Exam 2 Material Flashcards

Question

Effects of Cholinomimetics in Major Organ Systems | Eye, CV, GI, Resp, CNS, NMJ

Answer 1

Eye: -Muscarinic agonists cause contraction of the pupil -increase intraocular drainage CV: -Reduction in PVR -Vasodilation, reflex tachycardia. Large doses: bradycardia Respiratory: -Bronchiole smooth muscle contracts -Tracheobronchial secretions increased GI: -Increased motility -Salivary & gastric glands stimulated -Sphincters relax CNS: -Primarily have muscarinic receptors in brain with few nicotinic receptors -Nicotine crosses the BBB (unlike muscarine) and stimulates release of serotonin, dopamine, GABA, NE NMJ: -Immediate depolarization of the end plate -Increased permeability to Na+ and K+ -Muscle contraction, and if not hydrolyzed immediately, depolariation blockade

Answer 2

These drugs mimic the effects of ACh and are broken down into two categories: ACh stimulants or cholinesterase inibitors

Answer 3

-Act directly on the nACh-r or mACh-r. -Considered stimulants Alkaloids: Plant based -Muscarine: Activates PNS system -Nicotine: Stimulates nACh-r -Pilocarpine, lobelin

Answer 4

-Act directly on nACh-r or mACh-r -Not lipid soluble, permanently charged -ACh: Used primarily for pupil dilation, but we have better drugs -Methacholine: Dx of asthma -Succinylcholine: Paralytic -Carbachol: Decrease intraocular pressure -Bethanecol: Bladder dysfunction

Answer 5

-Carbamates: Neostigmine- Post Op ileus, MG Pyridostigmine- MG -Alcohols: Edrophonium: Dx for MG -Organophosphates: Echothiopate: Glaucoma, lasts over 100 hours

Answer 6

Nicotinic: Ligand gated ion channels (ionotropic) Muscarinic: metabotropic GPCR channels

Answer 7

In general, the iris of the eye is flat in comparison to the cornea. This allows aqueuos drainage to pass through the Canal of Schlemm. In open-angle glaucoma, we can use cholinomimetics to contrict the pupil, widening the angle, allowing for more drainage to pass, and decrease intraocular pressure. Open-angle glaucoma makes up for about 90% of glaucoma cases In narrow-angle glaucoma, the iris is being pushed forward towards the pupil. The Canal of Schlemm is very narrow because of this. Giving atropine to dilate the pupil, in this situation, would occlude the canal of schlemm and could result in blindness. This is a medical emergency

Answer 8

-SLUDGE-M Organophosphates: -Tx: Vital sign maintenance, decontamination, atropine or pralidoxime (must be given withint the first couple of hours) Mushrooms: Atropine

Answer 9

-Atropine (bradycardia) -Scopalamine (Motion Sickness) -Tropicamide (eye) -Ipratropium (COPD) -MOA: Blocks mACh-r -Block PNS effects -Eye indications: Miosis (contraction of pupil), mydriasis (dilation of the pupil), paralysis of cilliary muscle (cycloplegia), accomodation (focus)

Answer 10

-40mg is fatal dose. Usually happens if children eat cigarettes -Tremor, vomitting, convulsions, fatal coma, and death -Need to induce vomitting

Answer 11

Organophosphates target AChE. The organophosphate binds to the enzyme by hydrolysis and phosphorylation of the active site. A covalent bond is formed with the phosphorylated active site. After the intial covalent bond is formed, the aging process begins; meaning, the phosphorous-active site bond continues to become stronger and irreversible Pralidoxime needs to be given immediately, before aging progresses

Answer 12

Eye: -Dilation, decreased watering (via paralysis of the cilliary muscle) Heart: Increased HR Misc: Decreases salivation, decreases rate at which urine is produced

Answer 13

Belladona plant or deadly nightshade -Tachycardia, agitation, increased body temperature, dilated pupils, decreased salivation and sweat, dry skin -These symptoms can be overcome by increasing the amount of ACh in the synapse. -Physostigmine (dangerous CNS side effects), Neostigmine

Answer 14

Indications: Overproduction of PNS response, parkison's, poisonous mushroom toxicity Used to block toxic effects of muscarinic stimulants; use atropine if SLUDGE-M Contraindicated in narrow-angle glaucoma, BPH

Answer 15

-Do not use ganglion blockers anymore; their role was to block the release of ACh -Depolarizing: Succinylcholine; mimics two ACh molecules. Binds to the nACh-r in place of ACh, depolarizes the muscle. Muscle remains depolarized locally at the skeletal muscle end plate Nondepolarizing: Block ACh from binding. Only need one to bind. Long acting- pancuronium Intermediate- Atracurium Short- Mivacurium Reversed by neostigmine (increases ACh at the NMJ) or sugammadex (encapsulates the paralytic)

Answer 16

-Benzene ring with adjacent hydroxyl groups (cathechol) and an amine group -Substitution greatly reduces potency -Cannot be taken PO, inactivated immediately by cOMT in gut -Catecholamines are degraded by catechol-O-methyltransferase (COMT)

Answer 17

Indirect agonists: Cause the release of the catecholamines -Ephedrine, Amphetamine Direct Agonists: Stimulate the adrenoreceptor directly

Answer 18

-Mixed Adrenergic Agonist -Binds to A1, A2 (some), B1, B2 -Increases PVR, CO (HR, SV), BP -B2 vasodilates blood vessels in skeletal muscles, dilation of bronchioles

Answer 19

-Pure A1 agonist -Increases PVR -Can cause decrease in CO -Reflex bradycardia immediately after given -Decongestant if given PO Midodrine- pure A1 agonist -Decreases orthostatic HTN, can cause HTN in supine patient

Answer 20

-Beta 1 & 2 agonist -Increases HR, contraction, CO, SV -Decreases PVR, can cause decrease in BP

Answer 21

-Dose dependent -Low dose (0.3mcg/ml or less): D1 receptors in kidneys; Induces diuresis -Intermediate Dose (0.3mcg-0.7mcg): Beta 1 -High dose (>1mg/ml): A1 agonist. Increases the work of the heart, can induce arrythmias

Answer 22

-A1, A2, B1 agonist -Increases both SBP and DBP -Hardly any B2 activity

Answer 23

-B1 Selecive Agonist -Cardiogenic shock, CHF exacerbation

Answer 24

-Indirect acting; releases stored catecholamines -Direc acting; acts as epinephrine, crosses BBB -PO pseudoephedrine

Answer 25

-Which receptor activation is required? -Route of administration -Dosing and monitoring therapeutic dose

Answer 26

-Effects seen are a direct extension of their receptor effects -HTN -Cerebral hemorrhage -Pulmonary edema -Angina -Cardiac tamponade -MI CNS toxicity- convulsions

Answer 27

-Decrease PVR, reducing preload & blood pressure -Should have no direct effect on HR -Nonselective uses for alpha blockers: Useful in tx for pheochromocytoma Phentolamine, Phenoxybenzamine, and then typically end in "-osin" If it ends in "-zosin"--> BPH

Answer 28

Competitive antagonist of A1 & A2 -Reduces PVR -Causes some cardiac stimulation -Minor agonist of muscarinic and histamine receptors Adverse Effects: Cardiac stimulation (M-r in heart, can increase HR) Abdominal pain, N/V/D Used for treatment of HTN linked to pheochromocytoma ED- direct injections

Answer 29

-Mostly selective for A1 -Forms covalent bonds, non-competitive, insurmountable -Inhibits NE reuptake, blocks H1, ACh, and Serotonin receptors -

Answer 30

-Propranolol is the prototype: -Extensive first pass -Non Selective, B1 and B2 Metoprolol, Atenolol: Mainly B1 selectivity Safer in COPD and diabetics Esmolol: Ultra short acting Selective for B1 Safer in critically ill, fast on fast off Labetalol: Racemic mixture S,R isomer is a1 blocker R,R isomer is a B blocker

Answer 31

-Hydraulic Equation - BP = CP x PVR Factors that affect BP: PVR Vessel elasticity Blood volume CO (HR x SV) PVR is hard to measure. Three factors in PVR 1. Blood vessel diameter 2. Blood Viscosity 3. Total Vessel length

Answer 32

1. Arterioles: Provide resistance 2. Venules: Increase return to the heart, contributes to preload 3. Heart: CO 4. Kidneys: Volume regulation via RAAS

Answer 33

1. Diuretics (Lasix, Bumex, HCTZ): Deplete Na+ 2. Sympathoplegics (Alpha & Beta blockers): Decrease PVR, reduce CO 3. Direct vasodilators: Relax vascular smooth muscle 4. Anti- Angiotensins: Block activity or production of

Answer 34

-Targets vasomotor center in CNS -A2 agonist -Primary activity is due to inhibition of sympathetic outflow and increased parasympathetic outflow in brainstem -Crosses BBB, enters rapidly -Side effect is sedation, used as anesthesia adjunct as well as Clonidine is primarily used for ADHD, tourettes, w/d symptoms

Answer 35

-Target is vasomotor center in the CNS -Analog of L-dopa -Prodrug; works by replacing NE and decreasing NE release -Does not cross placental barrier -Does cross BBB -Primary use for pregnancy- induced HTN -S/E sedation

Answer 36

Alpha 2 Antagonist Does not work We don't use it

Answer 37

-Relax smooth muscle of arterioles (all vasodilators) and veins (nitroprusside & nitrates) -Reduces MAP and PVR -Elicits compensatory responses- RAAS system, so best when given in conjuction with anti-HTN that combat these responses

Answer 38

-Opens K+ channels in smooth muscle, hyperpolarizing membrane potential, less likely to contract -Dilates arteries and arterioles -Rogaine

Answer 39

Dilates arterioles--> possibly NO production? -Toxicity includes: HA, N, sweating, flushed. Symptoms are similary to lupus

Answer 40

-Relaxes venous and arterial smooth muscle by releasing NO -Rapidly lowers BP -Protect from light -HTN emergencies and heart failure -Breaks down into cyanide, begins to accumulate >48hours. Can cause metabolic acidosis, arrythmias, death Need to give sodium thiosulfate to metabolize CN

Answer 41

-Verapamil: Targets the heart -Diltiazem: Targets heart and peripheral vasc -Dihydropyridine blockers: end in -dipine, target the peripheral vasc

Answer 42

Low BP detected by kidneys --> Angiotensinogen (an inactive precurse made by the liver) is converted by renin into Angiotensin I--> Angiotensin I is converted into Angiotensin II by ACE which leads to: 1. Vasocontriction in the blood vessels 2. Aldoseterone release causing increased Na+ & water retention

Answer 43

Ace Inhibitors: By blocking ACE, we stop the conversion from Angiotensin I to Angiotensin II This also inhibits the breakdown of bradykinins, leading to increased inflammation in the lungs --> dry hacking cough as side effect Ace inhibitors end in -pril ARBs block the angiotensin II receptors in the blood vessels and adrenal cortex Arbs end in -sartan

Answer 44

- In the lungs, ET-1 binds to both ET-A and ET-B in the presence of things such as AngII, cytokines, thrombin. When bound, ET-A, ET-B both cause vasoconstriction and proliferation of smooth muscle cells - -Causes: High systemic BP, congenital, COPD, heart failure -Tx: In the hospital, can use IV prostaglandins to induce pulmonary vessel vasodilation; epoprostanol At home, can use endothelin receptor antagonists: Bosenten, Tezosentan

Answer 45

HTN Urgency: >180/110 w/o acute end organ damage. Need to lower BP in hours HTN Crisis: >180/110 w/ acute end organe damage (stroke, AKI). Need to be treated in the ICU with immediate lowering of BP

Answer 46

Mild: Decrease Na+ intake, exercise, weight reduction in obese patients. Evaluate whether taking decongestants, NSAIDS, contraceptives, ETOH Moderate: Meds, will often need a combination Emergent: IV meds

Answer 47

-Arterial: Consists of arteries and arterioles. Much more forceful than venous tone (16x more forceful in artery) -Venous tone: Much larger capacitance that arteries. This allows the venous system to function as a reservoir for blood volume and circulate blood volume back to the heart -Capillary tone: none

Answer 48

-Stable/Angina of Effort: Accumulation of metabolites. O2 requirement increases due to exercise or symapthetic stimulation, and those increased O2 demands are not met because blood flow does not increase proportionally -Vasospastic/Prinzmetal: O2 delivery decreased due to coronary vasospams -Unstable angina: Angina at rest; usually due to atherosclerotic plaque

Answer 49

Directly related to perfusion pressure (DBP) and the duration of diastole Coronary vessels are not perfused during systole

Answer 50

Stable Angina: Reduction of aggravating factor/demand. If HTN, CCB & beta blockers. Non-HTN, nitrates. pFox inhibitors Vasospastic: Potent vasodilators. Nitrates or CCBs Unstable: Medical emergency. PCI, stent placement, CABG

Answer 51

-Blocks Ca++ channel--> Ca++ cannot flux into the cell--> this leads to a direct decrease in calmodulin activity --> inhibiting myosin light chain kinase --> preventing contraction

Answer 52

-Causes K+ to leave the cell, hyperpolarizing the cell, making it more difficult to depolarize

Answer 53

-NO occurs naturally in the body, produced by vascular endothelial cells -Blood flow against the vascular endothelium cause the release of Ca+ which activates NO synthase -NO synthase converts L-Arginine into NO -NO activates the enzyme guanylyl cyclase, found in vascular smooth muscle -Guanylyl cyclase catalyzes the dephosphorylation of GTP to cGMP--> causes smooth muscle relaxation 1. Inhibits Ca+ entry into cell 2. Increases uptake of Ca+ into endoplasmic reticulum Increase venous capacitance, decrease ventricular preload, decrease CO output Can cause reflex tachycardiac, orthostatic hypotension Methhemoglobin

Answer 54

NO, Nitrates, Nitrites- MOA on other flashcard Beta-2 Agonists- Increases cAMP in pulmonary vessels --> relaxation here CCB: Block Ca++ channel, leading to decreased contraction Sildenafil: PDE inhibitor--> leads to increase in cGMP --> relaxation of vascular smooth muscle

Answer 55

Systolic: Thin, floppy ventricles. Causes decreased cardiac output, decreased EJ Diastolic: Thick, muscular ventricles. Unable to relax to allow to diastolic filling. Decreased CO, normal EJ

Answer 56

Left heart: Increased left ventricular pressure at the end of diastole. This causes pulmonary congestion. Right heart: Blood can backup into R IJ, hepatic vein

Answer 57

-Ca++ enters the cell through a Ca++ channel. That Ca++ (referred to as the '"trigger" Ca++) interacts with the Ca++ release channel on the wall of the sarcoplasmic reticulum --> stored Ca++ is released into the cytoplasm, allowing for actin to interact with myosin --> one heart bear

Answer 58

1. Preload: This is our EDP; however, often synonymous with EDV. Decreased in diastolic HF, increased in systolic HF 2. Afterload: Resistance in which the heart must pump against. Increases as CO decreases (compensatory) 3. Contractility: The force with which the heart contracts. Very poor in systolic HF. Too forceful in diastolic HF 4. Heart Rate: Main determinant of CO. First compensatory mechanism to respond to decreased CO. Lowering HR in diastolic HF will allow for more filling time

Answer 59

Strength of contraction increases the more the heart stretches (to a certain point)

Answer 60

Passive filling+ atrial contraction + ESV

Answer 61

-Positive Inotropes: Cardiac glycosides; digoxin -Phospodiesterase Inhibitors: indirectly increase inotropy by inactivating cAMP and cGMP (milrinone) -Beta adreneric stimulants: Dopamine & Dobutamine -Ca++ sensitizers: Positive Inotropy & vasodilations

Answer 62

-Diuretics: Reduce preload, reduce edema, reduce cardiac size, and improve efficiency of cardiac pump

Answer 63

-Reduce compensatory mechanisms in response to HF (RAAS); Ace inhibitors- captopril -ARBS: Losartan -Vasodilators: reducing preload and afterload

Answer 64

Inhibits the Na+, K+, ATPase pump on the heart and is a positive inotrope. Increases PR interval, decreases QT interval Has a narrow therapeutic index. Toxic doses can cause tachycardia, a fib, v fib, and cardiac arrest. Toxic doses also produce oscillatory after-depolarizations, increasing risk for v-fib and v-tach. Hyperkalemia: K+ competes with dig Hypercalcemia & hypomagnesium: Increased risk of arrhythmias EKG- downward schwoop after QRS Well absorbed, distributed widely in tissues and CNS T1/2 36-40hrs 2/3 excreted unchanged in the kidneys

Answer 65

-LVAD -Chronic biventricular resynchronization -Defibrillatory -Heart transplant -End stage: hospice

Answer 66

SA node --> enforces a contraction rate of 110bpm --> AV node, located in the junction of the atria and ventricles, slows down the rate of conduction to ~75bpm Conduction travels from the AV node down the Bundle of His --> down the left and right purkinje fibers

Answer 67

P-Q interval is atrial depolarization QRS complex is ventricular depolarization ST segment is ventricular depolarization

Answer 68

Phase 0: Depolarization of cardiac cells; action potential upstroke. AP is "over-shot" just a litte. Na+ moves in Phase 1: K+ begins to leave the cell, membrane potential decreases slightly Phase 2: K+ still leaving; however, Ca++ enters the cell, prolonging the action potential to allow the heart to pump Phase 3: K+ leaving the cell, repolarization Phase 4: Vrm

Answer 69

Disturbances in impulse formation: -SA/AV nodal abnormalities -Ion changes -SNS stimulation 1. Vagal Discharge: Slows the HR, hyperpolarizes the cell. Reduction in phase 4 slope 2. Acceleration of HR caused by beta agonists, fiber stretch, or acidosis. Will see an increase in phase 4

Answer 70

Disturbances in impulse conduction: -1st degree, 2nd degree (Type I & II), 3rd degree block -Re-entry: -Block is unidirectional, there must be an obstacle (scar tissue), and conduction time must be long enough to reenter same areas after refractory period

Answer 71

Class I: Sodium channel blockade Class II: Sympatholytic (beta blockers) Class III: Prolong action potential duration, K+ channels Class IV: CCB

Answer 72

IA: Sodium channel blocker -Procainimide, Quinidine -Prolongs action potential duration and increases effective refractory period IB: Sodium channel blocker -Lidocaine, Mexiltine -Shortens APD, decreases ERP IC -Flecainide, Propafenone -Minimal effects on APD, no effect on ERP

Answer 73

Amiodarone- i. Na+ channel blockade ii. Non-competitive alpha & beta inhibition iii. prolongs cardiac action potential iv. CCB, dilation in peripheral vasculature DOC for VT Toxicity: Bradycardia or heart block, precipitate heart failure, fatal pulmonary fibrosis, concentration in tissues

Answer 74

Verapamil; CCB -Blocks inactivated and activated Ca++ channels -Prolongs AV node conduction -Slows SA node -Can cause hypotension

Answer 75

Enhances K+ conductance Inhibits cAMP induced Ca++ influx T1/2: ~10seconds