pharmacology for diabetes and obesity and hormonal control of weight Flashcards
what is the drug of choice if you want to treat a relative lack of insulin in T2DM
sulfonylureas
action of sulfonylureas and mechanism of action
increases insulin secretion from B cells (specifically the initial phase 1 spike)
does this by inhibiting K(ATP) channels –> allows Ca entry and therefore insulin fusion with the cell membrane
adverse effects of sulfonylureas
hypoglycaemia
weight gain
what is the 1st drug of choice when treating T2DM
metformin
actions of metformin
- increases insulin-mediated peripheral glucose uptake
- reduces the hepatic glucose production
- decreases carbohydrate absorption in the gut
- reduces LDL cholesterol level and TGs
mechanism of action of metformin
activates AMP kinase
adverse effects of metformin
- GI disturbances
when is prescription of metformin contraindicated
in patients with renal disease –> would lead to increase dosage and side effects
what type of drug is metformin
biguanides
what drug would you use if you wanted to decrease the absorption of carbohydrates from the gut in a patient with T2DM
alpha-glucosidase inhibitors - acarbose
mechanism of action of alpha-glucosidase inhibitors
blocks the enzymes that digest and promote absorption of starches in the small intestin
adverse effects of alpha-glucosidase inhibitors
- flatulence or abdominal discomfort
- loose stools
when is the prescription of alpha-glucosidase inhibitors cotraindicated
in patients with IBD or cirrhosis
2 drug types that act through the incretin pathway
GLP-1 receptor agonists
DPP-4 inhibitors
action of DPP-4 inhibitors
prevents the inactivation of endogenous GLP-1 –> increases insulin and decreases glucagon
what is a name of a drug that is a DPP-4 inhibitor
sitagliptin
adverse effects of DPP-4 inhibitors
- URT infection
- headache
- hypoglycaemia when combined with insulin
- allergy
- pancreatitis
actions of GLP-1 agonists
- potentiates glucose-mediated insulin secretion
- suppresses glucagon release
- slow gastric emptying
- loss of appetite
drug name that is a GLP-1 agonist
exenatide
adverse effects of GLP-1 agonists
- nausea, vomiting, diarrhoea
- weight loss
- antibody formation - immune reactions, pancreatitis
with hormones/peptides increase hunger
- ghrelin
- melanin concentrating hormone
- agouti-related peptide
- orexin A and B
- endocannabinoids
which hormones/peptides decrease hunger
- alpha-MSH
- urocortin
- CRH
- serotonin
- NA
- leptin
- insulin
- CCK
where are the receptors for leptin
in the hypothalamus
what is the drug action of phentermine
sympathomimetic amine - increases the NA in the brain predominantly (also dopamine and serotonin) –> decreases food intake
when can phentermine be used?
- patient has BMI >30
- only in the short term
adverse effects of phentermine
- increased BP and HR
- insomnia
- nervousness
- headache
- dry mouth
which drug has been approved to be prescribed in conjunction with phentermine
topiramate
action of topiramate
increases energy expenditure and suppresses apetite
adverse effects of topiramate
dizziness
taste alterations
teratogenic
action of orlistat
inhibits gastric and pancreatic lipases to decrease dietary far absorption
orlistat has been shown to reduce what
- body weight
- waist circumference
- blood glucose
- dyslipidaemia
- blood pressure
ghrelin antagonizes which hormone
leptin
how does ghrelin act
it acts through the neuropeptide Y neurons in the arcuate nucleus of the hypothalamus to stimulate hunger (stimulates both release and synthesis of NPY)
where is ILP-5 released
predominantly in the colon
actin of ILP-5
stimulates hunger
where is CCK secreted from
the I cells of the small intestine
what is the action of CCK
- satiety
- stimulates emptying of the gall bladder and release of digestive enzymes when fat is in the small intestine
mechanism of how CCK release results in satiety
acts mainly via the CCK1R on the vagus nerve
where is PYY made
by the L cells of the distal GI tract
what is the action of DPP-4 on PYY
cleaves it to the active form
action of PYY
reduces food intake
where is oxyntomodulin released from
the L cells of the intestine (like PYY) in the GIT
action of oxyntomodulin
reduces food intake and increases energy expenditure
what is the main reason that most people who loose weight regain it againa
the gut hormones produce more hunger hormones if you loose weight as a way of defending against weight loss
what is the general result on weight by having microbiota
increases weight
action of microbiota in the gut
- increases the activity of lipoprotein lipase
- processing of dietary polysaccharides –> increased hepatic lipogenesis
results in increased TG storage in adipocytes
