Nov 12, 2021
Classroom Lecture Endocrine Pharmacology Part 1 of 1
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Auto Generated Transcript:
Okay, welcome to Endocrine Pharmacology: Diabetes, Thyroid Disorders, Bladder Disorders, and Erectile Dysfunction. So what I want to do is I’ll go over some of the hormonal issues first so Diabetes and Thyroid and Sex Hormones then we’ll talk about the Bladder Disorders and ED. So we’ll start with Diabetes Mellitus or the pathology.
There’s Type 1 which the pancreas doesn’t produce insulin it’s usually diagnosed in childhood and treatment requires insulin. Type 2 insulin is produced but not utilized very efficiently and traditionally diagnosed in adulthood and we’re seeing it in children now obviously with the American diet. And then treatment starts with oral medications.
Gestational Diabetes insulin is produced but not utilized very efficiently and occurs during pregnancy and continues shortly after delivery it’s treated like Type 2 Diabetes with some caveats. All forms of Diabetes result in excess glucose in the blood and the medications all focus on moving glucose out of the blood and into cells or out of the body.
The pathology of Diabetes Mellitus so multiple organs are involved in regulating insulin and glucose levels the liver the pancreas the small intestine and the circulatory system glucose is ingested with food it comes through the stomach into the small intestine where it’s absorbed from the small intestine it goes into the bloodstream that’s a donut the organs become targets.
And one we can stop the intestinal absorption of glucose two we can stop the liver from making glucose three we can increase insulin sensitivity for we can increase pancreatic insulin production and five we can just provide insulin.
So in the pancreatic beta cells uh the red cells are in the isolate and it’s called an isolate of longer hans because it looks a little bit like an island those are the beta cells they’re responsible for insulin production and release and eventually stop producing insulin this is problematic in diabetic patients.
One of the oral medications we can use for diabetes is are the biguanides or Metformin which is brand Glucophage it works on three of the targets one stops intestinal absorption of glucose two stops the liver from making glucose and three increases insulin sensitivity indications are Type 2 Diabetes Gestational Diabetes.
And adverse drug reactions include nausea and vomiting diarrhea and loose stools and lactic acidosis which is pretty rare. The diarrhea in loose stools can depend on how quickly someone has started someone on Metformin and it’s unfortunate because a lot of times this is a very good medication but when started too quickly, the patient will say I don’t want to take that stuff give me something else when if they had started at a lower dose it might have been okay.
The most common reason patients stop taking it is diarrhea 53 percent of patients experience it and it must be taken with meals so start with a low dose and gradually increase. Two oral medications for Diabetes Mellitus, The Sulfonylureas we don’t use them as much anymore because of hypoglycemia which I’ll talk about in a minute but Glyburide brand Diabeta and Glipizide brand Glucatrol these work on one of targets so one increased pancreatic insulin production a beta cells create insulin.
So indications again Type 2 Diabetes and really for Gestational Diabetes this would be last line adverse drug reactions this is real concern that we don’t really have with Glucophage that’s that we can have hypoglycemia nausea vomiting. The hypoglycemia is serious problem must be taken with meal to be prevented use it for limited time for years beta cells can only produce insulin for so long before they’re done.
Another oral medication for diabetes are DPP-4 inhibitors Cytoglyptin brand Januvia so Dipeptidyl Peptidase 4 inhibitors they work on one of targets that target is increased pancreatic insulin production so again increase indication will be Type 2 Diabetes adverse drug reactions we don’t really see too many but pancreatitis is rare.
Injectable meds for diabetes, The Insulins so Insulin is hormone that causes glucose to be taken up by cells there’s several different types of insulins difference is how long they work for so when we’re talking about um when we’re talking about um [Music] The Injectable Meds For Diabetes include Insulins so Insulin is hormone that causes glucose to be taken up by cells."
"There are several different types of insulin and differences in how long they work for. Two types are available over the counter, the others are prescription only. The indications are Type 1 Diabetes, Type 2 Diabetes, and Gestational Diabetes. The adverse drug reactions of course include hypoglycemia, that we reduce the glucose too much. Any form of insulin produces the highest risk of hypoglycemia. So even the highest dose of Sulfonylurea doesn’t come close to the risk of insulin, so this is a real concern.
One image that you want to kind of put in your brain is this one of how high the spike goes over time. So something’s very rapid acting, you see that it has a very high spike and then something short acting like regular its spike is a little lower, intermediate even lower than that and then long acting Glargine works over about a day and we’ll go through each of these but again this is something you want to kind of get in your brain that as I go and go longer I’m gonna have much lower effects overall.
So the insulin Lice Pro or brand Humalog it works within like 15 minutes with meals we use it 30 minutes before eating and it lasts for about two hours. Regular insulin works with 30 minutes within 30 minutes we use about an hour before eating and it lasts for about four hours. Now I say it’s over the counter but that doesn’t mean that you’re going to find it in the refrigerator next to the soda, it’s simply that you don’t need a prescription you can go to the pharmacy and just say hey I’d like to buy insulin and it’s possible to buy it although the cost is so prohibitive most use their insurance for it.
The other over-the-counter one is NPH Insulin or Humilin N. The P in NPH is for Protamine, it comes from trout and it works within four hours and it covers between meals and overnight so it lasts eight to twelve hours.
Finally there’s the long acting uh Insulin Glargine Lantis Baciglar and Toujeo Atlantis one way to remember it is it lasts all night. It’s very long acting and is used nightly to provide 24-hour insulin delivery.
So that’s a very very abbreviated review of insulin oral and injectables thyroid disorder agents so we begin with the thyroid it’s a butterfly shaped organ on the trachea and a healthy thyroid has a perfect balance of hormone levels not too low not too high.
If we get Hypothyroidism we go too low then we have fatigue weight gain cold all the time very shaky if on the other hand we’re way too high it’s the opposite where we can’t sleep rather than fatigue we have weight loss rather than weight gain we have sweating rather than being cold all the time and very jittery very bouncy so that’s what happens when it goes too high.
So Hypothyroidism is the most straightforward we replace it with hormone Levothyroxin and Synthroid which is literally squishing the word synthetic and thyroid together. The dose is modified based on the symptoms and the hormone levels and it takes about six to eight weeks to see the full effects.
The indication of course Hypothyroidism and adverse drug reactions kind of related to thyroid levels so we kind of look at symptoms but what we’re really worried about is going too far where we take some Hypothyroid and make them Hyperthyroid.
When we look at dosing a small dose makes a big change so it’s dosed in micrograms rather than milligrams and just conversion just remember that we have a thousand-fold difference between a microgram and a milligram so we take with water first thing in morning with nothing else is best way to do it.
And we want all dose to be absorbed consistently due to potency of hormone an anti-thyroid agent could be something like Propylthiouracil. It stops production of new thyroid hormones and dose is modified based on symptoms hormone levels so takes six to eight weeks see full effects indication is Hyperthyroidism average."
"Drug reactions are related to thyroid levels again see the Hypo Hyperthyroidism symptoms. Sex hormones and contraceptives so Testosterone it comes as Androgel or a transdermal gel it’s synthetically made but it’s identical to endogenous Testosterone. The application area should be covered to prevent transfer to children so we want to be very careful when the children around. Indications low Testosterone levels obviously and then the adverse drug reactions those things that you might expect acne prostate enlargement and Gynecomastia which is relatively rare.
Testosterone is available in a variety of dosage forms creams gels patches injections and implants and the hormone alone can be used for low Testosterone levels in men and women female to male gender conversion many different uses. Hormonal contraceptives the cycle overview looking at Estrogen and Progestin levels and how it goes from the Follicular phase the Ovulatory phase to the Ludial phase and then the egg releases from the ovary on day 14.
So as we look at the mechanism of action and kind of put this picture in our heads all the hormonal contraceptives they prevent ovulation the egg never gets released they thicken the cervical mucus so sperm can’t reach the egg all forms contain Progestins and some contain Estrogens but we don’t see Estrogen only contraceptives now. The pregnancy rates and oral contraceptives should be around half a percent but where humans, the way that we actually take it, it’s closer to eight percent but the theoretical number would require perfect adherence taking it every day exact same time.
One of the drugs this combination is Norethendron which is a Progestin with Ethanol Estradiol which is an Estrogen with Ferrous Fumarate which is iron replacement and this is Luestrin 24FE same hormone amounts in active pills for 24 to 28 days to reduce the length of menstruation but we also have these iron pills at the end. We have a combined oral contraceptive so Nordgestamate which is Progestin and again that just stem and then Ethanol Estradiol for Estrogen it’s all in Trisprintec.
And there are three different hormone amounts over 21 days each seven days days long so more Estrogen at the beginning more Progesterone at the end last week is placebo so why do we do this we’re just really mirroring the normal cycle. Another more recent not relatively recent combination is Nor Algostromine with Ethanol Estradiol in a transdermal patch so it’s applied to the torso the back or the buttock once per week for three weeks then a week off so very similar to dosing for tablets except only need one patch so it stays on all week long even when showering or bathing in actual failure rate closer to around 8 percent.
Same thing with vaginal ring so Edina Gestural Ethanol Estrodial vaginal ring or Nuvaring Progestin is Edina Gestural Estrogen is Ethanol Estrodiol it’s this flexible polymer ring that releases hormones slowly and it’s inserted vaginally for 21 days removed for seven then a new one’s inserted actual failure rate again around uh eight percent uh remote emergency hormonal contraception so we’re talking about Levonorgestrel oral tablet or Plan B One Step uh it’s a Progestin.
And it’s a Progestin only contraceptive and it’s effective up to 72 hours after unprotected sex but you really, the closer you get to uh when it happened, the better off you are. It doesn’t terminate a pregnancy, it simply is meant to prevent it. The odds of pregnancy with no contraception are normally eight percent uh Plan B is 89 percent effective so odds of pregnancy with Plan B go down to one percent but it comes at cost of extreme cramping and discomfort.
One thing that can be done is to take some soda let it go flat and sip on it, it can help with nausea. Contraceptives IUDs so Copper Intrauterine Devices Copper T380A is Paraguard so no hormones Copper is spermicidal in itself lots of cramping it’s uncomfortable at first actual failure rate is around 0.8 percent and it’s inserted once every 10 years.
There’s a hormonal Intrauterine Device IDU IUD and this releases very small amount of Progestin there’s less cramping with Copper IUD and then actual failure rate at 0.2 percent so inserted once every 5 years going on to some of bladder disorders so Overactive Bladder pathology there’s disconnect between nerves bladder muscle brain about urine quantity there’s sudden urge empty bladder even when not full.
And it’s most commonly seen in older adults but can occur anytime with male female medications focus on drying things up so Anti-Muscarinics or Anticholinergics."
However, you want to call them Oxybutynin brand Oxytroll and Ditropan Solophenosine which is Vesicare Dolterodine which is Detroit they relax the smooth muscle of the bladder the Detrusor muscle allowing more urine to fill in the bladder before needing to be emptied. Indications obviously OEB which is Overactive Bladder and then adverse drug reactions come from the Anticholinergic effects drowsiness confusion dry mouth and urinary retention.
The next issue we’ll talk about is that urinary retention which is inability to avoid the bladder content it’s caused by poor Detrusor muscle contractility so the contraction is voiding in the bladder inappropriate bladder relaxation and the medications focus on re-wetting so Cholinergic Muscarinic are the opposite of Anticholinergic so these would be ones that take care of that retention.
The one example we could use is Bethennicol or Urocholine it increases the muscle tone and contractility of the Trusor muscle allowing for bladder voiding. The indications are urinary retention adverse drug reactions so you can have excessive tear production loose stools diarrhea cramping urge to urinate all of these things are Cholinergic effects.
BPH a little bit different so the growth of the prostate that squeezes onto the urethra inhibits urine flow. The urge to urinate still there but the flow is blocked so there’s two treatment pathways we can one increase the diameter of the urethra or two shrink the prostate.
So a normal prostate is a bit larger and then benign prostatic hyperplasia we see that we have an expansion of the prostate and it puts this pressure on the urethra. The first group that we could use are Alpha One Blockers so Tamsulosin which brandon Flomax Alfuzosin which is Uroxytrol it causes relaxation of prostate increasing urine flow increases urethral diameter indications obviously BPH benign prostatic hyperplasia adverse drug reactions they’re all uncommon dizziness headache or static hypertension.
The Five Alpha Reductase Inhibitors Dutasteride Finasteride they decrease hormone production and prostate uses to grow eventually this leads to prostate shrinkage and indications BPH again and average drug reactions decreased libido and erectile dysfunction talking about that next topic ED.
So this is inability to attain or maintain an erection most men with ED have some underlying microvascular disorder whether it be hypertension coronary artery disease peripheral artery disease or diabetes mellitus type one or two treatment involves increasing blood flow to penis and we use Phosphodiesterase 5 PDE5 inhibitors Sociodenophil brain Viagra taken one hour before needed to Dalaphyl Cialis taken one hours before needed last 72 hours.
So it increases penile blood flow through Nitric Oxide induced vasodilation and indications of course ED adverse drug reactions you would expect with something that is like a nitrate so headache flushing hypotension. We do want to be careful though we don’t want to use these PDE5 inhibitors with nitrates so they must not be used with them Nitric Glycerin tablets patches gels Isosorbide minor nitrate Dinitrate okay.
The combination can cause extreme vasodilation and hypotension.
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