Pharm - Adrenergic Agonists and Antagonists Flashcards
What are the prototype non-competitive and competitive alpha adrenergic blockers?
Non-competitive = phenoxybenzamine
Competitive = phentolamine
Describe the mechanism of action for phenoxybenzamine (include receptor affinity, receptor binding, and metabolism)
Phenoxybenzamine preferentially binds alpha 1 over alpha 2 covalently. Can aldo bind H1, AChR, and serotonin receptors with high doses.
Half-time = 24 hours
Describe the pharmacologic effects of phenoxybenzamine on the CNS, cardiovascular system, eye, and penis
CNS - weakness, nausea, and vomiting
Cardiovascular - vasodilation through blocking alpha 1 and reflex tachycardia by blocking of presynaptic alpha 2 receptors near the heart
Eye - miosis
Penis - inhibition of ejaculation
What are the clinical uses (4) of phenoxybenzamine
- Pre-operative management of pheochromocytoma with propanolol or other beta blocker
- PVD
- Raynaud Syndrome
- Acrocyanosis
Describe the mechanism of action for phentolamine in reference to receptors bound
Phentolamine will bind alpha 1 and alpha 2 equally
Can also bind to H1 receptors in the gastric mucosa
Descirbe the effects of phentolamine on the cardiovascular system and GI tract
CV - causes vasodilation through alpha 1 and sometimes reflex tachycardia through the same mechanisms as phenoxybenzamine
GI - increases gastric motility and pepsin and HCl release
What are the clinical uses of phentolamine (3)?
- Surgical management of pheochromocytoma to prevent hypertensive crises
- Aid in withdrawal from clonidine
- Treat necrosis induced by local NE administration
What are the side effects phentolamine (4)?
- Nausea
- Vomiting
- Tachycardia
- Orthostatic hypotension
What type of adrenergic antagonists are ergot alkaloids from rye fungus?
Non-selective alpha blockers.
Some stimulation of serotonin receptors
What kind of antagonist is prazosin?
Selective alpha1 antagonist
What are the clinical uses and side effects of prazosin?
Used to treat hypertension, and does not cause relfex tachycardia
Syncope is the common side effect due to orthostatic hypotension
What type of drug is tamulosin?
Selective alpha 1A antagonist
What are the clinical uses and side effects of tamulosin?
This drug is specific for prostatic smooth muscle and is used to treat BPH
The specificity of the drug eliminates orthostatic hypotension
Describe the mechanism of action of propanolol
Non-selective competitive beta blocker
Note: this is a lipid soluble drug that is able to enter the CNS –> drowsiness
What are the effects of propanolol on the CV system, Respiratory system, and metabolism?
Cardiovascualr - decreases CO, HR, and AV nodal conduction and inhibits vasodilation.
Note: prolonged use can cause decreases in TPR
Respiratory - block bronchodilation
Note: avoid in asthmatics eedeot
Metabolism - block glycogenolysis and lipolysis
Describe the absorption and metabolism of propranolol?
This drug is absorbed orally, but variably susceptible to the first-pass effect. Each patient needs to be dosed individually
What are the cardiovascular uses (4) of propanolol?
- Hypertension
- Angina pectoris
- Arrhythmia
- Reduction of mortality after acute MI by decreasing the likelihood of ventricular arrhythmia and recurrent ischemia
What are the non-cardiovascular clinical uses (4) of propanolol?
- Management of preoperative pheochromocytoma along with phenoxybenzamine
- anxiety
- migraine headaches
- thyrotoxicosis - hyperthyroidism patients have lots of beta receptors
What are the common (6) and severe (6) side effects of propanolol use?
Common
- dizziness
- drowziness
- diarrhea
- depression
- constipation
- nausea
Severe
- fever
- rash
- purpura
- potentiate hypoglycemia
- increase VLDL and HDL
- interfere with SGOT and BUN assays
What are the four contraindications for propanolol use?
- Overt heart failure
- Cardiogenic shock
- Asthma
- AV nodal block
What is metoprolol and what is it used for?
Cardioselective Beta 1 antagonist used to treat hypertension
What is atenolol and what is it used for?
Cardioselective Beta 1 blocker used in the treatment of chronic stable angina and hypertension
Note: decreased risk of bronchospasm and does not prolong recovery from insulin-induced hypoglycemia
What is acebutolol and what is it used for?
A cardioselective beta blocker for hypertension and dysrrhythmias
What is betaxolol and what is it used for?
A beta 1 blocker for hypertension and glaucoma
What are the five catecholamines and describe there metabolism, distribution, and route of administration?
- Epinephrine
- Norepinephrine
- Isoproterenol
- Dopamine
- Dobutamine
These drugs are quickly metabolized, do not cross the BBB, and must be administered any other way than orally
Describe the three modes of action for catecholamines?
Direct - binds to adrenergic receptors
Indirect - induces the release of norepinephrine or inhibits its reuptake
Mixed - does both direct and indirect
Generally describe the effects of alpha receptor stimulation
Alpha 1 - Contraction of smooth muscle
Alpha 2 - inhibition of insulin release, relaxation of intestinal smooth muscle, and inhibition of presynaptic NE release
Generally describe the effects of beta receptor stimualtion
Beta 1 - increases cardiac output and renin release
Beta 2 - increases glycogenolysis, insulin release, and smooth muscle relaxation
Beta 3 - lipolysis
Describe the receptor affinity for epinephrine
Epinephrine has affinity for all adrenergic receptors. Affinity at low doses is greater for beta 2 than alpha 1, but vice versa at higher doses
Describe the effects of epinephrine on the cardiovascular system
Increased CO, HR, contractility, conduciton
Blood flow
- skeletal muscle undergoes vasodilation at low doses and constriction at high doses
- Vasoconstriciton of vessels in kidneys, mucosa, skin, and lungs
- vasodilation of coronary arteries
Systolic blood pressure will be slightly increased while diastolic blood pressure is decreased . Overall blood pressure remains unchanged or slightly increased.
What are the four clinical uses of epinephrine?
- pediatric asthma
- topical hemolytic - only works on capillaries and arterioles
- anaphylactic shock
- prolongation of local anesthetic duration
What are the adverse effects and contraindications of epinephrine?
Side effects - Headache, anxiety, and fear
Note: when mixed with halothane, arrhythmias can occur
Contraindications - hypertension, angina pectoris, shock, hyperthyroidism, and degenerative heart disease
Describe the receptor affinity of norepinephrine
High affinity for alpha 1, alpha 2, and beta 1….beta 3?
Note: very weak at beta 2
Describe the cardiovascular and metabolic effects of norepinephrine
Causes increase in blood pressure, heart rate, and cardiac output. Followed by reflex bradycardia resulting in slow forceful heart rate.
Blood pressure is increased by vasoconstriction.
alpha 1 stimulation modestly increases glycogenolysis, but beta 3 stimulation increases lipolysis
Describe the use, side effects, and contraindications of norepinephrine
Used as a pressor agent for spinal anesthesia
Side effects - headache, anxiety, and slow forceful heart rate
Contraindications - same as epinephrine
What receptors does isoproterenol interact with?
All beta receptors
What are the cardiovascular and metabolic effects of isoproterenol?
Cardiovascular - increased heart everything with vasodilation in skeletal muscle. Increase in systolic and decrease in diastolic blood pressures with a net decrease or no change in BP.
Metabolism - activation of lipolysis, but glycogenolysis is opposed by induced insulin release
What are the clinical uses (3) and side effects (5) of isoproterenol?
Clinical Uses
- bronchial asthma
- heart block
- cardiogenic shock following MI
Side effects
- tachycardia
- headache
- arrhythmia
- angina pectoris
- flushing of the skin
Describe the receptor affinity of dopamine
Agonist at beta 1 and D1 at low doses, and effecting alpha 1 at higher doses
What are the cardiovascular effects and clinical uses of dopam ine?
Causes a mild increase in cardiac output. Main effect is increased blood flow to the mesenteric and renal vascular beds. Note: this effect can be overriden with higher doses stimulating alpha 1 or chlorpromazine
Clinical uses - cardiogenic shock (increase CO and blood flow to vital organs) and chronic CHF (increase CO without increasing TPR)
What is dobutamine and what effects does it have?
Dobutamine is a beta 1 selective partial agonist with mild positive inotropic and chronotropic effects
What are the clinical uses of dobutamine?
Used to treat acute MI and chronic CHF with less chance of arrhythmia
Describe the mechanism of action, pharmacologic effects, and clinical uses of phenylephrine
Phenylephrine is a selective alpha 1 agonist which causes vasoconstriction and reflex bradycardia. Reflex can be blocked by atropine.
The clinical uses include nasal decongestant, infiltration with anesthetic, pressor agent for spinal anesthesia, and paroxysmal atrial tachycardia.
Note: Pressor agent causes reflex bradycardua for the atrial tachycardia
Name (3) beta adrenergic agonists used to treat asthma. What is their mechanism of action, pharmacologic effects, and side effects?
Albuterol - used for bronchial asthma, side effects include tachycardia, hypoglycemia, hypokalemia, and muscle tremors
Salmeterol and formoterol - are longer lasting agents which can be used for phrophylaxis of asthma
MOA - bind to beta 2 with a ten fold selectivity compared to beta 1. Long duration of action, but may develop tolerance quickly
All of these will cause bronchodilation
What the fuck is tyramine and why do you care?
Tyramine is a compound found in beer, red wine, and cheese (I love cheese). Normally this little fucker is degraded by GI and hepatic MAO, but little bitches taking MAOIs will feel the effects of tyramine.
Tyramine will enter the presynaptic nerve terminal and displace NE. Ya bitch!
What is the MOA of cocaine, tricyclic antidepressants, and SNRIs
They block the action of NET maintaining high concentration of NE in the synapse
What is the MOA of amphetamines and their pharmacologic effects?
Amphetamines indirectly cause the release of NE and inhibit its reuptake into the nerve terminal.
Pharmacologic effects
CNS - Improves concentration, confidence, alertness, and fatigue
CV - positively affects inotrope and vasoconstriction, negative effect on chronotrope
Urinary sphincter contraction
What are the clinical uses (3), side effects (6), and toxicity signs (3 and 3)/treatment for amphetamines?
Clinical Uses - ADHD, obesity, and narcolepsy
Note: tolerance to appetite suppression and mood effects develops quickly
side effects - insomnia, delerium, nausea, vomiting, anxiety, and arrhythmia
Acute toxicity - convulsions, coma, and death
Chronic toxicity - abnormal mental state, weight loss, and psychotic reactions
Toxicity treatment - Amphetamines are weak bases and can be removed quicker by making the urine acidic with ammonium chloride
Describe the MOA, metabolism, and pharmacologic effects of ephedrine
MOA - mixed action: direct action at beta receptors and indirect release of NE
Metabolism - not degraded by COMT or MAO, useful orally and long lasting
Pharmacologic effects - A modest CNS stimulant which causes increase in inotrope and weak vasoconstriction but no change in HR. Moderate sustained bronchodilation
What is tachyphylaxis and what drug does this pertain to?
Reduced efficacy with repeated use
Ephedrine
What are the clincial uses (3) and adverse effects (3) of ephedrine?
Clinical uses - pressor agent for spinal anesthesia, nasal decongestant, and treatment of severe acute bronchospasm
Adverse effects - insomnia, anxiety, and palpitations
Name the four zolines (ZOLTAN!!). What are they used for and how do they work
Naphazoline, tetrahydrozoline, xylometazoline, and oxymetazoline
These are alpha one agonists used to treat nasal decongestion
What should be noted about tetrahydrozoline and xylometazoline
tetrahydrozoline may cause sedation or shock in children (finally they’ll shut the fuck up!) and possibly rebound congestion
Xylometazoline can distribute systemically and should be used cautiously in hypertensive patients
What is the mechanism of action, clinical use, and side effect of guanethidine?
MOA - competes with NE at NET for uptake into the presynaptic terminal where it binds to chrommafin vesicles (?that’s probably what they’re called?) displacing NE and inhibiting its release
Clinical Uses - was used to treat essential hypertension in the medieval times
Adverse effects - orthostatic hypotension
What does reserpine do and what would you use it for?
Blocks VMAT’s pussy with it’s black dick so DOPA cannot enter the chrommafin vesicle (again ??).
Last line agent for hypertension
What is the MOA and pharmacologic effects of clonidine?
Clonidine binds slectively to alpha 2 receptors and activates them
When administered through IV clonidine causes increase in BP through peripheral alpha receptors and then a decrease through the central receptors. When administered percutaneous or orally the drug causes decreased cardiac output and preload.
What are the clinical uses (2) and adverse effects (4) of clonidine?
Clinical uses - last line agent for essential hypertension and adjunct in narcotic withdrawal
Adverse effects - dry mouth, sedation, impotence, and hypertensive crises with sudden withdrawal
Why would I ever use methyldopa?
If you have a preggers woman with hypertension
What is fenoldopam?
This is a D1 agonist used to treat cardiogenic shock
What is the sequence of effects in NE administration?
High action at Beta 1 and Alpha 1 receptors, with low affinity for Beta 2 receptors.
Blood pressure and peripheral resistance increase –> increased vagal tone causing a slowing of the heart rate regardless of the effects at Beta 1
What are the effects of low epinephrine infusion?
Mean pressure remains so there is no increased vagal tone causing a slowed HR. Peripheral resistance will decrease slightly.
What are the effects of low isoproterenol infusion?
No effect on systemic pressure, but resistance drops while HR increases
What are examples of 3rd generation beta blockers
Carvedilol and labetalol
Note: have effects at Beta 1, Beta 2, ad Alpha 1
