Atropine

PHARMACOLOGY

Dr. Husam Aldeen Salim Alnajar

Atropine

Characteristics of Atropine
Source
Atropa belladonna
Chemical nature
An alkaloid

ANTIMUSCARINIC AGENTS

BELLADONNA
ALKALOIDS
• ATROPINE
• SCOPOLAMINE
TX: USED WHEN A REDUCTION OF PARASYMATHETIC
TONE IS DESIRABLE
• PREOP TO REDUCE SALIVATIONS / BRONCHIAL SECRETIONS
• REDUCE INTESTINAL MOTILITY
• TREAT OVERACTIVE BLADDER
• OPHTHALMOLOGICAL EXAMINATIONS
• PREVENTING MOTION SICKNESS
• TREAT ASTHMA
• TREAT POISONING BY AChE INHIBITOR


Effect Of Atropine in Relation to Dosage ...
DOSE EFFECT
0.5 mg Slight decline in heart rate
Some dryness of mouth
Inhibition of sweating

DOSE EFFECT

1.0 mg Definit dryness of mouth
Thirst
Inreased heart rate, sometimes preceded by slowing
Mild dilatation of pupil

DOSE EFFECT

2.0 mg Rapid heart rate
Palpitation
Marked dryness of mouth
Dilated pupils
Some blurring of near vision

DOSE EFFECT

5.0 mg All the previous symptoms are marked
Difficulty in speaking and swallowing Restlessness and fatigue
Headache
Dry hot skin
Difficulty in micturition
Reduced intestinal peristalsis


DOSE EFFECT
10 mg Previous symtoms are more marked
and more Pulse, rapid and weak
Iris practically obliterated
Vision very blurred
Skin flushed, hot, dry, and scarlet
Ataxia
Restlessness and excitement
Hallucinations and delirium
Coma

ATROPINE: OVERVIEW OF TOXIC ACTIONS

 DRY AS A BONE
 HOT AS A PISTOL
 RED AS A BEET
 BLIND AS A BAT
 MAD AS A HATTER

Therapeutic Uses of Antimuscarinic Agents

Cardiovascular System - atropine is generally used for the following cases


Sinus or nodal bradycardia in cases of excessive vagal tone associated with myocardial infarct

Hyperactive carotid sinus (syncope and severe bradycardia)

Second degree heart block

Gastrointestinal Tract

Peptic ulcers
M1 muscarinic receptor antagonists such as pirenzepine and telenzepine are used
Spasticity of the g.i. tract

Excessive salivation associated with heavy metal poisoning and parkinsonism

Production of partial blockade of salivation in patients unable to swallow

Urinary Bladder

Reverse spasm of the ureteral smooth muscle (renal colic)

Increase bladder capacity in cases of enuresis

Reduce urinary frequency in cases of hypertonic bladder
Central Nervous System
Parkinson’s disease
Motion sickness
Anesthesia, to inhibit salivation
Prevent vagal reflexes induced by surgical manipulation of organs


Posioning by inhibitors of acetylcholinesterase
Mushroom poisoning due to muscarine
In conjunction with inhibitors of acetylcholinesterase when they are used to promote recovery from neuromuscular blockade after surgery
Prevent vagal reflexes induced by surgical manipulation of visceral organs

Drugs of Other Classes With Antimuscarinic Activity

Tricyclic antidepressants
Imipramine
Amitriptyline
Protriptyline
Phenothiazine Antipsychotic Agents
Chlorpromazine & Thioridazine
H1 Histamine receptor blocking agents
Diphenhydramine
Promethazine
Chlorpheniramine
Cyproheptadine

Contraindications to the Use of Antimuscarinic Agents

Narrow angle glaucoma
Hypertrophy of the prostate gland
Atony of the bladder
Atony of the G.I. Tract


NE
1, 2, 1
Adrenergic Receptors

ACh

ACh

ACh
CNS

C
T
L
S

SM

ACh

ACh


N

N

ACh

M
ACh
CNS

C
T
L
S

SM

ACh

N


ACh
NE

N

N

ACh

M
ACh
CNS

C
T
L
S

SM

ACh


NE

N

ACh
NE

N

1

2
1

N

ACh

M
ACh
CNS


C
T
L
S

SM

ACh

NE

N

ACh
NE

N

ACh

EPI


N
1
2
1

N

ACh

M
ACh
CNS

C
T
L
S

ACh

NE


SM

N

NE
EPI
1, 2, 1, 2
1, 2, 1

Adrenergic Receptors

Differences between autonomic and somatic nerves

Autonomic:

- Synapses located in ganglions outside cerebrospinal axis
- Extensive peripheral plexuses
- Postganglionic nerves are not myelinated
- Some level of spontaneous activity without intact innervation
Somatic:
- Innervates all organs/glands except skeletal muscle
- Innervates only skeletal muscle
- Synapses within CNS
- Does not form peripheral plexuses
- myelinated
- Denervation results in paralysis, atrophy


Differences between functions of the
parasympathetic and sympathetic nervous system

Parasympathetic:

- Bradycardia
- Salivation increased
- Vasodilator predominance
- Blood pressure reduced
Sympathetic:
- Conservation of energy
- Urine output increased
- Respiration reduced
- GI motility and secretions increased
- Renal blood flow increased
- Expenditure of energy
- Tachycardia
- Vasoconstrictor predominance
- Blood pressure increased
- Renal blood flow decreased
- Salivation reduced
- Urine output decreased
- Respiration increased
- GI motility and secretions reduced


• SITE EFFECT
•
•
•
•
•
EFFECTS OF STIMULATING MUSCARINIC RECEPTORS (SLUDE)
BRONCHOSPASM
BRADYCARDIA
VASODILATION
MIOSIS
INCREASED URINATION
INCREASED GI MOTILITY
INCREASED SALIVATION
INCREASED TEARS
LACRIMAL GLANDS
SALIVARY GLANDS
GI TRACT
BLADDER
IRIS
AIRWAYS
VASCULATURE
HEART
SWEAT GLANDS
INCREASED SWEATNG


1, 2
vasoconstriction
TPR
contractile force
heart rate
1

2

vasodilation,
TPR

EFFECTS OF STIMULATING ADRENERGIC RECEPTORS

• SITE EFFECT
•
•
•
•
•
•
EFFECTS OF STIMULATING ADRENERGIC RECEPTORS
BRONCHORELAXATION (2)


TACHYCARDIA (1)
VASODILATION
MYDRIASIS (2)

DECREASED URINATION (2)

DECREASED GI MOTILITY (2)

GI TRACT

BLADDER
IRIS
AIRWAYS
VASCULATURE
HEART
(2)
VASOCONSTRICTION
(1,  2)
UTERUS
RELAXATION (2)

 Dual Innervation

 Predominant Tone


Exceptions -
Primarily parasympathetic NS
blood vessels
(only sympathetic)
Exceptions -
blood vessels (sympathetic)
- sweat glands (sympathetic
cholinergic)

Predominate Autonomic Tone

Arterioles Sympathetic (adrenergic)
Veins Sympathetic (adrenergic)

Heart Parasympathetic (cholinergic)

Iris Parasympathetic (cholinergic)
Ciliary muscle Parasympathetic (cholinergic)
GI tract Parasympathetic (cholinergic)
Urinary bladder Parasympathetic (cholinergic)
Salivary glands Parasympathetic (cholinergic)

Sweat glands Sympathetic (cholinergic)

Site
Predominate Tone

PRESYNAPTIC

POSTSYNAPTIC
NE

Re-uptake 1

Metabolic Removal
Action

 / 

Receptor
Binding
NE synthesis

NE
COMT
MAO
Re-uptake 2


(-)

NE - predominately removed from synapse via re-uptake 1

2

1, 2

vasoconstriction
TPR
contractile force
heart rate
1

2

vasodilation,
TPR


renin release

MIXED ADRENERGIC AGONISTS

Norepinephrine
Epinephrine
1, 2, 1, 2
1, 2, 1
Dopamine
DA, 1, 1

MIXED ADRENERGIC AGONISTS

Norepinephrine (1, 2, 1)
Epinephrine (1, 2, 1, 2)
Dopamine (DA, 1, 1)
Tx: ● Asthma (but there are better drugs)
Tx: ● CHF
● Anaphylactic shock,
● Cardiogenic shock
● Prolong action of local anesthetics
● Topical hemostatic agent


ALPHA AGONISTS
- Phenylephrine (1)
- Oxymetazoline (1 and 2 in periphery)
- Ephedrine/Pseudoephedrine (1)
- Clonidine (2, Tx site of action is CNS)
- Methoxamine (1)
- Tetrahydrozoline (1)
- Naphazoline (1)

BETA AGONISTS

• Non-selective 1/2
• Isoproterenol
• Selective 1
• Dobutamine
Selective 2
Albuterol
Terbutaline
Isoetharine
Metaproterenol
Bitolterol
Ritodrine


ACh
NE

N
1
2
1

N

ACh

M
ACh
CNS

C
T
L
S


ACh

NE

SM

N
Adrenergic Antagonists

EPI
N
ACh
X
X
X

ALPHA ANTAGONISTS

- Phentolamine
- Prazosin
- Terazosin (water soluble)
- Phenoxybenzamine
Used in pts with pheochromocytoma
 Nonselective 1 and 2 receptor antagonists
 Selective 1 receptor antagonists
Used Tx as antihypertensive agents


NE

Re-uptake 1

Vasoconstriction

1

Phentolamine - 1 and 2 blockade Prozosin - 1 blockade

NE

(-)

Effects of Alpha-Receptor Blockade on

Vascular Smooth Muscle Tone

2

VSMC
Vasodilation
Vasodilation

● Non-selective 1, 2

BETA ANTAGONISTS
● ‘Cardio’- Selective 1
Propranolol
Nadolol
Timolol
Pindolol
Carteolol


Intrinsic
Sympathomimetic
Activity

Atenolol
Metropolol
Esmolol
Acebutolol (ISA)
● Non-selective
1, 2, 1

Labetalol

Carvedilol

INDIRECT ACTING ADRENERGIC

AGONISTS
Tyramine (dietary substance)

Cocaine

Tricyclic Antidepressants
Uptake Blockers


PRESYNAPTIC
POSTSYNAPTIC
NE

Re-uptake 1

Action

 / 

Receptor
Binding

NE

Cocaine

PRESYNAPTIC
POSTSYNAPTIC

Re-uptake 1

Action


 / 
Receptor
Binding

NE

Cocaine

NE

X
cocaine

Guanethadine

Inhibits NE release, also causes NE depletion, and can damage NE neurons
Neuronal Blockers
Reserpine
Depletes NE stores by inhibiting vesicular uptake of NE, NE then metabolized by intra-neuronal MAO

Pargyline

Monoamine Oxidase (MAO) Inhibitors
Tranylcypromine
Tyramine (or other drugs that promote NE release) may cause markedly increased blood pressure in patients taking MAO inhibitors