sympatholytics

Question 1

side effects of alpha 1 receptor antagonist

Answer 1

Orthostatic hypotension, inhibition of ejaculation, nasal stuffiness, tachycardia

Question 2

beta-haloalkylamines

Answer 2

-Non-selective a receptor
antagonist
-Also blocks acetylcholine,
histamine, and serotonin
receptors
-irreversible antagonist
resulting from covalent
modification of receptor

Question 3

imidazolines

Answer 3

-Non-selective a receptor
antagonist
-Competitive (reversible)
blocker
-Potent vasodilator, but
induces pronounced reflex
tachycardia
-Block of presynaptic a2
receptors may promote
release of NE
-Also blocks 5-HT receptors,
and is a muscarinic and
histamine receptor agonist

Question 4

action of phenoxybenzamine

Answer 4

-noncomptetive (irreversible) antagonist at a1 and a2 receptors
-new receptors must be synthesized in order to restore receptor function leading
to a long drug effect

Question 5

action of phentolamine

Answer 5

competitive (reversible) antagonist at a1 and a2 receptors

Question 5

clinical use of phenoxybenzamine and phentolamine

Answer 5

Perioperative management of patients with pheochromocytoma (tumor of
adrenal medulla that results in excessive epinephrine and norepinephrine
synthesis and release)

Question 5

problems of phenoxybenzamine and phentolamine

Answer 5

Not useful in treatment of hypertension due to a2 effects

Question 6

by blocking alpha 2 receptors, we get a greater release of _____ at the ______ and increased ___

Answer 6

NE, Heart, HR

Question 7

alpha 1 antagonist

Answer 7

• Vary in half-life:
  
  • Prazosin 3 hrs
  • Terazosin 12 hrs
  • Doxazosin 20 hrs
• Undergo extensive metabolism, excreted
  mainly in the bile
• Vasodilators
• Relaxation of smooth muscle in enlarged
  prostate and in bladder base
• Quinazolines produce peripheral
  vasodilation without causing reflex
  tachycardia or increased cardiac output
  (a presynaptic a 2 -antagonist effect)

Question 7

prazosin

Answer 7

decrease TPR via a1 antagonism -> activate baroreceptor reflex -> increase NE release into myocardium -> increase heart rate via b1 receptors -> negative feedback via a2 receptors in myocardium mitigates NE release

Question 8

phentolamine

Answer 8

decrease TPR via a1 antagonism -> activate baroreceptor reflex -> increase NE release into myocardium -> increase heart rate via b1 receptors -> antagonism of a2 receptors in myocardium blocks negative feedback -> cardiac overstimulation

Question 9

tamsulosin (flomax)

Answer 9

-alpha 1 antagonist
-very selective to prostate urethra as this is rich in a1 a receptors
-less prone to induce fall in BP as compared to classical a1 blockers such as Prazosin
**Benign Prostatic Hyperplasia (BPH)
-BPH is problem with voiding may lead to overactive bladder.
-Stimulation of a1 a receptors in the trigone muscle of the bladder & urethra contract, contributing
to the resistance to outflow of urine. a1 blockers antagonize this effect

Question 10

Beta 1 signal through Gs

Answer 10

-Activate adenylyl cyclase
-increase cAMP leading to protein kinase activation,
-Results in phosphorylation of ion channels and other proteins

Question 10

yohimbine (yocon) alpha 2 adrenergic receptor antagonist

Answer 10

-Indole alkaloid
-Found in Rubaceae and
related trees. Also in
Rauwolfia Serpentina.
-Blockade of a2 receptors
increases sympathetic
discharge
-Folklore suggests use in
the treatment of male
impotence

Question 11

beta blockers cardiovasular indications

Answer 11

angina, cardiac arrhythmia, post myocardial infraction, hypertension, congestive heart failure

Question 12

cardiac arrhythmia

Answer 12

Slow AV nodal conduction

Question 12

angina

Answer 12

Reduction in myocardial oxygen demand due to decreased heart rate and contractility

Question 13

post myocardial infarction

Answer 13

Reduction in myocardial oxygen demand
Slow AV nodal conduction

Question 14

hypertension

Answer 14

Decrease cardiac output
Inhibition of renin secretion

Question 15

congestive heart failure

Answer 15

Decreases chronic overstimulation/toxicity of compensatory catecholamines

Question 16

propranolol

Answer 16

-Non-selective beta antagonist
-Lipophilic
-Extensive hepatic metabolism, “first-pass”
-Local anesthetic properties
-Blockade is activity- dependent

Question 17

pindolol (visken)

Answer 17

-non selective beta antagonsit
-Possesses “Intrinsic sympathomimetic activity (ISA)
-Partial agonist
-Less likely to cause bradycardia and lipid abnormalities
-Good for patients who have severe bradycardia or little cardiac reserve
-Administered: Oral
-Uses: Hypertension, angina,
migraine

Question 17

propranolol pharmacologic effect

Answer 17

-Decreased cardiac output and heart rate
-Reduced renin release
-increase VLDL, Decrease HDL
-Inhibit lipolysis
-Inhibit compensatory glycogenolysis and glucose release in response to hypoglycemia
-Increase bronchial airway
resistance
-uses Hypertension, angina, cardiac arrhythmias, migraine, stage fright,
thyrotoxicosis, glaucoma, congestive heart failure (types II and III)

Question 18

nadolol (corgard)

Answer 18

-non-selective beta adrenergic antagonist
-Less lipophilic than propranolol
-Long half-life: ~20 hours
-Mostly excreted unchanged in
urine
-Administered: Oral
-Uses: Hypertension, angina,
migraine

Question 19

timolol (timoptic, blocadren)

Answer 19

-non selective beta antagonist -Thiadiazole nucleus with morpholine ring -Administered: Oral, Ophthalmic -Uses: glaucoma, hypertension, angina, migraine,

Question 20

carteolol (cartrol, ocupress)

Answer 20

-nonselective beta antagonist -Possesses “Intrinsic sympathomimetic activity (ISA) -Partial agonist -Less likely to cause bradycardia and lipid abnormalities -Administered: Oral, Opththalmic -Uses: Hypertension, glaucoma

Question 21

esmolol (brevibloc)

Answer 21

-selective beta 1 antagonist -Very short acting -Half-life: 9 minutes -Rapid hydrolysis by esterases found in red blood cells -Administered: Parenteral Note: incompatible with sodium bicarbonate -Uses: Supraventricular tachycardia, atrial fibrillation/flutter, perioperative hypertension

Question 21

para-substituted phenyl derivatives

Answer 21

-selective beta 1 antagonist -“Cardioselective” -Less bronchconstriction -Moderate lipophilicity -Half-life: 3-4 hours -Significant first-pass metabolism -Administered: Oral, parenteral -Uses: Hypertension, angina, antiarrhythmic, congestive heart failure

Question 22

atenolol (tenormin)

Answer 22

-selective beta 1 antagonist -“Cardioselective” -Less bronchconstriction -Low lipophilicity, “Water-soluble Metoprolol” -Half-life: 6-9 hours -Administered: Oral, parenteral -Uses: Hypertension, angina

Question 23

side effects of beta blockers

Answer 23

Bradycardia, AV block, sedation, mask symptoms of hypoglycemia, withdrawal syndrome

Question 23

contraindications of beta blockers

Answer 23

Asthma, COPD, congestive heart failure (Type IV)

Question 24

lavetalol (normodyne, trandate)

Answer 24

-mixed adrenergic receptor antagonist -Phenylethanolamine derivative -Two asymmetric carbons (1 and 1’) -Racemic mixture used clinically -(1R, 1’R)-isomer Non-selective b receptor antagonist -(1S, 1’R)-isomer a1 antagonist -(Administered: Oral, parenteral -Uses: Hypertension, hypertensive crisis -b-blocking activity prevents reflex tachycardia normally associated with a1 receptor antagonists -vasodilation via a1-blockade prevents bradycardia associated with b-blockade

Question 25

carvedilol (coreg)

Answer 25

-Non-selective b receptor antagonist -a1 receptor antagonist -Both enantiomers antagonize a1 receptors -Only (S)-enantiomer possesses b-blocking activity -b-blocking activity prevents reflex tachycardia normally associated with a1 receptor antagonists -Administered: Oral -Uses: Hypertension, congestive heart failure

Question 26

actions of catecholamine synthetic path: inhibiting with metyrosine

Answer 26

* Inhibits tyrosine hydroxylase * Depletes catecholamines everywhere

Question 27

clinical use of catecholamine synthetic path: inhibiting with metyrosine

Answer 27

* Perioperative management of pheochromocytoma (tumor of adrenal medulla that results in excessive epinephrine and norepinephrine synthesis and release)

Question 28

problems of catecholamine synthetic path: inhibiting with metyrosine

Answer 28

Depletes catecholamines everywhere

Question 29

bretylium tosylate (bretylol)

Answer 29

-drugs that reduce storage or release of NE -Aromatic quaternary ammonium -Precise mechanism unknown -Displace and release NE and prevent further release (depletion) -Local anesthetic -Administered: Parenteral -Uses: Antiarrhythmic (ventricular fibrillation)

Question 29

reserpine (serpasil)

Answer 29

-catecholamine depleters -Indole alkaloid obtained from the root of Rauwolfia serpentina -Block vesicular monoamine transporters -Deplete vesicular pool of NE -Slow onset of action -Sustained effect (weeks) -Used in the treatment of hypertension (rarely because of adverse effects) -May precipitate depression

Question 30

actions of VMAT inhibitor reserpine

Answer 30

-Nonselective, irreversible inhibitor of Vesicular Monoamine Transporter (VMAT) -Depletes stored NE

Question 31

clinical use of VMAT inhibitor reserpine

Answer 31

Hypertension but rarely used because of adverse effects

Question 32

problems of VMAT inhibitor reserpine

Answer 32

-Expected peripheral adverse effects (orthostatic hypotension, increased GI activity) -CNS effects such as sedation, severe depression and suicide in susceptible individuals