Targeting obesity W1 Flashcards
First line Medication for weight loss
Orlistat- a pancreatic lipase inhibitor
Widely used
An example of a withdrawn medication
Rimonabant - a CB1 inverse agonist
Repurposed
medications
Semaglutide - GLP1 agonist
Targeting obesity via medication
- Appetite suppression - eat less (semaglutide) or substances that expand in stomach to make us feel fu (methylcellulose). Nicotine also works to decrease appetite
- Decreased absorption - eat normal but absorb less (orlistat) and fibre supplements
- Increased metabolism - activation of brown adipose tissue (no drugs do this)
Fats are consumed as….
Glycerides which are Esthers of glycerol and fatty acids
They are too large to be absorbed
Pancreatic lipase breaks them down by Esther hydrolysis
Three fatty acids are then absorbed into the GI
Inhibition of lipase will reduce fat absorption
How are fatty acids absorbed and distributed?
- Emulsification by bile.
- Enzymatic digestion by pancreatic lipase.
- Absorption of products of fat digestion depend on size.
How are fatty acids absorbed and distributed flow diagram?
Large fat droplets are emulsified by bile salts in the intestine lumen
The fatty acids and monoglycerides leave the micells and enter the epithelial cell
Fatty acids linked to form triglycerides
Fatty globule combine with proteins to form chylomicrons inside the Goldie
Chylomicrons are extruded from the epithelial cell and enter a lacteal
Lymph in the lacteal transports chylomicrons away from the intestine
Orlistat mechanism of action
Resembles a triglyceride and is recognised by lipase as a substrate
The strained for membered ring ester is attacked by the serine residue
The covalent Accel intermediate is stable and hydrolysis requires 24 hours essentially making lipstatin and irreversible lipase inhibitor.
Production routes of orlistat
- Semisynthetic two steps.
- Synthetic more than 10 steps.
- Expensive and used by Roche who claims it gives higher purity
Orlistat as a drug
FDA approved in 1999
Prescription dose of 120 MG 3X daily
Significant GI side-effects, including wind and fetal incontinence
Is an example of aversion therapy where the side-effects encourage a patient to avoid eating fats?
Why is Orlistat prescribed?
Is used with an individualised low calorie and low-fat diet and exercise program to help people lose weight
It is used in overweight people who may also have high blood pressure, diabetes, high cholesterol, or heart disease
It is also used after weight loss to help people from gaining back that weight
Is a class of medication is called lipase inhibitors
Works by preventing some of the fat in food to eat from being absorbed into the intestines and then removed in the stall
How should Orlistat be used?
Comes as a capsule and a non-prescription capsule to be taken orally
Usually taken three times a day with each main meal that contains fat
GLP–1 agonist for type two diabetes treatment
The peptide hormone GLP-1 has multiple beneficial effects in diabetes management
It is destroyed by DPP-4 and has a short half life of two minutes
Observed to have weight loss effects in patient
Semaglutide repurposed drug for obesity
It is a synthetic GLP-1 approved for obesity treatment
Contains lipophilic fatty acid attached to the peptide backbone
High lipophilicity results in type binding to serum albumin and so escaping destruction by DPP-4
Has a bio availability of 89%
Dosage is 0.2 5MG once a week for four weeks and then increase 0.5 MG once a week for four weeks and then increased if necessary to 1MG once a week
