Transcript Adrenergic Drugs

ADRENERGIC TRANSMISSION
 Noradrenaline (NA) It acts as transmitter at
postganglionic sympathetic sites (except sweat glands,
hair follicles and some vasodilator fibres) and in
certain areas of brain.
 Adrenaline (Adr) It is secreted by adrenal medulla.
Adrenergic receptors
 There are two main groups of adrenergic receptors, α
and β, with several subtypes.
 α receptors have the subtypes α1 and α2.
 β receptors have the subtypes β1, β2 and β3.
α1 adrenergic receptors
 Smooth muscle
 Muscle contraction
 Vessels (skin, GI system,
 Mydriasis
kidney and brain)
 Glands
 Gut
 Liver
 Vasoconstriction in the
skin, mucosa etc.
 Gland secretion
 Gut relaxation but
sphincter contraction
 Glycogenolysis
α2 adrenergic receptors
 Prejunctional on nerve
ending
 Postjunctional in brain,
pancreatic β cells, etc.
 Extrajunctional in blood
vessels, platelets
 Negative feedback in the
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neuronal synapses presynaptic inhibition of NA
release
Inhibition of insulin release
Induction of glucagon
release from the pancreas.
Increased thrombocyte
aggregation
Vasoconstriction of veins
and coronary arteries
Decrease motility of
smooth muscle in GIT
β1 receptors
 Increase heart rate
 Increase force of cardiac
contractility
 Increases conduction of
atrioventricular node (AV
node)
 Renin release from
juxtaglomerular cells
β2 receptor
 Smooth muscle relaxation,
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e.g. in bronchi,GI tract
Relax non-pregnant uterus
Relax detrusor urinae muscle
of bladder wall
Dilate arteries to skeletal
muscle (in contrast to
vasoconstriction caused by α1
and α 2 adrenoceptors).
Coronary arteries have only β2
receptors.
Relaxation of Bronchioles
β2 receptor
β3 receptor
 It is located mainly in adipose tissue and is involved in
the regulation of lipolysis
 β3 activating drugs could theoretically be used as
weight-loss agents, but are limited by the side effect of
tremors.
Epinephrine (adrenaline)
 Epinephrine, also known as adrenaline, is a
medication and hormone.
 As a medication it is given intravenously, by injection
into a muscle, by inhalation, or by injection just under
the skin.
 Epinephrine is normally produced by both the adrenal
glands and certain neurons and plays an important
role in the “fight-or-flight” response.
Norepinephrine
 Norepinephrine (noradrenaline) is catecholamine that
functions in the human brain and body as a hormone
and neurotransmitter.
 Norepinephrine is synthesized and released by the
central nervous system and also by the sympathetic
nervous system.
 In the sympathetic nervous system norepinephrine is
used as a neurotransmitter.
Epinephrine vs Norepinephrine
 Adr : α1 + α2 + β1 + β2
 NA : α1 + α2 + β1 but no β2 action
Comparative effects of intravenous infusion
of adrenaline and noradrenaline
1. Heart rate
2. Cardiac output
3. BP—Systolic
Diastolic
Mean
4. Blood flow
Skin and mm
Sk. muscle
5. Bronchial muscle
6. Intestinal muscle
7. Blood sugar
Adr
↑
↑↑
↑↑
↓
↑
NA
↓(reflex bradycardia)
–
↑↑
↑↑
↑↑
↓
↑↑
↓↓
↓↓
↑↑
↓
↓
–
–, ↑
Adrenaline action
Heart
 Cardiac stimulation (β1), ↑ rate, force and conduction
velocity
Blood vessels
 Both vasoconstriction (α) and vasodilatation (β2) can
occur .
 Constriction predominates in cutaneous, mucous
membrane and renal arterioles.
 Dilatation predominates in skeletal muscles, liver and
coronaries arterioles.
Adrenaline action
BP
 Adr given by slow i.v. infusion or s.c. injection causes rise
in systolic (α) but fall in diastolic (β2) BP. Mean BP
generally rises.
 Rapid i.v. injection of Adr produces:
1) a marked increase in both systolic
as well as diastolic BP.
2) The BP returns to normal within
a few minutes and a secondary fall
in mean BP follows.
Norepinephrine and BP
 It does not cause vasodilatation (no β2 action).
 Peripheral resistance increases consistently due to α
action.
 NA causes only rise in systolic, diastolic and mean
BP.
Adrenaline action
Respiration
 Adr causes bronchodilatation (β2)(but not NA!)
Eye
 Mydriasis due to contraction of radial muscles of iris (α1)
 The intraocular tension tends to fall.
GIT
 Relaxation (both α and β receptors)
CNS
 Adr produces activation of brain →restlessness, apprehension and
tremor may occur.
 !Activation of α2 receptors in the brainstem results in decreased
sympathetic outflow → fall in BP and bradycardia.
Inducations
Hypotensive states (shock)/Anaphylaxis
 Adr is the drug of choice in anaphylactic shock (raise
BP + bronchodilation)
Along with local anaesthetics
 Duration of anaesthesia is prolonged and systemic
toxicity of local anaesthetic is reduced. Local bleeding
is minimised.
Control of local bleeding
Cardiac arrest (Adr may be used to stimulate the heart)
Bronchial asthma
Mydriatic
Adverse effects
 Tachycardia
 Arrhythmia
 Anxiety
 Panic attack
 Headache
 Tremor
 Hypertension
 Cerebral haemorrhage
 Angina
 Myocardial infarction
α1-adrenomimetics
 Phenylephrine It is an effective mydriatic and
decongestant and can be used to raise the blood
pressure (in hypotensive states).
 Methoxamine acts pharmacologically like
phenylephrine.
 Midodrine -the treatment of postural hypotension
α2-adrenomimetics
Nasal decongestant:
 Naphazoline
 Xylometazoline
 Oxymetazoline
 produce local vasoconstriction
 Regular use for long periods should
be avoided because atrophic rhinitis
and anosmia can occur due to
persistent vasoconstriction.
CNS-activating:
 Clonidine
 Guanfacine (Estulic)
to treat:
 high blood pressure,
 withdrawal (from alcohol, opioids or
smoking)
 Tizanidine
 spasms, cramping, and tightness of
muscles
Mechanism of Clonidine action
 Clonidine → stimulate presynaptic α2-receptors in the
vasomotor center → inhibiting the release of NE
→decrease in sympathetic tone → lowering blood
pressure.
 Clonidine → on the I1-receptor (imidazoline receptor),
which mediates the sympatho-inhibitory actions of
imidazolines to lower blood pressure.
Adverse effects of Clonidine
 Orthostatic hypotension (Drops in blood pressure
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upon standing up)
Sedation
Sleepiness
Dizziness
Fatigue
Rebound effect (sudden discontinuation can cause
rebound hypertension)
β1 STIMULANTS
 Dobutamine (in cardiogenic shock)
 Dopamine
 Cardiac stimulation
↑ rate, force and conduction velocity
 To treat:
 acute heart failure
 chronic heart failure in phase of cardiac
decompensation
 cardiogenic shock
 ADR:
Hypertension
Angina
Arrhythmia, including fatal arrhythmias
Tachycardia
Atrial fibrillation
β2 STIMULANTS
Short acting (4–6 hours) : 
 Salbutamol
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 Terbutaline
 Ritodrine
Long lasting (12 hours):
 Salmeterol
 Formoterol
 Clenbuterol
the relief of bronchospasm
in asthma
to relax the uterine smooth
muscle to delay premature
labor.
 for prevention of asthma
symptoms
 not for use in relieving an
asthma attack (not be used
to treat acute symptoms)
 should be used with a
corticosteroid
β2 STIMULANTS
Side effects
 Dizziness
 Headaches
 Tachycardia
 Arrhythmia
 Muscle cramps
 Paradoxical bronchospasm!
 Hypotension and collapse
β1β2-STIMULANTS
 Isoprenaline (isoproterenol)
For the treatment of:
 Bradycardia
 heart block
 For asthma (rarely)
ADR:
 Tachycardia
 Arrhythmia
 Hypotension
Sympathomimetic drugs
- stimulant compounds (indirect-acting)which mimic
the effects of epinephrine and norepinephrine
 These drugs can act through several mechanisms:
 Blocking breakdown of NA
 Blocking reuptake of NA
 stimulating production and release of NA.
Ephedrine (found in Ephedra)
Pseudoephedrine
Amphetamine (Benzedrine)
Phenylpropanolamine (norephedrine)
Ephedrine
 Ephedrine is a dangerous natural compound!
 Repeated injections produce tachyphylaxis.
 In traditional Chinese medicine, it is used as bronchodilators .
 Ephedrine crosses to brain and causes stimulation.
 Used as:
 A stimulant (it increases performance in athletes)
 Concentration aid,
 Appetite suppressant
 Weight loss (a popular supplement taken by body
builders to cut down body fat before a competition).
 For hypotension during spinal anaesthesia /postural
hypotension
 Bronchial asthma
Ephedrine
Adverse drug reactions :
 Cardiovascular: tachycardia, cardiac arrhythmias, angina
pectoris, vasoconstriction with hypertension
 Dermatological: flushing, sweating, acne vulgaris
 Gastrointestinal: nausea
 Genitourinary: decreased urination due to vasoconstriction
of renal arteries
 Nervous system: restlessness, confusion, insomnia,
mania/hallucinations, paranoia, panic, agitation
 Respiratory: dyspnea, pulmonary edema
 Miscellaneous: dizziness, headache, tremor, hyperglycemic
reactions, dry mouth
Pseudoephedrine
Medical uses:
 a stimulant (improvement in mental and physical
functions )
 a nasal/sinus decongestant (it reduces edema and
nasal congestion/rhinitis)
 a wakefulness-promoting agent (treatment of sleeping
disorders, excessive daytime sleepiness and
narcolepsy)
Pseudoephedrine
Adverse effects
 CNS stimulation- insomnia, nervousness, excitability,
dizziness and anxiety.
 Tachycardia
 Arrhythmias
 Hypertension
 Hallucinations
 Seizures
 Systemic contact dermatitis
 Paranoid psychosis
 Stroke
Amphetamine(Adderall)
Amphetamine is used to treat:
 Attention deficit hyperactivity disorder (ADHD)
 Narcolepsy (a sleep disorder)
 Obesity
Past medical indications:
 Depression
 Nasal congestion
Amphetamine(Adderall)
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Hypertension
Tachycardia
Erectile dysfunction
Loss of appetite and weight loss
Seizure and tics
Irritability
Repetitive or obsessive behaviors
Amphetamine psychosis (paranoia)
Cardiogenic shock and circulatory collapse
Cerebral hemorrhage
Pulmonary edema and hypertension
Kidney failure
Addiction and Drug tolerance
Phenylpropanolamine
is used as:
 A stimulant
 Decongestant
 Anorectic agent
In Europe, PPA is still available in prescription and overthe-counter cough and cold medications.