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
emesis
Ondansetron, granisetron, dolasetron and palonosetron
5ht-3 antagonist that has been MOST associated with QRS and QTc prolongation and should not be used in patients with heart disease
Dolasetron
Drug used in ergot alkaloids overdose, ischemia and gangrene
Nitroprusside
Reason ergot alkaloids are contraindicated in pregnancy
Uterine contractions
SE of ergot alkaloids
Hallucinations resembling psychosis
Ergot alkaloid used as an illicit drug
LSD
Dopamine agonist used in hyperprolactinemia
Bromocriptine
Peptide causing increased capillary permeability and edema
Bradykinin and histamine
Mediator of tissue pain, edema, inactivated by ACE, and may be a contributing factor to the development of angioedema
Bradykinin
Drug causing depletion of substance P (vasodilator)
Capsaicin
Prostaglandins that cause abortions
Prostaglandin E1 (misoprostol), PGE2, and PGF2alpha
Difference between COX 1 and COX 2
COX 1 is constitutive while COX 2 may be induced during inflammation, although COX 2 is constitutive in some tissues
Drug that selectively inhibits COX 2
Celecoxib
Inhibitor of lipoxygenase
Zileuton
Major SE of zileuton
Liver toxicity
Inhibitor of leukotrienes (LTD4) receptors and used in asthma
Zafirlukast and montelukast
Used in pediatrics to maintain patency of ductus arteriosis
PGE1 (Alprostadil)
Approved for use in severe pulmonary HTN
PGI2 (epoprostenol)
Prostaglandin used as 2nd line treatment of erectile dysfunction
PGE1 (Alprostadil)
Irreversible, nonselective COX inhibitor
Aspirin (or other salicylates)
Class of drugs that reversibly inhibit COX
NSAIDS
Primary endogenous substrate for Nitric Oxidase Synthase
Arginine
MOA and effect of nitric oxide
Stimulates cGMP which leads to vascular smooth muscle relaxation
Long acting beta 2 agonist used in asthma
Salmeterol
Muscarinic antagonist used in COPD
Ipratropium, tiotropium
MOA action of cromolyn
Blocks opening of Cl channels to prevent mast cell degranulation
Enzyme which theophylline inhibits
Phosphodiesterase
Methylxanthine derivative used as a remedy for intermittent claudication
Pentoxifylline
Antidote for severe CV toxicity of theophylline
Beta blockers
MOA of corticosteroids
Induce lipocortins to
SE of long term (>5 days) corticosteroid therapy and remedy
Adrenal suppression and weaning slowly, respectively
MOA of fluoroquinolones
Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV
MOA of penicillin
Block cell wall synthesis by inhibiting transpeptidase and block peptidoglycan cross-linkage
Drug used for MRSA
Vancomycin
Vancomycin MOA
Binds D-Ala-D-Ala on murein monomers and prevent polymerization of the murein monomers
Type of resistance found with vancomycin
Point mutation
Meningitis prophylaxis in exposed patients
Rifampin
Technique used to diagnose perianal itching, and the drug used to treat it
Scotch tape technique
Two toxicities of aminoglycosides
nephro and ototoxicity
Drug of choice for Legionnaires’ disease
Azithromycin (or macrolides)
MOA of sulfonamides
Inhibit dihydropteroate synthase
Penicillins active against penicillinase secreting bacteria
Methicillin, nafcillin, and dicloxacillin
Cheap wide spectrum antibiotic DOC of otitis media
Amoxicillin
Class of antibiotics that have 10% cross sensitivity with penicillins
Cephalosporins
PCN active against pseudomonas
Carbenicillin, piperacillin and ticarcillin
Antibiotic causing red-man syndrome, and prevention
Vancomycin, can be prevented by infusion
Drug causes teeth discoloration
Tetracycline
Mechanism of action of tetracycline
Decreases protein synthesis by binding to 30S ribosome and prevent binding of tRNA to A site
Drug that causes gray baby syndrome and aplastic anemia
Chloramphenicol
Drug notorious for causing pseudomembranous colitis
Clindamycin
Drug of choice for tx of pseudomembranous colitis
Metronidazole
Treatment of resistant pseudomembranous colitis
ORAL vancomycin
Anemia caused by trimethoprim
Megaloblastic anemia
Reason fluoroquinolones are contraindicated in children and pregnancy
Cartilage damage
DOC for giardia, bacterial vaginosis, pseudomembranous colitis, and trichomonas
Metronidazole
Treatment for TB patients (think RIPE)
Rifampin, Isoniazid, Pyrazinamide, and Ethambutol
Metronidazole SE if given with alcohol
Disulfiram-like reaction
Common side effect of Rifampin
Orange urine discoloration
MOA of nystatin
Bind ergosterol in fungal cell membrane
Neurotoxicity with isoniazid (INH) prevented by
Administration of Vit. B6 (pyridoxine)
Toxicity of amphotericin
Nephrotoxicity
SE seen only in men with administration of ketoconazole
Gynecomastia
Topical DOC in impetigo
Topical mupirocin (Bactroban)
DOC for influenza A and B
Oseltamivir or Zanamivir
DOC for RSV
Ribavirin
DOC for CMV retinitis
Ganciclovir
SE for ganciclovir
Myelosuppression
Anti-viral agents associated with Stephen Johnson syndrome
Nevirapine, amprenavir
HIV antiviral class known to have severe drug interactions by causing inhibition of metabolism
Protease inhibitors
Antivirals that are teratogens
Delavirdine, efavirenz, and ribavirin
Antivirals associated with neutropenia
Ganciclovir, zidovudine, saquinavir, interferon
HIV med used to reduce transmission during birth
AZT (zidovudine)
Drug used for African sleeping sickness
Suramin
Drug used in Chagas disease
Nifurtimox
Cephalosporins able to cross the BBB
Cefixime (2nd) and 3rd generation
DOC for N. gonorrhea
Ceftriaxone
Cephalosporins that cause kernicterus in neonates
Ceftriaxone or cefuroxime
SE of INH
Peripheral neuritis and hepatitis
Aminoglycoside that is least ototoxic
Streptomycin
Drug used in exoerythrocytic cycle of malaria
Primaquine
Oral antibiotic of choice for moderate inflammatory acne
Minocycline
Drug of choice for leprosy
Dapsone
DOC for herpes and its MOA
Acyclovir; activated by viral thymidine kinase, results in inhibition of viral DNA replication
Anti-bacterials that cause hemolysis in G6PD-deficient patients
Sulfonamides
Mechanism of action of macrolides (erythromycin, clarithromycin)
Inhibit protein synthesis by binding to domain V of 23S rRNA of 50S ribosome subunit
Antibacterials for optimal treatment of acute uncomplicated cystitis
Nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin
Antibacterials for optimal treatment of acute pyelonephritis
Fluoroquinolones (ciprofloxacin, levofloxacin), trimethoprim-sulfamethoxazole
Lactam that can be used in PCN allergic patients
Aztreonam
SE of imipenem
Seizures
Anti-viral with a dose limiting toxicity of pancreatitis
Didanosine (ddI)
Common side effect of hypnotic agents
Sedation
Occurs when sedative hypnotics are used chronically or at high doses
Tolerance
The most common type of drug interaction of sedative hypnotics with other depressant medications
Additive CNS depression
Major effect of benzodiazepines on sleep at high doses
REM is decreased
Neurologic SE of benzodiazepines
Anterograde amnesia
Reason benzos are used cautiously in pregnancy
Ability to cross the placenta
Main route of metabolism for benzodiazepines
Hepatic
Benzodiazepine that undergo extrahepatic conjugation (which are useful in older or hepatically impaired)
Lorazepam, oxazepam, and temazepam
MOA for benzodiazepines
increase the FREQUENCY of GABA-mediated chloride ion channel opening
Antidote to benzodiazepine overdose (antagonist that reverses the CNS effects)
Flumazenil
Benzodiazepine with useful relaxant effects in skeletal muscle spasticity of central origin
Diazepam
Benzodiazepine that has efficacy against absence seizures and in anxiety states, such as agoraphobia
Clonazepam
Benzodiazepines that are the most effective in the treatment of panic disorder
Alprazolam and Clonazepam
Benzodiazepine that is used for anesthesia
Midazolam
DOC for status epilepticus
Diazepam
Longer acting benzodiazepines used in the management of withdrawal states of alcohol and other drugs
Chlordiazepoxide and Diazepam
Agents having active metabolites, long half lives, and a high incidence of adverse effects
Diazepam, Flurazepam, chlordiazepoxide, and clorazepate
Barbiturates may precipitate this hematologic condition
Acute intermittent porphyria
Barbiturates decrease the effectiveness of many other drugs via this pharmacokinetics property
Liver enzyme INDUCTION
Barbiturates MOA
Increase the DURATION of GABA-mediated chloride ion channels
Barbiturate used for the induction of anesthesia
Thiopental
Important drug interaction with chloral hydrate
May displace coumadin from plasma proteins
Site of action for zaleplon and zolpidem
Benzodiazepine receptor BZ1 (although are not considered benzodiazepines)
Good hypnotic activity with less CNS SE than most benzodiazepines
Zolpidem, zaleplon
Agent that is a partial agonist for the 5-HT1A receptor
Buspirone
Drug of choice for generalized anxiety disorder, NOT effective in acute anxiety
Buspirone
Agent that is metabolized to acetaldehyde by alcohol dehydrogenase and microsomal ethanol-oxidizing system (MEOS)
Ethanol
Agent with zero-order kinetics
Ethanol, theophylline, tolbutamide, warfarin, aspirin, phenytoin
Rate limiting step of alcohol metabolism
Aldehyde dehydrogenase
System that increases in activity with chronic exposure and may contribute to tolerance
Microsomal ethanol oxidizing system (MEOS)
Enzyme that metabolizes acetaldehyde to acetate
Aldehyde dehydrogenase
Agents that inhibit aldehyde dehydrogenase
Disulfiram, metronidazole, certain sulfonylureas and cephalosporins
Agent used in the treatment of alcoholism, if alcohol is consumed concurrently, acetaldehyde builds up and results in nausea, headache, flushing, and hypotension
Disulfiram
The most common neurologic abnormality in chronic alcoholics
Peripheral neuropathy (also excessive alcohol use is associated with HTN, anemia, and MI)
Agent that is teratogen and causes a fetal syndrome
Alcohol
Agent that competes for alcohol dehydrogenase in the case of methanol overdose
Ethanol
Drug that inhibits alcohol dehydrogenase and is used in ethylene glycol exposure
Fomepizole
Most frequent route of metabolism
Hepatic enzymes
Mechanisms of action for Phenytoin, Carbamazepine, Lamotrigine
Sodium blockade
MOA for benzodiazepines and barbiturates
GABA-related targets
MOA for Ethosuximide
Calcium channels
MOA for Valproic acid at high doses
Affect calcium, potassium, and sodium channels
Drugs of choice for generalized tonic-clonic and partial seizures
Valproic acid, Phenytoin and Carbamazepine
DOC for febrile seizures
Phenobarbital
Drugs of choice for absence seizures
Ethosuximide and valproic acid
Drug of choice for myoclonic seizures
Valproic acid
Drugs of choice for status epilepticus
IV diazepam (or lorazapam) followed by phenytoin
Drugs that can be used for infantile spasms
Corticosteroids
Anti-seizure drugs used also for bipolar affective disorder (BAD)
Valproic acid, carbamazepine, phenytoin and gabapentin
Anti-seizure drugs used also for Trigeminal neuralgia
Carbamazepine
Anti-seizure drugs used also for pain of neuropathic orgin
Gabapentin
Anti-seizure agent that exhibits non-linear metabolism, highly protein bound, causes fetal hydantoin syndrome, and stimulates hepatic metabolism
Phenytoin
SE of phenytoin
Gingival hyperplasia, nystagmus, diplopia and ataxia
Anti-seizure agent that induces formation of liver drug-metabolism enzymes, is teratogen and can cause craniofacial anomalies and spina bifida
Carbamazepine
Agent that inhibits hepatic metabolism, is hepatotoxic and teratogen that can cause neural tube defects and gastrointestinal distress
Valproic acid
Laboratory value required to be monitored for patients on valproic acid
Serum ammonia and LFT’s
SE for Lamotrigine
Stevens-Johnson syndrome
SE for Felbamate
Aplastic anemia and acute hepatic failure
Anti-seizure medication also used in the prevention of migraines
Valproic acid
Carbamazepine may cause
Agranulocytosis
Anti-seizure drugs used as alternative drugs for mood stabilization
Carbamazepine, gabapentin, lamotrigine, and valproic acid
MOA of general anesthetics
Unclear, thought to increase the threshold for firing of CNS neurons
Inhaled anesthetic with a low blood/gas partition coefficient
Nitrous oxide
Inversely related to potency of anesthetics
Minimum alveolar anesthetic concentration (MAC)
Inhaled anesthetics metabolized by liver enzymes which has a major role in the toxicity of these agents
Halothane and methoxyflurane
Most inhaled anesthetics SE
Decrease arterial blood pressure
Inhaled anesthetics are myocardial depressants
Enflurane and halothane
Inhaled anesthetic causes peripheral vasodilation
Isoflurane
Inhaled anesthetic that may sensitize the myocardium to arrhythmogenic effects of catecholamines and has produced hepatitis
Halothane
Inhaled anesthetics, less likely to lower blood pressure than other agents, and has the smallest effect on respiration
Nitrous oxide
Fluoride released by metabolism of this inhaled anesthetic may cause renal insufficiency
Methoxyflurane
Prolonged exposure to this inhaled anesthetic may lead to megaloblastic anemia
Nitrous oxide
Pungent inhaled anesthetic which leads to high incidence of coughing and vasospasm
Desflurane
DOC for malignant hyperthermia that may be caused by use of halogenated anesthetics
Dantrolene
IV barbiturate used as a pre-op anesthetic
Thiopental
Benzodiazepine used adjunctively in anesthesia
Midazolam
Benzodiazepine receptor antagonist, it accelerates recovery from benzodiazepine overdose
Flumazenil
This produces “dissociative anesthesia”, is a cardiovascular stimulant which may increases intracranial pressure, and hallucinations occur during recovery
Ketamine
Opioid associated with awareness during surgery and post-operative recall, but still used for high-risk cardiovascular surgeries
Fentanyl
State of analgesia and amnesia produced when fentanyl is used with droperidol and nitrous oxide
Neuroleptanesthesia
Produces both rapid anesthesia and recovery, has antiemetic activity and commonly used for outpatient surgery, may cause marked hypotension
Propofol
MOA of local anesthetics (LA’s)
Block voltage-dependent sodium channels
This may enhance activity of local anesthetics
Hyperkalemia
This may antagonize activity of local anesthetics
Hypercalcemia
Almost all local anesthetics have this property and sometimes require the administration of vasoconstrictors (ex. Epinephrine) to prolong activity
Vasodilation
Local anesthetic with vasoconstrictive property, favored for head, neck, and pharyngeal surgery
Cocaine
Longer acting local anesthetics which are less dependent on vasoconstrictors
Tetracaine and bupivacaine
These LA’s have surface activity
Cocaine and benzocaine
Most important toxic effects of most local anesthetics
CNS toxicity
Commonly abused LA which has cardiovascular toxicity including severe hypertension with cerebral hemorrhage, cardiac arrhythmias, and myocardial infarction
Cocaine
LA causing methemoglobinemia
Prilocaine
Structurally related to acetylcholine, used to produce muscle paralysis in order to facilitate surgery or artifical ventilation. Full doses lead to respiratory paralysis and require ventilation
Neuromuscular blocking drugs
These drugs strongly potentiate and prolong effect of neuromuscular blockade (NMB)
Inhaled anesthetics, especially isoflurane, aminoglycosides, and antiarrhythmic
These prevent the action of ACh at the skeletal muscle endplate to produce a “surmountable blockade,” effect is reversed by cholinesterase inhibitors (ex. neostigmine or pyridostigmine)
Nondepolarizing type antagonists
Agent with long duration of action and is most likely to cause histamine release
Tubocurarine
Non-depolarizing antagonist has short duration
Mivacurium
Agent can block muscarinic receptors
Pancuronium
Agent undergoing Hofmann elimination (breaking down spontaneously)
Atracurium
One depolarizing blocker that causes continuous depolarization and results in muscle relaxation and paralysis, causes muscle pain postoperatively and myoglobinuria may occur
Succinylcholine
During Phase I these agents worsen the paralysis by succinylcholine, but during phase II they reverse the blockade produced by succinylcholine
Cholinesterase inhibitors
Agents acting in the CNS or in the skeletal muscle, used to reduce abnormally elevated tone caused by neurologic or muscle end plate disease
Spasmolytic drugs
Facilitates GABA presynaptic inhibition
Diazepam
GABA agonist in the spinal cord
Baclofen
Similar to clonidine and may cause hypotension
Tizanidine
DOC for malignant hyperthermia by acting on the sarcoplasmic reticulum or skeletal muscle
Dantrolene
Agent used for acute muscle spasm
Cyclobenzaprine
Antipsychotics, reserpine at high doses, and MPTP (by-product of illicit meperidine analog) and is irreversible
Drug induced Parkinsonism
Agent used in drug therapy of Parkinson’s instead of Dopamine which has low bioavailability and does not cross the BBB
L-dopa
This is combined with L-dopa, inhibits DOPA decarboxylase (active only peripherally) which allows lower effective doses of L-dopa and allows for fewer SE’s (GI distress, postural hypotension, and dyskinesias)
Carbidopa
Clinical response that may fluctuate in tx of Parkinson’s dx
On-off-phenomenon
Anti-Parkinson’s drug which increases intraocular pressure and is contraindicated in closed angle glaucoma
Levodopa
Ergot alkaloid that is a partial agonist at D2 receptors in the brain, used for patients who are refractory or cannot tolerate levodopa, causes erythromelalgia
Bromocriptine
Non ergot agents used as first-line therapy in the initial management of Parkinson’s
Pramipexole and ropinirole
Enhances dopaminergic neurotransmission SE’s include CNS excitation, acute toxic psychosis and livedo reticularis
Amantadine
Inhibitor of MAO type B which metabolizes dopamine, used adjunct to levodopa or as sole agent in newly diagnosed pt’s
Selegiline
Inhibitors of catechol-O-methyltransferase (COMT), used as adjuncts in Parkinson’s dx and cause acute hepatic failure (monitor LFT’s)
Entacapone and Tolcapone
Agent decreases the excitatory actions of cholinergic neurons. May improve tremor and rigidity but have LITTLE effect on bradykinesia. Atropine-like side effects
Benztropine
Agent effective in physiologic and essential tremor
Propranolol
Agents used in Huntington’s Disease
Tetrabenazine (amine depleting drug), Haloperidol (antipsychotic)
Agents used in Tourette’s dx
Haloperidol or pimozide
Chelating agent used in Wilson’s disease
Penicillamine
Extrapyramidal dysfunction is more common with these agents, which block this subtype of dopamine receptor
Older antipsychotic agents, D2 receptors
Side effects occuring in antipsychotics that block dopamine
EPS, hyperprolactinemia, amennorrhea, galactorrhea, neuroleptic malignant syndrome
Antipsychotics that reduce positive symptoms only
Older antipsychotics
Newer atypical antipsychotics that also improve some of the negative symptoms and help acute agitation
Olanzapine and aripiprazole
Atypical antipsychotic causing high prolactin levels
Risperidone
Newer atypical antipsychotic used for bipolar disorder, known to cause weight gain, and adversely affect diabetes
Olanzapine
Agent more frequently associated with extrapyramidal side effects that can be treated with benzodiazepine, diphenhydramine or muscarinic blocker
Haloperidol
Drug used in neuroleptic malignant syndrome
Dantrolene
Agents may exacerbate tardive dyskinesias (may be irreversible and there is no treatment)
Muscarinic blockers
Antipsychotics having the strongest autonomic effects
Chlorpromazine or Thioridazine
Antipsychotic having the weakest autonomic effects
Haloperidol
Only phenothiazine not exerting antiemetic effects, can cause visual impairment due to retinal deposits, and high doses have been associated with ventricular arrhythmias
Thioridazine
Agent with greater affinity to 5HT2A receptor; reserved for refractory schizophrenia, and can cause weight gain and agranulocytosis
Clozapine
Anti-psychotics shown not to cause tardive dyskinesia
Clozapine and quetiapine
Anti-psychotics available in depot preparation
Fluphenazine and haloperidol
Reduced seizure threshold
Low-potency typical antipsychotics and clozapine
Orthostatic hypotension and QT prolongation
Low potency and risperidone
Increased risk of developing cataracts
Quetiapine
Major route of elimination for Lithium
Kidneys
Patients being treated with lithium, who are dehydrated, or taking diuretics concurrently, could develop
Lithium toxicity, lithium-induced nephrogenic diabetes insipidus
Drug increases the renal clearance hence decreases levels of lithium
Theophylline
Lithium is associated with this congenital defect
Cardiac anomalies; contraindic: pregnancy&lactation
DOC for bipolar affective disorder
Lithium
SE of lithium
Tremor, sedation, ataxia, aphasia, thyroid enlargement, and reversible diabetes insipidus
Example of three antidepressants that are indicated for obsessive compulsive disorder
Clomipramine, fluoxetine and fluvoxamine
Neurotransmitters affected by the action of antidepressants
Norepinephrine and serotonin
Usual time needed for full effect of antidepressant therapy
2 to 3 weeks
Population group especially sensitive to side effects of antidepressants
Elderly patients
All antidepressants have roughly the same efficacy in treating depression, agents are chosen based on these criterion
Side-effect profile and prior pt response
Well-tolerated and are first-line antidepressants
SSRI’s, bupropion, and venlafaxine
Most useful in patients with significant anxiety, phobic features, hypochondriasis, and resistant depression
Monamine oxidase inhibitors
Condition will result from in combination of MAOI with tyramine containing foods (ex. wine, cheese, and pickled meats)
Hypertensive crisis
MAOI should not be administered with SSRI’s or potent TCA’s due to development of this condition
Serotonin syndrome
Sedation is a common side effect of these drugs, they lower seizure threshold, uses include BAD, acute panic attacks, phobias, enuresis, and chronic pain and their overdose can be deadly
Tricyclic antidepressants (TCA)
Three C’s associated with TCA toxicity
Coma, Convulsions, Cardiac problems (arrhythmias and wide QRS)
Agents having higher sedation and antimuscarinic effects than other TCA’s
Tertiary amines
TCA used in chronic pain, a hypnotic, and has marked antimuscarinic effects
Amitriptyline
TCA used in chronic pain, enuresis, and OCD
Imipramine
TCA with greatest sedation of this group, and marked antimuscarinic effects, used for sleep
Doxepin
TCA used in obsessive compulsive disorder (OCD), most significant of TCA’s for risk of seizure, weight gain, and neuropsychiatric signs and symptoms
Clomipramine
Secondary amines that have less sedation and more excitation effect
Nortriptyline, Desipramine
Antidepressant associated with neuroleptic malignant syndrome
Amoxapine
Antidepressant associated with seizures and cardiotoxicity
Maprotiline
Antidepressant having stimulant effects similar to SSRI’s and can increase blood pressure
Venlafaxine
Antidepressant inhibiting norepinephrine, serotonin, and dopamine reuptake
Venlafaxine
Antidepressant also used for sleep that causes priapism
Trazodone
Antidepressant which is inhibitor of CYP450 enzymes and may be associated with hepatic failure
Nefazodone
Unicyclic antidepressant least likely to affect sexual performance, used for management of nicotine withdrawal, SE’s include dizziness, dry mouth, aggravation of psychosis, and seizures
Bupropion
Antidepressant with MOA as alpha 2 antagonist, has effects on both 5-HT and NE, blocks histamine receptors, and is sedating
Mirtazapine
SE of mirtazapine
Liver toxicity, increased serum cholesterol
Except for these agents all SSRI have significant inhibition of CytP450 enzymes
Citalopram and its metabolite escitalopram
SSRI with long T1/2 and can be administered once weekly for maintenance, not acute tx
Fluoxetine
SSRI indicated for premenstrual dysphoric disorder
Fluoxetine (Sarafem)
Some of SSRIs’ therapeutic effects beside depression
Panic attacks, social phobias, bulimia nervosa, and PMDD (premenstrual dysphoric disorder), OCD
SSRI’s less likely to cause a withdrawal syndrome
Fluoxetine
Inhibit synaptic activity of primary afferents and spinal cord pain transmission neurons
Ascending pathways
Activation of these receptors close Ca2+ ion channels to inhibit neurotransmitter release and pain transmission
Presynaptic mu, delta, and kappa receptors
Activation of these receptors open K+ ion channels to cause membrane hyperpolarization
Postsynaptic Mu receptors
Tolerance to all effects of opioid agonists can develop except
Miosis, convulsions and constipation
All opioids except this agent (which has a muscarinic blocking action) cause pupillary constriction
Meperidine
SE of these drugs include dependence, withdrawal syndrome, sedation, euphoria, respiratory depression nausea and vomiting, constipation, biliary spasm, increased ureteral and bladder tone, and reduction in uterine tone
Opioid Analgesics
Strong opioid agonists
Morphine, methadone, meperidine, and fentanyl
Opioids used in anesthesia
Morphine and fentanyl
Opioid used in the management of withdrawal states
Methadone
Opioid available trans-dermally
Fentanyl
Opioid that can be given PO, by epidural, and IV, which helps to relieve the dyspnea of pulmonary edema
Morphine
Use of this opioid with MAOI can lead to hyperpyrexic coma, and with SSRI’s can lead to serotonin syndrome
Meperidine
Moderate opioid agonists
Codeine, hydrocodone, and oxycodone
Weak opioid agonist, poor analgesic, its overdose can cause severe toxicity including respiratory depression, circulatory collapse, pulmonary edema, and seizures
Propoxyphene
Partial opioid agonist, considered a strong analgesic, has a long duration of action and is resistant to naloxone reversal
Buprenorphine
Opioid antagonist that is given IV and had short DOA
Naloxone
Opioid antagonist that is given orally in alcohol dependency programs
Naltrexone
These agents are used as antitussive
Dextromethorphan, Codeine
These agents are used as antidiarrheal
Diphenoxylate, Loperamide
Inhalant anesthetics
NO, chloroform, and diethyl ether
Toxic to the liver, kidney, lungs, bone marrow, peripheral nerves, and cause brain damage in animals, sudden death has occurred following inhalation
Fluorocarbons and Industrial solvents
Cause dizziness, tachycardia, hypotension, and flushing
Organic nitrites
Causes acne, premature closure of epiphyses, masculinization in females, hepatic dysfunction, MI, and increases in libido and aggression
Steroids
Readily detected markers that may assist in diagnosis of the cause of a drug overdose include
Changes in heart rate, blood pressure, respiration, body temperature, sweating, bowel signs, and pupillary responses
Most commonly abused in health care professionals
Heroin, morphine, oxycodone, meperidine and fentanyl
This route is associated with rapid tolerance and psychologic dependence
IV administration
Lacrimation, rhinorrhea, yawning, sweating, weakness, gooseflesh, nausea, and vomiting, tremor, muscle jerks, and hyperpnea are signs of this syndrome
Abstinence syndrome
Treatment for opioid addiction
Methadone, followed by slow dose reduction
This agent may cause more severe, rapid and intense symptoms (abstinence syndrome) to a recovering addict
Naloxone
Sedative-Hypnotics action
Reduce inhibition, suppress anxiety, and produce relaxation
Additive effects when Sedative-Hypnotics used in combination with these agents
CNS depressants
Common mechanism by which overdose result in death
Depression of medullary and cardiovascular centers
Date rape drug
Flunitrazepam (rohypnol)
The most important sign of withdrawal syndrome
Excessive CNS stimulation (seizures)
