Autonomic Nervous System 1. Function of the Autonomic Nervous System 2.
Autonomic Nervous System (ANS)jude.edu.sy/assets/uploads/lectures/Chapter 2 Autonomic... ·...
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Autonomic Nervous
System (ANS)
Chapter 2
Ali Jaber, Ph.D.
MS in Pharmacy
MS in Pharmaceutical Chemistry
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Organization of The Nervous System
Central Nervous System Peripheral Nervous System
Somatic Nervous System Autonomic Nervous System
Sympathetic Parasympathetic
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Organization of the Peripheral
Nervous System Three major divisions:
– Efferent
» Somatic (motor)
» Autonomic
Sympathetic and Parasympathetic
– Afferent
» Sensory
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The Peripheral Nervous System
Sensory
Motor
Sympathetic
Parasympathetic
Parasympathetic
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Autonomic Nervous System
2 divisions:
– Sympathetic
» “Fight or flight”
» “E” division
Exercise, excitement, emergency, and embarrassment
– Parasympathetic
» “Rest and digest”
» “D” division
Digestion, defecation, and diuresis
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Sympathetic (adrenergic) with exceptions)
cardiac output increases
SA node: heart rate (chronotropic)β1, β2: increases
cardiac muscle: contractility (inotropic)β1, β2: increases
conduction at AV nodeβ1: increases
vascular smooth muscle M3: contracts; α = contracts; β2 = relaxes
smooth muscles of bronchiolesβ2: relaxes (major contribution); α1: contracts (minor contribution)
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Sympathetic (adrenergic) with exceptions)
pupil of eyeα1: relaxes
ciliary muscleβ2: relaxes
salivary glands: secretionsβ: stimulates viscous, amylase secretions; α1 = stimulates potassium cation
smooth muscles of GI tractα, β2: relaxes sphincters of GI tractα1: contracts
glands of GI tractinhibits
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Parasympathetic (muscarinic)
cardiac output M2: decreases
SA node: heart rate (chronotropic) M2: decreases
cardiac muscle: contractility (inotropic) M2: decreases (atria only)
conduction at AV node M2: decreases
smooth muscles of bronchioles M3: contracts
pupil of eye M3: contracts
ciliary muscle M3: contracts
salivary glands: secretions stimulates watery secretions
GI tract motility M1, M3: increases
smooth muscles of GI tract M3: contracts
sphincters of GI tract M3: relaxes
glands of GI tract M3: secretes
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Function Sympathetic and parasympathetic divisions
typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic.
For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake.
The sympathetic division typically functions in actions requiring quick responses.
The parasympathetic division functions with actions that do not require immediate reaction. Consider sympathetic as "fight or flight" and parasympathetic as "rest and digest".
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The Synapse
Gap between the axon and the dendrite
Neurotransmitters are released across this gap
Sometimes, if all of the transmitter isn’t absorbed it is
taken back up, this is known as reuptake
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There is lots of variation in synapses
Some are excitatory (Type I)
Some are inhibitory (Type II)
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The Seven Steps in
Neurotransmission Synthesis
Storage
Release
Receptor interaction
Inactivation
Reuptake
Degradation
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Mechanism: Acetylcholine Release and
Recycling 1. Acetylcholine synthesized
from choline and acetyl CoA by choline acetyltransferase (ChAT)
2. ACh loaded into synaptic vesicles by VAchT
3. Released ACh broken down by acetylcholinesterase (notable difference from other neuro-transmitters)
4. Choline taken up by presynaptic terminal as precursor to further ACh synthesis
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Mechanism: Norepinephrine Release
and Recycling
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Neurotransmitters and Receptors
The parasympathetic nervous system uses only
acetylcholine (ACh) as its neurotransmitter.
The ACh acts on two types of receptors, the
muscarinic and nicotinic cholinergic receptors.
Most transmissions occur in two stages: When
stimulated, the preganglionic nerve releases ACh at
the ganglion, which acts on nicotinic receptors of the
postganglionic nerve.
The postganglionic nerve then releases ACh to
stimulate the muscarinic receptors of the target organ.
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Summary of parasympathetic neurons
and synapses
Preganglionic neurons Long
Synapse with postganglionic neurons at or near organ
Release acetylcholine (ACH) to activate nicotinic receptors on
postganglionic neurons
Postganglionic neurons Short
Synapse on the target organ
Release acetylcholine (ACH) to activate muscarinic receptors on
the target organ
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Neurotransmitters and Receptors
At the effector organs, sympathetic ganglionic
neurons release noradrenaline (norepinephrine) to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla:
Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream which will act on adrenoceptors, producing a widespread increase in sympathetic activity.
In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter, to stimulate muscarinic receptors.
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Summary of sympathetic neurons
and synapses
Preganglionic neurons Short
Synapse with postganglionic neurons near spinal cord
Release acetylcholine (ACH) to activate nicotinic receptors on
postganglionic neurons
Postganglionic neurons Long
Synapse on the target organ
Release norepinephrine to activate adrenergic receptors on target
organs
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Sweat glands: » Postganglionic neurons
involved with stress-related
excretion release
norepinephrine (“sweaty
palms”)
» Postganglionic neurons
involved with
thermoregulation release
acetylcholine
Exceptions in the sympathetic nervous system:
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Kidneys: » Postganglionic neurons to the
smooth muscle of the renal
vascular bed release dopamine
Adrenal gland: » Preganglionic neurons do not
synapse in the paraverterbral
sympathetic ganglion
» Preganglionic neurons synapse
directly on the adrenal gland,
release acetylcholine, and
activate nicotinic receptors on
the adrenal gland
» Adrenal glands release
epinephrine into systemic
circulation
Exceptions in the sympathetic nervous system:
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How do drugs influence the ANS?
Mimic or block the effects of the two primary neurotransmitters,
Acetylcholine and Norepinephrine/Epinephrine
Drugs that mimic neurotransmitters are referred to as “receptor
agonists”
These drugs activate receptors
Drugs that block neurotransmitters are referred to as “receptor
antagonists”
These drugs block the endogenous neurotransmitters from
activating receptors
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Classification of drugs affecting the ANS
Parasympathetic nervous system Mimic acetylcholine = cholinergic = muscarinic agonists =
parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist =
parasympatholytic
Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist =
sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist =
sympatholytic
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Adrenergic Receptors
Adrenergic receptors are the sites where adrenergic drugs bind and produce their effects.
Adrenergic receptors are divided into alpha-adrenergic and beta-adrenergic receptors depending on whether they respond to norepinephrine or epinephrine.
Both alpha- and beta-adrenergic receptors have subtypes designated 1 and 2.
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Alpha Receptors
Alpha1-adrenergic receptors are located on the
postsynaptic effector cells.
Alpha2-adrenergic receptors are located on the
presynaptic nerve terminals.
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Beta Receptors
Both beta-adrenergic receptors are located on the
postsynaptic effector cells.
Beta1-adrenergic receptors are primarily located in
the heart.
Beta2-adrenergic receptors are primarily located in
the smooth muscle of bronchioles, arterioles, and
visceral organs.
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Dopaminergic Receptors
Dopaminergic receptors are only stimulated by
dopamine which causes the vessels of renal,
mesenteric, coronary, and cerebral arteries to dilate
and the flow of blood to increase.
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Adrenergic Receptor Specificity
Drug α1 α2 β1 β2 Dopaminergic
Epinephrine
Ephedrine
Norepinephrine
Phenylephrine
Isoproterenol
Dopamine
Dobutamine
terbutaline
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• The adrenengic drugs supplement, mimic & reinforce the message transmitted by the natural neuro hormones norepinephrine & epinephrine.
• These hormones are responsible for transmitting nerve impulses of the sympathetic nervous system.
Sympathomimetic (Adrenergic) Drugs
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ADRENERGIC AGONIST
Alfa agonist: 1. Norepinephrine 2. Epinephrin 3. Dopamine 4. Dobotamine(doubetrex) 5. Clonidina (catapress) 6. Metildopa (aldomet) 7. Phenilephrine (afrin)
Beta agonist: 1. Albuterol 2. Formoterol 3. Salmoterol
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1) Albuterol or salbutoml (Ventolin)
Class.: sympathomimetic agent, bronchdialtor
Action: stimulate β 2 receptors of the bronchi leading to bronchodilation.
Uses:
- Bronchial asthma.
- Bronchospasm due to bronchitis or emphysema.
- Parenteral for treatment of status asthmaticus.
ADRENERGIC AGONIST
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1) Albuterol or salbutoml (Ventolin)
Side effects:
Tachycardia, arrhythmias, anginal pain.
Nausea, vomiting.
Dizziness, sweating, flushing.
Headache, weakness, vertigo, and insomnia.
ADRENERGIC AGONIST
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2) Dopamine Hydrochloride (Intropin)
Class: Direct & indirect acting adrenergic agent.
N.B. : Available for hospital use only on 5 ml ampules containing 200 mg dopamin hydrochloride.
Action:
- It is the immediate precursor of epinephrine in the body.
ADRENERGIC AGONIST
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2) Dopamine Hydrochloride
Action:
- It produces direct stimulation of β1 receptors resulting in increasing myocardial contraction, cardiac output as well as increase renal blood flow & sodium excretion.
- It exerts little effect on diastolic B.P. & induce fewer arrhythmias that seen on other adrenergics drug.
ADRENERGIC AGONIST
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Indications:
- Cardiogenic shock specially in Myocardial Infarction associated with sever Congestive Heart Failure
- Hypotension due to poor cardiac output.
- Shock associated with septicemia, trauma, heart surgery, renal failure & C.H.F.
- Cardiomyopathy.
- In lower doses (1-5 Mcg/kg/min) used in renal failure.
ADRENERGIC AGONIST
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Contraindications:
- Pheochromocytoma, uncorrected tachycardia, arrhythmias.
- Hypovolemia.
- Safety and efficacy is not established in children.
Side effects:
- GI: Nausea and vomiting.
- CV: tachycardia or bradycardia, anginal pain, palpitation, hypotension or hypertension, dyspnea.
ADRENERGIC AGONIST
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3) Epinephrine:
Trade name: Adrenaline
Class : Direct acting-adrenergic agent.
Action:
A natural hormone produced from adrenal medulla, induce
marked stimulation of alpha, β1 + β2 receptors causing
cardiac stimulation, bronchodilation & decongestion..
ADRENERGIC AGONIST
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3) Epinephrine:
Uses:
1- Relief of respiratory distress due to
bronchospasm.
2- Rapid relief of hypersensitivity reactions.
3- Cardiac arrest.
4- Open- angle glaucoma.
5- To prolong the action of local anesthesia.
6- Topically to stop bleeding.
ADRENERGIC AGONIST
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3) Epinephrine:
Contraindications:
- Narrow angle glaucoma.
- Shock
- Lactation.
- Tachycardia
Side effects:
Fatal ventricular fibrillation.
Cerebral hemorrhage urinary retention, headache, necrosis
at injection side, blurring of vision, photophobia.
ADRENERGIC AGONIST
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3) Epinephrine:
Dose:
Available in ampules of 1ml containing 1 mg adrenaline
Can be given by I.M injection., I.V. & S.C.
0.2 – 0.5 mg, IM or S.C. + Q 20 min – 4 hr as needed.
ADRENERGIC AGONIST
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4) Dobutamine (Dobutrex)
Indications: In adults who require short-term treatment of cardiac failure secondary to acute myocardial infarction, or cardiac surgery.
Contraindication: DOBUTREX is contraindicated in patients with idiopathic hypertrophic subaortic stenosis
ADRENERGIC AGONIST
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4) Dobutamine (Dobutrex)
Adverse effects:
GI: Nausea and vomiting.
CV:
a) tachycardia or
b) bradycardia,
c) anginal pain
d) palpitation
e) hypotension or hypertension
f) dyspnea
ADRENERGIC AGONIST
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ADRENERGIC ANTAGONIST
Alfa antagonist: Alfazusin (Xatral) Prazosin (Cardura) yohimbin
Beta antagonist 1. Propanolol (Inderal) 2. Bisoprolol (concor) 3. Atenelol (tenormin) 4. Carvidolol (dilatrand) 5. Timolol (cospot)
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ADRENERGIC ANTAGONIST
1) Propranolol hydrochloride(Inderal)
Classification: beta-adrenergic blocking agent, antiarryhthmic.
Action: manifests both beta1 and beta 2 adrenergic blocking activity.
Indication:
1. Angina pectoris. 2. Hypertension.
3. Cardiac arrhythmias. 4. Prophylaxis of migraine.
5. Prophylaxis of MI. 6. Pheochromocytoma
Dosage: Tablets: initial dose of 40 mg bid
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ADRENERGIC ANTAGONIST
Propranolol hydrochloride(Inderal)
Contraindications:
• Bradycardia,
• C.H.F.
• diabetes,
• chronic bronchitis
• asthma
• emphysema
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ADRENERGIC ANTAGONIST
Propranolol hydrochloride(Inderal) Side effects:
• psoriasis-like eruptions.
• Bradycardia,
• C.H.F.
• hypotension,
• dyspnia, shortness of breath
• Nausea and vomiting
• bronchospasm
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ADRENERGIC ANTAGONIST
2) Bisoprolol fumarate.(Concor)
Indications: Hypertension and angina pectoris.
Contraindications:
• Acute heart failure
• Bradycardia
• Hypotension
• Severe bronchial asthma or severe chronic obstructive pulmonary disease.
Dose: 5 mg/10 mg once daily
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ADRENERGIC ANTAGONIST
2) Bisoprolol fumarate.(Concor) • Adverse effects:
• Bradycardia,
• C.H.F.
• hypotension,
• cold extremities (due to peripheral vasoconstriction)
edema
• dyspnia, shortness of breath
• Nausea and vomiting
• bronchospasm
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ADRENERGIC ANTAGONIST
3) Atenolol: (Tenormin)
Classification: beta 1 –adrenoreceptr blocking drug which
is a cardioselective.
Uses: Hypertension angina pectoris.
Dosage: Tablets: 50 mg or 100 mg daily
IV in case of acute MI: give 5 mg over 5 minutes, and if
there is no response, give another 5 mg after 10 minutes.
Specific nursing considerations:
3. For IV use, the drug may be diluted in sodium chloride,
dextrose, on dextrose saline.
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ADRENERGIC ANTAGONIST
General considerations:
1. Instruct patient/family to take blood pressure and pulse.
2. Provide written instructions as when to call physician (e.g. HR below 50 beat/min).
3. Instruct patient to dress warmly during cold weather.
4. Diabetic patient should be very careful about symptoms of hypoglycemia.
5. Report any asthma-like symptoms.
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ADRENERGIC ANTAGONIST
Alfazusin (Xatral)
Indication: Treatment of the functional symptoms of benign prostatic hypertrophy (BPH)
Contraindications:
• history of orthostatic hypotension;
• combination with other alpha-1 receptor blockers;
• hepatic insufficiency.
Dosage: 10 mg once daily
Side effects: tachycardia, palpitations, hypotension (postural)
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Parasympathomimetic (cholinergic) Drugs
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Parasympathomimetic (cholinergic) Drugs
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Cholinergic drugs have the following
pharmacological effects on various structures:
1- GIT: - Enhance secretion by gastric & other
glands & this may cause:
nausea & vomiting.
Increase smooth muscle tone & stimulate bowel
movement.
3. GU system: Stimulation of ureter & relaxation of
urinary bladder resulting in micturation .
Action of cholinergic agonist
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4. Cardiac muscle:
- Slowing heart rate (Bradycardia).
- Decrease atrial contractility, impulse formation &
conductivity.
5. Blood vessels: Vasodilation skin temperature &
local flushing.
Action of cholinergic agonist
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6. Respiration: Mucus secretion & bronchial
constriction wheezing. coughing, shocking (specially
in asthmatic patients).
7. Eyes: Pupillary constriction (miosis), in intraocular
pressure.
8. Skin: activation of sweat & salivary glands
Action of cholinergic agonist
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Classes of cholinergic agonist
Direct-acting
Receptor agonists
Choline esters ACETYLCHOLINE
BETHANECOL
Alkaloids PILOCARPINE
Cholinesterase inhibitors
Carbamates PHYSOSTIGMINE
NEOSTIGMINE
PYRIDOSTIGMINE
EDROPHONIUM
Phosphates ISOFLUROPHATE
Antidote
PRALIDOXIMINE
Indirect-acting
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Direct Acting Agonist
1) Betanechol (Urecholine) p.o or sc
Action: Stimulant of the smooth muscle of the GI
tract and the urinary bladder.
Uses:Urinary retention and inadequate emptying of
the bladder;
- postoperative
- postpartum urinary retention
Adverse effects: sweating, salivation, diarrhea
bradicardia, nausea and bronchospasmo
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Direct Acting Agonist
2) Carbachol (moistat) eye drops
Uses: Only to treat glucoma
Adverse effects: no systemic absorbtion at the doses
used
3) Pilocarpine nitrate(Salagen)
Chief alkaloid in pilocarpus
Uses: in emergency to treat glucoma
Dose: 1 gtt of 1-4 % solution
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Indirect Acting (reversible inhibitors of Achestrase)
1. Pyridostigmine Bromide (Mestinon)
Class. : Indirectly acting, cholinergic-
acetylcholinestrase inhibitor.
M of Action: inhibiting REVERSIBILY the enzyme
cholinestrase, that lead to increase the concentration
of acetylcholine at the myoneural junction which
facilitate the transmission of nerve impulse across the
myoneural junction, that lead to increase muscle
strength in myasthenia gravis.
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1. Pyridostigmine Bromide (MESTINON)
N.B. :
- It has a slower onset, longer duration of action &
fewer side effects than neostigmine.
- Atropine may be given to control side effects.
Uses: Myasthenia Gravis.
Contraindication:
- Hypersensitivity - Bradycardia
- Hypotension - Asthma
Indirect Acting (reversible inhibitors of Achestrase)
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1. Pyridostigmine Bromide (MESTINON)
Side effects:
Skin rash, thrombophlebitis after I.V. use
Nausea, vomiting, diarrhea.
Bradycarda, Hypotension, headache, dizziness.
Urinary frequency (Incontinence) , bronchosporn.
Dose: Tab. 600 mg daily.
Indirect Acting (reversible inhibitors of Achestrase)
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2) Neostigmine Bromide (Prostigmin).
Uses: Maestenia Gravis and atonic bladder
Dose: Tab. 150 mg daily.
All information as pyridostigmine.
Indirect Acting (reversible inhibitors of Achestrase)
3)Physostigmine salicylate(Eserine salicylate.)
Uses: For the treatment of glaucoma, and in the
treatment of severe anticholinergic
toxicity(atropina)
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General considerations:
1- In case of systemic absorption Have adrenaline &
atropine available for emergency treatment.
2- Stress the importance of taking eye drops exactly
as prescribed
3- Minimize side effects by taking medication at bed-
time.
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General considerations:
4- Advice client not to drive a car for 1-2 hrs after
administering eye drops.
5- Notify the physician, if side effects occurred.
6- Cold compresses for painful eye spasms.
7- Frequent eye examinations.
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Cholinergic Antagonists
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Cholinergic Antagonists(Parasympatholytic)
M. Of Action:
These agents prevent the neurotransmitter acetylcholine from
combining with receptors on the muscarinic site & nicotonic site.
The main effects:
1- Reduce spasm of smooth muscle such as spasm of the urinary
bladder or intestines.
2- To block vagal impulses to the heart which will increase heart rate
& conductivity.
3- To suppress or decrease gastric secretions, perspiration, salivation
and secretion of bronchial mucus.
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Cholinergic Antagonists(Parasympatholytic)
The main effects:
4- To relax the sphincter muscles of the iris & cause pupillary dilation
(mydriasis) & loss of accommodation for near vision.
5- Act on CNS producing such reactions as depression (scoplamine) or
stimulation (toxic dose of atropine) to produce antiparkinsonism
effect.
Contraindications:
Glaucoma, myocardial ischemia, Prostate hypertrophy,
Myasthenia gravis, paralytic ileus,
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Cholinergic Antagonists(Parasympatholytic)
Side effects:
Nausea,
vomiting, dry mouth,
constipation, dizziness,
headache,
insomnia, blurring of vision,
photophobia, flashing, euphoria.
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Cholinergic Antagonists (Parasympatholytic)
1) Atropine sulfate:
Class.: Cholinergic blocking agent.
Action:
It is a parasympatholytic agent which cause relaxation of smooth
muscles & inhibition of secretary glands.
Uses:
- Treatment of spastic disorders of biliary tract .
- During anesthesia to control salivation & bronchial secretions.
- Ophtalmolgy as cycloplegic
- Prophylaxis and treatment of toxicity due to cholinestrase inhibitor
including organophosphate pesticides.
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Cholinergic Antagonists (Parasympatholytic)
1) Atropine sulfate:
Contraindications: See parasympatholytics
Side effects: See parasympatholytics
Dose:
Tablets: 0.3 – 1.2 mg Q 4-6 hr
Available in 1ml-ampoule containing 1 mg atropine.”
IM, I.V. & S.C. 0.4 – 0.6 mg Q 4-6 hour for anticholinergic action
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Cholinergic Antagonists (Parasympatholytic)
2) Scopalamine Hydrobromide (Hyoscine).
M.O.Action : depress the cerebral cortex, especially the
motor area, act as a powerful hypnotic.
Uses:
1- Motion sickness ( prevention and control of nausea and vomiting).
2- With other narcotics to treat biliary and renal colic.
N.B. N-Butil scopalamine (Buscopan) used as spasmolytic with
success in intestinal cramps as in severe cramps during menstrual
cycle
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Cholinergic Antagonists (Parasympatholytic)
2) Scopalamine Hydrobromide (scopinal).
Contraindications:
- Hypersensitivity. - Glaucoma
- Bronchial asthma - Cardiac arrhythmias
- Pregnancy - Lactation.
Side effects:
Pupil dilation, photophobia, headache,
Dry mouth, constipation, nausea, vomiting. tachycardia, Suppression
of lactation.
.
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Cholinergic Antagonists (Parasympatholytic)
3) Ipratropium bromuro (Atrovent) only by inhalation
Indications: asthma as substitute of beta agonist
and chronic obstructive pulmonary diseases (COPD)
- Side effects: no systemic absorption duo to positive
charge