Adrenergic Agonists and Antagonists Flashcards
Physiologic and Pharmacologic Effects of ENDOGENOUS Catecholamines
- Epinephrine and norepinephrine act as AGONISTS at both alpha and beta adrenoceptors.
- At supra physiological (larger than would occur naturally), DOPAMINE can also act as an agonist at alpha and beta receptors.
- The overall effect of each catecholamine is complex and depends on the concentration of the agent AND on tissue-specific receptor expression.
- Pharmacological intervention is possible at each of the major steps in catecholamine synthesis:
1. STORAGE
2. REUPTAKE
3. METABOLISM
4. RECEPTOR ACTIVATION
Epinephrine
AGONST AT BOTH ALPHA AND BETA ADRENOCEPTORS.
At low concentrations…
-predominantly beta 1 and beta 2 effects
At high concentrations…
-the alpha 1 effects predominate
Effects at beta 1 receptors…
-Increases cardiac contractile force and cardiac output: results in increases in cardiac oxygen consumption and systolic BP.
Effects at beta 2 receptors…
-Causes vasodilation; results in a decrease in peripheral resistance and a decrease in a diastolic BP; causes an increased blood flow to skeletal muscle, relaxes bronchial smooth muscle, increases the concentrations of glucose and FFA in the blood!
Beta 1 and beta 2 effects are all components of the “flight or fight” response.
Clinical uses:
-acute asthmatic attack and anaphylaxis
-high doses of locally applied epinephrine cause vasoconstriction; PROLONG THE ACTION OF LAs.
-Rapid onset and a brief duration of action: INEFFECTIVE ORALLY!
-Results in increased cardiac excitability; can lead to cardiac arrhythmias, a sharp rise in BP can provoke cerebral hemorrhage.
Beta-adrenergic agonist
Clinical applications in bronchospasm, hypersensitivity reaction, anaphylactic shock, cardiac resuscitation, hemostasis (topical use), prolong LA effect (local use), open angle glaucoma, nasal congestion.
Serious side effects: cardiac arrhythmia including ventricular fibrillation, cerebral hemorrhage, severe hypertension.
Other side effects: Headache, nervousness, tremor, hypertension, palpitations, tachycardia.
Contraindications: active labor, angle-closure glaucoma, shock (other than anaphylaxis), organic brain damage, cardiac arrhythmias, coronary insufficiency, severe hypertension, cerebral atherosclerosis.
NONSELECTIVE AGONIST AT BETA 1, BETA 2, ALPHA 1 AND ALPHA 2 RECEPTORS.
High doses can cause tachycardia and lift threatening ventricular arrhythmias.
Norepinephrine
AGONST AT ALPHA AND BETA 1 RECEPTORS!
RELATIVELY LITTLE EFFECT AT BETA 2 RECEPTORS.
Systemic administration of norepinephrine:
-Increases systolic BP; Beta 1 effect
-Increases diastolic BP and total peripheral resistance
-Increases heart rate; effect is typically overcome by reflex vagal activity due to increased BP.
-Norepinephrine increases stroke volume; cardiac output remains unchanged because heart rate is ultimately DECREASED.
-Norepinephrine is frequently used in the emergency treatment of distributive shock.
Clinical applications in BP support in acute hypotensive states (shock), limiting GI bleeding via intraperitoneal or nasogastric administration.
Serious side effects: same as epinephrine (cardiac arrhythmia including ventricular fibrillation, cerebral hemorrhage, severe hypertension).
Other side effects: same as epinephrine (headache, nervousness, tremor, hypertension, palpitations, tachycardia).
Contraindications: peripheral vascular thrombosis, profound hypoxia, hypercapnia (excess CO2 in the bloodstream), hypotension from loss of blood volume.
NONSELECTIVE AGONIST AT BETA 1, ALPHA 1, AND ALPHA 2 RECEPTORS.
May cause tachycardias involving the SA node or ectopic atrial or ventricular sites in patients with contractile dysfunction.
Avoid coadministration with MAO inhibitors or amitriptyline or imipramine-type antidepressants due to risk of severe hypertension.
Droxidopa
BETA ADRENERGIC AGONIST
Prodrug
Converted to active norepinephrine by dopa decarboxylase
Recently approved for neurogenic orthostatic hypotension.
Clinical applications in the treatment of orthostatic dizziness in adults patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy.
Serious side effects: supine hypertension, increased CV risk.
Other side effects: hyperpyrexia (fever with an extreme elevation in body temperature) and confusion, headache, dizziness, nausea, hypertension, fatigue.
Contraindicatons: NONE!
Dopamine
BETA ADRENERGIC AGONiST
Prominent CNS neurotransmitter
-Systemic administration has few CNS effects because it DOES NOT READILY CROSS THE BBB!!!
-Dopamine activates one or more subtypes of catecholamine receptor in peripheral tissue (5 different types); the predominant effect is dependent on the local concentration of the compound.
Low doses, continuous IV infusion…
-Acts predominantly on D1 dopaminergic receptors; renal, mesenteric, and coronary vascular beds.
-D1 dopaminergic receptors activate adenylyl cycalse in vascular smooth muscle cells, which leads increased cAMP and vasodilation.
Supraphysiologic rates of infusion…
-Positive inotrope (changes force of heart contractions) via its activation of beta 1 adrenergic receptors.
-Intermediate doses cause widespread vasodilation via stimulation of D1 receptors.
At still HIGHER rates of infusion…
-Dopamine acts on alpha 1 adrenergic receptors to cause vasoconstriction.
Clinical uses:
-Treatment of shock; particular states of shock (caused by low cardiac output, accompanied by compromised renal function leading to oliguria-production of abnormally small amounts of urine).
Clinical applications in distributive or cardiogenic shock, use as adjunct to increase cardiac output, blood pressure, and urine flow; short term treatment of severe, refractory, chronic heart failure.
Serious side effects: bradycardia, asthma attacks, widening of QRS complex, cardiac arrhythmias.
Other side effects: hypotension, hypertension, palpitations, tachycardia.
Contraindications: pheochromocytoma, uncorrected tachyarrhythmias, ventricular fibrillation.
Coadministration of dopamine and MAO inhibitors results in decreased metabolism of dopamine, which can lead to significant tachycardia and arrhythmias.
Alpha-methyltyrosine
INHIBITOR OF CATECHOLAMINE SYNTHESIS; made in presynaptic terminal; this class is of limited clinical utility because such agents NONSPECIFICALLY INHIBIT THE FORMATION OF ALL CATECHOLAMINES!! If you affect early in the system, you lose the specificity in effect.
Occasionally in the treatment of hypertension associated with pheochromocytoma; tumor of the adrenal medulla that produces norepinephrine and epinephrine.
-Alpha-methyltyrosine is a structural analogue of tyrosine.
-It is transported into nerve terminals and INHIBITS TYROSINE HYDROXYLASE (rate-determining enzyme).
Clinical applications in pheochromocytoma associated hypertension.
Side effects: orthostatic hypotension, sedation.
Contraindications: hypersensitivity to alpha-methyltyrosine.
USED RARELY.
Inhibitors of catecholamine storage
Catecholamines originate from two pools:
1. de novo synthesis
2. recycled transmitter
An agent that inhibits catecholamine storage can have 2 effects…
1. Short term effect: agent can increase the net release of catecholamine from the synaptic terminal; mimics sympathetic stimulation (sympathomimetic).
2. Longer term effect: the agent depletes the pool of available catecholamine; acts as an inhibitor of sympathetic activity (sympatholytic).
Reserpine
INHIBITOR OF CATECHOLAMINE STORAGE
-Binds tightly to the vesicular antiporter VMAT and irreversibly damages VMAT.
-The result is that the vesicles loses their ability to concentrate and store norepinephrine and dopamine.
At low doses…
Reserpine causes neurotransmitter leak into he cytoplasm and the catecholamine is destroyed by MAO.
At high doses…
The rate of neurotransmitter leak can be sufficiently high to overwhelm the MAO in the terminal.
This leads to a high concentration of transmitter in the neuronal cytoplasm; the transmitter can exit from the cytoplasm to the synaptic space through NET acting in reverse.
The efflux of catecholamine has a transient sympathomimetic effect.
Deplete sympathetic transmission, so parasympathetic dominates.
New storage vesicles must be synthesized and transported to the nerve terminal; this recovery phase may require days to weeks after an individual stop taking reserpine.
REASONS WHY RESERPINE HAS FALLEN OUT OF USE TO TREAT HYPERTENSION:
-Irreversible nature of its action
-Association with psychotic depression
Safer more efficacious drugs are available for the treatment of hypertension.
Clinical application in hypertension.
Serious side effects: cardiac arrhythmia, GI hemorrhage, thrombocytopenia, dream anxiety disorder, impotence, psychotic depression.
Other side effects: dizziness, nasal congestion.
Contraindications: Active GI disease, depression, ECT, renal failure.
Tyramine
INHIBITOR OF CATECHOLAMINE STORAGE
Found in cheese and wine; dietary amine
Metabolized in the GI tract and liver by MAO.
In the patients taking MAO inhibitors (MAOIs)…
-Tyramine is absorbed in the gut
-Transported through the blood
-Taken up by sympathetic neurons
-Transported into synaptic vesicles by VMAT.
Large amounts of tyramine accumulate and cause acute displacement of vesicular norepinephrine; get a massive release of norepinephrine from the nerve terminal via reversal of NET (usually a reuptake receptor, reverse action means it is putting the transmitter back into the terminal).
-Tyramine is poorly retained in synaptic vesicles; it is hydroxylated to metabolite octopamine by vesicular dopamine beta-hydroxylase, which can be stored at high concentrations in the vesicles.
CONDITIONS OF CHRONIC MAOI TREATMENT AND MODEST DIETARY TYRAMINE INTAKE:
-Norepinephrine may gradually be replaced by octopamine in storage vesicles.
-OCTOPAMINE HAS LITTLE AGONIST ACTIVITY=FALSE TRANSMITTER
-Ultimately leads postural hypotension.
Guanethidine
INHIBITOR OF CATECHOLAMINE STORAGE
Guanethidine is actively transported into neurons by NET.
It concentrated in transmitter vesicles and displaces norepinephrine and leads to a gradual depletion of norepinephrine.
Guanethidine (like octopamine) is not an agonist=FALSE TRANSMITTER!
Was used to treat postural hypotension; inhibits cardiac sympathetic nerves leading to reduced cardiac output.
-Blocks sympathetically-mediated vasoconstriction leading to reduced cardiac preload (how much blood and pressure is used to bring blood to the heart).
Symptomatic hypotension following exercise or standing up (postural hypotension) may result because guanethidine inhibits the sympathetic response.
-Acute effects of guanethidine (indirect sympathomimetic): displace NE that is stored in the synaptic vesicles of adrenergic neurons; results in a massive efflux of NE through the NET acting in reverse; the resultant flooding of NE in the synapse causes marked sympathetic stimulation.
-Chronic effects of guanethidine (indirect sympathomimetic); guanethidine is concentrated in the synaptic vesicles and replaces NE; MAO degrades the small pool of NE that remains in the cytoplasm outside of the vesicle (normal reuptake of NE by NET).
Clinical applications in hypertension.
Serious side effects: kidney disease, apnea
Other side effects: orthostatic hypotension, fluid retention, dizziness, blurred vision, impotence (erectile dysfunction).
Contraindications: MAOI therapy, heart failure, pheochromocytoma.
Guanadrel
INHIBITOR OF CATECHOLAMINE STORAGE
Also acts as a FALSE NEUROTRANSMITTER
Can be used in the treatment hypertension
No longer a first line agent.
Adverse effect profile is similar to that of guenthidine
Clinical applications in hypertension treatment.
Serious side effects: kidney disease, apnea
Other side effects: orthostatic hypotension, fluid retention, dizziness, blurred vision, impotence (erectile dysfunction).
Contraindications: MAOI therapy, heart failure, pheochromocytoma.
Guanadrel has a similar mechanism of action as guanethidine.
-Inhibition of cardiac sympathetic nerves least reduced cardiac output; inhibition of sympathetic response leads to symptomatic hypotension following exercise.
Amphetamine
INHIBITOR OF CATECHOLAMINE STORAGE
-Amphetamine has several adrenergic actions:
Displaces endogenous catecholamines from storage vesicles (leak out)-similar to tyramine.
Weak inhibitor of MAO
Blocks catecholamine reuptake mediated by NET and DAT (dopamine transport, presynaptic terminal).
-Amphetamine binds to postsynaptic adrenergic receptors; has little action at alpha or beta adrenoceptors.
-Amphetamine has marked behavioral effects: increased alertness, decreased fatigue, depressed appetite, insomnia=STIMULANT EFFECTS.
-It has been used to treat depression and narcolepsy and to suppress appetite.
Adverse effects: fatigue and depression following the period of central stimulation.
Short term treatment of obesity.
Clinical applications in ADHD and narcolepsy.
Serious side effects: hypertension, tachyarrhythmia, Gilles de la Tourette’s syndrome, seizure, psychotic disorder with prolonged use.
Other side effects: restlessness, dysphoric mood (unease and dissatisfaction), rebound fatigue, addiction potential, loss of appetite, irritability, erectile dysfunction.
Contrindications: advanced CV disease, glaucoma, hyperthyroidism, MAOI therapy, severe hypertension.
Dependence and tolerance can occur.
Ephedrine, pseudoephedrine, phenylpropanolamine
INHIBITORS OF CATECHOLAMINE STORAGE
Structurally related agents to amphetamine.
Actions less marked that those of amphetamine
Ephedrine and phenylpropanolamine are now restricted in the US.
Pseudoephedrine was widely used as an OTC decongestant; now restricted because of potential as a starting material for methamphetamine.
-Found in some cold remedies and appetite suppressants.
Pseudoephedrine:
Clinical applications in allergic rhinitis and nasal congestion.
Serious side effects: atrial fibrillation, ventricular premature beats, myocardial ischemia.
Other side effects: hypertension, tachyarrhythmia, rebound congestion, insomnia.
Contraindications: Advanced CV disease, MAOI therapy, Severe hypertension.
OTC decongestant
Methylphenidate
INHIBITION OF CATECHOLAMINE STORAGE
Structural analog of amphetamine
Widely used in psychiatry to treat ADHD in children: major effect is thought to be related to enhanced attention.
Clinical application in ADHD
Serious side effects: hypertension, tachyarrhythmia, Gilles de la Tourette’s syndrome, seizure, psychotic disorder with prolonged use.
Other side effects: restlessness, dysphoric mood (unease and dissatisfaction), rebound fatigue, addiction potential, loss of appetite, irritability, erectile dysfunction.
Contrindications: advanced CV disease, glaucoma, hyperthyroidism, MAOI therapy, severe hypertension.
Dependence and tolerance can occur.
Methylphenidate displaces endogenous catecholamines from storage vesicles, weakly inhibits MAO, and blocks catecholamine reuptake mediated by NET and DAT.
Inhibitors of catecholamine reuptake
Inhibitors of catecholamine reuptake can exert an ACUTE AND POWERFUL SYMPATHOMIMETIC EFFECT BY PROLONGING THE TIME THAT RELEASE NEUROTRANSMITTER REMAINS IN THE SYNAPTIC CLEFT.
Cocaine
INHIBITION OF CATECHOLAMINE REUPTAKE
Potent inhibitor of NET-this keeps more transmitter out of the terminal and in the synaptic cleft to produce an effect.
Cocaine essentially eliminates catecholamine transport unlike other uptake inhibitors such as imipramine and fluoxetine.
Used occasionally as a LA.
MOST IMPORTANT ROLE IS IN AN AGENT OF ABUSE!!!
Clinical applications in mucosal and ophthalmic anesthetic and diagnosis of Horner’s syndrome pupil.
Serious side effects: accelerates coronary atherosclerosis, tachycardia, seizure.
Other side effects: CNS depression or excitation, anxiety.
Contraindications: hypersensitivity to cocaine-containing products.
Medium potency (one half that of lidocaine); medium duration of action, marked vasoconstrictive action, cardiotoxic.
Cardiotoxicity and euphoria limit the value of cocaine as a LA.
Tricyclic antidepressants (TCAs)
INHIBITORS OF CATECHOLAMINE REUPTAKE
Examples: imipramine and amitriptyline.
-Inhibit NET-mediated reuptake of NE into presynaptic terminals; allows accumulation of NE in the synaptic cleft.
-TCAs also inhibit serotonin reuptake into presynaptic terminals.
-TCAs block serotonergic, alpha-adrenergic, histaminergic, and muscarinic receptors.
-Display a prominent adverse effect profile.
May cause postural hypotension through alpha-adrenergic blockade.
May cause sinus tachycardia through potentiation of NE action on cardiac sympathetic nerves.
At high doses or in overdose…can have a quinidine like effect on cardiac ion channels and induce arrhythmia.
TCA therapy important for depression: these drugs begin inhibiting NE and serotonin reuptake immediately, but there is a latency period of several weeks before improvement in symptoms is seen; molecular mechanism for this delayed onset of benefit is the subject of investigation.
AMITRIPTYLINE AND IMIPRAMINE (TCAs)
Clinical application in depression, pain syndromes such as migraine, headaches, chronic fatigue syndrome, and other somatic pain disorders; nocturnal enuresis-bedwetting (imipramine).
Serious side effects: heart block, cardiac arrhythmia, orthostatic hypotension, MI, agranulocytosis (severe and dangerous leukopenia), jaundice, seizure, worsening depression with suicidal thoughts.
Other side effects: bloating, constipation, xerostomia, dizziness, somnolence (song desire for sleep), blurred vision, urinary retention.
Contraindications: Concomitant use of MAOI, cardiac conduction system defects, use in patients during acute recovery after a MI.
TCAs appear to affect cardiac sodium channels in a quinidine-like manner, leading to potentially lethal conduction delays, and ECG should done to rule out conduction system disease PRIOR to starting TCAs.
Inhibitors of catecholamine metabolism
Monoamine oxidase inhibitors (MAOIs): prevent secondary deamination following reuptake of catecholamines=more catecholamine accumulates in presynaptic vesicles for release during action potentials.
-Most MAOIs are oxidized by MAO to reactive intermediates; act as irreversible inhibitors of MAO.
NONSELECTIVE AGENTS IN THIS CLASS:
-Agents that inhibit both MAO-A and MAO-B: Phenelzine, iproniazid and tranylcypromine.
SELECTIVE INHIBITORS (as long as you can use low concentrations, with increased concentrations these drugs become nonselective):
Clorgyline: selective for MAO-A.
Selegiline: selective for MAO-B.
Brofaromine and moclobemide: newer REVERSIBLE inhibitors of MAO-A.
These are used to treat DEPRESSION.
-Patients taking MAOIs should avoid eating certain fermented foods containing large amounts of tyramine; MAOIs block oxidative deamination of these monoamines; in the GI tract and liver.
-Allows them to enter the circulation and precipitate a hypertensive crisis.
-Concomitant use of MAOIs and selective serotonin reuptake inhibitors (SSRIs); this is contraindicated because it may precipitate the serotonin syndrome; characterized by restlessness, tremors, seizures, and possibly coma and death.
-Reversible inhibitors of MAO-A may be less prone to adverse effects and interactions!!! (Brofaromine and moclobemide).
Iproniazid, Phenelzine, Tranylcypromine
NONSELECTIVE MAO INHIBITORS (INHIBIT MAO-A AND MAO-B).
Clinical application in treating depression.
Serious side effects: systemic tyramine toxicity from consumption of foods that contain tyramine (uncontrolled catecholamine release can induce a hypertensive criss characterized by headache, tachycardia, nausea, cardiac arrythmia, and stroke), fever associated with increased muscle tone, leukopenia, hepatic failure, drug0induced lupus, worsening depression.
Other side effects: dizziness, somnolence, orthostatic hypotension, weight gain, increased liver aminotransferase level, orgasm disorder.
Contraindications: concomitant use of sympathomimetic drugs, concomitant bupropion, buspirone, guanethidine, other MAOIs, serotonergic drugs, concomitant methyldopa, L-dopa, L-tryptophan, L-tyrosine, phenylalanine, concomitant CNS depressants, narcotics, dextropethorphan, concomitant, excessive coffee or chocolate intake, concomitant foods with high tyramine content (cheese, beer, wine, pickled herring, yogurt, liver, yeast extract), liver disease, pheochromocytoma, heart failure, general anesthesia, local anesthesia with vasoconstrictors.
-Due to the extensive effects of MAOIs on p450 enzymes, MAOIs can cause extensive drug-drug interactions; extreme caution must be used when prescribing medications to patients concurrently taking a MAOI.
-Iproniazid, tranylcypromine, and phenelzineu are IRREVERSIBLE, nonselective MAOIs.
-The most toxic effect of MAOI use is systemic tyramine toxicity; the older, nonselective MAOIs are no longer considered first-line therapy for depression because of their significant potential for systemic tyramine toxicity.
-MAOIs can precipitate manic or hypomanic episodes in some bipolar patients.
Clorgyline and Selegiline
SELECTIVE MAOIs
-Clorgyline selective for MAOI-A
-Selegiline selective for MAOI-B
AS LONG AS YOU USE LOW CONCENTRATIONS, WITH HIGH CONCENTRATIONS, THEY BOTH BECOME NONSELECTIVE).
Selegiline also approved to treat Parkinson’s disease
-Mechanism of action: potentiation of dopamine in the remaining nigrostriatal neurons; decreased formation of neurotoxic intermediates.
Clinical applications in depression
Serious side effects: same as iproniazid (systemic tyramine toxicity from consumption of foods that contain tyramine (uncontrolled catecholamine release can induce a hypertensive criss characterized by headache, tachycardia, nausea, cardiac arrythmia, and stroke), fever associated with increased muscle tone, leukopenia, hepatic failure, drug-induced lupus, worsening depression.
Other side effects: dizziness, somnolence, orthostatic hypotension, weight gain, increased liver aminotransferase level, orgasm disorder). EXCEPT less tyramine toxicity.
Contraindications: same as iproniazid (concomitant use of sympathomimetic drugs, concomitant bupropion, buspirone, guanethidine, other MAOIs, serotonergic drugs, concomitant methyldopa, L-dopa, L-tryptophan, L-tyrosine, phenylalanine, concomitant CNS depressants, narcotics, dextropethorphan, concomitant, excessive coffee or chocolate intake, concomitant foods with high tyramine content (cheese, beer, wine, pickled herring, yogurt, liver, yeast extract), liver disease, pheochromocytoma, heart failure, general anesthesia, local anesthesia with vasoconstrictors). EXCEPT, patients have GREATER FREEDOM WITH THEIR DIET.
Selegiline also inhibits MAO-A at higher doses.
Transdermal (across the skin for systemic distribution) selegiline reduces the risk of a tyramine-induced hypertensive crisis, allowing patients greater freedom with their diet!!
IRREVERSIBLE
Brofaromine and Moclobemide
NEWER, REVERSIBLE INHIBITORS OF MAO-A (SELECTIVE).
Clinical applications in treatment of depression.
Serious side effects: same as iproniazid (systemic tyramine toxicity from consumption of foods that contain tyramine (uncontrolled catecholamine release can induce a hypertensive criss characterized by headache, tachycardia, nausea, cardiac arrythmia, and stroke), fever associated with increased muscle tone, leukopenia, hepatic failure, drug-induced lupus, worsening depression.
Other side effects: dizziness, somnolence, orthostatic hypotension, weight gain, increased liver aminotransferase level, orgasm disorder). EXCEPT less tyramine toxicity.
Contraindications: same as iproniazid (concomitant use of sympathomimetic drugs, concomitant bupropion, buspirone, guanethidine, other MAOIs, serotonergic drugs, concomitant methyldopa, L-dopa, L-tryptophan, L-tyrosine, phenylalanine, concomitant CNS depressants, narcotics, dextropethorphan, concomitant, excessive coffee or chocolate intake, concomitant foods with high tyramine content (cheese, beer, wine, pickled herring, yogurt, liver, yeast extract), liver disease, pheochromocytoma, heart failure, general anesthesia, local anesthesia with vasoconstrictors.)
RIMAs (reversible inhibitors of monoamine oxidase A)
These are displaced by high concentrations of tyramine, resulting in significantly more tyramine metabolism and thus less tyramine toxicity.
Receptor Agonists
-Because of the important role that adrenoceptors play in mediating vascular tone, smooth muscle tone, and cardiac contractility, selective agonists and antagonists of these receptors are mainstays of therapy for HYPERTENSION, ASTHMA, AND MI.
Alpha 1-adrenergic Selective agonists
- Increase peripheral vascular resistance.
- Maintains or elevates BP.
- May also cause bradycardia through activation of reflex vagal responses.
Methoxamine
ALPHA 1-SELECTIVE ADRENERGIC AGONIST
Systemically administered alpha 1 agonist.
-Sometimes employed in the treatment of shock.
Clinical applications in treating hypotension and shock.
Serious side effects: bradycardia (vagal reflex), ventricular ectopic beat.
Other side effects: hypertension, vasoconstriction, nausea, headache, anxiety.
Contraindications: Severe hypertension
Very little clinical use in the treatment of shock.
Midodrine
ALPHA 1-SELECTIVE ADRENERGIC AGONIST
Systemically administered alpha1-agonist.
-Prodrug enzymatically hydrolyzed to selective alpha1-receptor agonist DESGLYMIDODRINE.
-Peak concentration of desglymidodrine is achieved in about 1 hour.
-Primary indication is the treatment of orthostatic hypotension due to impaired autonomic nervous system function.
-May also cause hypertension when the patient is supine.
Side effects: supine hypertension, piloerection (goose bumps), and urinary retention.
Contraindications: Severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma or thyrotoxicosis, persistent and excessive supine hypertension.
ORAL
Phenylephrine, oxymetazoline, tetrahydrazoline
TOPICALLY ADMINISTERED ALPHA1-SELECTIVE AGONISTS
Used in the nonprescription remedies ( afrin, visine).
-Constrict vascular smooth muscle in the symptomatic relief of nasal congestion.
-Constrict vascular smooth muscle in the symptomatic relief of ophthalmic hyperemia (excess of blood in the vessels supplying organ or other part of body).
-Phenylephrine is also used intravenously in the treatment of shock-hypotension.
Serious side effects: cardiac arrhythmia, hypertension.
Other side effects: headache, insomnia, nervousness, rebound nasal congestion.
Contraindications: narrow-angle glaucoma, severe hypertension or tachycardia (for IV form of phenylephrine).
REBOUND of symptoms often accompanies use of these drugs.
