ila Flashcards
2 main paired arteries supplying brain. arise/ascend where
vertebral, internal carotid
arise neck, ascend to cranium
make up CoW?
anterior cerebral anterior communicating internal carotid inferior communicating inferior cerebral
where ICA’s originate?
bifurcation of R&L common carotid at C4
where vertebral originate
subclavian arteries
why stroke symptoms contralateral
somatic and sensory nerve fibres to and from peripheries decussate @ spinal cord or brainstem (lesion in cerebral cortex on opposite side)
cause of amaurosis fugax
stenosis of central retinal artery or ICA
TIA lasts ? it has temporary focal ischaemia but no?
24hr then resolves, no infarction
how AF leads to TIA and most common place
fibrillating atria = stasis/pooling of blood = increased chance of clot formation
auricular appendage
pre central gyrus functions
motor
post central gyrus functions
sensory
increased icp triad name and components
cushings reflex:
bradycardia
hypertension
erratic breathing
explain why cushings reflex happens
icp increase, greater than arterial BP so supply is squashed and brain not perfused properly. alpha 1 adrenergic response, smooth muscle contract to re-perfuse = bp increases, baroreceptors detect this HPN and muscarinic responds by reducing HR. this presses on brainstem leading to resp centre dysfunction and irregular breathing
how does TIA lead to increased ICP
necrosis and ischaemia causes inflam response
odema in brain = extra fluid in cranial cavity
define pharmacokinetics
effect of body on drug
define pharmacodynamics
effect of drug on body
define bioavailability
total proportion of drug which reaches target location/can act on target
define first pass metabolism
drug is extracted/metabolised by gut wall and liver so not all drug makes it into systemic circulation
4 medical ethics
autonomy
beneficence
justice
non-maleficence
function of central nervous sys
spinal cord and brain
function of peripheral nervous system
connect organs and muscles to CNS - branches into somatic and autonomic
function of somatic nervous system
motor control of skeletal muscles
function of sympathetic nervous system
fight or flight
function of parasympathetic nervous system
rest and digest
function of autonomic nervous system
motor control of internal organs - branches into PNS and SNS
sympathetic system - what the neurons release and name of receptor
acetylcholine and norepinephrine, adrenergic receptor
parasympathetic system - what the neurons release and name of receptor
acetylcholine x2, muscarinic receptor
define agonist drug
binds to receptor and activates, mimics endogenous substance
full = same response
partial = partial response
define antagonist drug
binds to receptor and prevents its activation
competitive - binds to active site
non-competitive - allosteric site elsewhere
define efficacy of drug
how much of a response/how well it works on receptor
define potency of drug
how much of a drug is needed to elicit response
enteral administration
via gi tract eg. oral, rectal, sublingual
par-enteral administration
not gi tract eg. IV IM SC inhale
local administration
eg. topical, eye drops, intranasal
3 aspects that affect rate/effectiveness of absorption
surface area, pH, perfusion (reduced in shock)
absorption:
water sol drug
lipid sol drug
larger molecule drug
water - diffusion
lipid - cross phospholipid membrane
larger - facil diffusion, ATP-dependent, endocytosis
why is IV faster
directly into bloodstream so no membrane crossing or first pass metabolism (100% bioavailability)
distribution effectiveness depends on…
blood flow to area
permeability of capillaries (lots of slit junc in liver but less in brain so harder)
binding to proteins (drug travels bound, eg. to albumin which makes it slower, but must be free to cross membranes hence anaesthesia needing a low affin for prot)
lipophilicity (lipophilic drugs penetrate membrane easily hence anaesthesia needs to be lipid soluble)
if drug has high vol of distribution then…
more drug in tissues than in plasma so higher conc required
how does liver help kidney in drug metabolism
kidney cannot excrete/eliminate lipid soluble drugs
liver metabolises them first
2 phases of liver metabolism (and what might interfere with it)
phase 1: make drug hydrophilic using cytochrome p450
phase 2: if too lipophilic, make polar = acetylation by adding glutathione
altered by alcohol, inducer which increases Cp450 eg. phenytoin, inhibitor which decreases it eg. ciprofloxacin
what may inducers and inhibitors of cp450 result in
inducer = sub-therapeutic dose inhibitor = toxicity
where are drugs excreted
most excreted in liver
doses/drugs altered if renal failure
some excreted by liver in bile then faeces
treat paracetamol overdose if acute liver injury and overdose within last 8 hrs
IV N-acetylcysteine
describe phase 2 metab of paracetamol
para conjugates with glucuronide sulfates
excreted in urine
describe phase 1 cytochrome p450 metab of paracetamol
becomes NAPQI - highly reactive intermediate metabolite
this is conjugated with glutathione to make it non toxic
what happens to metab pathway in paracetamol overdose
phase 2 pathway becomes saturated/overwhelmed so more paracetamol shunted to phase 1 reaction leading to increase of NAPQI
Glutathione available is overwhelmed and NAPQI remains in liver where it reacts with cellular membrane molecules = hepatocyte damage = acute liver necrosis
treat paracetamol overdose if staggered over 1 hour
base treatment off paracetamol levels and further blood tests
if severe liver damage from paracetamol overdose
acidic blood, high blood lactate, poor clotting, hepatic encephalopathy = liver transplant
side effects of NSAIDs
GI upset, GI bleeding, renal impairment
side effects of anti-histamines
older ones can cross BBB and cause sedation
anti emetics bc H1 receptors in vom centre too
side effects of beta 2 agonist
can agonise b2 receptors in other tissue eg. sweating, tachycardia
side effects of ACE-I
dry cough due to bradykinin
dilates afferent glom arteriole so worsens kidney function
side effects of PPI
prolonged use in elderly can incr fracture risk
side effects of opioids
resp depression - give naloxone
n&V, constip, addiction, withdrawal
side effects of diuretics
hyperkalaemia
increased freq and dehydration
define zero order
enzymes saturated by high drug doses, rate of metabolism is constant
define first order
catalysed by enzymes, rate of metabolism directly proportional to drug concentration
high blood flow organs
brain heart kidney liver lungs
if site of action here then redistribution = termination of drug action
why is additional drug given to maintain anaesthesia
Well perfused tissues will receive drug first, lowering overall plasma conc
If a second anaesthetic agent is not given then as the plasma concentration of drug decreases the patient will start to wake up
what is thiopentone and how does it work
ultra-short acting depressant of the CNS
due to high lipid solubility, can cross blood brain barrier and membranes
distrib rapidly to highly perfused areas
continued muscle uptake lowers the blood concentration & indirectly the brain concentration
therefore fast recovery from drug
4 drug targets
receptors, ion channels, enzymes, carrier molecules
score for DVT assess
well’s score
suspected DVT, what is performed first
within 4hrs US doppler
if not then d dimer and LMWH, then US doppler within 24 hrs
arterial thrombosis signs
pulseless pallor perishingly cold paraesthesia paralysis pain
3 long term treatment DVT
warfarin - vit k antagonist
DOAC
LMWH
purpose of coag cascade
maintain haemostasis by repairing damaged vessel to prevent blood loss
primary haemostasis forms
unstable platelet plug at site of injury, then coag cascade activated
heparin mechanism
catalyzes the inactivation of thrombin
warfarin mechanims
vitamin k antagonist - inhibs synthesis of CF 10 9 7 2
prolongs prothrombin time
doac mechanism
direct acting oral anticoagulant
increases activity of endogenous antithrombin
high creatinine suggests…
kidney disfunction
define GFR
vol of fluid filtered from glomerulus to bowman’s space
AKI ECG findings
tall tented t waves
wide QRS
PR elongation
flattened p wave
which drug CI in AKI
NSAIDs - nephrotoxic med
3 classes of AKI
pre renal - inad blood supply to kidney, dehydration, hypotension, hf, low bp
renal - damage to kidney
post renal - blockage in urinary tract, tumours, renal stone
change in AKI symptoms with hydration
HR reduced, BP increased
how does insulin correct hyperkalaemia in AKI
stimulates activity of sodium ATPase pump = k+ into cell
insulin also reduces glucose so dextrose given to compensate
atherosclerosis and complications?
fatty deposit, hardening of arterial wall
chronic inflam/activation of immun sys
plaque rupture - thrombus can cause ischaemia
define stenosis
narrowing/reduction of blood flow
qrisk 3 >10% score …
start atorvastatin
secondary prevention 4a’s for athersclerosis
atorvastatin
aspirin
atenolol
ACE inhib
3 layers of vessel wall and constituents
adventitia - connective tissue layer, contains: CT, elastin, vaso varum (blood supply to vessels), nerve fibres
media - smooth muscle, external elastic lamina
intima - endothelium, basement membrane, internal elastic lamina
atheroscle: LDL conc inside lumen higher than inside lumen…
LDLs infiltrate damaged/altered endothelium deposits in tunica intima and becomes oxidised, trapping them in intima
prim, secon, preventions of atherosclerosis
- prevent disease: exercise, reduce red meat
2. prevent progression of disease: aspirin, atorvastatin, atenolol, ACE inhib
co benefit def and example
change to peoples life that will benefit climate and health
eg. walk instead of drive
non mod RF for atherosclerosis
1st degree fam hist, old age, race - south asian, male
mod risk factors for atherosclerosis
poor sleep, stress, sedentary, smoking, high chol diet, obese
atheroscle: trapped oxidised LDLs in intima activates what?
endothelial cells to express receptors on luminal surface. WBC adhere to these receptors allowing monocytes and THC from blood to also penetrate and differentiate into macrophages
atheroscle: what do macrophages do once in intima
engulf LDLs = foam cells
these cells promote migration of smooth muscle cells from media to intima via IGF-1
and promote smooth muscle cell proliferation
=intima growwwwwsss
atheroscle: what does increased smooth muscle cells do in intima
increases synthesis of collagen by fibroblasts = plaque hardens
atheroscle: what happens when foam cells die (apoptosis)
DNA material attracts neutrophils and pro inflam cytokines = inflam in plaque area
lipid content moves into plaque and grows it which increases pressure and leads to rupture
atheroscle: what happens when plaque ruptures
coag cascade occurs to stop plaque entering lumen = thrombus forms = impedes blood flow
triggers of anaphylaxis
flucloxacillin peanuts pollen mould bee stings shellfish plasters/latex
symptoms of anaphylaxis
SOB low o2 SATS high resp rate wheeze low bp high hr distressed itching
type 1 hypersensitivity reaction
Classical allergy, mediated by the inappropriate production of specific IgE antibodies to harmless antigens
type 2 hypersensitivity reaction
Caused by IgG and IgM antibodies that bind to antigens cells or tissues leading to cell or tissue damage
type 3 hypersensitivity reaction
Caused by antibody-antigen complexes being deposited in tissues, where they activate the complement system and cause inflammation
type 4 hypersensitivity reaction
A delayed type hypersensitivity reaction caused by T helper cells traveling to the site of antigens, recruiting macrophages and causing inflammation e.g. rheumatoid arthritis, contact dermatitis
define anaphylaxis
severe, life-threatening, generalised or systemic hypersensitivity reaction - rapidly developing life-threatening airway and/or breathing and/or circulation problems usually associated with skin and mucosal changes.
first exposure in anaphylaxis?
inappropriate antigen specific immune response to a benign pathogen
- allergen detected by antigen presenting - present antigens on surface
- T-helpers recognise and inform B-cells of antigen presence
- b cells trigger their proliferation into plasma cells via interleukin-21.
- Interleukin-4 ensures that these plasma cells secrete IgE antibodies
- mast cells have FC receptors bind to IgE and present them
subsequent exposure of anaphylaxis - within minutes
minutes = IgE on mast cell recog allergen, cross-linking, degranulation of histamine = vasodilation, bronchoconstriction, increase vasc perm and oedema
subsequent exposure of anaphylaxis - within hours
Leukotrienes → increased vascular permeability and bronchoconstriction → swelling and breathing trouble)
prostaglandins → bronchoconstriction → breathing problems
eosinophil chemotactic factor of anaphylaxis (ECF-A) → attracts eosinophils
initial manage anaphylaxis
Airways → Ensure and secure patent airway
Breathing → Provide O2 if needed or salbutamol if wheezing
Circulation → IV fluid bolus to support circulation and BP
Disability → lie flat to increase cerebral perfusion
Exposure → expose skin and look for flushing, angioedema (swelling), urticaria
manage anaphylaxis once confirmed
IM adrenaline (epipen, repeat after 5 mins if required) → vasoconstriction and prevent anaphylactic shock
Antihistamines (oral chlorpheniramine or cetirizine) → block the effects of histamine by blocking histamine 1 receptors
Steroids (IV hydrocortisone) → reduce inflammatory response
second dose of adrenaline in anaphylaxis?
short half life (Half life is the time taken for the concentration of the drug to reduce by 50% within the patients body)
anaphylaxis diagnostic bloodtest
mast cell tryptase is raised
