Adrenergics (Konorev) Flashcards
Direct acting adrenomimetics come in three broad flavors. What are they?
Alpha agonists
Mixed alpha and beta agonists
Beta agonists
What are the alpha agonists?
Phenylephrine (Neo-Synephrine) (a1>a2>>>B)
Clonidine (Catapres) (a2>a1>>>>B)
What are the mixed alpha and beta agonists?
Norepinephrine (Levophed) (a1=a2; B1>>>B2)
Epinephrine (Adrenalin) (a1=a2; B1=B2)
What are the Beta agonists?
Dobutamine (Dobutrex) (B1>B2>>>>a)
Isoproterenol (Isuprel) (B1=B2>>>a)
Albuterol (Ventolin) (B2>B1>>>a)
Indirect Adrenomimetics come in four flavors. What are they?
Reuptake inhibitors of DA and NE
Inhibitors of MAO
Reverse NE and DA uptake mechanisms and increase release
Releasing agent and direct adrenergic receptor agonist
What are the DA and NE reuptake inhibitors?
Cocaine
What are the inhibitors of MAO?
Selegiline (Eldepryl)
Phenelzine (Nardil)
What drugs reverse NE and DA uptake mechanisms and increase their release?
Amphetmines
Methyphenidate (Ritalin)
Tyramine (not a drug)
What drugs are releasing agents AND direct adrenergic receptor agonists?
Ephedrine
What are the two targets of adrenergic drugs?
Sympathetic cholinergic terminals at the target site (NE or DA)
Examples: Cardiac and smooth muscle, glands, nerve terminals (NE); renal vascular smooth muscle (DA).
What is the primary role of adrenergic drugs?
Modulate adrenergic transmission and primarily control the function of sympathetic nervous system
What is the effect of drugs that activate adrenergic transmission?
AKA adrenomimetics or sympathomimetics
These mimic/promote the effects of NE, epinephrine, DA, at adrenergic receptors in the sympathetic NS
What is the effect of drugs that inhibit adrenergic transmission?
AKA sympatholytics/antiadrenergics
These prevent the effects of NE/DA/epinephrine at adrenergic receptors in the sympathetic NS
Direct acting adrenergic drugs produce their effects how?
By interacting with adrenergic receptors
either: adrenergic receptor agonists or antagonists
Indirect acting adrenergic drugs produce their effects how?
By increasing or reducing the concentration of NE at target receptors
This works by altering NTM concentration at the target site
MAO inhibitors, reuptake blockers, and releasing agents all take place where?
at the presynaptic neuron (reuptake blockers and MAO inhibitors) and in the synapse (releasing agents)
These are all indirect acting
Adrenergic receptor agonists take place where?
At the post synaptic neuron
these are direct acting
What are the effects of epinephrine on cardiac function?
Acts on B1
Increases force of contraction (positive inotropic)
increase HR
increases conduction velocity at AV node
What are the effects of Epinephrine on vascular tone?
Acts on B2 and a1
increases systolic BP
may decrease diastolic BP and TPVR
MAP unchanged
Note: many different receptor types in vascular beds
What other tissues and receptor types can Epinephrine effect?
skin vessels and mucous membranes-mostly a1
skeletal muscle-a1 and B2
renal and cerebral-D1 and a1
What are the effects of epineprhine on the respiratory system?
relaces bronchial muscle at B2
decreases secretions and congestion in mucosa at a1
What are the effects of epinephrine on skeletal muscles?
causes muscle tremor at B2
increases K uptake at B2
promotes hypokalemia and decreases K excretion by kidney
What are the effects of epinephrine on serum concentrations of glucose/FFA, renin?
Enhances liver glycogenolysis and gluconeogenesis (B2)
increases FFA in blood (B)
increases renin release (B1)
What are the effects of NE?
a1=a2; B1>>B2
- stimulates cardiac muscle, reduces HR
- vasoconstrictor
- lacks B2 agonist effects, no bronchodilation or vasodilation
- increases PVR and BP
- role of baroreflex
What is the role of phenylephrine?
- a agonist, a1>a2>>>B
- effective mydriatic and decongestant
- severe vasoconstriction, BP elevation and severe bradycardia
- baroreflex in response to phenylephrine
What are the effects of Clonidine?
- Selective a2 agonist, >a1>>>>B
- central effect on presynaptic a2 receptors in lower brainstem
- decreases sympathetic outflow
- reduces BP
- bradycardia
- locally-produces vasoconstriction
What are the effects of Isopreterenol?
- B1=B2>>>a
- non-selective beta agonist
- positive inotropic and chronotropic action, increases CO (B1)
- vasodilator and decreases arterial pressure (B2)
- causes bronchodilation (B2)
What are the effects of Dobutamine?
- B1>B2, a1
- Selective B1 agonist with a1 receptor activity
- negative isomer is an agonist at these receptors while a positive isomer is an a1 antagonist
- potent inotriopic action
- less chronotropic action compared to isoproterenol
What are the effects of Albuterol?
- B2>B1>>>a
- selective B2 agonist
- causes bronchodilation
What are some unique features of indirect acting adrenomimetics?
- more lipophilic (not catecholamines)
- easily penetrate BBB (but not tyramine)
- central nervous effects/stimulants
- heavily abused drugs (amphetamines, methylhenidate, cocaine)
What is tyramine?
- a product of decarboxylation of tyrosin
- hydrophilic and doesn’t cross BBB
- accumulated at high concentrations in certain foods
- metabolized by MOA in liver
- causes elevation of systolic blood pressure when given IV
- Tyramine pressor test is used to evaluate peripheral adrenervic function
What drugs are used to treat hypotensive emergencies like hemorrhagic shock, overdose of antihypertensives, or CNS depressants?
Chronic hypotension?
Cardiogenic shock?
NE, phenylephrine
Ephedrine
Dobutamine
What drugs are used to treat heart failure?
HTN?
Emergency treatment for complete AV block and cardiac arrest?
short term dobutamine in acute HF
a2 agonists for long term treatment
Epinephrine, isoproterenol
What drugs are used to treat depression?
narcolepsy?
Phenelzine, Selegiline
Amphetamines, Methylphenidate
What drugs are used to treat ADHD?
Obesity?
Methylphenidate
Ephedrine, Amphetamines
What drugs are used to treat bronchial asthma?
Congestion?
Anaphylaxis?
Albuterol
Phenylephrine, ephedrine
Epinephrine (resp. and CV components)
What drugs are used to treat glaucoma?
Examine the retina?
Urinary stress incontinence?
a2 selective agonists
Phenylephrine-induces mydriasis
Ephedrine
What are the cardiovascular adverse effects of adrenomimetics?
- increased BP
- increased cardiac work leading to MI and HF
- Sinus tach. and serious ventricular arrhythmias, inducing sudden cardiac death
What are the central nervous system toxities related to indirect acting lipophilic drugs?
- insomnia
- lack of apetite
- anxiety, restlessness
- psychoses
- convulsions and hemorrhagic stroke (cocaine)
Direct acting antiadrenergic drugs come in three flavors. What are they?
a adrenoceptor antagonists
Mixed blockers
B adrenoceptor blockers
What are the a adrenoceptor antagonists?
non-selective a1 and a2 receptor antagonists
- Phentolamine (Oraverse)
- Phenoxybensamine (Dibenzyline)
a1 receptor selective
- Prazosin (Minipress)
- Tamsoluosin (Flomax)
- Doxazosin (Cardura)
What are the mixed antiadrenergic blockers?
Labetalol (Trandate, B and a1 antagonist)
Carvedilol (Coreg, B and a1 antagonist)
What are the B adrenoceptor blockers?
B1 and B2 blockers
- propranolol (inderal)
- Pindolol (Visken)
- Nadolol (Corgard)
B1 Selective
- Metoprolol (Toprol)
- Betaxolol (Kerlone)
- Acebutolol (Sectral)
- Atenolol (Tenormin)
What are the indirect acting antiadrenergic drugs?
NE relase inhibitor: Guanethidine (Ismelin)
Tyrosine hydroxylase inhibitor: Metyrosine (Desmer)
Where do tyrosine hydroxylase inhibitors act?
at the presynaptic neuron
Indirect acting
Where do NE release inhibitors function?
At the synapse
Indirect acting
Where do adrenergic receptor antagonists act?
at the post synaptic neuron
Direct Acting
Describe the dose response curve of Phentolamine
a reversible competitive a agonist
noncovalent binding to a receptor
shorter acting
effect antagonized by high concentration of agonist
Describe the dose response curve to Phenoxybensamine
a non-competitive irreversible a antagonist
covalent binding to receptor
longer acting
not antagonized by alpha agonist
What are the cardiovascular effects of alpha antagonists?
- decreased PVR and BP
- Postural hypotension
- Reflex tachycardia
What are the effects of alpha antagonists on the GU system?
Relaxation of smooth muscles in prostate
decreased resistance to flow of urine
What are the effects of alpha antagonists on the eye?
relaxation of the pupillary dilator muscle-miosis
What drugs are used to treat pheochromocytoma?
Phentolamine
Phenoxybenzamine
metyrosine
What drugs are used to treat chronic HTN?
Prazosin
Doxazosin
these are a1 selective; nonselective a blockers are NOT used for this
What drugs are used for ED?
combination of phentolamine and a nonspecific vasodilator papaverine (injected into penis)
What drugs are used to treat BPH (urinary obstruction)
Tamsulosin
greater selectivty for the a1A than a1B
a1A is the most important a receptor subtype mediating prostate smooth muscle contraction
effectively relieves urinary obstruction and pain with little effect on BP
prazosin and doxazosin are also effective by drop BP more
What are the adverse effects of alpha antagonists?
- fewer with a1 selective antagonists
- postural hypotension with antagonism of a1 in venous smooth muscle
- nasal stuffiness
- tachycardia
- retention of fluid and salt
- impaired ejaculation
Beta blockers: Antagonists
atenolol
nadolol
propranolol
Beta Blockers: Partial agonists
Acebutolol
labetolol
pindolol
Beta blockes: inverse agonists
betaxolol
metoprolol
What makes a beta blocker a partial agonist?
Beta blockers with Intrinic sympathomimetic activity are partial agonists at beta adrenergic receptors
block sympathetic effects but have submaximal effects of their own, causing a blunted sympathetic response
less risk for bradycardia, increase in VLDL/HDL, and other effects
What are the effects of beta blockers on the heart?
negative inotropic effect
negative chronotropic effect
slow conduction via AV node
What are the effects of beta blockers on the blood vessels
initially-rise in peripheral vascular resistance
chronic use-decrease in PVR (lower BP in hypertensive individuals)
What are the effects of beta blockers in the RAAS system?
Inhibits renin release
What are the effects of beta blockers on the respiratory system?
increase airway resistance
What are the effects of beta blockers on the eye?
reduces production of aqueous humor, reduces intraocular pressure
What are the metabolic effects of beta blockers?
inhibits lipolysis
increases VLDL and decreases HDL, reduces HDL cholesterol/LDL cholesterol ratio
inhibits glycogenolysis and gluconeogenesis in the liver
How do beta blockers treat HTN?
antihypertensive effect is delayed
both beta blockers and mixed a-B blockers are used
How are beta blockers used to treat angina pectoris?
blcoking cardiac beta receptors decreases cardiac work and reduces oxygen consumption
beta blockers reduce the frequency of anginal episodes and improve exercise tolerance
How are beta blockers used to treat MI?
long term use in post-infarction period prolongs survival
-propranolol or metoprolol
How are beta blockers used to treat cardiac arrhythmias?
effective in ventricular and supraventricular arrhythmias including A. flutter and A. fib and ventricular ectopic beats
How are beta blockers used to treat heart failure?
effective for the treatment of chronic heart failure in selected pts.
-metoprolol and carvedilol shown in CT to be effective
Contraindicated in acute or severe CHF
How are beta blockers used to treat glaucoma?
reduces aqueous humor produciton by ciliary body
Betaxolol (a blocker w/o local anesthetic activty, don’t use propranolol)
How are beta blockers used to treat hyperthyroidism?
Propranolol us used to treat excessive catecholamine action on heart, thyroid storm, tachycardia, supraventricular and ventricular ectopic arrhythmias
What are the adverse effects of beta blockers on the CNS?
sedation
sleep disturbances
depression
Switch to more hyrophilic drug
What are the adverse effects of beta blockers on the respiratory system?
increase airway resistance
trigger bronchospasm and asthma attach
Switch to b1 selective
What are the adverse effects of beta blockers on the cardiovascular system
Depresison of HR, cardiac contractility and excitability
switch to partial agonist
What are the effects of beta blockers on the lipid profile?
chronic use-increase in VLDL, decrease in HDL and decreased HDL/LDL ratio
seen with selective and nonselective B blockers
switch to partial agonist drug
Describe the adverse effect: hypoglycemic episodes due beta blockers
delays recovery from insulin induced hypoglycemia by inhibiting glucose output by the liver
blunts perception of hypoglycemia (no sx)
increased incidence and severity in pts with TIDM on insulin
safer in TIIDM
Switch to B1 selective
What happens with abrupt discontinuation of beta blocker therapy?
enhanced cardiac stimulation and arrhythmias
increased risk in pt’s with ischemic heart disease
need to gradually taper dosing to prevent sympathetic hyperresponsiveness and potential toxicity
