3. ALPHA 1 RECEPTOR
Excitatory effect in most organs, EXCEPT intestine (relaxation)
Calcium dependent K channel open – relaxation
Liver: glycogenolysis gluconeogenesis
4. LOCATION OF ALPHA 1 RECEPTOR
Alpha1A Prostatic urethra and Bladder sphincter contraction
Gluconeogenesis
Glycogenolysis
Alpha 1B Vasoconstriction
Alpha 1D Prostatic urethra and Bladder sphincter contraction
Vasoconstriction
5. ALPHA 2 RECEPTOR
Presynaptic: Decrease nor epinephrine release
Inhibit calcium channel and open k+ channel – relaxation
Presynaptic cholinergic receptor – inhibit release of acetylcholine
Postsynaptic in
Brain – decrease sympathetic outflow
Platelet – cause aggregation
Beta cell of pancreas - inhibit insulin release
Blood vessel – vasoconstriction
6. LOCATION OF ALPHA 2 RECEPTOR
Alpha 2A Decrease NE release
Alpha 2B Vasoconstriction
Alpha 2C Inhibit dopamine release in CNS
Inhibit catecholamine release from adrenals
Insulin release is inhibited by both alpha 2A and 2B
7. OTHER EFFECTS
Nasal stuffiness: vasodilation and congestion of mucosa
Miosis: radial muscle
Improve urinary flow: relax bladder
8. CONTROL OF NE RELEASE
• Beta receptor activate at low
concentration
• Alpha stimulated by higher
concentration
13. PHENOXYBENZAMINE
Oral
Treatment of pheochromocytoma
Pre operative – decrease hypertension risk in pheochromocytoma surgery
Alpha blocker followed by beta blocker (to reverse cardiac effect of excess
catecholamine)
14. PHENOXYBENZAMINE
Side effect
Orthostatic hypotension and reflex tachycardia – can precipitate
arrhythmias
Not used in hypertension
Nasal stuffiness and inhibition of ejaculation
Enters the CNS, it may cause less specific effects including fatigue, sedation,
and nausea.
15. PHENTOLAMINE
Used for erectile dysfunction
Control of hypertension in pheochromocytoma
Rapid infusion: hypotension risk
Hypertensive crisis following clonidine withdrawal, cheese reaction
Reverse local anaesthesia in soft tissue sites
local anaesthetics are often given with vasoconstrictors that slow their removal
Minor inhibitory effects at serotonin receptors and agonist effects at
muscarinic and H1 and H2 receptors
20. TAMSULOSIN
Higher affinity for α1A and α1D receptors than for the α1B subtype.
Less postural hypotension
α1A on iris: risk of the intraoperative floppy iris syndrome (IFIS)
Characterized by the billowing of a flaccid iris, propensity for iris prolapse,
and progressive intra-operative pupillary constriction
Ejaculation abnormalities
24. ROLE IN CHF
Dilation of both arteries and veins,
Reduction of preload and after load, which increases cardiac output and
reduces pulmonary congestion
Not been found to prolong life in patients with CHF
Location of subtype not known
Diff in mech not known
Selective 1 a antagonist – Tamsulosin
Stimulation of subtype : ince calcium and cause contraction at bv uterus bronchi radial muscle etc
in
MOST ORGAN : VASCULAR SMOOTH MUSCLE, SALIVARY GLAAND, BRONCHI, IRIS URINARY BLADDER, LIVER CELL
Irreversible : duration of action depends on restoration of tissue responsiveness after extensive α-receptor blockade is dependent on synthesis of new receptors, which may take several days.
Reversible : depends on half life
Venodilation : postural hypotension
Phenoxybenzamine forms a reactive ethyleneimonium intermediate (Figure 10–1) that covalently binds to α receptors, resulting in irreversible blockade
PATIENT PREPRATION
1-3 WK
1O MG BD
Starting with dosages of 10 mg/d; increasing dose until the desired effect is achieved up to 100 mg/day
Beta-receptor antagonists may be required after α-receptor blockade has been instituted to reverse the cardiac effects of exces-sive catecholamines.
since unopposed β-receptor blockade could theoretically cause blood pressure elevation from increased vasoconstriction
. The half-life of terazosin is 9–12 hours.
Doxazosin is efficacious in the treatment of hypertension and BPH. It differs from prazosin and terazosin in having a longer half-life of about 22 hours.
Apoptosis appears to be related to the quinazoline moiety rather than α1 receptor antagonism
Urapidil is an α1 antagonist and weak α2-agonist and 5-HT1a-agonist actions and weak antagonist action at β1 receptors
are not usually recommended as monotherapy for hypertension because other classes of antihypertensives are more effective in preventing heart failure. T
