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859 Cards in this Set

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Basic Pharmacokinetics
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 administered dose of a drug that reaches systemic circulation
Bioavailability (F)
When the rate of drug input equals the rate of drug elimination
Steady state
Metabolism
This step of metabolism makes drug more hydrophilic and hence augments elimination
Phase I
Different steps of Phase I
Oxidation, reduction, hydrolysis
Inducers of Cytochrome P450 (CYP450)
Barbiturates, phenytoin, carbamazepine, and rifampin
Inhibitors of CYP450
Cimetidine, ketoconazole, erythromycin, isoniazid and grapefruit
Products of Phase II conjugation
Glucuronate, acetic acid, and glutathione sulfate
Constant percentage of substrate metabolized per unit time
First order kinetics
Drug elimination with a constant amount metabolized regardless of drug concentration
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))
Pharmacodynamics
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
Potency
Ability of drug to produce a biologic effect
Efficacy
Ability of a drug to produce 100% of the maximum response regardless of the potency
Full agonist
Ability to produce less than 100% of the response
Partial agonist
Ability to bind reversibly to the same site as the drug and without activating the effector system
Competitive antagonist
Ability to bind to either the same or different site as the drug
Noncompetitive antagonist
Mechanism of action (MOA) utilizes intracellular receptors
Thyroid and steroid hormones
MOA utilizes transmembrane receptors
Insulin
MOA utilizes ligand gated ion channels
Benzodiazepines and calcium channel blockers
Median effective dose required for an effect in 50% of the population
ED50
Median toxic dose required for a toxic effect 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
Drug with a high margin of safety
High therapeutic index
Drug with a narrow margin of safety
Low therapeutic index
Antidotes and agents used in drug overdose
Antidote used for lead poisoning
Dimercaprol, EDTA
Antidote used for cyanide poisoning
Nitrites
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 (Mucomyst)
Antidote for arsenic, mercury, lead, and gold poisoning
Dimercaprol
Antidote used in poisonings: copper (Wilson's disease), lead, mercury, and arsenic
Penicillamine
Antidote used for heparin overdose
Protamine
Antidote used for warfarin toxicity
Vitamin and Fresh frozen plasma (FFP)
Antidote for tissue plasminogen activator (t-PA), streptokinase
Aminocaproic acid
Antidote used for methanol and ethylene glycol
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-blockers and hypoglycemia
Glucagon
Antidote useful for some drug induced Torsade de pointes
Magnesium sulfate
Antidote for hyperkalemia
sodium polystyrene sulfonate (Kayexalate)
Antidote for salicylate intoxication
Alkalinize urine, dialysis
Cancer Chemotherapy
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 "Thymine-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 toxic by scavenging free radicals
Dexrazoxane
Blows DNA (breaks DNA strands), limiting SE is pulmonary fibrosis
Bleomycin
Bleomycin+vinblastine+etoposide+cisplatin produce almost a 100% response when all agents are used for this neoplasm
Testicular cancer
MOPP regimen used in Hodgkin's disease (HD)
Mechlorethamine+ oncovorin (vincristine)+ procarbazine, and prednisone
ABVD regimen used for HD, but appears less likely to cause sterility and secondary malignancies than MOPP
Adriamycin (doxorubicin) +bleomycin, vinblastine +dacarbazine
Regimen used for non-Hodgkin's lymphoma
COP (cyclophosphamide, oncovin(vincristine), and prednisone)
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
Interact with microtubules (but unlike vinca which prevent disassembly of tubules), it stabilizes tubulin and cells remain frozen in metaphase
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
Aromatase inhibitor used in breast cancer
Letrozole, anastrozole
Newer estrogen receptor antagonist used in advanced breast cancer
Toremifene (Fareston)
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
Nitrosoureas with high lipophilicity, used for brain tumors
Carmustine (BCNU) and lomustine (CCNU)
Produces disulfiram-like reaction with ethanol
Procarbazine
Endocrine drugs: hypothalamic and pituitary hormones
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
Dopamine (DA) agonist (for Parkinson's disease), used also for hyperprolactinemia
Bromocriptine
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)
SE of OCs
Increased thromboembolic events
Thyroid and anti-thyroid drugs
Most widely used thyroid drugs such as Synthroid and Levoxyl contain
L-thyroxine (T4)
T3 compound less widely used
Cytomel
Anti-thyroid drugs
Thioamides, iodides, radioactive iodine, and ipodate
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 should be used with extreme caution in pregnancy
PTU
PTU (propylthiouracil) MOA
Inhibits thyroid hormone synthesis by blocking iodination of the tyrosine residues of thyroglobulin
Can be effective for short term therapy of thyroid storm, but after several weeks of therapy causes an exacerbation of hyperthyroidism
Iodide salts
Dose may need to be increased during pregnancy or with Ocs due to increased TBG in plasma
Thyroxine
Permanently cures thyrotoxicosis, patients will need thyroid replacement therapy thereafter. Contraindicated in pregnancy
Radioactive iodine
Radio contrast media that inhibits the conversion of T4 to T3
Ipodate
Block cardiac adverse effects of thyrotoxicosis such as tachycardia, inhibits the conversion of T4 to T3
Beta-blockers such as propranolol
Vitamins containing iron should NOT be taken simultaneously with levothyroxine because
Iron deiodinates thyroxine
Thyroxine dose may need to be increased in hypothyroid patient during pregnancy because
Estogens increase maternal TBG
Adrenocorticosteroid and adrenocortical antagonists
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, and triamcinolone
Long acting GC's
Betamethasone, dexamethasone, and paramethasone
Mineralocorticoids
Fludrocortisone and deoxycorticosterone
Some side effects of corticosteroids
Osteopenia, impaired wound healing, inc. risk of infection, inc. appetite, HTN, edema, PUD, euphoria, psychosis, stria, thinning of skin
Period of time of therapy after which GC therapy will need to be tapered
5-7 days
Inhibitors of corticosteroids biosynthesis
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
Gonadal hormones and inhibitors
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
Drug is used with testosterone for male fertility
Leuprolide
Pancreatic hormones, antidiabetics, and hyperglycemics
Alpha cells in the pancreas
Produce glucagon
Beta cells in the pancreas
Produce insulin
Beta cells are found
Islets of Langerhans
Delta cells in the pancreas
Produce Somatostatin
Product of proinsulin cleavage used to assess insulin abuse
C-peptide
Exogenous insulin
Little C-peptide
Endogenous insulin
Normal C-peptide
Very rapid acting insulin, having fastest onset and shortest duration of action
Lispro (Humalog)
Rapid acting, crystalline zinc insulin used to reverse acute hyperglycemia
Regular (Humulin R)
Long acting insulin
Ultralente (humulin U)
Ultra long acting insulin, has over a day duration of action
Glargine (Lantus)
Major SE 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
Nateglinide
MOA of nateglinide
Insulin secretagogue
Biguanide
Metformin
Drugs available in combination with 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
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
Drugs used in bone homeostasis
Available bisphosphonates
Alendronate, etidronate, risedronate, pamidronate, tiludronate, and zoledronic acid
MOA of Bisphosphonates
Inhibits osteoclast bone resorption
Only bisphosphonates available IV
Etidronate
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
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
Drugs with important actions on smooth muscle
Disease caused by excess ergot alkaloids
St. Anthony's Fire
Endogenous substances commonly interpreted as histamine, serotonin, prostaglandins, and vasoactive peptides
Autocoids
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; stomach, heart, and mast cells; nerve endings, CNS respectively
Prototype antagonist of H1 and H2 receptors
Diphenhydramine and cimetridine, respectively
1st generation antihistamine that is highly sedating
Diphendydramine
1st generation antihistamine that is least sedating
Chlorpheniramine or cyclizine
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
Antihistamine that can be used for anxiety and insomnia and is not addictive
hydroxyzine (Atarax)
H1 antagonist used in motion sickness
Dimenhydrinate, meclizine, and other 1st generation
Most common side effect of 1st generation antihistamines
Sedation
Lethal arrhythmias resulting from concurrent therapy with azole fungals (metabolized by CYP 3A4) and these antihistamines which inhibit the 3A4 iso-enzyme.
Terfenadine and astemizole (have been removed from the market)
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 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
Agents for reduction of postpartum bleeding
Oxytocin, ergonovine and ergotamine
Agents used in treatment of carcinoid tumor
Ketanserin cyproheptadine, and phenoxybenzamine
5HT-3 antagonist used in chemotherapeutic induced emesis
Ondansetron, granisetron, dolasetron and alosetron
5ht-3 antagonist that has been associated with QRS and QTc prolongation and should not be used in patients with heart disease
Dolasetron
DOC of chemo induced nausea and vomiting
Odansetron
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 found throughout the body and COX 2 is only in inflammatory tissue
Drug that selectively inhibits COX 2
Celecoxib and rofecoxib
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
Approved for use in severe pulmonary HTN
PGI2 (epoprostenol)
Prostaglandin used in the treatment impotence
Alprostadil
Irreversible, nonselective COX inhibitor
Aspirin
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 asthma
Ipratropium
MOA action of cromolyn
Mast cell stabilizer
Methylxanthine derivative used as a remedy for intermittent claudication
Pentoxifylline
MOA of corticosteroids
inhibit phospholipase A2
SE of long term (>5 days) corticosteroid therapy and remedy
Adrenal suppression and weaning slowly, respectively
Antimicrobials
MOA of quinolones
Inhibit DNA gyrase
MOA of penicillin
Block cell wall synthesis by inhibiting peptidoglycan cross-linkage
Drug used for MRSA
Vancomycin
Vancomycin MOA
Blocks peptidoglycan synthesis
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 and mebendazole
Two toxicities of aminoglycosides
nephro and ototoxicity
DOC for Legionnaires' disease
Erythromycin
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, infusion at a slow rate and antihistamines
Drug causes teeth discoloration
Tetracycline
MOA of tetracycline
Decreases protein synthesis by inhibiting 30S ribosome
Drug that causes gray baby syndrome and aplastic anemia
Chloramphenicol
Drug notorious for causing pseudomembranous colitis
Clindamycin
DOC 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
Red 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
Amantadine
DOC for RSV
Ribavirin
DOC for CMV retinitis
Ganciclovir
SE for ganciclovir
Neutro, leuko and thrombocytopenia
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, and 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
Cefuroxime (2nd) generation and Cefixime (3rd) generation
Drug used for N. gonorrhea in females
Ceftriaxone
Cephalosporin causes 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; incorporated into viral DNA and chain termination
Anti-microbials that cause hemolysis in G6PD-deficient patients
Sulfonamides
MOA of erythromycin
Inhibition of protein synthesis at the 50s subunit of ribosome
Anti-biotic frequently used for chronic UTI prophylaxis
sulfamethoxazole/ trimethoprim
Lactam that can be used in PCN allergic patients
Aztreonam
SE of imipenem
Seizures
Anti-viral with a dose limiting toxicity of pancreatitis
Didanosine
Sedative Hypnotics
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
Benzodiazepines used to promote sleep
Temazpam, trizolam, flurazepam
Benzodiazepine used for anxiety
Alprazolam
Non-benzodiazepine used as an anxiolytic
Buspirone
Non-benzodiazepine used for sleep
Zolpidem
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
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
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
Alcohols
Agent that is metabolized to acetaldehyde by alcohol dehydrogenase and microsomal ethanol-oxidizing system (MEOS)
Ethanol
Agent with zero-order kinetics
Ethanol
Rate limiting step of alcohol metabolism
Aldehyde dehydrogenase
System that increases in activity with chronic exposure and may contribute to tolerance
MEOS
Agent that metabolize acetaldehyde to acetate
Aldehyde dehydrogenase
Agents that inhibit alcohol 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
Ethanol
Agent that is the antidote for methanol overdose
Ethanol
Drug that inhibits alcohol dehydrogenase and is used in ethylene glycol exposure
Fomepizole
Anti seizure Drugs
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 and Phenytoin
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 for short term (acute) treatment; phenytoin for prolonged therapy
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
General Anesthetics
MOA of general anesthetics
Most are thought to act at GABA-A receptor - chloride channel
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 anesthetic, 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 respiratory depression, but is used in high risk patients who may not survive full general anesthetia
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
Local Anesthetics
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
Skeletal Muscle Relaxants
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 sost likely to cause histamine release
Tubocurarine
Non-depolarizing antagonist has short duration
Mivacurium
Agent can blocking 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
Spasmolytic drugs
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 sacroplasmic reticulum or skeletal muscle
Dantrolene
Agent used for acute muscle spasm
Cyclobenzaprine
Drugs Used in Parkinsonism & Other Movement Disorders
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
Antipsychotics
Extrapyramidal dysfunction is more common with these agents, which block this subtype of dopamine receptor
Older antipsychotic agents, D2 receptors
MOA of neuroleptics
Dopamine blockade
Side effects occuring in antipsychotics that block dopamine
Hyperprolactinemia, menorrhea, galactorrhea, confusion, mood changes, decreased sexual interest, and weight gain
Antipsychotics that reduce positive symptoms only
Older antipsychotics
Newer atypical antipsychotics that also improve some of the negative symptoms and help acute agitation
Olanzapine, aripiprazole, and sertindole
Antipsychotic used in the treatment of psychiatric symptoms in patients with dementia
Risperidone
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
Antipsychotic having the strongest autonomic effects
Thioridazine
Antipsychotic having the weakest autonomic effects
Haloperidol
Antipsychotic that does not block muscarinic or histamine receptors, and it prolongs the QT interval
Sertindole
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 having no effect on D2 receptors, blocks D4, reserved for resistant schizophrenia, and can cause fatal agranulocytosis
Clozapine
Anti-psychotic not shown to cause tardive dyskinesia
Clozapine
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
Lithium
Major route of elimination for Lithium
Kidneys
Patients being treated with lithium, who are dehydrated, or taking diuretics concurrently, could develop
Lithium toxicity
Drug increases the renal clearance hence decreases levels of lithium
Theophylline
Lithium is associated with this congenital defect
Cardiac anomalies and is contraindicated in pregnancy or lactation
DOC for bipolar affective disorder
Lithium
Concern using lithium
Low therapeutic index
SE of lithium
Tremor, sedation, ataxia, aphasia, thyroid enlargement, and reversible diabetes insipidus
Antidepressants
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
Monoamine oxidase inhibitors (MAOI)
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
Tricyclic antidepressants (TCA)
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 ADD
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
Side effects seen with tricyclic antidepressants
Muscarinic blockade (dry mouth, constipation); weak alpha-1 block (orthostatic hypotension); weak hisamine block (sedation)
Heterocyclics
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
Heterocyclic antidepressants 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
Selective serotonin reuptake inhibitors (SSRI)
Except for these agents all SSRI have significant inhibition of CytP450 enzymes
Citalopram and its metabolite escitalopram
Side effects frequently seen with SSRIs
CNS stimulation; GI upset
Antidepressants with no effect on BP, no sedation
SSRIs
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
Opioid Analgesics & Antagonists
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
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 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 agonist or mixed antagonists
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
Drugs of Abuse
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
Opioid Analgesics
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
Leads to respiratory depression progressing to coma and death
Overdose of opioids
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 to a recovering addict
Naloxone
Sedative-Hypnotics
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)
Treatment of withdrawal syndrome involves
Long-acting sedative-hypnotic or a gradual reduction of dose, clonidine or propranolol
These agents are CNS depressants
Ethanol, Barbiturates, and Benzodiazepines
Stimulants
Withdrawal from this drug causes lethargy, irritability, and headache
Caffeine
W/D from this drug causes anxiety and mental discomfort
Nicotine
Treatments available for nicotine addiction
Patches, gum, nasal spray, psychotherapy, and bupropion
Chronic high dose abuse of nicotine leads to
Psychotic state, overdose causes agitation, restlessness, tachycardia, hyperthermia, hyperreflexia, and seizures
Tolerance is marked and abstinence syndrome occurs
Amphetamines
Amphetamine agents
Dextroamphetamines and methamphetamine
These agents are congeners of Amphetamine
DOM, STP, MDA, and MDMA "ecstasy"
Overdoses of this agent with powerful vasoconstrictive action may result in fatalities from arrhythmias, seizures, respiratory depression, or severe HTN (MI and stroke)
Cocaine "super-speed"
Hallucinogens
Most dangerous of the currently popular hallucinogenic drugs, OD leads to nystagmus, marked hypertension, and seizures, presence of both horizontal and vertical nystagmus is pathognomonic
PCP
Removal of PCP may be aided
Urinary acidification and activated charcoal or continual nasogastric suction
THC is active ingredient, SE's include impairment of judgment, and reflexes, decreases in blood pressure and psychomotor performance occur
Marijuana
Cholinoreceptor-Activating & Cholinesterase-Inhibiting Drugs
Direct-Acting Cholinomimetic Agonists
Muscarinic agonists or parasympathomimetic
This agent has greater affinity for muscarinic receptors and used for postoperative and neurogenic ileus and urinary retention
Bethanechol
Only direct acting agent that is very lipid soluble and used in glaucoma
Pilocarpine
This agent used to treat dry mouth in Sjögren's syndrome
Cevimeline
Indirect-Acting ACh Agonist, alcohol, short DOA and used in diagnosis of myasthenia gravis
Edrophonium
Carbamate with intermediate action postoperative and neurogenic ileus and urinary retention
Neostigmine
Treatment of atropine overdose and glaucoma (because lipid soluable). Enters the CNS rapidly and has a stimulant effect, which may lead to convulsions
Physostigmine
Treatment of myasthenia gravis
Pyridostigmine
Organophosphates
Antiglaucoma organophosphate
Echothiophate
Associated with an increased incidence of cataracts in patients treated for glaucoma
Long acting cholinesterase inhibitors
Scabicide organophosphate
Malathion
Organophosphate anthelmintic agent with long DOA
Metrifonate
Toxicity of organophosphate:
DUMBELSS (diarrhea, urination, miosis, bronchoconstriction, excitation of skeletal muscle and CNS, lacrimation, salivation, and sweating)
The most important cause of acute deaths in cholinesterase inhibitor toxicity
Respiratory failure
The most toxic organophosphate
Parathion
Treatment of choice for organophosphate overdose
Atropine
This agent regenerates active cholinesterase and is a chemical antagonist used to treat organophosphate exposure
Pralidoxime
Cholinoreceptor Blockers & Cholinesterase Regenerators
Prototypical drug is atropine
Nonselective Muscarinic Antagonists
Treat manifestations of Parkinson's disease and EPS
Benztropine, trihexyphenidyl
Treatment of motion sickness
Scopolamine
Produce mydriasis and cycloplegia
Atropine, homatropine tropicamide
Bronchodilation in asthma and COPD
Ipratropium
Reduce transient hyper GI motility
Dicyclomine, methscopolamine
Cystitis, postoperative bladder spasms, or incontinence
Oxybutynin, dicyclomine
Toxicity of anticholinergics
block SLUD (salivation, lacrimation, urination, defecation
Another pneumonic for anticholinergic toxicity
"dry as a bone, red as a beet, mad as a hatter, hot as a hare, blind as a bat"
Atropine fever is the most dangerous effect and can be lethal in this population group
Infants
Contraindications to use of atropine
Infants, closed angle glaucoma, prostatic hypertrophy
Nicotinic Antagonists
Limiting adverse effect of ganglion blockade that patients usually are unable to tolerate
Severe hypertension
Reversal of blockade by neuromuscular blockers
Cholinesterase inhibitors
Tubocurarine is the prototype, pancuronium, atracurium, vecuronium are newer short acting agent, produce competitive block at end plate nicotinic receptor, causing flaccid paralysis
Nondepolarizing Neuromuscular Blockers
Only member of depolarizing neuromuscular blocker, causes fasciculation during induction and muscle pain after use
Succinylcholine
Chemical antagonists that bind to the inhibitor of ACh Estrace and displace the enzyme (if aging has not occurred)
Cholinesterase regenerators, pralidoxime
Used to treat patients exposed to insecticides such as parathion
Pralidoxime, atropine+C1206
Sympathomimetics
Pneumonic for beta receptors
You have 1 heart (Beta 1) and 2 lungs (Beta 2)
This is the drug of choice for anaphylactic shock
Epinephrine
Phenylisopropylamines that are used legitimately and abused for narcolepsy, attention deficit disorder, and weight reduction
Amphetamines
Alpha agonist used to produce mydriasis and reduce conjunctival itching and congestion caused by irritation or allergy, it does not cause cycloplegia
Phenylephrine
Epinephrine and dipivefrin are used for
Glaucoma
Newer alpha 2 agonist (apraclonidine and brimonidine) treat glaucoma
Reduce aqueous synthesis
Short acting Beta 2 agonists that is drug of choice in treatment of acute asthma but not recommended for prophylaxis
Albuterol
Longer acting Beta 2 agonists is recommended for prophylaxis of asthma
Salmeterol
These agents increase blood flow and may be beneficial in treatment of acute heart failure and some types of shock
Beta1 agonists
These agents decrease blood flow or increase blood pressure, are local decongestant, and used in therapy of spinal shock (temporary maintenance of blood pressure which may help maintain perfusion
Alpha1 agonists
Shock due to septicemia or myocardial infarction is made worse by
Increasing afterload and tissue perfusion declines
Often mixed with local anesthetic to
Reduce the loss from area of injection
Chronic orthostatic hypotension can be treated with
Midodrine
Beta 2 agonist used to suppress premature labor, but cardiac stimulatory effects may be hazardous to mother and fetus
Terbutaline
Sympathetic agent which stimulates heart rate and can dilate vessels in skeletal muscle at low doses
Epinephrine
Mast cells to reduce release of hisamine and inflammatory mediators
Epinephrine
Agent used in shock because it dilates coronary arteries and increases renal blood flow
Dopamine
Agent which stimulates cardiac contractile force more than rate with little effect on total peripheral resistance
Dobutamine
Long acting sympathomimetic, sometimes used to improve urinary continence in children and elderly with enuresis
Ephedrine
Alpha 1 agonist toxicity
Hypertension
Beta 1 agonist toxicity
Sinus tachycardia and serious arrhythmias
Beta 2 agonist toxicity
Skeletal muscle tremor, tachycardia
The selective agents loose their selectivity at
high doses
Adrenoceptor Blocker
Nonselective alpha-blocking drug, long acting and irreversible, and used to treat pheochromocytoma. Blocks 5-HT, so occasionaly used for carcinoid tumor. Blocks H1 and used in mastocytosis
Phenoxybenzamine
Nonselective alpha-blocking drug, short acting and reversible, used for rebound HTN from rapid clonidine withdrawal, and Raynaud's phenomena
Phentolamine
Selective Alpha 1 blocker used for hypertension, BPH, may cause first dose orthostatic hypotension
Prazosin, terazosin, doxazosin
Selective Alpha 2 blocker used for impotence (controversial effectiveness)
Yohimbine
Beta-Blocking Drugs
SelectiveB1 Receptor blockers that may be useful in treating patients even though they have asthma
Acebutolol, atenolol, esmolol, metoprolol
Combined alpha and beta blocking agents that may have application in treatment of CHF
Labetalol and carvedilol
Beta blockers partial agonist activity (intrinsic sympathomimetic activity) cause some bronchodilation and may have an advantage in treating patients with asthma
Pindolol and acebutolol
This beta blocker lacks local anesthetic activity (decreases protective reflexes and increases the risk of corneal ulceration) and used in treating glaucoma
Timolol
This parenteral beta blocker is a short acting (minutes)
Esmolol
This beta blocker is the longest acting
Nadolol
These beta blockers are less lipid soluble
Acebutolol and atenolol
This beta blocker is highly lipid soluble and may account for side effects such as nightmares
Propranolol
Clinical uses of these agents include treatment of HTN, angina, arrhythmias, and chronic CHF
Beta blockers
Toxicity of these agents include bradycardia, AV blockade, exacerbation of acute CHF, signs of hypoglycemia may be masked (tachycardia, tremor, and anxiety)
Beta blockers
Glaucoma (all agents topical except for diuretics)
Cholinomimetics that increase outflow, open trabecular meshwork, and cause ciliary muscle contraction
Pilocarpine, carbachol, physostigmine
Nonselective alpha agonists that increases outflow, probably via the uveoscleral veins
Epinephrine, dipivefrin
Selective alpha agonists that decreases aqueous secretion
Apraclonidine, brimonidine
These Beta blockers decrease aqueous secretion
Timolol (nonselective), betaxolol (selective)
This diuretic decreases aqueous secretion due to lack of HCO3- ion. Causes drowsiness and paresthesias, alkalinization of the urine may precipitate calcium salts, hypokalemia, acidosis
Acetazolamide
This agent cause increased aqueous outflow
Prostaglandin PGF2a
Antihypertensive Agents
Inhibit angiotensin-converting enzyme (ACE)
Ace inhibitors
Captopril and enalapril (-OPRIL ending) are
Ace inhibitors
SE of ACE inhibitors
Dry cough, hyperkalemia
Ace inhibitors are contraindicated in
pregnancy and with K+
Losartan and valsartan block
Angiotensin receptor
Angiotensin receptor blockers do NOT cause
Dry cough
Block L-type calcium channel
Calcium channel blockers
CCB contraindicated in CHF
Verapamil
CCB with predominate effect on arteriole dilation
Nifedipine
SE of CCB
Constipation, edema, and headache
Reduce heart rate, contractility, and O2 demand
Beta-blockers
B-blockers that are more cardioselective
Beta C2001-selective blockers
Cardioselective Beta 1-blockers
Atenolol, acebutolol, and metoprolol
Beta-blockers should be used cautiously in
Asthma (bronchospastic effects), diabetes (block signs of hypoglycemia) and peripheral vascular disease
Non-selective Beta-blocker also used for migraine prophylaxis
Propranolol
SE of beta blockers
Bradycardia, SEXUAL DYSFUNCTION, decrease in HDL, and increase in Triglycerols (TG)
Alpha 1selective blockers
Prazosin, terazosin and doxazosin (-AZOSIN ending)
Non-selective Alpha1blockers use to treat pheochromocytoma
Phenoxybenzamine
For rebound HTN from rapid clonidine withdrawal
Phentolamine
A1a-selective blocker with no effects on HTN used for BPH
Tamsulosin (Flomax)
SE of alpha blockers
Orthostatic hypotension (especially with first dose) and reflex tachycardia
Presynaptic Alpha 2 agonist used in HTN, and acts centrally
Clonidine, and methyldopa
SE of methyldopa
Positive Comb's test, depression
Methyldopa is contraindicated in
Geriatrics due to its CNS (depression) effects
SE of clonidine
Rebound HTN, sedation, dry mouth
Direct vasodilator of arteriolar smooth muscle
Hydralazine
SE of hydralazine
Lupus-like syndrome
Arterial vasodilator that works by opening K+ channels
Minoxidil
SE of minoxidil
Hypertrichosis
IV Drug used Hypertensive Crisis
Nitroprusside
Nitroprusside vasodilates
Arteries and veins
Toxicity caused by nitroprusside and treatment
Cyanide toxicity treated with sodium thiosulfate
Diuretics
Carbonic anhydrase inhibitor
Acetazolamide
Diuretic used for mountain sickness and glaucoma
Acetazolamide
SE of acetazolamide
Paresthesias, alkalization of the urine (which may ppt. Ca salts), hypokalemia, acidosis, and encephalopathy in patients with hepatic impairment
MOA of loop diuretics
inhibits Na+/K+/2Cl- cotransport
Site of action of loop diuretics
Thick ascending limb
SE of loop (furosemide) diuretics
Hyperuricemia, hypokalemia and ototoxicity
Aminoglycosides used with loop diuretics potentiate adverse effect
Ototoxicity
Loops lose and thiazide diuretics retain
Calcium
MOA of thiazide diuretics
Inhibit Na+/Cl- cotransport
Site of action of thiazide diuretics
Work at early distal convoluted tubule
Class of drugs that may cause cross-sensitivity with thiazide diuretics
Sulfonamides
SE of thiazide (HCTZ) diuretics
Hyperuricemia, hypokalemia and hyperglycemia
Potassium sparing diuretics inhibit
Na+/K+ exchange
Diuretic used to treat primary aldosteronism
Spironolactone
SE of spironolactone
Gynecomastia hyperkalemia, and impotence
Osmotic diuretic used for increased intracranial pressure
Mannitol
Antidiuretic hormone (ADH) agonist and antagonist
ADH agonist used for pituitary diabetes insipidus
Desmopressin (DDAVP)
Used for SIADH
Demeclocycline
SE of demeclocycline
Bone marrow and teeth discoloration for children under 8 years of age
Antiarrhythmic agents
MOA of class I A (eg. Procainamide), class IB (eg. Lidocaine), and class IC (eg. Flecainide) antiarrhythmics
Sodium channel blockers
SE of procainamide
Lupus-like syndrome
Limiting side effect of Quinidine
Prolongs QT interval
Other side effects of Quinidine
Thrombocytopenic purpura, and CINCHONISM
Major drug interaction with Quinidine
Increases concentration of Digoxin
DOC for management of acute Ventricular arrhythmias
Lidocaine
DOC for digoxin induced arrhythmias
Phenytoin
SE of phenytoin
Gingival hyperplasia
Class of anti-arrhythmics that has a pro-arrhythmic effect (CAST trial), therefore are used as last line agents
Class IC (flecainide, propafenone, moricizine)
Class II antiarrhythmics are
B-blockers
Antiarrhythmic that exhibits Class II and III properties
Sotalol
Side effect of sotalol
prolongs QT and PR interval
Used intravenously for acute arrhythmias during surgery
Esmolol
Anti-arrhythmics that decrease mortality
B-blockers
MOA of class III antiarrhythmics
Potassium channel blockers
Class III antiarrhythmic that exhibits properties of all 4 classes
Amiodarone
Specific pharmacokinetic characteristic of amiodarone
Prolonged half-life, up to six weeks
Antiarrhythmic effective in most types of arrhythmia
Amiodarone
SE of Amiodarone
Dysfunction, photosensitivity, skin (blue smurf syndrome), Pulmonary fibrosis, thyroid and corneal deposits
MOA of class IV antiarrhythmics
Calcium channel blockers
Life threatening cardiac event that prolong QT leads to
Torsades de pointes
Agent to treat torsades de pointes
Magnesium sulfate
Drug used supraventricular arrhythmias
Digoxin
DOC for paroxysmal supraventricular tachycardia (PSVT)
Adenosine
Adenosine's MOA
Activates acetylcholine sensitive K+ channels in SA and AV node
Anti-arrhythmic with 15 second duration of action
Adenosine
Vasodilators and treatment of angina
MOA of sildenafil (Viagra)
Inhibits phosphodiesterase-5, enhancing effects of nitric oxide-activated increases in cGMP
Drugs used in the management of angina
Aspirin, Nitrates, CCB, and Beta blockers
Aspirin reduces mortality in unstable angina by
Platelet aggregation inhibition
MOA of nitrates
Relax vascular smooth muscle, at low doses dilate veins and at high doses dilate arterioles
Nitrate used for acute anginal attacks
Nitroglycerin sublingual tablets
Nitrate used to prevent further attacks
Oral and transdermal forms of nitroglycerin
Nitrate free intervals are needed due to
Tolerance
SE of nitrates
Postural hypotension, reflex tachycardia, hot flashes, and throbbing headache due to meningeal artery dilation
CCB are DOC for
Prinzmetal's angina
Beta blockers are used for which type of anginal attack
Classic
Drugs used to treat CHF
MOA of Cardiac glycosides (eg. digoxin)
Indirectly increase intracellular calcium and cardiac contractility by inhibit Na+/K+ ATPase
Digoxin is used in
Atrial fibrillation and CHF
Digoxin toxicity can be precipitated by
Hypokalemia
Antidote for digoxin toxicity
Digibind
Phosphodiesterase inhibitors that increase mortality and have been found to have NO beneficial effects
Amrinone and milrinone
SE of amrinone
Thrombocytopenia
Beta 1 agonists used in acute CHF
Dobutamine and dopamine
Diuretics work in CHF by
Reducing preload
Beta blockers work in CHF by
Reducing progression of heart failure (never use in acute heart failure)
Peptide drug used to treat CHF
Nesiritide (BNP)
MOA of nesiritide
Increasing sodium excretion and decreases arterial and venous tone
SE of nesiritide
Excessive hypotension and kidney failure
Agent used in CHF that is a selective alpha and nonselective beta blocker
Carvedilol
Agent used in acutely decompensated CHF resembling natriuretic peptide
Nesiritide (Natrecor)
Drugs used in coagulation disorders
Vitamin K dependent anticoagulant
Warfarin (PT)
Warfarin is contraindicated in
Pregnancy
Anticoagulant of choice in pregnancy
Heparin
Heparin (PTT) increases activity of
Antithrombin 3
Route of administration of warfarin
Oral
Routes of administration of heparin
IM (only LMW) and IV
SE of both warfarin and heparin
Bleeding
SE of heparin
Heparin induced thrombocytopenia (HIT)
Alternative anticoagulant used if HIT develops
Lepirudin
Antidote to reverse actions of warfarin
Vitamin K or fresh frozen plasma
Antidote to reverse actions of heparin
Protamine sulfate
MOA of aspirin
Irreversibly blocking cyclooxygenase
Agent used to treat MI and to reduce incidence of subsequent MI
Aspirin, metoprolol
SE of Aspirin
GI bleeding
Antiplatelet drug reserved for patients allergic to aspirin
Ticlopidine
SE for ticlopidine
Neutropenia and agranulocytosis
Effective in preventing TIA's
Clopidogrel and ticlopidine
Prevents thrombosis in patients with artificial heart valve
Dipyridamole
Block glycoprotein IIb/IIIa involved in platelet cross-linking
Abciximab, tirofiban and eptifibatide
MOA of thrombolytics
Degradation of fibrin clots and are administered IV
Thrombolytics are used for
Pulmonary embolism and DVT
Thrombolytic that can cause allergic reaction
Streptokinase
Thrombolytic used for acute MI and ischemic (non hemorrhagic) CVA
Tissue plasmin activator
SE of tPA
Cerebral hemorrhage
Antidote for thrombolytics
Aminocaproic acid
Agents used in anemias and hematopoietic growth factors
Agent to treat hypochromic microcytic anemias
Ferrous sulfate
Chelating agent used in acute iron toxicity
Deferoxamine
Agent for pernicious anemia
Cyanocobalamin (Vit B12)
Agent used for neurological deficits in megaloblastic anemia
Vitamin B12
Agent used for megaloblastic anemia (but does NOT reverse neurologic symptoms) and decrease neural tube defects during pregnancy
Folic acid
Agent used for anemias associated with renal failure
Erythropoietin
Agent used neutropenia especially after chemotherapy
G-CSF (filgrastim) and GM-CSF (sargramostim)
Treatment of patients with prior episodes of thrombocytopenia after a cycle of cancer chemotherapy
Interleukin 11 (oprelvekin)
Antihyperlipidemics
Decrease intestinal absorption of cholesterol
Bile acid-binding resins
Cholestyramine and colestipol are
Bile acid-binding resins
Major nutritional side effect of bile acid-binding resins
Impair absorption of fat soluble vitamin absorption (A,D,E,K)
MOA of lovastatin (STATIN)
inhibits HMG COA reductase
HMG CoA reductase inhibitors are contraindicated in
Pregnancy
Drug or foods (grapefruit juice) that increase statin effect
Inhibit Cytochrome P450 3A4
SE of HMG COA reductase inhibitors
Rhabdomyolysis and Hepatotoxicity
Monitoring parameter to obtain before initiation of STATINS
LFT's
Decreases liver triglycerol synthesis
Niacin
SE of niacin
Cutaneous flush
Cutaneous flush and be reduced by pretreatment with
Aspirin
Fibrates (gemfibrozil) increase activity of
Lipoprotein lipase
Most common SE of fibrates
Nausea
Fibrates are contraindicated in
Pregnancy
Concurrent use of fibrates and statins increases risk of
Rhabdomyolysis
New class of drugs that works by inhibiting absorption of intestinal cholesterol and can be given concurrently with the Statins
Ezetimibe (Zetia)
NSAIDS and DMARDS
MOA of NSAIDS
inhibit prostaglandin synthesis by inhibiting cyclo-oxygenase (cox)
Difference between aspirin and other NSAIDS
Aspirin irreversibly inhibits cyclooxygenase
Four main actions of NSAIDS
Anti-inflammatory, analgesia, antipyretic and antiplatelet activity
Agent used for closure of patent ductus arteriosus
Indomethacin
Aspirin is contraindicated in children with viral infection
Potential for development of Reye's syndrome
SE of salicylates
Tinnitus, GI bleeding
NSAID also available as an ophthalmic preparation
Diclofenac
NSAID available orally, IM and ophthalmically
Ketoralac
NSAID that is used for acute condition, such as pre-op anesthesia and has limited duration (<5 days) of use due to nephrotoxicity
Ketoralac
Newer NSAID that selectively inhibits COX-2
Celecoxib
COX 2 inhibitors may have reduced risk of
Gastric ulcers and GI Bleeding
COX 2 inhibitors should be used cautiously in pts with
Pre-existing cardiac or renal disease
Acetaminophen only has
Antipyretic and analgesic activity
SE of acetaminophen
Hepatotoxicity
Antidote for acetaminophen toxicity
N-acetylcysteine
Drugs-Modifying Anti-Rheumatic Agents (DMARDS)
DMARDs are slow acting drugs for
Rheumatic disease
MOA of gold salts
Alter activity of macrophages and suppress phagocytic activity of PMNs
SE of gold salts
Dermatitis of the mouth aplastic anemia and agranulocytosis
Causes bone marrow suppression
Methotrexate
SE of penicillamine
Aplastic anemia and renal
Interferes with activity of T-lymphocytes
Hydroxychloroquine
Anti-malarial drug used in rheumatoid arthritis (RA)
Hydroxychloroquine
SE of hydroxychloroquine
Retinal destruction and dermatitis
MOA of Leflunomide (newer agent)
Inhibiting Dihydroorotate Dehydrogenase which leads to decreased pyrimidine synthesis
Proteins that prevent action of tumor necrosis factor alpha (TNF-alpha)
Infliximab and etanercept
Anti-rheumatic agent also used for ulcerative colitis
Sulfasalazine
Anti-rheumatic agent also used for Chron's disease
Infliximab
Drugs used in Gout
NSAID used in gout
Indomethacin
NSAID contraindicated in gout
Aspirin
MOA of Colchicine (used in acute gout)
Selective inhibitor of microtubule assembly
SE of colchicine
Kidney and liver toxicity, diarrhea
Agent used to treat chronic gout by increasing uric acid secretion
Probenecid and sulfinpyrazone
Allopurinol treats chronic gout by inhibiting
Xanthine oxidase
Insulins
Rapid acting insulins that do not self-aggregate
lispro insulin, aspart insulin, glulisine insulin
Peakless ling acting insulin
Insulin glargine
Cardiac drugs
DOC for paroxysmal supraventricular tachycardia; has high efficacy and short duration of action
Adenosine