EPINEPHRINE

NOREPINEPHR
INE

ACTIVITY: Interacts with both alpha and beta receptors, at low

concentrations beta effects on the vascular system
predominate but at higher concentrations, alpha effects on the
vascular system predominate.
ACTIONS: CVS: Positive ionotropic contractility (beta 1),
Positive chronotropic Rate of contraction (beta 1), Increases
the release of renin (beta 1), constricts arterioles in the skin,
mucous membrane and viscera (beta 1), Dilation of vessels on
the liver and skeletal muscles (beta 2), renal blood flow is
decreased. Respiratory system: Bronchodilation (beta 2),
inhibit histamine release. Hyperglycemic: Glycogenolysis
(beta 2 directly on the liver), Inhibit release of glucagon (beta
2), decrease release of insulin (alpha 2). Lipolysis: Increase
lipolysis through agonist activity of lipocytes Increase cAMP
Increase hormone sensitive lipase.
USES: 1) Bronchospasm (Acute asthma) BUT drug of choice is
ALBUTAROL for chronic asthma. 2) Anaphylactic shock: Drug of
choice in type 1 hypersensitivity reactions. 3) Cardiac arrest. 4)
Anesthesia: Greatly increase the duration of anesthesia by
vasoconstriction. Can also be applied topically in low
concentrations to produce constriction of mucosa.
DURATION OF ACTION: Rapid in onset, brief in action. Usually
given IM but is given IV in emergency. Can also be inhaled and
subcutaneously given. It is metabolized by COMT and MAO
Venylyl mendelic acid and metanephrine and is excreted in the
urine.
ADVERSE EFFECTS: 1) Anxiety, fear, tremors, headache, tension
and pulmonary edema.
CONTRAINDICATIONS: 1) People who are taking digoxin
arrhythmias. 2) People who are on non-selective beta blockers:
beta 2 receptors blocked, alpha receptor activity increases and
this results in increase TPR and BP.
ACTIVITY: Alpha adrenergic activity
ACTIONS: 1) Vasoconstriction: Increase in TPR including
kidneys (Alpha 1) and doesnt cause beta 2 vasodilation so it is
not used in treating asthma and anaphylaxis. 2) Baroreceptor
Reflex: Norepinephrine increases BP, stimulates baroreceptor
inducing a rise in vagal activity Reflex bradycardia (but it
doesnt affect ionotropic activity). If Atropine is given before
norepinephrine, it produces tachycardia.
USES: Treatment of shock.
DURATION/ONSET: It is given IV for rapid onset (Onset is 1 2
minutes following the end of infusion). It is metabolized by MAO
and COMT Inactive metabolites are excreted in the urine.
ADVERSE EFFECTS: Potent vasoconstriction Cause blanching
and sloughing of skin. Leakage in peripheral tissues causes
necrosis. PHENTOLAMINE is used to treat impaired circulation
from norepinephrine.

DOPAMINE

It is a metabolic precursor of norepinephrine. It occurs naturally

in the basal ganglia as well as in the adrenal medulla.
ACTIVITY: Alpha, beta and dopaminergic receptors.
ACTIONS: 1) High doses Vasoconstriction by activating alpha
1 receptors. Low doses Beta 1 cardiac effects. 2) D1 and D2
receptors Present in peripheral renal and mesenteric
vasculature. Binding produces vasoconstriction. D2 receptors
are also present on adrenergic neurons; activation interferes
with norepinephrine release (These receptors are not affected
by alpha and beta blocking drugs).
USES: 1) Cardiogenic and septic shock through continuous
infusion. 2) Hypotension and severe heart failure. 3) Low
peripheral vascular resistance. 4) Oliguria.
DURATION/ONSET: It is rapidly metabolized by MAO and COMT
so it is short lived
ADVERSE EFFECTS: 1) During overdose it produces the same
effects as sympathetic stimulation. 2) Nausea. 3) Hypertension.
4) Arrhythmias.

PHENYLEPHRI
NE

STRUCTURE: Directly acting synthetic adrenergic drug.

ACTIVITY: Binds to alpha 1 receptors primarily.
ACTIONS: 1) Vasoconstriction that raises both systolic and
diastolic blood pressure. 2) No effect on heart itself but causes
reflex bradycardia when given parenterally.
USES: 1) Treat hypotension in hospitalized or surgical patients
(those that have a rapid heart rate). 2) Acts as a nasal
decongestant when applied topically or orally. 3) Opthalmic
solutions for mydriasis.
ADVERSE EFFECTS: Hypertensive headaches and cardiac
abnormalities.

DOBUTAMINE

STRUCTURE: Sythetic direct acting catecholamine.

ACTIVITY: Beta 1 receptor agonist.
ACTION: 1) Increase cardiac rate and output with few vascular
effects. 2) Increase cardiac output without elevating oxygen
demand of the myocardium.
USES: 1) Increase cardiac output in acute heart failure. 2)
Ionotropic support after cardiac surgery.
CAUTION: In atrial fibrillation, as it increases AV conduction.
TOLERANCE CAN DEVELOP.

OXYMETAZOLI
NE

STRUCTURE: Direct acting synthetic adrenergic agonist.

ACTIVITY: Alpha 1 and Alpha 2 receptors.
ACTION: Directly stimulates Alpha receptors on blood vessels
supplying the nasal mucosa and conjunctiva Produces
vasoconstriction.
USES: 1) Many over the counter drugs and short term nasal
decongestant sprays. 2) Opthalmic drugs for relief of redness of
the eyes associated with swimming, cold and contact lenses.
DURATION OF ACTION/ONSET: Absorbed in the systemic
circulation regardless of the route of administration.
ADVERSE EFFECTS: 1) Nervousness. 2) Headache. 3) Trouble
sleeping. 4) Local irritation and sneezing may occur with
intranasal administration. 5) Rebound congestion and
dependence is observed with long term use.

FENOLDOPAM

STRUCTURE: It is a racemic mixture and the R isomer is the

active component.
ACTIVITY: Peripheral D1 receptors.
ACTIONS: Rapidly acting vasodilator.
USES: Treat severe hypertension in hospitalized patients acting
on coronary arteries, kidney arterioles and mesenteric arteries.
DURATION OF ACTION: It undergoes extensive first pass
metabolism Duration of action is 10 minutes after IV infusion.
ADVERSE EFFECTS: 1) Headache. 2) Dizziness. 3) Nausea. 4)
Vomiting. 5) Tachycardia (due to vasoconstriction).

MIRABEGRON

ACTIVITY: Beta 3 agonist.

ACTIVITY: Relaxes detrusor smooth muscle and increases
bladder capacity.
USES: 1) Patients with overactive bladder.
ADVERSE EFFECTS: 1) It may increase blood pressure should
not be used with people with uncontrolled hypertension. 2) It
increases the levels of digoxin in the blood. 3) It inhibits CYP2D6
isoenzyme enhance the effects of medications metabolized
by this pathway.

SALMETEROL
&
FORMOTEROL

STUDY: Shown to increase asthma related deaths.

ALBUTEROL &
TERBUTALINE

ACTIVITY: Short acting beta 2 agonists.

ACTIONS: Used primarily as bronchodilators.
USES: 1) Albuterol is a drug of choice for acute asthma. 2)
Terbutaline is used (inhaled) off label of suppress premature
labour (as a uterine muscle relaxant).
ADVERSE EFFECTS: 1) Tremours but tolerance to this effect is
developed. 2) Restlessness, apprehension and anxiety. 3)
Causes tachycardia and arrhythmias (due to beta 1 receptor
activation) when administered orally.
CONTRAINDICATION: 1) When a patient is already on MAOI
(Monoamine oxidase inhibitors) and concomitant use should be
avoided as the combination will cause adverse cardiovascular
effects.

ACTIVITY: long acting beta agonist/Beta 2 selective.

DURATION OF ACTION: Single dose gives twelve hours of
action.
ACTIONS: 1) Bronchodilation. 2) Salmeterol has a delayed onset
of action. 3) Formoterol has a quick duration of action.
USES: These are drugs of choide for the treatment of nocturnal
asthma in symptomatic patients.
NOTE: Not recommended in monotherapy but are efficacious
when combined with corticosteroids.

ALBUTEROL HAS 3 HOURS OF ACTION.

CLONIDINE

ACTIVITY: Alpha 2 agonist.

ACTION: Acts centrally on presynaptic alpha 2 receptors to
produce inhibition of sympathetic vasomotor centers,
decreasing sympathetic outflow to the periphery.
USES: 1) Treatment of hypertension. 2) Minimize the symptoms
of opiate and tobacco smoking and benzodiazepenes.
ADVERSE EFFECTS: 1) Lethargy. 2) Sedation. 3) Constipation. 4)
Xetostomia.

ISOPROTEREN
OL

ACTIVITY: Beta 1 and Beta 2 agonist.

ACTIONS: 1) Intense stimulation of the heart increasing heart
rate, contractility and cardiac output (beta 1). 2) Dilates arteries
of skeletal muscles (Beta 2) TPR decreases. 3) Decreases
mean arterial and diastolic pressure. 4) Potent bronchodilator
(beta 2 effect).
USES: In the treatment of AV block. Non selectivity is its
drawback.
ADVERSE EFFECTS: Similar to epinephrine.

TYRAMINE

AMPHETAMINE

Not clinically useful

Found in fermented foods like aged cheese and Chianti wine.
Normal byproduct of tyrosine metabolism
Normally it is oxidized by MAO in GIT but if patient is taking
MAOI, tyramine precipitates and results in serious vasopressor
episodes.

It enters nerve terminals and displaces stored epinephrine.

ACTIONS: (1) Marked central stimulation. (2) Beta 1 stimulates

effects on heart. (3)Alpha 1 agonist on vasculature increase
BP significantly.
MECHANISM OF ACTION: By mediating an increase in the
release of non vesicular catecholamines eg. Dopamine and nor
epinephrine from nerve terminals by entering and displacing
the catecholamines.

THERAPEUTIC USES: Children with attention deficit syndrome,

narcolepsy and appretite control.

COCAINE

ACTIONS: Blocks Na/Cl dependent norepinephrine transporter

for norepinephrine reuptake into adrenergic neurons.
Norepinephrine accumulates in the synaptic space.
Enhanced sympathetic activity as duration of action of
epinephrine and norepinephrine is increased.
Like amphetamine it can increase BP by alpha 1 and beta
stimulating effect.

EPHEDRINE &
PSEUDO
EPHEDRINE

ACTIVITY: Similar but less potent adrenergic actions than

epinephrine.
STRUCTURE: It is not a catechol therefore it is a poor substrate
for MAO and COMT. It has a longer duration of action and is non
polar so is absorbed orally and has CNS effects:
Ephedrine

Pseudoephedrine

Mild
CNS
affects
but
increases
alertness,
decreases fatigue, prevents
sleep and improves athletic
performances.
It has less clinical uses due to
its adverse effects but is
used to treat hypotension
and asthma attacks (less
potent than epinephrine and
isoproterenol)
Not metabolized and is
eliminated unchanged in the
urine.

Fewer CNS effects

Ephedrine
Long acting
Non polar
Good oral absorption
Adequate CNS penetration
Not metabolized by COMT
and MAO and is excreted in
the urine

Epinephrine
Short acting
Polar
Poor oral absorption
No CNS effects
Metabolized and products
venelyl
mendalic
acid
metanephrine excreted in
urine
It is better in treating

Less potent vasoconstrictor

Primarily used as oral and

nasal decongestant.

Partly metabolized before it is

eliminated in the urine.

PHENTOLAMI
NE

PHENOXYBENZAM
INE

ACTIVITY: Competitive block of alpha 1 and alpha 2 receptors.

DURATION OF ACTION: Lasts for 4 hours after single injection.
ACTIONS: 1) Epinephrine reversal. 2) Short term management
of pheochromocytoma. 3) Used locally to prevent dermal
necrosis following extravasation of norepinephrine. 4) Treat
hypertensive crisis due to abrupt withdrawal of clonidine and
from ingesting tyramine containing foods in patients taking
MAOI.
ADVERSE EFFECTS: 1) Postural hypotension. 2) Reflex cardiac
stimulation and tachycardia Baroreceptor reflex and by
blocking alpha 2 receptors of the cardiac sympathetic nerves. 3)
Trigger arrhythmias. 4) Anginal pain.

CONTRAINDICATIONS: In patients with coronary artery disease.

It has a limited clinical application.

ACTIVITY: Non-selective, irreversible binding(covalently) to
alpha 1 and alpha 2..
DURATION: Few hour delay after injection. Action lasts for about
24 hours. The only way to overcome the blockade is to develop
new receptors.
ACTIONS: CVS 1) Block alpha receptors on the blood vessels
Prevents vasoconstriction and causes reflex tachycardia. 2)
Blocks alpha 2 presynaptic receptors on the heart increase
cardiac output. SO IT IS NOT USED IN THE TREATMENT OF
HYPERTENSION. EPINEPHRINE REVERSAL: 1) Vasoconstrictive
action of epinephrine is blocked (Alpha 1 affect) but beta action
is not, it causes vasodilation of other vascular beds (beta 2), BP
is decreased in response to epinephrine. 2) Actions of
norepinephrine are not reversed but are diminished because it
lacks beta activity. 3) No effect on treatment with isoproterenol
pure beta agonist.
USES: 1) treatment in pheochromocytoma secreting tumor,
prior to operation to prevent hypertensive crisis. It is also used
in the management of inoperable tumors. 2) Reynauds disease.
3) Frostbite.
ADVERSE EFFECTS: 1) Postural hypotension 2) Nasal stuffiness.
3) Nausea. 4) Vomiting. 5) Inhibit ejaculation. 6) Reflex
tachycardia baroreceptor reflex.

CAUTION: Used in caution in cerebrovascular and cardiovascular

diseases.

PIPERAZINYL
QUINAZOLINE

YOHIMBINE

PRAZOSIN

TERAZOS
DOXAZOSIN
IN
Selective competitive alpha 1 blockers,
useful in treating hypertension.
Metabolites in urine

Metabolites in
feces and
hence long
acting
Decrease peripheral vascular resistance
and lower blood pressure (Relaxation of
both arterial and venous smooth
muscle).

TAMSOLUSI
ALFUZOSI
N
N
Selective
Alpha
1
antagonist,
used
in
treating BPH
Metabolites in urine.

Decrease
peripheral
vascular
resistance
( a little
more than
tamsolusi
n)
These drugs do not become tolerant but the first dose produces
exaggerated orthostatic hypotension thus causing syncope First
dose effect, it can be minimized by adjusting dose to 1/3 rd or 1/4th of
normal dose and by giving it during bedtime.
Modest improvement in lipid profile and glucose metabolism in
hypertensive patients because of inferior cardiovascular effects,
these are not used in monotherapy for hypertension but these are
used as an alternative to surgery in symptomatic BPH
Sam as
Dizziness, lack
doxazosin
of energy,
.
nasal
congestion,
headache,
drowsiness and
orthostatic
hypotension.
1) Inhibition of ejaculation. 2) Retrograde ejaculation. blocking
alpha receptors in ejaculatory ducts & impairment of smooth muscle

It has least
effect in
decreasing
peripheral
vascular
resistance*

ACTIVITY: Alpha 2 blocker.

USES: 1) Sexual stimulant and in the treatment of erectly
dysfunction but is no longer used due to lack of demonstrated
efficacy.
ACTION: It works at the level of CNS to increase sympathetic
outflow to the periphery.
CONTRAINDICATION: In CVS diseases, psychiatric conditions and
renal dysfunction.

ADVERSE
EFFECTS AND
CONTRAINDICATI
ONS OF
PROPANOL

LABETELOL
AND
CARVEDILOL

ADVERSE EFFECTS: Bronchodilation: Asphyxiation in patients

with asthma (beta 2 blockade). Arrhythmias: There is a risk of
precipitating arrhythmias if abruptly stopped. It should be
gradually tapered off as long term use leads to upregulation of
receptors. Sexual impairment: Some men do complain of
impaired sexual activity but ejaculation and internal bladder
sphincter
function
is
alpha
mediated.
Metabolic
disturbances: Decrease in glycogenolysis and decrease
glucagon secretion, it leads to fasting hyperglycemia.
Perception
of
symptoms
of
hypoglycemia
(tremours,
tachycardia and nervousness) are blunted. CNS: Depression,
dizziness, lethargy, fatigue, weakness, visual disturbances,
hallucinations, short term memory loss, emotional lability and
vivid dreams.
DRUG
INTERACTIONS:
CIMETIDINE,
FLOUXETINE,
PAROXETINE AND RITONIVAR Inhibit metabolism thereby
potentiates hypertension. BARBITURATES, PHENITOIN AND
RIFAMPIN It stimulates its metabolism and can decrease its
effects.

CONTRAINDICATIONS: COPD

ACTIVITY: Antagonist of both alpha and beta receptors.

ACTIONS: 1) Alpha 1 blocking actions that produce peripheral
vasodilation (contrast with beta blockers that produce initial
peripheral vasoconstriction). 2) Carvedilol decreases lipid
peroxidation and vascular wall thickening effects that benefil
heart over long time.
USES: 1) In hypertensive patients for whom increase peripheral
resistance is undesirable. 2) Labetilol is used alternative to
methyldopa in the treatment of pregnancy induced
hypertension, IV is used to treat hypertensive emergencies
because it rapidly lowers BP. They should not be (beta blockers
should not be) given to patients with an acute exacerbation of
heart failure. 3) Carvedilol, metoprolol and bisoprolol is used in
patients with stable chronic heart failure because it blocks
sympathetic stimulation on the heart and causes worsening of
heart failure OVER TIME.

ADVERSE EFFECTS: 1) Orthostatic hypotension. 2) Dizziness.

ACEBUTOLOL,
ATENOLOL,
BETAXOLOL,
ESMOLOL,
METOPROLOL,
NEBIVOLOL

ACEBUTOLOL
AND
PINDOLOL

ACTIVITY: Preferentially blocks beta 1 receptors and minimizes

the unwanted beta 2 blockage bronchoconstriction, beta 1
selectivity is lost at high doses.
ACTIONS: 1) lower BP in hypertension. 2) increase exercise
tolerance in angina. 3) Nebivolol releases nitric oxide from
endothelial cells and cause vasodilation.
USES: 1) Esmolol has a very short half-life, it is metabolized
very easily because of its ester linkage and is used to control BP
during surgery. 2) In contrast to proponol, these have fewer
effects on pulminory function, peripheral resistance and CHO
metabolism so it is used in hypertensive patients with impaired
pulmonary function. 4) These drugs are first line of therapy for
chronic stable angina. 5) Bisoprolol and metoprolol (in an
extended release form) is used for chronic heart failure.
NOTE: These drugs have less beta 2 blocking effect so coldness
of extremities and Reynauds phenomenon is less frequent.

ACTIVITY: These are not pure agonist and have the ability to
weakly stimulate both beta 1 and beta 2 receptors (these have
intrinsic sympathomimetic activity)
USES: CVS: They bind and stimulate, also simultaneously
inhibit binding of more potent catecholamines epinephrine,
norepinephrine so produce a diminished cardiac effect.
Metabolic effects: minimize the disturbance of of CHO
metabolism eg. Do not decrease plasma HDL levels.
Hypertension: Effective in patients with moderate bradycardia
further decrease is less pronounced with these drugs.
NOTE: Not used in stable angina or arrhythmias due to their
partial agonist effect.

ACTIVITY &
ACTION OF
PROPANOLOL

THERAPEUTIC
USES AND
PHARMACOKINETI
CS OF PROPANOL

THERAPEUTIC USES: Hypertension: 1) Doesnt reduce blood

pressure in people with normal blood pressure. It lowers
hypertension in hypertensive patients in several different ways:
A) decreased cardiac output. B) Inhibits release of renin from
the kidneys. C) Decrease TPR due to long term use. D) decrease
in sympathetic outflow from the CNS. Angina Pectoris: It
decreases oxygen requirement of the heart and is used in the
treatment of stable chronic angina. Myocardial Infarction: 1)
Protective effect on the myocardium, if prophylactically used, it
prevents a second heart attack. 2) If given immediately after an
infarct, it reduces infarct size and hastens recovery (probably
because of blocking catecholamine action). 3) Reduces
incidence of sudden arrhythmic death after MI. Migraine: Used
prophylactically to reduce incidence of migraine. It is lipophilic.
Hyperthyroidism: Blunts widespread sympathetic stimulation.
In acute hyperthyroidism (thyroid storm), beta blockers myight
have a lifesaving effect to prevent arrhythmias.

PHARMAKOKINETICS: It is completely absorbed and undergoes

ACTIVITY: Prototype beta adrenergic agonist, blocks both beta 1

and beta 2 receptors.
DOSAGE: Sustained release preparation for once a day dosing is
available.
ACTIONS: CVS: 1) Diminishes cardiac output (-ve ionotropic and
ve chronotropic effects). It directly depresses SA and AV nodal
activity and this limits the dose of the drug. 2) Cardiac output,
workload and oxygen consumption of the heart is decreased
and this is used in the treatment of angina. 3) Attenuate
supraventricular tachycardia (but only affect those tachycardias
that are caused by exercise). Peripheral vasoconstriction: 1)
Prevention of beta 2 vasodilation in skeletal muscles results in
increased peripheral vascular resistance. Reduction in cardiac
output by beta blockade leads to reflex vasoconstriction. 2)
Gradual reduction of both systolic and diastolic blood pressures
in hypertensive patients. Bronchoconstriction: Blocking beta
2 in lungs in susceptible patients causes contraction of
bronchial smooth muscles. Disturbances in glucose
metabolism: 1) Decrease glycogenolysis and glucagon
secretion. Propanol produces pronounced hyperglycemic effects
in diabetics after an insulin injection. 2) Beta blockers also
lessen the normal physiological response to hypoglycemia.
Blocked action of isoproterenol: In the presence of a beta
blocker, it does not produce cardiac stimulation. Beta 1 blocker
mediated reduction in mean arterial pressure and it also affects
the diastolic pressure (beta 2 blocker mediated action).
Epinephrine no longer lowers the diastolic pressure in the
presence of a beta blocker. Norepinephrine cardiac stimulation
(alpha mediated) remains unaffected.

first pass metabolism to such an extent that it has 25%

bioavailability. Its volume of distribution is 4L/kg. It passes the
blood brain barrier, is extensively metabolized and is excreted
in the urine.

RESERPINE

STRUCTURE: Plant alkaloid.

ACTIVITY: Blocks Mg/adenosine triphosphate dependent
transport of biogenic amines (NE, dopamine and serotonin) from
the cytoplasm into storage vesicles in the adrenergic nerve
terminals in all body tissues.
ACTIONS: 1) Sympathetic function is impaired because of
decreased release of norepinephrine.
ONSET/DURATION: Slow in onset, long duration of action, effects
persist for many days after discontinuation.
USES: Used for the management of hypertension but is replaced
with newer agents with better side effect profiles and fewer
drug interactions.

TIMILOL AND
NADOLOL

ACTIVITY: Block beta 1 and beta 2 adrenoreceptors and are

more potent than propranolol.
DURATION OF ACTION: Nadolol has a very long duration of
action.
USES: Timilol reduces production of aqueous humour in the eye.
It is used topically in the treatment of chronic open angle
glaucoma and, occasionally, for the systemic treatment of
hypertension.
TREATMENT OF GLAUCOMA: Topical administration of these
drugs is effective in diminishing intraocular pressure in
glaucoma. This occurs by decreasing the secretion of aqueous
humor.