2. Competency PH 4.2
Demonstrate the effects of drugs on blood pressure (vasopressor and
vaso-depressors with appropriate blockers) using computer aided learning
(CAL)
Learning Objectives
At the end of the learning session, the students should be able to:
1. Demonstrate the effects of various drugs on different haemodynamic
parameters in a pithed rat computer simulation.
2. Understand the underlying mechanism of action of these drugs.
3. Compare drugs belonging to either the same or different pharmacological
groups.
3. CAL Interface
ABP = Arterial blood pressure
LVP = Left ventricular pressure
VBP = Venous blood pressure
Con = Force of contraction of heart
HR = Heart rate
Select-
ABP
HR
4. Assessment through CAL
1. Demonstrate the effect of given drugs on Rat CVS.
2. Draw (use pencil ONLY) the tracing of changes on arterial
blood pressure and heart rate following intravenous
injection of the given drugs.
3. Make a relevant observation table.
4. Complete the set of questions.
5. Observation Table Format
Intervention Systolic ABP
mmHg
Diastolic ABP
mmHg
Heart rate
Beats/min
Control – before
the drug
After the drug
Change due to
the drug
6. Understanding the response to Adrenaline
Adrenaline produces biphasic responses in blood pressure. The initial increase in blood pressure is
due to the action of adrenaline on alpha 1 and beta 1 receptors. Alpha 1 stimulation produces
vasoconstriction of arterioles and veins resulting in increased peripheral resistance. Beta 1
receptor action on the heart produces increased heart rate and increased myocardial contraction
causing increased cardiac output.
BP = Cardiac Output * Peripheral Resistance
But action on beta 2 receptors produce vasodilatation of blood vessels of skeletal muscle resulting
in slight fall of BP. Since alpha 1 receptor action is predominant, we are able to see the net result
action of increase in BP, initially.
7. Gradually, the plasma concentration of exogenously administered adrenaline is reduced due
to
1. Dilution by diffusion and
2. Metabolization by MAO and COMT (mono amine oxidase and catechol O methyl
transferase enzymes)
The low concentration which is not able to stimulate alpha 1 receptors but is able to stimulate
only the beta 2 receptors (which is highly sensitive for even a small dose of adrenaline) fall in
BP below the baseline, by vasodilatation of blood vessels of skeletal muscle resulting in
lowering of peripheral resistance. This is responsible for the fall of BP before normalization.
This is known as biphasic response of adrenaline on BP.
9. Dale’s Vasomotor Reversal Phenomenon
Explain the chart and what is the phenomenon known as?
Adrenaline has alpha 1, beta 1 and beta 2 action. Thereby it produces biphasic response-
initial rise in BP followed by slight fall in BP. But after administration of alpha blocker, when
adrenaline was repeated there was stimulation of only cardiac beta 1 and skeletal muscle
vascular beta 2 adrenergic receptors by adrenaline. As the beta 2 response is overpowered,
there was fall of BP. This phenomenon is known as “Vasomotor Reversal of Dale” as it was
first demonstrated by Dale in the year 1906.
10. Nicotinic Effects of ACh
ACh: 10mcg/kg
Followed by
Atropine: 100
mg/kg
Followed by
ACh: 10 mg/kg
11. Explain the effect of Acetyl choline
ACh 10 micrograms (normal dose) produces fall in BP and bradycardia. Fall in BP due to
the following reasons:
1. Acts of M 3 receptors in all blood vessels (except skin of face and neck) produce
vasodilatation and decrease in peripheral resistance. M 3 receptors are present on
vascular endothelial cells. Vasodilatation is primarily mediated through the release of an
endothelium dependent relaxing factor (EDRF) which in all probability is nitric oxide (NO).
2. Acts on M 2 receptors in the heart and decreases the heart rate and force of contraction.
3. Inhibitory action of ACh on noradrenaline release from tonically active vasoconstrictor
nerve endings. Thereby decrease the cardiac output.
12. BP = Cardiac Output * Peripheral Resistance
Bradycardia due to direct action on M 2 receptors on the heart. Then the ACh is
destroyed by Acetyl cholinesterase enzyme and BP comes to normal. Atropine
produces no effect since it is a blocker (antagonist) ACh 10 mg/kg (high dose-many
times the normal dose) produces very high increase in BP and tachycardia. The
increase in BP is due to the following reasons:
High dose of ACh stimulates both sympathetic and parasympathetic ganglia (N N
receptors)
13. 1. Stimulation of N N receptors of parasympathetic ganglion results in release of ACh from the post
ganglionic terminal innervation of the vascular smooth muscle. In presence of atropine usually ACh
fails to lower BP, because of blockade of muscarinic receptors of the blood vessels.
2. Stimulation of sympathetic autonomic ganglionic nicotinic receptors results in release of
noradrenaline from the post ganglionic sympathetic nerve terminal and noradrenaline acts over
alpha adrenergic receptors causing vasoconstriction which results in increased peripheral resistance
and increase in BP. Noradrenaline also stimulates beta 1 receptors and increase rate of force of
contraction thereby increase in rate, cardiac output and increase in BP.
3. Stimulation of nicotinic receptors on chromaffin cells of adrenal medulla causes the gradual release
of adrenaline and there is a rising phase of BP followed by gradual reduction of BP.
14. Tachy- Fast
Phylaxis- Protection
Otherwise known as acute tolerance or rapid development of tolerance. When the drug is
repeated in quick succession (repeated application in short intervals) marked reduction in
response is seen.
This is usually seen with indirectly acting drugs, eg, Ephedrine, Tyramine, Nicotine. They act
by releasing catecholamines in the body, synthesis of which is unable to match release, and
stores get depleted.
Explain the Phenomenon of Tachyphylaxis
