EXAM 2:week 5/6- Sympathomimetics/sympatholytics

Beta-adrenergic selective agents -1. What drug are they? -2. As you go up on dose,specificity decrease and they act as beta 1 and 2 antagonist

-1. AABEsM Atenolol Acebutolol Bisoprolol Esmolol Metoprolol -2. True

Metabolism of endogenous cathecholamine(APEX/PPT) -1. How is NE and EPI metabolize?What is the end product of NE and epi?how are they "terminated "? -2. How is dopamine metabolize? What is the end product? -3. Where are COMT found?(2)MAO found?(4) -4.T/F when an NE goes back into the presynaptic neuron if it does not enter the vesicle it will be metabolized by MAO -5. What is the final end products after the metabolism of NE and Epi? ***EXAMM!!*** -6. What is a lab test that can be used to assess the ANS?

-1. Terminated by reputable in synaptic cleft but metabolized by COMT AND MAO -4. True -5.Final byproduct of NE/Epi Metabolism Vanillylmandelic acid (VMA) *EXAM!!* -6.urine VMA (Also help diagnose pheochromocytoma)

Epinephrine -apex/ppt -1. What are some does a scenario where if it would be a good drug to be given (three) -true or false. Adding epi to local anesthetic influenced DOA of LA. -2.How much of the drug would you give for a hypotension that is not responsive to other indirect acting drug like ephedrine.? -Is it Alpha or beta that dominates at low dose of Epi? -What is the most effective broncodilator of all the pressors? What other drug can you use besides a epi for broncodilation?how much epi would be effective for bromchodilation? -3.t/Fwhen epi administer there's a decrease impulse pressure? -4.What Receptor would be stimulated when you give up epi at larger doses? What is a clinical observation of this when it comes to renal blood flow? -5.how would giving this drug influence the liver? The insulin in the blood? Potassium in the blood? -6.T/F a1=a2 > B1=B2. Epi is the drug of choice for anaphylaxis, shock, acls

-1.Anaphylaxis (Histamine), CPR (mixed properties), & Shock (Poor O2 delivery & ↓ BP ); -.Added to LA to prolong DOA -2.5-10mcg bolus for HoTN when not responsive to Indirect acting like Ephedrine 𝛽 predominates at low doses (0.25-0.5mcg/min) Most Effective Bronchodilator Phenylephrine for vasoconstrictor of choice but can cause Bradycardia No "real" Max dose but when using high doses, alpha is saturated & you need beta. Can use Ephedrine or low dose Epi (5mcg is perfect). -3.↑ pulse pressure: ↑ SBP & DBP remains Normal or slight ↓ -4.↑ 𝛼 at larger doses Results in Renal & Splanchnic vasculature vasoconstriction that will ↑ Renal Blood Flow Epi, Norepi, & Isoproterenol → relaxation of gastrointestinal smooth muscle B → relaxes detrusor muscle of the bladders VS A → contracts the trigone and sphincter muscle Induces hypercoagulable state = accelerates coagulation -5.SNS stimulation causes Hepatocytes release glucose & (transient) K+ into bloodstream -Insulin secretion (B2) is Overrode Overriding beta stimulation leading to ↑ lipolysis, ↑ glycogenolysis, & ↑ gluconeogenesis. End result = ↑ Blood Sugar In order to use Glucose, Insulin has to be present, so SNS cause an ↑ insulin from Beta cells -Hyperkalemia 🔜 Hypokalemia -K released from liver → transient ↑ K. -Depending on Dosage, Epi may cause transient ↑ K Ffollowed by glucose coming out of the cells → longer Hypokalemia as further stimulation of Beta 2 act on skeletal muscle & erythrocytes → activating Na/K pump = Final result is a ↓ K -Hypokalemia wins -16. Beta 1>beta 2> alpha 1 and 2

Sympatholytics -1. What is a sympatholytic? -2.What receptors does it involve? (Three) -3.true or false. Alpha antagonism prevents effects of catecholamines & sympathomimetics on heart & peripheral vasculature -4.What effect will you see with sympatholytics(alpha antagonist)? On Insulin secretion? Drop in blood pressure? Reflects tachycardia? Impotence? -5.True or false. Select selective alpha one Equal less tachycardia. Why?

-1.Drugs that interfere with sympathetic function Antagonist to adrenergic receptor Block NE & Epi to bind to receptor 2.Involves Alpha/beta antagonists or Presynaptic Agonism of 𝛼2 receptor Clonidine, Dexmedetomidine, etc. -3.Alpha antagonism prevents effects of catecholamines & sympathomimetics on heart & peripheral vasculature -when receptors are blocked inhibit insulin secretion for ex. Are prevented -4.increase Insulin secretion, ↓ blood pressure (VD), (baroreceptor-mediated) reflex tachycardia, & impotence (when blocked) -5.Selective 𝛼1 = less tachycardia r/t No release of NE, leaves inhibiting effects of a2 intact Med is less likely than a non-selective to cause reflex tachycardia

Norepinephrine (NE)2/3 ppt -1.how is the drug eliminated? -2. T/F You can give levo to a pt with RV failure -3. you cn give levo to somebody with LV -4. levo can cause tachy, are arrhythmogenic potency more or less than epi? -5. why should you hav special consideration for a pt taking MAOI & TCA?

-1.Elimination = Reuptake into nerve ending where it is stored & recycled for subsequent release very small amount is metabolized -2.↑ peripheral vascular resistance (PVR) & ↑ MAP RV Failure = Caution NE ↑ Venous return to the heart → ↑ PAP via PA adrenergic alpha receptors Poorly tolerated -3.↑ peripheral vascular resistance & ↑ afterload = ↓ CO & ↑ work of LV -4.No. epi is more beta 1 Tachycardia arrhythmogenic potential < Epi -5.Caution w/ MAOI & TCA reduce NE clearance & reuptake, respectively → Excessive SNS stimulation -Unopposed alpha stimulation alpha < Epi Less beta-1 & 2 effect at low dose → careful with the unopposed alpha stimulation

Beta 2 agonist(ppt) -1. What are some ex of beta 2 agonist? How long will the short acting grass? -2.What is the most common route of administration ? -3.True or false. Beta 1 is likely to be stimulated. -4.How many puffs will you not see an increase in HR with albuterol? What is the normal dose for any inhaler -5. what is the not so obvious side effects of the drug? -6..what are some clinical Effect of the drug. .7-what is the preferred treatment? -8. True or false. Beta/2 agonist can be given PO, inhaled,SQ,IV. -What is the preferred route? Why? - What are four side effects when not given inhaled? -9.True or false. Beta2 agonist are resistant to COMT? -10.They are used system finisher you're in construction open first kisses to cool lyrics) -11.How many micrograms is in one puff of albuterol?how many puff to blunt the airway of an asthmatic pt? -11. What are diff route for terbutaline what is the rate of the drip if the drip when it is given as a tocilytic ? -12.Complete. No more than (...) Should be given of the medication. One puff equal (...) Microgram

Albuterol/levalbuterol (rapid onset 5 minspeak 1 r last 4-6 hrs), Metaproterenol, & Terbutaline // ETT administration dec 50 - 70% drug delivery Beta-2 specific or > Beta-2, you won't see as much of the effects on the heart (beta-1) Albuterol 1 puff no ↑ HR, but 5 puffs will A little Terbutaline, no change. A slug of it will ↑ HR* •dose for any drug is 2 puffss(thats for any drug in inhaler ehehe) S.E: tachycardia,tolerance Relax Bronchiole & Uterine smooth muscle (Tocolytic) ↑ cAMP - promotes Bronchodilation "Preferred treatment for Bronchospasm" Inhaled, PO, SQ, or IV Inhaled route is preferred bc ↓ SE: Tremors, hyperglceymia, hypokalemia, hypomagnesmia Resistant to COMT Sustained DOA OB - used to Stop premature uterine contractions (Tocolytic effect) d/t ↓ Ca levels Albuterol Relaxes bronchial smooth muscle 1 puff = 100mcg 2.5-5mg (0.5-1mL of 0.5% solution in 5mL NS) Blunt airway Usually 2 puffs normal dose 4 puffs to blunt airway reflex with asthmatic patients during intubation Terbutaline Inhaled, PO, or SQ 0.25mg SQ similar to Epi 0.01mg/Kg in Peds Tocolytic (Labor suppressant) - 0.01mg/min infusion MDI Inhaler - 1 puff 200mcg No more than 16 puff

Norepinephrine (NE)2/3 ppt -1. True or false. When levo is given there will be an increase in SVR but no better ones than epi. -2.True or false. Levo will increase venoconstriction and therefore increase preload. -3.True or false will Levo increase or decrease insulin production ? Increase or decrease blood sugar?

-1.Induced reflex Vagal Activity No chronotropic effect that is seen w/ Beta-1 stimulation just an ↑ SVR at Low doses resulting in: ↓ organ flow, but ↑ coronary artery perfusion bc ↑ DBP vs Epi ↑ pulse pressure ↑ SBP w/ normal or slight drop in DBP ↑ Renal Resistance = ↓ UOP -2.Venoconstriction = ↑ Preload -1st line tx for shock * Drug of choice over Dopamine better response with gram negative Sepsis bc ↓ beta effects & less adverse effects Also chosen for patients with adequate CO but ↓ SVR Intense peripheral constriction = ↓ tissue perfusion -3.Mild ↓ in insulin production Not the same degree as Epi May see Slight ↑ blood sugar

Phosphodiesterase Inhibitors -1. What is the mechanism of action of phosphodiesterase inhibitors? Where are CAMP found when it comes to PDE3? How about cGMP what type of nerve? -2. Quick note -3. When the patient is advanced in the disease process dopamine will not work as a inotrope, however why? -4. PDE inhibitor are also called inodilators,why? How do they decrease LVEDP? -5. True or false. PDE3 decreased pre-load. -6. Two or false. True or false. PDEI's have greater affect then cardiac glycoside and have an additive action with the catecholamines PDE5 -7. How did the drugs end? How will you recognize the family? -do they decrease cGMP or cAmp or both? -what organ does it target?(2) -T/F pde 5 like sildafinil will increase blood flow to penis and to heart. -what is the use of these drugs (for wjat disease they r good) then based on their effect? (2) PDE4 -8.How did the drugs end? How will you recognize the family? -do they decrease cGMP or cAmp or both? -what organ does it target?(3) PDE3 -8.How did the drugs end? How will you recognize the family? -do they decrease cGMP or cAmp or both? -what organ does it target?(3) -another use of pde3 .. guess!! -t/f. PDE3 prevent plt aggregation for thrombosis prophylaxis

-1.Inhibit breakdown of cAMP (adrenergic nerve) & cGMP(cholinergic nerve), both 2nd messenger modulating hormones & NTs → vasodilation & smooth muscle relaxation in heart, lungs, & genitals -PDE3 - ↓ hydrolysis of cAMP -2.(inhibit PDE-phosphodiesterase) Receptor stimulus is 1st messenger cAMP is 2nd messenger in cell Ca2+ is 3rd messenger in cell - so it keeps activation of 3rd messenger •there are 7 families of PDE PDE 1,5,6 GMP PDE 3,4,7 AMP PDE 2 is non selective (for both) •-3.Sometimes you give dobutamine and it doesnt work (maybe cause disease is progressing) receptors are worn out but you give milrinone and it still works because it goes inside the cell -4.Inodilators ↑ Ca2+ ↑ Contractility ↑ CO ↓ LVEDP -5.↓ both Preload & ↓ Afterload D/T vasodilaory effect along with inotropy Theoretically, ↓ wall tension & ↓ myocardial O2 consumption -6.Hemodynamic response to selective PDEIs are going to exceed that of the Cardiac glycosides & have a synergistic action with the Catecholamines → greater clinical usefulness PDE5 - selectively ↑ cGMP; the "-afils" PDE4 - inflammatory states; the "-lasts" PDE3 - both ↑ cAMP & cGMP -7.PDE5 -PDE5 - selectively ↑ cGMP; the "-afils" -increase cGMP -target lungs and penis -for pulm HTN -8.PDE4 -PDE5 - selectively ↑ cGMP; the "-afils" -target airway(reactivedsease), skin,immune sysem(affect skin bowel and jointd) -9.PDE3 -milrinone ad cilostazol PDE3 - both ↑ cAMP & cGMP -increasw inotropy and relaxation of vascular

Beta-adrenergic selective agents:atenolol (long term -1. What is pharmacology for class? -2.What are some clinical use? How is a Given orally or IV? -3.What is the dose orally and the frequency? -4.After how long do you start seeing effects when it's taken orally? -5.which is the most selective beta1 antagonist exam!!!! -6. T/F A renal dosing if patient has renal disease

-1.Most selective β1 antagonist (exam)(Cardioselective) may be ideal for asthmatic pt. -2.Significantly ↓ incidence of post-op myocardial ischemia(again BEST and most selective beta 1 antagonist0 -5-10 preoperatively -2. can be given orally and IV. 50-200mg daily and 5010 mg IVP -5.atenolol . So it significantly decrease the incidence of post op myocardial ischemia Renal dosing d/t elimination primarily Renal while most are liver

Vasopressin -1. Where in the brain is vasopressin? Where in the brain is it from? -2.What is the clinical effect oV1 stimulation? V2 stimulation?V3? -3.True or false. Vasopressin is the first line of therapy for vasoplegia not responsive to other catecholamine and also to ACE or ARB overdose . What is the 2nd line of tx? -4.what is infusion rate for bolus? Over how long? What is drip rate? -5.what are clinical effect of overdose of vasopressin? -6. Again what are rates for bolus? Infusion? What is DOA? -7. What are vasopressin major endogenous roles? -8. T/F When vasopressin is administered to healthy patients, there is increase in BP

-1.Produced by Hypothalamus & released by Posterior Pituitary Gland V1 receptor stimulation = intense Vasoconstriction (Gq) V2 stimulates synthesis/insertion of Aquaporins into the walls of collecting ducts → ↑ H2O reabsorption & ↓ serum osmolarity - (ADH) V3 are in pituitary gland and modulate "local Hormone" 1st line therapy for ACEI or ARB induced also for Vasoplegia, refractive to Catecholamines Refractory HoTN Not responsive to conventional therapies (catecholamine & fluid therapy) 2nd line tx is Methylene Blue - works on the Nitric Oxide pathway -dye given to see their ureter) Infusion: 1-2mg/kg bolus over 10-20 minutes followed by infusion 0.25mg/kg/hr; Not exceed 7mg/kg -*** vasopressin can be given as a bolus (1 to 2 units) and/or fusion 0.01 to 1 unit per minute which rapidly on cell and last 10 to 30 minutes. Overdose Hyponatremia & Seizures s(put on a pump) Vasopressin infusion Bolus = 0.5 - 1U Infusion = 0.01 - 0.04U/min Rapid onset & last 10 - 30 min -7. Water,osmolar, BP Homeostasis -8. When vasopressin is administered to healthy patients, there is no increase in BP. If pt has RAAS or BP prob then increase BP

Selective alpha 1 receptor antagonist: Prazosin "Ozin" -1. What is the Pharmacological classe of this drug? -2. What effect will you see after administration? -3.T/F this drug will cause severe bradycardia. -4.This drug will cause severe tachycardia. -5. What is the main side effect of this drug?

-1.Selective & Competitive(exam), postsynaptic α1 antagonist used for HTN -2.Dilates both arterioles > veins with lesser degree of tachycardia

Beta-adrenergic selective agents:metoprolol -1. What pharmacological class? -2.does it mostly act in HR or BP? Why is it given during MI Dx? -3.t/f drug is less likely to trigger bronchospasM -4. What are some of clinical use? -5. What is normal dose? -6.think of scenarios where drug can be used as a tx.

-1.Selective β1 that prevents inotropic & chronotropic responses to stimulation -3.bronchodilator, vasodilator, metabolic effect of β2 as far as insulin, glucagon, gluconeogenesis, glycolysis remain intact at normal doses so its less likely to cause adverse effects in pt w/ DM, PVD or Airway disease -6.Tx: Angina, HF, MI, AFIB, HTN

Non-Selective Adrenergic Antagonist:labetalol (apex) -1. What is the pharmacological class of labetalol? Is it mostly alpha or beta? -2.What is the primary indication for labetalol? -3.What are some clinical clinical effects you will see after administering drug? In the blood pressure? In a heartbeat? In the lungs? To what type of patients and not give it? -4.True or false. Labetalol will produce vasodilation while triggering baroreceptors increases in heart rate -5.what is the half-life of drug? -6.Where is drug metabolized? Where is it eliminated? -7..True or false. The drug can be administered orally an IV. What is the dose given orally? What is the dose given IV? -8. What are some side effects of labetalol?

-1.mostly beta -2.acute HTN -6 6 hrs (labetalol has 7 letters) -7. 200-1200mg and 5 mg IVP -8. Ppt

Dopamine (DA) -1.what are the effects of dopamine at a low-dose? Moderate dose? High dose? -2.T/F Adele's response to dopamine varies widely in the general population due to genetics, individual pharmacokinetic differences, and comorbidity. -3. What is the effect of simulation of post an optic D1 receptors? Presynaptic D2 receptors? -4. Where are D2 receptors found? -5. Dopamine is usually given via IV pump, drip why? -6. T/F Dopamine drip can cause limp ischemia -7. What other medication can prolong duration of dopamine? -8. T/F drug only stimulate alpha and dopamine receptors. -9.what is infusion dose? -10.T/F dopamine also increase aldosterone..increase Na released -11.T/F dopamine can cause limb ischemia so you need a good IV -12.EXAM!!! T/F effect can be prolonged with MAOIs and TCAsSome notes to read. can you give some exs of MAOI and TCA?-13.dopamine can neg affect the immune system -14. how will dopaminegiven a patient with glaucoma affect him? -15. some more notes ..read -16. what is effect of dobutamine on puml HTN?

-4. Hint! Dopamine is brain so pituitary gland, emetic center. Exception is kidney -6. True -7. MAOIs -8. False. DA1=DA2> B1>B2> a1=a2 -9.0.5-2mcg/kg/min -10.Used for it's Dopaminergic effect ↑ Renal blood flow, ↑ GFR, & ↑ UOP Inhibits Aldosterone = ↑ Na excretion & ↑UOP -11.Limb ischemia -Needs a good IV -12.EXAM!!! Effects can be prolonged with MAOI's & Tricyclic Antidepressants (TCA) Ex: MAIO: Nardil, Marplan, Parnate Ex: TCA: Elavil, Asendin, Anafranil, Afapine, Sinequan, Tofranil, Pamelor, Vivactil SEE Exam Type Question -13.Can negatively affect Immune System d/t effects on Hormones & Lymphocyte function, ↓ hypothalamic-pituitary system like chronic stress/illness & ↓ Prolactin levels which regulate T & B Lymphocytes -14.Con't infusions = ↑ IOP -Consider w/ Glaucoma -think of dopamine ↑contractility--> squeeze eye ball equally and ↑ IOP Infusion 0.5 - 2mcg/kg/min Elimination Half-life: 1-2 min -15. -Anything below neck.. No dopamine receptors -In periphery -Renal artery (2-5 mcg) -vasodilation Splenchic (gutt) -Dose-dependent effect -Renal dose (2-5 mcg)-dopamine receptors activated -Cardiac contractility (5-10mcg)-dopamine and beta receptors activated (ALSOALPHA BUT TO LESSER DEGREE) -Pressors (10-15 mcg)- dopamine, beta and alpha receptors activated ONE MORE TIME... Dose dependent stimulation of Dopamine, beta, & alpha receptors Low = dopamine (D1 & D2) 1 - 2 mcg/kg/min ⇒ ↑ Renal blood flow, ↑ GFR, & ↑ UOP Moderate = beta 2 - 10 mcg/kg/min ⇒ ↑ Contractility, ↑ HR & ↑ CO; ideal for CHF High = alpha 10 - 20 mcg/kg/min ⇒ Act like NE -Prolog use of anti-dopamine drug = tardive dyskinesia -Drug for that inhibit VMAT 2 (from cytoplasm into package) and VMAT1 isfrom synapse ito nerve -Valbenazine less VMAT2 inhibit → regulate catech intake into vesicke→ + NE intake into vesicles → less NE in synapse → less tardive dyskinesia- -16.↓ PA pressure & ↓ pulmonary vascular resistance via β2 stimulation Good for PHTN Inhibits Hypoxic Pulmonary Vasoconstriction

Nonselective alpha 1 an alpha 2 antagonist:phentolamine -1. What is the pharmacological class of this drug? Is it competitive or non-competitive? -2. What is the half life? -3. Reflex tachycardia is a side effect of an medication, why? What population need our special attention when using this drug? what drug will be given in conjunction with this drug very often? -4. What are the clinical use of this drug? (4) -5. -what is the dose IV? What is onset?what is duration?what is infusion rate? -T/Fit is often given with BBB -6. What are some SE of this drug( 5) -7. Drug can be given for HTN emergencies or ANS hyperreflexia. how much? -8.T/F this is the antidote to extravasation..what is dose?

-1.pic -2.PIC -3. flow limited CAD patients. Often given with Beta-blockers -4. the use of the drug -extravasation, -pheochromocytoma, -refractory hypertension from abrupt clonidine d/c , -hypereflexia -5.1-5mg IV: Peripheral vasodilation and ↓ BP within 2 minutes, lasting 10-15 minutes; 0.1-0.2mg/min infusion -true. Often given with beta-blocker (for reflex tachycardia) -↓ BP → BRR = ↑ SNS activity on a2 -↑ NE release from postganglionic nerve terminals -Don't want any other SNS r/t to pheochromocytoma's already labile nature, but applying beta blockers with alpha is Not commonly done -BB for HR control, Not BP control you normally wouldnt want to blunt this but in pheochromocytoma you want NO SNS at all. You will look at pt and it 150/60 then 240/170 -6.SE: Ach s/s --> Cardiac dysrhythmias, angina, hyperperistalsis, abdominal pain, and diarrhea -7.Hypertensive emergencies or ANS hyperreflexia -30-70 mcg/kg IV Used like Hydralazine but does Not last 6-8 hours -8. true. 2.5-10mg mixed with 10ml of NSS

Nonselective endogenous catecholamine -apex -1. T/F catecholamines can cause profound body weight affect as well as events like ischemia for arrhythmia

-1.true -2. What are the three endogenous catecholamines? -3. Name some of the systemic effects of them?(5) See next cards :)

EPINEPHRINE: α1=α2< β1>β2 -1.what is clinical effect when alpha 1 stimulated by epi,,does it make sense? -2.what is clinical effect when alpha 2 stimulated by epi,,does it make sense? -13what is clinical effect when beta 1 stimulated by epi,,does it make sense?

-1.α1 receptor ↑ Vasoconstriction ↑ PVR Receptors found in Cutaneous, Splanchnic, & Renal Vascular beds ↓ Mucosal Edema Mydriasis - Dilates Pupils- EXAM!!! Contracts Radial Muscles (Pupillary Dilator) muscles pulling the pupil open vs Circular muscles (pulpillary constrictions) Miosis Contraction of orbital muscles looks like Exophthalmos -2.α2 receptor ↓ Insulin release ↓ NE release -3.β1 receptor ↑ Contractility ↑ HR - chronotropic ↑ Conduction Velocity - dromotropic Can cause ischemia by ↑ Myocardial O2 requirements If the arteries are Not obstructed, you should have Autoregulation → ↑ O2 delivery to meet ↑ demand If there are lesions, Autoregulation may Not be enough to meet that ↑ demand = Ischemia

APEX-alpha 2 agonist -1.what is MAO of alpha 2 agonist? . -2. Where is alpha 2 receptors located in the nervous system? -3. can these drugs be reversed? -4. explain the rebound effect as it relates to alpha 2 agonist?

-1.𝛼2 Agonist - Bind selectively to Presynaptic 𝛼2 receptors & ↓ release of NE & ↓ sympathetic outflow Similar ↓ BP as an 𝛼1 Antagonist -2. Medulla (decrease SNS tone), vagus nerve? Locus Aureolus (sedation), spinal cord (analgesia), unknown location (anti shivering ) -3.Bind competitively - can be displaced & CNS effects reversed -4.Rebound effect - d/t withdrawal & ↑ in sympathetic outflow (dangerously HTN & tachycardia) More common in Clonidine than Precedex d/t upregulation of receptors

Nonselective alpha 1 an alpha 2 antagonist:phenoxybenzamine -1. What is the pharmacological category of this drug?How is this drug usually given? What route? -2. What is the mechanism of action of this drug? -3. What type of bonding is it between the drug and the receptor? Ionic? Hydrogen? Covalent? -4. After administration of this drug will heart rate increase,decrease why? -5. What is the only clinical use of this drug? -6. Falling secondary to orthostatic hypertension is a result of this drug, how can provider prevent it? -7.T/F Levo and E neo will be in effective in treating the severe hypotension induced by this drug -8. Explain the phenomenon of EPi- reversal that happens with this drug. Does the patient get hypotension or hypertension? -9. What would be the best treatments in case of hypotension?(2) -10. Drug is an alpha one antagonist, what clinical effect will you see? Drug is an alpha two antagonist, what clinical effect will you see? -11.what is the PO dose? -12. T/FIf pt wasn't hypertensive, the BP will drop even more -13.can this drug be used For extravasation?

-10. Alpha 1 antagonist equal drop in blood pressure. -10.Alpha-2 antagonist equal less reuptake of Norepi equal tachycardia (since NE can't stimulate alpha one, it will go and stimulate beta one (aka tachy and arrhythmia ) -11.0.5-1mg/kg PO -12. False. BP won't change.No change in BP if pt. is Not Hypertensive or Hypovolemic (or No pathology causing ↑ SNS activity) -13. True EXAM: Long-acting, nonselective, noncompetitive, irreversible(exam) 1 and 2 antagonis

Phenylephrine -9. What is the antidote for a neo overdose? In case of neo overdose would you give a beta receptor antagonist? Why? What is a common treatment for neo overdose? -10.what is the onset of neo? -11. T/f neo isan active ingredients in nasal sprays for decongestants -12.•if pt is on MAOIs, TCI etc psych meds do you give ephedrine or phenylephrine?

-10.immediate -11.true -12.Phenylephrine always.

Isoproterenol- chemical PPM apex/ppt -1.what drug is it derived from? -2. What is the IV infusion Dose? -3. What receptors does this drugs stimulate? -4.T/F drug has 2 to 3 times the potency of Epi and does have alpha activity. -5. Why is this drug called the chemical pacemaker?what other interventions have replaced this medications nowadays? Why? -6. T/F Drug can helpManage RV dysfunction and pulm congestion .. what other drug has better effect And less SE? -7. How is drug metabolize?by what route is prefered for this drug?

-2. 2-10 MCG/MIN (LIKE EPI) -4. True for beginning but not alpha activity

Alpha two receptors agonist- simulation and transient hypertension. -1. Can precedex cause transient hypertension? -2.what enzyme metab neo? -3.which adrenergic agonist is not arrhytmogenic -4. which selective alpha 2 agonist is highly protein?

-2. MAO -3. neo -4.precedex 94% protein bound and clonidine is 50%

Non-Selective Adrenergic Antagonist:carvedilol -1. What is a pharmacological class of cur of drug? Alpha 1? Beta 1? Beta 2? -2.True or false. Drug processes both antioxidant and anti-inflammatory properties. -3.What are some clinical use of drug? Heart failure? LV dysfunction? Hypertension? Acute MI? -4.What is the dose administered orally? What is the side effect of the drug?

-2. True.Given the known relation between cardiovascular risk and oxidative stress, inflammation, and C-reactive protein, the authors suggested that carvedilol may have anti-inflammatory effects, possibly by decreasing oxidative stress in mononuclear cells

Selective alpha 2 receptor antagonist:yohimbine -1.T/F this drug is mostly for females -2./F the supplement is legal in USA ? can you have it as an ingredient in a supplement? -3. What pharmacological category? -4. What are use of drug? (5) -5.is drug still use clinically? -6. Will it decrease Antihypertensive effect of drug we administer? -7.does drug crosses BBB?what clinical effect can you see as a result of BBB crossing? -8.what is pharmacological class? will you have increase NE release or decrease? -9.based on pharm class what are some SE you can think of? -10.T/F there is questionable thought about interaction with VAs?

-2. false it can be abusive (dissociative state) -4. erectile dysfunction, athletic performance, weight loss, hypotension, diabetic neuropathy -7.Crosses BBB - increased skeletal muscle activity and tremor -8.Selective & Competitive(exam) antagonist at presynaptic α2 receptors - enhances NE release ↑ Sympathtic tone by ↑ from Presynaptic nerve terminal = ↑ NE -9.Excessive doses = tachycardia, HTN, rhinorrhea(why?), paresthesias, and dissociative states -10.?? Interaction with VA -Can ↓ anesthetic requirements - SEE Exam

Phenylephrine -1.what is the classification of neo? -2.what Receptor does it stimulate? Does it cause arterial constriction or Venus construction? -what is the MAO of Neo? -3. What is the initial bolus del of Neo? What is the maximum of that bolus dose? -4. What is the infusion rate for Neo? -5. Ready cardia is a side effect of Neo. Why does it happen? -6. T/F neo and increase pulmonary pressure. -7.T/F meo cause arrhythmia. -8. T/F with neo beta 1> beta 2 so you need more of the drug to stimulate alpha 1

-2.•Increased SVR and venous return = Increased BP

Selective alpha 1 receptor antagonist: Terazosin, doxazosin, tamsulosin "Ozin" -1. Which of the alpha receptor antagonist is specifically for bladder issues? -2. what is some other use? -what pharm class are they?will you get tachy or no pos administration?

-2/ HTN tx -3.Selective, postsynaptic α1 antagonist used for HTN & BPH w/o ↑ release of NE from Sympathetic Postganglioinic nerve terminals = ↓ Tachycardia

Beta-adrenergic selective agents:esmolol -1. What is pharmacological class? -2.What is the main clinical use? -3.T/F The drug has a quick onset, duration less than 15 minutes, is titrable , decreases heart rate in a dose dependent manner. -5. How is the drug metabolized? -6.Can drug be given as a bolus? How much? Can the drug be given as a drip how much? -7.what is the pH of esmolol? -8. T/F Drug burn on injection and can only be given IV

-2/ rapid control of HR and BP -6.bolus is 10-80 mg and infusion 50-400mcg/kb/min -7.pH 4.5-5.5 so it burns on injection -8.true

Beta-Adrenegics antagonist -1. What are some indication for the use of beta blocker?(5) -2 what are some concern with the use of Betta Block?(6)... also read and see if make sense -3. What does Membrane stabilizing activity mean?what beta blockers have MSA properties? -4.t/F beta adrenergic antagonist can be classified as non selective and selective -5.T/F beta blocker are made of a benzene ring -6.notes (read) -7.how many % beta 1 in heart? vs beta 2? -8.what can t you suddenly d/c after years of taking in? -9.Which drug is considered standard as a beta antagonist? -10.True or false most beta agonist are structurally related to isoproterenol: how do they look alike? What makes them different? (Agonist versus Antagonist) -11.what is the difference between cardioselective drugs and known cardioselective drugs?

-3. MSA mean it prevent arrhythmia. Ex: propranolol Hint!-P-LAMP Pinonlol Labetalol Acebutalol Metropolol Propanolol -5.false -6. -Bind competitively to prevent actions of catecholamines & beta agonists unless [agonist] > [antagonist] at the receptor -Block Chronotropy, Inotropy, & Dromotropy → ↓ O2 consumption & ↑ Perfusion Blocked by BB -Prevents effects of catecholamines & sympathomimetic on Heart & Smooth muscles of Airway & Blood vessels -7.Tx. of CV disease blocks β receptors associated w/ vasoconstriction & cardioacceleration → BV dilate or prevents ↑ HR - can improve cardiac function in CHF, MI, etc SVT, Afib, blunting during intubation Post MI want to keep coronary vasodilated 75% of beta receptors in heart are 𝛽1 25% are 𝛽2 -8.Chronic use = ↑ beta receptors (Upregulation) -9.Propranolol is standard -10.Most are structurally r/t Isoproterenol Benzene ring= Beating =Isoproterenol - Substitution determines whether it is an Antagonist or Agonist -S: Better for Atrial tachycardia than CCBs -11.Cardioselective targets 𝛽1 vs. Non-cardioselective targets 𝛽1& 𝛽2 Nonselective ↑ Airway Resistance Avoid w/ Asthma pts

Ephedrine -1. What is the classification of ephedrine? -2. Ephedrine exerts both direct and indirect action on adrenoreceptors. Which one predominates direct or indirect? -3. What is the Ivy dose of the drug? IM dose? -4.What's receptors the drug Stimulate?what NT is released the ? -5.What is the indirect action of it? What is the direct action of it? -6.What does tachyphylaxis s mean? -7.T/F drug can c cross the BBB -8. Onset and Duration of the drug? Does the drug cause hyperglycemia.? -9. Does this drug have any effect on the heart?Chronotropic? Dromotropic? What population careful with? -10.between neo and ephedrine which one is preferred for a pregnant woman? -11. What route can the drug be? -12.T/F drug has antiemetic effect -13. Wjat receptors are stimulated?im what order -14.drug can be used for bronchospams? -15. What are the three "and" of this drug? -16.•if pt is on MAOIs, TCI etc psych meds do you give ephedrine or phenylephrine? -17. what is duration of epherdine? what is DOA?is it more orless potent thsn epi? does it last longer? if yes, how much longer? -18. T/F. if giving more than 25 mg of epherdine then you need another medications (like neo) -19.how is ephedrine metabolized

-3.(LISA) 10MG BOLUS..you get tachyphylaxis from it -11.PO,IM,SQ,IV -12. True -13. Alhoa1=alpha 2> beta 1=beta 2 -14. True (beta 2 properties) -15.•A)(Direct) and indirect-acting synthetic non-catecholamine. indirectly causes release of endogenous catecholamines •B)Stimulates both alpha and beta directly; •(alpha>beta) •C)Central and peripheral actions-few adrenergic that can cross BBB. -Inc SBP & Inc DBP unlike Epi; Inc HR & Inc CO unlike Phenlyephrine Most catecholamine levo,neo drip works from the neck down . they do not cross the blood-brain barrier. Whatever catecho is in the brain was made by the brain Thats why with alzheimer (missing dopamine) you cant give them dopamine you give them a precursor L-dopa and it will cross brain and brain will make dopamine -16.Phenylephrine always. Psych meds work by depleting cathecholamine (keep them i the synaptic cleft) and so ephedrine wont work as well -17. Immediate onset w/ variable Duration of action (5-25mg) DOA 15 min - 1.5 hours ↓ potent than Epi but lasts 10X longer(not metabolized by COMT and MAO but by liver) -18.If giving more than 25mg, need a heavier hitter (NE, Epi, or Vaso): Neo #1, Ephedrine #2 Metabolized in Liver by oxidative deamination, demethylation, aromatic hydroxylation, & conjugation w/ metabolites NE & benzoic acid; Most Renal - Unchanged Resistant to MAO metabolism Caution w/ MAOI

APEX-alpha 2 agonist:clonidine -1.clonidine can be used for various conditions. Name three. -2.T/F you cannot abruptly discontinue clonidine. -3. what is MAO of drug? -4.in what routes is drug avilable? -5.how is it metab and excreted? -6.what is half life? -7. T/F xerostomia is a SE -8.sidee..what are 3 locations for alpha 2?

-3.Presynaptic partial α2 agonist (400:1) (still preferential a2) that ↓ sympathetic outflow -Stimulates inhibitory neurons in Medullary Vasomotor Center -Dose-dependent ↓ sympathetic outflow → peripheral vasodilation, ↓ SBP, ↓ HR, & ↓ CO -1.Used to treat HTN, anxiety, pain conditions, & ADHD -4.Available PO, transdermal, IV, & epidural forms -Skipping → dangerously HTN & Tachycardia d/t to upregulation of receptors -5.Metabolized in the Liver but is excreted mostly unchanged in the urine & to a lesser extent in the bile & feces. -Hint! Clonidine = clone = unchanged -6.Terminal half-life - 12 to 16 hours but can vary w/ any Liver or Kidney dysfunction. -7.SE: Sedation & Serostomia (Dry mouth) -8. see pic

Beta-Adrenegics antagonist :propanolol -1.what is the pharmacological class of propaolol? -2.T/F Beta 2 antagonism =bronchoconstriction,vasoconstriction adhypoglycemiaand so propanolol would aggrevate raynaud s disease and vascular disease -3.what are some other nonselective beta adrenergic antagonist?which has the longest half life?which is a weak beta agonist with less decrease in HR and BP? -4.will propanolol = increase or decrease PVR -5.how much protein bound is propanolol? -6.T/F drug can increase clearance of amide L.A -7.T/Fpropanolol crosses the BBB- scratch that -8.drug can be given for thyrotoxicosis, essential tremor, and migraine -9.which anesthetic might be prolonged by propanolol

-3.carvedilol,nadolol,pindolol,sotalol,timolol.longest half life is nadolol ad weaker beta antagonist is pindolol HINT! The PPINS (like bby pins) Propanolol Pindolol Nadolol Sotalol Timolol -4.increase PVR (from beta 2 antagonist) -5.Highly protein bound (90-95%) -6.Decreases clearance of amide LA's -7.True-scratchthat -8.Control of thyrotoxicosis, essential tremor, and migraine -9.amide LA and fentanyl

Epinephrine -apex/ppt -1.what is the epi infusion dose for Epi? -2.T/F epi is a more potent alpha stimulator than levo? -3.The net effect of epi depends on 2 things,what are they? -4. What effect will the drug have if organ has a a lot of beta receptors? The organ has a lot of alpha receptors? The patient is given a low-dose? If a high dose? -5.Administration of epi results in decreaseof blood sugar and hyperkalemia -6.T/F epi can prolongue the effect of LA -7. T/F epi is the final product and catecholamines synthesis and it naturally body? epi works in a dennervated heart -8. Where is epi Synthesized stored and released from? -9. T/F epi is poor lipid soluble -10. Epi effect depends on doses tell me more about that. Low, medium and high dose , and what itwould target? would u see arhythmia with epi dose > 10? what type?

-5. Me: hypokalemia. because lots of ATP made and so na/K pump reestenlishimt balance pumping K into cell -7.Agonist at alpha & beta receptors, but Beta 1 > Beta 2 -7.Naturally occurring and final product in catecholamine synthesis -works on a denervated heart like isoproteronol & glucagon -8.Synthesized, stored, and released from adrenal medulla -9.Poorly lipid soluble. most catecholamines are only from neck down.dont cross brain -10.Low doses ▫ 0.01-0.03mcg/kg/min ▫> Beta-1 and Beta-2 ●Increased HR, CO, inotropy, decreased SVR and a widened pulse pressure •Intermediate doses ▫ 0.03-0.15mcg/kg/min ▫Mixed alpha and beta effects •High doses ▫ >0.15mcg/kg/min ▫> Alpha effects ▫Tachyarrhythmias are common -SVT -10. True

APEX-alpha 2 agonist:dexmedetomidine -1.what receptors are stimulated with this drug? At what location? -2. What are two severe side effects of the drug? -3. What are some other ANS effects of this drug? Think of the summary table of Alpha and beta receptors. -4. T/F drug can reduce emergence agitation. -5.some note -6.how much bolus?infusion?what if you give too much, too fast? -7. is it bound to protein?where is it metabolized?what would happen in case of liver impairement?is it clinically seen?

-5.Introduced as a Sedative & Analgesic d/t central sympatholytic effects -Selective α2 agonist with a 1600:1 preference to α2 -6.Bolus 4-12 mcg; 0.1-1.5mcg/kg/min con't infusion Large boluses (25 - 50mcg) can cause paradoxical HTN w/ ↑ HR d/t alpha 1 stimulation a1 stimulation → ↑ intracellular Ca & ↑ vasoconstriction (aka HTN) -7.Extensively protein bound (a1 glycoprotein) & undergoes Extensive Hepatic biotransformation Liver impairment can dramatically ↑ plasma levels & ↑ Duration of Action -Not clinically seen

Selective beta 2 agonist(apex) -1. What are the short drugs of the category?(3) what are the long acting ones?(2) -2. What are the bronchodilators used?(2) -3. What are three side effects of this drug? How can you minimize it? -4. Why should you use chronic beta 2 agonist with caution?(2)what is the FDA black box warning? -5.intracellularly wnat is the mechanism Of beta 2 agonist? -6. What is onset of short acting beta agonist? Duration? -7. What is dose for these drugs (in non intubated pt) -8. What SE of the drug -9. T/F drug can be used to stop premature uterine contraction -10. Do we have hyperglycemia? Hyperkalemia? Julomagnesemia?

-6. Onset 5 mins , duration 6 hrs -7. 2 puff (always) -8. Tachy,arrhytmia, tolerance, restlessness, anxiety -9. True -10. Hyperglycemia (SNS on need energy) hypokalememia (al but Erik used in renal Pt with high K) and hypomagnesemia (Mg follow K )

Norepinephrine (NE) -apex/ppt -Between the alpha and beta what is mostly stimulated by Norepi? Between beta 1 and beta 2? -what is infusion dose? -T/F The net effect of the drug depends on the dose. What receptor is simulated with low dose? What receptor is simulated with high dose? -T/F The systemic vasoconstriction effect is lesser than epi. -T/F drugs increase blood pressure by causing me venous vasoconstriction also -6.T/F drugs increase blood sugar. -7.T/F drug is first line in distributive shock that is refractory to hypotension -8. where is levo synthesizedand sotred? -9 what si the precursor ofepi? -10.T/F levo has a Dose dependent affinity for alpha-1, alpha-2 & beta an a very big affinity for beta-2 effects -what receptors are stimulated by low doses? wht is clinical effect? -10. would this drug cause metabolic acidosis or alkalosis? -11. Drug is of choice In cardiogenic shock -12. What is the dose for refractory hypotension -13T/F.drug comes in a 5% glucose solution . what other drug needs to be in a 5% glucose solution? -14. What is the antidote in case of extravasation EXAM!!

-6.False. Levo does not increase blood glucose -8.Endogenous NT synthesized & stored in Postganglionic Sympathetic Nerves also synthesized in Adrenal Medulla -9.Immediate precursor to Epi -10.Dose dependent affinity for alpha-1, alpha-2 & beta-1 Very little beta-2 effects Low doses → beta-1 selective > beta-2 ⇒ ↑ HR CO BP & Contractility High doses → ↑ alpha-1 & ↑ alpha-2 ↑ SVR, ↑ BP ↓ HR possible from BRR Overall = ↓ CO - BUT HR altertion clinically insignificant -10.Metabolic acidosis Peripheral vasoconstriction may ↓ tissue BF -11.Avoided in cardiogenic shock d/t ↑ SVR or afterload -12.Infusion 0.02 - 0.04 mcg/kg/min 2-16mcg/min for Refractory HoTN Good for ↓ SVR states like Sepsis -13.5% glucose solution - to sufficient acidity to prevent oxidation of the catecholamine Dobutamine as well needs to be in glucose concentration -14.Extravasation - Phentolamine (Regitine) Nonselective & Competitive alpha antagonist injected directly into the area that causes Vasodilation (2.5-10mg diluted in 10mL NS); hence why you need a CVC Can also do a Stellate Ganglion block → Vasodilation Produces severe local vasoconstriction & Necrosis

Notes about Asthma management and CRNA

-Bronchospasms during surgery Get them deeper , so increase the gas (bronchorelaxstion) Increase ketamine Can give prop (bronchi relaxatio) but very slow Give their own Ali but work med (Disconnect the circuit 8 to 10 puff and the tube -you need to give more as the medication will stick to the walls of the tube for reaching to the patient -and reconnect the circus and bag them ) Extubbation of an asthmatic the earlier the better but risk of loosing airway Best deep extubation (so no reflexes/irritation of tube) When in doubt, leave the ETT in Can give 25 mcg if fent (low dose) to suppress cough ,20 mg of lidocaine For muscle relaxing, if you're giving me neostigmine give less more is Robin all with it... Just gives suggamadex! The treatment for pregnant and non-pregnant woman is the same but for pregnant woman give less better agones as it will broncodilate but it will also relax the uterus. -AllGx reaction If it happens before intubation then it's an allergic reaction If it happens after intubation If there is no rash or no cardiac symptoms it's not an allergy it's bronchospasms so increase your gas If there is a rash or cardiac symptoms then it is an allergy

Synthetic catecholamines

-Isoproterenol - Dobutamine

Notes about Asthma management and CRNA

-Muscarinic antagonist-much milder than beta agonist •ex: ipratoprium(atropine analogue) -Severity and tx •If puffer o longer working, next step is steroid Tx;inhaled corticosteroid (best tx for chronic long term) • -I.Asthma different stages Stage 1:intermittent asthm(short acting beta agonist) Stage 2:persistent asthma-inhaled steroid Stage 3mod persistent asthma Stage 4: severe persistent asthma-increase dose of steroid Goes up to stage 6 and then patient has a tube(antibodies injection) -SE(all close to steroid long term SE) -Inhaled steroid only act ON THE LUNGs vs VA have systemic effect..mystery -NEXT..inhaled long acting Beta agonist (long- Acting Beta Agonist -LABAS high mortality rate II.Anesthesia and asthma If pt has elective sgx and showed up with wheeze and s/s , case needs to be canceled -If emergency Pre-tx w/ systemic steroid indicated(if case isemergency and you had to do it) Hydrocortisone or cortisone Give 1 dose of hydrocortisone or prednisone IV Can algo give 1 dose of robinul (Dr K would give after albuterol and it still hadnt worked) -Be careful w/ narcotics (Histamine)!..do it when you are asleep Morphine,demerol, codeine,phenanthrene The use of H2 histamine blockers is contraindicated, why? H2 receptor blocker (2 for neg feedback) will block histamine negfeedback ad so more histamine in synaptic cleft and = pt worst -IV sedation: Ketamine is the drug of choice (better than propofol or etomidate) -Muscle relaxant: avoid succinylcholine, atracurium, Mivacuriam.(histamine release) -Do you not give Beta blockers To asthmatic better = bronchodilation so better blocker = bronchoconstriction -Three populations that cannot have Betta blockers Asthmatics-Bronchoconstriction diabetics -Mask hypoglycemia symptoms vascular disease patient-vasoconstriction of vessels Watch out for Aspirin sensitive asthma: patient have an asthma attack when you take aspirin and he will know, he will tell you.

Adrenergic receptor antagonist -1. What to subclass comes under that?

-alpha receptor antagonist -beta receptor antagonist

-what 2 beta blockers are the most cardiac specific

-atenolol and metropolol

SYMPATHOMIMETIC -1. What is the chemical structure of sympathomimetic drug? -2.What receptors do these drugs stimulate? (Three) -3.true or false. Efficacy depends on concentration of receptor site, affinity for specific receptor, but not on receptors available. -4.What is Mechanism of action of direct sympathomimetic drugs act? indirect sympathomimetic drug act?

Benzene ring w/ Ethylamine side chain Stimulation of alpha, beta, & dopamine adrenergic receptors Efficacy depends on concentration at receptor site, affinity for specific receptor, & receptors available Direct Acting Sympathomimetic = Receptor Agonists Indirect = cause Release or Block Reuptake of NE Not uncommon to have mixed alpha & beta agonist properties

Beta receptor antagonist : non selective va selective -list the no. Selective drugs -list the selective drugs

Beta 1: A Bad Bitch Make Everything Allright

ALPHA1 1 - ADRENORECEPTORS -some note..just read and make sense of It -T/F restlessness is a SE of neo.

Bind on vascular Smooth Muscle to induce Contraction & Constriction mimics effects of Sympathetic adrenergic nerve activation on those vessels Alpha 1 & Alpha 2 Vascular smooth muscle Alpha 1 > Alpha 2 Gq proteins that activate smooth muscle contraction through IP3, DAG, Ca2+ signal transduction pathway Only 1 that does that Everything else manipulates cAMP Vasoconstriction = work of heart ↑ Phenylephrine SE: Headache, Reflex Bradycardia, Excitability, & Restlessness In cold medicine now d/t Sudafed & meth use

BETA ADRENORECEPTORS -just some note to read

Cardiac & smooth muscle tissues Cardiac stimulation & systemic vasodilation ↑ HR, ↑ contractility, ↑ conduction velocity & some systemic vasodilation Gs = ↑ synthesis of cAMP Gs = S = stimulate Beta 1 > Beta 2 in cardiac nodal tissue Primarily bind NE Also bind circulating catecholamines

Digoxin -1. What is two main use of the drug ? 2.True or false. Positive inotropic effect a' occur with decreased heart rate. -3.True or false calcium is contraindicated for a patient taking digoxin and why? One of true true or false. Calcium is contraindicated in patients being treated with a drug and can give you cardiac arrest. -4.Two or false. This drug will increase feeling and EF and increase heart rate -5.t/f drug is harmful in pt with hyperptrophic AS why? -6.What is the onset of the drug? What is the peak? -7.use has decreased because of SE. what are some sE(4)? -8. What is the first sign of dog toxicity under anesthesia ? (Two) -T/F some others SE Prolonged PR interval, culminating to complete heart -True or false. Principal and isoflurane may be protective. -9.What is the treatment for digoxin? (Three) di -10.Digoxin is well known for numerous drug interactions. What are some of them? How does it influence quinidine? Succs ? Better agonist? Calcium? Oral antacid.

Cardiac Glycoside used to treat CHF -1.Tx of Supraventricular Tachydysrhythmias (Paroxysmal atrial tachycardia, afib/aflutter) -2.Positive Ionotropic effects occur w/o changes in HR - R/T PNS activity Inc Less ↓ in LV Preload, Afterload, wall tension, & O2 consumption -3.↑ intracellularCa2+ calcium contraindicated w/ dig pt. -primary ionotropic effects = binds to alpha subunit on Na/K pump, causing ↑ intracellular Ca2+ → augmenting Myocardial Contractility Can selectively & reversibly inhibits Na/K ion transport Ca2+ is contraindicated in patients being treated with Digoxin → Cardiac Arrest -4.↑ diastolic filling & ↑ EF- it slows the H.R Enhances vagal tone = ↓ HR & prolongation of AV conduction -5.Harmuful in pts with hypertrophic subaortic stenosis because ↑ myocardial contracility ↑ resistance to ventricular ejection(these pts dont need contractibility) In 30% of pt w/ WPWS, digitalis Dec refractiorines in the accessory conduction pathway to the potin that rapid arterial impulses can → Vfib -6.Onset is 10-30 min & Peaks in 2-4 hours -7.Use has ↓ d/t Toxicity & side effects Toxicity = N/V, Diarrhea, HA, Fatigue, Vision problems 1st Sign under Anesthesia is PVC's or Arrhythmia, prolonged PRI, culminating in complete heart block Hypventilation → ↓ CO2 → ↓ K ⇒ ↑ glycosides myocardial binding Atrial Tachycardia (common), V-Fib (death) Tx: Lidocaine Fentanyl & Isoflurane may be protective Toxicity treatment Phenytoin 0.5-1/5mg/kg over 5 min Or Lidocaine 1mg/kg Atropine 25-70mcg/kg if ↓ Hr R/T PNS activity of glycoside Fixing everything that has gone wrong = ↓ K, ↓ Mg, Hypoxemia, Pacemaker if heart block, etc. Numerous drug interactions Quinidine - dose-dependent ↑ [plasma] Succinylcholine - additive effect Beta-agonists - ↑ cardiac dysrhythmias Ca2+ → can lead to cardiac arrest Oral antacids → ↓ oral absorption

-Which agent is NOT removed from the synaptic dleft by reuptake? -Phenylephrine -Dopamine -Norepinephrine -Epinephrine

Correct answer: Phenylephrine Explanation: Phenylephrine is a synthetic noncatecholamine and is not removed from the synaptic cleft by reuptake transportens. Phenylephrine is metabolized by MAO. Dopamine. norepinephrine, and epinephrine are endogenaus catecholamines and are removed from the synaptic cleft by reuptake transporters and are also metabolized MAO and COMT they escape reuptake.

ADRENORECEPTORS: dopamine -Exam!!! -1.where are dopamine receptors located (four)? -2.True or false. Dopamine receptors are the target for psych drugs and many drugs of abuse. -3.There are two types of dopamine receptors what are they? -4.Where is D 1 located? Is it presynaptic or post ? And what organs? Where is D2 located? Is it presynaptic or Postsynaptic? And what organs?

Dopamine Play role in smooth muscle, kidneys,mesenteric , & CNS Target of psych drugs & many drugs of abuse Receptors are classified as D1 or D2 D1 (postsynaptic) - Vasodilation of the Splanchnic Circulation & Vasodilation in Kidney, Intestines, & Heart D2 (presynaptic) activation - play a role in some Antiemetic actions

Phenylephrine -1. What press or would u used for a drop In BP post Neuraxial Anesthesia? - hat press or if mom has low BP And low hR? -2. T/F neo Can be given to pt with CAD and AS -3. Drug is given in nasal spray as decongestant and nasal intubation and fiber optic -4. What is clinical Effect of neo?

Drug of choice for ↓ BP after sympathetic blockade after Neuraxial Anesthesia Good for OB, Epidurals → drug of choice for now But if mom has ↓ HR → Ephedrine Good for CAD & Aortic Stenosis (AS) ↑ coronary perfusion pressure without chronotropic effects Active ingredient in many Nasal Sprays (decongestant) ENT, Nasal intubation, or nasal fiberoptic as it shrinks the vessels. Systemic manifestations of SNS HTN, ↑ HR, or BRR - ↓ HR Metabolized by MAO & Not arrhythmogenic -Phentolamine (Regitine) = antidote ** Beta Blockers are contraindicated to tx phenylephrine induced HTN Extravasaion d/t Norepi, Epi, or Phenylephrine Phenylephrine Toxicity if you accidentally inject Hot Neo. -Or use Nitroglycerin or Nitroprusside Phentolamine is a competitive Alpha 1 antagonist vs Phenoxybrzamine noncompetitive, but both are nonselective -Potent rapid IV vasodilators which causes BRR tachycardia so caution to coronary heart disease •Phentolamine = antidote *if injected 100 mcg/kg of neo by mistake then GIVEN PHENTOLAMINE.. if not phentolamine use vasodilator like nitroglyceride, nitroprusside .. itd oes have to be phentolamine •if pt is on MAOIs, TCI etc psych meds do you give ephedrine or phenylephrine? Phenylephrine always.

Phenylephrine -1. what is infusion rate for neo? -2.what is bolus dose? -3. what receptors are stimulated by neo?which one is more?

Good for HoTN with signs of myocardial ischemia as it ↑ Coronary Perfusion w/o Trachycardia & ↑ arterial BP Hypertrophic Cardiomyopathy & Tetralogy of Fallot (TOF) good when ↑ afterload is required Onset is immediate Duration of action 5 - 20 min Infusion 0.1-1.2mcg/kg/min 10-200mcg/min 50-200mcg bolus But You can even bolus higher than this

ALPHA2 2 - ADRENORECEPTORS -some note..just read and make sense of It -T/F dry mouth is not a SE of alpha 2agonist? Constipation is? Nausea is? Gastric upset is? -T/F these drugs can cause fluid retention and if prescribed chronically is usually given with diuretic

Linked to Gi proteins: "i" = inhibitory ↓ cAMP = smooth muscle contraction Also Dopamine 2 (Presnaptic) does the same: Gi → ↓ cAMP Can also inhibit release of NE act via Negative Feedback In peripheries , alpha 2 Constrict Veins > Arteries Variation between textbooks. She will stay away from this. SE: Sedation, dry mouth, bradycardia, orthostatic HoTN, constipation, nausea, & gastric upset Fluid retention & Edema can be problematic w/ Chronic Therapy Often used w/ diuretic Especially with clonidine Do Not discontinue abruptly → rebound HTN(not so much seen with precedex)

ADRENORECEPTORS: alpha 1 agonist -Exam!!! -Must remember location, stimulated vs agonist -1. Where are alpha-1 usually located? Or do usually excitatory or inhibitory? Vasoconstriction or vasodilation? -2.True or false. Alpha one agonist only increase arterial pressure. -3.What is effect In the eye? What is the effect in the bladder?

Must remember location, stimulated vs agonist α1 - Found in periphery & tissues innervated by SNS postganglionic neurons → Excitatory Vasoconstriction Arterial = ↑ SVR = ↑ BP Venous = ↑ Venous return, ↑ SV, ↑ CO = ↑ BP ↑ SVR/PVR ↑ BP Mydriasis - Pupils Dilate ↑ closure of internal sphincter of bladder

What is the difference between phenoxy benzylamine and phentolamine?

Phenoxybenzamine is irreversible. Body has to make new adrenergic receptors and it takes about 24 hrs -phentolamine is reversible and duration of action is about 4 hrs

METABOLISM (Quizlet) -Exam!!! -1.-tell me about the mechanism from start to finish from tyrosine taken in your food until Epi being released in the blood. -what is the preceptors of tyrosine and by which enzyme is it converted to tyrosine? -True or false you can give a medication that trickS the body into thinking it is NE when it's not and so you will make inactive catecholamine ?

Phenylalanine Phenylalanine hydroxylase Tyrosine Tyrosine hydroxylase L-DOPA DOPA decarboxylase Dopamine Dopamine β- hydroxylase Norepinephrine (Stored in presynaptic vesicles & converted to Epi in Adrenal Medulla) Phenylethanolamine N-methyltransferase Epinephrine Adrenal Medulla: Epi 80% & Norepi 20% —— Tyrosine or phenylalanine found in blood from amino acid (from food) -> taken up into the nerve At the stage where dopa is converted into dopamine, if this is a Neuron that contains dopamine then dopamine will go into the vesicles and that's it. But usually nerves release NE(mainly), Epi or dopamine in the synaptic cleft -However for most of the nerves, the synthesis process continues -YoU trick the body you can give other medication like ethyl methyl dopa -will replace the tyrosine medication synthesized through all the steps just like tyrosine -will give you ethyl methyl dopamine which the body thinks is NE but it's not.

APEX-Drug that modify the ANS and adrenergic Agonist -summary table for drugs and classes .. memorize!

Pic

Adrenergic Antagonists-apex -1. There are three categories of alpha antagonist, what are they? -2. Alpha antagonist require careful titration and monitoring, why?

Pic

APEX-alpha 2 agonist. Think clonidine is #1 and precedex #2 -1. Which drug is a partial agonist? Which drug is a full agonist? -2. Which drug has strong effects? Which drug has mild? -3. How many protein binding for Precedex? For clonidine? -4. What is the elimination half-life of Precedex? Of clonidine? -5. What is the distribution halflife for both dogs? Do they cause resp depression? -6. how are both drugs metabolized and eliminated?

Pic-3. precedex 100% and clonidine 50%

PPT-Drugs covered (the one we need to know)

Picc

Summary of mechanisms -1. What does positive chronotropy? Positive inotropic? Positive dromotropy ?

Positive Chronotropy: ↑ Heart rate Positive Inotropy: ↑ Contractility Positive Dromotropy: ↑ Conduction of impulse (velocity)

Presynaptic receptors(PPT) -T/F presynaptic is sympathomimetic and postsynaptic is sympatholytic.

Ppt

Adrenal medulla(ppt) -1. What neurotransmitter is released by pre ganglionic fibers connected to the adrenal medulla? -2.How much Epi and Nora EP is released by the adrenal medulla in the blood addressed? What is the rate? -3.Catecholamines remain in the bloodstream longer than the synaptic cleft. How much longer? -4.How are the catecholamines "terminated" in the synaptic cleft? -5.When they're "in the blood", how are "metabolized"? Do they go on exerted action after that? How is their action "terminated"? ***EXAM!!!***

Preganglionic fibers release ACh directly onto Chromaffin Cells SNS activation causes release of Norepi/Epi directly into the bloodstream 0.2mcg/kg/min of Epi & 0.05mcg/kg/min of Norepi Rate at rest (body release 14 mcg of epi/min at rest) Catecholamines remain in Bloodstream 5-10X longer than Synaptic cleft Synaptic cleft - Reuptake quickly removes Catecholamine Circulating - Kidneys/Liver where they're going to be metabolized & then go on to exert their action -EXAM!! ***Termination primarily via Reuptake & Diffusion & Metabolism by MAO/COMT in the Liver & Kidneys and plasma***

Practice questions You are preparing to induce general anesthesia in a patient taking propranolol for hypertension. Which drug would you anticipate to have substantially higher than normal plasma concentrations after administration? OA. Isoflurane OB. Fentanyl OC. Chloroprocaine OD. Propofol

Propranolol decreases the clearance of amide local anesthetics, but not ester anesthetics such as chloroprocaine. The pulmonary uptake of fentanyl, however, is substantially decreased in patients taking propranolol. As a result, plasma concentrations shortly after injection can be 2-4 times higher than normal.

BARORECEPTOR REFLEX (BRR) -1. Where is the BRR control center located in the brain? -certain medication/procedure can alter the BRR what are they? (7) -The KardasHian are Not MVP anymore (so BRR is impaired) (mnemo?)

Regulates short-term BP control & a little bit of long term ↑ BP → Reflex will ↓ HR, ↓contractility, & ↓SVR ↓ BP → Reflex will ↑ HR, ↑contractility, & ↑ Total peripheral resistance Chronic HTN causes readjustment to a higher set point Autoregulate at a higher range of MAPs → less tolerant to Hypotension Have the most labile BP Can have significant organ dysfunction at a MAP much higher than 50 Why you shouldn't do elective procedures on patients w/ uncontrolled BP Vasomotor center of Medulla & Pons - main control center for BRR "Preservation" HR adjusts appropriately when the BP changes. BRR is "Impaired" if ↓ BP w/o Tachycardia reflex or HTN w/o Bradycardia reflex Certain Medications/Procedures can alter (Not always impair) BRR Mediastinoscopy Phenylephrine- Potent Vasodilator Volatile Anesthetics Isoflurane the least Thiopental Ketamine Hydralazine Potent Vasodilator. Reduction in SVR is countered w/ an ↑ HR Does Not Impair, it Alters/Counters it NTG/Nipride Potent Vasodilator. Reduction in SVR is countered w/ an ↑ HR Does Not Impair, it Alters/Counters it ——— The KardasHian are Not MVP anymore (so BRR is impaired) -Thiopental -Ketamine -Hydralizine -Nitro/pride -Medianoscopy -Volatile Anesthetic -Phenylephrine

Milrinone -a few notes..

Summary pic -Differs structurally & functionally from catecholamines -Used for Cardiac SX & Heart Failure, acute LVF -30X more potent than Inamrinone & ↓SE -50mcg/kg loading dose -0.375-0.5mcg/kg/min infusion -Max Dose:1.3mg/Kg/day -Adjust if renal -Dose-dependent ↑ in CI -↓ LVEDP, MAP, CVP, PAOP, Pulmonary vascular resistance, & SVR -Good for PHTN - Better than Dobutamine; -Dobutamine preferred if significant vasodilation or renal dysfunction; otherwise, Milrinone for high filling pressure, elevated pulmonary artery pressured, need for continued B blockade, ↓ responsiveness to catecholamine, & high risk for tachyarrhytmias -Improves LV function d/t acceleration of Ca Uptake -Give slow to avoid HoTN - R/T Dec SVR & VR; -Reverse vasospasm in arterial grafts -Anti-inflammatory effect that can be used pre-operatively -PDE3 inhibitors prevent platelet aggregation for thrombosis prophylaxis

Inamrinone -a few notes NONSPECIFIC INHIBITORS -a few notes CALCIUM -see notes

Summary pic -↑ CO, ↑ CI, & ↑ EF -↓ LVEDP, ↓ Wedge pressure, ↓ PAP, ↓ RAP, & ↓ SVR -Inotropic & Vasodilatory effect -PO or IV -0.5-1.5mg/kg loading dose -2-10mcg/kg/min infusion -Max: 10mg/Kg -Give slow to avoid HoTN -Renal dosing adjustment -May respond when catecholamines did not work NONSPECIFIC INHIBITORS Theophylline ↑ cAMP, dilation of the airway smooth muscle & reduce inflammation. Good for Asthma & COPD CALCIUM is present in the body in greater amounts than any other mineral. Calcium is important for (a) neuromuscular transmission, (b) skeletal muscle contraction, (c) cardiac muscle contractility, (d) blood coagulation, and (e) exocytosis necessary for release of neurotransmitters. In addition, calcium is the principal component of bone. Calcium is a potent inotrope. Increasing the plasma concentrations of ionized calcium with exogenous administration of calcium chloride or calcium gluconate is commonly used to treat cardiac depression as may accompany delivery of volatile anesthetics, transfusion of citrated blood, and following termination of cardiopulmonary bypass. Acidosis → Inc ionized Ca+

PPT-Classification of drugs among the main one (she wants us to know) -what drugs are considered natural adrenergic drugs?(3) -what drugs are considered synthetic adrenergic drugs?(4) -What drug prevention of norepinephrine by the synapse?(2)

Sympathomimetics Natural - Amines Epinephrine Norepinephrine Dopamine Synthetic agents Phenylephrine Dobutamine Isoproternol Ephedrine NE Reuptake/Release - Predominately used in research Cocaine Methamphetamine

ppt -Dobutamine (Dobutrex)/ the beta drug /the CO /pu HTN drug -7. In what clinical to pulmonary is given? Dilate or constrict? -8. In what type of solution is the drip given? -9. What was the first does it affect? -10. What is the rate for the IV infusion?

Synthetic Analog of Dopamine & Sympathomimetic Amine (Modification of Isoproterenol) Predominantly beta-1 with mild beta-2 activity ↓ effects on alpha-1 receptors when infused at < 5mcg/kg/min ↑ cAMP = ↑ HR & ↑ contractility (B1) & ↑ CO w/ ↓ arterial vasomotor tone (B2) ↑ Contractility > ↑ HR R/T ↑ Ca from SR - May cause arrhythmias (Sinus Tach most common) ↑ Inotropy & ↑ SV with minimal chronotropy May have slight ↓ SVR d/t peripheral vasodilation Not drug of choice for pt that needs ↑ SVR rather than augmentation of CO. ↑ CO will compensate for ↓ SVR & BP will ↑ or stay the same. ↓ PA pressure & ↓ pulmonary vascular resistance via 𝛽2 stimulation Good for PHTN Inhibits hypoxic pulmonary vasoconstriction Must be given as con't infusion (d/t rapid metabolism) in glucose in water ↑ acidity & avoid inactivation of catecholamine NE as well needs to in glucose Infusion 2-15 mcg/kg/min

Isoproterenol- chemical PPM apex/ppt -8. How will drug affect hemodynamic? Map? DBP? CO? Pulm vessel? -9. What was it the tx for? (What scenarios)

Synthetic catecholamine (Derived from Dopmaine) Called the chemical Pacemaker of the Heart → effective on a denervated heart like epinephrine & glucagon d/t directly stimulating SA node Phenlephrine, atropine, & ephedrine will be ineffective since indirectly stimulate SA node Potent 𝛽1 & 𝛽2 β1 - ↑ HR & ↑ contractility β2 - ↑ CO ↓ SVR (Vasodilitation, ↓ SVR → may cause ↓ DBP & impair Coronary Perfusion) Most Potent activator of all sympathomimetics (EXAM!!!)& non-selective agonist B1 & B2. No alpha or Dopamine effect 2-3x more potent than Epi & 100x more potent than NE May ↓ MAP (Vasodilation), but overall ↑ in CO ↑ Myocardial O2 consumption, ↓ diastolic pressure, & ↓ in coronary artery perfusion Not drug of choice for active MI Not used much anymore d/t impact on coronary perfusion Similar to Epi in that Inc CO d/t inc SBP but MAP dec r/t dec in DBP Potent Bronchial/Pulmonary vasodilator good for PHTN & RV dysfunction Poor choice Septic Shock Tachycardia, Arrhythmias, & Myocardial Ischemia Replaced clinically with other drugs R/T severe dysrhytmias & tachycardia Tx of Bradycardia w/ Heart Block; Torsades; Chronotropy after heart Transplant Chemical pacemaker especially when Atropine fails or waiting for Pacemaker Only thing that will work on a Denervated Heart Infusion 0.02 - 0.05 mcg/kg/min Metabolized by COMT in the Liver rapidly hence need continuous infusion

Ephedrine -SUMMARY PIC -1.

Veins > Arteries Alpha Adrenergic stimulation ↑ venous return to heart Does activate 𝛽1 & 𝛽2 (Mimics Epi VS Phenylephrine mimics Norepi) Dose-related ↑ BP, ↑ CO, ↑ HR, ↑ SVR, & ↑ Myocardial Contractility ↑ myocardial O2 consumption SOOO Careful Phenylephrine > Ephedrine for OB Mom Tachycardia from Ephedrine → Fetal acidosis HR >60 then Phenylephrine HR <60 then Ephedrine Tachyphylaxis - R/T Repeated dose not effective D/T Indirect acting agents Not working as well → need Direct Acting Can also be given PO, IM, & SQ Shoulder SX or anything in beach chair position → ↓ pressure. IM works great for slow-release ephedrine & NE → BP stays nice & tidy. Antiemetic effects D/t preventing ↓ BP Bronchial asthma - Daily oral medication - same Bronchodilating effects from beta-2 receptors EXAMM!! Tachyphylaxis, IM ephedrine (slow release) - ex: pt BP is in procedure and you dont give lots of crystalloid but also cause they will pee the bed . antiemetic from preventing drop in BP (s o pt not feeling nasty??)

ADRENORECEPTORS: alpha 2 agonist -Exam!!! -1. Where are alpha-2 agonist found ? In the presynaptic era Do they inhibit or excite? How did he influence the release of NE? -2.In the postsynaptic synaptic of SNS and periphery What clinical effects will they have? What are some drugs that are alpha-2 agonist? -3.By what mechanism did they produce an analgesia ? -4.Will stimulation of the alpha-2 centers in the pancreas increase or decrease insulin?

α2 - Found on Presynaptic Nerve Terminals of SNS, Postganglionic Neurons & Postsynaptic Membranes (Brainstem, Peripheral tissue, etc.) Presynaptic Inhibition NE synthesis & release Negative Feedback Postsynaptic in Brainstem & SC Inhibits outflow to SNS → Analgesia, Sedation, ↓ HR, & ↓ BP Dexmedetomidine, Clonidine, etc. Inhibition of ACh release - Analgesia Inhibition of insulin release

ADRENORECEPTORS: beta 1 and beta 2 agonist -Exam!!! Beta 1 -1. In what organs are better 1 found? (Three) are they excitatory or inhibitory? -2.What will be some clinical sense of better one stimulation? Beta 2 -1.And all those organs where is beta 2 found? Is it excitatory or inhibitory? -2.What are some beta 2 effects on the vessels? The lungs? The liver? The pancreas? The uterus?

β1 - Found in Heart, Kidney, & Adipose tissue (Excitatory) ↑ HR → CO = ↑ BP ↑ Lipolysis ↑ Myocardial contractility → CO = ↑ BP ↑ release of Renin β2 - Found in smooth muscle & glandular tissue (Inhibitory) Vasodilation BV in Skeletal muscles to dilate = small ↓ SVR (Slightly) ↓ PVR Bronchodilation ↑ muscle/Liver Glycogenolysis ↑ release of Glucagon Relaxed Uterine smooth muscle

BEZOLD-JARISCH REFLEX vs BAINBRIDGE REFLEX ​​BEZOLD-JARISCH REFLEX -describe those 2 reflex. Remember mnemonic for them

↓ HR in setting of profound HoTN Preload is too Low (Hypovolemia) Allows heart time to fill a slow heart is better perfused. ↑ Preload. Bradycardia, HoTN, & Coronary Artery Dilation Memorization: BeZOLD = Hold → Hold HR d/t drop preload Bain = pAIN → ↑ HR d/t Venous Congestion BAINBRIDGE REFLEX ↑ HR in setting of Venous Congestion Preload is too High Minimize congestion & promote forward flow Keeps things from further backing up Both override the BRR. Not stronger, but override the effects.