Vasodilators and beta blockers are drugs that relax blood vessels or interfere with sympathetic nervous system response to lower blood pressure. Specific agents include metoprolol, labetalol, and esmolol beta blockers. Alpha blockers like prazosin work by blocking alpha-1 receptors to cause vasodilation. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent the formation or effects of angiotensin II to lower blood pressure. Calcium channel blockers like amlodipine and nifedipine work by inhibiting calcium influx into vascular smooth muscle cells to cause vasodilation. Each class of drug has different mechanisms, pharmac

1. VASODILATORS
MODERATED BY DR.REENA

2. •As the name implies, vasodilator
drugs relax the smooth muscle in
blood vessels, which causes the
vessels to dilate.

3. SYMPATHOLYTICS
Beta Adrenergic blockers
•Bind selectively to beta
receptors and interfere with
ability of catecholamines or
other sympathomimetics to
provoke beta response

4. Beta blockers classified
according to whether they
exhibit b1 selective properties
versus non sele
ctive properties and whether
they possess intrinsic
sympathomimetic activity

5. •b blocker with selective properties
binds primarily to b1 (cardiac)
receptors, whereas a b blocker with
nonselective properties has equal
affinity for b1 and b2 (vascular and
bronchial smooth muscle, metabolic)
receptors

6. •Beta blockers with intrinsic
sympathomimetic activity produces
less bradycardia ,& less likely to
unmask left ventricular dysfunction
•Also these drugs are less likely to
produce vasospasm

7. • Cardioselective beta1 blockers
{atenolol,metoprolol, bisoprolol}in low
to moderate doses are unlikely to
produce bronchospasm,decrease
peripheral blood flow or mask
hypoglycemia
• For these reasons ,they are preferred
drugs in pulmonary disease, insulin
dependent diabetes mellitus or
symptomatic PVD
• Non selective agent carvedilol also has
alpha1 blocking action has shown to
improve survival in systolic heart failure

8. .Presence of alpha blocking
properties results in less bradycardia
and negative inotropic effects but is
a/w orthostatic hypotension
•IV Labetalol is used in Hypertensive
Emergency and is useful in
managing typeB aortic dissection.

9. Most commonly used beta blockers in
perioperative settings
-Metoprolol (b1 blocker). Dose 1–5 mg
Onset 1–5 min Half-life: 3–7h
-Labetalol a1,b1,b2 blocker
• Initial recommnded dosee is 2.5 to 10mg administered iv over
2 min
• After the initial dose ,depending on response Dose of 5–20
mg or0.5to 2mg/min may be given at 10 min interval until
desired bp is obtained
.onset 1–5 min, Half-life: 6 h
Esmolol beta1 blocker. Dose 50–300 mg/kg/min
onset 1–2 min
Half life 9min

10. • Side effects of beta blockers
Bradycardia
Heart block
Congestive heart failure
Bronchospasm
Claudication
Masking of hypoglycemia
Sedation
Precipitate angina pectoris or myocardial infarction
when abruptly discontinued

11. .In general beta blockers are less commonly
used as first line agent in hypertension as other
agents may have better safety profile specially
in those older than 60 years
. However these are indicated for long term
treatment of patients with coronary artery
disease and heart failure and their
antihypertensive action in these patients

12. Alpha 1 Receptor Blockers
Prasosin,Terasosin and Doxazocin are oral , selective
postsynaptic alpha1 adrenergic receptor antagonist
resulting in vasodilation of both arterial and venous
vasculature.
Also absence of presynaptic alpha 2 receptor
antagonist leaves intact the normal inhibitory effect
on norepinephrine release from nerve endings.
These drugs are less likely to elicit reflex increase in
cardiac output and renin release.

13. .Oral Phenoxybenzamine and IV Phentolamine are
non selective alpha blockers which also block
presynaptic alpha 2 receptors and are exclusively
used in the treatment of pheochromocytoma.
• Prasosin in addition to treating essential
hypertension ,decreases afterload in congestive
heart failure
• Prasosin also useful for preoperative preparation
in pheochromocytoma,relieves vasospasm in
Raynaud's phenomenon.

14. Cardivascular Effects
• Prasosin decreases systemic vascular
resistance without reflex tachycardia or
increase in renin activity
• Failure to alter renin activity reflects
continued activity of alpha2 receptors that
normally inhibit the release of renin
• Vascular tone in both resistance and
capacitance vessels is decreased resulting in
decrease venous return and cardiac output

15. Side Effects of prasosin
• Vertigo ,fluid retention and orthostatic hypotension
• Dryness of mouth.nasal congestion, nightmares,urinary
frequency, lethargy may accompany
• Hypotension during epidural anaesthesia may exaggerate
in presence of prasosin due to drug induced alpha 1
blockade that prevents compensatory vasoconstriction in
unblocked portions of body.The resulting hypotension
may not be responsive to usual doses of alpha1 agonists
like phenylephrine. Administration of epinephrine may be
necessary to increase systemic vascular resistance and
systemic blood pressure

16. •Combination of prasosin and beta
blocker results In refractory
hypotension during regional anesthesia
due to blunted response of beta1 and
alpha1 agonists

17. Alpha 2 Agonists
• Clonidine is centrally acting selective partial alpha2
agonist (alpha2: alpha1 activity 220:1) acts as
antihypertensive drugs due to decrease in
sympathetic output from CNS
• Clonidine is particularly effective in treatment of
severe hypertension or renin dependent disease
• Daily adult dose.-0.2- 0.3mg orally
• Dexmeditomedine,a much more alpha2 selective
drug is approved for sedation rather than
hypertension

18. Mehanism of action
• Alpha 2 agonists bind to alpha 2 receptors which are of
three subtypes alpha2A,alpha2B and alpha2c
• alpha2A receptors mediate sedation , analgesia and
sympatholysis while alpha2B receptors mediate
vasoconstriction and antishivering effects
• Clonidine stimulates alpha2 inhibitory neurons in
medullary vasomotor center thus decreasing sympathetic
outflow from CNS to periphery resulting in vasodilation
and decrease in systemic blood pressure, heart rate and
cardiac output
• The ability of clonidine to modify the function of K
channels in CNS(ie hyperpolarize cell membrane)causes
profound decrease in anesthetic requirement by clonidine
• The homeostatic cardiovascular reflexes are maintained
thus avoiding orthostatic hypotension or hypotension
during exercise

19. PHARMACOKINETICS
• Clonidine is rapidly absorbed after oral
administration and reaches peak plasma
concentrations.within 60-90minutes
• Elimination half time of 9-12 hours
• 50%metabolized in liver ,rest excreted unchanged
in urine
• Transdermal route requires about 48 hours to
produce steady state plasma concentrations

20. SIDE EFFECTS
• M/c SIDE effects of clonidine is sedation and
xerostomia
• Retention of sodium and water occur so
combination of clonidine and diuretic is
necessary.Diuretic effect of clonidine occur at 2.5to
5microgm /kg as preanesthetic medication

21. • REBOUND HYPERTENSION
• Result from abrupt discontinuation of clonidine as soon as
8hours and as late as 36 hours after last dose
• Occur mostly in those receiving >1.2mg of clonidine daily
• Increase in systemic blood pressure is a/w >100%increase in
circulating catecholamines and intense peripheral
vasoconstriction.
• Symptoms of nervousness, diaphoresis, headache,abdominal
pain and tachycardia preced the actual increase in systemic
blood pressure
• Usually controlled by reinstituting clonidine therapy or by
vasodilating drug like hydralazine or nitroprusside
• For planned withdrawal clonidine should be
gradually decreased over 7days or longer

22. ANGIOTENSIN CONVERTING ENZYME
INHIBITORS( ACE INHIBITORS)
• These are most effective in treating systemic
hypertension secondary to increase in renin
production
• These drugs have been established as first line
therapy in systemic hypertension , congestive
heart failure and mitral regurgitation
• More effective and safer in treatment of
hypertension in diabetes

23. MECHANISM OF ACTION
• Angiotensin ll binds to cell membrane receptorAT1
that leads to increase release of calcium from
sarcoplasmic reticulum causing vasoconstriction
• ACE inhibitors causes decrease generation of
angiotensin ll thereby reducing vasoconstrictive
effect
• In addition decrease aldosterone results in less
sodium and water retention
• These also inhibit the breakdown of bradykinin
which is endogenous vasodilator thereby
contributing antihypertensive effect
•

24. Side effects
• M/c side effects are..
• Cough
• Upper respiratory congestion
• Rhinorrhea
• Allergic like symptoms
• Angioedema is life threatening complication
• Airway response is due to potentiation of
kinins due to drug induced inhibition of peptidyl
dipeptidase activity.Injection of epinephrine in dose 0.3to
0.5ml of1:1000dilution subcutaneously is advisable
• ACE inhibitors decreases GFR,so used cautiously in
preexisting renal dysfunction and not recommended in
renal artery stenosis
• Hyperkalemia results due to decrease production of
aldosterone

25. • ACE inhibitors are free of many CNS side effects as
with other antihypertensive drugs
• Effects like congestive heart failure, bronchospasm,
bradycardia, exacerbation of PVD not seen
• Metabolic changes induced by diuretic therapy like
hypokalemia ,hyponatremia and hyperglycaemia not
observed
• Rebound hypertension as with clonidine are not
observed with ACE inhibitors

26. Angiotensin ll Receptor Blockers
• ARB's block the vasoconstrictive action of angiotensin
ll without affecting ACE activity
• Most commonly used agents are losatan candesartan
and valdesartan,and these have longer duration of
action
• No IV agent available
• These have similar antihypertensive effect and
benefits in heart failure as ACE inhibitors
• Similar side effect profile as ACE inhibitors but donot
inhibit breakdown of bradykinin...reason that ACE
inhibitors are preferred as first line therapy
• Major difference b/w ARB's and ACE inhibitors is that
ARB donot cause cough

27. Calcium channel blockers
• Inhibit calcium influx through Voltage sensitive L type
Calcium channel in vascular smooth muscle
• These are arterial specific with little effect on venous
circulation
• Broadly categorized into Dihydropyridines
(nifedipine,amlodipine, nicardipine,clevidipine)and
Non Dihydropyridines (virapamil and diltiazem)
• Virapamil and diltiazem are less potent vasodilator
and both have negative inotropic and chronotropic
activity,thus limiting their use in cardiac
disease.These are more used for their antiarrhythmic
action than antihypertensive action

28. • The dihydropyridines are potent vasodilators and are
relatively safe to use in patients with heart failure and
cardiac conduction defects, with the exception of large
doses of short-acting nifedipine which may acutely
lower the blood pressure and cause myocardial
ischemia
• successful in treating hypertension in the elderly,
African Americans, and salt-sensitive patients. The use
of calcium channel blockers does not require
concurrent sodium restriction.
• IV nicardipine is used in treatment of Hypertensive
Emergency, Dose -100microgm or 5to15mg/h,onset
2to 10 minute, Half life of 2to4min

29. Nitric oxide
• It is recognized as a chemical messenger in modulation of
cardiovascular tone, platelet aggregation and
neurotransmitter role in CNS
• Also cause gastrointestinal smooth muscle relaxation and
immune regulation
• Therapeutically inhaled NO produce relaxation of
pulmonary arterial vasculature

30. • NO is synthesized in endothelial cells from the amino
acid L Arginine by Nitric Oxide Synthetase,which then
diffuses into arterioles where it induces guanylate
cyclase to increase cGMP which causes vasodilation
• N[tric oxide bind avidly to iron of heme based proteins
and inactivated by hemoglobin leading to half life of less
than 5seconds
• Inhaled NO affects pulmonary circulation but not
systemic circulation due to extremely rapid uptake by
haemoglobin
• Inhaled NO in 10to 20ppm has been used for therapy of
persistent pulmonary hypertension of newborn
• In premature infants with respiratory distress syndrome
it decreases the incidence of chronic lung disease and
death

31. Toxicity
• Inhaled NO increase methaemoglobin level as NO
combines with hemoglobin
• Life threatening rebound arterial hypoxemia and
pulmonary hypertension may occur on discontinuation of
inhaled NO therapy,so important to wean inhaled NO
slowly
• NO is oxidized to nitrogen dioxide in p/o high
concentration of O2
• Nitrogen dioxide is a known pulmonary toxin and it is
important to know early warning of possible pulmonary
toxicity

32. Nitrodilators... Sodium nitroprusside
and Nitroglycerin
Sodium Nitroprusside
• Direct acting non-selective peripheral vasodilator
cause relaxation of both arterial and venous vascular
smooth muscle
• Composed of ferrous ion center with five cyanide
moieties and nitrosyl group
• The molecule is 44%cyanide by weight and is soluble
in water
• SNP lacks significant effect on nonvascular smooth
muscle and on cardiac muscle

33. Mehanism of action
• SNP interacts with oxyhemoglobin, dissociate immediately
forming methemoglobin while releasing cyanide and NO
• NO activates guanylate cyclase in vascular smooth muscle
increasing intracellular cGMP which inhibit calcium entry
into vascular smooth muscle cells and increase calcium
updake by endoplasmic reticulum to produce vasodilation
• As such NO is active mediator causing direct vasodilating
effect in SNP than nitroglycerin which requires thio
compounds to generate NO

34. Merabolism
• .Metabolism of SNP begins with transfer of electron from
iron of oxyhemoglobin to SNP yielding methemoglobin
and unstable SNP radical
• The unstable SNP radical breaks down releasing all five
cyanide ions ,one of which reacts with methemoglobin to
form cyanomethemoglobin
• The remaining free cyanide ions are available to
rhodanese enzyme in liver and kidney for conversion to
thiocyanate
• Rhodanese uses thiosulfate ions as sulfur donor and
most adults can detoxify about 50mg of SNP using
existing sulfur stores

35. Dose and Administration
• The recommended initial dose is 0.3micro/kg/minute
IV tritrated to the max rate of 10m,icrogm/kg/minute
IV with max.rate not to be infused longer than
10minutes
• SNP infusion rate of more than 2microgm/kg/minute
IV results in dose dependent accumulation of cyanide
and risk of cyanide toxicity
• Onset of action 1to 2 min with half life of less than
10minutes
• With immediate onset of action, equipotent on
arteries and veins and transient duration, it requires
continuous IV administration with frequent
intraarterial blood pressure monitoring.

36. Toxicity
• Clinically cyanide toxicity may occur when rate of IV SNP
infusion is more than 2microgn/kg /min or when sulfur donor
and methemoglobin are exhausted allowing cyanide radical to
accumulate
• Cyanide radical bind to inactive tissue cytochrome oxidase and
prevent oxidative phosphorylation resulting in tissue anoxia,
anaerobic metabolism and lactic acidosis
• Cyanide toxicity should be suspected in any patient requiring
increasing doses of more than 2 microgm/kg/minute or in
previously responsive patient who become less or unresponsive
to drug
• Mixed venous Po2 is increased indicating paralysis of
cytochrome oxidase and inability of tissues to use oxygen
• In awake patient CNS dysfunction such as mental status changes
,seizures may occur

37. Treatment of Cyanide Toxicity
• Immediate discontinuation of SNP and administrative of
100%oxygen despite normal oxygen saturation
• Sodium bicarbonate is administered to correct metabolic
acidosis
• Sodium thiosulfate of 150mg/kg IV administered over
15minutes is the recommended treatment for cyanide
toxicity
• If cyanide toxicity is severe with deteriorating
hemodynamics and metabolic acidosis,the recommended
treatment is slow IV administration of sodium nitrate of
5mg/kg. Sodium nitrate converts hemoglobin to
methemoglobin which act as antidot by converting cyanide
to cyanmethemoglobin
• Alternatively hydroxocobalamin which binds cyanide to
form cyanocobalamin (vitamin b12) can be
administered@25 mg per hour IV to max of 100mg .

38. • Another treatment is methylene blue of 1to 2 mg
/kg IV over 5minutes which facilitate conversion of
methemoglobin to hemoglobin

39. Coronary steal phenomenon
• SNP dilates the resistance vessels in non ischemic
myocardium resulting in diversion of blood flow
away from ischemic areas where collateral blood
vessels are already maximally dilated, thereby
increasing the area of damage a/w myocardial
infarction

40. Thiocyanate toxicity
• Thiocyanate toxicity is rare as thiocyanate is 100fold less
toxic than cyanide
• In patients with normal renal function,SNP infusion of
2to5microgm/kg/minute for 7to 14 days produces potential
toxic thiocyanate blood concentration
• Nonspecific symptoms include fatigue,
tinnitus,nausea,vomiting
• Clinical evidence of neurotoxicity includes hyperreflexia,
confusion,psychosis,and miosis, progress to seizure and
coma
• Thiocyanate competitively inhibit uptake and binding of
iodine in thyroid gland producing clinical hypothyroidism
• Thiocyanate clearance can be facilitated by dialysis

41. Nitates(Nitroglycerin)
• NTG is an organic nitrate that acts principally on
venous capacitance vessels and large coronary
arteries producing peripheral pooling of blood and
decrease cardiac ventricular wall tension
• Increased doses can also cause relaxation of arterial
vascular smooth muscle
• NTG also produce pulmonary vasodilation equivalent
to degree of systemic arterial vasodilation

42. • M/c clinical use of NTG is sublingual or IV
administration for angina pectoris as a result of
either atherosclerosis of coronary arteries or
intermittent vasospasm of these vessels
• Controlled hypotension can also be achieved with
continuous infusion of NTG

43. Mehanism of action
• Like SNP it also generates NO which stimulates
production of cGMP to cause peripheral vasodilation
• NTG requires p/o thio containing compounds to
generate NO
• The nitrate group of nitroglycerin is biotransformed to
NO through glutathione S transferase

44. Dose and Administration
• SNP is usually diluted to conc. Of 100 mcg/ml and administered as
continuous iv infusion ,dose of 0.25 to 5 mcg/kg/min
• Onset of action 1to 2 minute
• Half life of 1to 3 minute
• Frequently administered by sublingual route but also available as
oraltablet ,buccal or transmucosal tablet, sublingual spray and
transdermal ointment or patch
• Sublingually it reaches peak plasma concentrations within
4minutes
• Only 15%of blood flow from sublingual route passes through liver
limiting the first pass metabolism of Nitroglycerin
• Orally it is largely inactive b/c of first pass metabolism

45. • Transdermal absorption of NTG of 5 to 10g over
24 hours provide sustained protection against MI
• Tolerance to the drug occur when patches are left
in place for more than 24 hours making necessary
to remove the patch after 14 to 16 hours to
prevent tolerance

46. • METHEMOGLOBINEMIA ---The nitrate metabolite of
NTG is capable of oxidizing the ferrous ion in hb to
ferric ion with production of methemoglobin
• TOLERANCE-----is dose dependent and duration
dependent manifesting within 24 hours of sustained
treatment.if ischemia occur during administered of
NTG , responsiveness to antiischemic effects of nitrate
can usually be restored by increasing the dose
• CLINICAL USE--NTG in all forms is used to treat
suspected MI as well as volume overloading heart
failure as preload reduction.Also used as systemic
antihypertensive

47. Isosorbide Dinitrate
• It is commonly administered oral nitrate for prophylaxis of
angina pectoris and for preload reduction in heart failure.
• It is well absorbed from GIT,and not subjected to
extensive first pass metabolism
• Doses of 60to 120 mg last upto 6 hours
• It improves exercise tolerance for upto 6hours
• It's metabolite isosorbide 5 mononitrate is more active
than parent compound
• Orthostatic hypotension accompanies with acute
administration while Tolerance develops with chronic
therapy

48. Hydralazine
• It is direct systemic arterial vasodilator,causes both
hyperpolarization of smooth muscle and activates
guanylate cyclase to produce vasodilation
• It produces reflex sympathetic nervous system
stimulation and myocardial contractility so not
recommended in myocardial ischemia or coronary
disease
• Although it has been widely used in hypertension
disorders in pregnancy
• Long term hydralazine is a/w systemic lupus
syndrome limiting it's widespread use

49. Fenoldopam
• Its a dopamine type 1 receptor agonist causing
systemic arterial dilation through cyclic c AMP
• It has a particular action of increasing renal blood
flow and increasing urine output.
• Also increases splanchnic blood flow due to density
of dopamine type 1receptors
• Only available in IV preparation ,has rapid onset of
action and half life of 10 min.
• Adverse effects are limited to increase in intraocular
pressure making the drug unsuitable in patients with
glaucoma

50. Thank you!!!