PNS: Adrenergic Drugs 2

Question 1

Phentolamine

Answer 1

competitive antagonist at a1 and a2 receptors (by forming a stable, covalent bond with a receptors), can block 5-HT receptors, K+ channels and histamine release at higher concentrations

used to prevent pheochormocytoma as a result of surgical excision or reverse dermal necrosis following extravasation of a agonists

clinical effects can last up to 7 days because it forms a covalent bond via nitrogen mustard (chlorine attached to side chain makes it reactive), adverse effects consistent with a blockade

note because a receptors are not working, reduction in feedback

Question 2

7. Explain the mechanistic difference between irreversible and reversible antagonist (phenoxybenzamine and prazosin)

Answer 2

phenoxybenzamine operates via a noncompetitive antagonist while prazosin operates as a competitive antagonist

Question 3

Prazosin (Minipress)

Answer 3

competitive antagonist at post synaptic a1 receptors, causing peripheral dilation

used primarily to treat hypertension, or in BPH

important: first-dose syncope due to central effects, caution with PDE5 inhibitors (enhances their vasodilator effects, care with ED treatment)

Question 4

Tamsulosin (Flomax)

Answer 4

a1 receptor competitive antagonist which is 10x selective for a1A receptor (located in neck of the bladder)

used in the treatment of benign prostatic hyperplasia

long acting, potent drug, which should not be taken with food, and is metabolized with CYP3A4 AND CYP2D6

caution with PDE5 inhibitors

Question 5

Yohimbine (Aphrodyne, Yocon)

Answer 5

anatomist at central presynaptic a2 receptors, increasing NE nerve activity and increasing sympathetic tone

efficacy and bioavailablity variable (natural derivative), used to treat erectile dysfunction

Question 6

Propranolol (Inderal)

Answer 6

nonselective B-adrenergic receptor leading to decrease in resting and exercise HR and CO, decrease in systolic and diastolic

tx. for hypertension, angina, tachy, acute MI, MI and migraine prophylaxis, anxiety, agitation and panic attack
note: B receptor blockade can decrease somatic symptoms of anxiety ugh as palpitations and tremor, resulting in improvement in psychological components as well

do not discontinue abruptly can cause myocardial ischemia, MI, arrhythmias or severe hypertension

Question 7

Use of a B blocker decreases the risk of mortality due to ______

Answer 7

second heart attack, note the suffix for beta blockers are -olol

Question 8

Timolol

Answer 8

competitive, nonselective B adrenergic receptor antagonist by reducing aqueous humor production

1st line tx. for open angle glaucoma

Question 9

Metoprolol

Answer 9

competitive B1-selective adrenergic receptor antagonist, decreases HR and CO in resting and exercise, and decreases systolic and diastolic BP

used in tx. of angina, HTN, migraines, MI and tremor

metabolized by CYP2D6, do not abruptly discontinue

Question 10

Pindolol (Visken)

Answer 10

non selective B receptor partial agonist (sympathomimetic activity) and parietal agonist of 5-HT receptors

used in bronchospasm when maintenance of adequate sympathetic tone is desirable, may also augment anti-anxiety effects of SSRIs

do not abruptly discontinue, excreted mostly unchanged in the urine

Question 11

Compare isoproterenol, Epi and NE regarding their action of a and B receptors

Answer 11

iso: mostly B effects
Epi: both a and B effects
NE: mostly only a effects

Question 12

What is the suffix for B blocker and a1 blocker?

Answer 12

B blocker “-olol”

a blockert “-cin”

Question 13

a-Methyltyrosine (Demser)

Answer 13

blocks tyrosine hydroxylase (reduces catecholamine, NE and Epi biosynthesis

used as a preop or chronic tx. for pheochromocytoma, can reduce cyanosis and mottling due to pheo.

concentrations in blood rise and taper after use slowly (2-3 days)

effects include sedation (in virtually all patients), patients should be advised to increase water intake because of danger of crystalluria

Question 14

a-Methyldopa (Aldomet)

Answer 14

major site of action is a2 auto receptors in the brainstem, acts as a false neurotransmitter that causes negative feedback to reduce NE release

drug of choice during pregnancy, second line anti-hypertensive

predictable central side effects, can reduce DA release, precautions with hepatic disease and dopamine antagonist

Question 15

Reserpine

Answer 15

inhibits vascular neurotransmitter storage causing long-lasting depletion of 5-HT, NE and DA by blocking the VMAT-2 protein that pumps catecols into the vesicle

previously used as an antihypertensive, use diminished due to its adverse CND effects, takes 2-3 weeks to become effective and can lead to severe depression, risk of seizures

important drug leading to the monoamine hypothesis of depression

Question 16

Botulinum toxin A (Botox)

Answer 16

cleaves SNAP-25 and other proteins (synaptobrevin, syntaxin) required for vesicular fusion with axon terminal, decreasing ACh release

neurtoxin mix that is used to treat facial wrinkles, axillary hyperhidrosis, cervical dystonia, blepharospasm and strabismus

can cause local muscle weakness, dysphagia and dystonia and immunogenic response

Question 17

Amphetamine (Adderall)

Answer 17

indirect acting sympathomimetic inhibiting NE, DA and 5-Ht and evokes MA reverse transport and reuptake of surrogate neurotransmitter (futile cycle)

used as a treatment for ADHD, is one of the most potent CNS stimulants available

metabolized by CYPS and MAO; can cause insomnia and psychosis at high doses, not indicated with those with anorexia or MAOIs

Question 18

Cocaine

Answer 18

inhibits neuronal transporters for uptake of 5-Ht, E, NE and DA (blocks AP transmission), producing local vasoconstriction; can also cause CNS effects leading to euphoria and stimulation

onset within 1min, duration 20-60min; can produce allergic reaction as with other ester-type local anesthetics

Question 19

Paroxetine

Answer 19

highest specificity for 5HT uptake transporters of all SSRIs

a third generation SSRI, used in tx of major depression and anxiety concerns

metabolized largely by CYP2D6 and CYP3A4, it is excreted via the urine 62%, onset may take 1-4 weeks and contraindicated with MAOI therapy or renal insufficiency, Risk category D

Question 20

Atomoxetine (Strattera)

Answer 20

norepiniephrine reuptake inhibitor, no appreciable 5-HT or DA transporter affinity

used as a non stimulant drug for ADHD, with black box warning for risk of suicidal ideation, although minimal peripheral side effects, QD dosing with extensive hepatic metabolism CYP2D6

side effects diminish with continued dosing, caution with hepatic disease

some people tolerate well and get benefits, others not, it is prudent to take baseline BP and pulse due to systemic effects

Question 21

What are monoamine oxidase inhibitors?

Answer 21

first class of antidepressants that increase monamine neurotransmitter by inhibiting metabolism of 5-HT, DA and NE

important the drugs take time to build in system and to be cleared from system (2 weeks)

patient on MAO-I should avoid tyramine containing foods (aged foods) and OTC sympathomimetics (ie. Pseudophed)

Question 22

Phenelzine (Nardil)

Answer 22

nonselective irreversible inhibitor of MAO

used as a 2nd line treatment for depression for patients who are unresponsive to newer medications, effective in refractory anxiety disorders

can cause sympathomimetic effects (some level adverse) and radiographic contrast should be avoided, can cause seizures