*Inhibition of Peripheral a-receptors

1. Non-compet inhibition (long acting phenoxybenzamine). not immediate but lasts long bc receptors are PERMANENTLY inactivated by drug. IRREVERSIBLE. Synthesis of new receptors can restore functions.

2. Compet inhib (all drugs except phenoxy) short in onset and reversible

3. Dec BP by dec peripheral arterial resistance bc block a1 vasoconstriction

Too much loss of a-receptor functions in body

-ex: nasal congestion, difficulty ejaculating, reflex tachycardia, systemic fluid retention, orthostatic hypotensive symptoms

Long acting, blocks a1 and a2

-Used in preventing severe hypertension from pheochromocytoma prior to surgery

- better than other drugs bc massive release of catechol from tumor cant overcome drug's irreversible blockade

-blocks extrasynaptic a2 receptors

-*Remember: a2 rec are first to face high circulating NE and E levels in pheo patients

1. may inhibit histamine, serotonin, Ach receptors

2. Miosis, sedation, drowsiness, vomiting, lethargy (CNS)

3. Shock and circulatory failure

Effects of:

Phentolamine 

- short acting, blocks a1 and a2, reversible

- used to DIAGNOSE pheochromocytoma (phentolamine test), also used during surgery to prevent rise in bp from catech released from tumor

- used to reverse excessive systemic vasoconstriction and hypertension from I.V. overdose with non-spec a-agonists like NE

- prevent local dermal tissue necrosis at sites of injection of a-agonists (ex if accidently inject in skin and not vein)

- ORAVERSE: reverses oral soft-tissue anesthesia from local anesthetics with vasoconstrictor (like Epi). <dental anesthetic reversal agent>

1. Nausea, vomiting, diarrhea

2. Increased GI motility, bad for ULCERS

3. May stimulate or block various non-adrenergic receptors

Effects of: 

Prazosin

-Prototype of selective a1 blockers

-useful in LONG TERM treatment of mild to moderate primary hypertension, esp when given with diuretic (offsets fluid retention)

- Relaxes smooth muscle of bladder sphincter, to inc urinary flow when u have dec urinary flow (BPH)

- Used for Raynaud's

- Maybe for nightmares/PTSD, likely to inhibit central a1 rec (CNS effects)

1. Orthostatic HYPOtension, but only severe during 1st day (first dose phenomenon)

2. Salt and water retention (so take diuretic)

3. Tachycardia but not as much as with non-selective drugs

- dont get into CNS (remember, prazosin does)

- newer a1 blockers than prazosin

-half lives are much longer so might be better for long term control of chronic hypertension bc need fewer doses

Effects of:
Tamsulosin and Silodosin

(FlowMax and RapaFlow) 

- Block subtype alpha-1A, found in smooth muscle of bladder sphincter and prostate

- treat BPH (by inc urination) bc more specific w/less systemic vascular actions/side effects 

-can still cause abnormal ejaculation due to a-1a in vas deferens

Effects of: 

Alfuzosin

-a1 blocker, treats BPH, not subtype selective

- has UROselectivity (accumulation in prostatic tissue), won't interfere w/ejaculation