CPEE TEST 1 Flashcards
Somatropin
- 191 AA GH analog
- Given 3-7/week SC or IM
- Activate GH receptor –> Jak-Stat Pathway
- Children with GH deficiency prior to epiphysial closure
- Doesn’t work in Laron form of dwarfism due to GH receptor defect
Sermorelin
- GHRH analog (1-29 AA residues, increase t 1/2)
- IV, SC, Nasal
- Activates GHRH receptor –> GH release –> IGF-1 release
- GH analog preferred
Mecasermin
- IGF-1 Analog
- Laron Dwarfism
- Hypoglycemia, Overgrowth of facial bones, antibodies may lead to resistance
Octreotide
- Synthetic Analog of somatotropin (8-AA cyclic peptide, stabilized)
- Longer T-1/2 and less decrease of insulin secretion
- 2-3 injections/day
- Treat acromegaly due to GH secreting tumor or hormone secreting tumors with SST receptors
Pegvisomart
- GH receptor antagonist
- Used to treat Acromegaly.
Prolactin System
-Release stimulated by TRH and inhibited by Dopamine
Cabergoline
- DA agonist analog to inhibit PRL release
- Orally effective 1-2/week
- PRL inhibition is via D2 receptor and Cabergoline is D2 selective
- Treat hyperprolactinemia, prolactinoma, suppression of lactation, inhibit GH release (acromegaly)
Arginine Vasopressin
- ADH analog short acting
- IV, IM, SC
- V1 (vasoconstriction) and V2 (aquaporin channels and von willebrand factor) effects.
- Choice for V1 applications
- Treatment of temporary diabetes insipidus
- CV: Local admin for constriction, Vasoconstriction in resuscitation of V tach or V fib
Desmopressin Acetate
- Modified synthetic analog of ADH
- Longer acting and more V2 action
- First orally available peptide
- First choice diabetes insipidus
- Caution with overnight use –> hyponatremia
Drugs used to INCREASE TH
Levothyroxine and Liothyronine
Levothyroxine
- Pure T4 with slow onset, but long duration
- Primary drug used in hypothyroidism due to long duration
- IV form used for Myxedema coma
Liothyronine
-Used mostly to maintain suppressive effects of TH on TSH prior to surgery thyroid cancer
Use of TH in older patients or patients with Cardiac disease
-Start small and slowly increase b/c increase metabolic demand can strain weakened hearts
TH hormone use in Myxedema Coma
-Levothyroxine IV initially followed by oral maintenance
Drugs used to treat HYPERTHYROIDISM
- Propanolol
- Thioamide (Propyluracil and methimazole) to block synthesis of T4
- Radioiodine to destroy thyroid.
Methimazole and Propylthiouracil: MOA, Uses, Pharmacokinetics, and Adverse effects
Inhibit Peroxidase, iodination, coupling, and block synthesis. DON’T inhibit release of preformed TH
- Used for first line therapy of hyperthyroidism
- Well absorbed orally and concentrated in thyroid so duration of action is longer than plasma half life.
- Agranulocytosis occurs, but rare. If person has sore throat and fever in the first few months of therapy stop and give antibiotics
Propylthiouracil
- Less potent and short half-life
- Preferred in THYROID STORM because it blocks T4 –> T3 conversion
- Also preferred in pregnancy due to lack of side effects (Generally treat to moderately hyperthyroid status
Methimazole
- more POTENT and longer acting than propylthiouracil
- Doesn’t cause liver toxicity/failure
Potassium Iodide
- Inhibits synthesis and release of TH
- Rapid effects, but short duration.
- Decreases vascularization and firms up gland prior to surgery
- Beneficial in THYROID STORM to stop release of preformed hormone
- Radiation emergencies to prevent uptake of radioactive iodine
Regular Insulin
Physiologic level of zinc and no protein added
- Short acting
- Onset 30-1 hr, Peak 2-4, duration, 5-8
- IV
Isophane insulin suspension
- Complex with protein at neutral pH
- Slower absorption and longer action than reg. insulin
- Cloudy suspension CAN’T be given IV
- Between meals
Insulin Lispro
- Analog
- Lys 28 Pro 29 (Normally opposite)
- Less aggregation –> Faster absorption
- Shorter Action
- Peak 30-60 w duration of 3-4 hrs
- Can be injected immediately before meals
- IV
- Less danger of hypoglycemia due to dosage close to meals
Insulin Aspart
- Pro 28 replaced with Asp
- Similar to Lispro but longer duration of action (between regular and lispro)
- Injected at meal times and CAN be given IV
Insulin Glulisine
- Lys 29 replaced by Glu and Asp 3 replaced by Lys
- Injected before or immediately after meal.
- IV
Insulin Glargine
- Gly 21 in A chain and 2 Arg added at C-terminus of B chain
- W/ Zn @ pH 4 to decrease aggregation
- Forms hexamers that precipitate at site of injection
- SC administration once per day
- DONT mix with other insulins in the same syringe
Insulin Detemir
- Similar kinetics to Glargine
- Thr 30 deleted and myristic acid chain added to Lys 29
- Binds to albumin via fatty acid chain
- Better and Less variable absorption than Glargine
Pramlintide
- Analog of Amylin which is released from Beta cells with insulin
- Decreases post prandial glucose, liver glucose production and slows gastric emptying
- Type 1 and 2 Diabetics who lack control with insulin alone
- Injected SC before meals
Glucagon
Counter regulatory to insulin.
- Used with hypoglycemia
- IM or SC
Diazoxide
-Opens ATP sensitive K+ channels to inhibit glucose release
Prototype Sulfonylurea
-Glimepiride
Sulfonylureas: MOA and PK
- Closes ATP sensitive K+ –> insulin release and increase tissue sensitivity to insulin and decrease glucagon
- Well absorbed orally, protein bound, liver metabolism w/ kidney excretion (Once daily)
Sulfonylureas: Side effects
- HYPOGLYCEMIA especially when used with insulin
- WEIGHT GAIN
- Dont use in patients with LIVER or KIDNEY DISEASE
- Falling out of favor
Meglitinide prototypic drug
Repaglinide
Meglitinide (Repaglinide) MOA, PK
- MOA: Similar mechanism to Glimepiride, closes K+ channels Lowest effects of all oral agents
- Faster than SU (glimepiride) but shorter duration
- 30 min before meal
Meglitinide (Repaglinide) Side effects
- HYPOGLYCEMIA
- WEIGHT GAIN
- MAY be safer than SUs in kidney disease
Biguanide Prototypic drug
METFORMIN BABY!
Biguanide (Metformin): MOA, Uses
- Primary effects in liver: decreases glucose production and increases uptake, and increases insulin effectiveness
- DOESN’T increase insulin secretion
- Upstream action on AMP kinase pathway (regulates glucose metabolism)
- Used with insulin to make insulin more effective
- 1ST LINE DRUG AGAINST DIABETES
- CAN BE USED WITH SUs AND OTHER ORAL AGENTS
Biguanides (Metformin): PK and Side effects
- Orally effective typically 2-4 times per day w/meals, ER available
- Renal excretion (KIDNEY DISEASE)
- Inhibits lactic acid metabolism (LIVER DISEASE)
- NO HYPOGLYCEMIA
- NO WEIGHT GAIN
- Inhibits lactate metabolism
Alpha Glucosidase Inhibitors
-Miglitol and Acarbose
Alpha Glucosidase Inhibitors (Miglitol and Acarbose): MOA and PK
- Microbial sugars that inhibit mammalian sugar metabolizing enzymes
- Immediately before meal
- NOT POWERFUL
- Used with insulin or other oral agents
- Acarbose = Complex = longer in gut
- Miglitol= Simple monosacchride = absorbed
Alpha glucosidase inhibitors (Miglitol and Acarbose): Side Effects
- HYPOGLYCEMIA w/ insulin/OA (Must use glucose to treat)
- Flatulence
- Avoid with Metformin
Thiazolidinediones (Pioglitazone and Rosiglitazone): MOA
- Bind to PPAR-Gamma, nuclear transcription factor –> ^transcription of insulin responsive genes (make insulin more effective)
- Also use AMP Kinase like Metformin
- Decrease: Gluconeogenesis, glucose output and triglyceride synthesis in liver
- Increase Glucose uptake and utilization in muscle
- Most often used with insulin, SU and/or Metformin
Thiazolidinediones (Pioglitazone and Rosiglitazone): PK
- Orally effective best with food once daily
- Metabolized in LIVER and excreted in FECES
Thiazolindinediones (Pioglitazone and Rosiglitazone): Side effects
- Hepatotoxicity and fatal liver disease
- NO HYPOGLYCEMIA
GLP-1 Agonist (Exenatide): Effects and Uses
- GLP-1 Analog
- Increases insulin secretion
- Slows gastric emptying
- Reduces post prandial glucose
- LACK OF WEIGHT GAIN (weight loss)
- Metformin/SU/Insulin Glargine for Type 2 (SC before meals
GLP-1 Agonist analog (Exenatide): Side Effects
- HYPOGLYCEMIA with SU
- Renal Failure risk
- Take antibiotics and Contraceptives before because of altered absorption.
DPP-IV Inhibitor (Stiagliptin): Mechanism, PK, and Uses
- Inhibits DPP-IV which degrades GLP-1
- Orally once/day
- Monotherapy
- Use with Meformin (Biguanide) or Rosiglitazone (Thiazolidinedione)
- NO WEIGHT GAIN OR HYPOGLYCEMIA
SLGT-2 Inhibitors (Canagliflozin): MOA and Side effects
- Inhibits SLGT2 that mediates reentry of glucose in to kidney –> More glucose excretion in the urine
- Orally once per day
- Increased risk of urinary tract infections
Hydrocortisone
- Active at both GC and MC receptors
- Orally effective
- Adequate for most endocrine uses
- Many OTC preparations for inflammation
Prednisone
- More potent due to slower metabolism
- Partially selective for GC vs MC (uses in inflammation)
Dexamethasone & Betamethasone
- Highly GC selective
- Very long duration of action
- Very potent (decrease protein binding and mods that slow metabolism)
- Very strong GC effects w/ no MC effects
- Used for inflammation if high doses of
- Bethamethasone used to increase surfactant production in infants.
Fludrocortisone
- Increased potency and activity at MC receptor w strong GC activity
- Once per day
- MC replacement therapy or action
COX-1
- Fever and Pain
- Increase platelet aggregation
COX-2
- Pain and inflammation
- Decreased endothelial aggregation
Metabolism of Salicylate
- Low doses: liver by conjugation (first order/saturable)
- Higher does: unmetabolized and excreted via the kidneys (zero-order)
Doses for inhibition of inflammation, analgesic, and anti pyretic effects
Inflammation: higher doses that saturate liver and renal elimination (COX-2)
Analgesic and anti-pyretic: lower doses (COX-1)
Aspirin effects to prevent thrombus and prolong bleeding time
- COX-1: make thromboxanes which increase clotting so want supression (low dose)
- COX-2: Make prostacyclins which decrease clotting and thrombosis risk (need a higher dose to inhibit, but don’t want to inhibit)
Propionic Acid Derivatives
Ibuprofen and Naproxen
Ibuprofen and Naproxen
- Reversible and competitive inhibition of COX
- Bind heavily to albumin (displace warfarin)
Ibuprofen
- Low dose for analgesia and antipyresis
- High dose for anti-inflammation
- Can block effects of low dose aspirin
Naproxen
-Higher doses with prescription
Acetic Acid Derivatives
-Indomethacin, Celecoxib, and acetaminophen
Indomethacin
- 20 times more potent than asprin
- Mainly used for severe inflammation
Celecoxib
- Selective COX-2 Inhibitor
- Treat inflammation and avoid COX-1 side effects
- Osteo and rheumatoid arthritis
- Fewer problems in asthmatics
- Increased risk of MI (clotting)
- Edema b/c decreases kidney function
Acetaminophen
- NO anti-inflammatory action
- Doesn’t really have any of the side effects that aspirin has
- cross sensitivity with aspirin can be serious
- Hepatic damage with alcohol (due to to reactive electrophile metabolites that can modify liver proteins
N-Acetylcysteine
-Sulfhydryl compound to capture reactive acetaminophen or replace glutathione levels jhfgj
Mu Receptors
- Morphine like actions
- CNS spinal cord and periphery
- analgesic, anti-anxiety, resp depression, euphoria, physical dependence, GI, and sedation
Kappa Receptors
- Pentazocine like actions
- CNS and spinal cord
- Analgesia, miosis, sedation, dependence, dysphoria, and Hallucinations
Delta Receptors
- Enkephalin like actions
- CNS periphery
- Dependence, euphoria, analgesia
Enkephalins
-Act at delta and mu receptors
Dynorphins
- Act at Mu and Kappa
- opiate receptor agonists longer acting than enkephalins
Endorphins
-Act at Kappa, Mu, and Delta receptors
Morphine
Natural constituent of opium
- Absorbed by all routes, EtOH can break down slow release matrix
- Conjugation with glucuronic acid in liver (morphine-3-beta-glucuronide can induce seizures)
- Develop tolerance
Morphine Analgesia
- Blocks peripheral and spinal transmission of pain and blocks response to pain
- More effective against continuous dull pain
- Raising pain threshold and anti-anxiety effect important for severe pain
Morphine Respiratory depression
- Primary cause of death in overdose
- decreases chemoreceptor sensitivity to CO2 but Hypoxia response still present
- FOR ALL OPIODS THE GIVEN RESPIRATORY DEPRESSION AT A GIVEN LEVEL OF ANALGESIA IS THE SAME
Morphine naseau and vomiting
-stimulation of chemoreceptor, tolerance develops quickly
Morphine and GI effects
-Constipation, no tolerance develops
Morphine and pupilary constriction
-No tolerance, diagnostic
Morphine Limitation and Contraindications
- Decreased respiratory reserves
- Head injuries
- Pregnancy
- Don’t use with CNS depressant
Codeine
- More reliable orally compared to morphine
- Mild to moderate pain
- Effective for cough suppression
- More constipation
Methadone
- Very effective orally
- CYP3A4
- T1/2 of 15 hrs
- Serious CV effects
- Parenteral euphoria and dependence
- Analgesia and treatment of drug dependence
Fentanyl
- Extremely potent opioid agonist
- Treats chronic (patch) and breakthrough pain (nasal spray or tablet)
- similar effects to morphine
- Muscle rigidity of
Hydrocodone
-most prescribed drug
Oxycodone
More potent than hydros
-Loperamide
-Potent anti-diarrheal agent full opioid agonist action limited to GI tract
Dextromethorphan
- Cough supressant
- No analgesia
Partial opioid agonist
- agonists when given alone
- most kappa receptors
- limited analgesic and respiratory depression effects
- Antagonists when on board with full agonist
- Pentazocine
- Buprenorphine
- Tramadol
Pentazocine
- similar to morphine
- Kappa partial agonist
- mu antagonist/partial agonists
- analgesia sedation and resp depression, similar to morphine at normal doses
- dysphoria at high dose
- may precipitate withdrawal in opioid dependent people due to antagonist action
- analgesia in moderate to severe pain
Buprenorphine
- partial agonist at mu receptors
- antagonist at kappa receptors
- analgesia in moderate to severe pain (has a ceiling)
- similar effects to morphine on eyes and gi tract
- uses analgesia and treatment of opioid dependence
Tramadol
- Weak mu agonist
- can produce dependence
- Inhibits NE and 5HT transport
- seizures serotonin syndrome
Opioid antagonists
-Naloxone
Naloxone
- opioid antagonist with no agonist actions at normal doses
- used to counteract effects of opioids
- will precipitate withdrawal
