Week 6 Objectives and Focus Points

8/11/2019 Week 6 Objectives and Focus Points

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Week 6 Objectives and Focus Points

Clinical Correlate:

1. Define the term polypharmacy.

Polypharmacy is taking many drugs at one time. Causes increased likelihood of adverse

side effects and drug-drug interactions.

2. Describe the prescribing cascade.

When patientis given prescription to treat side effects of other drugs, prevents physician

from recognizing present illness, and can cause health problems in patient. Also, adverse

drug effects can be confused as being symptoms of the presenting illness.

3. Recognize the clinical presentation and health care burden of Clostridium difficile

infections.

Infection occurs mostly in those who have had recent medical care and antibiotics

(within 2-3 months) Severity of infection can range from diarrhea to colitis to

perforation to death. Almost of infections in people < 65

>90% of deaths in people 65

Resistance to antibiotics to treat C. difficile isnt problem, but bacteria spreads rapidly

because it is naturally resistant to many drugs

Treatment:

Antibiotics. Probiotics, yeasts. Fecal transplantation for recurrent/resistant

Iatrogenesis - Any injury or illness that occurs because of medical care.

Examples: chemotherapy may cause nausea, vomiting, hair loss, or depressed white

blood cell counts. Foley catheter for incontinence can create a urinary tract infection andurinary sepsis. In the U.S., 0.67% of patients admitted to a hospital die because of health

care associated error.

side effect - effect of a drug other than that desired

Adverse drug event - unintended and undesired effects of a medication at the normal

dose.


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Peripheral Nervous System:

1. Describe and identify the structure and function of nerve fibers , nerves , and plexuses

Nerve consists of a bundle of nerve fibers outside the CNS (or a bundle of bundled

fibers, or fascicles, in the case of a larger nerve), the connective tissue coverings thatsurround and bind the nerve fibers, and fascicles together, and blood vessels ( vasa

nervorum ) that nourish the nerve fibers and their coverings

-Endoneurium, Perineurium, Epineurium (pictured)

Plexus a network of intersecting nerve fibers; combines ventral rami of sequential

spinal nerves Ex: Brachial Plexus (pictured)

2. Define and distinguish the components of a peripheral nerve

Peripheral nerve can have contributions from a number of spinal nerves

Ex: Radial Nerve (one branch of the brachial plexus) (pictured)


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3. Explain and demonstrate the discrepancy between the number of cervical vertebrae and

cervical spinal nerves

C nerves branch from superior of the C vertebrae with the exception of C8 which

branches from inferior of C7 vertebra. T vertebrae branch from inferior of T vertebra.

4. Explain the indications of an Ankle Foot Orthosis , and the peripheral nerve injury that

would necessitate its use

Fibular nerve=Peroneal nerve

If any trauma happened to the Fibular/Peroneal Nerve, drop foot could occur.

AFO

Ankle Foot Orthosis

Brace that is designed to be worn with appropriate footwear

Maintains ankle in a neutral position (90)

Assists patient with more normal gait

5. Describe the cutaneous distribution and motor deficits of selected nerves and nerve

injuries

Meralgia paresthetica:

Pins and needles tingling feeling in thigh after riding motorcycle 500 miles. Walking

alleviates at first, but after riding more, walking no longer alleviates. Lateral Femoral

Cutaneous Nerve is purely sensory. Combination of belt, belly, riding posture has put

pressure on this nerve, resulting in purely sensory dysfunction. Treatment is removing

aggravating factors.

Entrapment of cutaneous nerve originating from the lumbar plexus

No motor loss

Remove aggravating factors

Usually self-resolving


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The lumbar ventral rami form the lumbar plexus

Lumbosacral plexus:

Sciatic nerve (L4 S3) + Pudendal nerve (S2 S4)

When axon breaks, Proximal stump is part closest to soma (cell body) and is still given

nutrients. Distal stump will wither away.

Burner (stinger) injury Brachial plexopathy (pictured)

Traction (or compression) injury of C5 &/or C6 ventral rami (brachial plexus)

Motor and sensory involvement

Usually transient (hours to weeks)

Difficult to injure, but possible (pictured). Brachial Plexus protected by clavicle &muscles.

Limb Structure and Function:

1. Compare and contrast the similarities and differences between upper- and lower- limbs

Upper and lower limbs both

Appendages of the trunk

Attached by limb girdle (pelvic & pectoral)

Have 3 segments (proximal, medial, distal)

Only Upper Limbs

Positioning the hand - Fine motor

Only Lower Limbs

Support body weight

Provide locomotion


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Maintain balance

2. Describe and identify the structures that create upper- and lower- limb compartments

Lower Limbs:

Organized into 6 regions:

Gluteal, Femoral, Knee, Leg (between knee and ankle), Talocrural, Foot

Boundaries of Gluteal:

Iliac crest, Gluteal sulcus (fold), Greater trochanter, Natal (intergluteal) cleft

The Femoral Region

Bounded superiorly by the inguinal ligament. Anterior superior iliac spine -> Pubic

tubercle

Thigh musculature is enveloped in deep fascia ( Fascia lata )

Thickened laterally - Iliotibial tract (band)

Continuous with intermuscular septa -Divide the thigh muscles into compartments

Anterior, Medial, posterior compartments

The leg contains 2 bones, & 3 compartments:

Tibia & fibula Connected via:

Interosseous membrane, Anterior compartment, Posterior compartment, Lateral

Compartment. Anterior responsible for dorsiflexion. Crural refers to whole leg.

Sural refers to biggest compartment (posterior).

Ankle Joint = Talocrural joint = Bones of the crural region (Tibia & Fibula) and

Talus


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Allows for: Plantarflexion, Dorsiflexion

Upper Limbs

Proximal = Arm

Intermediate = ForearmDistal = Hand

Arm

Anterior compartment = Flexor

Posterior compartment = Extensor

Brachial fascia is deep fascia of the arm*

Forearm

Anterior compartment = Flexors

Posterior compartment = Extensors

Flexion and extension refers to motion of the wrist and the fingers.

Antibrachial fascia is deep fascia of forearm

The humero-ulnar joint allows for flexion/extension (pictured)

3. Define and explain the transition from trunk to thigh

Refer #2: Gluteal Boundary

4. Explain and demonstrate the carrying angle

carrying angle - When the arm is extended, with the palm facing forward or up, the bones of the upper arm (humerus) and forearm (radius and ulna) are not perfectly aligned.The deviation from a straight line is referred to as the "carrying angle" permits the arm to

be swung without contacting the hips. Women on average have smaller shoulders andwider hips than men, which may necessitate a more acute carrying angle.

5. Describe the basic motions available at each of the featured joints
http://en.wikipedia.org/wiki/Extension_(kinesiology)http://en.wikipedia.org/wiki/Humerushttp://en.wikipedia.org/wiki/Forearmhttp://en.wikipedia.org/wiki/Radius_(bone)http://en.wikipedia.org/wiki/Ulnahttp://en.wikipedia.org/wiki/Ulnahttp://en.wikipedia.org/wiki/Radius_(bone)http://en.wikipedia.org/wiki/Forearmhttp://en.wikipedia.org/wiki/Humerushttp://en.wikipedia.org/wiki/Extension_(kinesiology)


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Covered in other objectives.

Into to Pharmacology:

1.

Define pharmaceutics, pharmacokinetics and pharmacodynamics.Pharmaceutics - science that is concerned with understanding the interactions ofchemical substances with living systems, and the application of this understanding to thetreatment of patients.Pharmacokinetics - The study of the absorption, distribution, metabolism and excretion ofdrugs from the body. In operational terms. (what the body does to drugs)

Pharmacodynamics - The study of the relationship between concentrations of drug and thebiologic effects (physiological or biochemical) over time. (what drugs do to the body)

2. Describe the phases of drug clinical investigation and FDA approval

Clinical Investigation:I: Establish Safety (Healthy Volunteers)

II: Establish Efficacy and Dose (Small # of patients)

III: Verify Efficacy and detect adverse effects (Large # of patients)

IV: Obtain additional data following approval (commences after drug is marketed)

FDA Approval Process:

1. Drug companies submit data for NEW DRUG APPLICATION (NDA)

2. FDA approves drug for indications asked for by company based on efficacy andsafety data in the NDA

3. Once marketed, prescribers, however, can use drugs for non-FDA- approved or off -label indications

4. Drugs with an increased safety risk, high-cost, etc. may have prescribing restrictionsenacted by the FDA, hospital or payer.

3. Explain over-the-counter versus prescription drugs and the differen ces between a drugstrade, generic and chemical namesPrescription Drug Must be prescribed by a doctor

Embryology of Limb Development: ( Hand Written)

1. Identify and describe the embryonic tissues and structures that give rise to the limbs.

2. Discuss when limb development occurs, and identify the critical periods of time for limbdevelopment.


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3. Describe the following: body folding, somite formation, limb growth, hand/feetformation, limb rotation

4. Discuss development of bones, muscles, and nerves of the extremities

5. Identify and describe malformations of limb development, and give examples of howthey may occur.

Medical Mycology: ( Hand Written)

1. compare and contrast bacterial and fungal cells, including the constituents of theirrespective cell membranes and cell walls

2. outline the risk factors for fungal infection

3. briefly describe the three types of mycoses

4. relate dimorphism to yeast (or spherule) and mold lifestyles

as part of this, define and illustrate the terms blastoconidia, pseudohyphae,hyphae, septate, coenocytic, mycelium, conidia, sporangiospore,sporangium,conidiophore, sporangiophore

as part of this, explain the function of fungal spores

5. list fungal virulence factors, using Cryptococcus neoformans as an example of a capsule-former

6. explain how microscopy and culture are used in diagnosing fungal infections

Intro to Medical Safety (Pharm): (Hand Written)

1. Describe the factors to consider when evaluating new drug products (slide 9)

2. Discuss factors contributing to drug therapy costs (slide 10)

3. List and define causative factors that contribute to unsafe healthcare (slides 21-22)

4. Name priority areas in medication management for risk reduction including High AlertMedications (and High Alert Situations) (slides 33-35)

Medical Virology: (not complete)

HPV is the most common std in the United States.

Minimally, a virus has DNA or RNA plus a protein shell called a capsid

1. Describe the role of each of the basic components of enveloped viruses and naked virusesin viral replication.


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Naked Viruses only have capsid and genome.Enveloped Viruses have an envelope with a lipid bilayer, structural proteins, andglycoproteins. They also have an internal capsid around the genome.

Naked capsid viruses can survive well outside host; transmits easily by fecal-oral route.

Enveloped viruses are generally sensitive to their environment; easily inactivated bydetergents, heat, solvents, alcohol, etc.; prefers transmission by direct contact or via

blood

The capsid or envelope of a virus helps with entry into a new cell, protection of nucleicacid when extracellular, and helps package essential enzymes.Capsid made from proteins protects DNA and can be helicle (cylindrical) or isohedral(spherical).

Naked are only isohedral. Enveloped can be isohedral or helical

Surface structures (surface proteins) are used for attachment & penetration; may also beinvolved in release, maturation or immunity

Viral genomes are DNA or RNA. Genomes may be linear or circular; single or doublestranded; usually single copy (except HIV is diploid)HIV-retrovirus is one of only viruses with double strand.

Viral dna replicates in nucleus, rna in the cytoplasm.

2. Classify viral pathogens based on their virion structure and replication strategy.Viral dna replicates in nucleus, rna in the cytoplasmRNA+single stranded RNA use our machinery to be translated to proteins and replicate.

Negative (-) Single Stranded RNA uses its viral RNA polymerase to become +ssRNAwhich are then translated to proteins

Double Stranded RNA

+DSRNA -> enters cell and translated by it. -> viral protein -> makes DSRNA.+DSRNA is then packaged or translated, use cells RNA polymerase and is stored in the

cytoplasm.DNA

Retroviruses:

Breaks central dogma


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3. Explain the basic mechanisms of viral pathogenesis and how it relates to host defensesand antiviral therapies.Viruses can undergo mutation faster than we can create antibiotics.Interferon Cascade Infected cell releases interferons that kills virus coming in. Virusescan destroy the production of interferons, getting rid of the interferon response.

4. Explain common mechanisms that result in viral genetic variations and correlate themwith clinical or epidemiological outcomes or to biotechnology.Viruses have tropism binding protein preference. Different affinities for certainreceptors attract it to certain animals or tissues determined by genomes.Antigenic Drift: one virus mutates and evades defense. ie. Flu different every year.Antigenic Shift: two viruses come together. Mix genomes. ie. virus shifts from infectingonly pigs to infecting humans.

5. Explain five approaches to the diagnosis of viral diseases when using clinical specimen.

Pharmacodynamics and Drug Receptor Mechanisms pt. 1: (Hand Written)

Pathology pt. 2: (Hand Written)

Pharmacokinetics pt. 1:

1. Determine a drugs compartmental model and mode of elimination from a graphical plotof measured serum concentrations (slides 13, 22, 28)

Single Compartment model linear kinetics

Two Compartment Model Nonlinear kinetics


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First Order Drug elimination Zero Order Drug Elimination

2. From a serum concentration- time curve, determine a drugs elimination half -life (slide17)

Time passed during halving of the concentration.

3. Describe the relationship between a kinetic process, its half-life and the time it takes to be(nearly) completed (slide 16)

You can safely assume that a kinetic process is almost totally completed after 4 half-livesof that process: absorption; distribution; elimination; accumulation

4. Discuss the drug dosing implications of linear and non-linear drug elimination (slides 18-21, 23)

Looking at the graphs above, you can see how you would need to change dose to affectserum level of the drug in the body for first order vs. zero order.

5. Describe the differences between bioavailability and bioequivalence (slides 33, 36-39)

Bioavailability : fraction of drug reaching systemic circulation (extent of absorption; gutwall metabolism; efflux transporting; first - pass effect)

Bioequivalence : Compares drug dosage forms; compares a drug dosage form made bydifferent manufacturers (usually Trade Name vs. Generic)

To be bioequivalent, serum concentration time curves from the two products mustbe (nearly) superimposable; that is, they have the same peak level, time to peak leveland AUC.

Drugs can have the same bioavailability (have same AUC) but not be bioequivalent

First Order - Linear Kinetics: Relationship betweenadministered dose and achievedplasma concentration

Vmax

Dose Amount/Time

Zero Order / Non-Linear Kinetics: Relationship between administered dose and achievedplasma concentration


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Brand A and Brand B are not Bioequivalent, but probably are equally bioavailablebecause area under the curve is same for both.

6. Define first - pass effect and P -glycoprotein (slides 33, 45-46)

First Pass Effect (drug metabolized by liver before reaching systemic circulation)

P-glycoprotein is a common drug transporter; in the GI tract, it can send absorbed drugs back into intestinal lumen, decreasing their absorption and bioavailability

Intro to ANS Pharm:

1. Identify and list drug targets in the autonomic nervous system (slides 14-17; 30-32; 37-41)

Stimulation of the parasympathetic nervous system:

Cholinergics

Cholinergic agonists

Parasympathomimetics

Muscarinic

Nicotinic

Acetylcholinesterase (cholinesterase inhibitor) (indirect stimulation)

Inhibition of the parasympathetic nervous system:

Anticholinergics

Blockers

Parasympatholytics

Antimuscarinic

Indirect effects (drug-induced actions are mediated by the natural neurotransmitter)

Direct effects directly stimulate or block post-synaptic receptors

2. Explain the difference between direct and indirect drug activity and be able to giveexamples of both (slides 9-10; 16; 37-39)


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OrganCholinergic Drug Effect

(muscarinic drug receptors)Anticholinergic Drug Effect(muscarinic drug receptors)

Eye: iris sphincter muscle Contraction miosis Relaxation mydriasis Eye: ciliary muscle (controlsfocusing by the lens oraccommodation)

Contraction for near visionCycloplegia (paralysis of ciliary

muscle); relaxation for farvision

Lacrimal (tear) glands Increased secretion Decreased secretion

Salivary glands Increased secretion Decreased secretionSweat glands Increased secretion Decreased secretion

LungBronchoconstriction; increased

secretionsBronchodilation; decreased

secretions

HeartBradycardia; decreased AV node

conductionTachycardia; increased AV

node conductionGI Tract Diarrhea, nausea, vomiting ConstipationBladder Contraction, urination Relaxation, urinary retentionPrototype Drugs Neostigmine; pilocarpine Atropine; glycopyrrolate

Difference explained above.

Ex. Direct : Muscarinic (cholinergic) receptor stimulant:

Bronchoconstriction or bronchospasm

Muscarinic (cholinergic) receptor blocker : bronchodilationEx. Indirect: Acetylcholinesterase Inhibitors indirectly affect the amount of Achgetting to a receptor. & Examples: ephedrine, amphetamine cause realease ofnorepinephrine into blood from presynaptic cleft.

3. Describe the effects of drug-mediated muscarinic receptor stimulation and inhibitioninvolving the eye, salivary glands, lung, heart and GI tract (slides 22-27)

Cholinergic = stimulation of muscarinic receptors

Side Effects = DUMBELLS

Anticholinergic

Side Effects = opposite of

DUMBELLS


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4. Describe the effects of drug-mediated adrenergic receptor stimulation and inhibitioninvolving the lung, heart and blood vessels (slides 30-32; 36)

5. Explain semi-selective drug receptor activity (stimulation or blockade) (slide 33-35)

Example: Albuterol is a semi-selective

** beta-2-receptor agonist used as a bronchodilator**;**As its dose is increased, it tends to increase heart rate via beta-1-receptor stimulation**

Pathology pt. 3:

1. Define Cellular Adaptation and differentiate the different cellular adaptation termsCellular Adaptation - Prolonged exposure of cells to adverse or exaggerated normalstimuli which evokes various changes at the level of individual cells, tissues or wholeorgans.Types:

1. Atrophy2. Hypertrophy3. Hyperplasia

4. Metaplasia5. Dysplasia6. Anaplasia

Atrophy - Decrease in the size of a tissue, organ or the entire body.Physiologic: Thymus undergoing involution, Ovaries, uterus and breasts aftermenopause. The atrophic bones and muscles in the elderly become thin and prone tofracture.

Semi - Selectivity


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Pathologic:Ischemic organs are typically small (i.e. kidneys involved withatherosclerosis), Testicular Atrophy, Alzheimer Dementia

2. Distinguish between physiologic and pathologic hypertrophy.Hypertrophy - An increase in the size of tissues or organs due to enlargement of

individual cells.Physiologic : Enlargement of skeletal muscles in body builders due to weights.Pathologic: Hypertrophy of the heart that occurs as an adaptation to increased workload.

3. Distinguish between hyperplasia and hypertrophyHyperplasia - adaptive increase in the number of cells that can cause enlargement oftissues or organsEx: Endometrial Hyperplasia due to estrogens, Hyperplastic polyps of the colon orstomachHyperplasia & Hypertophy can be seen together. (enlargement of cells and increase # of

cells) Ex: Physiologic hypertrophy of the uterine smooth muscle cells during pregnancyis also accompanied by hyperplasia. Ex: hyperplastic prostate, (BPH) increases both thesize and number of glands and stroma.

4. Define metaplasia and be able to give examplesMetaplasia - adaptive change of one cell type for another to suit the environment.Ex: Squamous metaplasia of the bronchial epithelium due to smoking (smoking isenvironment), Gastric or glandular metaplasia of GE Junction in Barrett Esophagus.Metaplasia is reversible , but can also progress to more detrimental growth,Dysplasia.Dysplasia - disordered growth of tissues resulting from chronic irritation or infection.(precancerous condition) ** Best Example on test** : detection of cervical dysplasia(cervical intraepithelial neoplasia or CIN) based on PAP smears. ***Remember there isan association of dysplasias and cervical cancers with HPV!

Anaplasia - Undifferentiated and uncontrolled growth of cells-The hallmark of malignanttransformation. (Cancer) Ex: Squamous Cell Carcinoma of the Cervix, Cancer of theLung, Malignant Melanoma, Renal Cell Carcinoma

5. Identify changes in dysplastic tissue vs anaplastic tissueDysplastic bigger, irregularity of nucleus, Nucleus to cytoplasmic ratio become up to1:1. Loss of some cytosol.

6. Identify the best example of a dysplastic change in the human body7. Identify other names for Anaplasia pathologically and clinically.

Cancer, carcinoma8. List the microscopic hallmarks of anaplasia

Abnormal chromatin figures, prominent, big, misshapen nuclei. Loss of Cytosol.


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9. Distinguish between reversible and irreversible cell damage.Reversible Cell Injury Any damage to cell that is not damage to nucleus. mild orshort-lived. Characterized by cellular swelling, also known as hydropic degeneration,and reflects the increased influx of water into the cytoplasm and mitochondria fromaltered permeability of the plasma membrane. Ex: Hypoxia, for example, causes

dysfunction of the ATP-driven Na+-K+ pump altering the permeability. Once ATPfunction is restored, the Na+ and the water are pumped out of the cell and the swellingdisappears.Swollen mitochondria generate less energy, so instead of oxidative ATP production, thecell reverts to anaerobic glycolysis which results in excessive production of lactic acid,the cell pH becomes acidic which further slows down cell metabolism. Other organelles,like the RER swell and fragment, resulting in decreased protein synthesis.Irreversible Cell Injury - If acute stress to which a cell must react exceeds its ability toadapt, the resulting changes in structure and function lead to the death of a cell.Morphologically recognized by changes in the nucleus or by rupture of the cell

membrane and loss of cell integrity.

10. Differentiate the different terms for nuclear damageDamage to the nucleus can present in three forms:1. Pyknosis: condensation of the chromatin2. Karyorrhexis: fragmentation of the nucleus into small particles (nuclear dust)3. Karyolysis: involves dissolution of the nucleus and lysis of chromatin by

enzymes.Other irreversible cell damage: The cytoplasm is fragmented and lost. The dead cell,clinically, releases their cellular enzymes into the ECF and eventually the circulation.Diagnosis: Cytoplasmic enzymes, such as AST or LDH, are released from damaged cellsand can be measured in the blood where they are useful signs of cell injury. High levelsof these enzymes are typically found in patients with MIs or viral hepatitis.

11. Differentiate the various intracellular accumulationsIntracellular accumulation of coal . Living in the city, lung tissue will have some coal onthe surface. Dust cells in alveoli will engulf coal, and store on surface or bring to lymphnode.Intracellular accumulation of fat . Accumulation of fat seen in alcoholics. Fat stored inliver. Alcohol inhibits both protein synthesis and the export of fat from the liver in theform of lipoproteins. Results in fiberous scarring.Hemosiderosis is an accumulation of the blood-derived brown pigment hemosiderin, aniron-storage protein normally found in the spleen, BM and Kupffer cells of the liver.Excess iron (anemias or multiple transfusions) is stored intracellularly as both ferritin andhemosiderin in other organs, such as the skin, pancreas, heart and kidneys, and if severeenough, can damage those organsAccumulation of Lipofuscin


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Classically known as the wear and tear pigment, and is composed of a golden -browngranules found predominantly in neurons, myocardial cells and infrequently hepatocytes.It is a normal constituent of many cells, increases with age, and is derived from thenormal turnover of membrane constituents of the cell.Despite the occasional prominence of intracellular lipofuscin, this pigment does not

interfere with cell function.

Inherited Lysosomal Storage DiseasesBreakdown of certain complex lipids, mucopolysaccharides and glycogens areaccomplished by a sequence of enzymatic steps.Since these enzymes are located in the lysosomes of the cell, their absence results in theselysosomal storage disease because the substrate accumulates in the lysosomes, causingfunctional derangements of cells, tissues and organs.Examples include Tay-Sachs, Gauchers, Hurlers, Von Gierkes, Pompes and Niemann-

Pick DiseasesPharmacodynamics and Drug Receptor Mechanisms pt. 2:

1. Using a dose-effect curve, illustrate drug effectiveness and potencyPotency refers to the (EC 50) or (ED 50) of a drug required to produce 50% of the drugsmaximal effect.

a. EC = Effective Concentration b. ED = Effective Dose

2. Using a dose-effect curve, illustrate a partial vs. full agonistEfficacy (maximal efficacy) greatest effect an agonist can produce if dose is taken tohighest tolerated level

a. Full agonist b. Partial agonistc. Inverse agonist

3. Define competitive and non-c ompetitive antagonism and be able to recognize theseeffects from dose-effect curve.Competitive antagonist binds to active site and prevents agonist from binding(reversible) (decreases potency of agonist) (does not affect efficacy)

Non Competitive antagonist can bind to an active site or allosteric site (other site) thanthe active site (Decreases Efficacy) (also decreases potency)

a. Binds active site with covalent bond or high affinity (irreversible) b. At allosteric site prevents activation by agonist (effectively irreversible)


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Competetive Agonist Non Competetive Agonist

4. If given dose-effect curves of several drugs, determine comparative drug efficacy and potency.

5. Explain differences between drugs therapeutic window and therapeutic index Therapeutic Index represents the estimate of the safety of the drug

TI= TD50/ED50

Therapeutic Window is the range of doses that elicits a therapeutic response, withoutunacceptable adverse effects

Pharmacogenomics is the study of genetic variations that influence individualresponse to drugs.

Parmacodynamic Variability Drugs vary in effectiveness due to factors inindividuals. (genetics, tolerance, desensitization, physiological variables, pathologicalfactors)

Pathogen Adaptation: ( Incomplete)

Read Chapter 4 of Review of Medical Microbiology & Immunology, 12e Levinson

Terminology for prokaryotic gene expression:

Competetive Antagonist


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Operon One unit of transcription; contains promoter, operator, cistrons & terminator

Cistron A segment of DNA encoding a polypeptide

Promoter Site where RNA polymerase binds to initiate transcription

Operator Site near the promoter where regulatory protein or transcription factor binds

Terminator A segment of DNA that signals the end of transcription

RepressorA protein that binds the operator and blocks transcription; may be enhanced by a co-repressoror inhibited by an inducer

ActivatorA protein that binds the operator and is required for transcription; may be activated by aninducer or inhibited by inhibitor

Regulon A group of operons under the control of the a common regulator

1. Describe the essential features bacterial chromosomes and plasmids.

Bacterial chromosome - Usually, a single circular dsDNA of ~5 million base pairsencoding ~4,000 genes.

Nucleoid - Bacterial chromosome is tightly packaged in a central irregular structure

Bacterial plasmids - Small, usually circular extrachromosomal dsDNA elements.

They replicate independently of the main chromosome; usually dispensable

Copy number of bacterial plasmids ranges from 1 to 50 per chromosome depending onthe origin of replication (ori)

May be transferred within the same species or between different species

May carry supplementary genetic information (e.g., antibiotic resistance or virulencefactors)

Overview of translation


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Ribosomes = rRNAs + proteins

Features of bacterial ribosomes:

50S catalyzes peptide bond formation

30S decodes the mRNAPeptidyl site contains the growing peptide chain

Aminoacyl site accepts the incoming tRNAs

Prokaryotic transcription & translation are coupled

2. Explain how bacteria perform genome replication, transcription, and translation.

Bacterial genome replication starts at OriC

Bidirectional & semi-conservative

Multiple replication forks in log-phase growth

Relaxation of supercoiled DNA The unwinding of the DNA causes overwinding of thedouble helix ahead of the moving replication fork. To prevent a standstill, positivesupertwisting is relieved by DNA gyrase, a type II topoisomerase .

**Look up video, because this lady is all over the place.**

3. Explain potential causes and consequences of mutations for bacteria.


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Mutations can be spontaneous. Most are corrected via proofreading. Can also be due tochemical or radiation. Can also be repaired by Mismatch repair (using DNA as atemplate). Some mutations can make bacteria drug resistant. DNA mutation sometimesfixed by excision repair, recombination repair. Can result in frameshifts, translocations,neutral, inversions, duplications, deletions, etc.

Mutations occur at low frequency, but large population sizes

Haploid so mutations are immediately evident

Short generation time so if a mutation is advantageous, it will dominate

Mutations can alter drug targets and alter drug influx.

4. Explain how bacteria transfer DNA within a cell via transposons and programmedrearrangements.

5. Explain how bacteria transfer DNA between cells via conjugation, transduction, andtransformation.

6. Apply the above genetic mechanisms to the acquisition of virulence and antibacterialdrug resistance.

Cotrol of Microbes:

Review quiz questions from presentation and quiz file.

Healthcare associated infection (HAI) - often normal microbiota

1.

distinguish infection control, asepsis, sterilization, disinfection and antisepsis:

infection control - sum of all means used to prevent HAI

asepsis - preventing contact between microorganisms and susceptible sites

Acquisition of HAIs

Self - normal microbiota

Cross - staff, other patients, visitors

Environmental - air, food, dust, catheters, bedpans, endoscopes, respiratory equipment

Antibiotic-resistant infectious agents frequently associated w/ HAIs

control of microbial growth primary targets are microbes causing

infection food spoilage


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Sterilization= destruction or removal of all microbial life (inanimate objects) goal is todestroy endospores

Disinfection= destruction of most microbial life (destruction or removal of vegetative pathogens but not endospores) - inanimate objects

Antisepsis= disinfection of living surface

2. rank microbes from most resistant to least resistant to sterilization/disinfection/antisepsiscontrol of microbial growth:target proteins, nucleic acids, cell wall, CMTechniques:Physical:Heat, filtration, radiationChemical

Strongest to Weakest: prion>endospore>mycobacteria, naked viruses, protozoan cysts, fungi>most bacterialvegetative cells, enveloped viruses, protozoan trophozoites

3. Evaluate factors affecting death rates

Presence of interfering organic matter - completely clean off prior to disinfecting

Duration exposure, Temperature, Concentration of sterilant/disinfectant/antiseptic

4. distinguish the categories of sterilants and their applications

method of physical sterilization- moist heat autoclave 121C for 15 min

method of physical sterilization- dry heat , hospital incinerator, disposal of infectious materiale.g. syringes, dressings, pathology samples (150-180C, 2-4 hrs)

method of physical sterilization- filtration, pore size determines types microbes removed

applications: liquids that cant be heated , serum, vaccines, drugs, IV fluids enzymes, media,airborne contaminants, doesnt remove toxins

method of physical sterilization- ionizing radiation, speed, high penetrating power, absenceof heat.

method of physical sterilization- UV, poor penetration, air, surface sterilization

E.g. hospital rooms, ORs


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Chemical Sterilants:

heat sensitives, endoscopes and other microsurgical instruments, remove organic matterfirst!!, E.g. peracetic acid, also gas vapor chambers

sterilizing prions:

moist heat sterilization:

autoclave 132C, 60-90 min

chemical sterilization

1 N NaOH, 1 hr E.g. brain electrodes

Freezing does not sterilize, just isolates.

5.

list common antiseptic agentsE.g. of antiseptic agents:

ethyl, isopropyl alcohol, iodine, chlorhexidine, triclosan

pasteurization

milk is an ideal growth medium for microbes

pasteurization kills most, but not all microbes, extends shelf-life while retaining flavor

doesnt kill endospores or thermotolerant microbes (lactobacilli, micrococci, yeasts

Desiccation

disrupts microbial metabolism, stops growth

some microbes still viable

naked viruses, cysts, gram-positive bacteria, endospores relatively resistant

increase stability, shelf-life , food industry freeze -drying, pharmaceuticals

6. outline the modes of HAI transmission and prevention

Failure to perform appropriate hand hygiene is the leading cause of HAI and spread ofmultiresistant organisms!

Methods for different Scenarios:

Room Air UV

Plastic Syringe y radiation


24/24

Heat sensitive Liquid Drug filtration

Biohazardous Waste autoclave

Surgical Blade oven

Hospital Bathroom with Clostridium difficile bleach

7. Justify WHOs recommendations for alcohol-based handrub vs. soap and water

Use soap and water to remove endospore forming bacteria.

Use alcohol to kill non endospore forming bacteria.

Date post:	03-Jun-2018
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Week 6 Objectives and Focus Points

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