

➢ Receptor activation
○ The pattern and timing of the responses to a drug given acutely is affected by the selectivity of an agonist and the way the drug is distributed
throughout the body
○ After injection, the drug would first travel to and act on the heart. After leaving the heart and heading into the arterial tree, the drug will be distribut
in a larger volume as a result of mixing/dilution. Therefore, vascular responses would lag behind the cardiac components.
○ Heart --> arteries
○ Receptors in the heart: beta-1
▪ Activation of beta-1 receptors = increases heart rate and force of contraction of the heart (increase BP)
○ Receptors in the arteries: beta-2 and alpha receptors
▪ Activation of beta-2 receptors = relaxation of the vasculature (decrease BP)
▪ Activation of alpha receptors = contraction of the vasculature (increase BP)

➢ High dose epinephrine
○ When a high dose of epi is administered, there is an increase in BP, followed by a decrease, and then a further increase.
▪ Result of activation of all 4 adrenergic receptors

○ Epinephrine has greater affinity for beta-2 receptors, meaning it binds to those receptors longer before releasing them, so you see the beta-2 effect
first. BUT there are more alpha receptors in the vasculature overall, so overtime the alpha response predominates, resulting in the final increase in B

➢ Administration of norepinephrine
○ Causes an increase in BP

Flowchart

PHAR270 Page 2

,PHAR270 Page 3

, Midterm Review
Monday, February 10, 2020 11:28 AM

⚫ What happens to a drug within the body?
○ The path from drug administration to drug removal;
▪ Absorption
▪ Distribution
▪ Metabolism
▪ Excretion
- Primary organ of excretion= kidney (by urine)

⚫ Need to know phase 1 vs phase 2 transformation
○ Phase 1
▪ Purpose: make drug molecule able to accept a more water-soluble entity (so it can be excreted)
○ Phase 2
▪ Water soluble moiety is added

⚫ What do therapeutic index and therapeutic range tell us?
○ Therapeutic index
▪ Measure of how safe a drug is
▪ Therapeutic index = TD50/ED50
- Higher the result= safer the drug

○ Therapeutic range
▪ Want concentration of drug in blood above the concentration required for desired response and below the concentration leading to adverse respon

⚫ Parasympathetic and sympathetic nervous systems

Need to know differences, and their different effects

⚫ Neurotransmitters and receptors in the PNS
○ Need to know neurotransmitters and receptors of the peripheral nervous system
▪ PNS, sympathetic, somatic

PHAR270 Page 4

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