pharmacology one liners

REVISED - Summer, 2010; * = appeared one time on COMLEX; ** = appeared > one timeChecked by Dr. Tjioe

Basic Pharmacokinetics

*Half-life (T1/2)

Volume of distribution (VD)

Plasma concentration of a drug at a given time Cp

Clearance (CL)

First pass effect

Bioavailability (F)

Steady state

Metabolism

* Phase I

Different steps of Phase I Oxidation, reduction, hydrolysis

*

Prepared by four former LECOM students who are now Osteopathic doctors: Siamak Kazemi, Tom Mertz, Mohamad Sobh and Rahul Sood All four are pharmacists; two were pharmacy majors in college and two had their R.Ph. Degree

Time it takes for amount of drug to fall to half of its value; this is a constant in first order kinetics (majority of drugs)

Relates the amount of drug in the body to the plasma concentration

The ratio of the rate of elimination of a drug to its plasma concentration

The elimination of drug that occurs before it reaches the systemic circulation

The fraction of administered dose of a drug that reaches systemic circulation

When the rate of drug input equals the rate of drug elimination

This step of metabolism makes a drug more hydrophilic and hence augments elimination

Inducers of Cytochrome P450 (CYP450) Barbiturates, phenytoin, carbamazepine, and rifampin

*

Products of Phase II conjugation

First order kinetics

Zero order kinetics

Loading dose (Cp*(Vd/F))

Maintenance dose (Cp*(CL/F))

Pharmacodynamics

Affinity

Selectivity of a drug for its receptor Specificity

Potency

Maximum response achieveable from a drug * Efficacy

Full agonist

Ability to produce less than 100% of the response Partial agonist

Competitive antagonist

Noncompetitive antagonist

Inhibitors of CYP450 Cimetidine, ketoconazole, erythromycin, isoniazid and grapefruit

Glucuronate, acetic acid, and glutathione sulfate

Type of kinetics when a constant percentage of substrate is metabolized per unit time

Drug elimination with a constant amount metabolized regardless of drug concentration

Target plasma concentration times (volume of distribution divided by bioavailability)

Concentration in the plasma times (clearance divided by bioavailability)

Strength of interaction between drug and its receptor

Amount of drug necessary to elicit a biologic effect; refers to the drug's strength

Ability of a drug to produce 100% of the maximum response regardless of the potency

Ability to bind reversibly to the same site as the drug and without activating the effector system

Class of drugs with ability to decrease the maximal response to an agonist

* Thyroid and steroid hormones

* Insulin

Dose which is lethal to 50% of the population

Window between therapeutic effect and toxic effect Therapeutic index

Term for a high margin of safety High therapeutic index

Term for 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

** Atropine, pralidoxime (2-PAM)

Antidote used for iron salt toxicity Deferoxamine

Antidote used for acetaminophen (APAP) toxicity * N-acetylcysteine (Mucomyst)

A hormone whose mechanism of action (MOA) utilizes intracellular receptors

A hormone whose MOA utilizes transmembrane receptors

Class of drugs whose 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

LD50

Antidote used for organophosphate/anticholinesterase poisoning

Dimercaprol

Penicillamine

Antidote used for heparin overdose ** Protamine

Antidote used for warfarin toxicity *

** Aminocaproic acid

Antidote used for methanol and ethylene glycol Ethanol or fomepizole

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

Esmolol

Antidote for methotrexate toxicity Leucovorin

Antidote for beta-blockers and hypoglycemia Glucagon

Magnesium sulfate

Antidote for hyperkalemia

Antidote for arsenic, mercury, lead, and gold poisoning

Antidote used in poisonings: copper (Wilson's disease), lead, mercury, and arsenic

Vitamin K and Fresh frozen plasma (FFP)

Antidote for tissue plasminogen activator (t-PA), streptokinase

Digibind (also need to d/c digoxin, normalize K+, and lidocaine if pt. Is arrhythmic)

Antidote used for beta agonist toxicity (eg. Metaproterenol)

Antidote useful for some drug induced Torsade de pointes

sodium polystyrene sulfonate (Kayexalate)

Antidote for salicylate intoxication Alkalinize urine, dialysis

Cancer Chemotherapy

Log-kill hypothesis

Pulse therapy

Rescue therapy

Allopurinol

5-flouracil (5-FU)

Prednisone

Side effect of Mitomycin SEVERE myelosuppression

MOA of cisplatin Alkylating agent

Common toxicities of cisplatin Nephro and ototoxicity

6-mercaptopurine (6-MP)

** Allopurinol

* Dexrazoxane

* Bleomycin

Constant proportion of cell population killed rather than a constant number

Treatment with cancer chemotherapy at high doses every 3-4 weeks, too toxic to be used continuously

Toxic effect of anticancer drug can be lessened by rescue agents

Drug used concurrently with toxic anticancer agents to reduce renal precipitation of urates

Pyrimidine analog that causes "Thymine-less death" given with leucovorin rescue

Drug used in cancer therapy causes Cushing-like symptoms

Analog of hypoxanthine, needs HGPRTase for activation

Interaction with this drug requires dose reduction of 6-MP

May protect against doxorubicin toxicity by scavenging free radicals

Blows DNA (breaks DNA strands), limiting SE is pulmonary fibrosis

Testicular cancer

Regimen used for non-Hodgkin's lymphoma

Regimen used for breast cancer

Mechlorethamine

Cyclophosphamide

Vincristine

**Paclitaxel (taxol)

Cisplatin

Carboplatin

L-asparaginase

Bleomycin+vinblastine+etoposide+cisplatin produce almost a 100% response when all agents are used for this neoplasm

ABVD regimen used for HD, but appears less likely to cause sterility and secondary malignancies than MOPP

Adriamycin (doxorubicin) +bleomycin, vinblastine +dacarbazine

CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab

CMF (cyclophosphamide, methotrexate, and fluorouracil) and tamoxifen if ER+

Alkylating agent, vesicant that causes tissue damage with extravasation

Anticancer drug also used in RA, produces acrolein in urine that leads to hemorrhagic cystitis

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

Interact with microtubules (but unlike vinca which prevent disassembly of tubules), it stabilizes tubulin and cells remain frozen in metaphase

Toxicities include nephrotoxicity and ototoxicity, leading to a severe interaction with aminoglycosides

Agent similar to cisplatin, less nephrotoxic, but greater myelosuppression

Converts asparagine to aspartate and ammonia, denies cancer cells of essential AA (asparagine)

Interferon alpha

Flutamide (Eulexin)

** Tamoxifen

Aromatase inhibitor used in breast cancer Letrozole, anastrozole

Toremifene (Fareston)

Some cell cycle specific anti-cancer drugs

Some cell cycle non-specific drugs

*Odansetron, granisetron

Produces disulfiram-like reaction with ethanol Procarbazine

Octreotide

Somatrem

Sermorelin

Used for hairy cell leukemia; it stimulates NK cells

Anti-androgen used for prostate cancer

Anti-estrogen used for estrogen receptor + breast cancer

Newer estrogen receptor antagonist used in advanced breast cancer

Bleomycin, vinca alkaloids, antimetabolites (eg., 5-FU, 6-MP, methotrexate, etoposide)

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 ) antagonists

Nitrosoureas with high lipophilicity, used for brain tumors

Carmustine (BCNU) and lomustine (CCNU)

Endocrine drugs: hypothalamic and pituitary hormones

Somatostatin (SRIF) analog used for acromegaly, carcinoid, glucagonoma and other GH producing pituitary tumors

Somatotropin (GH) analog used in GH deficiency (dwarfism)

GHRH analog used as diagnostic agent

Leuprolide

Ganirelix

* Bromocriptine

Hormone inhibiting prolactin release * Dopamine

** Cosyntropin

* Desmopressin (DDAVP)

SE of OCs ** Increased thromboembolic events

Thyroid and anti-thyroid drugs

** L-thyroxine (T4)

Cytomel

Anti-thyroid drugs

Thioamide agents used in hyperthyroidism

*PTU

PTU (propylthiouracil) MOA*

Iodide salts

GnRH agonist used for infertility or different types of CA depending on pulsatile or steady usage respectively

GnRH antagonist with more immediate effects, used for infertility

Dopamine (DA) agonist (for Parkinson's disease), used also for hyperprolactinemia

ACTH analog used for diagnosis of patients with corticosteroid abnormality

Synthetic analog of ADH hormone used for diabetes insipidus and nocturnal enuresis

Most widely used thyroid drugs such as Synthroid and Levoxyl contain

T3 compound less widely used

Thioamides, iodides, radioactive iodine, and ipodate

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

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

**Thyroxine

Radioactive iodine

Ipodate

Beta-blockers such as propranolol

Iron deiodinates thyroxine

Estogens increase maternal TBG

3 zones of adrenal cortex and their products

Pneumonic for 3 zones of adrenal cortex GFR

Glucocorticoids

Short acting glucocorticoids

Intermediate acting glucocorticoids

Long acting glucocorticoids Betamethasone and dexamethasone

Mineralocorticoids

Dose may need to be increased during pregnancy or with Ocs due to increased TBG in plasma

Permanently cures thyrotoxicosis, patients will need thyroid replacement therapy thereafter. Contraindicated in pregnancy

Radio contrast media that inhibits the conversion of T4 to T3

Block cardiac adverse effects of thyrotoxicosis such as tachycardia, inhibits the conversion of T4 to T3

Vitamins containing iron should NOT be taken simultaneously with levothyroxine because

Thyroxine dose may need to be increased in hypothyroid patient during pregnancy because

Adrenocorticosteroid and adrenocortical antagonists

Glomerulosa (mineralocorticoids), fasciculata (glucocorticoid=GC), and reticularis (adrenal androgens)

Used for Addison's disease, Congenital Adrenal Hyperplasia (CAH), inflammation, allergies, and asthma (as a local inhalation)

Cortisone and hydrocortisone (equivalent to cortisol)

Prednisone, methylprednisolone, prednisolone, and triamcinolone

Fludrocortisone and deoxycorticosterone

Some side effects of corticosteroids

*

5-7 days

Inhibitors of corticosteroids biosynthesis

Dexamethasone suppression test

Aminoglutethimide

Ketoconazole

Mifepristone

* Spironolactone

Common SE of spironolactone ** Gynecomastia and hyperkalemia

Gonadal hormones and inhibitors

Estrogen

Clomiphene and tamoxifen

Common SE of tamoxifen and raloxifene Hot flashes

**Raloxifene

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

Used for Cushing's syndrome (increased corticosteroid)

Inhibits conversion of cholesterol to pregnenolone therefore inhibiting corticosteroid synthesis

Antifungal agent used for inhibition of all gonadal and adrenal steroids

Antiprogestin used as potent antagonist of GC receptor

Diuretic used to antagonize aldosterone receptors

Slightly increased risk of breast cancer, endometrial cancer, heart disease (questionable), has beneficial effects on bone loss

Antiestrogen drugs used for fertility and breast cancer respectively

Selective estrogen receptor modulator (SERM) used for prevention of osteoporosis and prophylaxis in women with risk factors for breast cancer

*Diethylstilbestrol (DES)

Estrogen mostly used in oral contraceptives (OC) Ethinyl estradiol and mestranol

Anti-progesterone used as abortifacient Mifepristone (RU-486)

Combination oral contraceptives (OC)

Oral contraceptive available in a transdermal patch Ortho-Evra

* Testosterone

Anabolic steroid that has potential for abuse

Cyproterone acetate

Drug is used with testosterone for male fertility ** Leuprolide

What do alpha cells in the pancreas produce? Glucagon

What do beta cells in the pancreas produce? Insulin

Where are beta cells found in the pancreas? Islets of Langerhans

What do delta cells in the pancreas produce? Somatostatin

* C-peptide

Non-steroidal estrogen agonist causes clear cell adenocarcinoma of the vagina in daughters of women who used it during pregnancy

Constant low dose of estrogen and increasing dose of progestin for 21 days (last 5 days are sugar pills or iron prep)

Converted to more active form DHT by 5 alpha-reductase

5 alpha-reductase inhibitor used for benign prostatic hyperplasia (BPH) and male pattern baldness

Finasteride (Proscar and Propecia respectively)

Nandrolone, oxymetholone, and oxandrolone

Anti-androgen used for hirsutism in females

Pancreatic hormones, antidiabetics, and hyperglycemics

Product of proinsulin cleavage used to assess insulin abuse

Exogenous insulin contains * Little C-peptide

Endogenous insulin contains Normal C-peptide

Lispro (Humalog), aspart, glulisine

Regular (Humulin R)

Long acting insulin * Ultralente (humulin U)

Glargine (Lantus), detemir

Major SE of insulin Hypoglycemia

GLUT 2

GLUT 4

Examples of alpha-glucosidase inhibitors (AGI) Acarbose, miglitol

MOA of AGI's

SE of AGI's

Acarbose

* Nateglinide

Very rapid acting insulin, having fastest onset and shortest duration of action

Rapid acting, crystalline zinc insulin used to reverse acute hyperglycemia

Ultra long acting insulin, has over a day duration of action

Important in synthesis of glucose to glycogen in the liver

Important in muscle and adipose tissue for glucose transport across muscles and TG storage by lipoprotein lipase activation

Act on intestine, delay digestion and absorption of glucose formed from digestion of starch and disacchrides

Flatulence (do not use beano to tx), diarrhea, abdominal cramps

Alpha-glucosidase inhibitor associated with elevation of LFT's

Amino acid derivative, active as an insulin secretagogue

MOA of nateglinide

Biguanide Metformin

Drugs available in combination with metformin Glyburide, glipizide, and rosiglitazone

MOA of metformin

Vascular effects of metformin

Most important potential SE of metformin Lactic acidosis

Incidence of hyoglycemia with metformin None

Meglitinide class of drugs Repaglinide

MOA of repaglinide

First generation sulfonylurea

Second generation sulfonylurea Glyburide, glipizide, glimepiride, etc.

MOA of both generations

Hypoglycemia

Chlorpropamide

Thiazolidinediones

Insulin secretagogue - closes ATP-sensitive K+ channel

Decreases hepatic glucose production and intestinal glucose absorption; increase insulin sensitivity

Decreased micro and macro vascular disease

Insulin release from pancreas; faster and shorter acting than sulfonylurea

Chlorpropamide, tolbutamide, tolazamide, etc.

Insulin release from pancreas by modifying K+ channels

Common SE of sulfonylureas, repaglinide, and nateglinide

Sulfonylurea NOT recommended for elderly because of very long half life

Pioglitazone, Rosiglitazone, Troglitazone (withdrawn/d from market)

Reason troglitazone was withdrawn from market Hepatic toxicity

MOA of thiazolindinediones

SE of Thiazolindinediones

Glucagon

Drugs used in bone homeostasis

Available bisphosphonates

MOA of Bisphosphonates Inhibits osteoclast bone resorption

Names of three bisphosphonates available IV Pamidronate, zoledronate, ibandronate

Uses of bisphosphonates

Major SE of bisphosphonates Chemical esophagitis

Etidronate

**

* Calcitonin (salmon prep)

Stimulate PPAR-gamma receptor to regulate CHO and lipid metabolism

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

Alendronate, etidronate, risedronate, pamidronate, tiludronate, and zoledronic acid

Osteoporosis, Paget's disease, and osteolytic bone lesions, and hypercalcemia from malignancy

Bisphosphonates that cannot be used on continuous basis because it caused osteomalacia

Used for prevention of postmenopausal osteoporosis in women

Estrogen (HRT-Hormone replacement therapy)

Increase bone density, also being tested for breast CA prophylaxis

Raloxifene (SERM-selective estrogen receptor modulator)

Used intranasally and decreases bone resorption

Calcium

Vitamin D

Disease caused by excess ergot alkaloids St. Anthony's Fire

Autocoids

Zollinger-Ellison Syndrome

Drug that causes contraction of the uterus * Oxytocin

Distribution of histamine receptors H1, H2, and H3*

Prototype antagonist of H1 and H2 receptors *

1st generation antihistamine that is highly sedating ** Diphendydramine

1st generation antihistamine that is least sedating Chlorpheniramine or cyclizine

2nd generation antihistamines *

Major indication for H1 receptor antagonist Use in IgE mediated allergic reaction

hydroxyzine (Atarax)

Used especially in postmenopausal women, dosage should be 1500 mg

Vitamin given with calcium to ensure proper absorption

Drugs with important actions on smooth muscle

Endogenous substances commonly interpreted as histamine, serotonin, prostaglandins, and vasoactive peptides

Syndrome of hypersecretion of gastric acid and pepsin usually caused by gastrinoma; it is associated with severe peptic ulceration and diarrhea

Smooth muscle; stomach, heart, and mast cells; nerve endings, CNS respectively

Diphenhydramine and cimetridine, respectively

Fexofenadine, loratadine, and cetirizine

Generation of antihistamine that has the most CNS effects

First generation due to being more lipid-soluble

Antihistamine that can be used for anxiety and insomnia and is not addictive

H1 antagonist used in motion sickness

Sedation

* Cimetidine

Clinical use for H2 blockers

Receptors for serotonin (5HT-1) are located

**

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 **

***

Dolasetron

Dimenhydrinate, meclizine, and other 1st generation

Most common side effect of 1st generation antihistamines

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

Acid reflux disease, duodenal ulcer and peptic ulcer disease

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

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

DOC to treat chemo-induced nausea and vomiting ** Odansetron

Nitroprusside

Uterine contractions

SE of ergot alkaloids Hallucinations resembling psychosis

Ergot alkaloid used as an illicit drug * LSD

Dopamine agonist used in hyperprolactinemia * Bromocriptine

Bradykinin and histamine

*Bradykinin

* Capsaicin

Prostaglandins that cause abortions *

Drug that selectively inhibits COX 2 Celecoxib and rofecoxib

Inhibitor of lipoxygenase * Zileuton

Major SE of zileuton Liver toxicity

Zafirlukast and montelukast

Drug used in ergot alkaloids overdose, ischemia and gangrene

Reason ergot alkaloids are contraindicated in pregnancy

Peptide causing increased capillary permeability and edema

Mediator of tissue pain, edema, inactivated by ACE, and may be a contributing factor to the development of angioedema

Drug causing depletion of substance P (vasodilator)

Prostaglandin E1 (misoprostol) PGE2, and PGF2alpha

Difference between COX 1 and COX 2 COX 1 is found throughoutthe body and COX 2 is onlyin inflammatory tissue

Inhibitor of leukotrienes (LTD4) receptors and used in asthma

* PGE1

Approved for use in severe pulmonary HTN PGI2 (epoprostenol)

Prostaglandin used in the treatment of impotence * Alprostadil

Irreversible, nonselective COX inhibitor Aspirin

Class of drugs that reversibly inhibit COX NSAIDS

Arginine

MOA and effect of nitric oxide *

Long acting beta 2 agonist used in asthma Salmeterol

Muscarinic antagonist used in asthma * Ipratropium

MOA action of cromolyn * Mast cell stabilizer

Pentoxifylline

inhibit phospholipase A2

*

Antimicrobials

MOA of quinolones ** Inhibit DNA gyrase

Used in pediatrics to maintain patency of ductus arteriosis

Primary endogenous substrate for Nitric Oxidase Synthase

Stimulates cGMP which leads to vascular smooth muscle relaxation

Methylxanthine derivative used as a remedy for intermittent claudication

MOA of corticosteroids

SE of long term (>5 days) corticosteroid therapy and remedy

Adrenal suppression and weaning slowly, respectively

MOA of penicillin

Drug used for MRSA * Vancomycin

Vancomycin MOA ** Blocks peptidoglycan synthesis

Type of resistance found with vancomycin Point mutation

Meningitis prophylaxis in exposed patients * Rifampin

*

Two toxicities of aminoglycosides nephro and ototoxicity

DOC for Legionnaires' disease Erythromycin

MOA of sulfonamides * Inhibit dihydropteroate synthase

Methicillin, nafcillin, and dicloxacillin

*** Amoxicillin

Cephalosporins

PCN active against pseudomonas Carbenicillin, piperacillin and ticarcillin

Drug causes teeth discoloration Tetracycline

MOA of tetracycline

Block cell wall synthesis by inhibiting peptidoglycan cross-linkage

Technique used to diagnose perianal itching, and the drug used to treat it

Scotch tape technique and mebendazole

Penicillins active against penicillinase secreting bacteria

Cheap wide spectrum antibiotic DOC for otitis media

Class of antibiotics that have 10% cross sensitivity with penicillins

Antibiotic causing red-man syndrome, and prevention

Vancomycin, infusion at a slow rate and antihistamines

Decreases protein synthesis by inhibiting 30S ribosome

Chloramphenicol

Clindamycin

** Metronidazole

Treatment of resistant pseudomembranous colitis ORAL vancomycin

Anemia caused by trimethoprim * Megaloblastic anemia

Cartilage damage

* Metronidazole

*

Metronidazole SE if given with alcohol Disulfiram-like reaction

Common side effect of Rifampin * Red urine discoloration

MOA of nystatin

Neurotoxicity with isoniazid (INH) prevented by Administration of Vit. B6 (pyridoxine)

Toxicity of amphotericin Nephrotoxicity

Gynecomastia

Topical DOC in impetigo Topical mupirocin (Bactroban)

DOC for influenza A * Amantadine

Drug that causes gray baby syndrome and aplastic anemia

Drug notorious for causing pseudomembranous colitis

DOC for tx of pseudomembranous colitis

Reason fluoroquinolones are contraindicated in children and pregnancy

DOC for giardia, bacterial vaginosis, pseudomembranous colitis, and trichomonas

Treatment for TB patients (think RIPE) Rifampin, Isoniazid, Pyrazinamide, and Ethambutol

Bind ergosterol in fungal cell membrane

SE seen only in men with administration of ketoconazole

DOC for RSV * Ribavirin

DOC for CMV retinitis Ganciclovir

SE for ganciclovir Neutro, leuko and thrombocytopenia

Nevirapine, amprenavir

* Protease inhibitors

Antivirals that are teratogens Delavirdine, efavirenz, and ribavirin

Antivirals associated with neutropenia

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

Cephalosporins NOT able to cross the BBB 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

Anti-viral agents associated with Stephen Johnson syndrome

HIV antiviral class known to have severe drug interactions by causing inhibition of metabolism

Ganciclovir, zidovudine, saquinavir, and interferon

Cefuroxime (2nd) generation, Ceftazidime, Ceftriaxone

Drug used in exoerythrocytic cycle of malaria Primaquine

Minocycline

Drug of choice for leprosy

DOC for herpes and its MOA *

* Sulfonamides

MOA of erythromycin

* 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

Tolerance

Additive CNS depression

Benzodiazepines used to promote sleep Temazpam, trizolam, flurazepam

Benzodiazepine used for anxiety Alprazolam

Non-benzodiazepine used as an anxiolytic Buspirone

Oral antibiotic of choice for moderate inflammatory acne

Dapsone, rifampin and clofazimine combination

Acyclovir; incorporated into viral DNA and chain termination

Anti-microbials that cause hemolysis in G6PD-deficient patients

Inhibition of protein synthesis at the 50s subunit of ribosome

Anti-biotic frequently used for chronic UTI prophylaxis

Occurs when sedative hypnotics are used chronically or at high doses

The most common type of drug interaction of sedative hypnotics with other depressant medications

Non-benzodiazepine used for sleep Zolpidem

* 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

* Flumazenil

Diazepam

Clonazepam

Alprazolam and Clonazepam

Midazolam

DOC for status epilepticus Diazepam

Chlordiazepoxide and Diazepam

Major effect of benzodiazepines on sleep at high doses

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)

Benzodiazepine with useful relaxant effects in skeletal muscle spasticity of central origin

Benzodiazepine that has efficacy against absence seizures and in anxiety states, such as agoraphobia

Benzodiazepines that are the most effective in the treatment of panic disorder

Benzodiazepine that is used for anesthesia

Longer acting benzodiazepines used in the management of withdrawal states of alcohol and other drugs

Barbiturates

Acute intermittent porphyria

Liver enzyme INDUCTION

Barbiturates MOA

Barbiturate used for the induction of anesthesia Thiopental

Others

Site of action for zaleplon and zolpidem

Zolpidem, zaleplon

Buspirone

Buspirone

Alcohols

*Ethanol

Agent with zero-order kinetics Ethanol

Rate limiting step of alcohol metabolism Aldehyde dehydrogenase

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

Barbiturates decrease the effectiveness of many other drugs via this pharmacokinetics property

Increase the DURATION of GABA-mediated chloride ion channels

Benzodiazepine receptor BZ1 (although do not have a benzodiazepine ring structure)

Good hypnotic activity with less CNS SE than most benzodiazepines

Agent that is a partial agonist for the 5-HT1A receptor

Drug of choice for generalized anxiety disorder, NOT effective in acute anxiety

Agent that is metabolized to acetaldehyde by alcohol dehydrogenase and microsomal ethanol-oxidizing system (MEOS)

*MEOS

Enzyme that metabolizes acetaldehyde to acetate Aldehyde dehydrogenase

Agents that inhibit acetaldehyde dehydrogenase

Disulfiram

*

Ethanol

Agent that is the antidote for methanol overdose Ethanol, fomepizole

Fomepizole

Anti seizure Drugs

Most frequent route of metabolism Hepatic enzymes

Sodium channel blockade

MOA for benzodiazepines and barbiturates GABA-related targets

MOA for Ethosuximide Calcium channels

MOA for Valproic acid at high doses

System that increases in activity with chronic ethanol exposure and may contribute to tolerance

Disulfiram, metronidazole, certain sulfonylureas and cephalosporins

Agent that inhibits alcohol dyhydrogenase and its clinical use

FOMEPIZOLE – used to prevent formation of toxic metabolites from methanol and ethylene glycol ingestion

Agent used in the treatment of alcoholism, if alcohol is consumed concurrently, acetaldehyde builds up and results in nausea, headache, flushing, and hypotension

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

Drug that inhibits alcohol dehydrogenase and is used in ethylene glycol exposure

Mechanisms of action for Phenytoin, Carbamazepine, Lamotrigine

Affect calcium, potassium, and sodium channels

* 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

Drugs that can be used for infantile spasms Corticosteroids

Carbamazepine

* Gabapentin

Phenytoin

SE of phenytoin *

Carbamazepine

Valproic acid

Serum ammonia and LFT's

Drugs of choice for generalized tonic-clonic and partial seizures

IV diazepam for short term (acute) treatment; phenytoin for prolonged therapy

Anti-seizure drugs used also for bipolar affective disorder (BAD)

Valproic acid, carbamazepine, phenytoin and gabapentin

Anti-seizure drugs used also for Trigeminal neuralgia

Anti-seizure drugs used also for pain of neuropathic orgin

Anti-seizure agent that exhibits non-linear metabolism, highly protein bound, causes fetal hydantoin syndrome, and stimulates hepatic metabolism

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

Agent that inhibits hepatic metabolism, is hepatotoxic and teratogen that can cause neural tube defects and gastrointestinal distress

Laboratory value required to be monitored for patients on valproic acid

SE for Lamotrigine Stevens-Johnson syndrome

SE for Felbamate

Valproic acid

Carbamazepine may cause Agranulocytosis

General Anesthetics

MOA of general anesthetics

Nitrous oxide

Inversely related to potency of anesthetics

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

Nitrous oxide

Aplastic anemia and acute hepatic failure

Anti-seizure medication also used in the prevention of migraines

Anti-seizure drugs used as alternative drugs for mood stabilization

Carbamazepine, gabapentin, lamotrigine, and valproic acid

Most are thought to act at GABA-A receptor - chloride channel

Inhaled anesthetic with a low blood/gas partition coefficient

Minimum alveolar anesthetic concentration (MAC)

Inhaled anesthetics metabolized by liver enzymes which has a major role in the toxicity of these agents

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

Methoxyflurane

Nitrous oxide

Desflurane

* Dantrolene

IV barbiturate used as a pre-op anesthetic Thiopental

Benzodiazepine used adjunctively in anesthesia Midazolam

*Flumazenil

Ketamine

*Fentanyl

Neuroleptanesthesia

Propofol

Local Anesthetics

MOA of local anesthetics (LA's)

Fluoride released by metabolism of this inhaled anesthetic may cause renal insufficiency

Prolonged exposure to this inhaled anesthetic may lead to megaloblastic anemia

Pungent inhaled anesthetic which leads to high incidence of coughing and vasospasm

DOC for malignant hyperthermia that may be caused by use of halogenated anesthetics

Benzodiazepine receptor antagonist, it accelerates recovery from benzodiazepine overdose

This produces "dissociative anesthesia", is a cardiovascular stimulant which may increases intracranial pressure, and hallucinations occur during recovery

Opioid associated with respiratory depression, but is used in high risk patients who may not survive full general anesthetia

State of analgesia and amnesia produced when fentanyl is used with droperidol and nitrous oxide

Produces both rapid anesthesia and recovery, has antiemetic activity and commonly used for outpatient surgery, may cause marked hypotension

Block voltage-dependent sodium channels

This may enhance activity of local anesthetics Hyperkalemia

This may antagonize activity of local anesthetics Hypercalcemia

Vasodilation

Cocaine

Tetracaine and bupivacaine

These LA's have surface activity Cocaine and benzocaine

CNS toxicity

Cocaine

LA causing methemoglobinemia Prilocaine

Skeletal Muscle Relaxants

Neuromuscular blocking drugs

Nondepolarizing type antagonists

Almost all local anesthetics have this property and sometimes require the administration of vasoconstrictors (ex. Epinephrine) to prolong activity

Local anesthetic with vasoconstrictive property, favored for head, neck, and pharyngeal surgery

Longer acting local anesthetics which are less dependent on vasoconstrictors

Most important toxic effects of most local anesthetics

Commonly abused LA which has cardiovascular toxicity including severe hypertension with cerebral hemorrhage, cardiac arrhythmias, and myocardial infarction

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

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)

Tubocurarine

Mivacurium

Pancuronium

Atracurium

Succinylcholine

Cholinesterase inhibitors

Spasmolytic drugs

Spasmolytic drugs

Facilitates GABA presynaptic inhibition Diazepam

GABA agonist in the spinal cord Baclofen

Similar to clonidine and may cause hypotension Tizanidine

* Dantrolene

Agent used for acute muscle spasm Cyclobenzaprine

*Drug induced Parkinsonism

Agent with long duration of action and is most likely to cause histamine release

Non-depolarizing skeletal muscle antagonist that has short duration

Skeletal muscle agent that can block muscarinic receptors

Skeletal muscle agent that undergoes Hofmann elimination (breaks down spontaneously)

One depolarizing blocker that causes continuous depolarization and results in muscle relaxation and paralysis, causes muscle pain postoperatively and myoglobinuria may occur

During Phase I these agents worsen muscle paralysis by succinylcholine, but during phase II they reverse the blockade produced by succinylcholine

Agents acting in the CNS or in the skeletal muscle, used to reduce abnormally elevated tone caused by neurologic or muscle end plate disease

DOC for malignant hyperthermia by acting on the sacroplasmic reticulum or skeletal muscle

Drugs Used in Parkinsonism & Other Movement Disorders

Irreversible condition resulting from the use of antipsychotics, reserpine at high doses, and MPTP (by-product of illicit meperidine analog)

L-dopa

Carbidopa

"On-off-phenomenon"

Levodopa

Bromocriptine

Pramipexole and ropinirole

Amantadine

Selegiline

Entacapone and Tolcapone

Benztropine

Agent effective in physiologic and essential tremor Propranolol

Agent used in drug therapy of Parkinson's instead of Dopamine which has low bioavailability and does not cross the BBB

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)

Clinical response that may fluctuate in tx of Parkinson's dx

Anti-Parkinson's drug which increases intraocular pressure and is contraindicated in closed angle glaucoma

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

Non ergot agents used as first-line therapy in the initial management of Parkinson's

Enhances dopaminergic neurotransmission SE's include CNS excitation, acute toxic psychosis and livedo reticularis

Inhibitor of MAO type B which metabolizes dopamine, used adjunct to levodopa or as sole agent in newly diagnosed patients

Inhibitors of catechol-O-methyltransferase (COMT), used as adjuncts in Parkinson's dx and cause acute hepatic failure (monitor LFT's)

Agent decreases the excitatory actions of cholinergic neurons. May improve tremor and rigidity but have LITTLE effect on bradykinesia. Atropine-like side effects

Agents used in Huntington's Disease

Agents used in Tourette's dx Haloperidol or pimozide

Chelating agent used in Wilson's disease Penicillamine

Antipsychotics

MOA of neuroleptics Dopamine blockade

*

Antipsychotics that reduce positive symptoms only Older antipsychotics

* Risperidone

Atypical antipsychotic causing high prolactin levels * Risperidone

Olanzapine

Haloperidol

Drug used in neuroleptic malignant syndrome * Dantrolene

Tetrabenazine (amine depleting drug), Haloperidol (antipsychotic)

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

Hyperprolactinemia, menorrhea, galactorrhea, confusion, mood changes, decreased sexual interest, and weight gain

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

Newer atypical antipsychotic used for bipolar disorder, known to cause weight gain, and adversely affect diabetes

Agent more frequently associated with extrapyramidal side effects that can be treated with benzodiazepine, diphenhydramine or muscarinic blocker

Muscarinic blockers

* Thioridazine

Haloperidol

Thioridazine

**Clozapine

* Clozapine

Anti-psychotics available in depot preparation Fluphenazine and haloperidol

Reduced seizure threshold

Orthostatic hypotension and QT prolongation

Increased risk of developing cataracts Quetiapine

Lithium

Major route of elimination for Lithium * Kidneys

*Lithium toxicity

Theophylline

Agents may exacerbate tardive dyskinesias (may be irreversible and there is no treatment)

Antipsychotic having the strongest autonomic effects

Antipsychotic having the weakest autonomic effects

Only phenothiazine not exerting antiemetic effects, can cause visual impairment due to retinal deposits, and high doses have been associated with ventricular arrhythmias

Agent having no effect on D2 receptors, blocks D4, reserved for resistant schizophrenia, and can cause fatal agranulocytosis

Anti-psychotic not shown to cause tardive dyskinesia

Low-potency typical antipsychotics and clozapine

Low potency phenothiazines and ziprasidone

Patients being treated with lithium, who are dehydrated, or taking diuretics concurrently, could develop

Drug increases the renal clearance hence decreases levels of lithium

Lithium is associated with this congenital defect

DOC for bipolar affective disorder * Lithium

Concern using lithium Low therapeutic index

SE of lithium *

Antidepressants

Norepinephrine and serotonin

2 to 3 weeks

Elderly patients

Well-tolerated and are first-line antidepressants SSRI's, bupropion, and venlafaxine

Monamine oxidase inhibitors

Hypertensive crisis

Serotonin syndrome

Tricyclic antidepressants (TCA)Tricyclic antidepressants (TCA)

Three C's associated with TCA toxicity

Cardiac anomalies and is contraindicated in pregnancy or lactation

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

Usual time needed for full effect of antidepressant therapy

Population group especially sensitive to side effects of antidepressants

All antidepressants have roughly the same efficacy in treating depression, agents are chosen based on these criterion

Side-effect profile and prior pt response

Monoamine oxidase inhibitors (MAOI) Most useful in patients with significant anxiety, phobic features, hypochondriasis, and resistant depression

Condition will result from in combination of MAOI with tyramine containing foods (ex. wine, cheese, and pickled meats)

MAOI should not be administered with SSRI's or potent TCA's due to development of this condition

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

Coma, Convulsions, Cardiac problems (arrhythmias and wide QRS)

Tertiary amines

Amitriptyline

TCA used in chronic pain, enuresis, and ADD * Imipramine

Doxepin

Clomipramine

Nortriptyline, Desipramine

Side effects seen with tricyclic antidepressants

Heterocyclics Amoxapine

Maprotiline

Venlafaxine

Venlafaxine

Trazodone

Nefazodone

*

Bupropion

Mirtazapine

Agents having higher sedation and antimuscarinic effects than other TCA's

TCA used in chronic pain, a hypnotic, and has marked antimuscarinic effects

TCA with greatest sedation of this group, and marked antimuscarinic effects, used for sleep

TCA used in obsessive compulsive disorder (OCD), most significant of TCA's for risk of seizure, weight gain, and neuropsychiatric signs and symptoms

Secondary amines that have less sedation and more excitation effect

Muscarinic blockade (dry mouth, constipation); weak alpha-1 block (orthostatic hypotension); weak hisamine block (sedation)

Antidepressant associated with neuroleptic malignant syndrome

Antidepressant associated with seizures and cardiotoxicity

Antidepressant having stimulant effects similar to SSRI's and can increase blood pressure

Antidepressant inhibiting norepinephrine, serotonin, and dopamine reuptake

Antidepressant also used for sleep that causes priapism

Antidepressant which is inhibitor of CYP450 enzymes and may be associated with hepatic failure

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

Antidepressant with MOA as alpha 2 antagonist, has effects on both 5-HT and NE, blocks histamine receptors, and is sedating

SE of mirtazapine

Selective serotonin reuptake inhibitors (SSRI)

Side effects frequently seen with SSRIs CNS stimulation; GI upset

Antidepressants with no effect on BP, no sedation SSRIs

Fluoxetine

SSRI indicated for premenstrual dysphoric disorder Fluoxetine (Sarafem)

SSRI less likely to cause a withdrawal syndrome Fluoxetine

Opioid Analgesics & AntagonistsAscending pathways

*

Postsynaptic Mu receptors

* Miosis and constipation

Meperidine

Opioid Analgesics

Strong opioid agonists

Opioids used in anesthesia Morphine and fentanyl

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

Some of SSRIs' therapeutic effects beside depression

Panic attacks, social phobias, bulimia nervosa, and PMDD (premenstrual dysphoric disorder), OCD

Inhibit synaptic activity of primary afferents and spinal cord pain transmission neurons

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

Tolerance to all effects of opioid agonists can develop except

All opioids except this agent (which has a muscarinic blocking action) cause pupillary constriction

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

Morphine, methadone, meperidine, and fentanyl

* Methadone

Opioid available trans-dermally * Fentanyl

*Morphine

Meperidine

Moderate opioid agonists *

Propoxyphene

Partial agonist or mixed antagonists Buprenorphine

* Naloxone

* Naltrexone

These agents are used as antitussive Dextromethorphan, Codeine

These agents are used as antidiarrheal Diphenoxylate, Loperamide

Drugs of AbuseInhalant anesthetics NO, chloroform, and diethyl ether

Organic nitrites

Steroids

Opioid used in the management of withdrawal states

Opioid that can be given PO, by epidural, and IV, which helps to relieve the dyspnea of pulmonary edema

Use of this opioid with MAOI can lead to hyperpyrexic coma, and with SSRI's can lead to serotonin syndrome

Codeine, hydrocodone, and oxycodone

Weak opioid agonist, poor analgesic, its overdose can cause severe toxicity including respiratory depression, circulatory collapse, pulmonary edema, and seizures

Partial opioid agonist, considered a strong analgesic, has a long duration of action and is resistant to naloxone reversal

Opioid antagonist that is given IV and had short DOA

Opioid antagonist that is given orally in alcohol dependency programs

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

Causes acne, premature closure of epiphyses, masculinization in females, hepatic dysfunction, MI, and increases in libido and aggression

*

IV administration

* Overdose of opioids

Abstinence syndrome

Treatment for opioid addiction

* Naloxone

Sedative-HypnoticsSedative-Hypnotics action

CNS depressants

"Date rape drug" * Flunitrazepam (rohypnol)

The most important sign of withdrawal syndrome Excessive CNS stimulation (seizures)

Treatment of withdrawal syndrome involves

These agents are CNS depressants *

Stimulants Caffeine

Nicotine

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

Leads to respiratory depression progressing to coma and death

Lacrimation, rhinorrhea, yawning, sweating, weakness, gooseflesh, nausea, and vomiting, tremor, muscle jerks, and hyperpnea are signs of this syndrome

Methadone, followed by slow dose reduction

This agent may cause more severe, rapid and intense symptoms to a recovering addict

Reduce inhibition, suppress anxiety, and produce relaxation

Additive effects when Sedative-Hypnotics used in combination with these agents

Common mechanism by which overdose result in death

Depression of medullary and cardiovascular centers

Long-acting sedative-hypnotic or a gradual reduction of dose, clonidine or propranolol

Ethanol, Barbiturates, and Benzodiazepines

Withdrawal from this drug causes lethargy, irritability, and headache

W/D from this drug causes anxiety and mental discomfort

Treatments available for nicotine addiction *

Chronic high dose abuse of nicotine leads to

Amphetamines

Amphetamine agents

These agents are congeners of Amphetamine DOM, STP, MDA, and MDMA "ecstasy"

Cocaine "super-speed"

HallucinogensPCP

Removal of PCP may be aided

*

Marijuana

Direct-Acting Cholinomimetic AgonistsMuscarinic agonists or parasympathomimetic

*Bethanechol

Pilocarpine

Cevimeline

Patches, gum, nasal spray, psychotherapy, and bupropion

Psychotic state, overdose causes agitation, restlessness, tachycardia, hyperthermia, hyperreflexia, and seizures

Tolerance is marked and abstinence syndrome occurs

Dextroamphetamines and methamphetamine

Overdoses of this agent with powerful vasoconstrictive action may result in fatalities from arrhythmias, seizures, respiratory depression, or severe HTN (MI and stroke)

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

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

Cholinoreceptor-Activating & Cholinesterase-Inhibiting Drugs

This agent has greater affinity for muscarinic receptors and used for postoperative and neurogenic ileus and urinary retention

Only direct acting agent that is very lipid soluble and used in glaucoma

This agent used to treat dry mouth in Sjögren's syndrome

Edrophonium

Neostigmine

Physostigmine

Treatment of myasthenia gravis Pyridostigmine

OrganophosphatesAntiglaucoma organophosphate Echothiophate

Long acting cholinesterase inhibitors

Scabicide organophosphate Malathion

Metrifonate

Toxicity of organophosphate:

*

Respiratory failure

The most toxic organophosphate Parathion

Atropine

Pralidoxime

Prototypical drug is atropine Nonselective Muscarinic Antagonists

* Benztropine, trihexyphenidyl

Treatment of motion sickness * Scopolamine, meclizine

Indirect-Acting ACh Agonist, alcohol, short DOA and used in diagnosis of myasthenia gravis

Carbamate with intermediate action, used for+A1170 postoperative and neurogenic ileus and urinary retention

Treatment of atropine overdose and glaucoma (because lipid soluable). Enters the CNS rapidly and has a stimulant effect, which may lead to convulsions

Associated with an increased incidence of cataracts in patients treated for glaucoma

Organophosphate anthelmintic agent with long DOA

DUMBELSS (diarrhea, urination, miosis, bronchoconstriction, excitation of skeletal muscle and CNS, lacrimation, salivation, and sweating)

The most frequent cause of acute deaths in cholinesterase inhibitor toxicity

Treatment of choice for organophosphate overdose

This agent regenerates active cholinesterase and is a chemical antagonist used to treat organophosphate exposure

Cholinoreceptor Blockers & Cholinesterase Regenerators

Treat manifestations of Parkinson's disease and EPS

Produce mydriasis and cycloplegia *

Bronchodilation in asthma and COPD * Ipratropium

Reduce transient hyper GI motility Dicyclomine, methscopolamine

Oxybutynin, dicyclomine

Toxicity of anticholinergics

Another pneumonic for anticholinergic toxicity

Infants

Contraindications to use of atropine

Nicotinic Antagonists

Severe hypertension

Reversal of blockade by neuromuscular blockers Cholinesterase inhibitors

Succinylcholine

Pralidoxime, atropine

SympathomimeticsPneumonic for beta receptors *

This is the drug of choice for anaphylactic shock * Epinephrine

Atropine, homatropine,C1208 tropicamide

Cystitis, postoperative bladder spasms, or incontinence

block SLUD (salivation, lacrimation, urination, defecation

"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, closed angle glaucoma, prostatic hypertrophy

Limiting adverse effect of ganglion blockade that patients usually are unable to tolerate

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; has short duration of action

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

You have 1 heart (Beta 1) and 2 lungs (Beta 2)

Amphetamines

Phenylephrine

Reduce aqueous secretion

Albuterol

Salmeterol

Beta1 agonists

*

Alpha1 agonists

Reduce the loss from area of injection

Midodrine

Terbutaline

Epinephrine

Epinephrine

Dopamine

Phenylisopropylamines that are used legitimately and abused for narcolepsy, attention deficit disorder, and weight reduction

Alpha agonist used to produce mydriasis and reduce conjunctival itching and congestion caused by irritation or allergy, it does not cause cycloplegia

Newer alpha 2 agonist (apraclonidine and brimonidine) treat glaucoma by acting to

Short acting Beta 2 agonists that is drug of choice in treatment of acute asthma but not recommended for prophylaxis

Longer acting Beta 2 agonist is recommended for prophylaxis of asthma

These agents increase cardiac output and may be beneficial in treatment of acute heart failure and some types of shock

These agents decrease blood flow or increase blood pressure, are local decongestants, and used in therapy of spinal shock (temporary maintenance of blood pressure which may help maintain perfusion

Shock due to septicemia or myocardial infarction is made worse by

Increasing afterload and tissue perfusion declines

Epinephrine is often mixed with a local anesthetic to

Chronic orthostatic hypotension can be treated with

Beta 2 agonist used to suppress premature labor, but cardiac stimulatory effects may be hazardous to mother and fetus

Sympathetic agent which stimulates heart rate and can dilate vessels in skeletal muscle at low doses

Mast cells to reduce release of hisamine and inflammatory mediators

Agent used in shock because it dilates coronary arteries and increases renal blood flow

Dobutamine

Ephedrine

Alpha 1 agonist toxicity * Hypertension

Beta 1 agonist toxicity

Beta 2 agonist toxicity Skeletal muscle tremor, tachycardia

The selective agents loose their selectivity at high doses

Adrenoceptor BlockerPhenoxybenzamine

Phentolamine

*Prazosin, terazosin, doxazosin

Tamsulosin

Yohimbine

Beta-Blocking Drugs

*

Labetalol and carvedilol

Pindolol and acebutolol

Agent which stimulates cardiac contractile force more than rate with little effect on total peripheral resistance

Long acting sympathomimetic, sometimes used to improve urinary continence in children and elderly with enuresis

Sinus tachycardia and serious arrhythmias

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

Nonselective alpha-blocking drug, short acting and reversible, used for rebound HTN from rapid clonidine withdrawal, and Raynaud's phenomena

Selective Alpha 1 blocker used for hypertension, BPH, may cause first dose orthostatic hypotension

Selective Alpha-1A blocker, used for BPH, but with little effect on HTN

Selective Alpha 2 blocker used for impotence (controversial effectiveness)

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

Beta blockers partial agonist activity (intrinsic sympathomimetic activity) cause some bronchodilation and may have an advantage in treating patients with asthma

*

Timolol

Esmolol

This beta blocker is the longest acting Nadolol

These beta blockers are less lipid soluble Acebutolol and atenolol

Propranolol

Beta blockers

Beta blockers

Pilocarpine, carbachol, physostigmine

Epinephrine, dipivefrin

Apraclonidine, brimonidine

These Beta blockers decrease aqueous secretion *

Acetazolamide

This agent cause increased aqueous outflow Prostaglandin PGF2a

Antihypertensive AgentsInhibit angiotensin-converting enzyme (ACE) * ACE inhibitors

Captopril and enalapril (-OPRIL ending) are * ACE inhibitors

SE of ACE inhibitors * Dry cough, hyperkalemia

This beta blocker lacks local anesthetic activity (a property which decreases protective reflexes and increases the risk of corneal ulceration) and used in treating glaucoma

This parenteral beta blocker is a short acting (minutes)

This beta blocker is highly lipid soluble and may account for side effects such as nightmares

Clinical uses of these agents include treatment of HTN, angina, arrhythmias, chronic CHF, and selected post MI patients

Toxicity of these agents include bradycardia, AV blockade, exacerbation of acute CHF; signs of hypoglycemia may be masked (tachycardia, tremor, and anxiety)

Glaucoma (all agents topical except for diuretics)

Cholinomimetics that increase outflow, open trabecular meshwork, and cause ciliary muscle contraction

Nonselective alpha agonists that increases outflow, probably via the uveoscleral veins

Selective alpha agonists that decreases 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

ACE inhibitors are contraindicated in * pregnancy and with K+

Losartan and valsartan block * Angiotensin receptor

Angiotensin receptor blockers do NOT cause * Dry cough

Agents that 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

* Beta-blockers

B-blockers that are more cardioselective Beta-1 selective blockers

Cardioselective Beta 1-blockers * Atenolol, acebutolol, and metoprolol

Beta-blockers should be used cautiously in

Propranolol

SE of beta blockers*

Alpha 1selective blockers *

Phenoxybenzamine

For rebound HTN from rapid clonidine withdrawal Phentolamine

* Tamsulosin (Flomax)

SE of alpha blockers*

Clonidine, and methyldopa

SE of methyldopa Positive Comb's test, depression

Agents that reduce heart rate, contractility, and O2 demand

Asthma (bronchospastic effects), diabetes (block signs of hypoglycemia) and peripheral vascular disease

Non-selective Beta-blocker also used for migraine prophylaxis

Bradycardia, SEXUAL DYSFUNCTION, decrease in HDL, and increase in Triglycerols (TG)

Prazosin, terazosin and doxazosin (-AZOSIN ending)

Non-selective Alpha1blockers use to treat pheochromocytoma

A1a-selective blocker with no effects on HTN used for BPH

Orthostatic hypotension (especially with first dose) and reflex tachycardia

Presynaptic Alpha 2 agonist used in HTN, and acts centrally

Methyldopa is contraindicated in *

SE of clonidine Rebound HTN, sedation, dry mouth

Direct vasodilator of arteriolar smooth muscle Hydralazine

SE of hydralazine * Lupus-like syndrome

Minoxidil

SE of minoxidil Hypertrichosis

IV Drug used Hypertensive Crisis Nitroprusside

Nitroprusside vasodilates Arteries and veins

Toxicity caused by nitroprusside and treatment

DiureticsCarbonic anhydrase inhibitor Acetazolamide

Diuretic used for mountain sickness and glaucoma * Acetazolamide

SE of acetazolamide

*

MOA of loop diuretics inhibits Na+/K+/2Cl- cotransport

Site of action of loop diuretics * Thick ascending limb

SE of loop (furosemide) diuretics *

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

Geriatrics due to its CNS (depression) effects

Arterial vasodilator that works by opening K+ channels

Cyanide toxicity treated with sodium thiosulfate

Paresthesias, alkalization of the urine (which may ppt. Ca salts), hypokalemia, acidosis, and encephalopathy in patients with hepatic impairment

Hyperuricemia, hypokalemia and ototoxicity

Aminoglycosides used with loop diuretics potentiate adverse effect

Sulfonamides

SE of thiazide (HCTZ) diuretics *

Potassium sparing diuretics inhibit * Na+/K+ exchange

Diuretic used to treat primary aldosteronism * Spironolactone

SE of spironolactone *

* Mannitol

ADH agonist used for pituitary diabetes insipidus * Desmopressin (DDAVP)

Used for SIADH Demeclocycline

SE of demeclocycline

Antiarrhythmic agents

*Sodium channel blockers

SE of procainamide * Lupus-like syndrome

Limiting side effect of Quinidine * Prolongs QT interval

Other side effects of Quinidine

Major drug interaction with Quinidine Increases concentration of Digoxin

* Amiodarone

DOC for digoxin induced arrhythmias Phenytoin

SE of phenytoin Gingival hyperplasia

Class II antiarrhythmics are B-blockers

Class of drugs that may cause cross-sensitivity with thiazide diuretics

Hyperuricemia, hypokalemia and hyperglycemia

Gynecomastia hyperkalemia, and impotence

Osmotic diuretic used to treat increased intracranial pressure

Antidiuretic hormone (ADH) agonist and antagonist

Bone marrow and teeth discoloration for children under 8 years of age

MOA of class I A (eg. Procainamide), class IB (eg. Lidocaine), and class IC (eg. Flecainide) antiarrhythmics

Thrombocytopenic purpura, and CINCHONISM

DOC for management of acute ventricular arrhythmias

Class of anti-arrhythmics that has a pro-arrhythmic effect (CAST trial), therefore are used as last line agents

Class IC (flecainide, propafenone, moricizine)

Sotalol

Side effect of sotalol prolongs QT and PR interval

Esmolol

Anti-arrhythmics that decrease mortality B-blockers

MOA of class III antiarrhythmics Potassium channel blockers

Amiodarone

Prolonged half-life, up to six weeks

Antiarrhythmic effective in most types of arrhythmia Amiodarone

SE of Amiodarone

MOA of class IV antiarrhythmics Calcium channel blockers

* Torsades de pointes

Agent to treat torsades de pointes Magnesium sulfate

Drug used supraventricular arrhythmias Digoxin

Adenosine

Adenosine's MOA

Anti-arrhythmic with 15 second duration of action Adenosine

Vasodilators and treatment of anginaMOA of sildenafil (Viagra)

***

Drugs used in the management of angina

Antiarrhythmic that exhibits Class II and III properties

Used intravenously for acute arrhythmias during surgery

Class III antiarrhythmic that exhibits properties of all 4 classes

Specific pharmacokinetic characteristic of amiodarone

Cardiac dysfunction, photosensitivity, skin (blue smurf syndrome), Pulmonary fibrosis, thyroid and corneal deposits

Life threatening cardiac event that prolong QT leads to

DOC for paroxysmal supraventricular tachycardia (PSVT)

Activattion on an inward K+ current and inhibition of Ca++ current resulting in marked hyperpolarization

Inhibits phosphodiesterase-5, enhancing effects of nitric oxide-activated increases in cGMP

Aspirin, Nitrates, CCB, and Beta blockers

Aspirin reduces mortality in unstable angina by Platelet aggregation inhibition

MOA of nitrates*

Nitrate used for acute anginal attacks Nitroglycerin sublingual tablets

Nitrate used to prevent further attacks

Nitrate free intervals are needed due to Tolerance

SE of nitrates

CCB are DOC for Prinzmetal's angina

Classic

Drugs used to treat CHFMOA of Cardiac glycosides (eg. digoxin)

Digoxin is used in Atrial fibrillation and CHF

Digoxin toxicity can be precipitated by Hypokalemia

Antidote for digoxin toxicity Digibind

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

Peptide drug used to treat CHF Nesiritide (BNP)

SE of nesiritide Excessive hypotension and kidney failure

Relax vascular smooth muscle, at low doses dilate veins and at high doses dilate arterioles

Oral and transdermal forms of nitroglycerin

Postural hypotension, reflex tachycardia, hot flashes, and throbbing headache due to meningeal artery dilation

Beta blockers are used for which type of anginal attack

Indirectly increase intracellular calcium and cardiac contractility by inhibiting Na+/K+ ATPase

Phosphodiesterase inhibitors that increase mortality and have been found to have NO beneficial effects

Reducing progression of heart failure (never use in acute heart failure)

MOA of nesiritide Increasing sodium excretion and decreases arterial and venous tone

Carvedilol

Nesiritide (Natrecor)

Drugs used in coagulation disordersVitamin 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 IV and IM (only LMW)

SE of both warfarin and heparin Bleeding

SE of heparin

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

Aspirin, metoprolol

SE of Aspirin * GI bleeding

Ticlopidine

SE for ticlopidine Neutropenia and agranulocytosis

Effective in preventing TIA's Clopidogrel and ticlopidine

Dipyridamole

Abciximab, tirofiban and eptifibatide

Agent used in CHF that is a selective alpha and nonselective beta blocker

Agent used in acutely decompensated CHF resembling natriuretic peptide

Heparin induced thrombocytopenia (HIT)

Agent used to treat MI and to reduce incidence of subsequent MI

Antiplatelet drug reserved for patients allergic to aspirin

Prevents thrombosis in patients with artificial heart valve

Block glycoprotein IIb/IIIa involved in platelet cross-linking

MOA of thrombolytics *

Thrombolytics are used for * Pulmonary embolism and DVT

Thrombolytic that can cause allergic reaction Streptokinase

Tissue plasmin activator

SE of tPA Cerebral hemorrhage

Antidote for thrombolytics Aminocaproic acid

Agent to treat hypochromic microcytic anemias Ferrous sulfate

Chelating agent used in acute iron toxicity Deferoxamine

Agent for pernicious anemia * Cyanocobalamin (Vit B12)

Vitamin B12

*Folic acid

* Erythropoietin

Interleukin 11 (oprelvekin)

AntihyperlipidemicsDrugs decrease intestinal absorption of cholesterol Bile acid-binding resins

Cholestyramine and colestipol are Bile acid-binding resins

MOA of lovastatin (STATIN) inhibits HMG COA reductase

Pregnancy

Degradation of fibrin clots and are administered IV

Thrombolytic used for acute MI and ischemic (non hemorrhagic) CVA

Agents used in anemias and hematopoietic growth factors

Agent used for neurological deficits in megaloblastic anemia

Agent used for megaloblastic anemia (but does NOT reverse neurologic symptoms) and decrease neural tube defects during pregnancy

Agent used for anemias associated with renal failure

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

Major nutritional side effect of bile acid-binding resins

Impair absorption of fat soluble vitamin absorption (A,D,E,K)

HMG CoA reductase inhibitors are contraindicated in

* Inhibit Cytochrome P450 3A4

SE of HMG COA reductase inhibitors Rhabdomyolysis and Hepatotoxicity

* LFT's

Decreases liver triglycerol synthesis * Niacin

SE of niacin * Cutaneous flush

Aspirin

Fibrates (gemfibrozil) increase activity of * Lipoprotein lipase

Most common SE of fibrates Nausea

Fibrates are contraindicated in Pregnancy

Rhabdomyolysis

Ezetimibe (Zetia)

NSAIDS and DMARDSMOA of NSAIDS

Difference between aspirin and other NSAIDS

Four main actions of NSAIDS

Agent used for closure of patent ductus arteriosus * Indomethacin

SE of salicylates Tinnitus, GI bleeding

NSAID also available as an ophthalmic preparation Diclofenac, ketoralac

NSAID available orally, IM and ophthalmically Ketoralac

Ketoralac

MOA of drug or foods (grapefruit juice) that increase statin effect

Monitoring parameter to obtain before initiation of STATINS

Cutaneous flush and be reduced by pretreatment with

Concurrent use of fibrates and statins increases risk of

New class of drugs that works by inhibiting absorption of intestinal cholesterol and can be given concurrently with the Statins

inhibit prostaglandin synthesis by inhibiting cyclo-oxygenase (cox)

Aspirin irreversibly inhibits cyclooxygenase

Anti-inflammatory, analgesia, antipyretic and antiplatelet activity

Aspirin is contraindicated in children with viral infection

Potential for development of Reye's syndrome

NSAID that is used for acute condition, such as pre-op anesthesia and has limited duration (<5 days) of use due to nephrotoxicity

Newer NSAID that selectively inhibits COX-2 Celecoxib

COX 2 inhibitors may have reduced risk of Gastric ulcers and GI Bleeding

Pre-existing cardiac or renal disease

Acetaminophen only has * Antipyretic and analgesic activity

SE of acetaminophen Hepatotoxicity

Antidote for acetaminophen toxicity * N-acetylcysteine

DMARDs are slow acting drugs for * Rheumatic disease

Initial DMARD of choice for patients with RA Methotrexate

Methotrexate

Causes bone marrow suppression Methotrexate

SE of penicillamine Aplastic anemia and renal toxicity

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)

Adalimumab, 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 GoutNSAID used in gout * Indomethacin

COX 2 inhibitors should be used cautiously in pts with

Drugs-Modifying Anti-Rheumatic Agents (DMARDS)

Drug ofter used in combination with TNF - alpha inhitors for RA

Inhibiting dihydroorotate dehydrogenase which leads to decreased pyrimidine synthesis, decreased T cell proliferation and decreased antibody production by B cells

Proteins that prevent action of tumor necrosis factor alpha (TNF-alpha)

NSAID contraindicated in gout Aspirin

MOA of colchicine (used in acute gout)

SE of colchicine Kidney and liver toxicity, diarrhea

Probenecid and sulfinpyrazone

* Xanthine oxidase

InsulinsRapid acting insulins that do not self-aggregate **

Peakless ling acting insulin ** Insulin glargine

Cardiac drugs

Adenosine

Selective inhibitor of microtubule assembly

Agent used to treat chronic gout by increasing uric acid secretion and excretion

Allopurinol treats chronic gout by decreasing uric acid production by inhibiting

lispro insulin, aspart insulin, glulisine insulin

DOC for paroxysmal supraventricular tachycardia; has high efficacy and short duration of action

pharmacology one liners

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