Pharmacology - Autonomics IV-V-VI Flashcards
Effect of alpha-1 adrenergic receptor
increase in IP3, DAG
smooth muscle contraction
Effect of beta-1 adrenergic receptor
increase force and rate of contraction of heart
increase cAMP
increased renin secretion in kidney
Effect of beta-2 adrenergic receptor
increase cAMP
smooth muscle relaxation
Effect of beta-3 adrenergic receptor
increase cAMP
lipolysis
What is the primary mechanism for reducing/terminating the effects of NE?
re-uptake;
repackaged for future release
Monoamine oxidase (MAO) and Catechol-O-Methyltransferanse break down what?
NE, Epi, exogenous adrenergic drugs ie tyramine
major metabolic enzymes;
prominent in liver
Elevated levels of plasma metanephrine is an indicator of:
Pheochromocytoma
Metanephrine is a metabolite of NE/E
Non-selective beta-1 and 2 antagonist
Propranolol
Non-selective beta-1 and 2 agonist
Isoproterenol
**most potent agonist of beta-1 and 2
Beta-2 agonist
Albuterol
D1 agonist
Fenoldopam
dopamine receptor agonist
**does not cause NE release - just acts on D1
Alpha-2 selective agonist
Clonidine
**most potent agonist of alpha-2
Alpha-1 selective agonist
Phenylephrine
Alpha-1 antagonist
Prazosin
Beta-1 antagonist
Atenolol
Vasculature have both alpha-1 and beta-2 receptors. Which dominates?
Effects of alpha-1 (constriction) are dominant
Dopamine acts on what receptors?
DA
alpha-1
beta-1
What is the most potent stimulator of alpha-2?
Epinephrine
Tyramine and amphetamine are what kinds of adrenergic drugs?
Indirect agonists - cause release of NE
Ephedrine and Hydroxyamphetamine are what kinds of adrenergic agents?
Mixed (direct and indrect effects) agents
Uses: Fenoldopam
to treat a hypertensive emergency, anuria
to increase blood flow at renal, mesenteric and cerebral arteries;
to lower blood pressure (hypertensive emergencies)
Uses: Epinephrine
control hemorrhage;
vasoconstriction in dental procedures
alpha-1
anaphylactic shock alpha and beta activation - vasoconstriction, bronchodilation and decrease histamine release from mast cells (beta-2)
Uses: Ephedrine, Phenylephrine
Nasal decongestions
alpha-1
Uses: Dopamine
treat hypotension ie to replace adrenal catecholamines like with spinal anesthesia, following pheochromocytoma surgery
Class: Ergotamine
Ergot alkaloid
alpha-adrenergic blocker BUT alpha-agonist??
Class: Ergonovine
Ergot alkaloid
alpha-adrenergic blocker BUT alpha-agonist??
Use: Ergonovine
to treat post-partum hemorrhage
“oxytocic”
Use: Ergotamine
to treat prodrome of migraines
Side Effects: Ergot alkaloids
Hallucinations (like LSD)
Use: Bromocriptine
Treat hyperprolactinemia;
Treat Parkinsonianism
DA2 agonist
Beta-1 selective agonist for cardiac stimulation
Dobutamine
also used during cardiac stress test
first generation beta blocker
non-selective
propranolol
non-seletive
second generation beta blocker
beta-1 selective
metoprolol
atenolol
third generation beta blocker
non-selective with additional actions
carvedilol
labetalol
third generation beta blocker
beta-1 selective with additional actions
betaxolol
plasma half life of metoprolol
about 4 hours
Metoprolo is a beta-1 selective 2nd generation beta blocker
plasma half life of atenolol
about 6-8 hours
Atenolol is the least lipid soluble beta blocker, thus not in CNS;
beta-1 selective second generation beta blocker
Use: Labetolol
to treat hypertension
lowers TPR with little tachycardia
3rd generation - beta blocker with additional actions (ie some alpha-1 antagonism)
Use: Carvedilol
to treat HTN and CHF;
3rd generation - beta blocker with additional actions (ie some alpha-1 antagonism)
Third generation beta blocker “additional actions” include:
NO production beta-2 agonism Ca entry blockade alpha-1 antagonism K channel opening antioxidant activity
Therapeutic uses of beta-blockers in general include:
Cardiac arrhythmias Angina Glaucoma Migraine Anxiety/stage fright Heart failure HTN
Use ONLY what kind of beta-blockers to treat heart failure?
2nd and 3rd generation
Too much stimulation of what receptor may precipitate an asthma attack?
Beta-2
Phentolamine
Phenoxybenzamine
Prazosin
these drugs are all:
alpha receptor antagonists
What are the major side effects of alpha-reeptor antagonists?
tachycardia;
postural hypotension
Which alpha-receptor antagonist covalently binds to alpha-1 receptors?
Phenoxybenzamine
therefore, long-acting
Which alpha-receptor antagonists are nonselective, in that they affect alpha-1 and alpha-2?
Phentolamine
Phenoxybenzamine
**Prazosin is selective for alpha-1
Therapeutic use: Prazosin
HTN
Peripheral vascular disease (including Raynaud’s and frostbite and atherosclerosis)
BPH
Therapeutic use: Phenoxybanzamine
Pheochromocytoma;
Peripheral vascular disease (including Raynaud’s and frostbite);
Phentolamine and Phenoxybenzamine have what unfortunate sexual side effect?
Inhibit ejaculation
Therapeutic use: Phentolamine
Pheochromocytoma;
Peripheral vascular disease (including Raynaud’s and frostbite);
Beta-2 blockers may not be appropriate for which patient population?
Diabetics
bc there can be a decrease in glycogenolysis and lipolysis in response to hypoglycemia
MOA: alpha-methyltyrosine
blocks synthesis of DA and NE by inhibiting tyrosine hydroxylase
Use: alpha-methyltyrosine
Mgmt of pheochromocytoma
Side effects are “many and serious”
MOA: Reserpine
Release of empty vesicles (NE is not taken into vesicles b/c it binds uptake transporter and stops it)
Class:
alpha-methyltyrosine
reserpine
guanethidine
nerve ending blocker
MOA: guanethidine
False neurotransmitter (vesicles become full of guanethidine rather than NE) --CNS shooting blanks essentially
Use: guanethidine
HTN
Side effects are “many and serious”
not commonly used clinically
What is one major side effect of Reserpine and a reason it is not commonly used clinically?
depression/suicide
MOA: cocaine
prevents NE uptake
Use: cocaine
Local anesthetic, vasoconstrictor
Side effects: cocaine
insomnia
anxiety
arrhythmia
NE acts on what receptors?
alpha-1
alpha-2
beta-1
Therapeutic use: NE
treat hypotension
NE vasoconstricts, increases BP and HR
Epinephrine acts on what receptors?
alpha-1
alpha-2
beta-1
beta-2
Therapeutic use: Epinephrine
anaphylactic shock;
glaucoma
Epinephrine increases HR and contractility, BP
Use: Isoproterenol
non-selective beta agonist:
asthma
shock
heart block
Isoproterenol decreases resistance, increases CO, increases HR and bronchodilates
Side effects: Isoproterenol
Palpitations
tachyarrhymias
headache
Therapeutic uses: dobutamine
cardiac decompensation
shock
heart block
Dobutamine increases contractility, increases HR directly and indrectly
Side Effects: Dobutamine
Tachyarrhythmia
HTN
beta-2 selective agonists, name 2:
albuterol
terbutaline
Therapeutic uses:
Albuterol
Terbutaline
asthma
COPD
Albuterol and Terbutaline relax bronchial and uterine smooth muscle
Side Effects:
Albuterol
Terbutaline
Tachycardia
Muscle tremor
Uses: Phenylephrine
Nasal congestion
Postural hypotension
Phenylephrine is a vasoconstrictor
Side effects: Phenylephrine
Reflex bradycardia
HTN
Therapeutic use:
Clonidine
alpha-methyldopa (prodrug)
HTN
shock
withdrawal from drug dependence
Actions: decrease sympathetic outflow from CNS, decrease resistance
Side effects:
Clonidine
alpha-methyldopa (prodrug)
Sedation
Side effects: Fenoldopam
Posturalhypotension
Uses: amphetamine
ADHD
Narcolepsy
recreational
CNS stimulation, increase BP, increase HR
Side effects: amphetamine
Insomnia
HTN
anxiety
arrhythmias
MOA: amphetamine
indirect acting release of NE
Uses: Dopamine
shock
renal failure
hypotention
Actions:
vasodilation, increase GFR, increase HR, increase BP
Side effects: dopamine
vasoconstriction at high doses
Give the agonist and antagonist for beta-1 receptor:
Agonist: Dobutamine
Antagonist: Atenolol
Give the agonist and antagonist for non-selective beta-1 and 2 receptors:
Agonist: Isoproterenol
Antagonist: Propranolol
An alternative to propranolol, that is also a non-selective beta antagonist, is:
Timolol
Uses:
Propranolol
Timolol
HTN
Angina
Arrythmias
Side effects:
Propranolol
Timolol
Bradycardia
Bronchoconstriction
sexual dysfunction
Give the agonist and antagonist for alpha-1 receptor:
Agonist: Phenylephrine
Antagonist: Prazosin
Therapeutic use: Betaxolol
CHF
HTN
Side effects: bradycardia
MOA Terazosin
vasodilatory effect via block of a1 receptors, leading to a reflex tachycardia
MOA Atropine
Atropine would lead to block of cholinergic M3 receptors
BPH is often managed with:
BPH is often managed with alpha blockers
ie Prazosin
Terazosin
MOA alpha-methyltyrosine
Alpha-methyltyrosine blocks tyrosine hydroxylase and would cause a depletion of norepinephrine (and dopamine and epinephrine) stores. This effectively produces a chemical sympathectomy, resulting in post-synaptic receptor up-regulation; thus, producing a
denervation supersensitivity.
Labetalol is:
a non-selective beta-blocker with additional α1 antagonist properties.
“third generation”
Therapeutic Use: Ipratroprium
COPD, asthma
antimuscarinic
