Effect of Drugs on BP
Competency
• At the end of this session Phase II Students
should be able to Demonstrate the effects
of drugs on blood pressure using computer
aided learning.
CAL
• Demonstrate the effects of vasopressor
agents on blood pressure using computer
aided learning.
• Vasopressor agents: Adr, NA, Iso
• Adr: alpha, beta 1, beta 2
• NA: alpha, beta 1
• Isoprenaline: beta 1, beta 2
• Alpha: smooth mu, beta 1: heart, beta 2:
smooth mu
CAL
• Regulatory body: CPCSEA
• Committee for purpose of control and supervision of
experiments on animals for research and education.
• IAEC
• Dog
• Both carotid arteries occluded.
• Sympathetic system and adrenal medulla are activated
because carotid artery baroreceptor sense sudden fall
in BP.
• Rise in BP
• To ascertain that sympathetic system is intact, CA
Occlusion is performed before administration of drugs
acting on sympathetic system
Observed parameters
• SBP, DBP
• Average BP = SBP+DBP/2, (100)
• Mean BP = SBP+(2*DBP)/3 or DBP+1/3 PP =
(90)
• Pulse Pressure = SBP-DBP (40)
Simple observation (Adr)
• Alpha
• Beta 1
Beta 2
• Sudden rapid i/v - Biphasic response
• Marked inc in SBP, DBP (Alpha mediated
-vasoconstriction)
• Beta 1 agonist, inc. foc, inc HR,
• small vagal notch – vagal stimu.
• Fall in MBP Beta 2,
Simple observation (NA)
• Alpha
• Beta 1
• Rise in SBP, DBP
• Significant rise in MBP
• No Beta 2 action
• Reduces HR due to vagal stimulation – reflex
bradycardia
Simple observation (Iso)
• Beta 1
Beta 2
• Slight increase in SBP
• Fall in DBP
• MBP fall
• HR increases
Effect of Vasopressors
Adr NA Iso
HR + - ++
Mean BP + ++ _
Exercise
• Demonstrate the effect of Carotid artery occlusion on
blood pressure using computer aided learning.
• Demonstrate the effect of Tolazoline / Phentolamine on
effect of (Adr, NA, Iso) vasopressor agents on blood
pressure using computer aided learning.
• Demonstrate the Dale’s vasomotor reversal
phenomenon using computer aided learning.
• Demonstrate the effect of Propranolol on effect of
vasopressor agents on blood pressure using computer
aided learning.
• Demonstrate the effect of Tolazoline / Phentolamine
and Propranolol on effect of vasopressor agents on
blood pressure using computer aided learning.
Carotid artery occlusion
• Due to occlusion of
both CA, sympathetic
system and adrenal
medulla are activated
because carotid artery
baroreceptors sense
sudden fall in BP.
• Rise in BP
Tolazoline / Phentolamine
• Pressor response of Adr is converted into depressor
response after alpha blocker
• Effect of NA on BP is blocked indicating that rise on
BP was due to alpha agonistic action
• Effect of Isoprenaline on BP was not blocked
indicating that effect was not due to action on alpha
receptors.
Dale’s vasomotor reversal
phenomenon
• Alpha blocker – blocks pressor effect
• Only beta 2 effect is observed
• Fall in BP
• Increase in HR through reflex action
• Pressor response of Adr is converted into
depressor response after alpha blocker
Effect of Propranolol
Effect not
altered
Effect blocked
pressor response
slightly increased
Dale’s vasomotor re - reversal
• Beta blocker – Propranolol
• Rise in BP
• Increase in HR through reflex action
Effect of Tolazoline / Phentolamine
and Propranolol on
• All effects are blocked
Effect of Tyramine on BP
• Indirectly acting sympathomimetic agents
• Rise in BP, On repeated administration gradual
decrease in response - Tachyphylaxis or acute
tolerance
Cholinergic drugs
• Peripheral vagal nerve stimulation – fall in BP
• Ach: i/v low doses
• Transient fall in BP (M3), reflex tachycardia
• Fall in BP – EDRF, nitric oxide (NO) acts on
vascular smooth muscles causing generalized
vasodilatation.
• Most of the bv lack cholinergic innervation but
muscarinic receptors M3 are present on
vascular endothelium
• Ach: i/v high doses- more fall in BP
Cholinergic drugs – Agonistic effect on muscarinic receptors - Fall
Effect of physostigmine on
vasodepressor effect of carbachol,
pilocarpine & low doses of Ach
• Effect of carbachol, pilocarpine on BP was
not changed after physostigmine as they
are not destroyed by cholinesterase
• Effect of low doses of Ach on BP was
potentiated, Ach rapidly destroyed by
cholinesterase
Effect of Atropine on vasodepressor
effect of carbachol, pilocarpine & Ach
• When used alone no significant effect on
blood vessels & BP, most of the resistance
vessels (arteries) lack the significant
cholinergic innervation.
• BP may rise with atropine due to
tachycardia and stimulation of vasomotor
centre.
• Atropine completely blocks the
vasodepressor effect of carbachol,
Effect of atropine on very high
doses of Ach on BP
• Atropine blocks the action of Ach on BP
• High doses of Ach given after atropine –
BP significantly increased
• Due to stimulation of nicotinic receptors –
• Nicotinic action of Ach
• Initial fall then rise
Effect of Histamine on BP using
CAL
• Effect of Histamine on BP; i/v fall in BP
• Effect of H1 blocker mepyramine on histamine
induced fall in BP
– Fall in BP is reduced but not totally blocked
– The partial fall in BP was due to agonistic effect on H2
receptors and is slow but sustained due to increased
cAMP concentration
• Effect of H2 blocker cimetidine on histamine induced
fall in BP
– Fall in BP is reduced but not totally blocked
– The partial fall in BP was due to agonistic effect on H1
receptors and is rapid but short lived due to release of
EDRF. H1 receptor stimulation causes release of EDRF.
H1 receptors present on endothelial cells
Effect of H1 blocker mepyramine
and H2 blocker cimetidine on
histamine induced fall in BP
• Fall in BP was totally blocked
• These findings indicate that fall in BP due to
histamine is because of action on both H1 & H2
receptors
• Clinical relevance
• To prevent or reverse histamine induced
hypotension both H1 & H2 blocker are required.
• For total blockade of allergic manifestation due to
histamine both H1 & H2 blocker are required.
