Final Review Flashcards

Question

Epinephrine

Answer 1

-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 2

-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 3

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

Answer 4

-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 5

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

Answer 6

-B1 Selecive Agonist -Cardiogenic shock, CHF exacerbation

Answer 7

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

Answer 8

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 9

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

Answer 10

-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 11

-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 12

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

Answer 13

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 14

-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 15

-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 16

-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 17

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

Answer 18

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

Answer 19

-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 20

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

Answer 21

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 22

-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 23

-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 24

-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 25

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 26

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 27

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 28

-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 29

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 30

-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 31

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 32

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 33

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 34

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

Answer 35

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 36

Amiodarone- prolongs cardiac action potential, dilation in peripheral vasculature Toxicity: Bradycardia or heart block, precipitate heart failure, fatal pulmonary fibrosis, concentration in tissues

Answer 37

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

Answer 38

-Pharmacodynamics: Describes what the drug does to the body. -Pharmacokinetics: Describes what the body does to the drug; absorption, distribution, metabolism, excretion -Pharmacogenomics: Looking at a genetic profile to determine how effective a drug will be -Toxicology: Specifically relates to poison, toxins, and how they relate to the body

Answer 39

Agonistic: Elicits a response from a receptor when it binds to the receptor -Effect may be lesser or greater than the native ligand (endogenous hormone or catecholymine) Antagonistic: Blocks the endogenous/native ligand from binding to the receptor -Does not activate a response

Answer 40

Allosteric: Binds anywhere but the active site on the receptor -Is a non competitive inhibitor because it does compete for the active site Orthosteric: Binds directly to active site on the receptor Specific Binding: Binds specifically to the receptor. There is a max dose because receptors are not infinite Non-specific Binding: The more drug that is given, the more non-specific the binding becomes. The drug saturates the receptors and must bind somewhere else. Ex: Albumin

Answer 41

Poison: A nonbiological substance such as arsenic, cadmium, lead Toxins: A biological substance such as toxic mushrooms, a puffer fish

Answer 42

Covalent Bond: Share electrons. Strongest bond, but least specificity. Irreversible Electrostatic: Ionic Bonds; -Charged molecules - Hydrogen bonds - Van der waals forces Hydrophobic, lipid soluble drugs: Weakest bond, highest specificity Bond strength and specificity are inversely related

Answer 43

-Isomers of a drug have the same chemical equation, but different shape. -Stereoisomerism (Optical Isomers) is when isomers are mirror images of each other, but do not behave the same way. This applies to more than half of all drugs -Racemic Mixtures are optical isomers Ex: (R) Ketamine- More toxic than (S) Ketamine, increased unwanted side effects (S) Ketamine: 4x more potent, less unwanted side effects

Answer 44

Competitive Inhibitor: Binds to the active site in place of agonist. If a high enough dose of the agonist is given, it can “out-compete” the competitive inhibitor Allosteric Inhibitors: Bind somewhere other than the active site on the receptor, so they are not competitive. Agonist response is always muted when given with an Allosteric inhibitor

Answer 45

Receptors live in equilibrium between the active and inactive state. These configurations can switch back and forth between active and inactive without a drug/endogenous ligand present. When a drug favors the active form of a receptor, a downstream response will be elicited

Answer 46

Two or more physiologic processes that have an opposite effect Ex: SNS vs PNS; epinephrine secreted acts on the B1 receptors, increases heart rate. Acetylcholine acting on the muscarinic receptors decreases heart rate

Answer 47

-Agonist + Allosteric Agonist/Activator: We will see an increased/maximal drug response here compared to giving an agonist alone -Agonist + Competitive Inhibitor: We can initially have a muted response; however, giving more of the agonist will allow it to out-compete the competitive inhibitor and we will have an increased response -Agonist + Allosteric Inhibitor: We will have a muted response here. There is no way to out-compete the Allosteric inhibitor because they do not bind to the same area on the receptor

Answer 48

Agonist mimics or Indirect Agonists are downstream inhibitors. You have a receptor activated that causes a cascade of effects: A—> B—>C. Let’s say there is an enzyme that is supposed to break down “C”. You give the agonist mimic and it breaks down that enzyme, increasing your amounts of “C”

Answer 49

Competitive inhibitors/antagonists: They are SURMOUNTABLE because you can continue to give increasing doses of the antagonist to overcome the competitive inhibitor as long as they do not form covalent bonds Competitive Orthosteric inhibitors/antagonists: Compete for the active site, but if they form covalent, irreversible bonds, it makes make them INSURMOUNTABLE Non-competitive Allosteric inhibitors/antagonists: They are INSURMOUNTABLE because they are not directly competing for the same site. These are irreversible

Answer 50

- A partial agonist, when given alone, will always have a muted/lessened response -When given with full agonist; acts as antagonist -Inverse Agonist: Favors the receptor in its inactive form. It lowers the receptors’ activity below its constituitive activity, causing it to be less active with the drug present than without. Clinically, these act as antagonists but stronger -A full agonist elicits a full downstream response once given

Answer 51

Ex: Protamine (+) binds to and inhibits the effect of Heparin (-)

Answer 52

-Potency is reflected on the dose axis (horizontal) -Potency refers to the EC50 or ED50. Concentration or dose required to produce 50% of the drugs maximal effect -Inversely related to the EC50/ED50 on the response curve -As potency decreases, the EC50 increases and shifts to the RIGHT -As potency increases, the EC50 decreases and shifts to the LEFT -If graph is shifting horizontally, we are seeing a change in POTENCY -Drugs can have different potency, but efficacy can be the same

Answer 53

-This parameter is reflected on the response axis (vertical) -Also depends on intrinsic activity, are these drugs agonists, antagonists, partial agonists, etc.. -If curve is shifting vertically, there is a change in efficacy -Drugs can have different potency, but efficacy can be the same Efficacy is more important than potency

Answer 54

The larger the therapeutic index, the safe the drug is. TD50= Median toxic dose ED50= Median effective dose Calculate therapeutic index: TD50/ED50 (LD50 for animals, not used in humans)

Answer 55

-Most drugs are weak acids or weak bases. pKa is the pH at which ionized & unionized concentrations are equal. -Drugs need to be uncharged in order to cross the cell membrane; pKa affects the charge -pH < pKa; favors protonated form -pH > pKa; favors unprotonated form Weak acids: protonated form is uncharged, unprotonated is charged Weak bases: protonated form is charged, unprotonated form is uncharged

Answer 56

1. Can be idiosyncratic 2. Patient is hyporeactive, hyperreactive 3. Hypersensitivity 4. Tolerance or tachyphylaxis

Answer 57

1. Alteration in drug concentration that reachese the receptor 2. Variation in concentration of the endogenous ligand; not everyone has the same amount of receptor sites 3. Functionality of receptors 4. Changes in the downstream cascade (most likely) due to proteins altering the response -Body has a natural ability to compensate for this

Answer 58

-GPCRs; Seven transmembrane receptors -Ligand-Gated Channels; Chanel opens when something binds to them -Ion Chanels; Do not need a ligand -Catalytic Receptors: Catalyze an enymatic response (RTK) -Nuclear Receptors; Located in the nucleus -Transporters; Transport from one side of cell to another -Enzymatic; The enzyme w/in the cell is the target

Answer 59

-Lag Period: Response takes 30+ minutes to several hours. This typically requires transcription/translation (so mrna drug) Persistence: Response hangs around for hours to days. Protein degradation pathways vary in each person

Answer 60

Drug or endogenous ligand binds to receptor -->receptor undergoes conformational change which activates the alpha subunit & binds GDP (inactive) -->GTP (Active) --> GTP activates the effector/signaling protein -->activates the second messenger -->downstream process

Answer 61

-Binding to the receptor actives the G-protein (guanine nucleotide binding protein). GDP -->GTP -Receptor has seven transmembrane alpha-helices -Binds to the active site on the cell wall, interacts with the G-protein inside the cell -Trimeric, have three subunits; alpha (binds to GDP, activates GTP) beta, gamma

Answer 62

-Ligands are growth factors or adhesion factors -Ligand binding stimulates -Dimerization (two monomers forming one dimer) -This then causes phosphorylation of tyrosine molecules on dimer (uses 6 ATP) --> downstream cascade of effects

Answer 63

-Second messengers play an important role in activating an effector protein or starting the downstream cascade of effects once a receptor is bound by a ligand or drug -cAMP: Exerts most of it's effects by phosphorylation **(this uses ATP);** mobilizes stored energy, increases rate & force of contraction DAG IP3 cGMP

Answer 64

Desensitization is the process of stopping the signaling cascade after a ligand has bound to a receptor. Ex in a GPCR: Ligand binds to receptor-->undergoes a conformational change (now in the open confirmation) -->The carboxyl end of the receptor has OH groups hanging off it within the cell -->Alpha subunit on the g-protein floats away, activating GDP -->GTP. GTP activates adenylyl cyclase--> cAMP (second messenger) is activated -->downstream cascade of effects. If the ligand forms a covalent bond, there are two options: 1. Beta-arestin binds to the OH groups on the carboxyl end of the receptor, drags it along the cell membrane to a clarithen coated pit. The pit engulfs the receptor, separates the receptor and ligand, and the receptor is recycled 2. If the bond cannot be broken, lysosomes will use their acidic, digestive enzymes to break up the receptor into it’s smaller AA counterparts and release those to be reused in the cell.

Answer 65

-Ion specific channels (Na+, K+, Ca++, Cl-) -Can be fast or slow, depends on the ion and the gradient -Found in excitable cells; neurons, muscle, endocrine -Closed at resting membrane potential - Na + Channel has two gates- Gate 1 opens when threshold is reached --> Gate two immediately inactivates (regulates how much of each ion can pass through) --> deactivates (both gates closed), then circles back to closed

Answer 66

Inotropic: -Most common -Ligand binding site & channel are on the same protein -Ligand binds, channel opens Ex: Nicotinic aCH receptor Metabotropic: GPCR in close proximity to the ion channel -Ligand binds to the site --> activates GPCR --> second messenger activity opens ion channel Ex: Olfactory nerve, scents/smell

Answer 67

-Must be a gas or lipid soluble Ex: Blood vessels lined with endothelial cells--> strong shearing force/turbulent blood flow against the endothelial cells--> activates nitric oxide synthase --> nitric oxide is produced--> diffuses out to smooth muscle (can freely diffuse across the cell membrane)--> relaxes smooth muscle, opens blood vessel Steroid Hormones: Can freely diffuse across membrane because they are lipid soluble and uncharged Steroid hormone binds to steroid receptor-> migrates to nucleus--> binds to steroid regulatory elements in the nucleus and increase transcription and translation of genes

Answer 68

Different forms of permeation: 1. Aqueous Diffusion; If water soluble, water diffuses down it's concentration gradients typically through aquaporins. Cannot cross this way if the molecule is highly charged or bound to a large protein 2. Lipid Diffusion: Lipid soluble drugs such as steroids. The ability to move between aqueous & lipid phases is important for good drug 3. Special carriers: Drug binds to the carrier, the carrier will internalize the drug and spit them out into the cell. This is not the target cell. Active transport & Facilitated diffusion 4. Endocytosis: Cell surface surrounds the drug, engulfs it, spits it out on the other side -Exocytosis: Secretion of a substance from the cell. Ex: Neurotransmitters are stored in membrane bound vesicles until ready to use

Answer 69

-The space available in the body to contain the drug (theoretical number) -Relates the amount of drug in the body to the amount of drug in the blood stream

Answer 70

-Ability of the body to eliminate the drug. Predicts the rate of elimination in relation to drug concentration. Multiple organs play a role here

Answer 71

-C: The amount of drug given in a volume -TC: The desired concentration at the effector site -ROE: Predicted by clearance

Answer 72

-The higher the Vd, the lower the amount of drug in the bloodstream -The lower the Vd, the higher the amount of drug in the bloodstream Vd along with clearance will determine the T1/2 of drugs

Answer 73

1) First order elimination; how most drugs are eliminated from the body. Clearance remains constant, ROE varies 2) Zero order elimination; ROE remains constant. Clearance varies with concentration. Occurs when the body's ability to eliminate a drug has reached its maximum capacity. (EtOH, ASA, phenytoin) Capacity limited elimination happens when we have zero order elimination. This can start as first order, but because of the drug amount in the body can become zero-order/ capacity limited

Answer 74

-The time required for the body to eliminate half of the drug. Half life is dependent upon the extraction ratio, organ health, Vd, and clearance -In “steady state” dosing (meaning no boluses of the drug have been given), it is generally assumed that it will take 4x half-lives in order to achieve target concentration. Conversely, it should take approximately 4x half lives for the drug to be eliminated from the body

Answer 75

The drug continues to accumulate in the body until dosing stops. Can reach toxic levels of the drug if our dosing intervals are shorter than 4x half-lives

Answer 76

The fraction of unchanged drug reaching systemic circulation

Answer 77

The drug is metabolically converted, either into an inactive metabolite or a metabolite that is *more* active. Primarily occurs in the liver

Answer 78

When an oral drug is absorbed, intact, from the small intestine and transported through the hepatic portal system through the liver, where it undergoes extensive metabolism before reaching systemic circulation

Answer 79

Phase I Reactions: -Converts a drug into a more polar metabolite. -Adds or unmasks a functional group (-OH, -NH) -Usually makes the drug more readily excretable; a lipophilic drug becomes more hydrophilic Oxidation: Loss of an e- Reduction: Gain of an e- Dehydrogenation: Remove an OH group Hydrolysis: Breaks down water Oxidation and reduction always happen together

Answer 80

Cytochrome P450: A protein with a heme. Function is to introduce an oxygen to xenobiotic compound Cyp450 Oxidation-Reduction requires P450, P450 Reductase (flavoprotein), NADPH, and molecular oxygen P450 (Fe3+) combines with RH group (drug) P450(Fe3+)-RH --> NADPH donates e- to P450 reductase --> P450 (Fe2+)-RH --> NADPH donates another e- to P450 reductase, reduces molecular oxygen--> O2-P450(Fe2+)-RH --> Activated oxygen is transferred to the drug substrate group to form P450(Fe3+)-ROH = making the drug more water soluble

Answer 81

-Adding molecules to something typically resulting in the compound being more polar, readily excretable, and inactivated Types of Conjugation: -Glucuronidation: UDP glucuronic acid carries a glucose-like substance to the drug compound & attaches it. -Glutathione: Glutathione-S-Transferase attaches glutathione molecule. Important for detoxification -Acetylation -Sulfation -Glycine -Methylation -Water conjugation

Answer 82

CYP3A4- Responsible for metabolization of 50% of all drugs undergoing Phase I CYP2B6, CYP2D6 also important CYP3A4 *1 is the "wild type," meaning, most commonly seen

Answer 83

Induction of P450: Increases the presence of P450 DECREASED drug effect if P450 deactivates drug INCREASED drug effect if P450 activates drug Ex: Drug 1 given (metabolized by P450) Drug 2 given (inducer of P450) --> Drug 1 becomes inactivated much more quickly Prodrug given --> activated by P450--> Drug 3 Drug 2 also given --> can reach toxic levels of drug 3 quickly because Drug 2 is an inducer of P450

Answer 84

P450 Inhibition: Decrease activity or irreversibly inhibit Ex: Drug 1 given (inactivated by p450) Drug 4 is given (inhibits P450) --> Drug 1 can reach toxic levels

Answer 85

-Drug transporters are located in the endothelial cells of many tissues (intestinal, renal, hepatic) and mediate selective uptake of endogenous compounds and xenobiotics -Molecular weight, pKa, lipid solubility, and plasma protein -Drug efflux transporters are membrane proteins that specialize in expelling foreign molecules

Answer 86

-These transporters bind ATP. ATP binding cassette (ABC) -ABCB: Broadest substrate specificity; Antineoplastics, HIV protease inhibitors, abx, antidepressants, antiepileptics, opioids -Drug interactions w/ ABCB: Cyclosporine, quinidine, ritonavir & dig. When loperamide & quinidine are given together, causes CNS effects -ABCC: Antineoplastics -ABCG: Breast cancer resistance protein; antineoplastic, toxins, food-borne carcinogens, folate transport

Answer 87

GI tract: Transporters are localized in microvilli, transport drugs from the intestine into the bloodstream Liver: Transporters typically bring drug into the liver.Metabolize xenobiotics and excrete metabolites into bile BBB: Allows certain drugs to cross into the BBB (highly hydrophobic), but overall most things are going to be pushed back out

Answer 88

-Functional separation of the circulating blood from the extracellular fluid in the CNS 1. Specific transporters 2. Endothelial cells & tight junctions 3. The cells that surround it; astrocytes and pericytes (podocytes)

Answer 89

Early stages: Histamine & Prostaglandins. Cause immediate bronchoconstriction from muscular contraction and vascular leakage Later Stages: Leukotrienes. Liberated from the lungs during inflammation. Cause bronchospasm, mucus secretion, microvascular permeability, and airway edema

Answer 90

-Bronchodilators -Nebulized Epi & Isoproterenol: Non-specific for beta cells. Can cause tachycardia and arryhthmias -Albuterol (SABA): B2 selective. Aerosol. Takes effect in 30 mins, lasts 3-4 hours -Salmeterol/Formotorol (LABA): B2 Selective. Aerosol. Lipid soluble, lasts 12 hours. Only 10-20% delivered due to droplet size Toxicity: Skeletal muscle tremors

Answer 91

-Inhibits PDE & adenosine receptors resulting in mild bronchodilation -Theophylline: Most effective methylxanthine, found in natural tea. -Toxicity: CNS stimulation, (+) chronotropy and ionotropy in heart, tremors

Answer 92

-Bronchodilators -Atropine: Given IV -Ipratropium Bromide: Inhaled, can combine with B2 agonists -Titroprium: Inhaled, long acting -No CNS effects

Answer 93

-Glucocoritcoids: Inhibit immune response by blocking DNA transcription/translation -Cortico: Reduce bronchial activity, increase airway caliber, reduce frequency of exacerbations -S/E: Increased risk of osteoporosis, slow growth rate in children, oropharyngeal candida & other opportunistic infections

Answer 94

-Inhibit 5-Lipoxygenase: Zileuton -Inhibit synthesis of leukotriene: -ukast -Both improve aspirin induced asthma

Answer 95

CNS: Stimulates pain & itching CV: Vasodilation (H1), increased HR GI/Stomach: Release of HCl, contraction Lungs: Bronchoconstriction (H1) 4 types- GPCR

Answer 96

CV: Vasocontriction, platelet aggregation Respiratory: ACh release --> bronchoconstriction, hyperventilation GI: Overproduction causes diarrhea Brain: Melatonin precursor. Mood, appetite, temperature regulation, pain perception, migraines, vomitting reflex, BP

Answer 97

-Used for allergy testing -Increased blood flow to capillary endothelium (redness) -Flare: Widespread dilation of surrounding arterioles -Wheal: Local swelling due to increased permeability in the walls of surrounding vessels

Answer 98

1st: Benadryl, Phenergan, Dramamine -Used for motion sickness, nausea, anesthesia -Cause sedation 2nd: Zyrtec, Claritin, Allegra -Used for allergic response, seasonal allergies, urticaria -No CNS effects. Near equal efficacy to first gen Toxicity: Sedation, urinary retention, blurred vision, convulsions, postural hypotension

Answer 99

-Reduce the amount of HCl produced in the stomach -Not as effective as PPI -Zantac, Pepcid

Answer 100

90% of body’s serotonin is created in the enterochromaffin cells. 10% from the Raphne Nuclei in the pons -Seven Families of 5-HT. 6 are GPCR, 5-HT3 is an ion channel

Answer 101

-Buspirone; 5-HT1a. Non-benzo anxiolytic, GAD, OCD -Sumatriptan; 5-HT1D/1B agonist. Tx for migraines. Non-prophylactic. Bind 5-HT in cranial blood vessels, preventing dilation and stretching of pain nerve endings. -Toxicity: Recurrence of migraine, coronary vasospasm (rare), serotonin syndrome if taking triptans + SSRI, MAOI

Answer 102

-Cyproheptadine & Phenoxybenzamine: 5-HT2. Carcinoid tumors and cold induced urticaria -Zofran: 5-HT3 N/V

Answer 103

* Serotonin Syndrome: HTN, hyperreflexia, clonus -Contributing Factors: SSRIs, MAOIs, Triptans, MDMA, St. John’s Wort -Tx: Sedation with benzos, 5-HT block with cyproheptadine or chlorpromazine * Neuroleptic Malignant Syndrome: HT, Hyperthermia, acute, sever parkinsonism -D2 blocking antipsychotics -Tx: IV diphenhydramine, cooling, sedation w/ benzos * Malignant Hyperthermia: HTN, hyperthermia, muscle rigidity -Volatile anesthetics & succinylcholine -Dantrolene, cooling

Answer 104

* SSRIs- Most common, first line -Inhibition of SERT -Fluoxetine, Citalopram, Paroxetine, Sertraline, Escitalopram * SNRIs- Used for major depression & pain disorders -Inhibition of SERT and NET -Desvenlafaxine, Duloxetine * TCAs- Supplanted by SSRIs -Amitrypyline * MAOIs- Rarely used, lethal drug interactions. For refractory depression -Irreversible: Phenelzine -Selegiline * All work by increasing monoamine neurotransmitter levels within the synapse * Adverse effects: Suicidal ideation, drug interactions, N/V/D, sexual dysfunction

Answer 105

-Start in small area of the brain 1. Simple: Not aware of occurence 2. Complex: LOC, automatisms 3. Secondarily generalzed: Just like general

Answer 106

- Start all over the brain 1. Tonic Clonic: Grand Mal i. Aura- Seizure- Post-ictal ii. Tonic - clonic (usually <5 mins) 2. Absence: Petite mal 3. Drop Attacks: Tonic, Atonic 4. Clonic: Jerking & myoclonus (twitching) 5. Infatile spasms: Indicative of underlying pathology

Answer 107

-Oldest non-sedative AED -Alters Na+, K+, and Ca++ conductance -Enhances gaba, inhibits glutamate -Highly protein bound: competes with carbamazepine, valproic acid, sulfonamides -Fosphenytoin- More soluble prodrug of phenytoin; can be given IV -Accumulates in brain, liver, muscle, and fat -Approaches zero order kinetics -Highly Toxic; dose related- nystagmus, loss of extraocular movement, diplopia, ataxia, sedation, gingival hyperplasia, hirsuitism

Answer 108

MOA is similar to Phenytoin, but blocks Na+ channels at therapeutic levels -TCA -DOC for focal seizures, can also be used in bipolar disorder, effective in trigeminal neuralgia -Can be used with Phenytoin -Induces CYP450, increasing it’s own metabolic rate with prolonged use -Enhances metabolic rate of other AEDS A/E: Diplopia, ataxia

Answer 109

-MOA Unknown. We think enhancing GABA -Sedative -Can worsen absence, drop, or infantile seizures -DOC in infants -Toxicity: Sedation, increase in hepatic enzymes

Answer 110

Lacosamide: Focal Seizures Lamotrigine: Partial & Absence Seizures. -MOA; Ion channel Vigabatrin: GABA analog

Answer 111

-DOC for absence seizures -Syrup -Ca++ channel inhibition -A/E: GI upset, sedation, tremor, hepatotoxicity

Answer 112

-MOA: Blocks sustained high frequency firing. Effects Na+ channels, increases GABA, increases K+ conductance -Absence seizures -Generalized tonic-clonic -Bipolar -Migraine ***Displaces phenytoin from proteins*** -Inhibits metabolism of phenobarb, phenytoin, carbamazepine -Toxicity: GI upset, n/v, abdominal pain, heartburn.

Answer 113

* Endocrine: Islets of Langerhans -Alpha Cells produce Glucagon -Beta Cells produce insulin, C-peptide, proinsulin * Exocrine: Produces digestive enzymes

Answer 114

* DM I: Insulin Dependent (IDDM) - Destruction of beta cells, severe or absolute insulin deficiency. Immune or idiopathic * DM II: Non-insulin dependent (NIDDM) -Metabolic syndrome. Combination of relative deficiency of insulin secretion with tissue insulin resistance * DM III: Other causes: drugs, pancreatitis * DM IV: Gestational -Hormones block insulin. Higher birth weight. Infant 30% more likely to develop DMII

Answer 115

Insulin is released from the beta cell and by sulfonylurea drugs. In a resting cell, ATP levels are low, and K+ diffuses down its concentration gradient through ATP-gated K+ channels maintaining Vrm. If glucose concentration increases, ATP production increases --> K+ channels close, causing the cell to depolarize. Ca++ channels open in response to depolarization, and the increase in intracellular Ca++ results in an increase in insulin secretion.

Answer 116

* After insulin has entered circulation, it diffuses into tissues and binds to specialized receptors. * Insulin receptors consist of two covalently linked heterodimers each containing an extracellular Alpha subunit (recognition site) and a Beta subunit, a tyrosine kinase, that spans the membrane. Insulin binds to the alpha subunit-->receptor undergoes conformational change bringing the catalytic loops of the B subunits closer together -->facilitating mutual phosphorylation of tyrosine residues->>ultimately resulting in translocation of GLUT transporters (2, 4) to the cell membrane to increase intake of glucose, increase in glycogen formation, and multiple effects on protein synthesis, lipolysis, and lipogenesis, as well as the activation of DNA transcription factors. i. GLUT 2- Located in beta cells, liver, kidney, gut ii. GLUT 4- Muscle, adipose

Answer 117

* Rapid Acting: Lispro, Aspart, Glulisine i. Given w/ meals * Short Acting (Regular): Novolin, Humalin i. Given BID; not tightly controlled * Intermediate Acting: NPH (Neutral protamine Hagedorn) i. Given BID; not tightly controlled * Long Acting: Glargine, Detemir i. Given once daily * Basal + Bolus is the best way to control, or use of an insulin-pump

Answer 118

i. First line therapy in NIDDM ii. Reduction in hepatic glucose production iii. GI toxicities iv. Metformin

Answer 119

i. Bind to K+ channel in beta cell causing depolarization ii. Sulfonylureas (-ide), Meglitinide, Phenylalanine derivatives iii. Black box warning: Increased risk of cardiovascular mortality

Answer 120

i. Decrease Insulin Resistance, Increase insulin signal transduction ii. Risk of MI: If using insulin w/ nitrates, or Avandia

Answer 121

i. Block digestion of complex carbohydrates ii. Flatulence, diarrhea, abdominal pain

Answer 122

i. Bind bile acids and prevent reabsorption ii. GI upset

Answer 123

i. Suppresses glucagon release ii. Decrease circulating glucose iii. Use w/ insulin

Answer 124

i. GLP-1 -> stimulates insulin release ii. Risk of pancreatic cancer

Answer 125

i. Prevents glucose reabsorption in PC ii. Causes glucosuria, osmotic diuretic, weight loss, dehydration, genital necrosis iii. -liflozin

Answer 126

Platelets go through four phases: a. Adhesion b. Aggregation c. Secretion of vasocontrictive factors (5-HT, ADP, TXA2) d. Cross-linking of adjacent platelets

Answer 127

Injury--> reactive proteins collagen & vWF exposed --> results in platelet adherence, activation, and secretion of 5-HT, TXA2, and ADP from platelet granules --> vasoconstriction and platelet aggregation due to increased 5-HT --> fibrinogen cross-links platelets --> resulting in the formation of platelet plugs

Answer 128

Disseminated Intravascular Coagulopathy i. Excessive consumption of clotting factors and platelets ii. Spontaneous bleeding iii. Causes: Massive tissue injury, malignancy, bacterial sepsis, abruptio placentae iv. Tx: Plasma transfusions, treat underlying cause, up to 50% mortality

Answer 129

Fibrinolysis refers to the process of fibrin digestion Precursor- Plasminogen circulates in its inactive form. Tissue factor plasminogen activator is released by endothelial cells in response to injury, converting plasminogen into plasmin --> plasmin releases fibrin degradation products and begin to digest the fibrin clot

Answer 130

Indirect Thrombin Inhibitors: Enhances antithrombin activity i. Inactivation of factor Xa iii. Ex: Heparin, LMW heparin, fondaparinux Direct Thrombin Inhibitors: i. Bind to both active and substrate recognition sites of thrombin ii. Hirudin iii. Bivalrudin iv. Bind only to thrombin active sites: Argatroban, Melagatran, Dabigatran

Answer 131

Heparin i. Binds and activates antithrombin III (enhances the activity 1000x) ii. High molecular weight/unfractionated iii. Extracted from porcine intestinal mucosa & bovine lung LMW Heparin- (Enoxaparin, Dalteparin, Tinzaparin) i. More specific for factor Xa, less effective on antithrombin ii. Less effective coagulation Fondaparinux i. Not as effective; selective for factor X ii. Less bleeding risks iii. Can give with HIT

Answer 132

Warfarin: An anticoagulant that inhibits vitamin K epoxide reductase. blocking the formation of clotting factors II, VII, IX, X ii. 8-12 hour delay in onset of action; bridge with Heparin iii. Therapeutic range defined by INR. Normal : 0.8-1.2, Warfarin: 2-3 Drug Interactions: 1. Pharmacokinetic: Enzyme induction, inhibition, and reduced plasma protein binding 2. Pharmacodynamic: Synergism, Competitive Antagonism, Altered vitamin K Reverse w/ large dose vitamin K, FFP, factor IX Toxicity: Hemorrhagic disorder in the fetus, birth defects, cutaneous necrosis

Answer 133

Eliquis, Xarelto, Bevyxxa, Pradaxa (Factor Xa inhibitors) i. No reversal agent ii. Inhibits factor Xa and thrombin

Answer 134

Streptokinase i. Synthesized by streptococci Urokinase i. Lyses thrombus from within Tissue plasminogen activator (TPA) i. Preferentially activates plasminogen that is bound to fibrin ii. Physiologic TPA confines fibrinolysis to the formed thrombus & avoids systematic activation. Pharmacologic TPA loses clot specificity

Answer 135

ASA i. Cox-1 selective ii. Inhibits TXA2 formation inhibiting platelet aggregation Plavix, Ticlid i. Irreversibly inhibit ADP receptors on platelets reducing platelet aggregation ii. Reduction in ischemic events by 8.7% compared to ASA Abciximab- Monoclonal antibodies i. Antiplatelet ii. Targets IIb/IIIa receptor complex leading to inhibition of platelet aggregation

Answer 136

Aminocaprioc Acid/ Tranexamic Acid i. Inhibitor of the fibronolytic system; competitively inhibits plasminogen activation Vitamin K: i. Precursor prothrombin and factors VII, IX, X Plasma Fractions: i. Used for deficiencies in plasma coagulation factors; diseases such as hemophilia and antithrombin III deficiency ii. Concentrated plasma & plasma recombinant can be given to reduce bleeding e. Desmopressin: i. Tx for mild hemophelia A and von Willebrand disease ii. Increases factor VIII activity

Answer 137

a. Tremor: Rhymic movement around a joint, repetitive b. Chorea: Muscle jerks in various areas, quick i. Ballismus: Violent abnormal movements c. Athetosis: Slow, writhing, rotational d. Dystonia: Abnormal posture

Answer 138

The basal ganglia, motor cortex, and thalamus work together to control movement. The basal ganglia help plan and coordinate movements, while the motor cortex sends signals to the muscles. The thalamus acts as a relay station, passing information between these areas. The substantia nigra is a key player in movement control. It's part of the basal ganglia and produces dopamine, a chemical that helps regulate movement. In movement disorders this communication is disrupted. For example, in Parkinson's, there's less dopamine in the basal ganglia due to degradation of the substantia nigra, leading to tremors, stiffness Huntingtons- Destruction of GABAnergic neurons; need to decrease dopamine

Answer 139

Idiopathic, progressive Caused from dopaminergic neuron degradation and decreased dopamine levels Rigidity, bradykinesia, tremor, postural instability, cognitive decline Decreased risk: Cigarette smoke, coffee, anti-inflammatories, uric acid Increased risk: i. lead, manganese, vit D deficiency ii. 60 or older iii. Hereditary iv. Men: Women 2:1 v. Occupation; teaching, healthcare, farming vi. Toxin Exposure

Answer 140

Alpha-synuclein is a protein involved in regulating neurotransmitter release in the brain. In Parkinson's disease, it clumps together to form Lewy bodies. These clumps disrupt brain cells, leading to cell death, particularly in the substantia nigra

Answer 141

-Exercise -Physical Therapy -Speech Therapy -Deep brain stimulation -Lesional Ablation -Stem cell therapy i. Implantation of fetal substantia nigra ii. Controversial

Answer 142

a. Levodopa: L-Isomer of Dopa i. Crosses BBB. Prodrug that is converted into dopamine as it crosses the BBB (1-3% of the drug makes it across). A lot of it is deactivated in the gut before reaching the bloodstream b. Carbidopa prevents the breakdown of L-dopa by cOMT c. Decreased effectiveness overtime On-Off Phenomenon with long term use i. Periods of increased mobility followed by marked akinesia ii. Drug holiday- D/C drugs for a period of time

Answer 143

a. N/V- decreased with carbidopa b. Depression, anxiety, hallucinations and delusions worsen with carbidopa -Can treat with Pimavanserin; antipsychotic c. Tachycardia/ afib d. Dyskinesias Contraindications: Psycosis, Glaucoma, Melanoma Drug Interactions: Vit. B6, MAOIS

Answer 144

a. MAO-B antagonists: i. Specifically target dopamine. Increase dopamine in the substantia nigra ii. Selegeline iii. Rasagiline b. cOMT Inhibitors i. Inhibit cOMT, increasing circulating dopamine ii. Tolcapone, Entacapone c. Dopamine Receptor Agonists: i. Pramipexole ii. Ropinirole iii. Rotigotine iv. All less effective than levodopa, early disease tx v. Reduced side effects

Answer 145

i. Autosomal dominant, chromosome 4 ii. Gene produces huntington protein- function unkown iii. Losing GABAnergic neurons, overproduction of dopamine, reduction in choline acetyltransferase iv. Tx: Tetrabenazine (reduces dopamine activity), speech therapy, PT/OT; Need to do genetic counseling v. Onset in 30-40’s i. Progressive loss of muscle control ii. Chorea iii. Dementia iv. Death 15-20yrs after onset

Answer 146

Stimulus--> leads to disruption of cell membrane and the release of phospholipids (Phospholipase inhibitors and corticosteroids work here) This activates arachadonic acid which is then converted into Lipoxygenase and COX 1/2 --> (lipoxygenase inhibitors, nsaids work here) -Signaling molecules such as prostaglandins, TXA2, and leukotrienes are released which results in inflammation Leukotrienes also promote bronchoconstriction and vascular permeability

Answer 147

Cox 1 is always active- helps maintain kidney function, protect the lining of the stomach, and produce thromboxane. Also plays a role in prostaglandin synthesis Cox 2 is activated during inflammation and is responsible for the production of prostaglandins

Answer 148

1200mg -1500mg TID for pain Clot prevention dose 81mg-325mg Anti-platelet effect takes 8-10 days Gi upset, bleeding, increased incidence of gastric ulcers due to inhibition of GI protective prostaglandin

Answer 149

Celecoxib- Analgesic, antipyretic, anti-inflammatory Sulfanomide (allergies), expensive, BB warning- serious risk of thrombotic events Meloxicam- Less effective than celebrex

Answer 150

Ibuprofen: Pain, inflammation. Less GI upset than ASA Ketorolac: Used for severe pain in conjunction w/ opioids, good for sports medicine APAP: Pain, fever, not anti-inflammatory, 15gm fatal dose Diclofenac: Pain, inflammation, fever (GI upset 20%, decrease w/ misoprostol) Indomethacin: Arthritis, gout, patent ductus arteriosus (GI upset 1/3rd of patients)

Answer 151

Acute use: Supresses inflammation Mobilize energy stores Improve cognitive function Salt and water retention Chronic use of them affects: Immunosuppresion Diabetes, obesity, muscle wasting Depression HTN

Answer 152

Glucocorticoids bind to receptors inside the cell, forming a complex that enters the nucleus. This complex binds to DNA, influencing the transcription of specific genes. This decreases the synthesis of Annexin-1; which decreases phospholipase A2 and inhibits leukocyte response Inhibits nuclear factor kappa pathway Increases synthesis of IL-10, an immunosuppresive enzyme, but also helps to reduce inflammation Increases levels of SLPI- protects tissue from damage by inhibiting enzymes that break down proteins during inflammation Inh-NFkB

Answer 153

Disease Modifying Anti-Rheumatic Drugs -Initially targeted to join disorders -Reduce inflammation rate, by decreasing sedimentation rate, c-reactive protein, and rheumatoid factor -Decreases damage to bones and joints Often given w/ NSAIDS Drugs: MTX, Cyclophosphamide, Cyclopsorine Biologic: Orencia, Rituximab, Humira

Answer 154

a. A-beta fibers; Non-noxious mechanical stimuli b. A-delta fibers: Noxious heat, mechanical stimuli (sharp pain, produces reflex response) c. C-fibers: Un-myelinated, slower. Noxious, chemical, heat, slow/burning pain d. A-fibers can suppress pain from C-fibers

Answer 155

Harmful substances that cause pain- Histamine Tissue Damage- Bradykinin, PKA, PKC Arachadonic Acid Pathway: Cox & Lox Pathway --> prostaglandins

Answer 156

a. Spinothalamic (Primary): Spinal Cord --> Pons -->Thalamus -->Somatosensory cortex b. Spinoreticular (Limbic System): Spinal Cord-->Reticular formation of medulla --> reticular formation of pons --> Thalamus --> Somatosensory cortex c. Spinomesencephalic: Spinal cord -->Pons -->Periaqueductal grey of the midbrain. PAG initiates the descending inhibitory pathway

Answer 157

A: Well absorbed (IM, SQ, ORAL) i. Nasal, patch can avoid first pass ii. Codeine has a low first pass D: Highly perfused tissues- accumulation i. Brain, heart, kidney, liver ii. Skeletal muscle; reservoir M: Varies i. Morphine- phase II to active forms (M3G, M6G) ii. Esters (heroin) – converts to morphine E: Mainly in urine MOA: Bind to receptors in brain and spinal cord: modulate pain, reduce neurotransmitter release (glutamate, ACh, NE, 5-HT, substance-P), hyperpolarize post-synaptic neurons

Answer 158

i. CNS: Analgesia, euphoria, sedation, respiratory depression (brainstem), cough suppression, miosis (always), hyperthermia (mu), hypothermia (kappa) ii. CV: Most have no direct effects. Bradycardia from brainstem stimulation, Demerol causes tachycardia iii. GI: Constipation

Answer 159

Analgesia: Severe, constant (chronic), terminal illness, OB, renal or biliary colic in infants. Not as effective for sharp, intermittent pain Acute Coronary Syndrome: MONA Acute Pulmonary Edema: Reduce preload, afterload, and anxiety; Lasix is a better option Cough Diarrhea Post-op shivering Anesthesia adjunct

Answer 160

a. Tolerance develops quickly through multiple mechanisms (receptor phosphorylation, cAMP, uncoupling w/ G-Proteins) b. Dependence i. Physically dependent -->withdrawal symptoms if discontinuation -->can lead to addiction W/D symptoms: Rhinorhhea, lacrimation, yawning, chills, N/V/D, hyperthermia, muscle aches Degrees of tolerance: -High Degree of Tolerance: Analgesia, euphoria, dysphoria, mental clouding, sedation -Moderate degree of tolerance: bradycardia -Minimal or no degree of tolerance: Miosis, constipation, convulsions

Answer 161

i. Phenanthrenes: Morphine, dilaudid, heroin (UK) ii. Phenylheptylamines: Methadone (morphine tolerance, chronic opioid use) iii. Phenylpiperidines: Fentanyl, meperidine

Answer 162

i. Phenanthrenes: Codeine, Oxycodone (more effective in combination with APAP or ASA) iii. Phenylpiperidines: Tramadol, Loperamide

Answer 163

i. Naloxone, naltrexone, naloxegol ii. Reverse opioid effects in 1-3 minutes

Answer 164

MOA- Beta-lactam antibiotics attach to the enzymes that cross-link peptidoglycans and prevent cell wall synthesis i. Penicillin, cephalosporins, carbapenems, vancomycin ii. Selectively damage gram (+) cocci iii. Contain B-Lactam Ring

Answer 165

-More resistant to beta-lactamase -Broad spectrum, better gram (+) -First Generation, alternative to PCN if allergy

Answer 166

Hypersensitivity i. Most common drug allergy ii. Anaphylactic shock, hemolytic anemia, interstitial nephritis, rash

Answer 167

a. Gram (+), supposed to be “last resort: b. Resistant to beta-lactamase c. 10% have adverse reactions d. Irritating to tissues e. Chills, fever, red man syndrome f. Ototoxicity, nephrotoxicity

Answer 168

i. Act as detergents, bind to phospholipids ii. Especially effective against Gram (-) that have an outer membrane iii. Polymixin, Daptomycin

Answer 169

i. Widest spectrum of activity ii. Bind to bacterial ribosomes and inhibit protein synthesis. Attack bacterial cells without significantly damaging animal cells;however, destroy normal microbiota, bone deposition disorder iii. Tetracyclines, macrolides, aminoglycosides

Answer 170

Prototype- Erythromycin Clarithromycin Azithromycin Mostly Gram (+) MOA: Inhibit protein synthesis

Answer 171

Differentiate between the enzymes used by bacterial cells and animal cells Rifamycin disrupts mRNA synthesis Quinolones (Cipro, Levaquin, Floxin)- Inhibit DNA gyrase in bacteria Excellent gram (-) Good gram (+) UTI, RTI, bone and joint infections

Answer 172

-Sulfonamides -Treat pneumocystitis, toxoplasmosis Use w/ trimethoprim (Bactrim Septra) -Toxicity: Allergic rxns, may precipitate urine, hematopoetic disturbances

Answer 173

-Infectious particles that are active or inactive Not an organism that is alive or dead Obligate intracellular parasites: Cannot multiply unless they invade a specific host Must instruct the machinery of the host to make and release new viruses i. If host cell is kept alive- lysogenic cycle (prolonged/chronic) ii. If host cell is killed; “bursts”: Lytic cycle (acute)

Answer 174

i. Naked: Capsid (protein shell) with a viral spike (targets cell proteins) ii. Enveloped: Additional lipid membrane- Takes part of the host cell’s cell membrane, and creates an envelope around itself

Answer 175

Mimics a DNA building block (dGTP) and gets incorporated into viral DNA during replication. Virus mistakes acyclovir for dGTP and it prevents further DNA elongation, causing irreversible chain termination Acyclovir- similar to HSV virus makeup, missing an OH group

Answer 176

HIV/HBV Viral spike protein (gp120) specifically targets our CD4+ cells (T-Cells) -AZT- Zidovudine, Azidothymidine i. Reverse transcriptase inhibitor ii. HIV Cocktail- HAART; Highly Active Antiretroviral Therapy c. Lamivudine i. Inhibits HBV polymerase and HIV reverse transcriptase

Answer 177

a. Oseltamivir i. FDA approved for early tx (first 48hrs) ii. BID x 5 days iii. Targets N1, N2 b. Zanamivir (Relenza) i. Targets N1, N2 ii. Must be taken when exposed to flu, not when symptoms appear c. Baloxivir Marboxil (Xofluza) i. Targets polymerase ii. Not for pregnant women, breast feeding mothers, may shorten flu by about a day

Answer 178

Triglycerides: i. Consist of glycerol esters (3) combined with free fatty acids ii. Form adipose tissue and are the main storage form of fats in the human body iii. Stored triglycerides can be catabolized into free fatty acids and used for energy during fasting or between meals Cholesterol: i. Important precursors to steroid hormones, cell membranes, Vit D, bile salts ii. Produced via dietary intake (20%), or De Novo Synthesis (made in liver) iii. Acetyl-Coa is converted by HMG-CoA into Mevalolate --> Cholesterol

Answer 179

Chylomicrons: i. Formed in intestine ii. Carry triglycerides and cholesterol through the lymphatic system, then the blood stream, to the liver VLDL i. Secreted by the liver, transported to peripheral tissues ii. Converted into IDL, LDL LDL i. “Bad” cholesterol. Transported to cells from liver ii. In excess, deposited into arteries HDL i. “Good” cholesterol ii. Scavenges cholesterol from other cells and lipoproteins iii. Low HDL associated with atherosclerosis

Answer 180

a. Total: <200 b. LDL: < 130 c. HDL: >40 Men, >50 Women d. Triglycerides <120 1.00- One half the average 3.5- Average 6- Twice the average 8- Three times the average

Answer 181

a. Statins- HMG-CoA Reductase Inhibitors. Decrease cellular cholesterol synthesis (LDL) significantly, increases HDL. Decreases LDL 65% when combine with Mab i. Muscle Pain

Answer 182

b. Niacin- Reduces transport of VLDL from liver; Decrease LDL, decrese triglycerides, ***increases HDL*** i. Flushing

Answer 183

c. Fibrate: PPAR mediated lipolysis in liver (increases the breakdown of fatty acids and reduces triglyceride levels in the blood); decrease VLDL, LDL, increase HDL i. GI Upset- Rare

Answer 184

e. Absorption Inhibitors- Inhibit intestinal cholesterol absorption (LDL) i. Ezetimbe ii. Possible hepatotoxicity iii. Promoting arterial wall thickening?

Answer 185

PCSK9 inhibitors are drugs that help lower cholesterol levels. They block the PCSK9 protein, which normally tags LDL receptors for destruction. By inhibiting PCSK9, more LDL receptors remain on liver cells to remove LDL cholesterol from the blood. PCSK9 increase in circulation after long-term statin use

Answer 186

-process of forming atherosclerotic plaques in arteries. It begins with damage to the artery wall, leading to the accumulation of lipids and inflammatory cells. Macrophages begin to engulf LDL that is stored in the arterial wall, and that causes the formation of foam cells. These begin to accumulate and contribute to plaquestion formation

Answer 187

* Benzodiazepines -Diazepam, midazolam * Barbituates -Phenobarbitol, Thiopental (replaced by propofol), methohexital * Sleep Aids -Zolpidem * Anxiolytics -Buspar * Ethanol These are all GABAa Receptor agonists. Potentiate inhibition at all levels of the CNS -Increase flow through GABA receptor -Increase channel opening time

Answer 188

-Rehab -Naltrexone; Approved by FDA to tx ETOH dependance. Opioid- antagonists -Can cause acute opioid w/d in a patient physically dependent on opioids -Acamprosate: Reduces urge to drink. Adjunct therapy, used in Europe -Disulfiram

Answer 189

1. Ethanol goes through a redox reaction where alcohol dehydrogenase converts ethanol into acetaldehyde -This pathway creates calories from ETOH, causing weight gain 2. With chronic ETOH use, overtime the body begins to metabolize ETOH via the microsomal ethanol-oxidizing system. This system does not produce calories, chronic alcoholics will be thinner -Acetaldehyde is converted into acetate via aldehyde dehydrogenase -Disulfiram inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation (hang over symptoms)

Answer 190

-Stimulation of immune system, anti-inflammatory -Anti-depressant (cyp450)

Answer 191

-HMG CoA Reductase inhibitor- reduces cholesterol -Improved blood flow, free radical scavenger

Answer 192

-Memory, immune, analgesia -Reduction in hepatotoxicity

Answer 193

- BPH - Anxiety, muscle relaxant, sedative - Yeast and bacteria

Answer 194

● Largest and most diverse class (CCNS) ● Either alkylate DNA or interfere by crosslinking (platinum compounds) ● Groups: ○ Nitrogen Mustards ■ Cyclophosphamide, chlorambucil ○ Nitrosoureas- cross BBB ■ Carmustine, lomustine, streptozocin ○ Alkyl Sulfonate ■ Busulfan ○ Platinum Analogs ■ Cisplatin, Carboplatin

Answer 195

MOA: Enters cells, forms highly reactive platinum complexes, damages DNA with intrastand and interstrand crosslinks, inhibits cell proliferation Highly bound to plasma proteins Concentrates in kidney, intestine, testes ● Poorly penetrates BBB ● Slowly excreted in urine ● Uses ○ Testicular cancer (85% - 95% curative) ○ Ovarian cancer ○ Other solid tumors: lung, esophagus, gastric ● Adverse effects ○ Emesis ○ Nephrotoxicity ○ Peripheral neuropathy ○ Ototoxicity Alternative: ● (Carboplatin – better tolerated)

Answer 196

-inhibits the enzyme dihydrofolate reductase (DHFR). This blocks the synthesis of DNA, RNA, and proteins, affecting rapidly dividing cells. -Cytoxic actions: Predominant on bone marrow Ulceration of intestinal mucosa Cross placenta, fetal malformations & death Immunosuppressive action: Prevents clonal expansion of B & T lymphocytes Anti-inflammatory

Answer 197

-6-MP, 5-FU Vincristine, Paclitaxel Dantinomycin, Doxorubicin, Bleomycin

Answer 198

Corticosteroids, Tamoxifen, Fulvestrant -Imatinib, Trastuzumab, Rituximab

Answer 199

Cell types: Carcinoma, sarcoma, leukemia, lymphoma Treatments: Primary, neoadjuvant, adjuvant