Pb&t General Concept Review

Front 1

4 mechanisms of cell injury

Back 1

Depletion of ATP
Mito membrane damage
Loss of Ca++ homeostasis
Reactive Oxygen species

Front 2

Hypoxia vs Ischemia

Back 2

Loss of O2
vs
Loss of Blood (O2 and nutrients)

Front 3

5 Effects of ATP depetion

Back 3

Compromised PM Na pump
Anaerobic glycolysis
Compromised PM Ca pump
Ribosomal damage
Mito and Lyso membranes don't remain intact

Front 4

Mito membrane damage

Back 4

Preventing maintenence of proton motive force for oxidative phos and ATP syn.
Leakage of cytochrome C
Mito permeability transition (MPT)

Front 5

Loss of Ca homeostasis

Back 5

ATPase
Endonuclease (N chromatin damage)
Protease (disruption of membranes)
Phospholipase

Front 6

Reactive Oxygen Species
3 major antioxidant enzymes

Back 6

Superoxide Dismutase
Glutathione
Catalase

Front 7

Reactive Oxygen Specied
Antioxidants (3)
Binding of metal ions to storage and transport proteins, minimizing OH formation (2)

Back 7

Vitamins A,C,E
Iron storage (Ferritin)
Cu storage and transport (Ceruloplasmin)

Front 8

Characteristics of Coag Necrosis

How long until you can tell at light microscope level?

Back 8

Most common type
Typical of hypoxic cell death
Ghost outlines for several days
Ischemia
Gradual nuclear degeneration
LL clotted blood
6-12 hours

Front 9

Caseous and Gangrenous Necrosis are what type of necrosis?
But can look like, especially caseous,...

Back 9

Coag necrosis

Liquifactive necrosis

Front 10

Characteristics of Liquefactive Necrosis

Back 10

Rapid influx of neutrophils
No macrophage ring or giant cells
Seen in hypoxic death of the CNS
Complete enzymatic digestion of cells, becoming a viscous mass of amorphous material containing dead cells.

Front 11

What should you know about "acellular" liquifactive necrosis?

Back 11

There are inflammatory cells present, but no parenchyma left.

Front 12

Dry vs Wet Gangrenous Necrosis

Back 12

Wet is With superimposed infection, and is wet due to action of leukocytes and bacteria.

Front 13

Apoptosis
4 components

Back 13

Initiitation by 2 pathways (ex & intrinsic)
Regulatory molecules (Bcl-2)
Caspases (death program)
Phagocytossis

Front 14

2 each
Intrinsic pathway initiated by:
Extrinsic pathway initiated by:

Back 14

In: WIthdrawal of Growth factor and hormones
Extrinsic: Receptor ligand interaction Fas Ligand and TNF receptor (Fas Receptor or CD95)

Front 15

Apoptosis

Back 15

Lysosomal Catabolism
Induction of SER
Mito alterations
Cytoskeletal Abnormalities

Front 16

Cholesterol Accumulations
In macrophages in Intimal layer of lrg arteries
In macrophages in dermis of patients with hypercholesterolemia
In macrophages of lamina prop of gallbladder

Back 16

Atherosclerosis
Xanthoma
Cholesterolosis

Front 17

HGF

Back 17

Mitogenic for epi cells, HGF receptor is produce of proto-oncogene

Front 18

TGF beta

Back 18

Inhibits epi proliferation, stimulates fibrogenesis

Front 19

VEGF

Back 19

Promotes vasculogenesis and angiogenesis

Front 20

FGF

Back 20

Migration of macro, fibro and endo

Front 21

PDGF

Back 21

Proliferation and migration of fibro, sm muscle, hepatic stellate

Front 22

EGF/TGF alpha

Back 22

Binds to EGF receptor with intrinsic tyr kinase activity, mainly ERB B1 inducing proliferation of epi, fibro and hepatocytes.

Front 23

Signal Transduction Systems
Receptors with Tyr Kinase Activity (3)

Back 23

PI3
MAP --> Ras/Raf
IP3 --> Ca++

Front 24

Signal Transduction Systems
Via G protein

Back 24

cAMP

Front 25

Signal Transduction Systems
Receptor w/o Tyr kinase activity

Back 25

JAK/STAT

Front 26

3 phases of response to partial hepatectomy
Priming
Proliferation
Growth Inhibiton

Back 26

Priming: G0-G1 c-fos, c-jun, c-myc
Proliferation: G1-S Cyclin D-CDK4
Growth Inhibiton: TGF beta, activin others,

Front 27

Most common enzmatic defect

Back 27

Gauchers's (glucocerebrosides)

Front 28

Most common receptor protein disorder:

Back 28

Hypercholesterolemia

Front 29

What chromosomes are associated with the following disorders:
Cystic Fibrosis
Marfan's
NF1
NF2
Prader Willi
DiGeorge

Back 29

7
15
17
22
15
22q11.2

Front 30

Most common cause of Down Syndrome

Back 30

Non-disjunction during mitosis
(

Front 31

results when the long arms of two acrocentric chromosomes fuse at the centromere and the two short arms are lost.

Back 31

Roberstsonian Translocation

Front 32

Child with Prader Willi, due to 2 possible causes regarding chromosome 15

Back 32

Deletion of paternal or imprinting of maternal

Front 33

Child with Angelman Syndrome, due to 2 possible causes regarding chromosome 15

Back 33

Deletion of maternal or imprinting of paternal

Front 34

5 chemical forces involved in drug-receptor interactions.

Back 34

Covalent Bonds
Van der Waals-London Forces
Ionic Bonds
Hydrophobic Interactions
Hydrogen bonds

Front 35

Covalent bonds in therapeutics

Back 35

Not common
2 bonding atoms share electrons
Usually irreversible
Often toxic

Front 36

Ionic bonds in therapeutics

Back 36

More common than covalent bonds
Weaker than covalent bonds
(ex cationic head of acetylcholine to the anionic site of cholinesterase)

Front 37

Characteristics in therapeutics
Ionic

Back 37

More common than covalent bonds
Weaker than covalent
Opposite electrostatic charges
ex: cationic head of acetylchoiine to the anionic stie of the cholinesterase

Front 38

Characteristics in therapeutics
Hydrogen Bonds

Back 38

Individual bonds are weak but parallel arrays result in high energy of association

Front 39

Characteristics in therapeutics
Hydrophobic

Back 39

Impt in highly lipid soluble drugs and lipids in cell membranes and receptor pockets
Lack strxrl specificity

Front 40

Characteristics in therapeutics
Van der Waals-London Forces

Back 40

Very weak
Molecules which utilize weaker bonds will bind more selectively than those with stronger bonds
Bind reversibly

Front 41

T or F
Competitive antagonists bind a different receptor than agonist.

Back 41

False
They bind the same receptor

Front 42

T or F
Re: Irreversible antagonist, it cannot be displaced by high conc of agonist

Back 42

True

Front 43

Competative or noncompetative
A non-receptor antagonist (acts at a site beyond receptor for agonist)

Back 43

So, noncompetative.
Effects cannot be surmounted via large quantities of agonist.

Front 44

Gs Go Gi or Gq
Activates Ca channels, activates adenylate cyclase

Back 44

Gs

Front 45

Gs Go Gi or Gq
Activates K channels, inhibits adenylate cyclase

Back 45

Gi

Front 46

Gs Go Gi or Gq
Inhibits Ca channels

Back 46

Go

Front 47

Gs Go Gi or Gq
Activates phospholipase C...DAG, IP3

Back 47

Gq

Front 48

Rapid desensitization following continued receptor stimulation. Is this reversible?

Back 48

Tachyphylaxis
This is readily reversible.

Front 49

What type of receptors are found in the SA node of the heart, the cardiac muscle, and adipose tissue?

Back 49

Beta one

Front 50

What type of receptors are found in the bronchial smooth muscle, the GI sm muscle, uterus, bladder, liver and pancreas.

Back 50

Beta two

Front 51

What type of receptors are found only in adipose tissue?

Back 51

Beta three

Front 52

What do Beta3 receptors do in the adipose tissue?

Back 52

Increase Lipolysis

Front 53

What do Beta 1 receptors do in the SA node of the heart, the cardiac muscle, and adipose tissue?

Back 53

SA node of the heart=increase hrt rate
cardiac muscle=increase contractility
adipose tissue= Increase lipolysis

Front 54

What do Beta2 receptors do in the bronchial smooth muscle, the GI sm muscle, uterus, bladder, liver and pancreas.

Back 54

bronchial smooth muscle=dilates bronchioles
GI sm muscle=constricts sphincters and relaxes gut wall
uterus=relaxes uterine wall
bladder=relaxes bladder
liver=increase gluconeogenesis and glycolysis
pancreas=increase insuline release

Front 55

In a log dose response curve, what is on the x and y axes?

Back 55

X axis: dependent variable
Y axis: Indepndnt variable

Front 56

Which is more impt, efficiency or potency?

Back 56

Efficiency

Front 57

A relationship btwn receptor occupancy and pharmacological response.

Back 57

Efficacy

Front 58

Term used to compare relative positions of dose response curves on horizontal axis.
Described in absolute dosage or in relative comparisons to other drugs in the same class.
Concentration at which drug will elicit 50% of its maximal response.

Back 58

Potency

Front 59

Used to describe relative maxima achieved by a drug.

Back 59

Intrinsic activity

Front 60

EC50

Back 60

Concentration at which drug will elicit 50% of its maximal response.

Front 61

The Kd corresponds to the ligand concentration at which __% of the receptors are bound.

Back 61

50%

Front 62

______ depends on the following two factors: affinity of receptors (Kd) for binding the drug, and efficacy with which D-R interaction is coupled to response

Back 62

Potency

Front 63

Aggregation of platelets to form a platelet plug at the site of endothelial injury is
mediated by which two substances released by platelets?

Back 63

ADP and thromboxane A2

Front 64

Type of embolism often caused by physical trauma?

Back 64

Fat Embolism

Front 65

An HIV-positive patient with AIDS is most likely to have which lab result?

Back 65

Hypergammaglobulinemia

Front 66

oncogenic viruses usually activate oncogenes by gene amplification, inactivation of
suppressor genes, or inducing translocations

Back 66

viral carcinogenesis

Front 67

Tumor Grading primarily refers to

Back 67

differentiation of cells in the tumor

Front 68

epidermal basement membrane contains what three components?

Back 68

Type IV collage
Proteoglycans
Laminin

Front 69

Interaction of epithelial cells and mesenchymal cells with extracellular matrix
proteins is mainly mediated by which class of membrane receptors?

Back 69

Integrins

Front 70

Within activated macrophages,interaction of nitric oxide and

Back 70

superoxide anion

Front 71

The destruction of infectious agents within a neutrophil’s phagocytic vacuole is
most effectively accomplished by halogenation, a process requiring which
enzyme?

Back 71

myeloperoxidase

Front 72

In equations:
E=
Emax=
EC50=

Back 72

E=effect
Emax=efficacy
EC50=Potency

Front 73

When is EC50<Kd

Back 73

In the case of spare receptors

Front 74

What does a steep dose effect curve imply?

Back 74

There is a small difference between the dose which would be therapeutic vs the dose that causes negative outcome. It implies a safety concern.

Front 75

Used to determine whether an antagonist interacts at a receptor in a competitive surmountable manner or in a competitive irreversible manner.

Back 75

Log dose graded response curve

Front 76

What effect will higher concentrations of both the competitive antagonist and the agonist have on a dose response curve?

Back 76

It will shift the curve to the right w/o chg in slope or maximal intrinsic activity. A competitive antagonist reduces the potency of an agonits with out affecting the intrinsic activity of agonist (efficacy)

Front 77

All or none response based on predetermined criteria. Plot of fraction of pop that responds to a given dose of a drug against the drug dose.

Back 77

Log Quantal Dose Response

Front 78

ED50=
TD50=
LD50=

Back 78

ED50=50% have therapeutic response
TD50=50% have toxic response
LD50=50% have die

Front 79

What is the equation to understand therapeutic index (TI)
A drug with a large therapeutic index will be ________ safe than a drug with a small therapeutic index.

Back 79

LD50/ED50 or TD50/ED50
ie a less steep slope

A drug with a large therapeutic index will be more safe than a drug with a small therapeutic index.

Front 80

Phase I versus Phase II

Back 80

Phase I trials are the first stage of testing in human subjects. Normally, a small (20-80) group of healthy volunteers will be selected.
Phase II is when the ED50 in humans is determined, b4 marketing the new drug.

Front 81

What is the most important and most common mechanism of drug permeation?

Back 81

Passive Transfer(Simple diffusion)
only non-ionized, lipid soluble drugs are passively absorbed.

Front 82

Membrane Transfer Mechanisms
Epi lining of body surfaces:
Most capillaries & glom of kidney:

Back 82

Only small mw molecules <150

Permit passage of large mw molecules, 20,000 to 30,000, but larger molecules and protein bound drugs are not filtered.

Front 83

Energy is required for active transport or facilitated diffusion?
What types of carriers exist for facilitated diffusion?

Back 83

Active Transport

AA in BBB
Weak acids in prox convoluted tubule of kidney.
Glucose

Front 84

Receptor mediated endocytosis

Back 84

Pinocytosis

Front 85

Intramuscular and subcutaneous have the same range of bioavailability. What is it?

Back 85

75-100%

Front 86

Bioavailability of IV, transdermal topical, Inhalation and oral

Back 86

IV = 100%
Transdermal = 80-<100%
Inhalation = 5-<100%
Oral = 5-<100%
Rectal = 30-<100%

Front 87

Most quick to most delayed methods of drug delivery

Back 87

IV
Inhalation
Intrperitoneal
Subcutaneous
Intramuscular
Intradermal
Oral
Topical

Front 88

Where is the likely site of absorption for acidic and basic drugs respectively?

Back 88

Acidic: In the stomach
Basic: In the intestines

Front 89

Range of pKa of acid to base compatible with rapid absorption

Back 89

3 (acid) to 7.8 (base)

Front 90

Enterohepatic circulation

Back 90

the circulation of bile from the liver, where it is produced, to the small intestine, where it aids in digestion of fats and other substances, back to the liver

Front 91

CYP3A4 a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. What impact does grapefruit juice have?

Back 91

Grapefruit juice inhibits the CYP3A4 isoform, drugs (such as felodipine) are not metabolized and therefore have a higher bioavailability.

Front 92

Duration of action of a drug and MEC

Back 92

Duration of action of a drug begins when plasma conc reaches minimal effective conc and ends when plasma conc drops below MEC

Front 93

TIme course of drug action

Back 93

Determined by its rate of absorption, its distribution in body compartments and its rate of elimination.

Front 94

Iontophoresis
Electrophoration
Sonophoresis

Back 94

Iontophoresis-low voltage pulses enhance transport of low MW molecules.
Electrophoration-high voltage pulses enhance transport of lrg chrged molecules by inducing temporary pores in membranes.
Sonophoresis-ultrasound enhances transport by temporarily forming air-filled cavitations in lipid bilayers of stratum corneum.

Front 95

Steady State Conc -
Time to acheive it?
Rate of drug admin =

Back 95

Plateau should fall in the therapeutic range
Normally acheived after 4-5 half lives
Rate of drug admin = rate of drug loss

Front 96

Loading Dose = Vd X Css

Back 96

Volume of distribution X desired steady state plasma conc

Front 97

Dose maintenence =

Back 97

Clearance X Desired steady state conc

Front 98

The _____ for a drug is a common measure of the extent of availability. It reflects the absorption, dist, metab, and excretion of the drug.

Back 98

AUC area under the curve

Front 99

Drugs with quaternary ammonium (ex curare) are very _______ and not _____ ___________ and will be poorly absorbed across cell membrane.

Back 99

Drugs with quaternary ammonium (ex curare) are very polar and not lipid soluble and will be poorly absorbed across cell membrane.

Front 100

Weak acids are predominantly __________ at acid pH.
Weak bases are predominantly __________ at basic pH.

Back 100

non ionized
non ionized
Weak acids tend to conc in regions of high pH, therefore, alkalinization of the urine increases the clearance of weak acids.

Front 101

What is peritoneal dialysis?

Back 101

An isotonic fluid is placed in the peritoneal cavity, then evacuated and replaced periodically.

Front 102

Blood Brain Barrier characteristics

Back 102

Only Lipid soluble can enter
TJx btwn endo cells
Fewer pinocytotic vessecles
Surrounded by pericytes and astroglial processes
More mito for transport energy
Produces 20-30% of the CSF volume

Front 103

Adrenal medulla, type of receptor, releasing epi and norepi

Back 103

Nicotinic

Front 104

First order elimination - (most drugs) a consistent fraction of the drug is eliminated per time period. When is the graph curved? When is it straight?

Back 104

First order is curved when plotted on rectilinear curve.
First order is straight when plotted on semilogarithmic Graph

Front 105

Zero order elimination - zero change in amt of drug eliminated per unit time (fixed amt) When is the graph curved? When is it straight?

Back 105

The graph is curved on a semiligarithmic and straight on a regular cartesian plot.

Front 106

Vd (volume of distribution)

Back 106

Amt of drug in body/conc of drug in plasma

Front 107

A fictitious volume, allows one to get a rough indication into which body compartment a drug is distributed.

Back 107

Volume of distribution
Plasma 4
EC volume 20
Total Body Water 60

Front 108

Warfarin is 99% bound to plasma proteins at steady state. Therefore only 1% is free and can

Back 108

only free drug can produce an effect

**Aspirin can displace warfarin from plasma proteins.

Front 109

T 1/2 =

Back 109

0.7 X Vd / CL

or

0.7 / Ke

Front 110

CL =

Back 110

0.7 X Vd / T 1/2 or

Rate of elimination / Drug plasma conc

Front 111

Dosing rate =

Maintenance dose =

Loading dose =

Back 111

CL X Target Conc

Dosing rate X Dosing interval

Vd X TC

Front 112

Initial conc =

Steady State conc =

Back 112

Loading dose / Vol of dist

(Frac abs X Maintenance dose) / (dosing interval X CL)

Front 113

Muscarinic Receptors
M1
M2
M3

Back 113

M1= cns & presynaptic autonomic ganglia
M2=Heart
M3=Sm muscle

Front 114

Nicotinic Receptors
Nm
Nn

Back 114

Nm=skeletal muscle
Nn= postganglionic autonomic neurons, adrenal chromaffin cells.

Front 115

Alpha Adrenergic receptors
alpha1
alpha2

Back 115

alpha1=postsyn effector cells, sm muscle
alpha2=presyn adrenergic nerve terminals, platelets, lipocytes

Front 116

Beta Adrenergic receptors
Beta1
Beta2
Beta3

Back 116

Beta1=heart
Beta2=postsyn vascular sm muscle
Beta3=lipocytes

Front 117

Which receptor starts the PIP2 (DAG, IP3, Ca, PKC) cascade?

Back 117

Alpha 1

Front 118

Which receptor(s) start the cAMP cascade?

Back 118

Beta 1&2

Front 119

Humanized antibody against C5, a complement protein that mediates late steps in complement activation and assembly of the membrane attack complex, specifically against C5.

Back 119

Eculizumab

(See 5 planes going to ecquador)

Front 120

associated with c-myc gene translocation. The most common variant is t(8;14)(q24;q32)

Back 120

8urkitt's 14ymphoma

(8,14)

Front 121

Type I pneumocytes

Type II pneumocytes

Back 121

Gas exchange

Production of surfactant

Front 122

Lung tissue b4 and after chronic smoking.
Esophageal tissue b4 and after chronic gastric reflux.

Back 122

Lung tissue will be columnar (to produce mucus) and will chg to squamous.
Esophageal tissue will be squamous and will chg to colomnar.

Front 123

A disorganized mass of mature cells or tissue indigenous to the site.

Back 123

Hamartoma

Front 124

An ectopic rest of normal tissue. ie normal tissue in the wrong place.

Back 124

Choristoma

Front 125

Less than complete differentiation

Back 125

Anaplasia

Front 126

Characteristics of benign neoplasms (5)

Back 126

Well differentiated
Slow Growing
Expansile masses pushing margins
Encapsulated
Remain Localized
Don't infiltrate or metastasize

Front 127

When will you see an increased nuclear to cytoplasm ratio?

Back 127

In malignant neoplasms

Invasion is the hallmark of malignancy. Most malignant cells are aneuploidy.

Front 128

The cell prepares for mitosis during which phase?

Back 128

G2

Front 129

List the order of the cell cycle

Back 129

G0
G1 S G2 M

Front 130

Inhibitors of microtubule function affect cells in ___ phase

Back 130

M

Front 131

Glucocortoids inhibit cells in the __ phase

Back 131

S

Front 132

Antimetabolites, and folate pathway inhibitors inhibit cells in ___ phase

Back 132

S

Front 133

Anti-tumor antibiotics inhibit cells in

Back 133

G2

Front 134

Topoisomerase inhibitors inhibit cells in ___ and ___ phases

Back 134

G2 and S

Front 135

Alkylating and platinum complexes affect cell function in ____ phase(s)

Back 135

all