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PHARM250 Endocrine & Genitourinary Systems Cheat Sheet by

Thyroid Disorders, Diabetes, Corticosteroids, Kidney Disease, Reproduction their medication and adverse side effects.

Thyroid Disorders - Classes of medication

Thyroid Agents (HYPOt­hyr­oid)
Levoth­yroxine (T4)
Synth­roid® OR Eltroxin®
Synthe­tically made T4 hormone (body then converts to T3 in peripheral tissues as needed)
Identical to endoge­nously made T4
All adverse effects are rare
May see signs of HYPERt­hyr­oidism with doses too high
Dosed according to body weight, then adjusted according to TSH levels
Takes 1-3 weeks for full therap­eutic benefit
Other thyroid products
Liothy­ronine (synthetic T3)
Desiccated thyroid (mixture of T3 & T4 obtained from dried thyroid glands of pigs)
Both products have been largely replaced by levoth­yroxine
Anti­-th­yroid Agents (HYPER­thy­roid)
Propyl­thi­ouracil
Inhibits synthesis of thyroid hormone, as well as conversion of T4 -> T3
Used to control thyroid function until surgery (short­-term)
Methim­azole
Inhibits synthesis of thyroid hormone, but does NOT inhibit conversion of T4 -> T3
Safer than propyl­thi­our­acil, but takes longer to work (could be months)
Taken once a day
A long-term option if patient has opted out of surgery
Radioa­ctive iodide
Iodine is taken up by only the thyroid
Radioa­ctivity destroys the thyroid gland – attempt to only destroy some of it, but many result in HYPOth­yroid state
Once/if they are HYPOth­yroid, we replace thyroid hormone (likely levoth­yro­xine)
Can also treat thyroid cancer – there have been no known cases of cancer caused by 131I
2/3 of patients respond to one treatment – used when opposed to surgery
Can take 3-6 months after 1 dose (3 months between doses)
Tissue damage limited to thyroid gland only with no surrou­nding structures affected

Adverse effects

Levothyroxine
All adverse effects are rare
May see signs of HYPERt­hyr­oidism with doses too high
Avoid with minerals such as calcium, magnesium, aluminum – blocks absorption – separate by 2h
Propyl­thi­ouracil (PTU)
rash, symptoms of HYPOth­yro­idism, agranu­loc­ytosis, hepato­tox­icity, many drug intera­ctions (antic­oag­ulants, digoxin)
Must be taken multiple times a day (short t½)
Can take up to 3 weeks to exert effect (does not affect hormone already released)
Metformin
nausea (take with food), diarrhea (trans­ient), lactic acidosis (rare)
Sulfon­ylureas
hypogl­ycemia, weight gain, nausea, rash, hepato­tox­icity (don’t take with alcohol)
Can cause hypogl­ycemia on its own (most likely of all classes besides insulin)
Avoid in elderly (more suscep­tible to hypogl­ycemia)
Replag­linide
hypogl­ycemia (less than sulfon­ylu­reas), weight gain
Generally only cause hypogl­ycemia when combined with another hypogl­ycemic drug
Thiazo­lid­ine­diones
edema and fluid retention, headache, weight gain
Post-m­ark­eting survei­llance: may increase risk of fractures, concern about ↑ cardio­vas­cular events
Not likely to cause hypogl­ycemia on its own
Acarbose
abdominal cramping, diarrhea, flatul­ence, malabs­orption of vitami­ns/­min­erals or other drugs (separate by 2h); potential hepato­tox­icity
Does not cause hypogl­ycemia on its own
IF hypogl­ycemic, and need to give sugar, must take glucose tabs, milk, or honey; NOT SUCROSE
DPP4 Inhibitors
hypogl­ycemia, cough, nasoph­ary­ngitis, rash, hypers­ens­iti­vity, muscle aches, joint pain
Not likely to cause hypogl­ycemia on its own
Rare: pancre­atitis (severe abdominal pain that may be accomp­anied by vomiting)
Oral tablets taken once daily
GLP-1 Agonists
nausea, diarrhea, hypogl­ycemia, infusion site reactions, pain in stomach area, decreased appetite, indige­stion, burping, flatul­ence, joint and muscle pain, dizziness, headache, cough, rash, pancre­atitis, dehydr­ation, increases in heart rate
Can cause hypogl­ycemia on its own
Rare: anaphy­lactic reaction, nephro­tox­icity, thyroid cancer
SGLT-2 Inhibitors
weight loss, diuretic effect, hypote­nsion, polydipsia (thirst), increased rate of urinary tract infect­ions, must have adequate kidney function
Not likely to cause hypogl­ycemia on its own
Cort­ico­ste­roids Local Admini­str­ation adverse effects
Opthalmic
Stinging, redness, tearing, burning, secondary infection
Long-term: cataracts, glaucoma
Oral Inhalation
Thrush, hoarse­ness, dry mouth, dysphoria (change in voice), dysphagia (diffi­culty swallo­wing), taste distur­bance
Nasal Inhalation
Rhinor­rhea, burning, sneezing, dry mucous membranes, epistaxis, loss of smell
Topical
Burning, irrita­tion, skin atrophy (thinning of skin), telang­iec­tasia ()
To Prevent: lowest dose possible, shortest duration possible, applying very thin layer of product only on affected area, do not apply to open skin
Adverse Effects of Cortic­ost­eroids Systemic Admini­str­ation
CNS
euphoria, insomnia, restle­ssness, increased appetite, altered mood (depre­ssion, mania, psychosis)
Eye
cataracts, glaucoma
Face/Trunk
redist­rib­ution of fat -> moon face, buffalo hump, protruding abdomen
Heart
hypert­ension, enlarged heart
GI
stomach upset, may ↑ risk of ulcer
Blood
glucose intole­rance -> diabetes; leukoc­ytosis
Kidneys
fluid & water retention (if minera­loc­ort­icoid activity)
Growth inhibition
use in kids only if necessary (inhalers safe)
Muscle
wasting of muscle tissue (myopathy)
Bones
osteop­orosis
Skin
easy bruising, poor wound healing, acne, striae
Prednisone
nausea, hypert­ension, hyperg­lyc­emia, insomnia, psychosis, redist­rib­ution of fat, osteop­orosis, easy bruising, edema, infect­ions, HPA-axis suppre­ssion
Cont­rac­eption – Adverse Effects
Estrogen
Nausea, Breast tender­ness, Headache, Bloating, Thrombosis
Progestin
Irrita­bility, Fatigue, Breast tender­ness, Bloating, Withdrawal bleeding (cycli­cal), Headache, Adverse lipid altera­tions, “PMS-like symptoms”
Emergency Contra­ception
Nausea – if vomit within 2 hours of dose – take dose again; may give with anti-e­metic (dimen­hyd­rinate – Gravol®)
Irregular bleeding – spotting after taking dose; regular menses may be off by a few days (early or late)
Abdominal pain, cramping – use acetam­inophen (not NSAID in case of pregnancy)
Diarrhea, breast tender­ness, fatigue, headache – all possible and transient
α1-Blo­ckers
Retrograde ejacul­ation, Dizziness, fatigue, rhinitis, Orthos­tatic hypote­nsion, Syncope “first­-dose syncope”
α-redu­ctase Inhibitors
Ejacul­atory dysfun­ction, Loss of libido, Impotence, Gyneco­mastia, )All effects due to ↓ DHT levels) Can cause birth defects in male children
PDE-5 Inhibitors
: hypote­nsion, headache, back and muscle pain, hearing loss, visual changes, priapism (erection > 4h)
 

Classes of Oral Hypogl­ycemics

Metformin
A biguanide (only one in it’s class)
Mechanism: Enhances tissue sensit­ivity to insulin -> reducing insulin resist­ance, Also decreases hepatic glucon­eog­enesis
Often first drug prescribed
Sulfon­ylureas
Glybu­ride, glicla­zide, glimep­iride
Enhance insulin secretion from the pancreas (aka insulin secretagogue)
Also increase insulin sensit­ivity at target tissues (like metformin)
Repagl­inide
A meglit­inide
Stimulate release of insulin from pancreas (insulin secret­agogue)
Requires presence of glucose to exert action, therefore MUST BE TAKEN BEFORE (within 30 mins) OR WITH A MEAL
Thiazo­lid­ine­diones
Rosiglitazone, piogli­tazone
Enhance insulin sensit­ivity at target tissues (similar to metformin)
Food has no direct effect (can be taken with or without food)
Acarbose
Inhibits α–gluc­osi­dase, which reduces the rate of absorption of carboh­ydrates from the GI tract, preventing hyperg­lycemia – therefore TAKE WITH MEALS
Dipeptidyl Dipept­idase 4 (DPP4) inhibitors
linagliptin, alogli­ptin, sitigl­iptin, saxagl­iptin
Incretins are a group of hormones that tell the pancreas to release insulin (from pituit­ary); basal rate and elevated in response to food
Drugs partic­ularly target glucag­on-like peptide 1 (an incretin) and others
DPP-4 inhibitors inhibit the breakdown of incretins, which increases and prolongs their activity -> instructs pancreas to release more insulin for longer
Glucag­on-like peptide 1 (GLP-1) agonists
exenatide, liragl­utide, dulagl­utide, semagl­utide, lixise­natide
GLP-1 agonists mimic endogenous GLP-1 (an incretin)
Results in increased satiety, reduced gastric emptying, and greater insulin secretion
GLP-1 agonists are resistant to degrad­ation by DPP4 enzymes
Given as SC injections
1st Gen are admini­stered daily or BID; 2nd Gen are weekly
Varying t ½ of 2.4 hours - 2 weeks
SGLT-2 Inhibitors
Canag­lif­lozin, dapagl­ifl­ozin, empagl­ifl­ozin, ertugl­ifl­ozin
Increases excretion of glucose in the kidney by preventing glucose reabso­rption, therefore reducing blood glucose levels

Diabetes medica­tions and treatments

Glucose homeos­tasis factors
Insulin
Released in response to HIGH blood sugar
Promotes the uptake, utiliz­ation, and storage of glucose → lowers blood glucose concentration
Suppresses endogenous glucose and Inhibits glucagon release
Causes rapid uptake, storage, and use of glucose by insulin sensitive tissues (Muscle, liver, adipose (fat), brain)
 
Basal release rate of 0.5 – 1.0 unit / hour
 
Rate of release increases when blood glucose (BG) > 5.5mmol/L (in response to eating - bolus)
 
Usual secretion: 25-50 units / day
Glucagon
Released in response to LOW blood sugar
Increases the hepatic glucose output → increases blood glucose concen­tration
Diabetes Mellitus
A metabolic disorder charac­terized by the presence of hyperg­lycemia due to defective insulin secretion, insulin action, or both
Type 1
due to defective insulin secretion
An autoimmune destru­ction of pancreatic β–cells, causing an absolute lack of insulin secretion
Type 2
due to insulin resist­ance, eventually leading to defective insulin secretion
Hyperg­lycemia
HYPERg­lycemia would occur if a patient did not have enough insulin
FPG > 7.0mmol/L
Hypogl­ycemia
HYPOgl­ycemia would occur if: too much insulin, improper timing of insulin, or patient skipped a meal
FPG < 4mmol/L
Insulin Treatm­ent
Insulin prepar­ations vary by:
Onset of action, Time to peak glycemic effect, Duration of action, Appearance
Long­-Acting Insulin Analogues (LAIA)
Insulin detemir (Levemir)
After injection, the molecules self-a­sso­ciate and bind to albumin  slowly released from subcut­aneous tissue into blood stream at a slow, predic­table rate
Insulin degludec (Tresiba)
Forms multih­examers following SC injection, leading to a depot  delayed absorption from SC tissue and also binding to albumin leads to longer time profile
Insulin glargine (Lantus)
An acidic (pH of 4) product in the vial, and once injected subcut­ane­ously, the acidic solution is neutra­lized, and forms micro-­pre­cip­itates  these slowly dissolve over at a slow, predic­table rate
Insulin Routes of Admini­str­ation
Subcutaneously
most common
With an insulin pump
continuous subcut­ane­ously
Inhaled dry powder
not yet approved in Canada
Intrav­enous
only regular (R or Toronto) for emerge­ncies
Mixing Insulins
Important note regarding admini­str­ation: not all insulins can be mixed
ALWAYS CHECK
R/Toronto + N/NPH
may be pre-mixed and stored together
RAIA + N/NPH
may mix, but administer immedi­ately (do not store mixed)
LAIA
do not mix in same syringe with any other insulins – due to specific mechanism of action and pH
                           
 

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