Adrenergic Antagonists Flashcards
What are adrengergic antagonists mainly used for? In the case of alpha antagonists, what phsyiological variables do they target? Beta?
- used for blood pressure and BPH
- alpha: used to reduce TPR (blood pressure is an alpha tone)
- Beta: management of cardiac work
What drugs are the non-specific alpha antagonists? Alpha 1 selective antagonists? Non specific beta antagonists? Selective beta-1 antagonists? Alpha 2 selective antagonists? NE depleting agents? (DRUG LIST)
- non specific alpha antagonists: phenoxybenzamine, phentolamine
- alpha 1 selective antagonists: prazosin, tamsulosin
- non-specific beta antagonists: propranolol, nadolol, pindolol, sotolol, carvedilol, timolol
- selective beta-1 antagonists: metoprolol, atenolol, esmolol
- alpha 2 selective antagonists: yohimbine
- NE depleting agents: guanethidine, reserpine
How do you categorize non-specific alpha antagonists (alpha blockers)? Use?
-non-specific alpha antagonists either bind covalently and are therefore long-acting (phenoxybenzamine) or are reversible and short acting (phentolamine and tolazoline). used in the control of pheochromocytoma.
How are alpha 2 blockers named? What is the alpha 2 blocker that we need to know for the exam? for boards? discuss applications and toxicity for boards drug?
with an -osin ending (prazosin, terazosin, doxazosin, tamsulosin)
- alpha 2 for class: yohimbine
- alpha 2 for boards: mirtazapine. used in depression and toxicity is sedation, increased serum choolesterol, and increased appetite
What are some additional benefits of beta blockers outside their antagonism?
-possess partial agonist activity and local anesthetic actions
What is the classic triad of symptoms with patients w/ pheochromocytoma? What cells make this tumor type and what is its embroyolic origin? What do the cells look like? What is the RUle of 10? (first aid)
- triad of episodic headaches, diaphoresis (sweating), and tachycardia
- derived form chromaffin cells (those that make catecholamines)
- arises from neural crest cells
- cancer cells are enlarged dysmorphic nuclei typical of malignancy
- Rule of 10: 10% malignant, bilateral, extraadrenal, calcify, and kids
What disease is pheochromocytoma associated with? symptoms? findings, and treatment? (First aid)
- findings: pressure, pain, perspiration, palpitations, pallor (symptoms occur in spells)
- associated w/ von Hippel Lindau disease, MEN 2A and 2B
- findings: urinary VMA (a breakdown product of noepi and epi) and plasma concentrations elevated
- treatment: first with phenoxybenzamine and then with a b-blocker followed by tumor resection (alpha before beta so you avoid hypertensive crisis)
What is phenoxybenzamine MOA, effects, clinical use, toxicity, and pharmacokinetics?
- MOA: irreversible. covalent binding to alpha 1»alpha 2 and is non-surmountable. Requires re-synthesis of receptor to reinstate function
- effects: blocks SANS activity; little effect on BP when patient in supine (no SANS), but significant orthostatic hypotension when rising and light headedness when standing. After this, HR and CO will increase reflexively, nasal stuffiness, inhibition of ejaculation, and sedation reflecting its entry into CNS
- clinical: pheochromocytoma used preop to prevent hypertensive crisis
- pharmo: long acting due to covalent binding (48 hrs)
What is phentolamine? MOA? Effects? Clinical use? pharmo?
- MOA: reversible, competitive inhibitor of both alpha receptors
- effects: same as phenoxybenzamine w/ less sedation. Due to alpha 2 blockage, leads to greater cardio-stimulation since baroreceptor reflexes are more pronounced due to less attenuation of NE release acting through autoreceptors
- clinical use: give to patients w/ MAO inhibitors who eat tyramine-containing foods
- pharmo: short acting so used in surgery to alter changes in BP
What is the rationale for giving a alpha blocker before a beta blocker in the treatment of pheochromocytoma?
- to allow the alpha blocker to full titrate the receptors. If beta blocker given too quick, faster acting beta blocker will markedly increase BP due to its beta effects in muscle (vascular pooling) leading to significant drops in BP w/ potentially harmful effects.
- alpha blocker will cause vasodilation and will block the baroreceptor reflex because alpha receptors are what respond in this reflex. beta receptors will try to upreg to increase hr to increase BP so you give beta blocker afterwards
what is the MAO, effects, clinical use, and toxicity for alpha 1 selective receptors?
- MAO: specific, reversible, competitive antagonists for alpha 1
- effects: marked reduction in TPR with little reflex cardiac stimulation
- clinical use: hypertension and BPH
- toxicity: 1-st dose orthostatic hypotension, dizziness, headache
What are symptoms of BPH? comobilities? treatment? and receptors in prostate?
- symptoms: increased urinary freq, urgency, urgency incontinence, nocturia, urination may involve interrupted stream and hesitancy.
- comob: reduced voiding leads to increased risk of infections and stone formation
- treatment: tamsulosin, competitive alpha 1 blocker w/ greater affinity for 1a and 1d alpha 1 receptors
- receptor subtype: alpha 1 1a
How does Yohimbine? Effects? Clinical use?
- Yohimbine is an alpha 2 blocker used clniically. it can be used to treat orthostatic hypotension. As an alpha 2 antagonist it prevents released NE from acting on its auto-receptor. The absence of this negative feedback will actually increase the amount of released NE, which can then act on alpha 1 receptors as well as beta receptors.
- Effects: increases NE release by preventing normal feedback inhibition of NE on its autoreceptor. can also increase Ach release by inhibiting alpha 2 receptors located on cholinergic terminals
- orthostatic hypotension and ED
What are common uses of beta blockers? Discuss propranolol MOA? effects? clinical use? pharmacokinetics? toxicity?
- management of blood pressure, angina, chronic heart failure, ,and following infarctions, glaucoma, local anesthetic
- MOA: competitive non-specific beta antagonist w/ some local anesthetic action.
- Effects: reduces beta tone. w/ beta 1 effects, negative inotropic and chronotropic effect limits heart’s work to relief angina. Its effect on dromotropy (negative) helps w/ arrhythmias. TPR increases due to loss of beta 2 vasodilation (off set by the reduced beta 1 effects on inotropy and chronotopy). Beta 1 blocking also reduced renin release. Beta 2 blockage prevents skeletal muscle vasodilatation, bronchiole relaxation, and glycogenolysis in liver. Beta 3 prevents lipolysis.
- Clinical: migraine heaches, stage fright, CNS effects and produce sedation, reduces tremor
- pharmoco: biotransformation becomes saturated (zero order). significant first pass. inter-individual variation in bioavailability.
Describe how the renin-angiotensin system works. How does blockers affect the system?
- when blood volume is low, juxtaglomerular cells in kidney secrete renin. Renin stimulates production of angiotensin I from angiotensinogen. Angiotensin I is then converted to angiotensin II by ACE. Angiotensin II causes blood vessel constrict, resulting in increased BP. Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidney to increase the reabsorption of sodium and water in the blood. increased volume leads to increased BP
- beta 1 blockade prevents renin release and initiation of the cascade
