PHARM 1 LINERS ALL Flashcards
Time it takes for amount of drug to fall to half of its value, constant in first order kinetics (majority of drugs)
Half-life (T1/2)
Relates the amount of drug in the body to the plasma concentration
Volume of distribution (VD)
Plasma concentration of a drug at a given time
Cp
The ratio of the rate of elimination of a drug to its plasma concentration
Clearance (CL)
The elimination of drug that occurs before it reaches the systemic circulation
First pass effect
The fraction of unchanged drug that reaches systemic circulation after administration
Bioavailability (F)
When the rate of drug input equals the rate of drug elimination
Steady state
Different steps of Phase I
Oxidation, reduction, hydrolysis
Barbiturates, phenytoin, carbamazepine, and rifampin all do this
Induce CYP450
Cimetidine, ketoconazole, isoniazid, and grapefruit all do this
Inhibit CYP450
Name 3 Phase II conjugation reactions
Glucuronidation, acetylation, glutathione conjugation, glycine conjugation, sulfation, methylation, water conjugation
Constant percentage of drug metabolized per unit time
First order kinetics
Constant amount of drug metabolized per unit time
Zero order kinetics
Target plasma concentration times (volume of distribution divided by bioavailability)
Loading dose (Cp*(Vd/F))
Concentration in the plasma times (clearance divided by bioavailability)
Maintenance dose (Cp*(CL/F))
Strength of interaction between drug and its receptor
Affinity
Selectivity of a drug for its receptor
Specificity
Amount of drug necessary to elicit a biologic effect compared with another drug
Potency
Ability of drug to produce the maximal biologic effect
Efficacy
Ability of a drug to produce maximal response after binding to the receptor
Full agonist
Ability to produce less than maximal response after binding to the receptor
Partial agonist
Ability to bind reversibly to the same site as the drug and without activating the effector system
Competitive antagonist
Ability to bind irreversibly to the active site or bind to a site distinctly separate from the agonist binding site
Noncompetitive antagonist
Mechanism of action (MOA) utilizes intracellular receptors
Steroid and hormones
Mechanism of action (MOA) utilizes transmembrane receptors that have intrinsic enzymatic activity
Insulin, EGF, TGFbeta, PDGF, ANP
Mechanism of action (MOA) utilizes ligand gated ion channels
Acetylcholine, nicotine
Dose which produces therapeutic response in 50% of the population
ED50
Dose which is toxic in 50% of the population
TD50
Dose which is lethal to 50% of the population
LD50
Window between therapeutic effect and toxic effect
Therapeutic index
Drugs that have a high margin of safety is indicated by
High therapeutic index
Drugs that have a narrow margin of safety is indicated by
Low therapeutic index
Antidote used for lead poisoning (without encephalopathy)
Dimercaprol, Edetate calcium disodium, or succimer
Antidote used for cyanide poisoning
Nitrites, sodium thiosulfate, hydroxocobalamin (cyanokit)
Antidote used for anticholinergic poisoning
Physostigmine
Antidote used for organophosphate/anticholinesterase poisoning
Atropine, pralidoxime (2-PAM)
Antidote used for iron salt toxicity
Deferoxamine
Antidote used for acetaminophen (APAP) toxicity
N-acetylcysteine
Antidote for severe lead poisoning (with encephalopathy)
Dimercaprol AND CaEDTA (edetate calcium disodium)
Antidote for arsenic, mercury, and gold poisoning
Dimercaprol
Antidote used in Wilson’s disease (copper poisoning)
Penicillamine
Antidote used for heparin toxicity
Protamine Sulfate
Antidote used for warfarin toxicity
Vitamin K and Fresh frozen plasma (FFP)
Antidote for tissue plasminogen activator (t-PA), streptokinase
Aminocaproic acid
Antidote used for methanol and ethylene glycol toxicity
Ethanol
Antidote used for opioid toxicity
Naloxone (IV), naltrexone (PO)
Antidote used for benzodiazepine toxicity
Flumazenil
Antidote used for tricyclic antidepressants (TCA)
Sodium bicarbonate
Antidote used for carbon monoxide poisoning
100% O2 and hyperbaric O2
Antidote used for digitalis toxicity
Digibind (also need to d/c digoxin, normalize K+, and lidocaine if pt. Is arrhythmic)
Antidote used for beta agonist toxicity (eg. Metaproterenol)
Esmolol
Antidote for methotrexate toxicity
Leucovorin
Antidote for beta-blocker overdose and hypoglycemia
Glucagon
Antidote useful for some drug induced Torsade de pointes
Magnesium sulfate
Antidote for hyperkalemia
sodium polystyrene sulfonate (Kayexalate)
Method to reduce salicylate intoxication
Alkalinize urine, dialysis
Constant proportion of cell population killed rather than a constant number
Log-kill hypothesis
Treatment with cancer chemotherapy at high doses every 3-4 weeks, too toxic to be used continuously
Pulse therapy
Toxic effect of anticancer drug can be lessened by rescue agents
Rescue therapy
Drug used concurrently with toxic anticancer agents to reduce renal precipitation of urates
Allopurinol
Pyrimidine analog that causes “Thiamine-less death” given with leucovorin rescue
5-flouracil (5-FU)
Drug used in cancer therapy causes Cushing-like symptoms
Prednisone
Side effect of Mitomycin
SEVERE myelosuppression
MOA of cisplatin
Alkylating agent
Common toxicities of cisplatin
Nephro and ototoxicity
Analog of hypoxanthine, needs HGPRTase for activation
6-mercaptopurine (6-MP)
Interaction with this drug requires dose reduction of 6-MP
Allopurinol
May protect against doxorubicin cardio-toxicity by chelating iron
Dexrazoxane
Blows DNA (breaks DNA strands), limiting SE in pulmonary fibrosis
Bleomycin
MOPP regimen used in Hodgkin’s disease (HD)
Mechlorethamine + oncovorin (vincristine) + procarbazine, and prednisone
Regimen used for non-Hodgkin’s lymphoma
CHOP (cyclophosphamide, oncovin(vincristine), doxorubicin and prednisone), rituximab (rituxan)
Regimen used for breast cancer
CMF (cyclophosphamide, methotrexate, and fluorouracil) and tamoxifen if ER+
Alkylating agent, vesicant that causes tissue damage with extravasation
Mechlorethamine
Anticancer drug also used in RA, produces acrolein in urine that leads to hemorrhagic cystitis
Cyclophosphamide
Prevention of cyclophosphamide induced hemorrhagic cystitis
Hydration and mercaptoethanesulfonate (MESNA)
Microtubule inhibitor that causes peripheral neuropathy, foot drop (eg. ataxia), and “pins and needles” sensation
Vincristine
Binds tubulin and prevents the disassembly of microtubules during the M phase of the cell cycle inducing mitotic arrest
Paclitaxel (taxol)
Toxicities include nephrotoxicity and ototoxicity, leading to a severe interaction with aminoglycosides
Cisplatin
Agent similar to cisplatin, less nephrotoxic, but greater myelosuppression
Carboplatin
Converts asparagine to aspartate and ammonia, denies cancer cells of essential AA (asparagine)
L-asparaginase
Used for hairy cell leukemia; it stimulates NK cells
Interferon alpha
Anti-androgen used for prostate cancer
Flutamide (Eulexin)
Anti-estrogen used for estrogen receptor + breast cancer
Tamoxifen
Some cell cycle specific anti-cancer drugs
Bleomycin, vinca alkaloids, antimetabolites (eg., 5-FU, 6-MP, methotrexate, etoposide)
Some cell cycle non-specific drugs
Alkylating agents (eg., mechlorethamine, cyclophosphamide), antibiotics (doxorubicin, daunorubicin), cisplatin, nitrosourea
Anti-emetics used in association with anti-cancer drugs that are 5-HT3 (serotonin receptor subtype ) antagonist
Odansetron, granisetron, dolasetron, palonosetron
Nitrosoureas with high lipophilicity, used for brain tumors
Carmustine (BCNU) and lomustine (CCNU)
Alkylating agent that produces disulfiram-like reaction with ethanol
Procarbazine
Somatostatin (SRIF) analog used for acromegaly, carcinoid, glucagonoma and other GH producing pituitary tumors
Octreotide
Somatotropin (GH) analog used in GH deficiency (dwarfism)
Somatrem
GHRH analog used as diagnostic agent
Sermorelin
GnRH agonist used for infertility or different types of CA depending on pulsatile or steady usage respectively
Leuprolide
GnRH antagonist with more immediate effects, used for infertility
Ganirelix
Hormone inhibiting prolactin release
Dopamine
ACTH analog used for diagnosis of patients with corticosteroid abnormality
Cosyntropin
Synthetic analog of ADH hormone used for diabetes insipidus and nocturnal enuresis
Desmopressin (DDAVP)
Agent of choice for the treatment of hypothyroidism
Levothyroxine (T4)
An isomer of T3 which may be used in myxedema coma
Liothyronine (T3)
Anti-thyroid drugs
Thioamides (methimazole, propylthiouracil), potassium iodide, radioactive iodine (131I)
Thioamide agents used in hyperthyroidism
Methimazole and propylthiouracil (PTU)
Thioamide less likely to cross placenta, inhibits peripheral conversion of T4 to T3 in high doses, and indicated for pregnant women in 1st trimester
Propylthiouracil (PTU)
Propylthiouracil (PTU) mechanism of action
Inhibits thyroid peroxidase
Can be effective for short term therapy of thyroid storm, but after several weeks of therapy causes an exacerbation of hyperthyroidism
Iodide salts (potassium iodide)
Permanently cures thyrotoxicosis, patients will need thyroid replacement therapy thereafter. Contraindicated in pregnancy
Radioactive iodine
Used for the symptomatic treatment of thyrotoxicosis by blocking cardiac adverse effects
Beta-blockers such as propranolol and esmolol
3 zones of adrenal cortex and their products
Glomerulosa (mineralocorticoids), fasciculata (glucocorticoid=GC), and reticularis (adrenal androgens)
Pneumonic for 3 zones of adrenal cortex
GFR
Used for Addison’s disease, Congenital Adrenal Hyperplasia (CAH), inflammation, allergies, and asthma (as a local inhalation)
Glucocorticoids
Short acting GC’s
Cortisone and hydrocortisone (equivalent to cortisol)
Intermediate acting GC’s
Prednisone, methylprednisolone, prednisolone, oaramethasone, fluprednisone and triamcinolone
Long acting GC’s
Betamethasone, dexamethasone, and paramethasone
Mineralocorticoids
Fludrocortisone and deoxycorticosterone
Some side effects of corticosteroids
Hyperglycemia, Osteopenia, impaired wound healing, inc. risk of infection, inc. appetite, HTN, edema, PUD, euphoria, psychosis
Period of time of therapy after which GC therapy will need to be tapered
5-7 days
Used for Cushing’s syndrome (increased corticosteroid) and sometimes for adrenal function test
Metyrapone
Inhibits conversion of cholesterol to pregnenolone therefore inhibiting corticosteroid synthesis
Aminoglutethimide
Antifungal agent used for inhibition of all gonadal and adrenal steroids
Ketoconazole
Antiprogestin used as potent antagonist of GC receptor
Mifepristone
Diuretic used to antagonize aldosterone receptors
Spironolactone
Common SE of spironolactone
Gynecomastia and hyperkalemia
Slightly increased risk of breast cancer, endometrial cancer, heart disease (questionable), has beneficial effects on bone loss
Estrogen
Antiestrogen drugs used for fertility and breast cancer respectively
Clomiphene and tamoxifen
Common SE of tamoxifen and raloxifene
Hot flashes
Selective estrogen receptor modulator (SERM) used for prevention of osteoporosis and currently being tested for treatment of breast cancer (Stars study)
Raloxifene
Non-steroidal estrogen agonist causes clear cell adenocarcinoma of the vagina in daughters of women who used it during pregnancy
Diethylstilbestrol (DES)
Estrogen mostly used in oral contraceptives (OC)
Ethinyl estradiol and mestranol
Anti-progesterone used as abortifacient
Mifepristone (RU-486)
Constant low dose of estrogen and increasing dose of progestin for 21 days (last 5 days are sugar pills or iron prep)
Combination oral contraceptives (OC)
Oral contraceptive available in a transdermal patch
Ortho-Evra
Converted to more active form DHT by 5 alpha-reductase
Testosterone
5 alpha-reductase inhibitor used for benign prostatic hyperplasia (BPH) and male pattern baldness
Finasteride (Proscar and Propecia respectively)
Anabolic steroid that has potential for abuse
Nandrolone and stanozolol
Anti-androgen used for hirsutism in females
Cyproterone acetate
Alpha cells in the pancreas produce
Produce glucagon
Beta cells in the pancreas produce
Produce insulin
Beta cells are found
Islets of Langerhans
Delta cells in the pancreas produce
Produce Somatostatin
Product of proinsulin cleavage used to assess insulin production
C-peptide
Endogenous insulin
Normal C-peptide
Very rapid acting insulin, having fastest onset and shortest duration of action
Lispro (Humalog)/Apidra (glulisine)
Rapid acting, crystalline zinc insulin used to reverse acute hyperglycemia
Regular (Humulin R)
Long acting insulin
NPH insulin
Ultra long acting insulin, has over a day duration of action
Glargine (Lantus)
Major side effect of insulin
Hypoglycemia
Important in synthesis of glucose to glycogen in the liver
GLUT 2
Important in muscle and adipose tissue for glucose transport across muscles and TG storage by lipoprotein lipase activation
GLUT 4
Examples of alpha-glucosidase inhibitors (AGI)
Acarbose, miglitol
MOA of AGI’s
Act on intestine, delay absorption of glucose
SE of AGI’s
Flatulence (do not use beano to tx), diarrhea, abdominal cramps
Alpha-glucosidase inhibitor associated with elevation of LFT’s
Acarbose
Amino acid derivative for treatment of Type II diabetes
Nateglinide
MOA of nateglinide
Stimulates rapid and transient release of insulin through closure of the ATP-sensitive K+ channel
Biguanide
Metformin
Drugs available in combination with metformin
Acroplus Met progutazone and metformin, Janumet and Janumet XR Sitagliptin and Metformin, Glyburide, glipizide, and rosiglitazone
MOA of metformin
Decreases hepatic glucose production and intestinal glucose absorption; increase insulin sensitivity
Most important potential SE of metformin
Lactic acidosis
Meglitinide
Repaglinide
MOA of repaglinide
Insulin release from pancreas; faster and shorter acting than sulfonylurea
First generation sulfonylurea
Chlorpropamide, tolbutamide, tolazamide, etc.
Second generation sulfonylurea
Glyburide, glipizide, glimepiride, etc.
MOA of both generations
Insulin release from pancreas by modifying K+ channels
Common SE of sulfonylureas, repaglinide, and nateglinide
Hypoglycemia
Sulfonylurea NOT recommended for elderly because of very long half life
Chlorpropamide
Thiazolidinediones
Pioglitazone, Rosiglitazone, Troglitazone (withdrawn/d from market)
Reason troglitazone was withdrawn from market
Hepatic toxicity
MOA of thiazolindinediones
Stimulate PPAR-gamma receptor to regulate CHO and lipid metabolism
SE of Thiazolindinediones
Edema, mild anemia; interaction with drugs that undergo CytP450 3A4 metabolism; if used over one year, bladder Cancer; with CHF, may cause new or worsening CHF
Hyperglycemic agent that increases cAMP and results in glycogenolysis, gluconeogenesis, reverses hypoglycemia, also used to reverse severe beta-blocker overdose and smooth muscle relaxation
Glucagon
Available bisphosphonates
Alendronate, etidronate, risedronate, pamidronate, tiludronate, and zoledronic acid
MOA of Bisphosphonates
Inhibits osteoclast bone resorption
Uses of bisphosphonates
Osteoporosis, Paget’s disease, and osteolytic bone lesions, and hypercalcemia from malignancy
Major SE of bisphosphonates
Chemical esophagitis
Bisphosphonates that cannot be used on continuous basis because it caused osteomalacia
Etidronate
Used for prevention of postmenopausal osteoporosis in women
Calcium reguators Bisphosphonates: alendronate, risedronate, ibandronate, Estrogen (HRT-Hormone replacement therapy)
Increase bone density, also being tested for breast CA tx.
Raloxifene (SERM-selective estrogen receptor modulator)
Used intranasally and decreases bone resorption
Calcitonin (salmon prep)
Used especially in postmenopausal women, dosage should be 1500 mg
Calcium
Vitamin given with calcium to ensure proper absorption
Vitamin D
Disease caused by excess ergot alkaloids
St. Anthony’s Fire
A class of endogenous substances that include histamine, serotonin, prostaglandins, and vasoactive peptides that work in autocrine or paracrine manner
Autacoids
Syndrome of hypersecretion of gastric acid and pepsin usually caused by gastrinoma; it is associated with severe peptic ulceration and diarrhea
Zollinger-Ellison Syndrome
Drug that causes contraction of the uterus
Oxytocin
Distribution of histamine receptors H1, H2, and H3
Smooth muscle and mast cells; stomach, heart, and mast cells; nerve endings, CNS respectively
1st generation antihistamine that is highly sedating
Diphendydramine
1st generation antihistamine that is least sedating
Chlorpheniramine
2nd generation antihistamines
Fexofenadine, loratadine, and cetirizine
Generation of antihistamine that has the most CNS effects
First generation due to being more lipid-soluble
Major indication for H1 receptor antagonist
Use in IgE mediated allergic reaction (allergic rhinitis, urticaria)
Antihistamine that is indicated for allergies, motion sickness, and insomnia
Diphenhydramine
H1 antagonist used in motion sickness
Dimenhydrinate and other 1st generation
Most common side effect of 1st generation antihistamines
Sedation, anticholinergic
H2 blocker that causes the most interactions with other drugs
Cimetidine
Clinical use for H2 blockers
Acid reflux disease, duodenal ulcer and peptic ulcer disease
Receptors for serotonin (5HT-1) are located
Mostly in the brain, and they mediate synaptic inhibition via increased K+ conductance
5HT-1D/1B agonist used for migraine headaches
Sumatriptan, naratriptan, and rizatriptan
Triptan available in parenteral and nasal formulation
Sumatriptan
H1 blocker that is also a serotonin antagonist
Cyproheptadine
5HT2 antagonist mediate synaptic excitation in the CNS and smooth muscle contraction
Ketanserin, cyproheptadine, and ergot alkaloids (partial agonist of alpha and serotonin receptors)
Agents for reduction of postpartum bleeding
Oxytocin and ergonovine
Agents used in treatment of carcinoid tumor
Cyproheptadine