THIS CLASS IS IN BRIEF FOR UNDER GRADUATE UNDERSTANDING AND EXAMINATION PURPOSE

1. ANTI ADRENERGIC
(SYMPATHOLYTIC) DRUGS
DR RAGHU PRASADA MS
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2. ANTI ADRENERGIC (SYMPATHOLYTIC) DRUGS
•DRUGS BLOCK THE ACTIONS OF CIRCULATING CATECHOLAMINE (EP & NE)
ON ADRENERGIC RECEPTORS
•ALSO INHIBITTHE EFFECTS OF ADRENERGIC NERVE STIMULATION

3. ADRENERGICRECEP
TOR
ALFA 1 ALFA2
LOCATION POST JUNCTIONAL ON EFFECTOR
ORGANS
PREJUNCTIONAL ON NERVE ENDINGS , ALSO
POST-JUNCTIONAL IN BRAIN, PANCREATIC BETA CELLS AND
EXTRA JUNCTIONAL IN BLOOD VESSELS, PLATELETS
FUNCTION GI SMOOTH MUSCLES-CONTRACTION
GLAND-SECRETION
GUT- RELAXATION
LIVER-GLYCOGENESIS
HEART-ARRHYTHMIAS
INHIBITION OF TRANSMITTER RELEASE
VASOCONSTRICTION, DECREASED SYMPATHETIC FLOW
NEGATIVE FEEDBACK CAUSES LESS NOREPINEPHRINETO BE
RELEASED SO BP IS REDUCED
DECREASED INSULIN RELEASE
PLATELET AGGREGATION
SELECTIVE
AGONIST
PHENYLEPHRINE
METHOXAMINE
CLONIDINE
SELECTIVE
ANTAGONIST
PRAZOCIN, TERAZOCIN
TAMSULOSIN
YOHIMBINE, ROUWOLCINE
EFFECTIVE
PATHWAY
IP3/DAG, PHOSHOLIPASEA2
PG RELEASE
CAMP
K+ channel, Ca CHANNEL, IP3 /DAG

4. ALPHA ADRENOCEPTOR ANTAGONISTS
NONEQUILIBRIUM TYPE: Β-HALOALKYLAMINES: PHENOXYBENZAMINE
EQUILIBRIUM: I. NONSELECTIVE: 1. ERGOTS: ERGOTAMINE AND ERGOTOXINE 2.
HYDROGENATED ERGOT ALKALOIDS: DHE, DIHYDROERGOTOXINE 3.
IMIDAZOLINES: TOLAZOLINE, PHENTOLAMINE
4. SELECTIVE Α-1: PRAZOSIN, TERAZOSIN, DOXAZOSIN AND TAMSULOSIN,
ALFUZOSIN
SELECTIVE Α-2: YOHIMBINE, IDAZOXAN

5. PHARMACOLOGICAL EFFECTS
•ANTAGONISM OF Α-RECEPTORS OF ARTERIOLES & VEINS 
DECREASE PVR, DECREASE BP
•2) PREVENT PRESSER EFFECT OF USUAL DOSES OF Α-AGONISTS 
DEPRESSOR EFFECT
• POSTURAL HYPOTENSIONPOSTURE IS CHANGED FROM SITTINGTO
UPRIGHT POSITION SUDDEN FALL IN BP (POOLING OF BLOOD IN
EXTREMITIES DUE TO GRAVITY)
•4) REFLEX TACHYCARDIA USUALLY BY NON-SELECTIVE BLOCKERS

6. PHARMACOLOGICAL EFFECTS
•NASAL CONGESTION (DILATATION OF BLOOD VESSELS OF NASAL MUCOSA)
2) BLOCKING OF Α 1 RECEPTORS OF DILATOR PUPILLAE MUSCLES MIOSIS+
DECREASED INTRAOCULAR PRESSURE
•3) BLOCKING OF Α 1 RECEPTORS OF TRIGONE+SPHINCTOR MUSCLES 
RELAXATIONURINARY OUTFLOW

7. PHARMACOLOGICAL EFFECTS
•1)NON-SPECIFIC Α 1+ Α 2 ANTAGONIST
•A)PHENTOLAMINE IMIDAZOLINE-DERIVATIVE PHARMACODYNAMICS:MOA BLOCKS
BOTH Α 1+ Α 2-RECEPTORS
• ANTAGONISM OF Α 1–RECEPTORS (POSSIBLY Α 2) OF VASCULAR SM.MUSCLES 
DECREASE PVR AND DECREASE BP  CARDIAC STIMULATION IN RESPONSE TO
BAROREFLEX MECHANISM
• ANTAGONISM OF PRESYNAPTIC Α 2-RECEPTORS RELEASE OF NE FROM
SYMPATHETIC NERVES CARDIAC STIMULATION

8. PHARMACOLOGICAL EFFECTS
•INHIBITS RESPONSE TO SEROTONIN, AGONIST OF MUSCARINIC, H1 & H2
HISTAMINE RECEPTORS
•INHIBITIONOF EJACULATION – DUE TO INHIBITION OF CONTRACTION OF VAS
DEFERENS AND OTHERS
•CLINICAL USE: PHEOCHROMOCYTOMA, CLONIDINE WITHDRAWAL, CHEESE
REACTION AND IN EXTRAVASATIONS OF NA AND ADR INJECTION PREVENT TISSUE
•NECROSIS & MALE ERECTILE DYSFUNCTION
•ADVERSE EFFECTS: TACHYCARDIA, ARRHYTHMIAS, MYOCARDIAL ISCHEMIA,
DIARRHOEA, GASTRIC ACID PRODUCTION

9. PHENOXYBENZAMINE
PHARMCODYNAMICS
MOA IRREVERSIBLE (COVALENT) BINDING TO Α-RECEPTORS ( SELECTIVE FOR Α1)
LONG DURATION (14-48 H) BLOCKADE
EFFECTS: INHIBITS REUPTAKE OF NE BY PRE-SYNAPTIC NERVE TERMINALS
BLOCKS H1, ACH & 5-HT RECEPTORS
BLOCKS CATECHOL-INDUCED VASOCONSTRICTION
DECREASE BP DURING HIGH SYMPATHETIC TONE (UPRIGHT POSITION)
INCREASE CO  REFLEX EFFECT + BLOCKADE OF Α2 RECEPTORS

10. PHENOXYBENZAMINE
•USUALLY GIVEN ORALLY  WITH LOW STARTING DOSE OF 10-20 MG/D
ADVERSE EFFECTS
•POSTURAL HYPOTENSION, TACHYCARDIA, NASAL STUFFINESS, INHIBITION
OF EJACULATION, FATIGUE, SEDATION AND NAUSEA

11. SPECIFIC Α1 ANTAGONISTS
•PRAZOSIN -PIPERAZINYL QUINAZOLINE, HIGHLY SELECTIVE FOR Α1
RECEPTORS,
•LOW AFFINITY FOR Α2 ( TACHYCARDIA )
•MOA BLOCKS Α1 RELAXATION OF ARTERIAL AND VENOUS SM. MUSCLES
•EXTENSIVELY METABOLIZED BY LIVER, 50% DRUG IS AVAILABLE AFTER ORAL
ADMINISTRATION
•TERAZOSIN- MOA REVERSIBLE Α1 SELECTIVE ANTAGONIST
•USES HYPERTENSION & BENIGN PROSTATIC HYPERPLASIA (BPH)
BIOAVAILABILITY - HALF LIFE IS 9-12 H

12. DOXAZOSIN
•MOA HIGHLY SELECTIVE FOR Α1 RECEPTORS,
•LOW AFFINITY FOR Α2
•PK: MODERATE BIOAVAILABILITY,
•LONGER HALF LIFE OF ~ 22 H, EXTENSIVELY METABOLIZED
•USES HYPERTENSION & BPH
TAMSULOSIN MOA: COMPETITIVE Α1 ANTAGONIST, STRUCTURALLY D/F FROM
OTHERS, UROSELECTIVE (VASICOSELECTIVE) - Α1A AND Α1D BUT NOT Α1B
• VERY HIGH BIOAVAILABILITY, LONG HALF LIFE (9-15H)

13. TAMSULOSIN
NO CHANGE IN BP AND HR AT THERAPEUTICDOSES AND POSTURAL HYPOTENSION
PREFERRED DRUG IN BHP
ONLY ONCE DOSING REGIME (MR CAPS)
USES: EFFECTIVE FOR BPH (Α1A )
ADRS: RETROGRADE EJACULATION AND DIZZINESS

14. SPECIFIC Α2 ANTAGONISTS
•TOLAZOLINE SIMILAR TO PHENTOLAMINE,
•RARELY USED CLINICALLY FOR PULMONARY HYPERTENSIONIN NEW BORNE
•B) YOHIMBINE -- INDOLE ALKALOID, SELECTIVE Α2 ANTAGONIST ,
NO CLINICAL ROLE, RESEARCH DRUG
ERGOT DERIVATIVES-ERGOTAMINE, DIHYDROERGOTAMINE CAUSE REVERSIBLE Α-
RECEPTOR BLOCKADE, NO CLINICAL EFFECT

15. CLINICAL USES
•PHEOCHROMOCYTOMA TUMOR OF ADR.MEDULLA; RELEASES MIX OF EP, NE; PATIENTS
HAVE ↑BP, TACHYCARDIA, ARRHYTHMIA
•MAJOR CLINICAL USE OF PHENOX. & PHENTOLAMINE
•PHENOXYBENZAMINE USED IN A) PREOPERATIVE EPISODE =ORAL DOSE OF 10-20
MG/D INCREASED IN SEVERAL DAYS B) CHRONIC TREATMENT OF INOPERABLE OR
METASTATIC CONDITIONC) PHENTOLAMINE USED TO MANAGE ↑BP

16. CLINICAL USES
•2) HYPERTENSIVE EMERGENCIES
•LIMITED USE OF Α-ANTAGONIST, ONLY LABETALOL IS USED
•3) CHRONIC HYPERTENSION MEMBERS OF PRAZOSIN FAMILY ARE
EFFECTIVE FOR MILD TO MODERATE SYSTEMIC HYPERTENSIONMAJOR
ADVERSE EFFECT IS POSTURAL HYPOTENSION, DIZZINESS

17. CLINICAL USES
4) PERIPHERAL VASCULAR DISEASE PHENTOLAMINE,PRAZOSIN,PHENOXYBENZAMINE
RAYNAUD’SPHENOMEN; EXCESSIVE REVERSIBLE VASOSPASM IN PERIPHERAL
CIRCULATION
5) LOCAL VASOCONSTRICTOR EXCESS PHENTOLAMINE REVERSE INTENSE LOCAL
VASOCONSTRICTION CAUSED BY INFILTRATION OF Α-AGONISTS INTO
SUBCUTANEOUS TISSUES

18. CLINICAL USES
URINARY OBSTRUCTION
PARTIAL REVERSAL OF SM MUSCLE CONTRACTIONIN ENLARGED PROSTATE & IN
BLADDER BASE B) EFFECT ON CELLS IN PROSTATE & IMPROVE SYMPTOMS OF BPH E.G.
PRAZOSIN, DOXAZOSIN & TERAZOSIN USEFUL FOR BPH + HYPERTENSIVE PATIENTS
TAMSULOSIN EFFECTIVE FOR THOSE BPH PATIENTS HAVING POSTURAL HYPOTENSION
7) ERECTILE DYSFUNCTION E.G PHENTOLAMINE

19. THANK YOU
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