Pharmacology Flashcards
Somatropin
Identical to human GH (191 aa)
Somatrem (extra methionine)
PK: IM or SC 3-7x/week, depot IM 1-2x/month
MOA: activate GH receptor (cell surface, Jak-Stat pathway–>nucleus effects)
Tx: replacement tx for GH deficiency, prior to epiphysial closure, maintenance therapy (increased linear growth, bone/muscle formation, decreased fat, increased sense of well being), $$$$
Other: Turner’s syndrom, Prader-Willi syndrome, idiopathic short stature
Problems: increased mortality v. general population, abuse for anabolic effects, does not work for Laron dwarfism (GH receptor defect, requires IGF for treatment)
Sermorelin
Synthetic GHRH analog (shortened version)
PK: daily IV, SC, or nasal
MOA: activates GHRH receptor (GPCR), stimulates endogenous GH release –> stimulates IGF-1 release and growth
Tx: GH deficiency
Problems: ineffective with pituitary defect (no GHRH receptors) (require GH or IGF tx)
Octreotide
Synthetic analog of SST (8 aa: shorter, more stable)
Longer t1/2 than SST
Less effect on insulin (select for GH release)
PK: 2-3 SC injections/day, monthly IM depot
MOA: activates SST receptors (GPCR), selective for SST-2 and -5 subtypes (hormone-secreting tumors)
Tx: acromegaly dt GH-secreting tumor, hormone-secreting tumors with SSTRs, GI-secretion disorders
Problems: inhibition of GI motility and secretions (loose stools, nausea, malabsorption, flatulence, gallstones), $$$$
Cabergoline
DA agonist analog –> inhibit PRL release
Not a peptide = orally effective
long t1/2 = 1-2x/wk dosing
Same drug used in PD (decreased PRL is a side effect)
MOA: PRL inhibition via D2 receptors (GPCR); cabergoline is D2-selective
Tx: hyperprolactinemia (and resulting infertility), prolactinoma, suppression of lactation, inhibit GH release (acromegaly; in normal patients it stimulates GH release)
Problems: Nausea, dizziness, hypotension (D2 receptors); tolerance
Arginine vasopressin (AVP)
Synthetic, identical to natural hormone
Short acting
PK: IV, IM, SC, or nasal
MOA: V1 and V2 effects
Tx: V1 receptor-related applications (short duration); temporary diabetes insipidus following pituitary surgery (V2); local administration for bleeding artery constriction (rapid hydrolysis); prevent/treating hemorrhage; vasoconstriction in resuscitation of V tachycardia and fibrillation
Problems: increased blood pressure, GI/uterine contractions/cramps (cross-reactive with oxytocin receptors), headaches and nausea
Desmopressin acetate (DDAVP)
Modified synthetic analog of vasopressin
Long-acting (10-20 hours)
V2 (antidiuretic)»_space;» V1 (pressor) activity
PK: IV, SC, inhaled nasal, oral (first orally administered peptide hormone drug)
MOA: activate V2 vasopressin receptor
Tx: diabetes insipidus, hemophilia, vonWillebrand’s disease, oral desmopressin for nocturnal enuresis (inhaled caused hyponatremia –> seizure and death for this)
Problems: V1-side effects of AVP are minimal with DDAVP dt V2 selectivity
Levothyroxine
Pure T4
Low onset, long duration (more protein bound)
Converted to T3 in body
Dose: 100 ug
Oral
Tx: Primary drug due to daily dosing, given IV for myxedema coma, slow onset/long duration (plasma stores)
Small dose for old patients or those with cardiac disease, continued use during pregnancy (requirements increase)
Adverse: overdose, hyperthyroidism
Liothyronine
Pure T3
Rapid onset, short t1/2 (less protein bound)
Rapid onset, sudden dramatic physiological changes (dangerous)
Dose: 25 ug (4x more potent than T4)
Oral
Tx: rarely used in chronic therapy, used prior to surgery for thyroid cancer (maintain suppressive effects as patient tapered off T4), short-term support prior to/following radio iodine, limited use in treating depression
Adverse: overdose, hyperthyroidism
Methimazole (MMI)
Thioamide: inhibit TH synthesis
Inhibit peroxidase, iodination, and coupling
More potent than PTU, longer-acting (qd dosing)
Delayed effect dt latent period from stored T3/T4
Direct anti-autoimmune effects –> disease remission (possible)
Tx: first line therapy (“non-destructive”), rapid control of thyroid hormone production, 1 year
PK: oral, cleared from circulation, concentrated in thyroid (action longer than plasma half-life), metabolism by conjugation, urine excretion
Adverse: agraunulocytosis **, rare fetal problems
Propylthiouracil (PTU)
Thioamide: inhibit TH synthesis
Inhibit peroxidase, iodination, and coupling
Less potent than MMI, shorter half-life (2-4x/day dosing)
Inhibits peripheral conversion of T4 –> T3 (more rapid effect in acute thyroid storm)
Delayed effect dt latent period from stored T3/T4
Direct anti-autoimmune effects –> disease remission (possible)
Tx: first line therapy (“non-destructive”), rapid control of thyroid hormone production, 1 year, THYROID STORM, PREGNANCY (mild hyperthyroidism, treat prior to pregnancy)
PK: oral, cleared from circulation, concentrated in thyroid (action longer than plasma half-life), metabolism by conjugation, urine excretion
Adverse: agranulocytosis**, liver toxicity/failure
Propranolol
Beta blocker: treat hyperthyroid (SNS) symptoms
Potassium iodide
Inhibit TH synthesis
Acute inhibition of synthesis and RELEASE of T3/T4
No effect on T4–>T3 conversion
Rapid effects, short duration (gland “escapes” inhibition) (increased iodine available increases hormone synthesis)
Vasoconstrictor effect (decreased size/vascularity of gland)
Tx: “firm up” the gland for easier removal, not useful for long-term therapy, immediate pre-op period (10 days), thyroid storm (acute effect, inhibit release of preformed thyroid hormones), radiation emergencies (inhibit uptake of radioactive iodine)
Do not use before radio iodine therapy
Adverse: sore throat, burning mouth, rash, diarrhea
Radioactive iodine
Non-surgical destruction of thyroid gland
t1/2 = 8 days
15% gamma radiation (diagnosis); 85% weak beta radiation (1-2 mm travel)
oral, concentrates in thyroid
Tx: large (mCi) doses for destruction of thyroid tissue, pretreat with thioamides (lower TH –> increase TSH –> increase/max radioiodine uptake; decreased TH levels lessen risk of treatment-induced thyroid storm)
Concerns: minimal radiation danger, very localized effects, contraindicated in pregnancy, nursing, and young children, high doses –> radiation thyroiditis & salivary adenitis; transient/permanent hypothyroidism (treat with replacement T4)
Regular insulin
Natural
Original rapid/short-acting
Prep with physiological level of Zn (readily soluble, readily absorbed)
Onset: 30-60 min. Peak: 2-4h. Duration: 5-8h.
True solution (clear) (IV)
Use: 30 minutes before meal
Non-prescription
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Isophane insulin (NPH)
Natural
Insulin complex with protamine (protein) at neutral pH
(Neutral Protamine Hagedorn = NPH; ISOPHane)
Slower absorption, longer action
Onset: 1-2h. Peak: 6-12h. Duration: 18-24h.
Cloudy suspension (no IV)
Use: between meals and overnight
Non-prescription
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Inhaled insulin
Old: complications with dosing, device, and lungs
New: fewer lung problems (some cough and throat irritation), rapid-acting prep.
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Insulin lispro
Rapid, short, synthetic
Lys(28)Pro(29) NOT Pro-Lys in B chain
PK: no dimerization = absorbed more quickly, aggregates less (monomer); similar to physiologic pattern of insulin release with meal
Shorter duration of action
Peak: 30-60m. Duration: 3-4h.
Use: immediately before meal (less danger of insulin-induced hypoglycemia)
IV
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Insulin aspart
Rapid, short, synthetic
Pro replaced by Asp
Longer duration than Lispro
B/w regular insulin and lispro in terms of duration
Use: at meal time
IV
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Insulin glulisine
Slow, long, synthetic Lys replaced by Glu; Asp replaced by Lys PK: similar to regular/lispro/aspart Fastest onset Use: before or immediately AFTER a meal IV Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy) Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers--mask symptoms of hypoglycemia), surgery, pregnancy
Insulin glargine
Slow, long, synthetic
Gly substitution in A chain, two Arg at C-terminus of B chain
Formulated with Zn at pH 4 (decrease aggregation, increase solubility, clear sol’n)
Hexamers form at site of injection (pH 7.4) –> slowly, variably absorbed
**Very long, low, constant action
Use: subQ qd at HS (flat PK properties)
Opposite effect of lisper and apart
Do not mix in same syringe as other insulins
May be used in combo with other insulins
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Insulin detemir
Long-acting analog
The is deleted, Myristic acid (14C) att. at Lys(29)
PK: similar to Glargine
Binds to albumin via FA chain
Neutral pH formula
Better, less variable absorption than glargine
Do not mix in same syringe as other insulins
Use: subQ qd at HS
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
NPL/NPA insulins
Isophane (NP) versions of synthetic insulins (protamine complexed)
Synthetic rapid insulins formulated with protamine
Slows and prolongs action
PK: similar to isoprene
Available in premix combos
NPL: NP + Lispro
NPA: NP + Aspart
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy
Pramlintide
Analog of Amylin (peptide hormone from pancreatic B cells)
Effects: decrease post-prandial glucose, decrease liver glucose production, slows gastric emptying, increases satiety
Use: DMI/DMII who lack adequate control with insulin alone
Tx: subQ before meals along with insulin
Adverse: mild nausea, HA, risk of hypoglycemia (reduce dose of short-acting insulin)
Interactions: drugs that slow GI motility or decrease GI drug absorption, renal excretion (kidney disease)
Glucagon
Counter-regulatory hormone to insulin
From pancreas in response to hypoglycemia
Increases glucose
Tx: IM of subQ to treat hypoglycemia
Diazoxide
Inhibits release of insulin
Opens ATP-sensitive K channels (opposite effect of SUs)
Oral
Glimepiride
Sulfonylurea
Enhance insulin secretion from beta cells
MOA: Block ATP-sensitive K+ channels (physiologically, glucose blocks these channels, leading to depolarization, Ca2+ entry, and Ca2+-dependent exocytosis of insulin)
Decrease glucagon and increase tissue sensitivity to insulin
PK: Well absorbed orally, slowed by food; protein bound; qd dosing; metabolized by liver; excreted by kidneys in bile
Effects: hypoglycemia, wt gain, GI/skin/liver/blood abnormalities, c/i in pots with liver or kidney disease
Repaglinide
Meglitinide
Enhance insulin secretion from beta cells
MOA: bind ATP-sensitive K+ channels to increase insulin secretion; not a very strong effect = not very useful
PK: faster effect than SUs, but shorter duration; take 30 minutes before meal to decrease post-prandial glucose
Effects: hypoglycemia (less of a risk), wt gain, safer in kidney disease
Metformin
Biguanide
Decreases glucose production (liver) and increases glucose uptake; increases insulin effectiveness; does not increase insulin secretion (ie. no hypoglycemia)
MOA: upstream action on AMP kinase pathway (regulates glucose metabolism)
Useful in insulin patients with insulin resistance
Used in combo with SUs, etc.
First/best drug to try in DM2
PK: oral, 2-4x/day (after breakfast and supper), absorbed from GI tract, not protein bound, renal excretion w/o metabolism
Effects: c/i in kidney or liver disease (lactic acidosis), does not induce wt gain, inhibits lactate metabolism, unpleasant GI effects (metallic taste, diarrhea, nausea, vomiting, anorexia)
Acarbose
Decrease glucose absorption from gut
MOA: microbial sugars inhibit mammalian sugar-metabolizing enzymes (alpha-glucosidase, amylase); inhibit hydrolysis of disaccharides and complex carbs slows formation/absorption of glucose
Take immediately before meals (lower post-prandial glucose)
Not powerful effects (use in mild disease)
Can be combined with insulin, etc.
PK: Complex oligosaccharide, poorly absorbed, ie. remains in gut (site of action)
Effects: no hypoglycemia, increase hypoglycemia risk when combined with insulin, glucose (not sucrose–disaccharide) required to treat hypoglycemia, flatulence, cramps, diarrhea, avoid with metformin (avoid GI effects)
Miglitol
Decrease glucose absorption from gut
MOA: microbial sugars inhibit mammalian sugar-metabolizing enzymes (alpha-glucosidase, amylase); inhibit hydrolysis of disaccharides and complex carbs slows formation/absorption of glucose
Take immediately before meals (lower post-prandial glucose)
Not powerful effects (use in mild disease)
Can be combined with insulin, etc.
PK: simple monosaccharide, does get absorbed
Effects: no hypoglycemia, increase hypoglycemia risk when combined with insulin, glucose (not sucrose–disaccharide) required to treat hypoglycemia, flatulence, cramps, diarrhea, avoid with metformin (avoid GI effects)
Pioglitazone
Thiazolidinedione
MOA: bind peroxisome proliferator-activated receptor-gamma (PPAR-gamma) (nuclear TF that enhances transcription of insulin-responsive genes); AMP kinase signaling
Decrease gluconeogenesis, glucose output, and TG synthesis in liver
Increase glucose uptake and utilization in muscle
Increase glucose uptake and decrease FA production in adipocytes
Used with insulin, SU, and/or metformin
PK: oral, take with food, qd, metabolized in liver, excreted in feces (safe in renal disease)
Effects: hepatotoxicity, fatal liver disease (liver fxn testing), CV disease/death risk (edema, CHF, ischemia, angina MI), no hypoglycemia risk, increase fracture risk (elderly, women, osteoporosis), less effective than hoped
Rosiglitazone
Thiazolidinedione
MOA: bind peroxisome proliferator-activated receptor-gamma (PPAR-gamma) (nuclear TF that enhances transcription of insulin-responsive genes); AMP kinase signaling
Decrease gluconeogenesis, glucose output, and TG synthesis in liver
Increase glucose uptake and utilization in muscle
Increase glucose uptake and decrease FA production in adipocytes
Used with insulin, SU, and/or metformin
PK: oral, take with food, qd, metabolized in liver, excreted in feces (safe in renal disease)
Effects: hepatotoxicity, fatal liver disease (liver fxn testing), CV disease/death risk (edema, CHF, ischemia, angina MI), no hypoglycemia risk, increase fracture risk (elderly, women, osteoporosis), less effective than hoped
Exenatide
Incretin-based
Analog of GLP-1 (glucagon-like peptide-1)–released in response to food
Potentiate insulin secretion, decrease glucagon secretion, slow gastric emptying (satiety), moderate reductions in fasting glucose, reduced post-prandial glucose
Wt. loss
Use: with SU and/or metformin, with insulin glargine (DMII)
Inject SC from pre-filled pens (before morning/evening meals); now available in XR for weekly injection
Effects: nausea, hypoglycemia risk (with SUs), renal failure, thyroid C-cell tumors and pancreatitis
Alters absorption of antibiotics and contraceptives (so takes these before injection); avoid in kidney disease
Pramlintide
Amylin-based
Amylin analog
Used in DMII who are already on insulin and who lack adequate control
Sitagliptin
DPP-IV inhibitors
Similar effect as GLP-1 agonist
MOA: inhibits DPP-IV (degrades endogenous incretins), prolongs endogenous incretin action
PK: oral, qd, effective as monotherapy
Fixed-dose combo with metformin and/or pioglitazone available
DMII only (and still slightly risky)
Effects: no wt gain or loss, increased hypoglycemia risk when combined, increased risk of respiratory tract infection (DPP-IV important there too), renal elimination
Canaglifozin
SGLT2 inhibitor
MOA: inhibit sodium-glucose co-transporter 2 (SGLT2) (mediates glucose reabsorption in kidney); reduces glucose reabsorption –> increases glucose excretion
PK: oral, qd in am
No direct effect on insulin
Effects: risk of genital and UTI, diuretic effect (dehydration, hypovolemia, hypotension)
Hydrocortisone/cortisone (endocrine)
Cortisol Cortisone: prodrug of hydrocortisone Activity at GC and MC receptors Orally effect, IV prep available Short acting, 8-12h duration, multiple doses needed
Prednisolone/Prednisone (endocrine)
Modified hydrocortisone structure Prednisone: prodrug of prednisolone More potent, slower metabolism Longer duration, 18-36h, qd dosing Selective for GC v. MC effects (important for anti-inflammatory effects)
Fludrocortisone (endocrine)
Increased potency and selectivity at MC receptor
Also retains strong GC potency and efficacy
Long duration of action, qd dosing
Use: when MC replacement therapy or action is primary goal (adrenal failure, 21-hydroxylase deficiency)
Spironolactone (endocrine)
Aldosterone antagonist K+ sparing diuretic Treat aldosterone-secreting tumors Anti-androgenic effects (gynecomastia, hirsutism) Progesterone agonist activity
Dexamethasone
Used if very high doses of Hydrocortisone/Prednisolone or their prodrugs are inadequte
Reduce reddness, swelling (vasoconstriction, decreased permeability, direct effect on bv, decreased release of kinins and histamine), fever, and pain (decrease prod of AA metabolites, inhibit prostaglandin, thromboxane, and leukotriene release, decrease expression of phospholipase A2 and COX-2)
Immunosuppression
MOA: alter transcription (decreases pro-inflammatory genes, increase anti-inflammatory genes)
Tx: arthritis, bursitis, skin inflammation, collagen vascular disorders, hypersensitivity, allergic reaction, asthma, renal disease, ulcerative colitis, IBD, eye disease, prevent organ/graft rejection, AFTER BRAIN/SC INJURY (minimize cerebral edema)
Effects: MC effects (edema, low Na, low K, alkalosis, HTN,), GC effects (similar to Cushing’s syndrome)
C/I: heart disease, HTN, diabetes, peptic ulcer, infection, osteoporosis, glaucoma, psychoses
Bethamethasone
Glucocorticoid
Stimulate surfactant production for lung maturation in premature infants
Give to mother before delivery (less protein bound, better delivery to fetus)
