Antipsychotics, antidepressants, opioids, drugs of abuse, endocrine Flashcards
target action of typical antipsychotics
D2 receptors in caudate putamen, nucleus accumbens, cerebral cortex, hypothalamus
dopaminergic tract-regulating mentation and mood
meso-cortical, meso-limbic
dopaminergic tract-extrapyramidal function
nigrostriatal
dopaminergic tract-control of prolactin relace
tuberoinfundibular
dopaminergic tract-eating behavior
medullary-periventricular
dopaminergic tract-anticipatory motivational phase of copulatory behavior
incertohypothalamic
antipsychotic of choice for drug resistance
clozapine
caused by supersensitivity of dopamine receptors
tardive dyskinesia
tx for acute dystonia
diphenhydramine
tx for parkinsonism
benztropine
tx for rabbit syndrome
benztropine
tx for tardive dyskinesia
nonerome
tx for akathisia
decrease dose, diphenhydramine
tx for neuroleptic malignant syndrome
withdraw drug, dantrolene, diazepam, dopamine agonist
typical antipsychotic; SE: corneal and lens deposits, neuroleptic malignant syndrome, contact dermatitis
chlorpromazine
typical antipsychotic; SE: retinal deposits, cardiotoxicity, w/ strongest autonomic effects, fatal ovedose
thoridazine
typical antipsychotic known for major EPS, also used for Huntington’s and Tourette’s, least sedating among typicals
haloperidol/droperidol
only antipsychotic that reduces the risk of suicide
clozapine
weight gain attributed to atypical antipsychotics
probably from H1 and 5-HT2 blockade
atypical antipsychotic also used for manic episodes; SE: cataracts, hypnagogic hallucinations, priapism
quetiapine
only antipsychotic approved in the youth
risperidone
atypical antipsychotic; SE: QT prolongation, increased mortality in elderly with dementia-related psychosis
ziprasidone
least sedating among atypical anti-psychotics
aripiprazole
atypical antipsychotics with no atropine like effects, do not cause hypergly, hyperprolactinemia or weight gain
ziprasidone, aripiprazole
features of neuroleptic malignant syndrome
FEVER: fever, encephalopathy, vitals unstable, elevated CPK, rigidity`
MOA of lithium
decreases cAMP, inhibits inositol-1-phosphatase
SE of lithium; Tx
LITH: leukocytosis, insipidus, teratogen (Ebstein’s anomaly), thyroid enlargement, tremors, heart (bradycardia); also acneiform skin eruptions; hemodialysis
threshold for lithium toxicity
2 mEq/L
NTs responsible for mood
NE and serotonin
back-up drug for MDD
TCAs: imipramine (clomipramine, desipramine, amitryptyline, nortryptiline)
toxic dose of TCAs; lethal dose
7mg/kg; 15 mg/kg
ECG findings in TCA overdose
abnormal QRS morphology, prolonged QRS, abnormal R and S waves in AVR
features of TCA overdose; Tx
coma, convulsions, cardiotoxicity; bicarbonate (for QRS>100msec)
first line for MDD
SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine)
notable SE of SSRIs
erectile dysfunction
tx for serotonin syndrome
cyproheptadine
inhibits neuronal reuptake of serotonin and NE
SNRIs (venlafaxine, duloxetine, desvenlafaxine)
SNRI with hepatotoxicity SE
duloxetine
SNRI with cardiotoxicity and CYP450 inhibitio
venlafaxine
weak 5-HT reuptake inhibitors that blocks 5-HT2 receptors to make serotonin available to other receptors, SE: priapism; SE: hepatotoxicity
trazodone and nefazodone; trazodone; nefazodone
tetracyclic antidepressant which causes amenorrhea-galactorrhea syndrome and lowers seizure threshold
amoxapine
tetracyclic antidepressant which can be used as appetite stimulant; can cause nightmares
mirtazapine
tetracyclic antidepressant which can also be used for smoking cessation; also causes priapism, aggravation of psychosis, lower seizure threshold
bupropion
inhibits monoamine oxidase type A and B, increases NE and serotonin
MAOIs (phenelzine, tranylcypromine, selegiline)
causes hypertensive crisis when taken with tyramine (indirect acting sympathomimetic in cheese)
MAOIs
features of serotonin syndrome
FAT CHD; fever, agitation, tremors, clonus, hyperreflexia, diaphoresis
features of malignant hyperthermia
FCHART; fever, acidosis, rhabdomyolysis, trismus, clonus, HPN
precipitating drugs for serotonin syndrome
SSRIs, MAOIs, TCAs, meperidine, MDMA, St. John’s wort
opioids with shortest and longest half-lives
remifentanil; buprenorphine
mu opioid receptor (function, affinity)
inhibition of respiration, endorphins
delta opioid receptor (function, affinity)
dev’t of tolerance, enkephalin
kappa opioid receptor (function, affinity)
slowed GI transit, dynorphin
opioid analgesic which may be given trandermally or via lollipop
fentanyl
most potent opioid
ohmefentanyl
opioid of choice for relief in pancreatitis and labor pains
meperidine
opioid which causes serotonin syndrome w/ SSRIs or MAOIs
meperidine
agonist of mu and kappa receptors
meperidinethadone
opioid used for opioid dependence/withdrawal, can cause drug-induced hyperthyroidism, currently being investigated as a novel treatment for leukemia
methadone
partial opioid agonist; SE: hypogonadism, hearing loss
hydrocodone/oxycodone
partial opioid agonist which depresses medullary cough center through sigma receptor stimulation
dextrometorphan/ codeine
weak opioid agonist withdrawn due to fatal cardiotoxicity
propoxyphene
opioid which is a strong agonist of kappa receptors but weak antagonist of mu receptors
nalbuphine, buprenorphine, butorphanol, pentazocine
effects resistant to naloxone reversal
nalbuphine, buprenorphine, butorphanol, pentazocine
systemic opioid antagonist
naloxone
systemic opioid antagonist which also reduces alcohol dependence
naltrexone
dual-acting opioid analgesic, weak agonist of mu receptor, also inhibits reuptake of serotonin and NE, lowers seizure threshold and may cause serotonin syndrome
tramadol
CI of tramadol use
epilepsy
triad of opioid overdose
PRC: pupillary constriction, respiratory depression, coma
NT believed to cause addiction
excessive dopaminergic stimulation
antidepressants with limited benefit against amphetamine withdrawal symptoms
amineptine, mirtazapine
congeners of amphetamines
dimethoxymethylamphetamine (DOM), methylene dioxyamphetamine (MDA), methylene dioxymethamphetamine (MDMA/ ecstacy)
electrolyte imbalance which may be caused by ecstacy
profound hyponatremia
“speed”, “superspeed”
methamphetamine, cocaine
causes crack lung (hemorrhagic alveolitis), mydriasis, HPN, vasoconstriction, psychomotor agitation, hyperthermia, dyspnea, bowel ischemia, thrombus formation
cocaine overdose
presents with agitation, hypertension, tachycardia, delusions, hallucinations, hyperthermia, seizures
methamphetamine overdose
teratogenic, causes cystic cortical lesions on CT
cocaine
psychotomimetic effect
phencyclidine/ ketamine
most dangerous hallucinogenic agent
phencyclidine
“angel dust”
phencyclidine
causes nystagmus, hypertension and seizures; tx
phencyclidine; IV diazepam/lorazepam
no actions on dopaminergic neurons unlike most drugs of abuse
phencyclidine
psychedelic effects
lysergic acid diethylamide (LSD), mescaline, psilocybin
purified more potent form of marijuana
hashish
reddened conjunctiva
marijuana
increases IGF-1 in liver and cartilage; used for short stature syndromes (Turner, Noonan, Prader-Willi), AIDS wasting, failure to thrive
somatropin
somatostatin analog, suppresses GH, IGF-1, serotonin and GI peptides; used for acromegaly, pituitary GH-secreting adenoma, carcinoid, gastrinoma, glucagonoma, variceal bleeding
octreotide/lanreotide
syndrome of ovarian enlargement, ascites, hypovolemia, possible shock
ovarian hyperstimulation syndrome
FSH analog, used for controlled ovarian hyperstimulation, infertility due to hypogonadism in male
follitropin alfa, menotropins (hMG)
LH analog, used for ovulation induction and hypogonadotropic hypogonadism
choriogonadotropin alfa, hCG, menotropins (hMG), lutropin
GnRH analog
leuprolide (gonadorelin, goserelin, histrelin, nafarelin, triptorelin)
effect of leuprolide
increased LH and FSH with intermittent admin; dec with prolonged continuous admin; may temporarily exacerbate precocious puberty or prostate CA
GnRH antagonist
ganirelix, cetrorelix, abarelix, degarelix
does not cause tumor flare-ups when used for tx of advanced prostate CA
ganirelix, cetrorelix, abarelix, degarelix (GnRH antagonist)
drug against hyperprolactinemia, pituitary adenoma (prolactin-secreting), acromegaly, Parkinson’s which may cause erythromelalgia and Raynaud’s phenomenon
bromocriptine (pergolide, cabergoline, quinagolide)
may cause fluid retention (water intoxication), placental/uterine rupture
oxytocin
CI for oxytocin
fetal distress, prematurity, CPD, predisposition for uterine rupture
increases F VIII activity in patients w/ mild hemophilia A
desmopressin
used for central DI, vW disease, variceal bleeding, primary nocturnal enuresis
desmopressin
ADH antagonist used for SIADH, hyponatremia
conivaptan, tolvaptan, lixivaptan
tyrosine residues are iodinated to form MIT or DIT
iodine organification
T4
levothyroxine
T3
liothyronine
T4 must be lowered in patients with
CV disease or longstanding hypothyroidism
Tx for myxedema coma
IV loading dose of levothyroxine (300-400mcg) followed by 50-100 mcg daily, IV hydrocortisone if w/ adrenal or pituitary insufficiency
inhibits thyroid peroxidase
thioamides (PTU, methimazole)
inhibits thyroid peroxidase and peripheral conversion of T4 and T3, DOC for thyroid storm and pregnant patients; SE: fulminant hepatitis; thrice daily dosing
PTU
inhibits thyroid peroxidase, can cause cholestatic jaundice and cutis aplasia; once daily dosing
methimazole
onset of action of thioamides
3-4 weeks
tx for agranulocytosis
d/c PTU/methimazole, administer recombinant G-CSF (Vilgrastine); prophylactic antibiotics
emits beta rays causing destruction of thyroid parenchyma; CI
radioactive iodine; pregnant and nursing mothers
inhibits iodine organification and hormone release; reduces size and vascularity of thyroid
potassium iodide/lugol’s solution
used as preparation for thyroidectomy or radiation prophylaxis
potassium iodide
should not be used alone (escape in 2-8 weeks)
potassium iodide
fetal exposure causes fetal goiter
potassium iodide
ingestion of iodine causes hypothyroidism due to negative feedback
Wolff-Chaikoff effect
ingestion of iodine causes hyperthyroidism (e.g. endemic goiter)
Jod-Basedow phenomenon
utility of beta blockers in thyroid dse
inhibits peripheral conversion
used to treat thyrotoxicosis-related arrhythmias
esmolol
causes clinical improvement without altering thyroid hormone levels
propranolol
inhibit peripheral conversion of T4 to T3
PTU, propranolol, hydrocortisone
granulocyte count in thyroid storm
<500 cells/mm3
high dose of methimazole increasing risk for throid storm
> 40mf/d
done to prevent Jod-Basedow effect
administer PTU before SSKI
Tx for thyroid storm
PTU, SSKI, Propranolol, Hydrocortisone
Drugs which cause drug-induced hyperthyroidism
Clofibrate, amiodarone, methadone
drug which can cause either hyper or hypothyroidism
amiodarone
difference of 21 and 11 B-hydroxylase deficiency
21-hypotension, 11-hypertension (due to accumulation of 11-B deoxycortisol)
glucocorticoid with highest anti-inflamm property
betamethasone
glucocorticoid with highest salt-retaining potency
fludrocortisone
low potency hydrocortisone
desonide (“di sanay”)
medium potency hydrocortisone
fluticasone, mometasone (fruity moment)
high potency hydrocortisone
desoximetasone, clobetasol (di saucy kubeta)
glucocorticoid used for prevention of organ transplant rejection, beain swelling, post-chemo vomiting, lowering ICP secondary to brain tumors
prednisone
SE: steroid rage (behavioral changes), osteoporosis, glucose intolerance, growth inhibition
prednisone
GC which hastens fetal lung maturation
betamethasone
mineralocorticoid used for chronic adrenal insufficiency, CAH, adrenal replacement post-adrenalectomy; additive hypoK with loop and thiazide diuretics
fludrocortisone/deoxycorticosterone
corticosteroid antagonist which inhibits desmolase, blocking conversion of cholesterol to pregnenolone, used for breast Ca and Cushing’s
aminoglutethimide
azole antifungal which can inhibit cholesterol side chain cleavage, preventing steroid synthesis; used for adrenal CA, breast and prostate CA, hirsutism
ketoconazole
selective inhibitor of 11-hydroxylation used for diagnosis and Tx of Cushing’s
metyrapone
DOC for pregnants w/.Cushing’s
metyrapone
ethinyl estradiol use increases risk of ____; prevent by combining w/ ____
endometrial CA and breast CA; progestin
synthetic estrogen used for atrophic vaginitis, HRT, metastatic prostate CA
DES
notable SE of progestings
HPN, decreased HDL, weigh gain, reversibly dec in bone mineral density
type of OCPs with constant dosage throughout menstrual cycle
monophasic
type of OCPs with change/s in dosage throughout menstrual cycle; mimics hormonal changes in menstrual cycle
biphasic/triphasic
association of combined OCPs and breast CA
lifetime risk will not change, but there is earlier onset
IM depot preparation of progestin-only contraceptive
medroxyprogesterone acetate (depo-provera)
used for emergency contraception
levonorgestrel
estrogen agonists in some tissues but partial agonists or antagonists in other tissues
selective estrogen receptor modulators
estrogen antagonist in breast and CNS, agonist in uterus, liver and bone; used in ER+, PR+ breast CA; decreases risk of_____ and ____, increased risk of ______
Tamoxifen; osteoporosis and atherosclerosis; endometrial CA
estrogen antagonist in breast, uterus and CNS, agonist in liver and bone; used in osteoporosis and breast CA prevention
Raloxifene
partial agonist of estrogen in pituitary, increases FSH and LH; used for induction of labor; notable SE
Clomiphene; ovarian enlargement, multiple pregnancies (CLONE ME PHLEASE), increase risk of low-grade ovarian CA with long term use
SERM inhibiting aromatase used for precocious puberty and tamoxifen resistant breast CA
anastrozole
SERM used for endometriosis, fibrocystic disease (cyclical painful breast mass), hemophilia
danazol
medical abortifacient which may cause sepsis due to Clostridium sordelli
Mifepristone
sex hormone-binding globulin is increased by; decreased by
estrogen, thyroid hormone, cirrhosis; androgen, growth hormone, obesity
site of conversion of testosterone to DHT; enzyme involved
prostate, penis scrotum; 5 alpha reductase
androgen agonist aside from testosterone; increases muscle bulk and RBC production but can cause paradoxical feminization
oxandrolone
androgen antagonist; administered with leuprolide to prevent acute flare-up of prostate cancer
flutamide
androgen antagonist used for surgical castration
nilutamide
androgen antagonist with progestational effect; orphan drug status
cyproterone
inhibits 5-alpha reductase, used for BPH, male pattern baldness and hirsutism; controversial use in prevention of prostate CA
finasteride/ dutasteride
all insulin preparations contain
zinc
glucose transporter for basal uptake of glucose
GLUT 1
glucose transporter for transport across blood brain barrier
GLUT 1
glucose transporter for regulation of insulin release and glucose homeostasis
GLUT 2
glucose transporter for uptake into neurons
GLUT 3
glucose transporter for insulin mediated uptake of glucose
GLUT 4
transporter for absorption of fructose
GLUT 5
glucose transporter found in all tissues
GLUT 1
rapid acting insulin
lispro, aspart, glulisine
short acting insulin
regular
intermediate acting insulin
NPH, lente
ultra long acting insulin
glargine, detemir, lantus
MEN 1
Wermer syndrome; parathyroid adenoma/hyperplasia, pancreatic tumor, pituitary tumor
MEN 2A
Sipple syndrome; pheochromocytoma, parathyroid hyperplasia, medullary thyroid CA
MEN 2B
pheochromocytoma, neuroma/ganglioma, medullary thyroid CA
long acting insulin
ultralente
group of drugs which can block signs and symptoms of hypoglycemia
B-blockers
counter-regulatory hormones of insulin
GH, cortisol, glucagon, epinephrine
tx for somogyi effect
decrease evening dose of insulin
tx for dawn phenomenon
increase evening dose of insulin
tx for waning of insulin dose
increase evening dose of insulin
period in type 1 DM when exogenous insulin reqts decrease due to an increase in endogenous production of insulin
honeymoon period
depolarizes pancreatic B cell and triggers insulin release
insulin secretagogue
insulin secretagogue; 1st gen sulfonylurea, causes disulfiram reaction, weight gain, highest risk for hypoglycemia
chlorpropramide, tolbutamide, tolazamide
insulin secretagogue; 2nd gen sulfonylurea, causes less hypoglycemia than 1st gen, cholestatic jaundice
glipizide, glimepiride, glibenclamide (risk for cholestatic jaundice), gliclazide
insulin secretagogue; effective for postprandial hyperglycemia, least hypoglycemic among secretagogues, can cause URTI, used in diabetics with sulfa allergies
repaglinide, nateglinide, mitiglinide
insulin secretagogue; least hypoglycemic, may be used in CKD patients
nateglinide
activates AMP-stimulated protein kinase leading to inhibition of hepatic and renal gluconeogenesis; associated with lactic acidosis; DOC for obese diabetics and DM prevention among high risk
metformin
increases tissue sensitivity to insulin by activating PPAR-y receptor; also for DM prevention; can cause fluid retention, CHF, hepatotoxicity, macular edema, dyslipidemia; CI in pregnant and CHF pts
pioglitazone (thiazolinediones)-pampaPOGI ng insulin
slows down glucose absorption causing reduction in postprandial hyperglycemia (not fasting); causes GI disturbance(flatulence), minor glucose-lowering defect
alpha glucosidase inhibitors (e.g. acarbose, miglitol, voglibose)
amylin analog which suppresses glucagon release, delays gastric emptying, reduces appetite (anorectic effect)
pramlintide
activates GLP-1 receptors to augment glucose-stimulated insulin release
exenatide (incretin modulator)
inhibits dipeptyl peptidase-4, degrading GLP-1 and other incretins
sitagliptin
antiobesity drug inhibiting GI and pancreatic lipases; causes rebound weight gain upon discontinuation; CI in pregnancy
Orlistat
antiobesity drug inhibiting NE and serotonin reuptake, reduces appetite (anorectic effect); withdrawn due to increased CV risk
sibutramine
antiobesity drug inhibiting cannabinoid-1 receptors, reduces appetite (anorectic effect); withdrawn due to increased suicidal risk
rimonabant
bangkok pills; increased risk for ____
ephedrine, fenfluramine, phentermine; valvular heart dse
increases heart rate and force of contraction hence useful for B-blocker overdose
glucagon
present w/ decreased aa in blood, anemia, diarrhea, weight loss and necrolytic migratory erythema
glucagonoma
recombinant PTH used for osteoporosis; must be administered in _______ to stimulate bone formation
teriparatide; low intermittent dosing
used for rickets and osteomalacia commonly added to dairy products
ergocalciferol/ cholecalciferol
indication for active vitamin D (calcitriol)
secondary hyper PTH in CKD, hypocalcemia in hypoparathyroidism, psoriasis, liver dse
inhibits bone resorption, used in Paget’s dse of bone, hypercalcemia, osteoporosis, tumor marker for medullary thyroid CA
calcitonin/ salcatonin
suppresses activity of osteoclasts, used in Paget’s dse of bone, hypercalcemia, osteoporosis, causes esophagitis (100%) so take with large quantities of water
alendronate, pamidronate, zoledronic acid
phosphate binding resin used to treat hyperphosphatemia in CKD, vit D intoxication and hypoparathyroidism
sevelamer
