Vasoactive Drug, Serotonin, Histamines

1. Vasoactive drugs acting on vascular
smooth muscle:
Vasoactive substance is an endogenous agent or
pharmaceutical drug that effects blood pressure and heart
rate by vasodilation or vasoconstriction.
It helps the body's homeostatic mechanisms to
keep hemodynamic under control.

2. Vascular Smooth Muscle Cell:
Vascular smooth muscle cells are present in majority of the
blood vessels.
They determine tone of vessel, diameter, and change in blood
pressure.
Excessive vasoconstriction leads to high blood pressure.
Excessive vasodilation leads to low blood pressure.

3. Vasoconstrictor Drug:
Vasoconstrictor drugs cause contraction of
vascular smooth muscle which leads to
narrowing of vessel.
Mostly used for treatment of hypotension
and shock.

4. Classes of vasoconstrictor drugs:
On the basis of mechanisms of action, there are two
general classes:
1. Sympathomimetic drugs
2. Vasopressin Analogs
 Sympathomimetic drugs mimic the effect of endogenous
agonist of sympathetic nervous system.
These drugs have α- adrenoceptor agonist
properties.

5. Mechanisms of action:
Smooth muscle cell have 2 receptors:
α1- receptor:
Linked to Gq- protein,
 when alpha agonist binds,
 activates smooth muscle contraction.
by IP3 signal transduction
pathway.

6. α2- receptor:
linked with Gi-protein,
 when alpha agonist binds,
decrease intracellular cAMP
cause vasoconstriction.
Therapeutic use: treatment of hypotension, shock & nasal
decongestants.
Adverse effects: Headache, dry mouth, gastric upset, reflex
bradycardia.
Examples: Methoxamine , Phenylephrine, Oxymetazoline,
Tetrahydrozoline

7. 2.Vasopressin Analogs:
Vasopressin: is a hormone released from posterior
pituitary. It regulate extracellular fluid volume by
affecting water reabsorption in kidneys. It constrict
blood vessel.
Vasopressin analogs has 2 sites of action kidney and
blood vessel.

8. Mechanisms of action:
 Act through V2 receptors. Increase water reabsorption.
 Increase blood volume, cardiac output, arterial pressure.

9. 2. Bind with V1 receptor coupled with Gq protein.
Increase vascular resistance.
Increase workload of heart, and arterial pressure.
Adverse effects: Headache, nausea, bronchoconstriction,
abdominal cramp.
Example:
Arginine vasopressin
Terlipressin

10. Vasodilator Drugs
Drugs which relax the smooth muscle, causes
dilation of vessel are called vasodilator drugs.
Dilation of vessel leads to reduction in vascular
resistance, which leads to decreased blood
pressure.

11. Arterial dilators: reduce arterial pressure,
reduce after load of heart
Venous dilators: reduce venous pressure, decrease
cardiac preload.
Therapeutic Use:
Heart failure
 Angina
 Hypertension.

12. Drug Classes used as vasodilator
agents:
 Angiotensin converting enzyme inhibitor
 Alpha adrenoceptor antagonist.
 Calcium channel blocker.
 Direct vasodilators
 Nitro dilators
 Angiotensin receptor blockers
 Rennin inhibitors.

13. Drug Class Action Example Adverse
effect
ACE Inhibitors • Blocking Angiotensin II
formation and inhibiting
bradykinin metabolism.
Captopril,
Ramipril
Lisinopril
Dry Cough
Hyperkalemia
Direct
Vasodilators
• Directly act on smooth
muscle
• Reduce vascular
resistance.
• Inhibit IP3 Calcium release.
Hydralazine
Headaches,
flushing
Tachycardia
Nitro Dilators • Cause Smooth muscle
relaxation by inhibit Ca2+
• Reduced Preload, After
load.
Isosorbide
mononitrate
Nitroglycerin
Headache
Reflex Tachycardia
Ca2+ Channel
Blocker
• Decrease Contractility
• Smooth muscle relaxation
• Reduced Hypertension
Nicardipine
Nifedipine
Verapamil
Flushing,
Headache,
Excessive
hypotension

14. Serotonin
Serotonin is a chemical ( neurotransmitter)
produce by nerve cells . Serotonin is found mostly
throughout the central nervous system ( different
parts of brain ) and GIT.
Serotonin is converted from the essential amino
acid tryptophan. This amino acid enter the body
through diet such as nuts, cheese n red meat.

15. Functions of Serotonin
A natural mood stabilizer
Makes happier
Helps in sleeping , eating, digestion
Reduce depression
Regulate anxiety
Heal wounds
Control bowl movements

16. Its presence other that CNS
Serotonin is present in enterochromaffin
cells of GIT . It helps in bowl movement.
 It is actively taken up by blood platelets which
store it.
 When the platelets bind to a clot, they release
serotonin, where it serves as
a vasoconstrictor and helps to
regulate hemostasis and blood clotting.

17. Normal Range of serotonin
Generally, the normal range for serotonin
levels in blood is 101 to 283
nanograms/milliliter (ng/m L).

18. Low level of serotonin
Low levels of serotonin in the brain may cause
depression, anxiety, and sleep trouble.
Selective serotonin reuptake inhibitor SSRI
are used to treat depression.
factors that boost serotonin levels:
exposure to bright light
exercise
a healthy diet

19. Selective serotonin reuptake
inhibitor (SSRI)
 (SSRIs) are a class of drugs that are typically
used to treat depression caused by low level of
serotonin levels.
The exact mechanism of SSRIs is unknown.
They decrease the amount of serotonin in
presynaptic cell and increase the amount in
post synaptic cell for different activities

20. Drugs in this class include:
Most common:
citalopram
escitalopram
Fluoxetine
paroxetine
fluvoxamine
sertraline

21. Mechanism of action
In the brain, messages are passed from a nerve
cell to another via a chemical synapse, a small
gap between the cells.
 The presynaptic cell sends the information
releases neurotransmitters including serotonin
into that gap.
The neurotransmitters are then recognized
by receptors on the surface of the recipient
postsynaptic cell.

22. Mechanism of action
About 10% of the neurotransmitters are lost in
this process.
 the other 90% are taken up again by
presynaptic cell, a process called reuptake.
SSRIs inhibit the reuptake of serotonin. As a
result, the serotonin stays in the synaptic gap
longer than it normally would , and
postsynaptic neuronal activity increases.

25. Therapeutic uses
SSRI are use to treat following:
Depression
Anxiety
 psychiatric disorders
Post traumatic stress disorders
Social anxiety disorder

26. Pharmacokinetics
Orally absorbed
Food has little effect on its absorption
Metabolism by liver
Excretion through kidneys or feces

27. Adverse effects
sweating
Nausea , vomiting
Dry mouth
Insomnia
Diarrhea
Nervousness,
restlessness
Dizziness
Sexual dysfunction (loss of libido)
Headache

28. Serotonin Norepinephrine reuptake
inhibitor SNRIs
SNRIs are class of drugs that are typically used in
patient in whom SSRIs may be ineffective to treat
 depression
 Chronic nerve pain due to depression
 Muscle aches

29. Drug in this class include
 Venlafaxine
 Desvenlafaxine
 Duloxetine
 levomilnacipran

30. Mechanism of action
SNRIs inhibit reuptake of two neurotransmitters
in presynaptic neuron such as
1. Serotonin
2. Norepinephrine
• Increase the amount of neurotransmitters in
synaptic cleft

31. Drug action

32. Therapeutic use
SNRIs use to treat following
To treat depression in patient SSRIs ineffective
Relieving pain associated with diabetic
neuropathy
Postherpetic neuralgia
Fibromyalgia
Low back pain

33. Pharmacokinetics
• Orally absorbed
• Food has little effect on its absorption
• Extensively metabolized in liver

34. Adverse effect
• Nausea
• Dry mouth
• Constipation
• Insomnia
• Dizziness
• Sweating
• Sexual dysfunction

35. Serotonin presence
• Serotonin receptors or 5 –Hydroxytryptamine
is a monoamine neurotransmitter
Serotonin is found in
GIT
Platelets
CNS

36. Serotonin production
• Approximately 90% human body ,s total
serotonin is located in the enterochromaffin
cells in the alimentary canal
• Where serotonin regulate intestinal movements
• The remainder is synthesized in serotonergic
neurons of the CNS

37. Enterochromaffin cells
EC cells EC function

38. Serotonin presence
• Serotonin secreted from the enterochromffin
cells eventually finds its way out of tissue in to
the blood
• Then serotonin actively taken up by the
platelets
serotonin released from platelets perform
following function
Vasoconsrictor
Attract platelets toward injury site

39. What Is Histamine:
Histamine is a chemical messenger mostly generated
in mast cells. It mediates a wide range of cellular
response ,including:
Allergic Reactions
Inflammatory Reactions
Basically, histamine has no clinical applications but
the agents that inhibit the action of histamine
(histamine receptor blockers) have important
therapeutic applications.

40. Location:
Histamine is particularly present in all tissues, lungs, skin,
blood vessels and GI Tract. It is found at high concentrations
in Mast cells
Synthesis:
Histamine is an amine formed by the decarboxylation of
amino acid Histidine by the enzyme histidine decarboxylase.
It is expressed in cells throughout the body.
If histamine is not stored ,it is rapidly inactivated by the
enzyme amine oxidase.

41. • Biosynthesis of Histamine:

42. Mechanism of Action:
Histamine is released in response to certain stimuli. It
exerts its effect by binding to various type of
Histamine receptors (H1,H2,H3 and H4).H1 and H2
receptors are widely used. Histamine has wide range
of pharmacological effect that are mediated by both
H1 and H2 receptors.
For Example:
H1 receptors are important in producing smooth
muscle contraction and increasing capillary
permeability.

43. H1 AntiHistamines:
These block the receptor-mediated response of a target
tissue. These are effective in preventing symptoms
than reversing them, once they have occurred.

44. • H1 Antihistamine Drugs:
Cyclizine
Loratidine
Olopatadine
Doxylamine
Meclizine

45. Pharmacokinetics :
These are given orally. Their half life is 4-6
hours.
Therapeutic Uses:
During Motion Sickness and Nausea
During Allergic and Inflammatory conditions

46. Adverse Effects:
Drowsiness
Tachycardia
Hypotension
Dry Mouth
Increased Appetite
Vertigo