2-DRUGS ACTING ON THE

6hours
ADRENERGIC SYSTEM
INTRODUCTION
Location.
Neurotransmission.
Receptors.
Drugs.
 LOCATIONS OF NEURONS
 In the (CNS).

 In the sympathetic nervous system

 Adrenergic drugs act on adrenergic

receptors, located either

presynaptically on the neuron or

postsynaptically on the effector organ.

 HO
OH
HO CH CH2 NH2
Termination:
results from several processes such as reuptake into
the nerve terminal (reuptake), diffusion away from
the synaptic cleft and subsequent reuptake into the
perisynaptic glia or smooth muscle or degradation
by enzymes.

Reuptake into the

nerve terminal is the most important mechanism for
termination of the effects of noradrenaline.
Degradation of adrenergic neurotransmitters
Enzymes:
 MAO(monoamine oxidase)
 COMT(catechol-O-methyltransferase)
 2. Adrenergic Receptors
(Adrenoceptor)

Type G Second Tissue Actions

protei messenge
n r

Alpha Gq DAG,IP Most vascular smooth Contraction

1 3 m. Mydriasis
α1 Pupillary dilator
muscle

Alpha Gi cAMP Adrenergic nerve Inhibition of transmitter

2 terminals release
α2 Platelets Aggregation

Beta1 Gs cAMP Heart incr. rate and force of

β1 Contraction
Beta2 Gs cAMP Respiratory, uterine,
β2 and Relaxation
 3. DRUGS ACTING ON THE
ADRENERGIC RECEPTOR SUBTYPES

Adrenaline stimulates all the four receptor subtypes

Noradrenaline stimulates both alpha receptors and beta1
but has very poor affinity for beta2 receptors

α1 α2 β1 β2
Agonist: Phenylephrine Clonidine Dobutamine Salbutamol

Antagonist: Prazosin Yohimbine Propranolol Butoxamine

Labetalol
blocks all beta receptors as well as some alpha receptors.
SELECTIVITY
DRUGS ACTING ON THE
SYMPATHETIC SYSTEM

Types
1. Sympathomimetics.
2. Sympatholytics.
 Sympathomimetics

CLASSIFICATION ACCORDING TO CHEMICAL STRUCTURE

1. Catecholamines: 2. Noncatecholmines

 have the catechol  lack the catechol

nucleus. nucleus.
 Examples:  Examples:

adrenaline, Ephedrine &

noradrenaline, phenylephrine
dopamine,
HO
and
OH CH 2 CH NH 2
dobutamine
HO CH CH2 NH2
CH 3
Noradrenaline Amphetamine
CLASSIFICATION
ACCORDING TO MODE OF ACTION
Direct:
 Interact directly with receptors
e. g. Adrenaline and noradrenaline

Indirect:
This may be
i. Displacement of stored catecholamies from the
adrenergic nerve endings,
e.g.: amphetamine, tyramine.
ii. Inhibition of reuptake of catecholamines already
released,
e.g. cocaine, tricyclic antidepressants TCA

Mixed:
 Stimulate adrenoceptors directly & enhance release of
NE from the adrenergic neuron
 E.g. Ephedrine and pseudoephedrine
1. EPINEPHRINE:
This is the prototype of adrenergic drugs.
ACTIONS:
1. CVS:
a. Heart: increased rate and force of contraction,
increased cardiac output(ß1), myocardial demand, and
AV conduction
b. Blood Vessels and Blood pressure: constriction of
blood vessels in the skin and mucous membranes(α).
Dilatation of skeletal muscle vessels(ß2)
- Adrenaline increases systolic and decreases diastolic
blood pressure at low doses
but increases both at higher doses
- Platelet aggregation(α).
EFFECT OF EPI ON CVS
 Heart rate.
 Blood pressure.

 Peripheral resistance
2. Smooth Muscle:
a. Bronchi: relaxation(ß2).
b. Uterus: relaxation of the pregnant
uterus(ß2)
c. GIT: relaxation of wall muscles and contraction of sphincters
d. Bladder: relaxation of detrusor muscle;
contraction of sphincter and trigone muscle
3. Eye: mydriasis(α); reduction of IOP in
normal and glacucomatous eyes
4. Respiration: Bronchodilatation(ß2) & relief
of congestion
5. Metabolic: Increased hepatic
glycogenolysis(α); decreased peripheral glucose
intake (hyperglycemia); increased free fatty
acids in the blood (lipolysis)
6. CNS: excitement, vomiting, restlessness
7. Skeletal muscle: facilitation of
neuromuscular transmission and
vasodilatation(ß2).
INDICATIONS:
1. Acute bronchial asthma
2. Anaphylaxis
3. Local haemostatic to stop bleeding in epistaxis
4. With local anesthesia to prolong the action of anesthetic
5. Cardiac arrest

Adverse reactions
1. Anxiety, restlessness, headache tremor
2. Anginal pain
3. Cardiac arrhythmias and palpitations
4. Sharp rise in blood pressure
5. Sever vasoconstriction resulting in gangrene of extremities

Contra indications
1. Coronary diseases
2. Hyperthyroidism
3. Hypertension
4. Digitalis therapy
 2. NOREPINEPHRINE

Baroreceptor reflex

 NE increases blood pressure, and this stimulates the

baroreceptors, inducing a rise in vagal activity.

 The increased vagal activity produces a Reflex

Bradycardia, which is sufficient to counteract the

local actions of NE on the heart, although the reflex

compensation Does not affect the positive inotropic

effects of the drug .

 When use atropine, (anticholinergic drug), stimulation of the

heart by NE is evident as tachycardia

3. ISOPROTERENOL,
DOPAMINE, DOBUTAMINE.
These are the other catecholamines which have
similar properties to adrenaline and noradrenaline

These drugs have advantage over the others

because they are
more selective in their action so that they
have fewer side effects than adrenaline

Dopamine and Dobutamine are very

useful drugs for the treatment of
shock.
ISOPROTERENOL
Selective beta
receptor agonist
 4. EPHEDRINE
Indications:
1. Bronchial asthma
2. Nasal decongestion
3. Mydriasis
4. Heart block
5. Nocturnal enuresis

Side effects
The side effects are similar to those of adrenaline; but in
addition it may produce insomnia and retention of urine.
THERAPEUTIC USES
SUMMARY

Epinephrine Norepinephrine Dobutamine Isoprenaline Ephedrine

Chemistry Catechol Catechol- Catecho Catecho Non-catecholamine

- amine amine l-amine l-amine

Mechanism Direct Direct Direct Direct Indirect

of action

Receptor Alpha Alpha Beta-1 Beta-2 Alpha and beta

stimulated and beta

Site of All organs All organs Heart Lung and Respiratory

action uterus system
MCQS

1. Which of the following classes of adrenergic

agents has utility in the management of
hypertension?
A. α1 Agonist
B. α2 Agonist
C. β1 Agonist
D. β3 Agonist
2. Which of the following adrenergic
agonists is commonly present in nasal
sprays available over-the-counter (OTC) to
treat nasal congestion?
A. Clonidine
B. Albuterol
C. Oxymetazoline
D. Formoterol
 Cases studies

Case 1
A 22-year-old male is brought to the emergency room
with suspected cocaine overdose. Which of the
following symptoms is most likely in this patient?
A. Hypertension
B. Bronchoconstriction
C. Bradycardia
D. Miosis.
 CASE 2:
A 12-year-old boy with a peanut allergy is
brought to the emergency room after
accidental consumption of peanuts. He is
in anaphylactic shock. Which of the
following drugs is most appropriate to
treat this patient?
A. Norepinephrine
B. Phenylephrine
C. Dobutamine
D. Epinephrine
2. ADRENERGIC
BLOCKERS
Types
1.Drugs blocking the α adrenergic receptor

2.Drugs blocking the β Adrenergic receptor

1. Α ADRENERGIC RECEPTOR BLOCKERS
1. Reversible such as Phentolamine and prazosin.
2. Irreversible such as Phenoxybenzamine.

Pharmacologic Effects:

1. Lower peripheral vascular resistance(PVR).

2. Lower Blood pressure(BP).
3. Postural hypotension and reflex tachycardia.
α adrenergic R Blockers
1. PHENTOLAMINE
NON SELECTIVE
COMPETITIVE ALPHA BLOCK

Uses:
1. The diagnosis & short-term management of Pheochromocytoma
2. Treat hypertensive crisis due to abrupt withdrawal of clonidine or
ingestion of tyramine containing foods in patients taking MAOIs.
 2. PHENOXYBENZAMINE
USED IN HPT ASS. PHAEOCHROMOCYTOMA

 Nonselective, Noncompetitive blocker.

 Actions:

1. Cardiovascular effects:

The drug prevents α1-R vasoconstriction of peripheral blood

vessels caused by endogenous catecholamines, which leads
to decreased PR and resultant reflex tachycardia However,
by blocking presynaptic α2 Rs on the sympathetic nerve
terminals in the heart, phenoxybenzamine causes an
increase in the release of NE, which in turn increases HR
and CO (mediated by β1 receptors).
 Lead to cardiac arrhythmias and anginal pain.

 So unsuccessful in maintaining lowered BP in HPT

2. EPINEPHRINE REVERSAL
 in the presence of phenoxybenzamine, the systemic
BP decreases in response to epinephrine
 3. PRAZOSIN, TERAZOSIN & DOXAZOSIN
Selective competitive Alpha1 receptor blocker.

Mechanism of action:
Relaxation of both arterial and venous smooth muscles due to the
blockage of alpha1 receptors. Thus, it lowers BP, Unlike
phenoxybenzamine and phentolamine, these drugs cause minimal changes
in CO, renal blood flow, and glomerular filtration rate

Tamsulosin :
• Less effects on BP because they are less selective for α1B Rs found in the BVs.
• More selective for α1A Rs in the prostate and bladder. Blockade of the α1A-Rs
decreases tone in the smooth muscle of the bladder neck and prostate & improves
urine flow.
 ADVERSE EFFECTS

1. Dizziness, a lack of energy, nasal congestion, headache,

drowsiness, and orthostatic hypotension

2. An additive antihypertensive effect occurs when α1

antagonists are given with vasodilators such as nitrates
or PDE-5 inhibitors (for example, sildenafil), thereby
necessitating cautious dose titration and use at the
lowest possible doses

3. Floppy iris syndrome.

Minimized
• By adjusting the first dose to one-third or
one-fourth of the normal dose
• By giving the drug at bedtime
Indications of alpha blockers:
1.Essential hypertension.
2.Benign prostatic hyperplasia

Note:
α1 antagonists are not used as monotherapy for
the treatment of hypertension
2. Β - ADRENERGIC
RECEPTORS BLOCKERS
Selective β1 -R
Non-selective
blockers
β1, β2 β1 in the heart,
less effect on the
bronchi and blood
e.g. Propranolol
vessels,
and Timolol.
e.g. Atenolol &
Acebutalol.
1. PROPRANOLOL
Nonselective β antagonist
ACTIONS:
1. CVS
 Negative inotropic and chronotropic effects

 Bradycardia

 Decrease Cardiac output, workload, and oxygen

consumption( use in angina).
 Reduces BP because decrease CO

2. Peripheral vasoconstriction:
It prevents β2-mediated vasodilation in skeletal muscles,
increasing peripheral vascular resistance
2. Respiratory system
Bronchoconstriction
3. Metabolic system
Hypoglycemia (decrease glycogenolysis & glucagon
secretion).
4. Kidneys:
Decrease renin secretion
ADVERSE
REACTIONS

Long-term treatment with a β antagonist

leads to up-regulation of the β receptor.
USES OF BETA BLOCKERS
1. Cardiacarrhythmias
2. Hypertension
3. Prophylaxis against angina
4. Myocardial infarction.
5. hyperthyrodism.
6. Anxiety states (suppression of the physical
manifestations of situational anxiety)
7. Prophylaxis against migraine attacks
CONTRAINDICATIONS AND PRECAUTIONS:

1.Bronchial asthma
2.Diabetes mellitus
3.Heart failure
4.Peripheral vascular disease

Drug interactions
• Enzyme inhibitors such as cimetidine and fluoxetine, potentiate
antihypertensive effects of propranolol.
• Enzyme inducers, such as barbiturates, phenytoin, & rifampin, can
decrease its effects.
2. ATENOLOL
 selective Beta-1 receptor blocker, Cardioselective
Use:
 in hypertensive patients with impaired pulmonary function.

 first-line therapy for chronic stable angina

3. Bisoprolol and metoprolol (selective):

indicated for the management of chronic heart failure

4. Timolol
Non-selective
use: only for chronic management of
glaucoma. By decrease secretion of aqueous humor from ciliary
body
5. ACEBUTOLOL AND PINDOLOL:
ANTAGONISTS WITH PARTIAL AGONIST ACTIVITY

Therapeutic uses:

β-Blockers with ISA are effective in hypertensive

patients with moderate bradycardia, because a
further decrease in heart rate is less pronounced
with these drugs
6. LABETALOL
 Mixed alpha and beta- adrenoceptor antagonist
 Reduces heart rate (beta1 effect) and Reduces
TPR by preventing vasoconstriction (alpha1
effect)
 Used: Hypertension
SUMMARY
Drug Phentol Phenoxybe Prazo Propran Aten Labet
amine nz sin olol olol alol
amine
Type of Alpha Alpha Alpha Bata Beta 1 Alpha
receptor 1 &
blocked beta

Site of CVS CVS CVS CVS CVS CVS

action Eye
Uses 1. hypertensive
crisis
Pheochromo Essentia 1.Cardiac arrhythmias
2.HPT
HPT HPT
2. Peripheral cytoma l HPT 3.MI
vascular 4.Thyrotoxicosis
diseases 5.Migraine Timolol
(PVD) 6.glaucoma
in
Glaucoma

Contra- 1.Bronchial asthma

indications 2.Diabetes mellitus
3.Heart failure
4.PVDs
CASES STUDIES
CASE 1:

An asthma patient was given a nonselective β

agonist to relieve bronchoconstriction. Which
adverse effect would you expect in this patient?

A. Bradycardia

B. Tachycardia

C. Hypotension (reduction in blood pressure)

D. Worsening bronchoconstriction
CASE 2:
A 60-year-old patient started a new antihypertensive
medication. His blood pressure is well controlled, but

he complains of fatigue, drowsiness, and fainting when

he gets up from the bed (orthostatic hypotension).

Which of the following drugs is he most likely taking?

A. Metoprolol

B. Propranolol

C. Prazosin

D. Alfuzosin
CASE 3:
A β-blocker was prescribed for hypertension in a patient with

asthma. After a week of treatment, the asthma

attacks got worse, and the patient was asked to stop taking the

β-blocker. Which β-blocker would you suggest as an alternative

that is less likely to worsen the asthma?

A. Propranolol

B. Metoprolol

C. Labetalol

D. Carvedilol