Flashcards in Final Review Deck (112):
Diabetic agents that cause pancreatitis?
Exenatide - GLP-1 (incretin) analog
Sitaglipitin - DPP-IV inhibitor (inhibits incretin break down)
Diabetic agents that liver function needs to be monitored?
TZDs (Pioglitazone and Rosiglitazone) - increase insulin sensitivity [Pioglitazone has a good lipid profile, both also cause fluid retention]
Acarbose - a-glucosidase inhibitor
Inhibits gluconeogenic enzymes via AMPK -- weight loss os common
AE - B12 def, lactic acidosis, possible disulfiram rxn (in the sense that alcohol causes hypoglycemia and metformin decrease glucose production)
Binds SUR1 subunit and blocks ATP-sensitive K+ channels
1st gen - Chlorpropamide -- watch for SIADH and DISULFIRAM rxn
2nd gen - Glyburide, Glipizide, Glimepiride
AE - infections and osmotic imbalance
Growth hormone antagonist
Somatostatin analog - inhibits release of GH, TSH, glucagon, Insulin and gastrin
45x more potent in inhibiting GH release compared to somatostatin
2x more potent in reducing insulin secretion
t1/2 = 80 minutes
Octreotide acetate - long acting suspension given at 4 week intervals
Clinical application - reduce hormone-secretion tumor symptoms, localize neuroendocrine tumors, acute control of bleeding from esophageal varices
AE - nausea, vomiting, abdominal cramps, flatulence, steatorrhea, constipation, biliary sludge, gallstones, sinus bradycardia, vit B12 def (with long term use), pain at injection site (common)
Ganirelix and Cetrorelix
Desmopressin and Vasopressin?
ADH analogs -- MINIMAL V1 affinity (SM cells on efferent)
1. DOC for diabetes insupidus
2. Esophageal bleeding and colonic diverticular bleeding (vasopressin)
3. Coagulopathy tx in hemophilia A and vWF disease (Desmopressin)
AE - headache, nausea, abdominal cramps, allergic reaction
Glucocorticoid agonists and antagonists?
Hydrocortisone (Cortisol) [equal amt of anti-inflammatory and salt-retaining activity]
Triamcinolone (aerosol) [no salt retaining ability]
Dexamethasone [no salt retaining ability]
Mineralocorticoid agonists and antagonists?
Agonists... Aldosterone and Fludrocortisone
Antagonists... Spirnolactone (watch out for hyperkalemia)
Tx of cerebral edema and Hodgkins Lymphoma?
Cerebral edema = dexamethasone
Hodgkin's lymphoma = prednisone
Desmolase inhibitor - used to block all adrenal cortex hormones (ex. adrenal cancer)
Ketoconazole in tx of cushings and prostate cancer?
Non-selective inhibitor - inhibits desmolase, 17 hydrox and 17,20 lyase
11B hydroxylase inhibitor -- tx PREGNANT women with cushings
AE... salt and water retention, hirsutism, transient dizziness, GI disturbances
B blockers used in the treatment of hyperthyroidism?
Propranolol, Nadolol, Esmolol (short acting)
MOA - competitive block of B receptors inhibiting conversion of T4 to T3
With pts with asthma, can be given calcium channels instead (diltiazem and verapamil) as alternatives.
Oral Diatrizoate and IV iohexol?
iodinated radiocontrat media that suppress the conversion of T4 to T3 (5-deiodinase) in the peripheral tissue, kidney and liver. It is useful in rapidly reducing the T3 concentration in thyrotoxicosis.
Perchlorate, thiocyanate, pertechnetate?
Rarely used antithyroid drugs that inhibit iodide concentration in the gland by blocking the transportation of iodine in to the thyroid gland.
Possible development of APLASTIC ANEMIA.
Drugs that may provoke autoimmune/destructive inflammatory thyroiditis which can induce hypothyroidism?
2. INF-a and IL-2
3. Lithium - inhibits release of hormones and thyroid enlarge (hypothyroidism)
4. imatinib, sunitnib (TKRI-tyrosine kinase receptor decrease)
5. aminoglutethimide, sulfonylurea
Prostaglandins used for cervical ripening; uterine contractions; postpartum hemorrhage?
Cervical ripening and contraction = misoprostol (PGE1), Dinoprostone (PGE2)
Postpartum hemorrhage = misoprostol and Carboprost Tromethamine (PGF2 analog give IM administration)
-partial a-agonist and some serotonin receptor activity
-tx postpartum hemorrhage
-ergot alkaloid [says erg in the name..]
-contraindicated if pt has CV or cardiac issues
Magnesium sulfate - uncouples excitation-contraction in myometrium inhibiting AP - may cause resp depression or cardiac arrest in mom or baby
Indomethacin - NSAID - may cause oligohydramnios and close PDA early
Nifedipine - Calcium channel blocker - safer than other tocolytics
Atosiban - oxytocin competitive antagonists - not approved in the US
B2 adrenoceptor agonist - phosphorylation of SmMKLCK inhibiting its interaction with calcium-calmodulin complex -- black box warning in the US as it may cause maternal death
Fibroblast growth factor-23?
Produced by osteoblasts and osteoclasts. FGF-23 inhibits calcitriol (activated vit D) production decreasing calcium and phosphate reabsorption in the kidneys and intestines.
*PTH stimulates calcitriol (1a-hydroxylase) activity in kidney whereas FGF-23 inhibits it
-low levels cause bone anabolism
-high levels cause bone catabolism
AE - hypercalcemia, hypercalciuria, osteosarcoma
19-nor-1,25 - dihydroxyvitamin D2
vit D derivative used to treat psoriasis
Suppresses activity of osteoclasts and inhibits bone resorption. It inhibits osteoclastic activity via decreasing farnesyl pyrophosphate synthesis by disrupting mevalonate pathway decreasing osteoclast H+ ATPase.
Uses - osteoporosis and Paget's disease
AE - adhynamic bone, esophageal irritation (risk reduced by drinking water and remaining in upright position for 30 minutes after taking medication), osteonecrosis of jaw
Ex. Risedronate, Ibandronate, Pamidronate, Zoledronate -- all very similar to aledronate
Monoclonal antibody that binds RANKL (rank ligand). Binding to the RANKL leads to inhibition of osteoclastic activity.
Uses - osteoporosis
Subcutaneous every 6 months
AE - increase risk of infections
Calcimemtic that stimulates the calcium-sensing receptors (CaSR) in parathyroid to circulating Calcium leading to decrease in PTH. When the receptors is activated by cinaclcet or free ionized calcium, it activates a signaling pathway to suppress PTH synthesis and release.
Uses - hyperparathyroidism
AE - nausea, vomiting, hypocalcemia, adynamic bone
-tx of hypocalcemic tetany
-Counteracts magnesium sulfate overdose used in eclampsia tx
This is a cytotoxic anticancer drug used in cancer-related hypercalcemia.
AE - thrombocytopenia, hepatic and renal toxicity
Hyperphosphatemia occurs due to renal failure, PTH or vitamin D issue.
Sevalamer treats hyperphosphatemia by decreasing dietary absorption of phosphate by binding phosphate in the GI tract.
Dopa prep containing Carbidopa AND Levodopa.
1. wearing-off reactions - end of dose akinesia which can be related to the timing of levodopa so take more frequently at smaller doses
2. The on-off phenomenom - fluctuations in response that are unrelated to the timing of doses, mechanism is unknown and for pts with severe off-periods may take SC apomorphine
3. Vit B6 is required for dopa decarboxylase reaction so do not give with B6 b/c it increases peripheral metabolism of levodopa?
4. do not coadminister with MAOI as it may precipitate a hypertensive crisis
5. Do not give to psychotic patients b/c it may exacerbate the mental disturabance
6. contraindicated in angle-closure glaucoma
7. may lead to possible arrhythmias
Ergot dopamine receptor agonists?
Bromocroptine (at D2)
AE - pulmonary infiltrates, pleural and retroperitoneal fibrosis, erythromelalgia
Non-ergot dopamine receptor agonists?
Pramipexole and Ropinirole (transdermal patch)
*may cause increased somnolence
Nonergot dopamine agonist used for rescue therapy for tx of "off" episodes of akinesia in pts on dopaminergic therapy. It also has emetogenic properties so should be pretreated with the antiemetic, trimtheobenzamide.
AE - QT prolongation, dyskinesias, drowsiness, sweating, hypotension
MAO and COMT inhibitors used to treat parkinsons?
MAO B inhibitors - Selegitine (metabolite is methamphetamine which may lead to insomnia) and Rasagiline
COMT - tolcapone [may lead to fulminating hepatic necrosis!!] and entacapone
Selegiline (MAO B at normal levels, MAO A at high levels)
-possible hypertensive crisis
AE-sexual dysfunction, SIADH, GI distress
-block SERT and NET
-block a, H, M, Na as well leading to tons of side effects
AE - hypertension
Trazadone ("bone") ad Nefazodone
5HT reuptake antagonist
Nefazodone - associated wit hepatotoxicity
Trazodone - blocks a1 and h1 receptors, extreme sedation, good hypnotic, but there is a troublesome side-effect of priapism
Noradrenergic and specific serotonergic antidepressant (NASSA)
Antagonist of central presynaptic a2 receptors and antagonist of 5-HT2 and 5-HT3 receptors. Little H1 antagonism.
Sedation, weight gain, dry mouth
*helps with smoking cessation
AE - seizures
1. Chlorpromazine (low potency) - may lead to ventricular arrhythmias, corneal deposits
2. Fluphenazine (high potency)
3. Haloperidol (high potency)
4. Thioridazine (low potency) - retinal deposits
1. clozapine -prototype [D1, D2, D4, 5HT2, a, M blockers - may cause seizures, agranulocytosis and weight gain] -- safest with pregnancy with a risk of hyperglycemia
2. risperidone - [DOC!!!! - blocks 5HT2 way more than D2]
6. aripiprazole - partial agonist at D2 and 5HT1A as well as antagonist at 5HT2A receptors
7. paliperidone - 9-hydroxyrisperidone [active metabolite of risperidone]
**more of an effect on weight gain
AE of antipsychotics?
4 hrs - Dystonia (muscle spasms)= tx with anti-muscarinics
4 days - Akathisia (rigidity) = tx with propranolol and clozepam
4 weeks - Parkinsonism (bradykinesia) = tx with antimuscarinics
4 months - Tardive Diskynesia = tx with clozapine and diazepam
Neuroleptic malignant syndrome?
R - rigidity
**tx with dantrolene or bromocriptine
-2nd line agent for GAD
-2 week onset
-really good profile
Why should alprazolam not be used in panic disorder tx?
Rebound anxiety b/t doses and withdrawal
Performance anxiety tx?
B blockers with high lipophilicity [propranolol and nadolol]
acute - Sertraline and Paroxitine [SSRIs]
chronic - Sertraline [SSRI]
-BZ1, BZ2 binding on GABAa increasing frequency of channel opening
-Diazepam, Lorazepam, Triazolam, Temazepam, Oxazepam, Midazolam, Chlordiazepoxide, Alprazolam
LOT - does not go through phase I reaction
AE - CNS depression, ataxia, dependence, drowsiness, confusion
Benzo receptor antagonist -- rapid onset reversal but may precipitate withdrawal in dependent pts
-bind GABA channels and increase duration of opening
-glutamate and sodium channel blocks as well
Phenobarbital, pentobarbital, thiopental, secobarbital
AE - CNS, CV and respiratory depression [exacerbated by alcohol as alcohol also binds GABA receptors so increases potentiation], dependence, hangover effect, decrease ain tolerance
Non-benzo benzodiazepine receptor agonist?
1. zolpidem - sleep initiation
2. zaleplon - tx insomnia
3. eszopiclone - longest half life of 6 hrs and maintains sleep
**act at BZ1 subtype of benzodiazepine receptors acting as hypnotics with minimal muscle relaxing/anticonvulsant activity, lack of tolerance and low AE incidence
Melatonin receptor agonist - MT1 and MT2 melatonin receptors indicated for tx of insomnia
*short half life and used for people who have problems of sleep onset
Antihistamine with antiemetic activity that is also approved for symptomatic relief of anxiety.
Gabapentin and pregabalin?
Block presynaptic VG Ca2+ channels preventing release of glutamate - seizure tx
AE - sedation and ataxia
binds synaptic vesicle glycoprotein 2A (SV2A) - may affect release of glutamate and GABA - very unclear as to what it does other than binding to protein in the vesicle membrane
**low AE profile
DOC of absent seizures (3Hz)
steven Johnson syndrome
Sodium channel inactivator preventing AP transmission.
AE - weight gain, GI disturbance, tremor, pancreatitis, hepatotoxicity, neural tube defects if taken during pregnancy
Tx of status epilepticus?
1. IV lorazepam
2. if seizure continues - IV phenytoin or Fosphenytoin (soluble with better bioavailability)
3. if seizure continues - IV phenobarbital
4. if seizure continues - general anesthesia with IV midazolam, propofol or barbiturates
Sodium channel inactivator
AE - diplopia, ataxia, GINGIVAL HYPERPLASIA, HIRSUTISM, stevens johnson syndrome, lupus like syndrome
ZERO order kinetics
Sodium channel blocker
STEVENS JOHNSON SYNDROME
Sodium channel blocker and GABA activator
AE - weight loss, fatigue, kidney stones
prevents GABA metabolism
AE - irreversible visual field loss
prevents GABA reuptake
Blocks NMDA channels and potentiates GABA
**used for refractory epilepsy
AE - aplastic anemia, hepatotoxicity
antimuscarinic poisoning antidote?
Stimulant overdose tx?
B blocker poisoning antidote?
CCB poisoning antidote?
IV calcium with glucagon and NE
TCA poisoning antidote?
sodium bicarb with NE
Methanol and Ethylene glycol toxicity antidote?
Fomepizole or ethanol [alcohol dehydrogenase inhibitor]
Cyanide toxicity antidote?
nitrite+nitrate+thiosulfate [methylene blue required for methemeglobin production]
Lead poisoning tx?
Arsenic poisoning tx?
Acute tx - dimercaprol and unithiol
Chronic tx - succimer
gas poisoning - mannitol (osmotic diuresis), bicarb, dimercaprol within 24 hrs then unithiol and succimer after 24 hrs
Mercury toxicity tx?
acute - dimercaprol, unithiol or succimer
chronic - unithiol and succimer
Iron toxicity tx?
Prodrug that is converted to ethinyl estradiol - used in contraceptives
ER antagonists at the hypothalamus that inhibits the negative feedback leading to increased LH and FSH production -- stimulates ovulation
AE - ovarian hyper-stimulation leading to enlargement of ovary, multiparity, hot flashes, nausea, vomiting, breast tenderness, weight gain
ER antagonists everywhere in the body -- treats hormone-responsive breast cancer that is resistant to the other first-line anti-estrogen therapies
Similar to anastrozole which is an aromatase inhibitor decrease the synthesis of estrogen
AE - hot flashes, musculoskeletal disorders, reduced bone mineral density, joint symptoms
Irreversible aromatase inhibitor
GnRH antagonist used to treat advanced prostate cancer
partial agonist at androgen receptors - weak CYP450 inhibitor
AE - acne, hirsutism, weight gain, menstrual disturbances, hepatic dysfunction
Competitive inhibitor at progesterone receptor - helps stop pregnancy with misoprostol leading to abortions
AE - GI disturbances, vaginal bleeding, atypical infection
5a-reductase inhibitor preventing conversion of testosterone to DHT
Tx - BPH and hair loss
AE - impotence, gynecomastia
Competitive inhibitor of androgen receptors
Tx - advanced prostate cancer
AE - gynecomastia, hot flashes, impotence, hepatotoxicity
What is the MOA of oral contraceptives?
1. prevent ovulation - suppress LH and FSH release by preventing estrogen fluctuations by providing pt with stable estrogen level
2. impair implantation - by maintaining elevated progesterone level by providing pt with stable elevated progestin
Compare progestins and levels of androgen activity?
Highest androgen activity = levonorgestrel [post-coital and implants] and noregestrel [progestin only pill]
Lower androgen activity = norethindrone [progestin only pill]
Even lower activity = desogestrel and noregestimate
Antiandrogenic = Drospirenone
What are the benefits of combined oral contraceptives?
• Reduction on the risk of endometrial cancer
• Reduction in the risk of ovarian cancer
• Improved regulation of menstruation
• Relief of benign breast disease
•Prevention of ovarian cysts
• Reduction in the risk of symptomatic pelvic inflammatorydisease
• Improvement in acne control
AE associated with oral contraceptives?
Nausea, bloating, breakthrough bleeding that improve spontaneously by 3rd cycle.
Breakthrough bleeding is more of a problem with lower doses of estrogen b/c estrogen stabilizes the endometrium.
Insulin resistance b/t progestins may cause insulin resistance by competing with insulin for its receptor. It is very rare that oral contraceptive swill lead to hyperglycemia.
Hirsuitism - due to androgenic progestins
Melasma - due to estrogen stimulation of melanocyte production
Dyslipidemia - low-dose have no impact on HDL, LDL, TAG or total cholesterol levels
CV disorders - increased risk of thromboembolism, thrombiphlembitis, HTN, MI, cerebral and coronary thrombosis esp in women with other risk factors - this is due to estrogen causing increased production of factor VII, factor X , and fibrinogen
Carcinogenic - possible increase in risk of cancer (NOT for endometrial and ovarian though! - oral contraceptives decrease the incidence of these cancers)
Depression - requires cessation of therapy
What are the progestin-only pills?
These are not widely used, but contain NORETHINDRONE or NOREGESTREL. They are slightly less effective compared to the combined pills. There is no risk of thromboembolic evens due to lack of estrogen which is really what stimulates the increased risk of thrombosis.
MOA - effectiveness lies within thickening cervical mucus and altering endometrial surface to impair sperm implantation
Caffeine, theophylline, Theobromine -- caffeine is the most widely consumed stimulant -- these substances block presynaptic adenosine receptors. Normally the adenosine receptors inhibit NE release, so blocking the receptors potentiates the NE release therefore acting as a stimulant. Adenosine is also a natural promoter of drowsiness, so by blocking adenosine receptor there is a potential of insomnia.
100-200mg caffeine - decrease fatigue and increase mental alertness
1.5g caffeine - produces anxiety and tremors
2-5g of caffein - spinal cord stimulation
Tolerance can rapidly develop and withdrawal leads to fatigue and sedation.
mild - pt is irritable, sleepy, relapse is common
Nicotine addiction tx..
1. nicotine replacement therapy - transdermal patch, gym, nasal spray, etc
2. sustained-release bupropion
3. Varenicline - partial agonist at nicotinic receptors in CNS
How do you tx opioid withdrawal?
1. Replace with long-acting opioid then slowly reduce dose -- methadone and buprenorphine are the most commonly used
2. Detox with adrenergic agonists - Clonidine and Lofexidine [both are a2 agonist] that prevent the rebound firing of the adrenergic neurons that occur with the withdrawal symptoms
3. Naltrexone - opioid antagonist with high affinity to mu opioid receptors that do not satisfy craving but rather relieve withdrawal symptoms
How do you treat alcohol addiction?
1. Disulfiram - aldehyde dehydrogenase inhibitor - creates aversion to drinking
2. Naltrexone - orally available opioid antagonist -reduces alcoholic craving
3. Acamprosate - NMDA receptor antagonist - prevents relapse
4. Topiramate - facilitates GABA function and antagonizes glutamate receptors - this may reduce cravings, but is not FDA-approved for this indication
Tx benzo withdrawal?
Diazepam and chlordiazepoxide - long half-life benzos b/c they prevent rebound withdrawal symptoms
In elderly and people with liver failure - it is better to administer intermediate-acting drugs, Lorazepam and Oxazepam - these go straight to phase II glucuridation so put less stress on the liver
• Gases -N2O [megaloblastic anemia]
• Volatile halogenated hydrocarbons
-Halothane [hepatotoxicity, heart depression]
-Enflurane [seizure potential, heart depression, most resp depression]
-Isoflurane [TPR depression, resp depression]
-Desflurane [TPR depression]
-Sevoflurane [TPR depression]
MAC vs potency vs oil:air partition coefficient vs induction?
low MAC - high potency - high oil:air coefficient - slow induction
high MAC - low potency - low oil:air coefficient - fast induction
[ex nitrous gas]
• Barbiturates - thiopental [ultra-fast barb]
• Propofol - massive hypotension, GABAa potentiator
• Ketamine - NMDA blocker, bad dreams, dissociative anesthesia
• Etomidate - stable CVS, GABAa potentiator
short-acting = procaine [METABOLIZE TO PABA ANALOG so do not give with sulfonamides!], chloroprocaine
intermediate-acting = lidocaine, mepivacaine, prilocaine [converts hemoglobin to methemoglobin]
Long-acting = tetracaine, bupivacaine [CARDIOTOXIC], etidocaine, ropivacaine
Amide (2 i's -- liver excretion) vs ester (1 i -- esterase)
Benzylisoquinolines - tubocurarine (prototype), atracurium, cistracurium, mivacurium
Ammonio steroids - pancuronium, rocuronium [alt to succinylcholine], vecuronium
Atracurium - metabolizes t o Laudanosine which leads to seizures and hypotension so Cistacurium was created to decrease the AE profile an dit also has decreased histamine release
**AE - hypotension from histamine release (B) and tachycardia from M2 block (A)
Succinylcholine -- two ACh molecules linked end-to-end
AE - bradycardia (musc agonist), histamine release, muscle pain, HYPERKALEMIA, increase intraocular and intragastric pressure
Do not give it....
• History of malignant hyperthermia
• History of skeletal muscle myopathies.
• Major burns.
• Multiple trauma
• Denervation of skeletal muscle
• Upper motor neuron injury.
Drugs for chronic spasms that act in CNS?
1. Diazepam - facilitates GABAa receptor activation increasing frequency of Cl- channel opening
2. Baclofen - GABA agonist at GABAb receptors [CNS receptor that is a G-protein coupled receptor that is also inhibitory so when you activate it, you relax the skeletal muscle]
3. Tizanidine - a2 agonist in CNS
Drugs for chronic spasms that act on skeletal muscle?
1. Dantrolene - interferes with release of Ca2+ by binding to the ryanodine receptor in the SR of skeletal muscle -- also used in malignant hyperthermia
2. botulinum toxin