Adrenergic Agents Flashcards
1
Q
Epinephrine (Primatene Mist, Twinject)
A
Description
- Endogenous catecholamine synthesized in adrenal medulla; one of the most potent vasopressors known
- TX for acute bronchospasm, asthma, CPR; DOC for anaphylaxis
- Often combined with local anesthetics to prolong anesthetic duration of action
Mechanism of action
- Mixed-acting agonist, activates both a and b receptors throughout the body
- In open-angle glaucoma, epinephrine in the eye ↓ IOP and produces a brief mydriasis
Pharmacokinetics
- Administered by IV or intracardiac injection, by inhalation, or topically to the eye
- Poor PO bioavailability; metabolized by COMT and MAO in liver and other tissues
- Duration varies, generally 1-4 hr regardless of route
Adverse reactions
- CNS: anxiety, nervousness, insomnia, aggressive behavior
- CV: arrhythmias, PVCs, tachycardia
Precautions
- Narrow-angle glaucoma
- Intraarterial administration
- Nonanaphylactic shock (2° to other causes e.g. hypovolemic shock)
- Labor; can cause fetal anoxia or ↓ HR due to ↑ uterine contractility or ↓ uterine blood flow
- Extravasation
- Hypertension
- Hyperthyroidism
- Diabetes
2
Q
Phenylephrine (Neo-Synephrine, Sudafed PE)
A
Description
- Synthetic sympathomimetic amine commonly used PO, alone or in combination with other drugs, or intranasally, to treat nasal congestion (nasal mucosa rich in a1 receptors)
- When administered topically to the eye, it induces mydriasis and it is often used as a diagnostic aid in ophthalmology
Mechanism of action
- Selective a1 agonist; main effect is vasoconstriction (pressor effect)
- In therapeutic doses, the drug has no substantial effect on b1 receptors of the heart nor on b2 receptors of the bronchi or peripheral blood vessels
- Local application causes vasoconstriction of nasal vessels, decreasing mucosal edema to produce a decongestant effect
Pharmacokinetics
- Administered by injection, PO, intranasally, or ophthalmically
- Metabolized by MAO in liver and other tissues
- Duration varies; after intranasal administration, active for 30 min to 4 hr
Adverse reactions
- Few reactions when given by intranasal or opthalmic route
- Parenteral dosing can produce angina, hypertension, anxiety, insomnia
Precautions
- CV diseases: MI, coronary artery disease, angina, atrial or ventricular flutter or fibrillation, arrhythmias, hypertension, tachycardia
- Narrow-angle glaucoma
- Labor
- Extravasation
- Hyperthyroidism
3
Q
Clonidine (Catapres, Duraclon)
A
Description
- Antihypertensive agent and epidural agent for opioid-refractory cancer pain
- Used mainly in the TX of hypertension, but has been used in other conditions including ADHD, opioid and nicotine withdrawal, vascular headaches, and Tourette’s syndrome
Mechanism of action
- Agonist at presynaptic a2 receptors, results in inhibition of sympathetic outflow and tone → decreased sympathetic tone reduces HR, TPR, MAP, CO, and SV
- Hypotensive effect is mainly due to actions on the brain stem
- Epidural clonidine produces analgesia that is not blocked by opioid antagonists
Pharmacokinetics
- Administered epidurally, PO, and via transdermal patch
- PO bioavailability approaches 100%
- Highly lipid soluble, distributes widely throughout the tissues, including the CNS
- Antihypertensive effects last up to 8 hr (PO) and up to 7 days with transdermal patch system
Adverse reactions
- CNS: sedation (33-50%), lethargy, dizziness (10%) (first dose at bedtime)
- CV: orthostatic hypotension (3%), palpitations, tachycardia, bradycardia
- GI: xerostomia (40-50%), NV, constipation
- Effects generally will subside with continued therapy
Precautions
- Abrupt DC → withdrawal syndrome consisting of rebound ↑ in catecholamines → severe hypertension, tachycardia, agitation; doses should be slowly tapered to avoid symptoms
- Breast-feeding; concentration of clonidine in breast milk is ~ 2X that in the maternal plasma
- CV disease: MI, or severe heart failure; the hypotensive effects of clonidine may decrease perfusion and worsen ischemia in these conditions
4
Q
Isoproterenol (Isuprel)
A
Description
- Norepinephrine analog used to improve AV conduction during heart block and as cardiac stimulant in cardiac arrest
- Also used to treat acute bronchospasm, asthma, COPD
Mechanism of action
- Isoproterenol is a potent agonist at b1 and b2 adrenergic receptors, with little or no effect on a receptors
- Clinical effect is marked increase in CO (+ inotropic, + chronotropic) with a decrease in vascular resistance → ↓ BP; prevents or relieves bronchoconstriction
Pharmacokinetics
- For cardiac effects, usually administered by IV infusion or IV bolus, for brochodilation, used as aerosol
- Metabolism mainly via COMT
Adverse reactions
- CNS: nervousness, headache
- CV: palpitations, tachycardia, angina
- Flushed skin
Precautions
- Arrhythmias
- Heart block caused by digitalis compounds
- Coronary artery disease, coronary insufficiency
- Diabetes (b receptors in liver leads to increased glycogenolysis and gluconeogenesis)
- Hyperthyroidism (sensitive to catecholamines)
5
Q
Dobutamine (Dobutrex)
A
Description
- Intravenous inotrope used to treat acute heart failure
- similar to dopamine
Mechanism of action
- Dobutamine has complex pharmacology; overall, it is primarily an agonist at b1 adrenergic receptors, with minor b2 and a1 effects; the R (+) isomer is a potent, mostly b1 agonist and a1 antagonist while the S (-) isomer is a weaker mixed b agonist and a1 agonist
- Clinical effect is ↑ myocardial contractility and stroke volume with modest chronotropic effects, resulting in increased CO (increased perfusion to kidney)
Pharmacokinetics
- Administered via continuous IV infusion for < 72 hr
- Onset of action occurs within 2 min, peak effect can take ~ 10 min
- Plasma t1/2 ~ 2 min
- Metabolized in the liver by COMT and by glucuronidation to inactive metabolites
- Excretion occurs mainly by the kidney as the metabolites and conjugates
Adverse reactions
- CV: PVCs, tachycardia, angina
Precautions
- Idiopathic hypertrophic subaortic stenosis
- Arrythmias
- Hypovolemia
6
Q
Albuterol (Proventil, Ventolin)
A
Description
- Widely used as a short-acting bronchodilator; indicated for the management of acute asthmatic episodes or other COPD (inhalation –> local effects)
Mechanism of action
- Moderately selective b2 adrenergic receptor agonist
- Stimulates receptors of the lung smooth muscle, causing relaxation and bronchodilation
- Albuterol can also inhibit the degranulation and subsequent release of inflammatory substances from mast cells
Pharmacokinetics
- Commonly administered by oral inhalation; onset of bronchodilation occurs within ~ 7 min after oral inhalation, peaks in 0.5-2 hr, and lasts 2-6 hr
- Metabolism occurs primarily in the liver
- Excretion of albuterol occurs through the urine and feces
Adverse reactions
- CNS: anxiety (< 10%), tremor (< 15%), headache (3%)
- CV: ↑ BP (5%), angina (< 1%), palpitations (< 10%) , sinus tachycardia (10%), arrhythmia
- GI: NV (6%), dyspepsia (5%)
Precautions
- Angioedema; indicates propensity for hypersensitivity reactions
- Patients should be warned that increasing use of inhaled short-acting b-agonists is a signal of deteriorating asthma, which may be a life-threatening condition (continued use may indicate need to switch to prophylatic corticosteroid Rx)
- Coronary artery disease
- Hypertension
- Hyperthyroidism
- Diabetes
7
Q
Salmeterol (Serevent)
A
Description
- Long-lasting bronchodilator used for long-term prophylactic treatment of asthma and for prevention of bronchospasm in adults with reversible COPD
- Formulated with fluticasone (Advair®)
- Delayed onset; never used to treat an acute attack but very effective for prophylaxis
Mechanism of action
- Highly selective b2 adrenergic receptor agonist
- Stimulates receptors of the lung smooth muscle, causing relaxation and bronchodilation
Pharmacokinetics
- Administered by oral inhalation with BID dosing
- Onset of therapeutic effects occurs in ~ 14 min, peak effects are observed in 3-4 hr, effects persist at greater than half of the maximum effect for 12 hr
- Excretion is primarily in the feces
Adverse reactions
- Most common adverse effects are cough (7%), headache (28%), pharyngitis (14%), disease of nasal cavity/sinus (6%), and upper respiratory tract infection (14%) (mostly related to bronchial tree)
Precautions
- It is crucial to inform patients that an inhaled, short-acting b-agonist, such as albuterol, should be used for TX of an acute attack
- Should not be the first drug used to treat asthma and should only be added to the TX regimen if other drugs do not control asthma
- Coronary artery disease
- Hypertension
- Hyperthyroidism
- Diabetes
- FDA black box warning of increased risk of asthma-related death w/ long-acting B2 agonist
8
Q
Phentolamine (Regitine)
A
Description
- Short-acting alpha adrenergic antagonist
- Used to prevent hypertensive episodes that may occur in a patient with pheochromocytoma as a result of manipulation during surgical excision; and to prevent dermal necrosis following extravasation of alpha agonists. (such as after administration of epinephrine)
Mechanism of action
- Competitive antagonist at a1 and a2 receptors at nanomolar concentrations
- Also can block 5-HT receptors, K+ channels, and release histamine from mast cells at micromolar concentrations
- Clinical effect is inhibition of vasoconstriction → ↓ BP
Pharmacokinetics
- Supplied as a lyophilized powder that is reconstituted in NS and used immediately
- Administered IV for BP control or SC as multiple injections for necrosis prevention
- Plasma t1/2 ~ 19 min
Adverse reactions
- CNS: dizziness
- CV: orthostatic hypotension, reflex tachycardia, arrhythmias
- GI: NVD
- Nasal congestion (swelling of membranes)
Precautions
- MI, coronary insufficiency, angina, etc. (due to baroreceptor response)
9
Q
Phenoxybenzamine (Dibenzyline)
A
Description
- Main use is for TX of sweating and hypertension associated with pheochromocytoma (given several days ahead of surgery to knock out receptors)
- Used to treat urinary symptoms of BPH and symptoms of certain peripheral vasospastic conditions such as acrocyanosis, Raynaud’s disease, and frostbite
Mechanism of action
- Noncompetitive, selective a1 antagonist (100:1 vs. a2); forms stable, covalent bond with a receptors
- Clinical effects are vasodilation, decreased pupillary dilation, lid retraction, inhibition of adrenergically mediated sweating, and reflex tachycardia
Pharmacokinetics
- Oral absorption is variable; only 20-30% of the drug is bioavailable
- Distribution is extensive because phenoxybenzamine is highly lipophilic and may accumulate in fatty tissues
- Clinical effects can last up to 7 days after discontinuation of therapy
Adverse reactions
- CNS: dizziness, syncope, fatigue
- CV: reflex tachycardia, orthostatic hypotension
- UG: impotence
- Eye: miosis
- Nasal congestion
Precautions
- Congestive heart failure, coronary artery disease, renal disease: hypotensive effects can worsen these conditions
10
Q
Prazosin (Minipress)
A
Description
- Oral agent used primarily to treat hypertension
- Has been used off-label to treat benign prostatic hyperplasia (BPH)
Mechanism of action
- Competitive antagonist at postsynaptic a1 receptors
- Causes peripheral vasodilation, reducing vascular resistance and BP
- In the TX of BPH, prazosin relaxes the bladder neck and the prostate by blocking a1 receptors located in the smooth muscle, causing less pressure on the urethra and leading to increased urine flow
Pharmacokinetics
- Dose is typically 2-5 mg TID
- Antihypertensive effects peak in 2-4 hr, but complete antihypertensive effects may not occur for 4-6 weeks
- Metabolized in the liver by demethylation and conjugation, with the majority being eliminated via biliary excretion (in the feces)
Adverse reactions
- CNS: dizziness (first-dose syncope –> take first dose at bedtime), lightheadedness, drowsiness, headache
- CV: palpitations, orthostatic hypotension
- GI: pain, NVD
- GU: impotence, incontinence
Precautions
- Angina; prazosin-induced hypotension may worsen condition
- Syncope can be hazardous for patients in occupations for which alertness is required
- Caution with PDE5 inhibitors
11
Q
Tamsulosin (Flomax)
A
Description
- Potent oral agent used to treat benign prostatic hyperplasia (BPH) (preferred over Prazosin)
- First a1 subtype-selective antagonist approved for BPH
Mechanism of action
- Competitive antagonist at postsynaptic a1 receptors; 10X selective for a1A receptors vs. a1B receptors; ~70% of a1 receptors in prostate are a1A subtype
- In the TX of BPH, tamsulosin relaxes the bladder neck and the prostate by blocking a1A receptors, causing smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH
Pharmacokinetics
- Long-acting, dosing is 0.4-0.8 mg QD
- Food decreases peak plasma concentration and bioavailability by ~30%
- Protein binding is 94-99%, mostly to a1-acid glycoprotein
- Metabolized in the liver by CYP3A4 and CYP2D6
Adverse reactions
- CNS: dizziness, insomnia, syncope
- CV: orthostatic hypotension (5-8%)
- GU: abnormal ejaculation (8%)
Precautions
- Caution with PDE5 inhibitors
12
Q
Yohimbine (Aphrodyne, Yocon)
A
Description
- Alkaloid found in the bark of Rubiaceae and related trees
- Used to treat erectile dysfunction (alternative not frequently used)
Mechanism of action
- Antagonist at central presynaptic a2 receptors, produces an ↑ in noradrenergic nerve activity and an ↑ in sympathetic tone
- This action increases penile blood inflow, decreases penile blood outflow, or both, which causes erectile stimulation without increased sexual desire
Pharmacokinetics
- Administered PO
- Bioavailability is highly variable, ranging from 7 to 87%
- Precise metabolic fate has not been fully determined; ~ 1% of unchanged drug is excreted renally
- The elimination t1/2 is ~ 36 min
Adverse reactions
- CNS: anxiety, dizziness, headache, restlessness, irritability
- CV: hypertension, tachycardia, chest pain
Precautions
- Angina
- Cardiac disease
- Hypertension
- Generally not used in ♀; pregnancy risk unassigned, but likely category D due to chemical similarity to known teratogens
13
Q
Propranolol (Inderal)
A
Description
- Prototype of the b-adrenergic receptor antagonists
- TX for hypertension, angina, tachycardia, acute MI, prophylaxis of MI, prophylaxis of migraine, anxiety, agitation, panic attack
Mechanism of action
- Competitive, nonselective b-adrenergic receptor antagonist
- Effects include ↓ in both resting and exercise HR and CO, and ↓ in both systolic and diastolic BP, ↓ skeletal muscle perfusion
- b receptor blockade can ↓ somatic symptoms of anxiety such as palpitations and tremor, resulting in an improvement in psychologic components as well
Pharmacokinetics
- Administered PO or IV; highly lipophilic, widely distributed throughout the body
- Extensively metabolized upon first pass through the liver; metabolites excreted renally
Adverse reactions (well tolerated)
- Generally mild and temporary; usually occur at the onset of therapy and diminish over time
- CNS: dizziness, fatigue, depression
- CV: bradycardia, cold hands and feet
- GI: NVD
Precautions
- Abrupt DC can produce myocardial ischemia, MI, arrhythmias, or severe hypertension
- Acute bronchospasm, pulmonary edema, asthma
- Bradycardia, AV block
- Hepatic disease
- Raynaud’s disease
- Diabetes (reflex tachy when hypoglycemic, used as sign for sugar; reflex is blocked w/ Rx)
14
Q
Timolol (Timoptic XE)
A
Description
- First-line TX for open-angle glaucoma
Mechanism of action
- Competitive, nonselective b adrenergic receptor antagonist
- Reduces IOP by reducing aqueous humor production
Pharmacokinetics
- Supplied as a 0.25% or 0.5% gel-forming ophthalmic solution; dose is 1 gtt QD
- Some systemic absorption occurs
- Partially metabolized in liver; metabolites and parent drug are excreted renally
Adverse reactions
- Eye (12%): pain, conjunctivitis, itching
- CNS (1-5%): dizziness, headache
Precautions (related to possibility of limited systemic absorption)
- Acute bronchospasm, pulmonary edema, asthma
- Bradycardia, AV block
- Hepatic disease
- Raynaud’s disease
- Diabetes
15
Q
Metoprolol (Lopressor)
A
Description
- TX of angina, hypertension, migraine headaches, MI, and tremor
- Increasingly utilized in the management of heart failure
Mechanism of action
- Competitive b1-selective adrenergic receptor antagonist
- Effect is ↓ in both resting and exercise HR and CO, and ↓ in both systolic and diastolic BP
Pharmacokinetics
- Dosing range is 100-450 mg PO QD
- Metoprolol is quickly absorbed, but F ~ 0.5 because of extensive first-pass metabolism
- Moderately lipid-soluble; widely distributed throughout the body
- Metabolism occurs primarily in the liver by CYP 2D6; t1/2 ~ 3-4 hr
- Excretion occurs mainly via the kidney as metabolites, only ~ 5% is excreted unchanged
Adverse reactions
- Adverse effects are generally mild and temporary
- CNS: depression, dizziness, fatigue
- CV: bradycardia, AV block, hypotension, cold hands and feet
- GI: xerostomia, NVD
Precautions
- Abrupt DC can produce myocardial ischemia, MI, arrhythmias, or severe hypertension
- Acute bronchospasm, pulmonary edema, asthma
- Bradycardia (< 45 BPM), AV block
- Hepatic disease
- Raynaud’s disease
- Diabetes
