Pharm Block 3: Thy, Hypo, Lipid Flashcards
What roles to TH orchestrate within the body?
Homeostasis Metabolism Growth Development Kids- growth/development Adults- metabolic stability
Function of TSH
Stimulates thyroid to iodinize thyroglobulin and produce T3/T4
Funtion of Thyroid Peroxidase
Oxidizes iodide to iodine to make TH
What protein carries T3/T4?
Thyroxine Binding Globulin
T4 is converted to T3 in ___
Peripheral tissue
Liver is primary site of T3 production
T3- 3-5x greater activity
T4- longer t1/2
T3/4 bind to what 3 proteins?
TGB- thyroxine binding globulin
TBP- thyroxine binding pre-albumin
Albumin
TSH is AKA
Thyrotropin alfa (Thyrogen)
Define Hypothyroidism
Dec TH production
Primary- majority= Hashimotos
Secondary- hypothalamus/pituitary insufficiency or drug induced (Lithium)
What are the TSH and FT4 levels in primary hypothyroidism?
Secondary?
1*= High TSH, low FT4 2*= Low TSH and low FT4
Hyposecretion of T3 and T4 in adults causes ?
Nontoxic goiter
Constant TSH stimulation but no T3/T4= hypertrophy
Define Cretinism
Untreated hypothyroidism in infants/kids
Hypothyroidism that has inhibited body/brain development
What are the treatment goals for hypothyroidism
Normalize TSH and FT4
Minimize Sx
Minimize long term consequences
What is the drug name for Synthetic T3
Liothyronine
What is the drug name for Synthetic T4
Levothyroxine- DOC for thyroid replacement
What is the drug name for Synthetic T4:T3 (4:1)
Liotrix
What is the drug name for thyroid replacements from animal sources?
Dessicated Thyroid- Armour
MOA of thyroid replacement meds
Provide exogneous thyroid in doses adjusted every 6 wks w/ recommendations to take in AM on empty stomach
What needs to be monitored in Thyroid Repalcement PTs
TSH/FT4 baseling and every 6-8wks until normal, then every 6-12mon
S/Sx of improvement/hyperthyroidism
What decreased absorptions does thyroid meds cause?
Dec abosprtion of Antacids, Ferrous SUlfate, Bile Acid sequestarants, Acid Reducers or Sucralfate
What drugs interact with thyroid replacement meds and increase clearance?
Phenytoin
Carbamazepine
Rifampin
What drugs interact with thyroid replacement and decrease FT4?
What drugs can prevent conversion of T4 to T3
Estrogens
Amiodarone, Propranolol
How are Warfarin and Thyroid replacement meds related?
Warfarin inverse to thyroid hormone
Hyperthyroid= Dec Vit K= Dec coagulation
S/Sx of Myxedema Coma and how it’s treated
Weak, stupor, hypotherm/vent/glycemia/Na, shock and death
Levothyroxine IV 300-400mcg
Hydrocortisone until coexisting adrenal suppression is ruled out
What are the TSH and FT4 levels in Hyperthyroidism
Low TSH
High FT4
Define Thyrotoxic Crisis
Define Thyroid Storm
Excessive amount of thyroid hormone
Emergency characterized w/ decompensated thyrotoxicosis, fever, Tachy, delirum, N/V/D
Define Toxic Diffuse Goiter
Most common cause of hyperthyroidism
Thyroid stimulating Abs on TSH receptors mimic TSH and stimulate T3/4 production
What is the second most common cause of Hyperthyroidism
Drug induced
Define Pituitary Adenoma
Excessive TSH secretion doesn’t respond to normal T3 feedback
Define Plummer’s Dz
Toxic Multi-Nodular Adeonoma
Autonomous nodules hyperfunction causing excess thyroid secretion
Define Painful Sub-Acte Thyroiditis
Inflammation of gland by virus invasion of parenchym causing hormone release
Define Toxic Adenoma
Least common
Hot nodule, operating independently of pituitary and TSH
What are the treatment foals for hyperthyroidism
Minimize/eliminate Sx and consequences
Eliminate excess hormone and normalize TSH/FT4 levels
What are methods of treatment approaches for hyperthyroidism
Thionamides- block synthesis
Iodides- block release
Radioactive Isotope- ablates gland
Adrenergic blockers- controls Sx
What are the Thionamide drug names?
Propylthiouracil
Methimazole
What are the Iodides drug names
K iodide- SSKI, Lugols solution
What are the drug names of radioisotopes used to ablate thyroid gland?
Sodium Iodide 131
What adrenergic blockers are used for hyperthyroidism
BB- esp Propranolol
What is the treatment of choice for non-pregnant PTs +21y/o with Graves, Multinodular or Toxic adenoma?
Radioactive Iodine
Also most cost effectice
What is the treatment of choice for severe hyperthyroidism
Surgery
Also for PTs unwilling/unable to take anti-thyroid drugs
Pregnancy
When are anti-thyroid pharmacotherapies used for hyperthyroidism?
Likely to achieve remission in 1yr
Refusal of ablation/surgery
Failed ablation/surgery
Mod/severe exophthalmos
MOA of Thioamide
Inhibits thyroid peroxidase which blocks iodination and sythesis of thyroid hormones
What is the preferred med for Graves Dz?
Methimazole unless in 1st trimester then PTU is preferred, 10x potent, dose Q1D, Pregnancy Cat D, DOC for long term
Propythiouracil- 1st trimester, thyroid storm and adverse reactions to methimazole (other than agranulocytosis or hepatitis), higher incidence of liver failure
How long is Thioamide use expected before improvement is seen?
3-8wks r/u w/ radioiodine or surgery
Remission: 20%; TSH and T4 normal for 1 yr after d/c
What needs to be monitored in PTs on Thioamide
Baseline CBC w/ differential
LFTs w/ bilirubin
CBC w/ Diff and d/c if agranulocytosis occurs
Jaundice
What drugs does Thioamide interact with?
Rad. Io 131- d/c Thioamide 3-5 days prior
Iodides- inc stores od iodine and may delay onset of Thioamide
Adverse effects of Thioamide
Black Box- liver injury/failure Cholestatic jaundice Agranulocytosis Leukopenia Arthralgia, Lupus like Rash
MOA of Iodides
Inhibits hormonal secretion in hrs to temporarily inhibit thyroid hormone synthesis
Red vascularity to reduce size prior to ectomy
When are Iodides used?
Pre-op prep for Graves Dz
Protection prior to radiation exposure
May exacerbate hyperthyroidism
Adverse effects of Iodides?
Rash Hypersalivation Swollen/sore gums Metallic tase Itch Rhinitis
Don’t use Iodides with what drugs?
RI 131- d/c 3-4 days prior
Lithium
Potassium iodide also used for ?
Antiseptic
Expectorant
Reduce thyroid cancer after nuclear accident
MOA of RI131
What is monitored
Accumulates in thyroid and emits B/G radiation to destroy thyroids tissue
Neg pregnancy must be confirmed 48hrs pre-treatment
TSH and FT4 at 4-6wk intervals?
Adverse effects of TI131
Hypothyroidism
Pain
Exophalmosis exacerbation, esp in smokers
Contraindications of using RI131
Pregnant
Breast feeding
Severe ophthalmopathy
Non-Sel BBs used in hyperthyroidism
Propranolol
Nadolol
Metoprolol
Esmolol
What drugs can’t be used w/ BBs in hyperthyroidism
B2 agonists
Non-DHP CCBs- can be used in PTs w/ tachy who are contraindicated to use BBs
Define Thyrotoxicosis Factitia
Low TSH, High FT4
Any state of excess hormone including ingestion and itis
What drugs are used to managing thyroid storms?
Propylthiouracil SSKI Propranolol (Diltiazem if BBs are contraindicated) Acetaminophen Hydrocortisone Cholestyramine
What are the major lipids in the body?
CHolesterol
Triglycerides
Phospholipids
What is cholesterol needed for?
Bile acids
Steroids
Cell membrane- phospholipid bilary
Define TG
Fat from 3 FAs to supply energy to muscles
Systemic circulating cholesterol comes from what wo sources?
Endongenous- liver; HMG-COA to mevalonate catalyzed by HMG-CoA Reductase (rate limiting step of synthesis) and this is the site of Statin action
Exogenous- diet
How are cholesterol and TGs carried through the body?
Lipoproteins
What is the make up of chylomicrons
TGs: 85-95%
Cholesteral: 3-6%
Protein: 1-2% (higher protein=higher density)
What is the make up of VLDLs
TGs 50-60
Cholesterol 20-30
Protein 6-10
What is the make up of LDLs
Cholesterol 50-60
Proteins 18-22
TGs 5-10
What is the make up of HDLs
Protein 45-55
Cholesterol 5-20
TGs 5-10
What are the AKAs for HDL, LDL, and Chylomicrons
HLD- apo-A1
LDL- apo-B100
Chylo- apo B-48
Define Type 1 Lipid Abnormality
Chylomicrons
Familial hyperchylomiconemia
Not associated w/ inc CHD
No drug treatments
Define Type 2A Lipid Abnormality
LDL
Familial Hypercholestolermia, Polygenic Hypercholesterolemia
Most common
Ischemic heart Dz accelerated
Type 2A Lipid Abnormality
Cholestyramine and niacin or,
Statin
Lomitapide
Mipomersen
Define Type 2B Lipid Abnormality
LDL and VLDL
Familial Combined Hyperlipidemia
Common, from over production of VLDL in liver
Same diet/treatment as 2A
Define Type 3 Lipid Abnormality
Familial Dysbetalipoproteinemia
IDL, LDL 1
Inc/poorly used IDL from mutant Apolipoprotein E
Xanthomas and VascDz in middle age
How are Type 3 Lipid Abnormality treated
Diet
Niacin and Fenofibate or a statin
Define Type 4 Lipid Abnormality
VLDL
Family Hypertriglyceridemia, Isolated hypertriglyceridemia
Common dz from inc production/dec removal of VLDL and TG
PT obese, DM, and hyperuremic
How are Type 4 Lipid Abnormality treated
Niacin and or Fenofibrate
Define Type 5 Lipid Abnormality
VLDL and Chylomicrons
Familial Mixed Hypertricyleridemia
Inc production/dec removal of VLDL in adults obese or DM
How are Type 5 Lipid Abnormality treated
Niacin and/or Fenofibriate or statin
Define Secondary Prevention
Define Primary Prevention
PTs w/ previous CHD event
PTs w/ no Hx of CHD w/ A-Sx dyslipidemia
Total cholesterol ranges
HDL ranges
<200 desireable
>240 high
>280 very high
<40, low/bad
>60 high/good
LDL ranges
TG ranges
<100 optimum
160-189 high
>190 very high
<150 normal
100-499 high
>500 very high
Factors used to assess need for statin therapy
Non hispanic/Caucasion/AfAm 40-79 W-W/out Diabetees LDL 70-189 w/out hx of ASCVD No statin therapy
What are the 4 major statin benefit groups
1- ASCVD- primary prevention
LDL >190
40-75y/o w/ DM and LDL 70-189
40-75y/o w/ LDL 70-189 and ASCVD >7.5%
What are the types of Hypolipidemic Agents
HMG-CoA Reductase Inhibitors (statins)
Alteration Lipid/Lipoprotein metabolism (Niacin, Fibric Acid, PCSK9 Inhib)
BAS- Colisterpol, Cholestyramine, Colesevelam(
Absorption Inhibitor (Ezetimibe)
MOA of HMG-CoA Reductase Inhibitors
Inhibit first step of sterol synthesis by blocking Hydroxymethylglutaryl CoA reductase and depletes the intracellular supply of cholesterol
When are HMG-CoA Reductase Inhibitors clinically used?
DOC for high LDL and or CHD/risk
Not for under 18y/o
What are the clinical effects of HMG-CoA Reductase Inhibitors
Best PO med for reducing LDL
Reduce coronary events/CHD mortality/stroke
When do HMG-CoA Reductase Inhibitors need to be taken?
PM to increased efficacy and coincides with night upturn of cholesterol biosynthesis at night
What are the two exceptions for Statin dosing at night?
Atorva
Rosuva
How long of a period needs to pass between changing statin dosages?
4wks
What are the adverse effects of HMG-CoA Reductase Inhibitors?
Myalgia
Mypoathy
Rhabdo
Liver toxicity- obtain baseline LFTs and at 6 and 12wks
What 2 statins don’t require dose adjustments for reduced renal function?
What one is not highly protein bound?
Atrova and Pita
Pravastatin (may displace warfarin)
Absolute contraindications for using HMG-CoA Reductase Inhibitors
Liver Dz
Pregnancy X
Nursing
Drug interactions of HMG-CoA Reductase Inhibitors
P450 (except Prava and Fluva) Grapefruit Red Yeast Rice- contains monacolin K (inc myopathy and rhabdo risk) Fibric Acid derivatives Gemfibrozil Niacin
What drug is considered best for lowering TGs?
Fibric acid derivatives, PPAR-a agonists which inc speed of chylomicron/VLDL removal
What drug is used to lower TGs but may also cause an increase of HDL?
Fibrates
When are Fibrates used clinically?
Hypertriglyeridemias when VLDL predominates
Dysbetalipoproteinemia
HIV hypertriglyceridema
Option for PTs who can’t use statins
What are the drug names in Fibrates
Fibric Acid Derivative= Gemfibrozil (take w/ food)
Fenofibrate
Fenofibric acid
What are the averse effects of statin?
What monitoring is done?
Myopathy/rhabdo when Genfibrozil used w/ statin
HA, rash, GU malignancy
Monitor LFTs when used w/ statin
Avoid using Gemfibrozil w/ ?
Contraindications for using Fibrates?
Any statin
Liver/kidney/biliary dz
MOA of B3
What is used for?
Inhibits formation/secretion of VLDL and inhibit lypolysis
Best for raising HDL
PTs intolerable to statin
PTs with Heterozygous Familial Hypercholesterolemia use what med combo?
Niacin w/ resin/HMG-CoA reductase inhibitor
Adverse effects of using NIacin
Flushing/warmth (red w/ aspirin 30m prior)
GI upset
Adverse effects of Niacin?
Contraindications for use?
Liver toxicity
Hyperuricemia/glycemia
Liver Dz, Gout, peptic ulcer, allegy
Monitor LFTs at base, 6-12wks and annual
MOA of BABA
Bind to bile salts leading to more cholesterol being converted to bile salts w/out being absorbed
When are BABAs used?
PTs can’t use statins
T2DM adjunt
What are the names of the BABAs?
Colistepol- Cat B
Cholestyramine- Cat C
Colesevelam- Cat B
Adverse effects and contraindications of using BABAs?
GI distress
Constipation
Dec drug absorption
Inc TG >400
What is the name of the selective cholesterol absorption inhibitor drug
Ezetimibe
Inhibits absorption in small intestine of all cholesterols
When is Ezetimibe used?
Adjunct to statins
Reduces LDL in Primary Hyperlipidemia and Homozygous Family Hyperlipid
What are the Ezetimibe combos?
Take 2hrs prior or 4 hrs after
Atrovastatin/Eze
Simbastatin/Eze
MOA of PCSK9 Inhibitors
Inhibits enzyme from binding to LDLReceptors and promote LDL degradation in liver
Clinical uses of PCSK9 Inhibitors
Effective LDL lowering
Adjunt w/ diet and max statin dose
Adverse effects of PCSK9 Inhibitors
Nasopharyngitis
Influenza
Site reactions
What are the names of the PCSK9 inhibitors
Alirocumab
Evolocumab
Use of Omega 3 FAs
Lowering TG
Modest HDL increase
May raise LDL if TG is high
What are the medications for Omega 3 FAs?
Lovaza (burps, fish taste aversion, dyspepsia)
Icosapent Ethyl- only has EPA
When is Icosapent Ethyl used
Adjunct to diet to reduce TGs in PTs w/ severe hypertriglyceridemia
Use for Psyllium
Metamucil
Bulk forming laxative w/ LDL lowering abilities
Pharmacological applications for Hypothalamus/Pituitary
Replace hormone deficiency
Antagonist for excess hormone production
Dx for endocrine issues
Use of CRH in clinical
Dx agent between Pituitary (Cushings) and Ectopic production of ACTH
What happens to PT with Cushings who receives CRH
Corticoreline Ovine Triflutate
ACTH and cortisol secretions
Ectopic production won’t respond
What is the HPA axis
Hypothatlamus CRH Ant Pituitary ACTH Adrenal Cortex CORT
Function of pulsatile and sustaine GnRH
P= stimulate gonadotroph cell to release LH and FSH until puberty S= inhibit release of FSH and LG resulting in hypogonadism
Role of FSH in men and women
W= ovarian follicle development M= Regulate spermatogenesis
Role of LH in men and women
W= stimulates androgen production in folicular stage of menstrual cycle M= testosterone synthesis stimulation in Leydig cells
When are GnRH or LHRH used clinically
Treat infertility Precocious puberty Transgenders Prostate cancer Assisted reproductive technology Ovarian suppression
Adverse effets of GnRH and LHRH use
Flare of of dz in first week of therapy
Hot flash
Erectile impotence
Dec libido
LHRH is released by the ___ in a ___ manner
Hypothalamus
Pulsatile
What hormone is under study for it’s role in aiding/developing prostate cancer?
FSH
What are the names of the GnRH/LHRH drugs
Goserelin Leuprolide Nafarelin Histrelin Acetate Triptorelin
What are the approved scenarios for using GnRH and LHRH
Prostate cancer
Enometriosis
Central Precocious Puberty (Nafarelin)
MOA of GnRH Antagonists
Suppresses LH and FSH
Turns GnRH receptor off to avoid testosterone surges
What drugs are used as GnRH antagonists to inhibit premature LH surges in women undergoing ovarian hyperstimulation procedures?
Ganireliz
Cetrorelix
Men w/ prostate cancer= Degarelix
What are the Ant Pituitary Hormones
G FLAT GH TSH ACTH FSH LH PRL
What inhibits growth hormone/somatotropin
Somatostatin
IGF-1
What inhibits TSH
T3/T4
What inhibits ACTH
Cortisol
What inhibits FSH
Inhibin
Estrogen
What inhibits LH
Estrogen
Progestine
Testosterone
What inhibits PRL
Dopamine
What causes Acromegaly and Gigantism
Pituitary adenoma secreting growth hormone
What causes hyperprolactinemia
Prolactinoma
CNS lesion
What are the three hyper secretion Dzs
Acromegaly
Gigantism
Hyperprolactinemia
What are the hyposecretory Dzs
GH deficiency
Panhypopituitarism
What drugs are used for Acromegaly
Somatostatin analogs
GHR Antagonist
Dopamine antagonists
Somatostatin inhibits release of ?
GH
Glucagon
Insulin
Gastrin
When is Somatostatin used?
Acromegaly
Vasoactive Intestinal peptide secretory diarrhea
Esophageal varices bleeding
What are the Somatostatin drugs?
Octreotide
Lanreotide- Acromegaly only
MOA of Pegvisomant
Blocks GH binding and DEC IGF-1 levels
Used in Acromegaly resistant/intolerable to other therapies
When can GH therapy be used for kids?
Inadequate GH- Turner, Noonan Synd
Chronic renal insufficiency
Catch-up if failing at 2-4yrs
Prader-Willi Syndrome
When can GH therapy be used for adults?
HIV wasting
GH deficiency replacement
Short bowel syndrome
What is the use of TSH
Thyrotropin
Dx agent for detecting thyroglobulin from cancer after extomy
Thyrotropin Alfa
What is ACTH used for?
Differentiate between Addisons 1* or 2* pituitary disorder
Cosyntropin
What are the FSH LH drug names
Follitropin alfa
Follitropin beta
Urofollitropin- urine of post-menopause women
Lutropin alfa- LH
What drugs are used for hyperprolactinemia
D2 Agonists- Bromocriptine or Cabergoline
What are the two Posterior pituitary hormones
ADH (AVP)
Oxytocin
When is ADH clinically used?
DI
Esophageal varices
Vasodilatory shock
When is Desmopressin used?
DI Polyuria/dipsia Hemophilia A von Willebrand Dz Nocturnal enuresis
Treatment of hyponatremia needs to be weighed against the risk of inducing ?
Central Pontine Myelinolysis
What are the treatment goals of SIADH
Raise serum Na by 0.5-1 mEq/hr
No more than 10-12 mEq in first 24hrs
What drugs can be used as vasopressin antagonists for SIADH
Conivaptan- hospitalized PT
Tolvaptan- PT w/ HF and SIADH
What causes oxytocin to be released
Neuroendocrine reflex
What is oxytocin used for in clinic
Stimulate lactation
Labor induction
Post-partum bleeding
What drug has off label use for stimulating lactation in women
Metoclopramide