alpha antagonists and beta antagonists test 2

Question 1

endogenous catecholamines (3)

Answer 1

epinephrine
norepinephrine
dopamine

Question 2

CNS neurotransmitters (6)

Answer 2

epinephrine
norepinephrine
dopamine
serotonin
GABA
acetylcholine

Question 3

synthetic catecholamines

Answer 3

isoproterenol

dobutamine

Question 4

catecholamine affinity for alpha receptors in order

Answer 4

norepinephrine>epinephrine>isoproterenol

Question 5

catecholamine affinity for beta receptors in order

Answer 5

isoproterenol>epinephrine>NE

Question 6

a1 physiology: which synapse, organs, action

Answer 6

postsynaptic
vasculature, heart, glands, gut
vasoconstriction

Question 7

a2 physiology: which synapse, organs, action

Answer 7

presynaptic: found in peripheral vascular smooth muscle, coronaries, brain
inhibition of NE release, decrease in BP and HR
postsynaptic (less often): coronaries, CNS. constriction, sedation, analgesia

Question 8

b1 physiology: organs, action

Answer 8

myocardium, SA node, ventricular conduction system, coronaries, kidney
increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, renin release

Question 9

b2 physiology: organs, action

Answer 9

vascular, bronchial, uterine smooth muscle, smooth muscle in the skin, myocardium, coronaries, kidneys, GI tract
vasodilation, bronchodilator, uterine relaxation, gluconeogenesis, insulin release, potassium uptake by the cells (because decreased intracellular calcium activates potassium channels and hyperpolarize cell)

Question 10

ephedrine MOA, action, dose, DOA, SE

Answer 10

mostly indirect action by increasing catecholamine release, also direct. acts on alpha and beta
vasoconstriction, HR increase, inotropy increase. used to increase BP
5-25mg, give in increments of 5-10mg
DOA 15m-1h
SE: tachyphylaxis

Question 11

phenylephrine MOA, uses, dose, DOA

Answer 11

direct a1 agonism
used to increase BP, also used for nasal intubations (nasal spray)
bolus of 50mg or 100-200mcg depending
infusion ranges from 20-100mcg/min
DOA 5-20min
SE: baroreceptor mediated reflex bradycardia

Question 12

a1 signal, 2nd messengers, physiologic response example

Answer 12

excitatory blood vessels
1. PLC activated 2. IP3&DAG 3. PKC and increased free Ca2+ versus?
2. increased calcium, increased ca calmodulin activation, increased actin/myosin interaction, smooth muscle contraction
smooth muscle vasoconstriction

Question 13

a2 signal, 2nd messengers, physiologic response example

Answer 13

inhibitory, blood vessels pre synaptic, CNS post synaptic
1. inhibit adenylate cycle 2. decrease cAMP 3. increase K conductance
decreased cAMP increases smooth muscle contraction and increased K creates hyperpolarization

Question 14

B1,2,3 signal, 2nd messenger output, physiologic response examples

Answer 14

excitatory or inhibitory, depends on cAMP actions

1. activate adenylate cyclase to increase cAMP
2. increased intracellular cAMP relaxes smooth muscle BUT stimulates cardiac contractility

Question 15

where are a1 adrenoreceptors found and what is their action (5)

Answer 15

1. most vascular smooth muscle, contraction
2. iris, contraction (which dilates pupils), mydriasis
3. pilomotor smooth muscle, erects hair)
4. prostate and uterus, contraction
5. heart, increased force of contraction

Question 16

where are a2 adrenoreceptors found and what is their action (5)

Answer 16

1. platelets, aggregation enhancement
2. adrenergic and cholinergic nerve terminals, presynaptic, inhibits transmitter release so decreases BP and HR
3. vascular smooth muscle, contraction (postsynaptic) or dilation (presynaptic, CNS)
4. GI tract, relaxation (presynaptic)
5. CNS, sedation and analgesia via decreased SNS outflow from brainstem

Question 17

where are B1 receptors found and that is their action

Answer 17

heart, kidneys. increases force and rate of contraction, chronotropy and inotropy, stimulation of renin release

Question 18

where are B2 receptors found and what is their action (6)

Answer 18

1. respiratory, uterine, vascular, GI, GU (visceral smooth muscle), promoted smooth muscle relaxation
2. mast cells, decreases histamine release
3. skeletal muscle, potassium uptake, dilation of vascular beds, tremor, increased speed of contraction
4. liver, glycogenolysis
5. pancreas, increased insulin secretion
6. adrenergic nerve terminals, increased release of NE

Question 19

where are B3 receptors found and what is their action

Answer 19

fat cells, activates lipolysis, thermogenesis

Question 20

classes of drugs to treat hypertension

Answer 20

SNS antagonists (B, alpha, mixed, centrally acting a2)
RAAS antagonist (ACEI, ARB, diuretics)
endothelium derived mediator and/or ion channel modulators (direct vasodilators, CCB, K channel opener)

Question 21

hypertension first line therapy

Answer 21

thiazide diuretic unless there is a compelling indication

Question 22

tx goal for 18-59 with no co morbidities or >60 with DM or CKD

Answer 22

140/90

Question 23

tx goal for >60 with no DM or CKD

Answer 23

150/90

Question 24

hypertensive urgency threshold, goal, drug of choice

Answer 24

DBP >120 without end organ damage
goal: decrease DBP to 100-105 within 24h
clonidine

Question 25

hypertensive emergency threshold, goal, drug of choice

Answer 25

>120 DBP with evidence of end organ failure goal: decrease DBP to 100-105 ASAP drugs: nitroprusside, nitroglycerin, labetalol, fenoldapam

Question 26

competitive alpha antagonist examples (3)

Answer 26

phentolamine, prazosin, yohimbine

Question 27

covalently bound alpha antagonists

Answer 27

phenoxybenzamine (DOA long)

Question 28

clinical uses of a1 antagonists (3)

Answer 28

HTN, BPH, Pheochromocytoma

Question 29

which alpha antagonists are a1 selective

Answer 29

prazosin, terazosin, doxazosin, tamulosin

Question 30

which alpha antagonist has moderately higher affinity for alpha 1 than alpha 2

Answer 30

phenoxybenzamine

Question 31

which alpha antagonist has equal affinity for a1 and a2

Answer 31

phentolamine

Question 32

which alpha antagonists have higher affinity for a2 than a1

Answer 32

yohimbe, tolazoline

Question 33

name the mixed alpha and beta antagonists and their affinity for the receptors

Answer 33

labetalol, carvidelol | b1=b2>a1>a2

Question 34

which beta antagonists are selective for b1

Answer 34

metoprolol, atenolol, esmolol

Question 35

which beta antagonists have equal affinity for B1 and B2

Answer 35

propanolol, nadolol, timolol

Question 36

which beta antagonist is beta 2 selective

Answer 36

butoxamine

Question 37

first generation non selective beta antagonists

Answer 37

nadolol, penbutolol, pindolol, propanolol, timolol

Question 38

third generation non selective beta antagonists

Answer 38

carteolol, carvedilol, bucindolol, labetalol

Question 39

GU, eye, nasal effects of alpha antagonists

Answer 39

blockade in prostate and bladder cause muscle relaxation and ease micturition miosis increased nasal congestion

Question 40

Phenoxybenzamine binding, receptor affinity, action, onset, t1/2, uses, dosage

Answer 40

binds covalently non selective but greater affinity for alpha 1 than alpha 2 (less associated tachycardia with decrease in SVR) decreases SVR, vasodilation onset 1h (slow, not great for OR) t1/2 24h (long acting) used preop for control of BP in patients with pheochromocytoma, will start them on this 1-2w pre surgery at .5-1mg/kg used for patients with raynauds

Question 41

Phentolamine receptor affinity, MOA, uses

Answer 41

non selective alpha antagonist produces peripheral vasodilation and decrease in SVR reflex mediated and alpha 2 associated increases in HR and CO used: intraop management of hypertensive emergencies at 30-70mcg/kg pheochromocytoma manipulation autonomic hyperreflexia, tamps this. SQ for extravasation 2.5-5mg

Question 42

Prazosin receptor affinity, actions, uses

Answer 42

selective a1 antagonist less likely to cause tachycardia dilates both arterioles and veins used: preop preparation of patients with pheochromocytoma, essential HTN (combined with thiazides), decreasing after load in patients with heart failure, raynauds (PO drug)

Question 43

Yohimbine receptor affinity, action, uses

Answer 43

(not used so much anymore) alpha 2 selective blocker increases release of NE from post synaptic neuron used with orthostatic hypotension, impotence

Question 44

Terazosin and Tamulosin receptor affinity, action, uses, t1/2 consideration, SE

Answer 44

long acting selective alpha 1 antagonist, particularly effective in prostatic smooth muscle relaxation varying t1/2 orthostatic hypotension biggest concern

Question 45

Beta antagonist mechanism of action, receptor effect

Answer 45

competitive and reversible inhibition, large doses of agonists will completely overcome antagonism. chronic use associated with up regulation of receptors

Question 46

clinical uses of BB's

Answer 46

tx of HTN management of angina decrease mortality in treatment of post MI patients used periop and preop for pts at risk of MI suppression of tachyarrhythmias prevention of excessive SNS activity

Question 47

BB relative contraindications

Answer 47

pre existing heart block or cardiac failure reactive airway disease DM (without BS monitoring) blunts response to hypovolemia, so dont give during hypovolemia

Question 48

BB SE's

Answer 48

1. decrease HR, contractility, BP 2. exacerbation of peripheral vascular disease (block of B2 vasodilation) 3. airway resistance, bronchospasm 4. metabolism, alter carbohydrate and fat metabolism, mask hypoglycemia increase in HR 5. distribution of extracellular potassium, inhibit uptake of potassium into skeletal muscles 6. interaction with anesthetics, may have decreased BP with IA's 7. nervous system fatigue, lethargy 8. N/V/D 9. eye- reduction in IOP (esp if pt has glaucoma) d/t decreased aqueous humor production 10. decreased concentrations of HDL's have been seen with chronic use that may increase risk for CAD

Question 49

Propanolol receptor selectivity, CV effects, alternative concerns, tx goal, dosing, protein binding, metabolism, interaction with other drugs

Answer 49

non selective BB decreased HR and contractility, CO. increased vascular resistance, due to decreased O2 demand, this is ok. reduction in renin release extensive first pass effect goal: 55-60bpm oral much larger than IV dose r/t 1st pass effect (but still give PO more than IV) .05mg/kg IV or 1-10mg (give slowly 1mg q5m) 90-95% protein bound metabolized in liver t1/2 2-3h (will be increased in low hepatic BF states) concerns with patients who have been treated chronically- decreases clearance of amide LA's due to decrease in hepatic BF inhabiting metabolism in liver, risk of systemic toxicity of amide local anesthetics, decreased pulmonary clearance of fentanyl (both are lipophilic amines)

Question 50

Metoprolol receptor selectivity, dose, dosing consideration, metabolism, onset, t1/2, route of administration, patient population that would benefit

Answer 50

``` beta 1 selective (selectivity is dose related) 60% goes through first pass PO 50-400mg IV 1-15mg (max dose) onset 3min t1/2 3-4h metabolized by liver beta 2 receptors remain intact (bronchodilation, vasodilation, metabolic effects) ```

Question 51

Atenolol receptor affinity, t1/2, excretion, uses

Answer 51

most selective B1 antagonist, thought to have least CNS effects t1/2 6-7h, increases markedly in patients with renal disease excreted via renal system PO for HTN, long lasting HTN effects, good for pts with lung disease

Question 52

Esmolol receptor affinity, onset, t1/2, DOA, metabolism, uses:

Answer 52

b1 selective antagonist onset 60 seconds t1/2 9 min DOA 10-30min metabolism plasma esterase poor lipid solubility, does not cross BBB or placenta useful in tx HTN and tachycardia associated with laryngoscopy. also useful for hyper dynamic effects of pheochromocytoma, thyrotoxicosis, thyroid storm

Question 53

Timolol receptor affinity, uses

Answer 53

non selective BB used to tx glaucoma, decreases intraocular pressure by decreasing production of aqueous humor eye drops can cause decreased BP and HR and increased airway resistance

Question 54

Nadolol receptor selectivity, metabolism, t1/2, how often to take, use

Answer 54

nonselective BB no significant metabolism (renal/biliary elimination) t1/2 20-40h take 1x daily good for esophageal varices

Question 55

betaxolol receptor selectivity, t1/2, how often to take, uses

Answer 55

b1 selective t1/2 11-22h single dose daily for HTN topical, useful for glaucoma, with less risk of bronchospasm as seen with timolol, so good alternative choice in asthmatics with glaucoma

Question 56

labetalol receptor affinity, metabolism, t1/2, max drop in BP time, dose

Answer 56

combined non selective antagonists (alpha 1, B1/2) metabolism: conjugation of glucoronic acid t1/2: 5-8h, prolonged in liver disease but not affected by renal dysfx max drop in BP 5-10min after IV admin dose .1-.5mg/kg, usually 2.5-5mg at a time for mild HTN in OR)

Question 57

labetalol uses

Answer 57

decreases systemic BP with attenuated reflex tachycardia. decrease in BP SVR and HR but CO unaffected used to tx intraop HTN and HTN crisis can be used in hypotensive technique (not super popular anymore)

Question 58

centrally acting agents MOA, site of action, clinical uses

Answer 58

reduce sympathetic outflow from vasomotor centers in brain stem. selective partial alpha 2 adrenergic agonist. site of action: CNS non adrenergic binding sites and a1 receptor agonism clinical uses: HTN, sedation, decrease anesthetic requirements, improve periop hemodynamics, analgesia

Question 59

Clonidine effects, SE, route of admin, metabolism, excretion

Answer 59

BP reduction from decreased CO due to decreased HR and peripheral resistance. rebound HTN with abrupt cessation happens. sedative property dissipates over time SE: bradycardia, sedation, xerostomia, impaired concentration, nightmares, depression vertigo, EPS, lactation in men avail as PO or transdermal patch hepatic metabolism renal excretion

Question 60

withdrawal syndrome of centrally acting agents

Answer 60

occurs with doses >1.2mg/day occurs 18 hours post acute d/c of drug lasts 24-72h tx is rectal or transdermal clonidine