Sympathomimetics and Lytics
Sympathomimetics and Lytics
Sympathomimetics and Lytics
AND
SYMPATHOLYTICS
NAME-BISWAJIT SAHOO
H.T NO – 23PH201A01
M. PHARM PHARMACOLOGY
SCHOOL OF PHARMAY
DEPARTMENT OF PHARMACOLOGY
ANURAG UNIVERSITY
OVERVIEW
INTRODUCTION
RELEASE OF ADRENERGIC NEUROTRANSMITTER
ADRENERGIC RECEPTOR
CLASSIFICATION OF SYMPATHOMIMETICS
MECHANISM OF ACTION OF DRUG
THERAPEUTIC USES
Sympathomimetic :
- Neurotransmitter – NA , Ach
- Pre ganglion – shorter
-Post ganglion – longer
RELEASE OF ADRENERGIC NEUROTRANSMITTER
Step involve in release of neurotransmitter
synthesis :
. vesicular membrane actively take up dopamine from cytoplasm and final step of synthesis of
NA takes place in side the vesicles
. In Adrenal medulla NA is formed with in chromaffin granules diffuse out in to cytoplasm and
methylated then adrenaline is formed
CLASSIFICATION OF SYMPATHOMIMETICS
DIRECT SYMPATHOMIMETICS :-These are the drugs which are directly acts to the alfa or
beta receptors or both of the receptor
ex .Adrenaline ,noradrenaline ,isoprenaline ,methixamine,xylometazoline,solbutamol.
• Uses:
• Used mainly in cardiac arrest (Parenteral).
• Rarely in acute attack of asthma (inhalation).
• Contraindicated in hyperthyroidism & CHD
MECHANISM OF ACTION
Amphetamine
• Synthetic non-catecholamine.
• amphetamine addicts use sodium bicarbonate to obtain the “kick”.
• Acts indirectly, it depletes vesicles from stored NE -Tachyphylaxis
• has CNS stimulant effect
• Increase euphoria - causes its abuse
• decrease Weight - decrease appetite - increase energy expenditure
Mixed-Acting Sympathomimetics -
Ephedrine
• use for treatment of bronchial asthma and hay fever .
• It is the vasopressor of choice in pregnancy because due to β2
mediated vasodilatory action
• Ephedrine is a non-catechol ,it has high bioavailability and a relatively long
duration.
• Crosses BBB, it is a powerful stimulant.
• Repeated dosing – tachyphylaxis
PHARMACOLOGICAL ACTION
CVS :
Heart
Increase in heart rate and force of contraction
Followed by reflex bradycardia. Increase
cardiac output.
Blood vessels :
Adrenaline constricts artery due to alpha effect
Dilation due to action
Beta receptor more sensitive than alpha receptor.
• Blood pressure :
NA increase systolic ,diastolic and mean BP
Respiratory System:
• Adrenaline and isoprenaline produce a powerful relaxation of smooth
muscle of bronchi, through stimulation of adrenoceptors.
• Adrenaline produce transient apnoea due to inhibition of respiratory centre.
High dose of Adrenaline cause pulmonary edema by shifting blood from systemic
to pulmonary circuit.
• Noradrenaline does not produce any significant action .
GIT:
• Both a and ß adrenoceptor are inhibitory in nature.
• Produce relaxation of smooth muscle.
• Thus decrease in tone and motility.
Eye:
• Mydriasis occur due to contraction of radial muscle of iris (al).
This effect is minimum after topical application because Adrenaline
penetrate cornea poorly.
• Intraocular tension tends to fall in wide angle glaucoma
Urinary Bladder:
• Detrusor muscle is relaxed and trigone is constricted.
• Cause retention of urine.
Uterus:
•Response of uterus is dependent on state of uterus.
• Human uterus is constricted by adr. and noradr., if it is non
pregnant.
• This action is mediated through a adrenoceptor.
• Pregnant uterus is again constricted in first two trimester by
adrenaline.
depression.
• Metabolic:
• Produce hyperglycemia by enhancing glycogenolysis.
Lipolysis.
•
Hyperkalaemia
1.Palpitations
2.Anxiety
3.Trachycardia
4.Loss of appetite
5.Insomnia
6.Hypertension
Adrenergic Antagonist /Sympatholytics
• An adrenergic antagonist is a drug that inhibits the function of adrenergic
receptors .
Adverse effects
•Postural hypotension ( less with α1 selective - venodilatation is less)
•Reflex tachycardia ( less with α1 selective)
•Salt and water retention
•Nasal stuffiness
•Miosis
•Failure of ejaculation
α1 Selective Blockers
CARDIAC EFFECTS:
• Beta 1 blockade - decrease in Heart rate and myocardial contractility - decreased
Cardiac output .
• Effects on HR and C.O. prominent during exercise or in presence of sympathetic
nervous system activity
• HR slowing lasts longer than negative inotropic effect
• decrease peripheral vascular resistance
• Can relieve myocardial ischemia
• Sodium retention may be associated due to intrarenal hemodynamic changes
(decrease C.O. )
Therapeutic Uses
Propranolol is indicated for the management of various conditions
Hypertension
Angina pectoris
Tachyarrhythmias
Myocardial infarction
Hyperthyroidism
Essential tremor
Side effect
Common side effects of propranolol:
Chronic Trouble Sleeping Less Severe
Feeling Weak Less Severe
Low Energy
Pharmacokinetics:
• Readily absorbed from GIT, offset by substantial first pass metabolism
• Low protein binding
• No active metabolite
• Two formulations: metoprolol tartarate, metoprolol succinate
• Elimination T ½ =2-3 hours
ESMOLOL
• Rapid onset , Short acting .
• Selective beta1 adrenergic receptor antagonist
• Only IV
• Useful in phaeochromocytoma and perioperative management of thyrotoxicosis,
pregnancy induced HTN, epinephrine or cocaine induced cardiotoxicity)
Pharmacokinetics
• available for IV administration
• PH 4.5-5.5 (commercial preparation)
• compatible with commonly used IVF and NMBD
• Elimination T ½ = 9 minutes
• Rapid hydrolysis in plasma by esterase
• Independent of hepatic and renal clearance
• Poorly lipid soluble
α + β Blocker
LABETALOL
• Selective alpha1 and nonselective beta1 & beta2 adrenergic antagonist effect
• Presynaptic alpha2 receptors are spared
• Beta : alpha potency -oral labetalol - 3:1
• IV labetalol-7:1
• Pharmacokinetic : Conjugation with glucuronic acid
• 5% drug recovered unchanged in urine elimination T ½ =5-8 hours (prolonged in liver
disease, unchanged in renal dysfunction)
CVS EFFECTS:
• alpha blockade - decreases systemic vascular resistance - decrease BP
• Beta blockade - attenuates reflex tachycardia
• Cardia output unchanged
• Vasodilatation is caused by alpha 1 blockade and beta2 agonist activity
CLINICAL USES
• Hypertensive emergencies
• Useful in pheochromocytoma
• clonidine withdrawal
• Excessive doses 2mg/kg iv - excessive decrease in BP
• Small doses 20-80mg - undesirable decrease in BP
Side effect
• Postural hypotension
• Bronchospasm in suspected patients
• In case of prolonged therapy - fluid retention - therefore combined with diuretics
• Rashes and liver damage