PNS: Adrenergic Drugs 2 Flashcards
Phentolamine
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
- Explain the mechanistic difference between irreversible and reversible antagonist (phenoxybenzamine and prazosin)
phenoxybenzamine operates via a noncompetitive antagonist while prazosin operates as a competitive antagonist
Prazosin (Minipress)
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)
Tamsulosin (Flomax)
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
Yohimbine (Aphrodyne, Yocon)
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
Propranolol (Inderal)
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
Use of a B blocker decreases the risk of mortality due to ______
second heart attack, note the suffix for beta blockers are -olol
Timolol
competitive, nonselective B adrenergic receptor antagonist by reducing aqueous humor production
1st line tx. for open angle glaucoma
Metoprolol
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
Pindolol (Visken)
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
Compare isoproterenol, Epi and NE regarding their action of a and B receptors
iso: mostly B effects
Epi: both a and B effects
NE: mostly only a effects
What is the suffix for B blocker and a1 blocker?
B blocker “-olol”
a blockert “-cin”
a-Methyltyrosine (Demser)
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
a-Methyldopa (Aldomet)
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
Reserpine
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
Botulinum toxin A (Botox)
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
Amphetamine (Adderall)
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
Cocaine
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
Paroxetine
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
Atomoxetine (Strattera)
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
What are monoamine oxidase inhibitors?
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)
Phenelzine (Nardil)
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
