Case of crash Dieter Flashcards
lipoproteins?
lipid with amphipathic molecules surrounding (phospholipids) and apoliproteins so can float around in plasma
Classes of Lipoprotein?
chylomicron
VLDL
IDL
LDL
HDL
A1/2 role?
transfer of cholesterol from periphery to liver
endogenous lipid cycle in fasting ?
liver produces VLDL, which is broken down by lipoprotein lipase into free fatty acids and glycerol so IDL. then free fatty acids stored into fat tissue and the IDL is back in liver to be disposed of or moved into LDL to peripheral tissues
endogenous lipid cycle in fasting ?
liver produces VLDL, which is broken down by lipoprotein lipase into free fatty acids and glycerol so IDL. then free fatty acids stored into fat tissue and the IDL is back in liver to be disposed of or moved into LDL to peripheral tissues
role of the liver in endogenous?
triglyceride synthesis
export as VLDL
take up particles when triglyceride removed
LDL delivers cholesterol to peripheral cells
cholestrol is produced from?
acetate converted by HMG- CoA reductase
statins inhibit?
HMG coA reductase
when free cholesterol is low in cell?
N-SREBP transcription factor is switched on and the LDL receptor gene codes for LDL receptor protein
endogenous pathway, HDL particles produced from liver, what do they do?
absorb cholesterol from cells in the vascular endothelium and recycle it back to liver as LDL
exogenous pathway?
from dietary lipids- chylomicron particle are absorbed and broken down by lipoprotein lipase into free fatty acids and glycerol which then stored in adipose tissue
the remaining chylomicron is transported to liver
cholesterol and fatty acid in the gut are?
absorbed into intestinal mucosa cells and the reesterified to cholestrol ester and triglyceride and packaged with phospholipids and lipoproteins. they are then secreted into lymphatic vessels as chylomicrons
what happens to glycerol?
it is processed in liver to form more triglycerides or converted to glucose
what happens to the chylomicron remenant?
taken up by LDL receptors in liver
hepatic lipase features?
no cofactor,
substrate is IDL, HDL and LDL
present in liver, adrenal and endocrine
lipoprotein lipase features?
cofactor- ApoCII
substrate- CM and VLDL
tissues- adipose and skeletal muscle
regulation in feeding fasting and exercise
normal serum lipid concentration?
should be less than 5mmol/L
upper limit of normality for fasting triglycerides?
1.7mmol/L
HDL levels
above 0.9 mmol/l in men and 1.2 mmol/l
FH?
autosomal dominant disorder of lipid metabolism, usually hetereogenous
occurs in 1 in 270 people, raised cholestrol specifically LDL cholestrol
tendon and skin xanthomata
pathognomic for hypercholesterolaemia?
corneal arcus before age of 40
mutations of FH found?
ApoB
PCSK9
LDLR
causes of hypertriglyceridaemia?
obesity, DM, excess alcohol, renal failure, gout, drug treatment, thiazides, beta blockersm retinoic acid derivatives, oestrogen therapy
causes of hypercholestrolemia?
hypothyroidism, nephrotic syndrome, high saturated fat diet, cholestatic liver disease, anorexia nervosa
obesity?
over 30
normal weight?
18.5-24.9
as obesity increases so does?
insulin resisitance
metabolic/ X syndrome?
reduced glucose tolerance, hyperinsulinaemia, hypertension, visceral obesity, homeostatic disorder, lipid disorder (high triglycerides, low HDL, normal or elevated LDL)
clinical identification metabolic syndrome
waist circumference:
men> 94cm
women> 80 cm
plus any 2 of
fasting triglycerides over 1.7
HDL men less than 1.03
women less than 1.29
blood pressure over 130/85
fasting glucose over 5.6
dying of cardiovascular disease in UK?
1: 3
Q Risk score?
age, cholestrerol, RA, renal, AF, sex, smoking status, FH, BMI, systolic blood pressure, left ventricular hypertrophy, T2DM
PCSK inhibitors?
block PCSK 9 protein which is responsible for degrading cholesterol receptors thus preventing removal of LDL from blood
Metabolic adaptation?
decreased energy expenditure, decreased satiety, improving metabolic efficiency, increased cues for energy intake
the only appetite inducing (orexigenic) hormone is?
ghrelin
ghrelin acts on?
NPY and AgRP neurons
what stimulates brain feeding?
accelerator neurons produce NPY
What causes inhibition of eating?
melanocortin peptides (brake)
acclerator and brake neurons work on?
arcuate nucleus
NPY neurons also?
produce agouti related peptides which block neuronal melanocortical receptors
ghrelin rises when?
stomach is empty, stimulates hunger neurons
PYY?
released before nutrients arrive in lower small intestine and colon and then a bit more, decreases food intake by inhibiting gut motility
PYY?
released before nutrients arrive in lower small intestine and colon and then a bit more, decreases food intake by inhibiting gut motility
GLP1?
secreted by EEC- l cells and certain neurons in the nucleus of the solitary tract in the brainstem.
in response to food consumption
glucose dependent insulinotropic peptide (GIP) is co secreted
enhances insulin secretion
leptin is secreted by?
white adipose tissue
leptin interacts with?
mesolimbic dopamine system (motivation/reward)
nucleus of solitary tract (satiety)
what happens in low energy diet?
increased hunger/desire
reduction in PYY, cholecystokinin, insulin leptin and amylin
ghrelin, GIP and pancreatic polypeptide increased?
how does exercise affect food?
increase in PYY levels so less appetite and ghrelin
in people with obesity?
intestinal enteroendocrine cell responsiveness is reduces
blunted ghrelin reduction post meal
reduced baseline and meal stimulated levels of anorectic peptides NT, GLP1 and PYY
leptin resistance
drugs associated with?
antipsychotics: lithium, risperidone, quetiapine, apiprazole, olanzapine, valproic acid
antidepressant: citalopram, duloxetine, venlafaxine
sleep inducing agents: zopiclone, trazadone, zolpidem
neuropathic- pregabalin/ gabapentin
steroids
insuline
anti- obesity agents?
CNS stimulants: phentermine, benzaphetamine, lorcaserin
antidepressant/ dopamine reuptake inhibitor, opiod antagonist- naloxone, bupropion
orlistat GLP1 RA
metformin amylin agonists SGLT2 inhibitors
weight loss surgery requirements?
BMI over 40
between 35 and 39.9 with severe obesity related comorbidity
between 30 and 34.9 and poorly controlled diabetes
weight loss surgery requirements?
BMI over 40
between 35 and 39.9 with severe obesity related comorbidity
between 30 and 34.9 and poorly controlled diabetes
hind gut hypothesis?
glycaemic improvement is due to accelerated nutrient delivery to distal intestines
GLP1 main contributor
likert scales?
unipolar (neutral/nothing to one extreme)
or bipolar (negative extreme to positive extreme)
statistical test choice?
difference or correlation/association
independent vs repeated
parametric (meets normal distribution)
vs non parametric
when comparing groups what test do you use?
2 groups- t test
more than 2 groups - ANOVA
compare the means
when testing association in a categorical or binary data then you use?
chi-square test
sertraline can cause?
low sodium/ GI bleeds
prochlorperazine can cause?
parkinsonism
why do you avoid giving ldopa at meal times?
it completes with meals
how to give bisphosphonates?
take on empty stomach, sitting up 30 mins before food
changes in elderly that will affect drug distribution?
decreased muscle mass
increased body fat
decreased serum albumin
why does low muscle mass affect drug distribution?
less volume of distribution for drugs that distribute into muscles, therefore greater plasma concentration e.g digoxin
digoxin toxicity?
bradycardia, junctional tachycardia, heart block, delirium confusion dizziness, anorexia, abdominal pain, green yellow vision double vision, photophobia
why is increased body fat bad?
increased volume of distribution of fat soluble drugs, therefore increased t1/2
e.g diazepam
side effects of benzodiazepines?
drowsiness, confusion, ataxia and dependency
treatment reversa for benzodiazepine?
iv flumazenil 200mcg
why is serum albumin important?
decreased albumin 12-25%- can reduce drug binding capacity and therefore more free drugi.e phenytoin/warfarin
albumin could be further depressed by heart failure, renal disease, RA, hepatic cirrhosis and some malignancies
phenytoin toxicity?
CHANNT
coarse facies
hepatitis
ataxia
nystagmus
nausea vomiting
tremor
what can cause bleeding?
warfarin has a small volume of distribution, 99% bound
asprin can replace, and a 1-2% displacement can double warfarin or triple concentration of free
adverse effects of antiplatelets (aspirin)?
renal failure
fluid retention
peptic ulcer disease
bleeding tendency
how quick does GFR decline?
1% per year from age of 40
which drugs may be increased due to renal function reduction?
morphine, lithium
early toxicity lithium 1.5 mmol/L?
agitation, tremor, twitching
late toxicity lithium> 2 mmol/l?
fits, arrhythmia, renal failure
morphine undergoes?
phase 2 metabolism by conjugation, renal impariemnt leads to build up of metabolite
morphine toxicity?
DR CHAN
drowsiness
respiratory depression
constipation
hypotension
and
nausea vomiting
treatment for morphine?
iv naloxone 400 mcg
what pharmacodynamic effect on heart of elderly person?
reduced and delayed bronchodilatory response to b agonist
decreased calcium channel block effect on PR interval
prescribing cascade?
medicines are being prescribed to treat side effects of other medicine
side effects of ACE i i.e ramipril?
dry cough
hypotension
potassium increase
renal failure
calcium channel blockers side effects e.g amlodipine?
hypotension
negatively inotropic
fluid retention, facial swelling, ankle swelling
diuretics side effects?
hypotension
hypokalaemia
hyponatraemia
confusion
dehydration
