Adrenergic Pharmacology Flashcards

Flashcards for reviewing adrenergic pharmacology, covering adrenergic neurotransmitters, receptors, agonists, and antagonists.

What is the major neurotransmitter of postganglionic sympathetic fibers?

Norepinephrine (NE)

What is the major hormone released by the adrenal medulla?

Epinephrine (Epi)

What is the function of D1 dopaminergic receptors?

Vasodilation of renal, coronary, cerebral & mesenteric blood vessels.

What enzyme is the rate-limiting step in the synthesis of norepinephrine?

Tyrosine Hydroxylase

What enzyme can destroy monoamines like dopamine (DA) and norepinephrine (NE)?

MAO Enzyme

What is a peripheral decarboxylase inhibitor that can be used with DOPA?

Carbidopa

Activation of central/presynaptic beta receptors will do what to NE Release?

Increase NE Release

Activation of central/presynaptic alpha-2 receptors will do what to NE release?

Decrease NE Release

What drugs inhibit Neuronal Reuptake (Uptake I) of NE?

Cocaine and Tricyclic Antidepressants (TCA)

What drug inhibits Vesicular Uptake (Uptake III) of NE?

Reserpine

What inhibits Non Neuronal Uptake (Uptake II) of NE?

Corticosteroids

What is the end product of norepinephrine and epinephrine metabolism?

Vanillylmandelic Acid (VMA)

What condition is diagnostic for increased VMA in a 24-hour urine sample?

Pheochromocytoma

What are the types of MAO enzyme and what do they metabolize?

MAO-A: metabolism of NE and 5HT>>> DA. MAO-B: metabolism of DA>>>NE ad 5HT

What is the mechanism of action of alpha-1 adrenergic receptors?

Gq, PLC, IP3 & DAG, ↑Ca²+ Intracellular → Smooth Muscles Contraction

What is the mechanism of action of beta 1,2,3 adrenergic receptors?

Gs, Adenyl Cyclase, ↑cAMP

What is the mechanism of action of alpha-2 and M2 receptors?

Gi, Adenyl Cyclase, ↓cAMP

What are the effects of Alpha-1 receptor stimulation on blood vessels?

Vasoconstriction, ↑ Venous Return and ↑COP, ↑Peripheral Resistance (PR) & ↑B.P., Nose and eye decongestion

What are the effects of Alpha-1 receptor stimulation on eye?

Active mydriasis: due to contraction of dilator papillae

What are the effects of Alpha-1 post synaptic receptor stimulation?

↓ Central sympathetic outflow → ↓ BP, Inhibit renin release: ↓ BP, Inhibit insulin secretion (predominant), Inhibit lipolysis, Stimulate platelet aggregation & vasoconstriction (some areas).

What are the effects of Alpha-2 pre synaptic receptor stimulation?

Inhibit NE release from sympathetic nerves, ↓ Ach release in the heart & intestine.

What are the effects of Beta-1 Receptor stimulation?

SAN: ↑ Heart Rate, AVN: ↑ Conduction Velocity, Ventricular Muscles: ↑ Contractility, ↑ Cardiac Output and Oxygen Consumption, ↑ Renin Secretion: ↑ Blood pressure, Stimulates Lipolysis

What are the effects of Beta-2 Receptor stimulation?

Bronchodilation & mast cell stabilization, Vasodilatation of skeletal & coronary blood vessels, Stimulate glucagon release: ↑ blood glucose, Liver & muscle glycogenolysis: ↑blood glucose, Stimulate insulin release, Increases potassium (k+) uptake by muscles: →hypokalemia, Skeletal muscle tremors, Intestinal and uterine relaxation.

What are the therapeutic effects of Beta-3 Receptor stimulation?

Lipolysis and Relaxation of Urinary Bladder Wall

What is the difference between Catechol Amines and Non-Catechol Amines agonists?

Catecholamines: Short duration, High potency +Rapid onset, Not Given Orally, Poorly cross BBB (Polar)| Non-Catechol Amines: Long duration, Slow onset, Can be given Orally, Can cross BBB

What is the mechanism of action of direct, indirect, and dual (mixed) adrenoceptor agonists?

Direct: bind Receptors, Indirect: *NE in Synapse *Release of NE: Amphetamine & Tyramine Reuptake: Cocaine, Dual (Mixed): ephedrine and pseudoephedrine

What effect does activation of alpha2 receptors have on blood pressure?

Decreases Blood Pressure through Reduction of Central Sympathetic Outflow, Reduction of NE Release From Sympathetic Neurons, Reduction of Renin Release

What are the therapeutic uses of Norepinephrine [Levarterenol]?

Septic Shock 2nd line in cardiogenic shock if DA failed

What are the therapeutic uses of Epinephrine?

Anaphylactic Shock, With local Anesthetic, Acute attack of bronchial Asthma, Cardiac Arrest, Arrest bleeding e.g. Epistaxis

What are the therapeutic uses of Isoproterenol?

Refractory Bradycardia and AV Block (Complete Heart Block)

What are the therapeutic uses of Dobutamine?

Short term in acute Heart Failure, Cardiogenic shock

What are the therapeutic uses of Albuterol and terbutaline?

Acute attack of asthma

What are the therapeutic uses of salmeterol & Formeterol?

Prophylaxis (Mainly) for asthma

What are the therapeutic uses of Oxymetazoline?

Local nasal and eye decongestant

What are the therapeutic uses of Phenylephrine?

Local nasal decongestant, Hypotension state

What are the adverse effects of B2 Agonist?

Anxiety, Arrhythmia, Tachycardia, Tolerance, Tremors, Hypotension, Hypokalemia

What are the adverse effects of Alpha 1 Agonist?

Hypertension, Reflex bradycardia, Rebound nasal congestion

What are the adverse effects of Epinephrine?

Tacycardia, Tremors, Hypertension, Anxiety, Arrhythmia

What are the effects of Dopamine at low, moderate, and high doses?

D1-agonist (at low dose): VD of renal blood vessels, β1-agonist (at moderate dose): Cardiac stimulation, α1-agonist (at high dose): VC ↑Blood Pressure

What are the adverse effects Dopamine and Dobutamine?

Headache, nausea, vomiting (with dopamine), Hypertension (with Dopamine), Gangrene if extravasation occurs (with dopamine), Palpitation- anginal pain- arrhythmia (Less with dobutamine)

What the Use of Fenoldopam?

IV for the treatment of severe hypertension in hospitalized patient

What are the use of Amphetamine?

Attention deficit hyperactivity disorder (ADHD) in children, Narcolepsy, Appetite control (replaced with other agents)

What are the Adverse Effects of Amphetamine?

Marked CNS stimulation →hallucination, psychosis, convulsions & dependence on prolonged use, CVS stimulation → palpitation, arrhythmia, hypertension, Marked Anorexia.

What are the Uses of Ephedrine and pseudoephedrine?

Oral nasal decongestants: pseudoephedrine, Spinal shock: ephedrine IMI (during spinal anesthesia), Nocturnal enuresis (in children), Urine incontinence (in adults).

What are the Adverse Effects of Ephedrine and pseudoephedrine?

Minimal CNS stimulation: insomnia, anxiety, Minimal CVS stimulation: palpitation, hypertension, Urinary retention.

What are the the drug classes of Adrenergic Antagonists?

Alpha Blockers, Beta Blockers, Alpha and Beta Blockers

What are some examples of Nonselective Beta Blockers?

Propranolol, Nadolol, Timolol and Pindolol

What are some examples of Alpha 1-selective Blockers?

Prazosin, Doxazosin, Tamsulosin and Alfuzosin

What are some examples of Alpha 2-selective Blockers?

Yohimbine and Mirtazepine

List the Nonselective βB & α1-selective blockers

Labetalol & Carvedilol

What are the antianginal effects of Beta Blockers?

improve imbalance between O2 supply & demand: (B1 Blockade)

How do Beta Blockers produce an Antihypertensive Effect?

Suppress renin release (mainly) and Negative Inotropic & Chronotropic effects: ↓ COP, ↓Central sympathetic outflow, ↓Peripheral NE release

What are the Antiarrhythmic effects of Beta Blockers?

Block sympathetic activity in SAN and AVN, ↓slope of Phase 4 → slow automaticity of ectopic focus

What are the Non-Cardiovascular Actions of Beta Blockers?

Bronchoconstriction in susceptible patients, Inhibit epinephrine -induced glycogenolysis, Long term use may↓ Insulin release→ glucose intolerance, ↑ Plasma TG, ↑ Plasma K+ during exercise, Inhibit conversion of T4 → T3, CNS- Depression

What properties make a Beta Blocker Cardioselective?

Less risk of bronchospasm, Less risk of reduction in peripheral Blood flow, Less risk of disturbed Glucose metabolism

What is meant by Membrane Stabilizing Activity (MSA) of a Beta Blocker?

block also Na channels (i.e. with local anesthetic effect): Higher Antiarrhythmic effect

What is meant by Intrinsic Sympathomimetic Activity (ISA) of a Beta Blocker?

Minimal reduction in H.R., Not preferred in angina

What are the benefits of Vasodilatory Beta Blockers?

More efficient as antihypertensive and Not decrease peripheral blood flow

Describe the properties of Lipophilic Beta Blockers

Cross BBB, Metabolized in liver, Short duration (given 2-3 times/d), Adjust the dose or avoided in liver diseases

Describe the properties of Hydrophilic Beta Blockers

Not Cross BBB, Excreted in Kidney, Long duration (given once/d), Adjust the dose or avoided in Renal diseases

List the CVS Uses of Beta Blockers:

Hypertension, Ischemic Heart Diseases [IHD], Cardiac arrhythmias, Decrease hypertrophy and mortality in Systolic Heart Failure

List the Non-Cardiovascular Uses of Beta Blockers:

Hyperthyroidism & Thyrotoxic crisis, Open-angle glaucoma, Prophylaxis of migraine, 2ry to CNS effects: propranolol

List the Adverse Effects of Beta Blockers:

Bradycardia, AV block, Heart failure with high dose in susceptible patient, Hypotension especially with vasodilatory β blockers, Sudden withdrawal after prolonged use→, Bronchial Asthma in susceptible Patient, Peipheral Ischemia, Hyperkalemia in susceptible patients, Risk of silent hypoglycemia in diabetic patient, Risk of Glucose intolerance with long term use, CNS: depression and night mares with lipophilic BB, Sexual impairment

When is it appropriate to use Cardio-selective Beta Blockers?

Patient with associated condition as: Bronchial asthma, Diabetes Mellitus, Peripheral Vascular Diseases (PVD) as Reynaud

List the Contraindications of Beta Blockers:

Sinus bradycardia and AVN block

List the Uses of Phentolamine:

Pheochromocytoma: during surgery, Hypertensive episodes , Topical in extravasation of NE

Why Non Selective Alpha Blockers are not preferred to be used in HTN

Severe Reflex tachycardia, Postural (Orthostatic) hypotension, Impaired ejaculation in male, Nasal stuffiness

What are the Members with Uroselective α1A blocker property that are used to ↓Urinary symptoms in BPH

Tamsulosin and Alfuzosin

What are the Adverse effects of Clonidine?

Sedation - dry mouth- Bradycardia- Sexual dysfunction, Rebound hypertension on sudden withdrawal

What are the Uses of Clonidine?

Pre-anesthetic medication, Morphine withdrawal, Menopausal hot flushes, Migraine prophylaxis, Hypertensive urgencies, Glaucoma

What are the Adverse effects Alpha Methyl dopa?

Sedation-dry mouth-Bradycardia- Sexual dysfunction, Hepatitis, Hemolytic anemia, Depression, Parkinsonism & hyperprolactinemia

What is the major neurotransmitter of postganglionic sympathetic fibers?

Norepinephrine (NE)

What is the major hormone released by the adrenal medulla?

Epinephrine (Epi)

What is the function of D1 dopaminergic receptors?

Vasodilation of renal, coronary, cerebral & mesenteric blood vessels.

What enzyme is the rate-limiting step in the synthesis of norepinephrine?

Tyrosine Hydroxylase

What enzyme can destroy monoamines like dopamine (DA) and norepinephrine (NE)?

MAO Enzyme

What is a peripheral decarboxylase inhibitor that can be used with DOPA?

Carbidopa

Activation of central/presynaptic beta receptors will do what to NE Release?

Increase NE Release

Activation of central/presynaptic alpha-2 receptors will do what to NE release?

Decrease NE Release

What drugs inhibit Neuronal Reuptake (Uptake I) of NE?

Cocaine and Tricyclic Antidepressants (TCA)

What drug inhibits Vesicular Uptake (Uptake III) of NE?

Reserpine

What inhibits Non Neuronal Uptake (Uptake II) of NE?

Corticosteroids

What is the end product of norepinephrine and epinephrine metabolism?

Vanillylmandelic Acid (VMA)

What condition is diagnostic for increased VMA in a 24-hour urine sample?

Pheochromocytoma

What are the types of MAO enzyme and what do they metabolize?

MAO-A: metabolism of NE and 5HT>>> DA. MAO-B: metabolism of DA>>>NE ad 5HT

What is the mechanism of action of alpha-1 adrenergic receptors?

Gq, PLC, IP3 & DAG, ↑Ca²+ Intracellular → Smooth Muscles Contraction

What is the mechanism of action of beta 1,2,3 adrenergic receptors?

Gs, Adenyl Cyclase, ↑cAMP

What is the mechanism of action of alpha-2 and M2 receptors?

Gi, Adenyl Cyclase, ↓cAMP

What are the effects of Alpha-1 receptor stimulation on blood vessels?

Vasoconstriction, ↑ Venous Return and ↑COP, ↑Peripheral Resistance (PR) & ↑B.P., Nose and eye decongestion

What are the effects of Alpha-1 receptor stimulation on eye?

Active mydriasis: due to contraction of dilator papillae

What are the effects of Alpha-1 post synaptic receptor stimulation?

↓ Central sympathetic outflow → ↓ BP, Inhibit renin release: ↓ BP, Inhibit insulin secretion (predominant), Inhibit lipolysis, Stimulate platelet aggregation & vasoconstriction (some areas).

What are the effects of Alpha-2 pre synaptic receptor stimulation?

Inhibit NE release from sympathetic nerves, ↓ Ach release in the heart & intestine.

What are the effects of Beta-1 Receptor stimulation?

SAN: ↑ Heart Rate, AVN: ↑ Conduction Velocity, Ventricular Muscles: ↑ Contractility, ↑ Cardiac Output and Oxygen Consumption, ↑ Renin Secretion: ↑ Blood pressure, Stimulates Lipolysis

What are the effects of Beta-2 Receptor stimulation?

Bronchodilation & mast cell stabilization, Vasodilatation of skeletal & coronary blood vessels, Stimulate glucagon release: ↑ blood glucose, Liver & muscle glycogenolysis: ↑blood glucose, Stimulate insulin release, Increases potassium (k+) uptake by muscles: →hypokalemia, Skeletal muscle tremors, Intestinal and uterine relaxation.

What are the therapeutic effects of Beta-3 Receptor stimulation?

Lipolysis and Relaxation of Urinary Bladder Wall

What is the difference between Catechol Amines and Non-Catechol Amines agonists?

Catecholamines: Short duration, High potency +Rapid onset, Not Given Orally, Poorly cross BBB (Polar)| Non-Catechol Amines: Long duration, Slow onset, Can be given Orally, Can cross BBB

What is the mechanism of action of direct, indirect, and dual (mixed) adrenoceptor agonists?

Direct: bind Receptors, Indirect: *NE in Synapse *Release of NE: Amphetamine & Tyramine Reuptake: Cocaine, Dual (Mixed): ephedrine and pseudoephedrine

What effect does activation of alpha2 receptors have on blood pressure?

Decreases Blood Pressure through Reduction of Central Sympathetic Outflow, Reduction of NE Release From Sympathetic Neurons, Reduction of Renin Release

What are the therapeutic uses of Norepinephrine [Levarterenol]?

Septic Shock 2nd line in cardiogenic shock if DA failed

What are the therapeutic uses of Epinephrine?

Anaphylactic Shock, With local Anesthetic, Acute attack of bronchial Asthma, Cardiac Arrest, Arrest bleeding e.g. Epistaxis