Pharmacotherapy

of Hypertension
(HTN)

1
 Definition
A sustained increase in blood pressure (140/90 mm Hg)
[on repeated BP measurement]

Criteria for HTN in Adults

Classification Blood Pressure (mm Hg)

Systolic Diastolic
Normal < 120 < 80
Pre-hypertension 120 139 80 89
Hypertension, Stage 1 140 159 90 99
Hypertension, Stage 2 160 100
2
 Contd
Is the most common cardiovascular disease in the west (up
to affecting approximately 60 million people of US)

Varies with age, race, education, income, environment

etc

Is one of the most important risk factors for both coronary

artery disease and cerebrovascular accidents

Effective treatment of HTN reduces morbidity and

mortality

3
 Regulation of normal BP
Arterial BP = CO x TPR
Physiologically CO and PVR is maintained minute to
minute by four anatomical regulating sites

1. Arterioles

2. Post-capillary Venules

3. The heart

4. The kidneys
4
 Mechanisms of BP control

1. Baroreceptor reflex:

Mediated by autonomic nerves

2. Humoral mechanism:

The Renin-Angiotensin-Aldosterone system (RAAS)

All antihypertensives act via interfering with normal

mechanisms

5
 Baroreceptor reflex
For rapid adjustment of BP
Sensory input: receptors on carotid sinus and aortic arc
Stimulus: stretch

If BP is increased
Carotid receptors are stimulated by stretch of blood
vessels
Results in the inhibition of sympathetic discharge

If BP is decreased
Stretch of blood vessels is reduced ed baroreceptor
activity
disinhibition of sympathetic discharge
6
 Humoral control
For long term control of BP

If mean arterial BP is reduced ,

Renal perfusion pressure is reduced

Increased secretion of renin and the resulting increase

in Angiotensin II, which in turn causes
Direct arteriolar vasoconstriction

Increased secretion of aldosterone (Increased

reabsorption of salt & water)

7
 Classification of HTN
Based on etiology
Primary (essential) HTN
85-90% of all cases

No cause is identified

Secondary HTN
10-15% of cases

Identifiable cause present

8
 Non-pharmacological therapy of
hypertension

1. Reduction of weight

2. Salt restriction - 5mg/d of salt

3. Alcohol restriction

4. Physical exercise

5. Relaxation

6. Stop smoking

9
 Classification of
Antihypertensive agents
1.Diuretics
Thiazide diuretics eg. Chlorthiazide

Loop diuretics eg. Furosemide

K+ sparing diuretics eg. Triamterene

Mechanism: reducing blood volume

10
 Classification (contd)
2. Antiadrenergic agents
I. Centrally acting 2 agonists

II. Ganglionic Nicotinic receptor blocking

agents

III. Adrenergic neuron blocking agents

IV. Adrenergic receptor blocking agents

-AR blockers

-AR blockers

mixed -, -AR blockers

11
 Classification (contd)
3. Vasodilators
Arteriolar dilators

Mixed artery & venous dilators

4. Blockers of production or action of

Angiotensin II
Angiotensin converting enzyme inhibitors

Angiotensin II receptor blockers

12
 DIURETICS
Antihypertensives alone, and enhance the efficacy of
other antihypertensive drugs

Exact mechanism for reduction of arterial BP is not certain

Initial in extracellular volume fall in CO

Maintained hypotensive effect during long-term therapy

is due to in vascular resistance; CO returns to
pretreatment values and extracellular volume
returns almost to normal

Diuretics are effective in lowering blood pressure by 1015

mm Hg in most patients 13
Thiazide diuretics
Less potent diureticsmost frequently used
class of antihypertensive agent

Include : chlorothiazide, hydrochlorothiazide.

Used in mild to moderate HTN

Along with other antihypertensive agents

In patients with normal renal & cardiac function

14
 Loop diuretics
Are most potent diuretic and a weaker antihypertensive
than thiazides.

Include such drugs as furosemide, bumetanide.

They are indicated in hypertension only when it is

complicated by:

(a) Chronic renal failure: thiazides are ineffective,

(b) Coexisting refractory CHF.

(c) Resistance to combination regimens containing a

thiazide, or marked fluid retention due to use of
15
potent vasodilators.
K+ sparing diuretics
Drugs include spironolactone, triamterene and
amiloride

Weakest in diuretic potency

Act distally in the collecting duct to either inhibit

binding of aldosterone to mineralocorticoid
receptors or inhibit epithelial Na+ channel
(ENaC)

Avoid excessive K+ depletion

16
Vasodilators
1. Oral vasodilators
Hydralazine, Minoxidil
Used for long term treatment of HTN
2. Only Parenteral vasodilators
Nitroprusside, Diazoxide
For treatment of hypertensive emergencies
3. Ca++ channel blockers
Verapamil, Diltiazem
For long term treatment of HTN & treatment of
hypertensive emergencies
17
Mechanism (vasodilators)
All reduce TPR by relaxing arteriolar smooth
muscle
Elicit baroreceptor & renal reflexes

Cause tachycardia ,salt & water retention

Vasodilators should be combined with other

antihypertensive agents
To counteract the reflex adverse effects

18
 Hydralazine
Causes direct relaxation of arteriolar smooth muscle, but
does not relax venous smooth muscle

The vasodilation induces powerful stimulation of

sympathetic system (ed HR and contractility, ed plasma
renin activity & fluid retention)

Well absorbed after oral administration and rapidly

metabolized by acetylation in the liver during the first pass
and variable among individuals

Postural hypotension is not a common problem

19
Adverse effects
Tachycardia, aggravation of angina, fluid retention,
headache, sweating, flushing nausea, anorexia

Uses: Hydralazine is used in moderate-to-severe

hypertension not controlled by the first line drugs.

Usually, low doses are added to the diuretic and

blocker already being administered

Hypertensive emergencies in pregnant women

20
 Minoxidil
.It is more potent and longer acting than hydralazine
Metabolized by hepatic sulfotransferase to the active
molecule, minoxidil N-O sulfate

Activates ATP-modulated K+ channel and results in

hyperpolarization & relaxation of smooth muscle (ed TPR)

ed CO (activation of sympathetic system)

Potent stimulator of renin release

Well absorbed orally

21
Adverse effects
Retention of salt and water

CVS effects: in HR, myocardial contractility, and

myocardial O2 consumption

Hypertrichosis due to K+ channel activation.

Topical minoxidil is marketed for the treatment of

baldness.

Therapeutic use

Severe HTN that does not respond to other agents

22
 Sodium Nitroprusside
Potent parentally administered vasodilator

Activates guanylyl cyclase via release of NO

Dilates both arteriolar & venial vessels

Causes only a modest in HR and an overall

reduction in myocardial demand for oxygen

plasma renin activity

Has rapid onset (30 s) & brief duration of effect (3

min)
23
Adverse effects are secondary to
Excessive lowering of BP; and
Accumulation of CN-
Metabolic acidosis, arrhythmias etc

Hypothyroidism (thiocyanate inhibits uptake of iodine)

Although cyanide toxicity is rare, it can be effectively treated
with an infusion of sodium thiosulfate to produce
thiocyanate and Hydroxocobalamin to produce
cyanocobalamin which are less toxic and eliminated by the
kidneys
Therapeutic use
Treatment of hypertensive emergencies
(continuous IV infusion) 24
 Ca2+ channel blockers (CCB)
Inhibit Ca++ influx in to arteriolar smooth muscle
Cause arteriolar dilatation; hence reduce TPR
Specific drug classes
Dihydropyridines: Nifedipine, Nicardipine
Potent arteriolar vasodilators
Less effect on heart rate & contractility
Adverse effects Tachycardia, headache, flushing,
peripheral edema
Phenylalkylamine: Verapamil
Decrease heart rate & contractility
Adverse effects: headache, dizziness, edema, bradycardia
Benzothiazepines: Diltiazem
Intermediate effect on heart rate and blood vessels

25
Therapeutic uses
Maintenance (long term) treatment of HTN

hypertensive emergencies

HTN coexisting with

Ischemic heart disease, Chronic pulmonary disease,
DM, and Variant angina

26
 Drugs that alter sympathetic
nervous system function

Primary mechanism of action

sympathetic activity to heart &/or blood vessels

decease CO and/or TPR

All the drugs elicit compensatory renal effects

Sodium & water retention expand blood volume

Effective if used concomitantly with diuretics

27
SNS BP REGULATION & SITES OF DRUG ACTION
 Centrally acting 2 agonists
Include such drugs as -methyldopa ,clonidine.

Alpha-Methyldopa: a prodrug

MOA: Converted to alpha methyl noradrenaline which acts

on alpha-2 receptors in brain and causes inhibition of
adrenergic discharge in medulla fall in PVR & in BP

It cause plasma volume increases and should be used in

conjunction with a diuretic;

Methyldopa is preferred drug for treatment of

hypertension during pregnancy
Clonidine: Imidazoline derivative, partial agonist of central
alpha-2 receptor

It acts in the same general area in the brain as does

methyldopa, With exception is that clonidine acts
directly 2 receptors.

Clonidine can be use is in mild and moderate

hypertension that has not responded adequately to
treatment with a diuretic or beta blocker

Because of tolerance and withdrawal hypertension now

a day not frequently used.
 Ganglionic nicotinic receptor blockers
Eg. Trimethaphan
Historically, drugs that block activation of postganglionic
autonomic neurons by acetylcholine were among the first agents
used in the treatment of hypertension.

Currently no longer in use due to intolerable adverse effects

Adverse effects

Sympathetic: orthostatic hypotension, sexual dysfunction

Parasympathetic: constipation, urinary retention, dry

mouth, blurring of vision..

31
 Adrenergic neuron blocking agents
These drugs lower blood pressure by preventing normal
physiologic storage or release of norepinephrine from
postganglionic sympathetic neurons

Reserpine
MOA

Inhibits the catecholamine transporter from cytoplasm into

storage vesicles in the adrenergic nerves of all body
tissues

Depletes amines in CNS and peripheral adrenergic neuron

Results in pharmacological sympathectomy 32

 Pharmacological Effects
in CO and TPR, in HR and renin secretion

Salt and water are retained,

Adverse effects
Sedation, impaired concentration, depression that
can lead to suicidal attempt

Nasal stuffiness, exacerbation of peptic ulcer disease

Therapeutic use: mild to moderate hypertension

33
Guanethidine
MOA
Transported into neuronal terminals by uptake1
Concentrated in vesicles and deplete NE from these stores

Inhibits nerve impulse coupled release of NA.

blocks NA uptake mechanism at the axonal membrane
Adverse effects
Marked orthostatic hypotension, bradycardia, impotence
Doesnt cross the BBB; hence no central adverse effects

Therapeutic use:
Reserved for the treatment of severe HTN
Due to severe adverse effects & its high efficacy.
34
 -adrenoceptor blockers
-adrenoceptor blockers
MOA
- adrenoceptor blockade
myocardial contractility, HR & CO
renin secretion (reduced levels of angiotensin II)

Drugs differ in
Lipid solubility
Selectivity for the 1-AR subtype
Presence/absence of intrinsic sympathomimetic activity
Membrane-stabilizing properties
All have similar antihypertensive efficacy
35
 Drugs with out ISA : Propranolol & Metoprolol
Initially reduce CO, TPR; no change in BP.
Latter TPR returns to pretreatment values while CO remains
reduced, hence BP is reduced
Drugs with ISA: Pindolol, Acebutolol, & Penbutolol
less effect on HR & CO (at rest)
Reduce TPR reduced BP (2- stimulation)
Precautions
Asthma , SA or AV nodal dysfunction
Acute CHF, DM

THERAPEUTIC USES - receptor antagonists provide effective

therapy for all grades of hypertension.
 1-AR blockers
Prazocine, Doxazocine, Terazocine etc..

produce most of their antihypertensive effects by selectively

blocking 1-AR receptors in arterioles and venules

Initially reduce arteriolar resistance and increase venous

capacitance reduce BP

Then sympathetically mediated reflex increase in heart rate

and plasma renin activity

On long term use, vasodilatation persists; but the CO, HR,

and renin activity return to normal

in BP 37
 Adverse effects
Increased risk of CHF

Therapeutic use
Not useful for monotherapy (should be combined with
blockers, diuretics or other antihypertensive agents)

For hypertensive patients with benign prostatic

hyperplasia since they also improve urinary symptoms

38
 Drugs that alter the formation or action of
Angiotensin II
ACE inhibitors & ARB are first choice in the management of HTN
patients with
Asthmatics , diabetics, heart failure and myocardial infarction.
They have no hyperuricemia or deleterious effect on plasma lipid
profile
 Conditions warranting special emphasis
Hypertension and pregnancy:
No drug is safe in pregnancy
Avoid diuretics, propranolol, ACE inhibitors, Sodium
Nitroprusside etc
Safer drugs: Hydralazine, Methyldopa, cardioselective
beta blockers and prazosin
Elderly: use smaller doses; simpler regimens
Monitor for adverse drug effects
DM: use drugs with fewer adverse effect on carbohydrate
metabolism
ACEIs, AT1 receptor blockers, CCB, and 1-AR
blockers
Asthma: avoid - blockers
40
Lipid Lowering
agents
 Introduction
Lipid:
Free fatty acid (FFA) [4%]
Triglycerides (TG) [16%]
Phaspholipids [30%]
Cholesterol [14%] and cholesterylesters [36%]
Lipids are insoluble in water (hence in blood)
Transport:
FFA bound to albumin
TGs, cholesterol, phosphplipids Protein
complexes
LIPOPROTEINS
General structure of lipoproteins
 Lipoproteins: classification based on
density
Chylomicrons

Very low-density
lipoproteins(VLDL)

Intermediate-density
lipoproteins(IDL)

Low-density
lipoproteins(LDL)

High-density
lipoproteins(HDL)
Catabolism of Chylomicrons, VLDL and formation of LDL
 Why Should we lower Lipids?
To lower risk of
1. Coronary heart disease
ed LDL associated with atherogenesis
ed HDL associated with ed coronary vascular diseases

2. Pancreatitis
Associated with ed levels
47
Terms:
Hyperlipidemia; TG &/or cholesterol

Hypertriglyceridemia : Hyperglycemia

Hypercholesterolemia

Hyperlipoproteinemia; Chylomicrons, VLDL, LDL

Hyperlipidemias can be :-
Primary

Secondary
Classification of Total, LDL, and HDL
cholesterol and triglycerides
Total cholesterol
<200 mg/dl.. Desirable
200-239 mg/dl.. Border high
240 mg/dl.. High
LDL cholesterol
<100 mg/dl Optimal
100-129 mg/dl. Near or above optimal
130-159 mg/dl. Borderline high
160-189 mg/dl. High
190 mg/dl Very high
HDL cholesterol
< 40 mg/dl Low
60 mg/dl High
Triglycerides
< 150 mg/dl. Normal
150-199 mg/dl.. Borderline high
200-499 mg/dl.. High
500 mg/dl.. Very high
 Frederickson-Levy-Lees Classification of
Hyperlipoproteinemia

Type Lipoprotein elevation

I Chylomicrons
IIa LDL
IIb LDL + VLDL
III IDL
IV VLDL
V VLDL + Chylomicrons
 Classification of Lipid lowering Agents

HMG-CoA reductase inhibitors /statins/

Fibrates: fibric acid derivative.

Bile acid Binding Resins

Nicotinic acid /Niacine/

Miscellaneous: Ezetimibe

Dextrothyroxine

Neomycine etc.
 3-Hydroxy-3-methylglutaryl (HMG) coenzyme A
(COA) reductase inhibitors Statins

Are the most efficacious and best tolerated

hyperlipidemic drugs which include:-

Lovastatin, simvastatin, fluvastatin, pravastatin,

atorvastatin, and rosuvastatin

MOA : They competitively inhibit conversion of 3-Hydroxy-

3-methyl glutaryl coenzyme A (HMG-CoA) to mevalonate
(rate limiting step in CH synthesis) by the enzyme HMG-
CoA reductase
 Statins (contd)

They are most effective in reducing LDL by

Reduce free cholesterol content in hepatocytes.
ed expression of LDL receptors in hepatocytes
Reduced degradation of LDL receptors

ed removal of LDL ed LDL-C levels.

Modest decreases in plasma triglycerides and

Small increases in HDL also occur.
 Pharmacokinetics
All given orally

Prodrugs: Lovastatin, Simvastatin

Active drugs; others

All are extensively metabolized by the liver (first pass effect)

low systemic bioavailability.

Due to first-pass extraction, the primary action of these

drugs is on the liver.

Most are highly plasma protein bound; > 95%

Elimination: mainly liver : feces.

Adverse effects
Usually well tolerated
Mild GI complaints, muscle pain, rush, headache
Myopathy
Hepatotoxicity
C/I: pregnant & lactating women

Clinical use : the first-line for patients with elevated LDL

cholesterol (Mono therapy or together with bile binding
resins , niacin, or ezetimibe) as well as for secondary
(diabetes, nephrotic syndrome) hypercholesterolemia
 Fibric acid derivatives( PPAR Activators)
Drugs: colfibrate - proto type and the 1st
Gemfibrozil:- Non halogenated; commonly used
Fenofibrate, bezafibrate, ciprefibrate

MOA: Not clear, The brates activate nuclear receptor

peroxisomal proliferation activated receptor (PPAR) & ed
transcription of the LPL gene and ed transcription of the
apolipoprotein CIII gene (apo CIII).
Enhanced removal of triglyceride from the
circulation
LDL-C levels may or Not affected or ed
Pharmacokinetics
Absorption: rapid & almost complete - given with a meal
Elimination; mainly renal: unmodified
Contraindicated in Renal failure.
Adverse effects:
GI distress, Cholestatic, myopathy, hepatitis
Both agents potentiate the action of coumarins
anticoagulants
Clinical use:
Fibrates are first line in hypertriglyceridemias in which
VLDL predominate ( type IV and type V) alone and together
with statins in dysbetalipoproteinemia (type III ) and
Combined hypercholesterolemia( type lIb ) patients
Fibrates should not be used by children or pregnant women.
 Bile acid sequestrates (Bile -acid binding
resins)
Are polymeric cationic Resins: insoluble in
water
Drugs
Cholestyramine
Colestipol
Colesevelam
 MECHANISM OF ACTION
Normal: Cholesterol eliminated as it is (free cholesterol) or
converted to bile acids (-vely charged)
95% of bile-acid reabsorbed (small intestine).
BABR (BAR): bind to bile acid excreted in the feces.
Hepatocytes are depleted of cholesterol
Enhanced bile acid synthesis
Enhanced LDL-C clearance
Also: enhanced de novo cholesterol synthesis
Up regulation of HMG-CoA reductase..
Increase hepatic TG synthesis
Effect:
Reduce LDL-C
Increase VLDL levels
 Pharmacokinetics
Given as powder, tablets and capsules are also available
Not absorbed eliminated in feces.
Adverse effects
Constipation, abdominal pain & distention
N.V.D. heart burn etc.
Interferes with absorption of many drugs.
Interfere with absorption of fat- soluble Vitamins (ADEK)
Use:
Elevated LDL-c (usually together with statins) & combined
hyperlipidemia (niacin)
The Only currently recommended drugs in children
 Nicotinic acid ( Niacin - Vit B3)
Nicotinamide has no lipid lowering effect
MOA: has multiple effects
Adipose Tissue:
Inhibits lipolysis of TGs delivery of FFA to liver
Reduce hepatic TG synthesis
In the liver
Reduce TG synthesis by inhibiting synthesis &
esterification of FFA.
Reduce VLDL production: reduce LDL levels
Enhance LPL activity:
Promote clearance of VLDL & chylomicron TGs.
Raise HDL- C level (best agent in this regard)
By decreasing its clearance.
Pharmacokinetics:
Almost completely absorbed

Elimination: dose dependent

low dose: hepatic metabolite excreted in the
urine

Larger: eliminated unchanged in urine

Adverse effects:
Cutaneous flushing, pruritis (prostaglandin mediated
and alleviated by ASA)
Dyspepsia, heart burn, GI ulceration
Hepatotoxicity, hyperglycemia, hyperuricaemia etc.

Avoid use;-
PUD, Gout, Liver disease, DM
Use:
Hypercholesterolemia or Hypertriglyceridemia or both
Hyperlipoproteinemia etc
 Ezetimibe
Prodrug active metobolite glucuronide conjugate

Undergoes enterohepetic circulation

Blocks the intestinal absorption of cholesterol

Reduce total cholesterol, LDL- C & TGs

Adverse effects: rarely can cause allergic reactions

Use; Hypercholesterolemia, as an adjunct to dietary Rx &

statins

Available as combination products containing ezetimibe

and a statin
Neomycin:- inhibit absorption of bile acids

Dextrothyroxine: increase LPL activity

 Treatment of Hyperlipidemia
1. Treat underlying cause; Secondary
2. Dietary treatment:
Limit;- cholesterol intake
Saturated fat intake
Limit total fat intake (in hypertriglyceridemia)
Limit simple sugar intake
3. Pharmacological;
Dietary treatment should continue
Avoid drugs in women likely to be pregnant & lactating
Children : only acid binding Resins.
 Lipoprotein phenotype and recommended drug
treatment
Lipoprotein Drug of choice Combination therapy
Type
I Not indicated ---------
IIa Statins Niacin or BAR
Cholestyramine or colestipol Statins or Niacin
Niacin Statins or BAR
Ezetimibe
IIb Statins BAR or fibrates or Niacin
Fibrates Statins or Niacin or BAR
Niacin Statins or fibrates
Ezetimibe
III Fibrates Statins or Niacin
Niacin Statins or Fibrates
Ezetimibe
IV Fibrates Niacin
Niacin Fibrates
V Fibrates Niacin
Niacin Fish oils
Pharmacotherapy of
Shock

69
 Shock
Shock ;-is a life-threatening condition characterized by
inadequate perfusion of tissues, hypotension, and,
ultimately, failure of organ systems

Cause can be various, but classified as

Hypovolemic
Cardiogenic (intracardiac vs extracardiac)
Distributive
Sepsis
Neurogenic (spinal shock)
Anaphylaxis

70
 Hypovolemic Shock
Hypovolemic shock, also called hemorrhagic shock, is a
life-threatening condition that results when you lose
more than 20 percent (one-fifth) of your bodys blood

It is the most common type

Results in decreased CO

SVR is typically increased in an effort to compensate

Causes:

Hemorrhagic trauma, GI bleed, hemorrhagic

pancreatitis, fractures

Fluid loss induced Diarrhea, vomiting, burns

71
 Treatment of Hypovolemic Shock
Maximize oxygen delivery

Control further blood loss

Tourniquets

Surgical intervention

Fluid resuscitation (Restore circulating volume)

NS fluid boluses (3:1 rule- 3 ml of isotonic crystalloid for every 1 ml

of estimated blood loss)

Blood product administration

Medications that increase the hearts pumping abilities also may be

administered. These include dopamine, dobutamine, epinephrine,
and/or norepinephrine
72
 Cardiogenic Shock
Shock caused as a result of cardiac pump failure
Results in a decrease in CO
SVR is increased in an effort to compensate to
maintain organ perfusion
Causes:
Myocardial Infarction

Arrythmias (Atrial fibrillation, ventricular tachycardias,

bradycardias, etc)

Mechanical abnormalities (valvular defects)

Blunt cardiac injury (trauma)

Extracardiac abnormalities (pulm HTN, tension pnmothorax)

 Treatment of Cardiogenic Shock
Correct hypotension:

Fluid resuscitation to correct hypovolemia (Start an

IV infusion of D5W)

Optimizing myocardial contractility :

Dopamine, Dobutamine, Epinephrine, NE, Milrinone may be
required to increase blood pressure &heart functioning.

Oxygenation

If MI ASA, Heparin, and Revascularization

If arrthymia correct arrthymia

If extracardiac abnormality reverse or treat cause

 Distributive Shock
Shock as a result of severely diminished SVR
CO is typically increased in an effort to maintain
perfusion

Subtypes:

Septic secondary to an overwhelming infection

Anaphylactic secondary to a life-threatening

allergic reaction

Neurogenic secondary to a sudden loss of the

autonomic nervous system function
 Septic shock
Septic shock- Presence of sepsis with hypotension.
severe bacterial infections and toxins damage vessel
walls, Leads to dilation of vessels and loss of plasma
Primary therapy involves use of broad Spectrum
Antibiotics like cephalosporin, aminoglycosides, Metronidazole.
It also needs vigorous fluid therapy with close monitoring
and Bicarbonate if pH < 7.1.
Treat the cause:- drainage of abscess, laparotomy for
peritonitis.

Ventilator support, dobutamine /dopamine /NA to maintain

BP and urine output.
76
 Anaphylactic Shock
Acute and life-threatening allergic (hypersensitivity) reaction

Can be caused by drugs, chemicals, vaccines, food and

insect venom

Causes massive vasodilation, release of vasoactive

mediators, and an increase in capillary permeability

Fluid shift from the vascular space to the interstitial

space

Respiratory distress secondary to laryngeal edema, severe

bronchospasm, or circulatory failure from vasodilation
 Treatment of Anaphylactic Shock
Remove offending agent and Establish an airway and
return circulation
Pharmacologic support:
Epinephrine reverses peripheral vasodilation, dilates
bronchial airways, increases myocardial contractility, and
suppresses histamine/ leukotriene release
Antihistamine (Diphenhydramine) may help
counter histamine-mediated vasodilation and
bronchoconstriction
Corticosteroids (hydrocortisone) may help shorten
reaction
Bronchodilators :salbutamol (inhaled or IV)
Fluid replacement - primarily with colloids
Consider IV atropine for severe bradycardia
 Neurogenic Shock (spinal shock)
Neurogenic shock is a result of severe nerve damage
(spinal injury at T5 or above) that affects the heart and
blood vessels.

Nerve impulse to blood vessels impaired, blood vessels

remain dilated and blood pressure decreases

Usually within 30 minutes of injury, can last up to 6 weeks

Can also be caused by spinal anesthesia

 Treatment of Neurogenic Shock
Establish an airway to maintain adequate oxygenation
and ventilation

Fluid resuscitation

Inotropic support

Dobutamine

Dopamine

Atropine for severe bradycardia

High dose methylprednisolone therapy

 Intravenous fluids
There are more than 200 types of IV-fluids

Can be classified as

Colloids

Crystalloids
Isotonic

Hypotonic

Hypertonic
Colloids :- are a group of fluids containing large molecules
designed to remain in the intravenous space longer than
crystalloid fluids. Large molecules include:-

e.g. Albumin, Dextrans, Hydroxyethyl starch

They draw fluid out of the interstitial and intracellular spaces

into the plasma, hence colloids are commonly termed
Plasma expanders.

Colloids are used in cases of shock where cardiovascular

function needs to be improved rapidly:

Haemorrhage

Severe dehydration. 82
Crystalloids :- Clear fluids that consist of water and
dissolved crystals, such as salts and sugar; can be
Hypotonic: 5% DW which contain Glucose
exclusively is Isotonic until the glucose is metabolized,
but after changes to be Hypotonic.
Primarily used to maintain water balance in patients
who are not able to take anything by mouth.
Isotonic: 0.9% NS widely used preparations which
contain electrolytes as Na+, Cl-
Ringer lactate also widely used containing Na+, Cl-,
Ca++ and Lactate.
Hypertonic: Hypertonic saline [7.5% Nacl], used in
emergency to replenish intravascular volume from
Intracellular and interstitial fluids.
DO NOT use in patients with Cardiac failure &Liver disease
 Treatment of shock; principles
1. Correct the underlying cause
Antibiotics, Anti-arrhythmic drugs, Blood transfusion
3. Correct secondary causes /consequences/ of
shock.
Acidosis NaHCO3
Hypoxemia oxygen, etc.
4. Maintain function of vital organs.
CO, SBP, RBF: Sympathomimetic agents.
5. Identify & correct aggravating factors;
Hypoglycemia - glucose
Pain morphine, etc.
84