Christmas Exam bits & pieces Flashcards
Define a tumour
An abnormal growing mass of tissue, growth is uncoordinated with surrounding tissue & continues after the external stimulus is removed
What is the prefix for glandular epithelial tumorus?
Adeno-
What do we call Epithelial malignant tumours?
Carcinomas
What is differentiation like in benign/malignant tumours?
Benign are well differentiated
Malignant tumours are poorly differnetiated
What are the 2 types of neural malignant tumour?
Astrocytoma in the CNS
Schwannoma in the PNS
How does invasion work?
multi-step process
Proteolytic enzymes degrade ECM
Cells lose cell-cell & cell-matrix adhesion
What are the 4 types of Tumour spreaD?
Lymph
Blood
Local
Trans-coleimic
Examples of a diagnostic tumour biomarker:
ALpha-fetoprotein
Marker for hepatocellular carcinoma & Testicular Teratoma.
Common metastasis sites:
- Axial Skeleton
- Adrenal Gland
- Liver
- Lung
- Brain
Example of a predictive biomarker:
OEstrogen receptors are monitored in breast cancer as theyre prescence/type can indicate the specific type of cancer & therefore the best treatment
Common metastasis for breast, prostate & colorectal cancer?
Breast/Prostate -> Bone
Colorectal - > Liver
Whats the abnormal morphology of cancer cells speciically?
Cellular & Nuclear Pleomorphism
MArked difference in cell & nucleus size/shape
Dysplasia?
Uncontrolled growth of abnormal cell type
Characteristics of Dysplasia:
- Graded (high/low)
- Disorganised (Increased nuclear size & mitotic activity + abnormal mitosis)
- No invasion
Example of abnormal hormone secretion by a tumour?
Lung Carcinoma can secrete ADH & ACTH
Systemic effects of malignant tumours:
Weight loss cachexia
PAraneoplasstic syndrome
Abnormal hormones
Treatments effects
Causes of pain in cancer:
Commonly:
= Perineural infiltration
- Pathological fractures
- Ulceration/haemorrhage
External stimuli/inhibitors of cell growth:
- Growth facors
- Hormones
- Cytokines
Define cell cycles?
Time between mitotic division
3 types of enviromental carcinogens?
Radiation
Chemical
Oncogenic viruses
How do enviromental cacinogens cause cancer?
- Radiation mutates bases
- Chemical binds to DNA fomrming adducts which eventually causes oncogenesis
- Oncogenic viruses either isnert oncogenes into cells ( Retrovirals) or viral promoters cause proto-oncogene overexpression
Difference between inherited & sporadic oncogenesis?
Inherited involves being born with atleast one mutated allele
Sporadic involves both hits occuring as sporadic point mutations
Difference between inherited cancer syndromes & familial cancers?
- Inherited is autosomal dominent of a single mutant gene
- Familial has multifactorial inheritence with no clear predisposing gene
Some inherited/ familial cancers:
Inherited - MEN, FAP, Familial retinoblastoma
Familial - Some breast/ovarians
How do proto-oncogenes becomeoncogenes?
Overexpresssion or mutation
Some common oncogenic viruses and their cancers?
HEP B - > LIver
EBV and herpes -> Burkitts lymphoma
HPV -> Cervical
What is the henderson-hasselbach equation and what do we use it for/
pH = pKa + log10 (conjugate base/unionised acid)
Determing the relationship between local pH and a drugs ionisation
What 4 thins affect bioavailiabilty & what is it?
Bioavaliability is the amount of drug reachin the systemic circulation acitive and useable.
- GI factors
- Ability to cross physiologicak barriers
- Formulation
- First Pass MEtabolism
How do GI factors affect bioavailability?
Increased gut motility improves time to the site of absorption
Food & diseases can both impair/enhance the amount of drug absorbed
How does fomrulation affect bioavailiabitly?
Some durgs are slow-release formualtions
What effects a dugs ability to cross barriers?
- Ionisation/pH
- Lipid solubility
- Particle Size
What is taken up by Active transport?
- Levidopa in brain (for parkinsonism)
- Iron
- Calcium
- Sodium
- Potassium
What is taken up by facilitated diffusion?
- Monosacchrides
- AMino acids
- Vitamins
What drives filtration/bulk flow?
Hydrostatic and/or osmotic pressure
What is the aparent volume of distributio?
Vd
Volume is which a durg needs ot be distributed to produce observed blood conc.
What does an increased Vd tell us?
The drug is better at crossing membranes
What is drug clearence?
Cl
Volume of fluid cleared of drug every unit time
e.g. ml/min
What is clearnece dependant on?
Renal clearence - Conc. urine flow rate
Hepatic clearence - Metabolism & biliary excretion
Where does most drug excretion occur?
Kidneys
What other places can du excretion occur?
- lung
- milk
- liver
yadda yadda
What are the 3 types of renal excretion emchanisms?
- Active tubular secreiton
- Passive tubular reabsorbtion
- Glomerular filtraion
What occurs in active tubular secretion?
Acid/alkali drugs (often protein bound) are secreted into urine
What occurs in passive tubular reabsorption?
Small unionised drugs are reabsorbed into circulation
What occurs in Glomerular filtration?
All unbound drugs are filtered from the blood and excreted
How does the liver deactivate metabolsied drugs?
by conjugating them
What happends to non-conjugated drugs after theyre secreted into bile?
Theyre reabsorbed (entero-hepatic cirulation)
What happens to conjugated drugs secreted into bilE?
They cant be reabsorbed so they are shat out
What effects bound drug levels?
- Renal failure
- Hypoalbumineia
- Pregnancy
- Other drugs
- Sturability of bindin
What affects tissue distribution of drugs:
- Plasma binding protein
- Membrane characteristics
- Tissue perfusion
- Transport mechanisms
- ELimnation
- Siseas/otherdrugs
What would make a drug unable to be filteerd out at the glomerulus?
LArge particles or large charges
Whats the difference in metabolism at different ages?
Infants have reduced renal funciton & fewer enzymes
Pubescent kids have the highest metbolic rate of all ages
Waht 3 reactions could occur in phase 1 metabolism?
Hydrolysis
Oxidation
or reduction
What is the purpose of phase 1 metabolism?
To increase polrity & provide ana ctive site for phase 2
What family of enzymes act in phase 1 and examples:
Cytochrome P-450s
CYP1A2
CYP3A4
CYP2D6
What CYP1A2 metabolize?
Theophylline
What does CYP2D6 metabolixe? What about CYP2C9
Cyp2d6;
- Anti-depressents
- Anti-psychotics
- Codeine->morphine
Vs Cyp2c9 :
-warfarin
Which cytochrome p-450s are smoking induced
CYP1A2
CYP2D6
Where is CYP1A2 found?
Liver
Some common enzyme inhibitors?
Grapefurit
Clarythromycin
Erythromycin
What occurs in phase 2 metabolism?
Conjugation
Makes drugs more water soluble & inactive
What are common conjugates in phase 2 metabolism?
GLucuronic acid
Glutathione
Suplahte
Acetate
How does metabolism vary between race?
Races have different Cytocrhome P-450 expression
How does pregnancy affect metabolism?
in 2nd/3rd timerseter hormonal changes induce enzymes
What drug do we enteric coat to protect itt form the stomach?
Omeprazole
Why do enteric coated drugs survive the stomach?
They only break down in high pHs like small intestine
What delivery modes are prolonged release
- Intramuscular
- Subcutanoues Pellet
- Tablet
What has a systemic effect in inhalation?
Inhalation anesthetics
What kind of drugs are Intramuscular?
Insoluble or formulated in an oil base
How Many inpateitns suffer ADRS?
Admissions are ADR relateD?
hospital deaths are due to ADRS?
- 10-20% of inpatients
- 6.5% of admission
- 0.2-3% deaths (5-10k/yr)
Examples of TYPE A ADRs?
Beta-blockers causing bradycardia
Insulin causin hypoglycaemia
Examples of Type C ADRs?
long term Excess cortisol causing iatrogenic cushings
Examples of Type E ADRs?
Stopping Beta blockers causing unstable angina/Myocardial infarction
Examples of Type D ADRs?
Isotretinoin causing kids born with craniofacial deformation
What do loop diuretics do?
Increase tubular reabsorbtion
What are the characteristics of the most serious drug interactions?
Drugs involved have:
- Steep dose-respponse curves
- Narrow therapeutic indexes
- Very high protien binding
- Can affect renal function
- Induce/inhibit hepatic enzymes
How do drug interactions affect absorption?
- Insoluble complexes
- Alter pH cauing ionisation
- Affect gut motility
- Alter gut bacteria
What proto-oncoene is mutated to cause MEN2?
The RET gene
What mutation predisposses you to breast/ovarian canceR?
Tumour supressor genes BRCA1 & BRCA2
wHAT KIND OF defect leads to HNPCC?
Defective DNA repair genes
What mutation cuases colon cancer?
- APC tumour supressor gene (adenomatous polyposis COli)
What can a Kras mutation cause?
Lung cancer
Or Colorectal cancer if following an APC mutation
What shapes does the secondary protein struction take?
Alpha helices
Beta-pleated sheets
What bonds stabilise protein alpha helixes?
H bonds between CO & NH in adjacent turns
What bonds stabilize protein beta-pleated sheets?
H bonds between amide groups
What do hydrophobic interactions need?
A water free enviroment internal to the protein
What do disulphide bridges bind?
Cysteine residues
Caues of protein denaturation?
- Acid
- Heat
- Chaotrophic agents (Urea)
- Cross-linking reagent (Formaldehyde)
- Disulphide-Bond Reducers (2-mercaptoethanol)
Where does glycosylation occcur?
Endplasmic Reticulum
Golgi Apparatus
Main glycoproteins?
Immunoglobulins
Using of metalloproteins?
- Storage
- Transport
- Enzymes
- Signalling
What change in proteins causes sickle cell anaemia?
Hydrophilic glutamte is replaced by hydrophobic valine
What causes scurvy?
Vitamin C deficiency
Less STable collagen cross links
Weaker collagen
What does osteogenesis imperfecta cause?
Amino acid substitution
Collagen polypeptides cant coil tightly
Loses secondary/tertiary strucutre
Weak/brittle collagen
What does an LDL receptor mutation cause & how?
Familial Hypercholesterolemia -> early cardiovascular disease
The cells have a glycoprotein LDL receptor that detects apoB, when its mutated LDL cant be internalized. This leads to an excess in the blood.
Whats the difference between central & peripheral tolerance?
Central tolerance involves destroying auto-reactive lymphocytes in the primary lymhoid organs
Peripheraltolerance involves inhibiting auto-reactive lymphocytes that slip thorugh central tolerance
Whats the difference between +ve & -ve selection in T cell educaiton?
Positive selection removes an T cells that ail to recognize MHC1
NEgative selection removes any T cells that recognise & bind to self-antigen
What are the 5 chemo drugs?
SPindle poisons - Vinca Alkaloids & taxanes
Alkylating Agents
Anitmitotic antibiotics
Anti metabolites
How do vinca alkaloid work?
They bind to tubuli preventing microtube/spindle formation, this arrests mitosis at the metaphase
How do taxanes work?
Taxanes inhibit spindle dissaelmbly, freezing the cell at that stage
How do alkylating agents wokr?
The alkyl group causes DNA to cross link between free guanines in adjacent strands at the N6 level preventin unzipping
At what stages of the cell cycle do alkylating agents work?
All of them
What are the 2 types of antimitotic antibiotic?
Anthracycline or non-anthracyclines
How do antimitotic antibiotics work?
- Metal ion chelation produces cytotoxic agents
- Increasing the membrane permeability to ions
- Alkylation
Hw do anti-metabolites work?
- Nucleoside analogues stop DNA synthesis
- Some bind ireversibly to viral enzymes
What can we taret in targeted cancer treatments?
Epidermal growth factor receptor (EGFR)
Vascular Endothelial Growth Factor (VEGF)
What do we target VEGF with?
aVastin
What do we target EGFR with?
Erlotinib E for E 💋
What drugs can be used to target hormones in breast & prostate canceR?
Prostate - Anti-androgens like CPA
Breast - Anti-oestrogens like tamoxifen & aromatase inhibitors
What is cystisis?
Bladder inflammation
What is myelosuppresion?
Bone marrow suppression
Hair loss?
Alopecia
Phlebitis?
Clots causing vein inflammation
What food are linked to cancers?
Red meat to CRC
Saturated fat to breast cancer
What are the 5 Rs of radiology?
Radiosensitivity Repair Re-population Re-oxygenation Re-assortment
Is hormones therapy treatment or prophylactic?
Both
What re the 4 stages of staging?
Examination
Imaging
Genomics
Classification
Do cancer cells have contact inhibition?
No they lose it when they beocme malignant
What are the most common chemical carcinogens?
SMoking & alcohol
What chemical carcinogen causes liver cancer?
Aflatoxin in peanuts
What are the initiation, promotion, progression stages?
Inititation is a carcinogen induced mutation
PRomotion is growth promoted by oncogenes, mutant anti-oncogenes & growth factors
Progression is spread
What ways does ionising radiation cause cancer?
- Translocates chromosomes
- Amplifies certain genes
- Activates oncogenes
When are tumour supressor genes normally activated?
By DNA damage or hypoxia
What would you use to treat an unkown gram -ve infection?
Gentamicin
WHat would you use to treat a Staph. Aureus strain thats producing B-lactamasE?
Flucloxacillin
Whats the best IV treatment for serious pneumococcal, meningicoccal & strep. Pyogene infections?
IV Benzyl Penicillin
What is ciprofloxacin?
A flouroquinolone that inhibits nucliec acid synthesis
Which DNA analysis system doesnt need an electric field?
PCR
In what direction do strands form in DNA replication?
5’ to 3’
What enzymes form new DNA strands & which bind okizake fragments together?
DNA polymerase forms DNA
DNA ligase binds okizake fragments
(more are involved)
Does mitosis involve recombination?
It can but not always
What does nitrofurantoin treat?
Just UTIs
What are the main eukaryotic histones
H1, H2A dimer, H2B dimer, 2x H3, 2x H4
Which eukaryotic histoens isnt the DNA wrapped around?
H1
What do you use to treat all chlamydia infections?
Azithromycin (macrolide)
What would treat Chlamydia psittacci, Coxiella burnetti and Mycoplasma pneumoniae
Erythromycin
Clarithromicin
Levofloxacin
Treating pseudomonas?
Ciprofloxacin
Describe cephalosporin generations
Gram -ve activity increase from 1st generation to 3rd
Gram +ve activity increases from 3rd to 1st generation One of the 4Cs!
(examples of cephalosporins- Cephradine, cefuroxime, ceftriaxone [1st-3rd generation])
Name a first gen cephalosporin
Cephradine
Gram +ve
Name a 2nd Gen cephalosporin
Cefuroxime
Even
NAme a 3rd gen cephalosporin
Ceftriaxone
Gram -ve
What are the 4 Cs that cause C.diff infection?
Cephalosporins
Clindamycin
Ciprofloxacin
Co-Amoxiclav
What commonly causes pseudomembranous colitis?
Clindamycin
