10 - Adrenergics Flashcards
What are the effects of alpha 1 receptor activation in the:
- Eyes
- Arteries
- Veins
- GU Smooth muscle male
5: Vas deferens
- Eyes: constriction of radial muscle of the iris
- Arteries: constriction
- Veins: constriction
- GU smooth muscle male: constriction
- Vas Deferens: ejaculation
What are the effects of alpha 2 receptor activation in the:
- Pre-synaptic nerve terminals
- CNS
Presynaptic nerve terminals: inhibition of transmitter release
CNS: Inhibition of sympathetic outflow to blood vessels
What are the effects of B1 receptor activation in the heart and kidney?
Heart: increased rate and forces of contraction and increased AV nodal conduciton velocity
Kidney: renin release
What are the effects of B2 receptor activation in the:
- Arteries
- Bronchi:
- Skeletal muscle
- liver
- Arteries: dilation
- Bronchi: dilation
- Glycogenolysis
- Glycogenolysis and gluconeogenesis
What is the effect of domamine1 receptor in the arterteris of the kidney and mesentery?
Dilation
Sympathomimetics mimic the effects of ______ activation?
sympathetic
What type of smooth muscles and glands do sympathomimetics have excitatory actions on? What other excitatory action does it have?
Blood vessels, radial muscle, salivary glands, sweat glands
Cardiac excitatory actions
What type of smooth muscle is inhibited by sympathomimetics?
Wall of the gut, bronchial tree, blood vessels supplying skeletal muscle.
What are the metabolic actions of sympathomimetics?
Glycogenolysis (liver and skeletal muscle), gluconeogenesis (liver), and liberation of free fatty acids from adipocytes.
What are the endocrine actions of sympathomimetics?
Decrease release of insulin and increase release of renin.
What actions do sympathomimetics have in the CNS?
Respiratory stimulation, increase wakefulness, psychomotor activity, reduction in appetite.
What are the three types of adrenergic agonists?
Direct acting, mixed acting, and indirect acting.
What are the two types of direct acting adrenergic agonists?
Selective and non-selective
What are the types of indirect-acting adrenergic agonists?
Releasing agents, uptake inhibitors, MOA inhibitors, COMT inhibitors.
What are the catecholamines? What metabolizes them? What are some important properties?
Norepinephrine, epinephrine, dopamine.
Rapidly metabolized by MAO and COMT and not effective by oral administration
Short T1/2 and must be given parenterally
What receptors are selective for epinephrine?
a1, a2, B1, and B2.
What are the cardiovascular effects of epi? What are the respiratory effects? Metabolic effects?
CV: potent vasopressor (a2) but can dilate some vascular beds (B2), cardiostimulatory (B1)
Resp: bronchodilation (B2)
Metabolic: increases blood glucose and fatty acids
What are the therapeutic uses of epinephrine?
Hypersensitivity reaction; anaphylaxis.
Increases duration of action of local anesthetics,
Bradyarrhythmias (slow HR)
Mydriatic (dilation) , decreases hemorrhage and conjunctival congestion.
What is the result of low epinephrine concentrations in blood vessels of skeletal muscles? High?
Low concentration: B2 dilation
High concentration: a1 constriction
What is the receptor selectivity of norepinephrine?
a1, a2, B1
What are the CV effects of norepi?
(a1 mainly)
- Increases pulm. vascular resistance
- Increases mean BP
- can cause reflex bradycardia
What are the therapeutic uses of norepinephrine?
Vasoconstrictor under certain intensive care situations such as shock and hypotension during reduced sympathetic tone.
What is the effect of a low dose of dopamine? What receptor is involved?
“renal dose” dilation of renal and mesenteric arteries
causes a decrease in peripheral vascular resistance (D1 receptor)
What is the effect of an intermediate dose of dopamine? What receptor is involved?
“cardiac dose”
Increases HR, contractive force, cardiac output
D1 + B1 receptor
What is the effect of a high dose of dopamine? what receptor is involved?
“pressor dose”
Vasoconstriction and increased peripheral vascular resistance
D1 + B1 + a1
What is the absorption, fate, and excretion of dopamine? What is the therapeutic use?
Similar to epinephrine; administered IV and dose is titrated to achieve desired effect.
Therapeutic use: severe decompensated heart failure, shock (cardiogenic or septic).
What is the receptor selectivity of isoproterenol?
B1 and B2
What are the CV and respiratory effects of isoproterenol?
CV: decrease PVR, increase HR, contractile force, CO, decreased mean BP.
Rep: bronchodilation
what is the absorption and fate of isoproterenol? What is the therapeutic use?
Metabolized by COMT and has a brief duration of action.
Emergency use to stimulate heart rate during bradycardia or heart block.
What is the overall effect of Dobutamine?
It’s a racemic mixture that functions as a B1 agonist.
What are the CV effects of dobutamine?
Increased HR, contractility, and CO.
Minimal change in peripheral vascular resistance and BP.
What is the absorption and fate of dobutamine? What are the therapeutic uses?
Metabolized rapidly, brief duration of action.
Uses: short-term treatment of cardiac decompensation (card surgery, CHF, infarction), cardiac stress testing
What receptors does albuterol act on? How is it administered?
Mainly B2 adrenergic receptors (agonist).
Administered by inhalation or orally. Short acting and rapid onset.
What is the therapeutic use of albuterol? What are some adverse effects?
Used for relief of bronchoconstriction (asthma)
Adverse effects: tremor, anxiety, tachycardia.
What is Salmeterol? How is it given and what’s the duration of action?
A B2 adrenergic receptor agonist given by inhalation.
> 12 hour duration of action.
What is the therapeutic use of Salmeterol? Can it be used for acute bronchospasm?
Chronic obstructive pulmonary disease, moderate to severe persistent asthma.
Slow onset of action so not suitable as monotherapy for acute bronchospasm.
What is phenylephrine? What is its action?
An agonist of a1 adrenergic receptors.
Increases systolic and diastolic BP.
Reflex decreases heart rate.
Decreases blood flow in most vascular beds.
What are the therapeutic uses of phenylephrine?
Ophthalmic: mydriatic, decreases hemorrhage and congestion
Nasal decongestant (oral or nasal spray)
Used with local anesthetics ti increase duration of action
Treat hypotension
What is Clonidine?
Orally active alpha2 adrenergic receptor agonist that directly stimulates central alpha2 receptors to reduce sympathetic outflow.
What is the therapeutic use of Clonidine? What isa major adverse effect?
It’s an anti-hypertensive agent.
Xerostomia (dry mouth) and drowsiness occur in 50% of patients.
What is the action of clonidine
It gets into the CNS and activates alpha2 receptors to dampen sympathetic signals to the heart and vessels.
What is Methyldopa? What type of receptor agonists are they?
Orally active pro-drug metabolized in nerve terminals to alpha-methyldopamine and alpha-methylnorepinephrine which are stored and released with nerve stimulation.
Both are potent alpha2 receptor agonists and stimulate central a2 receptors to reduce sympathetic outflow.
What is the therapeutic use of methyldopa? What are the side effects?
Anti-hypertensive.
Side effects similar to clonidine: xerostomia and drowsiness.
What is the process by which methyldopa is activated in the body? What is a unique characteristic of methyldopa?
It uses the same enzymes as tyrosine to be activated, and then activates a2 receptors in the CV control centers in the CNS to cause a decrease in sympathetic outflow.
It is save to use on pregnant women.
What is Tyramine? What happens when people take MAOIs?
Something we get through diet and is rapidly metabolized by MAO.
When taking MAOIs, tyramine can’t be broken down and builds up in the nerve terminals.
This causes the release of norepinephrine and can result in a hypertensive emergency.
What are three additional sympathomimetics?
Amphetamine, methamphetamine, ephedrine/pseudoephedrine
What is amphetamine? How can it be given?
Powerful CNS stimulant effective with oral admin (long t1/2), depresses appetite, stimulates resp. center and increases respirations.
Releases norepi and other biogenic amines (dopamine from granules)
Psychological dependence can occur.
What is the therapeutic use of amphetamine?
Narcolepsy, attention deficit/hyperactivity disorder.
How does amphetamine get into the nerve terminal? What happens next?
Via the Norepinephrine transporter (NET), then it causes the release of norepi and other biogenic amines from storage granules.
What is pseudoephedrine? How can it be affectively given?
Direct alpha1 agonist with some B2 agonist acgtivity.
Orally effective but less stimulation compared to amphetamine.
What is the therapeutic use of pseudoephedrine?
Nasal decongestant.
Availability is restricted.
What are general adverse effects/toxicity of adrenergic agonists?
Throbbing headache from vasocontriction- alpha agonists
Increased HR (palpitations)-B agonists
Pericardial pain (angina due to increase HR)- B agonists
Cardiac arrhythmias - B agonists
Cerebral hemorrhage due to increased BP - alpha agonissts
Restlessness, anxiety - alpha and B agonists.
What are adrenergic neuron blockers? What are they historically used to treat?
Drugs that disrupt adrenergic neuron function by inhibiting the storage, synthesis, or release of norepinephrine.
Historically used to treat hypertension.
What is the function of guanethidine and guanadrel? How can it be taken?
Inhibit norepi release and deplete neuronal amine stores.
Orally active and long-lasting.
Do not penetrate into CNS.
What is the mechanism of action of guanethidine and guanadrel? What inhibits their effects?
Taken into adrenergic nerves via NET, depletes stores of norepi.
Effects inhibited by tricyclic antidepressants that also inhibit the NET.
What drugs are used to treat essential hypertension but have side effects of orthostatic hypotension, male sexual dysfunction, diarrhea, muscle weakness and edema?
Guanethidine and guanadrel
What drug diffuses into adrenergic neurons and depletes nerve of nts by inhibiting VMAT? How it is administered and what is it used to treat?
Reserpine.
Orally active; treatment of hypertension.
What are the adverse side effects of reserpine?
Can enter brain and had adverse CNS effects including depression (suicidal tendencies) and sedation.
Diarrhea, orthostatic hypotension, increased gastric acid secretion.
What is the function of adrenergic receptor antagonists?
Inhibit the interaction of norepinephrine, epinephrine, and other sympathomimetics with alpha and B receptors.
What are the types of alpha adrenergic receptor antagonists?
Non-selective and alpha1 selective
What are the types of B-adrenergic receptor antagonists?
Non-selective (1st generation)
B1 selective (2nd gen)
Antagonists with additional CV actions (3rd gen)
What two non-selective drugs that work by blocking both alpha1 and alpha2 adrenergic receptors? Compare the two.
Phenoxybenzamine: irreversible antagonist; orally active with a long duration of action
Phentolamine: competitive reversible antagonist; orally active with a shorter duration of action (2-4hr). Can be overcome with increasing agonist.
What are the therapeutic uses of phenoxybenzamine and phentolamine? What are side effects?
Pheochromocytoma - a small vascular tumor of the adrenal medulla.
Hypotension, reflex cardiostimulation (tachy and inotropy)
What is the cause of adverse side effects with nonselective alpha blockers?
alpha blockers prevent norepinephrine from binding to alpha1 and alpa2.
Since alpha2 is the breaking system of norepi, inactivating it will result in a not of norepi being released into the cleft.
The only receptor it can bind to is B1 now, which will cause tachycardia.
What are two alpha1 selective receptor antagonists?
Prazosin and tamsulosin
What is prazosin? What are some side effects that are avoided with this drug?
Selective, orally active competitive antagonist of alpha1 receptors
Minimal tachy b/c little blockage of pre-synaptic a2 receptors.
Decreases vascular tone in resistance (arteries) and capacitance (veins) beds.
Favorable effects on lipid profile.
What are the clinical uses of Prazosin? What are the side effects?
Use: hypertension, short-term treatment of congestive heart failure.
Side effects: “first dose” phenomenon, orthostatic hypotension.
What is Tamsulosin?
Orally active a1 adrenergic receptor antagonist with some subtype selectivity for a1A and a1B subtypes.
Favors blockage of a1A receptors in prostate (vs in blood vessels)
What drug is effective for treatment of benign prostatic hyperplasia (BPH) with little effect on blood pressure and is not approved for HTN treatment?
Tamsulosin.
What are distinguishing features among the B adrenergic receptor antagonists?
Relative affinity for B1 and B2 receptors, intrinsic sympathomimetic activity (act as partial agonists).
Capacity to induce vasodilation or other pharmacological properties.
Pharmacokinetic properties.
What are the cardiovascular effects of B adrenergic receptor antagonists?
Slow heart rate and decreased myocardial contractility (determinants of O2 demand).
Reduced sinus rate, decrease activity of ectopic pacemakers, slow atrial and AV nodal conduciton.
Anti-hypertensive.
What are the pulmonary and metabolic effects of B adrenergic receptor antagonists?
Pulm: bronchoconstriction (B2 antagonism)
Metabolic: block sympathetic-mediated mobilzation of glucose and free FAs into the circulation
What are some CV adverse effects and precautions about B adrenergic receptor antagonists?
May induce heart failure in susceptible patients.
Bradycardia.
May worsen symptoms of peripheral vascular disease (B2 receptors)
What are some adverse effects and precautions pertaining to B adrenergic receptor antagonists on the pulmonary and CNS systems?
Pulm: can increase airway resistance in those with asthma or COPD
CNS: fatigue, sleep disturbance (insomnia, nightmares), depression
What are some adverse effects and precautions pertaining to B adrenergic receptor antagonists on metabolism?
Blunt recognition of hypoglycemia and may delay recovery from insulin-induced hypoglycemia.
What are some CV therapeutic uses of B adrenergic receptor antagonists?
Hypertension, angina, acute coronary syndromes (MI), congestive heart failure.
What are other cardiovascular therapeutic uses of B adrenergic receptor antagonists?
Topical administration for chronic open angle glaucoma.
Migraine prophylaxis, symptoms during anxiety-provoking situations, essential tremors.
What are some important clinical consideration when using B adrenergic receptor antagonists (ie how do you know which B adrenergic receptor antagonist to use on a pt)?
Selection of drug is based largely on pharmacokinetics and pharmacodynamic differences as well as cost.
Specific drugs given based on certain diseases with documented efficacy.
B1 selective antagonists preferable in pts with bronchospastic disease, diabetes, and peripheral vascular disease.
What are examples of non-selective B adrenergic receptor antagonists?
Propanolol and timolol
What is the function of propranolol?
Prototype orally bioavailable antagonist of both B1 and B2 receptors,.
What are clinical uses of propranolol?
Hypertension, angina, cardiac arrythmias, MI, pheochromocytoma, migraine prophylaxis, essential tremors.
What is timolol? What are the therapeutic uses?
Orally bioavailable antagonist of both B1 and B2 receptors.
Similar uses to propranolol, but also widely used topically in treatment of wide-angle glaucoma.
What are the B1-selective (2nd gen) adrenergic receptors antagonists?
Metoprolol and atenolol
What is the function of metoprolol? What are the clinical uses and adverse effects?
Orally bioavailable B1 selective antagonist.
Similar to propranolol, also used to treat heart failure.
Adverse effects similar to propranolol, but less bronchoconstriction at lower doses.
What is atenolol?
Orally bioavailable B1 selective antagonist with a longer duration of action that allows once/day dosing.
Less penetration into the CNS (less CNS side effects)
What are the therapeutic uses of atenolol?
Similar to propranolol, but less potential for bronchoconstriction at lower doses.
What are two adrenergic receptor antagonists with additional CV actions (3rdg en)?
Labetolol and carvedilol.
What is the Labetolol? What are the therapeutic uses?
Orally bioavailable antagonist of a1 and both B1 and B2 receptors (non-selective)
Used orally for essential HTN and IV for hypertensive emergencies.
What is Carvedilol? What is it used to treat?
Orally bioavailable antagonist of a1 and both B1 and B2 receptors (non-selective). Also has anti-oxidant propertides and blocks L-type calcium channels at higher doses.
HTN, heart failure, MI
What is the “first dose” phenomenon? What alpha1 selective drug causes this?
A small percentage of patients can develop fainting or severe hypotension after the first dose, which will go away when taking the medicine longer.
Seen with Prazosin.
