Basic Science/Principles Flashcards
Antibio for leprosy that works in same way as sulphanomide
Dapsone
Which antibio inhibits p450 liver enzymes and causes drug interactions/toxicity?
Ciprofloaxacin
Common combo with sulphonamide
Trimethoprim
co-trimoxazole
Role of penicillin/beta-lactams
Inhibits a transpeptidation reaction involved in peptidoglycan utilization in the cell wall
Polymixin action
Disrupts bacterial membr in gm-bacteria
Ethambol and Isoniazid target … and … of mycolic acid
Incorporation and synthesis
Macrolide action
Binds to P-site, preventing the translocation step of the growing polypeptide chain
Clavulanic acid
Combo w beta-lactam antibios to inhibit beta-lactamase
Atypical pneumonia treatment
Azithromycin
Sulphonamide action
Inhibition of folic acid synthesis by acting as a p-aminobenzoic acid analogue
Why is metronidazole for anaerobics?
Only active when reduced by anaerobic cell enzymes
Why are cephalosporins useful in meningitis?
Penetrate blood-brain barrier well
Ototoxicity from which drugs?
Aminoglycosides e.g. gentamicin
Role of albumin
Regulates oncotic pressure of blood
Nine essential AAs
My (methionine) Tall (threonine) Handsome (histidine) Vegan (valine) Friend (phenylalanine) Is (isoleucine) Watering (tryptophan) Kale (lysine) Leaves (leucine)
Apolipo spec to chylomicrons
Apo B48
Where are bile salts formed?
Liver
From glycine or taurine
Role of NK cells
Recognise virus-infected/malignant cells without interacting w thymus
Cohort study vs case-control
Cohort -
Two groups are selected according to their exposure to a particular agent and followed up to see how many develop a disease or other outcome
Case-control - Compares a group with a disease to a group without, looking at past exposure to a possible causal agent for the condition
Immunoglobulin types
IgG - phagocytosis of bac/virus, passes to fetal circ
IgA - sweat and tears
IgM - first released
IgD - unknown role, activ B cells
IgE - least common, parasites, hypersensitivity
Metformin action
Activation of AMP-activated protein kinase (AMPK)
Fructose intolerance enzyme
Aldolase B
Noradrenaline binds to…
Alpha 1 receptors
Lincomycin action
Inhibit protein synthesis
Th1 vs Th2
Th1 - cell-mediated
Th2 - humoral
What happens to rate of excretion if you incr conc of drug in plasma kinetcs?
Rate is unchanged
Assoc gene in neuroblastoma
N-MYC proto-oncogene
Phases of drug metabolism
Phase I: oxidation, reduction, hydrolysis
Phase II: conjugation
What type of receptor do insulin and oestrogen bind to?
Insulin - tyrosine kinase receptor
Oestrogen - nuclear receptor
Down’s syndrome characteristics
Single palmar crease, prominent supra-orbital ridge, brush spots, slanted ears and hypotonia
Neurotransmitter in pre/post-ganglionic neurones
Symp - pre = ACh - post = NA Parasymp - pre + post = ACh
Order of potency of agonists in adrenoceptors
- ⍺-adrenoceptor: noradrenaline > adrenaline > isoprenaline
- β-adrenoceptor: isoprenaline > adrenaline > noradrenaline
Function of beta adrenoceptor subtypes
b1 - stim ad cyclase - incr HR and contraction force
b2 - “” - relax bronch/vasc SM
a1 - stim phospho C - contract vasc SM
a2 - “” - inhibit NA release
Muscarinic cholinoceptor functions
M1 - stim phos C - incr stomahc acid
M2 - inhib ad cyclase, opening of K channels - decr HR
M3 - stim phos C - incr saliva and visc SM contraction in bronch
Action of atenolol
Selective competitive B2 antagonist
angina, HT
Salbutamol action
Selective B2 antagonist
asthma bronchodila
Atropine action
Comp antag of musc ACh receptors
reverse bradycardia after MI and anticholinesterase poisoning
How does a G protein work when there’s no signalling?
- Receptor unoccupied
- ⍺ subunit binding site occupied by GDP
- Effector is not modulated
How does G protein receptor work with signal turning on?
- Agonist activates receptor, causing a conformational change
- G protein couples with receptor
- ⍺ subunit releases GDP and GTP binds in its place (guanine nucleotide exchange)
- ⍺ subunit dissociates from receptor and β𝛾 dimer
- ⍺ subunit and β𝛾 dimer are both signaling units
- ⍺ subunit combines with effector and modifies its activity
- Agonist may dissociate from receptor but signaling can persist because G protein and receptor are now separate
How does G protein receptor work in turning signal off?
- ⍺ subunit acts as an enzyme - hydrolyses GTP to GDP and Pi (signal is now off)
- ⍺ subunit recombines with β𝛾 subunit
Kinase-linked receptor
Hydrophillic protein mediators in plasma membrane that works in hour timescale
e.g. insulin
Nuclear receptor
Hydrophobic signalling molecules e.g. steroid hormones in nucleus/cytoplasm
Ligan-gated trans. factors
Driving force for Na (in) and K (out)
Na+ influx = Vm - ENa
K+ influx = Vm - EK+
Phases of membr potential
Resting potetial Depol stimulus to reach threshold Upstroke to overshoot (depol) Downstroke (repol) to undershoot (hyperpol) Resting
Depol vs repol vs hyperpol
D - opening of Na channels (pos feed)
R - closure of Na, opening of K (neg feed)
H - K remains open
WHat is saltatory conduction?
Action potential jumps from one node of Ranvier to the next
Pharmacology vs pharmakinetics
- Pharmacology: what a drug does to the body
- Pharmacokinetics: what the body does to a drug
Potency vs efficacy
- Potency: amount of drug required to produce a desired effect
- Efficacy: maximum response achievable from drug
EC50
Concentration of agonist that elicits half maximal effect
Phase 1 vs 2 metabolism
Phase 1: change in the drug by oxidation, reduction or hydrolysis
Phase 2: involve the combination of the drug with one of several polar molecules to form a water-soluble metabolite - conjugation
Drug that can go directly to phase 2
Codeine (pharmaco active metabolites)
Glucuronidation
- Enzyme - uridine disphosphate-glucoronosyltransferases
- Cofactor - uridine diphosphate glucuronic acid
Definition for fates of drug abs in body
Absorption: drug is absorbed from site of administration, entry into the plasma
Distribution: drug leaves bloodstream and is distributed into interstitial and intracellular fluids
Metabolism: drug transformation by metabolism - liver and other tissues
Excretion: drug and/drug metabolites excreted in urine, faeces or bile
pKa
pH at which 50% of the drug is ionized and 50% is unionised
HH equation
pKa = pH + log(AH/A)
What does lower pKa and higher Ka mean?
Stronger acid (lower pH)
pH trapping
Weak bases accumulate in compartments with low pH (+ reverse)
Apparent vol of distribution (Vd)
Vd: extent to which a drug partitions between the plasma and tissue compartments
- Low Vd = drugs retained in vascular compartments - High Vd = drugs retained in non-vascular compartments – adipose, muscle etc.
Effect of albumin on Vd
- Reduces the ability of the drug for diffusion to target organ
- May also reduce transport of the drug to non-vascular components
Factors influencing drug elim
Abs>elim before optimum conc (first order)
Abs
Clearance def
An expression of the elimination of a drug from the body - the volume of blood removed of a drug per unit time
CLR, CLH, CHO, CLT
Equation for CL
CL = rate of drug elimination/[D] plasma
Steady state
When rate of drug admin=rate of elim (R0=RE)
Elim half-life equation
t½ = (0.693 x Vd)/CL
Gm + vs gm -
Gm + thick peptidoglycan, purple
Gm- thin peptidoglycan, pink
What are biofilms more resistant to?
Antimicrobials
Aerobes vs anaerobes
- Aerobic: grow in oxygen
- Obligate aerobes: require oxygen
- Obligate anaerobes: killed by oxygen
- Facultative anaerobes: tolerate oxygen
Coagulase vs haemolysis
Coag - stah aureus (+) vs - staph
Haemolysis - diff between strep
Why do gm - sepsis patients deteriorate so quickly?
Gram-negative sepsis get very unwell very quickly due to endotoxin released when Gram-negative bacteria die
Process of fever
- Antigen/LPS interacts with macrophages
- Macrophages release cytokines into bloodstream
- Cytokines travel to anterior hypothalamus
- Prostaglandin E released - increases body’s thermal set point
- Body perceives it as cold - starts to ‘shiver’
- FEVER
Examples of each bac type
Gm- cocci - neisseria men and gonn
Gm+ cocci - strep, GAS, staph epi and aureus, enterococcus, clostridium
Symmetry of viruses
- Icosahedral symmetry: virus consists of repeated subunits that make up equilateral triangles arranged in a symmetrical fashion
- Helical symmetry: made up of a single repeated unit
Process of viral infection
Replication Attachment ENtry Uncoating NA and protein synth Assembly Release
How do they become resistant?
Genetic mutation
Transfer of bac DNA (transformation, conjugation, transduction)
Empirical antibios
- Staph aureus: flucloxacillin IV
- Staph epidermidis: vancomycin IV
- Strep pyrogenes: doxycycline
- Gram negatives: clindamycin
- Anaerobes: metronidazole, cotriomazol
Mechs of resistance to antibiotics
Altered binding site
Destruction of antibio (ESBLs*****)
Incr efflux
Bacteriostatic vs cidal
- Bacteriostatic: inhibit growth of bacteria
- Bactericidal: kill bacteria
ANtibiotics acting on cell wall
Penicillins (fluclox, amox)
Cephalosporins (cefaclor, cefadroxil)
Glycopeptides (vancomycin)
Antibios inhibiting protein synth
Macrolides (erythro, azithro)
Aminoglycocides (gentamicin)
Clindamycin, tetracycline, cholarmphenicol
Antibios on bac DNA
Metronidazole
Trimethoprim
Fluoroquinolones - c diff (ciprofloxacin, levofloxacin)
Cell cycle
G1
S (DNA synth)
G2
M
SNPs and CVNs
SNP - single nucleotide polymorph, most have no effect
CVN - extra/missing stretches of DNA; deletions or duplications
Unbalanced chromosome rearragement
- Extra or missing chromosomal material, usually 1 or 3 copies of gene
- Causes major developmental problems
Aneuploidy
Whole extra/ missing
X chromosome is better tolerated
Monosomy - lack of one
Trisomy - 3 copies (trisomy 21 - downs)
Turner’s
Female w only one X
Specific aneuplodies
- 47XY +21 (trisomy 21) - Down’s syndrome
- 47 XY +14 (trisomy 14) - miscarriage
- 47 XY +18 - Edward syndrome, trisomy 18
- 45 X - Turner syndrome
- 47 XXY - Klinefelter syndrome
Somatic mosaicism
Two genetically distinct populations of cells within an individual, derived from a post-zygotic mutation
Robertsonian vs reciprocal
Rob
- Two acrocentric chromosomes stuck end to end
- Increased risk of trisomy in pregnancy
Recip
- Two broken off chromosome pieces of non-homologous chromosomes are exchanged
Gene analysis tests
aCGH - 1st line, detects missing/dup chroms FISH - fluorescent probs PCR - amp small piece Whole genome seq - all exons Genetic filter
Types of mutations
Missense (change to single AA, most likely activate oncogene)
Change to AA seq
Insertion/deletion (frameshift)
Promoter and splice site change
How is mitochondrial disease transmitted?
Mitochondrial DNA is transmitted maternally, in the ovum
How is mitochondrial disease transmitted?
Mitochondrial DNA is transmitted maternally, in the ovum
DNA methylation
- Usually occurs on cytosine bases just before guanine bases
- Prevents transcription (leads to modification of histones)
How are proto-oncogenes activated?
Point mutation (BRAF) AMplification (HER2) Translocation (Philadelphia)
Lynch syndrome
Hereditary form of cancer due to mutation in mismatch repair gene
Incidence vs prevalence
- Incidence rate: (number of NEW cases of a disease occurring in a population during a specific time period/number of persons exposed to the risk of developing the disease during that time period) x 1000
- Prevalence rate: (number of cases of a disease present in a population at a given time/number of persons at risk of the disease at that point in time) x 1000
Cytokines
- Interferons released by virally infected cells signal to neighbouring uninfected cells:
- Destroy RNA and reduce protein synthesis
- Undergo apoptosis
Macrophages and mast cells
Macro - Phagocytose bacteria
Mast - deal w pathogens too large for phagocytosis
Transendothelial migration
Recruitment of neutrophils to the site of infection/damage during acute inflammation
Killing pathogen mechanisms
- Phagocytosis: phagolysosomal killing (like macrophages) via production of reaction oxygen species (ROS)
- Degranulation: release of anti-bacterial granules
- NETs: release of a net-like structure that traps pathogens, leading to phagocytosis
Pinocytosis
ingestion of fluid of surrounding cells
Acute phase proteins
- C3 - involved in complement
- CRP - activates complement via classical pathway (incr in inflam)
- MBL - activates complement via MBL pathway
Classical pathway activated by which Ig
IgM and IgG
What signals do B cells require to become active and proliferate?
Antigen
Helpr signals
T cell types
- CD4+ Helper T cells: activate B cells & stimulate production of memory B cells
- CD8+ Killer T cells: kill infected cells via perforin/granzymes/granulysin
- Regulatory T cells: lymphocyte suppression
- Memory T cells: involved in the adaptive immune response
Class 1 and 2 MHC
- Class I MHC: expressed on all nucleated cells, present peptide antigens to CD8+ killer T cells
- Class II MHC: expressed only on antigen presenting cells (e.g. dendrites, macrophages), present peptide antigens to CD4+ helper T cells
CD4+ cells and CD8+ cells diff into which cells?
CD4+ T cells → T helper cells
CD8+ T cells → CTLs (TC cells)
Fick’s law of diffusion
- ↑ concentration gradient (𝝙C) = ↑ rate of diffusion (Q)
- ↑ surface area of membrane (A) = ↑ rate of diffusion
- ↑ lipid solubility = ↑ rate of diffusion
- ↑ molecular weight of substance = ↓ rate of diffusion
- ↑ distance (thickness) = ↓ rate of diffusion
Fick’s law of diffusion
- ↑ concentration gradient (𝝙C) = ↑ rate of diffusion (Q)
- ↑ surface area of membrane (A) = ↑ rate of diffusion
- ↑ lipid solubility = ↑ rate of diffusion
- ↑ molecular weight of substance = ↓ rate of diffusion
- ↑ distance (thickness) = ↓ rate of diffusion
Secondary active transport
- Symport: solute and Na+ move in the same directio
- Antiport: solute and Na+ move in opposite directions (Na+ in, solute out)
Exo vs endocytosis
- Exocytosis: vesicle fuses with plasma membrane, releasing its contents to the ECF
- Endocytosis: ‘pinching off’ of membrane to engulf substance
Exer vs endergonic reactions
Exer - Total free energy of products is less than total free energy of reactants
Ender - Total free energy of products is more than total free energy of reactants
When does pH = pKa?
When the concentration of acid is equal to the concentration of the conjugate base
Structures of RNA and DNA
- Nucleoside: base and 5 carbon sugar
- Nucleotide: nucleoside and phosphate group
- Purines: adenine and guanine
- Pyrimidines: cytosine, thymine, uracil
- Phosphodiester bonds: form between 3’ OH group and 5’ triphosphate, link nucleotides
How is DNA synthesised?
5->3 direction
Stages of translation
Initiation
Elongation
Peptide bond formation and translocation
Termination
Apo vs holoenzyme
- Apoenzyme: enzyme without cofactor (metal ion req)
- Holoenzyme: enzyme with cofactor
Michaelis-Menten Kinetics
- S: solute concentration
- V0: initial rate (velocity) of reaction
- VMAX: the maximum rate of reaction when all enzyme active sites are saturated with substrate velocity
- Km (Michaelis constant): the substrate concentration that gives half maximal velocity
Km = ?
Km = [S] at 0.5(VMAX) Km = (k-1+k2)k1
Low Km (only need little substrate to work at half max velocity and vice versa)
k1, k-1, k2
- k1 = forward rate for enzyme association with substrate
- k-1 = backwards rate for enzyme dissociation with substrate
- k2 = forward rate of enzyme conversion from energy to product
Control points of glycolysis
Phosphofructokinase
Glyceraldehyde 3-phosphate
Pyruvate kinase
H+
Warburg effect
Cancer cells produce energy by high rate of glucose metabolism to lactate - anaerobic glycolysis
(low Km hexokinase)
How is NAD regenerated?
Krebs cycle
Stages of TCA cycle (krebs)
- pyruvate enter
- pyruvate -> acetyl coA
- acetyl coA + oxaloacetate -> citrate
- citrate decarboxylated twice (yields 2 CO2)
- 4 ox reactions to yield NADH, H, FADh
- GTP formed
- oxaloacetate reformed
What is generated from each acetyl-coA?
- 3 NADH + H+
- 1 FADH2
- 1 GTP
- 2 CO2
Per glucose how many NADH etc are yielded?
- 10 NADH and 10 H+
- 2 FADH2
(eac one has 2 high energy electrons for ETC/ox phosph)
Process of oxidative phosph
- resp chain where electrons are handed down incr pos potentials (O2 is final accepto -> H2O)
- coupled to H transport from matrix
- 4 resp complexes pump H into IM space
- H flows back into matrix through ATP synthase
Inhibition of ox phosph
Cyanide
Azide
CO
How many ATP?
Net 30-32 from ETC
Types of plasia
Dys - abnorm growing w/o stm
Meta - reversible change between cell types
Hyper - incr in number from stim
Hallmarks of cancer
- Resisting apoptosis
- Sustained proliferative signaling
- Evading growth suppressors
- Activating invasion and metastasis
- Inducing angiogenesis
Stage vs grade in caner
Stage - how far
Grade - how bad
Mechs of disease mnemonic
VINDICATE
Types of necrosis
Coag - MI
Liquefactive - Bac/fung/brain
Caseous - TB
Cell changes in resp to injury
Stasis Margination Rolling Adhesions Transendo migration
What are the 4C antibiotics most likely to cause C. diff?
Co-amoxiclave
Clindamycin
Ciprofloxacin
Cefuroxime
Which immunoglobulin is transported across placenta for foetal immune protection?
IgG
Group A strep shows what type of haemolysis?
Complete haemolysis
Function of oligodendrocytes
Secretion of insulating material in CNS
