Pharm - Endocrine and GI Flashcards
Anti-thyroid classes
Iodides (Iodide 131, inorganic iodid)
Iodide 131 info
- Carcinogenic at low doses, thyroablative at high doses
- beta wave emission destroys surrounding tissues
- generally results in hypothyroid
Inorganic iodide mechanism
- High levels inhibit organification and hormone release (Wolff-Chaikoff effect)
- Negative feedback loop
Inorganic iodide uses
- Not for long-term therapy (function returns in a few days)
- Prevent thyroid from radioactive iodide exposure
Thioamide exemplar
Methimazole
Methimazole mechanism
Compete with thyroglobulin for oxidized iodide –> less available for T4 production (affects synthesis)
Methimazole adverse effects
- Goiter, pruritic rash early in treatment, arthralgia
- serious: agranulocytosis, hepatotoxicity, vasculitis
Methimazole treatment exceptions
- Thyroid storm treatment (propylthiouracil preferred)
- pregnancy, d/t teratogenicity
Hypothyroid treatment
Levothyroxine (equivalent to oral T4)
Levothyroxine dosing/ interactions/ side effects
- take on empty stomach in morning, 4 hours away from calcium and iron supplements
- monitor TSH if taking with PPI or antacids
- may interfere with glycemic control
- over-replacement/ long-term assoc w/ decreased bone mineral density
Combination contraceptives progestins of note
Cyproterone acetate (used in Diane 35 - only for acne) Drospirenone (used in Yaz/Yasmine - CV mortality)
Combination contraceptives mechanism
- suppress gonadotropin section –> inhibit ovulation
- causes endometrial atrophy, viscous cervical mucus, alter secretion and peristalsis in fallopian tubes
Non-contraceptive benefits
Increased bone mineral density
Decreased acne; ovarian, endometrial, colorectal cancer; peri-menopausal sxs; fibroids; benign breast disease
Combination contraceptives absolute contraindications
- <6 weeks postpartum if breastfeeding
- smoker over 35 (>15 cigarettes/day)
- hypertension
- current/past hx blood clots , cerebrovascular accident
- complicated valvular heart dz
- current breast cancer
- migraine HA w/ neuro sxs
- diabetes w/ end organ involvement
Combination contraceptives side effects
Irregular bleeding, breast tenderness and nausea, amenorrhea, chloasma, possibly weight gain and mood changes
Contraceptive risks
- blood clots
- cervical cancer
- breast cancer (controversial
- Heart attack and stroke when taking >50yg ethinyl estradiol
Contraceptive drug interactions
- May cause contraceptive failure: antiseizure meds, ritonavir, griseofulvin, rifampin, St John’s Wort
- Increase activity: acetaminophen, erythromycin, fluoxetine and fluvoxamine, fluconazole, grapefruit juice, vitamin C
Insulin types and info
Rapid - for postprandial glyemia
Short acting - regular, IV in hospital for ketosis
Intermediate - basal insulin level support
Long acting - best basal insulin support
Insulin adverse effects
- hypoglycemia/ hypoglycemic support
- lipodystrophy at injection site
- allergic rxns
- worsened hypokalemia
Drugs increase glucose
Corticosteroids, diltiazem, diuretics, estrogens, thyroid hormones
Drugs decrease glucose
Alcohol, ACEi, beta blockers, clonidine, fluoroquinolones, MAOi
Glucose regulating agents that increase body weight
Thiazolidinedione (or no effect), sulfonylureas
Glucose regulating agents that increase LDL
Thiazolidinedione (or no effect)
Glucose regulating agents that decrease LDL
Metformin
Insulin secretagogue (Sulfonylureas) exemplar
Glyburide
Sulfonylureas mechanism
Direct inhibition of channels in beta cells –> cellular depolarization and opening of ca2+ channel –> insulin release
Glyburide indications
In conjugation with metformin when additional glucose lowering is necessary, may stabilize sugars and reduce adverse effects
Glyburide adverse effects
Hypoglycemia, skin rashes, N/V, cholestasis
rarely leukopenia, thrombocytopenia, hemolytic anemia
Renal glucose reabsorption inhibitors
Sodium-glucose cotransporter 2 inhibitors
Sodium-glucose cotransporter 2 inhibitors exemplar
Canagliflozin
SGLT2 mechanism
decreased renal reabsorption –> increased glucose excretion
Canagliflozin adverse effects
- increased UTI and yeast infection
- may cause volume depletion
- may cause acute renal injury (more likely in dehydration, heart failure, low BP, ACEi)
- increased risk of osteoporosis, fracture
Insulin sensitizing classes and exemplars
Biguanides - Metformin
Thiazolidinedione - Rosiglitazone
Metformin effects
- reduction of hepatic glucose output by inhibiting gluconeogenesis
- increases insulin sensitivity in peripheral tissues
Metformin adverse effects
- most common are GI (diarrhea)
- increased risk of lactic acidosis in some pop
- clinically relevant deficiency of B12
Rosiglitazone mechanism
activation of PPAR-gamma –> increased insulin sensitivity in skeletal muscle and adipose tissue
less effect on the liver than metformin
Rosiglitazone adverse effects
- edema, increased plasma volume, increased risk of HF
- CI in pts w/ or high risk of HF
- increase risk of CV mortality
- weight gain
- decrease bone mineral density and increase risk of osteoporosis, fracture
Incretin mimetic classes and exemplars
Glucagon-like peptide-1 agonists: Dulaglutide
Dipeptidyl peptidase-4 inhibitors: Sitagliptin
GLP1 agonists mechanism
stimulates insulin by binding to pancreatic CPCR
GLP1 agonist half life
2 minutes
Dulaglutide indications
when other glucose lowering agents are ineffective
Dulaglutide adverse effects
Nausea
Increased risk of pancreatitis
Possible increased risk of thyroid and pancreatic cancer
Sitagliptin info
Do not cause hypoglycemia or GI side effects
can be used in renal insufficiency
may cause joint and skeletal muscle pain
Dipeptidyl peptidase 4 inhibitors mechanism
doubles plasma GLP-1 levels
Alpha glucoside inhibitors exemplar
Acarbose
Acarbose mechanism
inhibits brush border breakdown of polysaccharides
Acarbose adverse effects
- increased flatulence
- increases bioavailability of metformin
- decreases iron absorption
H2 receptor antagonist exemplar
Ranitidine
H2 receptor antagonist mechanism
Competitive inhibition –> reduces gastric acid, pepsin, secretion of intrinsic factor
Ranitidine indications
- dyspepsia/ GERD/ heartburn
- Peptic ulcer disease - requires 6-8 weeks to heal 90% of ulcers
PPI exemplar
Omeprazole
PPI mechiasm
activated by protonation, irreversibly inactivate H+/K+/ATPase pump
Omeprazole indications
Peptic ulcer disease
Zollinger-Ellison syndrome
Most effective for dyspepsia/ GERD/ heartburn
Prevents ulcers in pts taking NSAIDs
Omeprazole adverse effects
- commonly HA, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, rash, pruritis
- Allergic rxns, kidney disorders, dementia (inconclusive)
- Long term - pneumonia, GI infections, vitamin and mineral deficiencies, osteoporosis and fracture
- CI with clopidogrel
Cytoprotective drugs
Sucralfate, Misoprostol
Sucralfate mechanism
binds to ulcers, creating physical barrier
Misoprostol mechanism
Prostoglandin E1 analog
- binds to Pg receptors in stomach –> enhanced mucus production, blood flow, bicarbonate secretion
- binds to PG receptors in parietal cells –> decreased acid secretion
Misoprostol indications
gastric and duodenal ulcers, pts taking NSAIDs long term
high risk pts
Misoprostol adverse effects, CI
Diarrhea and intestinal cramping
CI in pregnancy d/t inducing labor
Antacids exemplars
Aluminum and magnesium hydroxide
Antacids drawback
work for short time, aluminum causes constipation and magnesium diarrhea (together hopefully neither)
Antidiarrheal exemplar
Loperamide
Loperamide mechanism
opioid agonist with greater effect in intestinal smooth muscle
Loperamide CI
children under 2, possibly not when signs of infection are present
Prokinetic exemplar
Metoclopramide
Metoclopramide mechanism
Blocks D2 receptors –> prevents relaxation
increases release of ACh from enteric plexus
Metoclopramide indications
GERD, diabetic gastroparesis, intractable hiccup, drug induced / migraine related nausea
Metoclopramide adverse effects, CI
- drowsiness, extrapyramidal effects, seizures
- CI in seizure disorders, mechanical obstruction, HI hemorrhage, pheochromocytoma
