Adrenergic blocking agents: Lect 8 Flashcards
what is the short term effect of beta blockers on blood pressure
- negative inotropic and chronotropic effect which slows the heart and decreases contractility
- relaxation of skeletal muscle vasculature: B2 receptor blocked
- decreased CO increases sympathetic input -> an initial rise in peripheral resistance due to blockade of β2 receptors in blood vessels, allowing the effect of α receptors to become dominant
what is the long term effect of beta blockers on blood pressure
There may be an initial rise in peripheral resistance due to blockade of β2 receptors in blood vessels, allowing the effect of α receptors to become dominant. Over time, however, peripheral resistance returns to normal and blood pressure goes down
Effects of beta blockers on respiration
- causes Bronchoconstriction
Beta blockers will inhibit the vasodilation caused by β2 receptors, increasing the pressor effect of epinephrine. They should never be given to someone with pheochromocytoma without administering what drugs
concomminant administration of an alpha blocker!
why should beta-blockers not be given in people who have asthma/COPD
Beta-blockers causes bronchoconstriction and can be fatal!
- beta1 selective drug might be tolerated
function of beta-blockers in the eye
- lowers intraocular pressure
- decreases formation of aqueous humor
why should beta blockers be used with great caution in insulin dependent Type I diabetics
- Glycogenolysis mobilizes glucose in response to hypoglycemia. This effect is decreased by β antagonists
- In normal patients, when glycogenolysis and gluconeogenesis are inhibited, release of glucagon in response to hypoglycemia acts to increase the blood glucose
- in type I diabetics, the glucagon response becomes impaired, and inhibition of glycogenolysis and decreased release of glucose from the liver due to beta blockade may impair the ability of diabetics to recover from hypoglycemia
- Furthermore, beta antagonists will mask the normal symptoms of hypoglycemia, such as tremor and shakiness.
Beta blockers have what effect on lipolysis, VLDL, and HDL?
- inhibts lipolysis in fat cells (beta 3)
- increases VLDL and decreases HDL
Beta blockers with local anesthetic activity (acebutolol, labetalol, metoprolol, pindolol, propranolol) should not be used in the eye because
- they will anesthetize the cornea
- corneal damage/scratching can occur
MOA of propranolol
- competitive antagonist at B1 and B2 receptors
Propranolol has what CV effects
- Slows heart rate and decreases force of contraction
- Slows conduction through the A-V node
Propranolol has what effect on renin and glycogenolysis
- decreases renin (B1)
- decreases glycogenolysis (B2)
What beta blockers can be used as a local anesthetic
- acebutolol
- labetalol
- metoprolol
- pindolol
- propranolol
pharmacokinetics of Propranolol
- route of administration
- can it enter CNS?
- where is it metabolized
- oral
- lipid soluble, enters CNS -> sedation
- metabolized in the liver, cytochrome P450
clinical uses of propranolol
- treats HTN: not first line agent
- decreases mortality following MI
- improves symptoms of angina: decreases O2 demand
- treat arrhythymias
- improve long-term survival in stable congestive heart failure
- Useful to slow heart and decrease blood pressure in hyperthyroidism
- prevent migraine
- decrease sympathetic symptoms of stage fright
- Decreases catecholamine-induced tremor
Main side effect of beta blockers
- Bronchoconstriction
- do not use in asthmatics or COPD
- Bradycardia
- abrupt discontinuation -> arrhythmias
- exercerbate unstable heart failure
Why should a person not take Cimetidine (Antacid and Antihistamine) and Propranol together
- Cimetidine inhibits cytochrome P450 and will increase effects of propranolol -> bradycardia
MOA and clinical use of Timolol
- non-selective beta blocker
- used in eye to treat glaucoma
- caution in asthma
What are the three beta 1 selective blockade drugs that have effects primarily on the heart
- Metroprolol
- Atenolol
- Bisoprolol
Metroprolol, Atenolol, and Bisoprolol have what effects on the heart? clinical uses?
- decrease HR and contractility
- decrease oxygen consumption and demand
- decrease renin release -> decrease blood pressure
- used for treatment of HTN, increase life expectancy after MI, and migraine proplylaxis
Why does taking selective beta 1 blocking agents give a better exercise tolerance?
- There is no block of B2 effect on blood vessels to skeletal muscle
Why does taking selective beta 1 blocking agents better to use to diabetes ?
- No block on B2 gives less of an effect on glycogenolysis
MOA and clinical use of Betaxolol (Betoptic)
- selective β1 blocker
- used for treatment of glaucoma
- It is thought to be less likely to cause bronchoconstriction when used in the eye than timolol.
MOA of Nebivolol (Bystolic)
- Beta 1 selective blocker that also produces vasodilation
- produces vasodilation due to NO release
- Most selective drug for β1 receptors currently available
MOA and clinical use of Esmolol (Brevibloc)
- VERY short acting beta 1 blocker
- half-life 8 min
- Must be injected intravenously
- Used when very short β blockade is wanted, or in critically ill patients in whom it may be necessary to rapidly remove the β-blocker effect
β- Antagonists with intrinsic sympathetic activity (ISA): what does this mean?
- beta blockers that have partial agonist activity
- stimulate receptors when sympathetic activity is low
- reduce effects when (NE, epi) is high
- may decrease risk of bronchoconstriction or bradycardia
MOA of Pindolol (Visken), carteolol (Cartrol), and penbutolol (Levatol)
non-selective β blockers which have some intrinsic sympathomimetic activity (ISA)- that is, they are partial agonists
MOA and clinical use of carteolol (Cartrol)
- non-selective β blockers which have some intrinsic sympathomimetic activity (ISA)
- used in eye to treat glaucoma
- fewer systemic effects than timolol
MOA of Acebutolol
- selective β1 antagonist which has some intrinsic sympathomimetic activity (ISA)
MOA of Labetalol and Carvedilol
- Blocks β1 and β2 receptors, as well as α1 receptors
- α1 blockade leads to relaxation of arterial smooth muscle and decreased blood pressure
- β1 blockade prevents a compensatory increase in heart rate, so that the decrease in blood pressure is less likely to cause tachycardia than when α-blockers are used alone
clinical use of Labetalol
- blocks B1, B2, and A1 receptors
- Administered IV for the treatment of hypertensive emergencies
clinical use of Carvedilol (Coreg)
- blocks B1, B2, A1 receptors
- used in CHF, post MI
DOC in treatment of glaucoma
- Prostaglanin analogues (Iatanoprost-Xalatan)
- increases uveoscleral outflow and increase flow through trabecular meshwork
What beta blockers are commonly used in the treatment of glaucoma
-
Timolol
- non-selective blocker, placed in eye. May be absorbed and cause bronchoconstriction
- Betaxolol
- B1- selective blocker. Fewer side effects but also less effective
What alpha 2 agonists are commonly used in the treatment of glaucoma? MOA?
- Brimonidine and Apraclonidine
- decrease production of aqueous humor
- cause vasoconstriction
- increase outflow directly by increasing prostaglandins
MOA of carbonic anhydrase inhibitor in the treatment of glaucoma
- decrease production of intraocular fluid
What drug class is used primarily in narrow angle glaucoma
- cholinergic agonists: pilocarpine
- affect vision**
MOA of Guanethidine (Ismelin)
- inhibits NE release from nerve terminals
- needs to enter presynaptic terminal: cocaine will prevent effect
- loss of sympathetic tone occurs with time
side effects of Guanethidine (Ismelin)
- was once used in the treatment of severe hypertension. It is no longer used
- it causes complete loss of sympathetic activity
- postural hypotension
- decreased blood flow to the brain and heart
- problems with ejaculation in men
- diarrhea
MOA of Reserpine
- Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals.
- It will cause depletion of norepinephrine, dopamine and serotonin, both from the peripheral nerve terminals and in the brain
side effects of Reserpine
- Low doses decrease blood pressure, possibly as a result of central effects, similar to methyldopa
- Side effects include severe diarrhea, depression, sedation, and Parkinson’s-like symptoms
- **No longer used clinically
MOA of Metyrosine
- blocks tyrosine hydroxylase; rate limiting step in formation of L-DOPA from tyrosine
- inhibits synthesis of dopamine, NE, and Epi
clinical use of Metyrosine
- treatment of pheochromocytoma if alpha blockers are not sufficient to control BP
