1 PHL. 313 Dr. Khairy Zoheir. Lab.1 INTRODUCTION TO NS PHARMACOLOGY and DOSE- RESPONSE CURVE.
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Transcript of 1 PHL. 313 Dr. Khairy Zoheir. Lab.1 INTRODUCTION TO NS PHARMACOLOGY and DOSE- RESPONSE CURVE.
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PHL. 313
Dr. Khairy Zoheir
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Lab.1INTRODUCTION TO NS PHARMACOLOGY and DOSE- RESPONSE CURVE
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Nervous System
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Central Nervous System
Brain stem
Cerebrum
Spinal cord
Peripheral Nervous System
Afferent Efferent Sensory division Autonomic
Somatic
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Afferent and efferent neurons
• Afferent is known as sensory or receptor neurons which carry nerve impulses from receptors or sense organs toward the central nervous system.
• Efferent is known as motor or effector neurons which carry nerve impulses away from the central nervous system to effectors such as muscles or glands
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The Peripheral Nervous System
Somatic nervous system
(voluntary)
Skeletal muscle
Autonomic nervous system
(involuntary)
Heart, blood vessels,glands, other visceralorgans, smooth muscle
Efferent nervous system
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Anatomic classification
1- sympathetic (fight and flight)
To maintain homeostasis
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2- Parasympathetic (rest and digest)
• Its actions can be summarized as "rest and digest", as opposed to the "fight-or-flight" effects of the sympathetic nervous system..
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Neurotransmitter:A chemical that transmits signals from one neuron to another
or from a neuron to an effector cell.
ElectricalStimulation
(impulse)
Chemical(neurotransmitter)
Chemical(intracellular
messengers)
Electrical(membrane
ion channels)
Physiologicalfunctions
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Neurotransmitter-based classification
1- Cholinergic, 2- Adrenergic, and 3- Dopaminergic
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1- Cholinergic transmitter
• It means related to the neurotransmitter Acetylcholine.• The parasympathetic nervous system is entirely cholinergic.
Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, and the sweat glands
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Definition of Agonist and Antagonist
Agonist: A structural analog that is capable of stimulating a biological response.
Antagonist: A receptor-specific blocker (e.g., enzyme inhibitor) or a physiologic agent (e.g., hormone), that prevents the action of another molecule.
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Mode of Action
Direct-acting: Molecule that physically binds to the target for its effect.
Example: ACh activates cholinergic receptors.
Indirect-acting: Molecule that exerts effect on the target by interacting with another molecule.
Example:neostigmine blocks AchE, causing Ach accumulation.
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Acetylcholine (ACh) • Cholinergic neurotransmitter.• Parasympathomimetic.• Muscarinic action.(M3)
Sites of release: Preganglionic synapses of both sympathetic and
parasympathetic ganglia. Parasympathetic postganglionic neuroeffector junctions. All somatic motor end-plates on skeletal muscles.
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Muscarinic Autonomic Effects of Ach
• Affect on gatsrtointestinal tract (GIT) as follow• 1- Motility (Increase contraction)• 2- Secretion (increase)• 3- Sphincters (relaxation)
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Muscarinic Actions
• The “Muscarinic Actions” -- Similar to those of parasympathetic stimulation
• • (M1): CNS, PNS, gastric parietal cells • • (M2): conducting tissue • • (M3): exocrine glands; smooth muscle
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Action of acetylcholine on smooth muscle.
• Contraction of smooth muscle by acetylcholine is mediated by activation of muscarinic receptors M2 and M3 subtypes.
• Acetylcholine (ACh) has virtually no systemic therapeutic applications because its actions are diffuse, and its hydrolysis, catalyzed by both acetylcholinesterase (AChE) and plasma butyrylcholinesterase, is rapid.
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Dose-Response Curve
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Apparatus
Valve
(Wash)
valve
H2O
physiogragh
Tyroide
Solution
Intestine part
25 ml
Oxygen supply
NaCl:
Isotenicity
CaCl2:
Contraction of muscle
Glucose:
Energy
NaHCO3:
PH
MgCL2:
relaxation
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Why Tryroid Solution:
• 1- To maintain the muscle alive throughout the experiment.
• 2- To maintain the same environmental condition for the cells inside the animal (In vivo) as outside the animal (In vitro).
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Why small intestine?
• 1- Easy handling in the lab.• 2- Good model to study the effects of
cholinergic drugs.• 3- Longitudinal muscle of guinea pig intestine
contains muscarinic receptors of which M2 and M3 subtypes.
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Definition of dose- response curve:
• It is a relationship between dose & response which describes the change in effect on an organ caused by differing levels of exposure (or doses) to a stressor (usually a chemical) after a certain exposure time.
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Dose – Response Curve
• It is a relationship between Dose and (Response %)• From this curve we can see :
Potency (a measure of the activity of a drug in a biological system)
Efficacy (the capacity to produce an effect)Therapeutic index (dose of a drug for 50% of the population
divided by the minimum effective dose for 50% of the population ED 50 :dose in pharmacology is the amount of drug that produces a therapeutic response in 50% of the people taking it
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Procedure1- Cut 1 Cm from Guine pig small intestine and hang it in the organ bath which has tyroid solution.2- Use MP36 to measure the contraction of the intestine inside the organ bath.3- Add 0.1 ml Acetylcholine (Ach) (0.1 %) to the intestine which in the organ bath and record the response then stop the MP36 and make washing for the tyroid in the organ bath. 4- Add 0.2 ml of Ach and record the response and then wash.3- Add 0.4, 0.8, 1.6,>>>>. Till get maximum response for the contraction of the intestine as showing in next slide.4- Tabulate the relationship between the dose and response (cm) and % of response .5- Make histogram between the dose and % response to get ED50 as shown .
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Dose – Response Curve
D + R DR complex Response
cm
0.1ml 0.2ml 0.4ml 0.8ml 1.6ml
wash
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Dose – Response Curve
Response %
)x/ max*( 100
Response (cm)
Dose )ml(
33.3 1 0.1
60 1.8 0.2
83.3 2.5 0.4
100 3 0.8
100 3 1.6
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ED 50 = xxx ml