sympathomimetics 30 31
TRANSCRIPT
-
7/28/2019 Sympathomimetics 30 31
1/27
Sympathomimetics
Dr Attia & dr Razza
1430-1431
2009-2010
-
7/28/2019 Sympathomimetics 30 31
2/27
Autonomic Nervous System
-
7/28/2019 Sympathomimetics 30 31
3/27
ANS is divided into
Sympathetic Parasympathetic
Origin From all thoracic andupper 3 lumber
segments
From cranial 3,7,9,10
and Sacral 2,3,4
segments
Character Short preganglionic
and long postganglionicfibres
Long preganglionic and
short postganglionic
-
7/28/2019 Sympathomimetics 30 31
4/27
Autonomic Nervous System
-
7/28/2019 Sympathomimetics 30 31
5/27
ANS Stimulation - Response
Structure Sympathetic
Stimulation
Parasympathetic
StimulationFight & fright or flight Rest & digest
HeartHR
AV conduction
VentricularBlood Vessels
Tachycardia
Vasoconstriction &
Dilatation
Bradycardia
No effectVasodilation of some vessels
Smooth muscleEye
BronchiGIT
Urinary Bladder
Mydriasis
BronchodilationRelax wall, Contract Sphincters
Urine retention
Miosis
Bronchospasm(Contract)Contact Wall & Relax sphincters
Micturation
SecretionsSalivary
Sweat
Thick viscid ()
(Perfuse watery)NO effect
Sex Organs Ejaculation Erection
-
7/28/2019 Sympathomimetics 30 31
6/27
Adrenergic receptors
Receptor Location Effect1 Postsynaptic in smooth
Muscle of
Blood vessels
GIT & Urinary
sphincters
Vasoconstriction
contraction
2 Presynaptic NA release
1 Heart
Kidney
Rate and Contraction Renin release
2 Sm. Muscle ofBlood vessels
Bronchi
Intestine
Urinary
liver
Relaxation
Relaxation
Relaxation
Relaxation
glycogenolysis
3 Adipose tissue Lipolysis
-
7/28/2019 Sympathomimetics 30 31
7/27
Alpha-1 receptors Sites; mainly post-synaptic on effector organs
Actions:= Contractions
1. Smooth m of BVVC (skin, MM, renal)TPR
hypertension
2. Spasm of GIT & urinarysphincters
3. Contraction of DPMmydriasis
4. Ejaculation & contraction of prostatic capsule
5. Contraction of pregnant uterus
6.
Viscid salivation7. Facilitate neuromuscular transmission
8. Pilomotor smooth muscleerection of hair
Specific agonists: Phenylephrine
Specific antagonists:Prazocin
-
7/28/2019 Sympathomimetics 30 31
8/27
Alpha-2 receptors1. Sites:1. CNS 2. Presynaptic 3. postsynaptic (some
organs)
2. Actions: Inhibition Except1. CNSsedation sympathetic centers
2. Presynaptic (autoreceptors)
1. Release of NA
2. Release of Ach in enteric gangliarelax of wall GIT
3. Kidneyrelease of renin
4. Pancreas release of insulin
5. Fat cellsLipolysis
6. Eye:aqueous humor formation
7. Platelets aggregation & Some vascular BV
3. Selective agonist: Clonidine
4. Selective anta onist:Yohimbine
-
7/28/2019 Sympathomimetics 30 31
9/27
Beta- receptorsB1
Heart
B2
Bronchi (SM)
B3
Fat cellsPresynaptic release of Noradrenaline
Postsynaptic CNS
Anxiety
BV vasodilation
sk m BV
Fat cells
Lipolysis
HeartCOP
BronchodilationRelax GIT, UB, uterus
thermogenesis
Kidney
renin
Glycogenolysis
Liver, muscle
Fat cells
Lipolysis
FFA
Release of insulin
K uptake by Sk m
SK M tremors
Selective agonist Dobutamine Salbutamol Octopamine
Selectiveantagonist
Atenolol Butoxamine??
-
7/28/2019 Sympathomimetics 30 31
10/27
General notes on
Sympathetic receptors
1. Alpha + beta relax wall of GIT
2. Alpha-1 contraction of pregnant uterus +
VC while B-2 the opposite
3. Alpha-2 lipolysis While Beta1 + beta-3
lipolysis
4. Alpha-2 Renin While beta1 renin
5. Alpha-2 Insulin while Beta 2Insulin6. Dopamine D1 receptors (on renal and
splanchnic, coronary BVVasodilatation
-
7/28/2019 Sympathomimetics 30 31
11/27
-
7/28/2019 Sympathomimetics 30 31
12/27
Noradrenaline (Norepinephrine; NA)
Synthesis
Tyrosine +OH DOPA (+MAO)(-CO2)Dopamine (+OH) Noradrenaline (Inside granules)
In adrenal medulla & some areas in bra`
NA is the chemical transmitter at postganglionicsympathetic (Exception Sweat glands/ BV) andinside CNS.
-
7/28/2019 Sympathomimetics 30 31
13/27
-
7/28/2019 Sympathomimetics 30 31
14/27
Adrenergic SystemTermination of
(nor)epinephrine action:1. Reuptake into presynaptic nerve
ending; 80%
Predominant mechanism
active transport; inhibited byCocaine & TCA
2. Catechol-O-methyltransferase (COMT)
In the cytoplasm of post-junctional
cells
3. Monoamino-oxidase (MAO)
In mitochondria of nerve and post-
junctional cells
4. Presynaptic a2-receptors Negative feedback that inhibits
norepinephrine release
-
7/28/2019 Sympathomimetics 30 31
15/27
-
7/28/2019 Sympathomimetics 30 31
16/27
-
7/28/2019 Sympathomimetics 30 31
17/27
Sympathomimetics (Adrenergic Agonists)
Classification
-
7/28/2019 Sympathomimetics 30 31
18/27
I. Catecholamines
A. Epinephrine (Adrenaline) Direct ( 1,2, 1, 2, 3)Pharmacological Actions:
1. CVSCardiac stimulation (1) actionHR, contractility,Vasoconstriction, BP2. Smooth muscle:Stimulation of 2 receptors in GIT and Bronchi
Relaxation
3. Eye: Mydriasis (1)
4. Metabolic: Hyperglycemia & Lipolysis
Therapeutic Uses:1. Cardiac arrest (intracardiac injection)2. Anaphylaxis It is antidote to histamine. (In anaphylactic shock histamine release vasodilation severe hypotension antagonized by Epinephrine Inj. 1:1000Dilution)
3. Prolongation of action of local anesthetics-Epistaxis
4. Acute bronchial asthma
Side effects: 1, 1, 2,1. CVS: hypertension, cerebral hemorrhage, cardiac arrhythmia, tachycardia,palpitation, Angina, MI
2. CNS: Nervousness, tremors
Contraindications:
Hypertension, hyperthyroidism, Diabetes mellitus, coronary arterydisease, CHF, old patients
-
7/28/2019 Sympathomimetics 30 31
19/27
I. Catecholamines Contd
1. B. Norepinephrine (NA) (1, 2, 1, 3) Effects are predominantly on
1
, has stimulant effect on 1
receptorsof heart, No 2 action.
Used in
1. Shock, weaker metabolic effects than epinephrine.2. Why norarenal ine can cause abor tion bu t Ad .no t?
3. What is the ef fec t o f alpha b locker on Ad & Norad?
4. What is the effect on Noradrenaline on HR?
C. Dopamine (D1, B1, 1) Precursor of epinephrine and norepinephrine, Low conc. Of Dopamine
stimulate D1 receptors in renal vessels, mesentryvasodilatation,renal blood flowuseful in cardiogenic & hypovolemic shock
At high Conc. Stimulate 1receptors in the heart+ve inotropicand contractlity & higher concentration1-receptorsBloodpressure
USES:
Various shock (Cardiogenic shock & Septic shock, &
Refractory heart failure & acute renal dysfunction
-
7/28/2019 Sympathomimetics 30 31
20/27
I. Catecholamines Contd
D. Isoprenaline (Isoproterenol); Beta only (B1,B2)1. Powerful action on
1
& 2
receptors, no effect on receptors
2. Used in emergency to HR (1 effect) in bradycardia &
3. heart block & Bronchial asthma
4. Expect its adverse effects? Contraindicaons?
5. In a table form compare between adr, noradr., isopren.?
As regards (Receptors-BP-pulse pressure-HR-uses)
E. Dobutamine: Selective 1 Selective 1 action contractility > than HR t very short (2min), given by IV route
Used to treat cardiogenic shock (improves contractility, O2consumption)
1. Resistant heart failure& heart block
2. myocardial infarction
3. After cardiac surgery
-
7/28/2019 Sympathomimetics 30 31
21/27
II. Selective 2 agonist
Salbutamol: Selective 2 Stimulates 2 receptors selectively located in
bronchi Bronchodilatation.
Used in bronchial asthma
by inhalation or Orally.
Ritodrine
Selective stimulant for2
receptors in uterusuterine relaxation.
Used as prophylactic in repetitive abortion or
premature labor.
-
7/28/2019 Sympathomimetics 30 31
22/27
III. Selective 1 agonist
Phenylephrine: Stimulates 1 receptors inBV vasoconstriction it activates receptors only at much higher conc.
uses1.Hypotension by
intravenous infusion.
2. Nasal decongestant3. Mydriatic in various
ophthalmic formulations
-
7/28/2019 Sympathomimetics 30 31
23/27
IV. Selective 2 agonistClonidine & -methyldopa (Aldomet)
Clonidine & -methyldopa (Aldomet) C-2,P-2,R-2) They act on presynaptic 2 receptorsstimulationrelease NE in CNSCsympathetic discharge fromCNSVasodilatation/BP (& HR) + (I1-receptor)
Clonidine is used to treat
1. Hypertension (renal patients)2. Autonomic neuropathy in diabetics, migraine, IT analgesic
3. Withdrawal symptoms in addicts (Tobacco-morphine), menopause
4. Can you use them in glucoma? Why?
Side effects: Hypertension, Stop rebound, sedation,
bradycardia, constipation, and sexual dysfunction
-methyldopa (Aldomet) is used to treat (C-2,P-2,R-2)
hypertension during pregnancy & renal impairment. Why?
Side effects: Sedation, depression, postural hypotension,edema, hemolytic anemia (Allergic), impotence
-
7/28/2019 Sympathomimetics 30 31
24/27
V. Indirect acting agonistsAmphetamine, Ephedrine act by releasing noradrenaline at sympathetic
nerve endings, they have marked effects on CNS
AmphetaminePharmacological actions
A. Indirect: Stimulation of -adrenergic receptors BP (like NA but weaker,slower, longer, with tachyphylaxis)
b. CNS: Strong CNS stimulant effect:1. Small dose: alertness, wakefulness, mental activity, delays mental fatigue, improves
physical performance Euphoria But followed by Fatigue, depression.
2. Moderate dose: Anxiety, nervous tension, tremors.3. Large dose: Abnormal behaviour (Parania like syndrome), hyperthermia, convulsion
4. Appetite suppressant
5. Medullary centers & Spinal reflexes
Therapeutic Uses: Produces addiction (Obsolete)1. Attention deficit disorder in children (No addiction) (methyphenidate)
2. Narcolepsy (No Addiction)3. Obesity, psychic depression
Side Effects
1. CNS: irritability, tremors, restlessness, hallucination, paranoia, suicide
2. CVS: palpitation, hypertension, arrhythmia
3. Tolerance, addiction
-
7/28/2019 Sympathomimetics 30 31
25/27
V. Indirect acting agonists
Ephedrine: Like adrenaline But1. Dual action: Mainly indirect (weaker, slower, longer & tachyphylaxis
2. CNS stimulant: < amphetamine
Actions: Found in many dietary supplements: Energy-Boosters, Dietpills (Metabolife) etc.
A. local1. Nose decongestion
2. Eye: decongestion + mydriasisB. Systemic:1. CNS stimulant: Insomnia, anxiety, Medullary C, Spinal reflexes
2. CVS: Heart, BP
3. Smooth muscles like adrenaline
4. Skeletal muscle stimulant
Uses:1. Analeptic2. ADHD-Bronchial asthma
3. Mydriatic-nasal decongestant-Nocturnal enuresis
4. Prevent hypotension in spinal anesthesia
Adverse effects; Contraindications1. CNS
2. CVS retention of urine in old age3. Tolerance & tachyphylaxis but not addiction
-
7/28/2019 Sympathomimetics 30 31
26/27
Sympathomimetics Clinical uses
-
7/28/2019 Sympathomimetics 30 31
27/27
Questions for Revision of sympathomimetics?A. Classify sympathomimetics according to their nature?
B. Classify them accordring o their chemistry?
C. Classify them according to mechanism of action?D. Classify them according to their selectivity complete;
1. Selective alpha-1 agonist like
2. Selective Alpha2 agonist like.
3. Non selective Alpha1 + alpha 2 like.
4. Selective B1 agonist like.
5. Selective B2 agonist like.6. Non selective B1 + B2 like..
7. Alpha1+ Alpha2 + B1+B2+B3 like
8. Alpha1 + Alpha2 + B1 +B3 like
9. D + B1 + Alpha1 like
10. Vasopressor like
11. Nasal decongestant like12. Added to local anesthetic like
13. Cardiac stimulant.
14. Vasodilator like.
15. Uterine relaxant like.
16. Anorexigenic like.
17. CNS stimulant like..