NBEO Systemic Pharm

What is first-pass metabolism?

Metabolism of a drug before it enters circulation; usually thru stomach, liver, intestine, rectum, lung.

A large Vd = ?

Drug is stored in fat, lipophilic, likely req hepatic metabolism, able to bind tight w/ tissue sites.

Low Vd = ?

Drug does not preferentially bind to fatty sites, hydrophilic, large, bound to plasma proteins, likely elim by kidneys in non-metabolized form

Plasma in body = __ L?

3

Blood in body = __ L?

5.5

Extracellular fluid (outside of blood) = __ L?

12

Total body water = __ L?

42

Vd = ?

Amt of drug in body (mg) / conc of drug in plasma (mg/L)

Unit = Liters (L)

Clearance (CL) = ?

Volume / Time

or (0.7 x Vd) / half-life

Most drugs are elim by ___ order kinetics

first

T/F - Elimination of drugs occur at a linear fashion.

False - log

It takes ___ half-lives to elim a drug from the body.

4-5

T/F - Zero-order rate kinetics have a linear relationship with plasma conc and time.

True

T/F - Zero-order rate kinetics obey half-life rules.

False - constant amt of drug is elim per unit time (linear)

T/F - If a drug follows zero-order kinetics, the drug will take twice as long to elim if the conc is doubled.

True

Alcohol obeys (first/zero) order rate kinetics.

zero (more you consume, longer it takes to elim)

What is ED?

Effective Dose = amt of drug to produce a therapeutic effect

What is TD?

Toxic Dose = amt of drug to produce Sx of poisoning

How do competitive antagonists shift the dose response curve?

to the right

How do noncompetitive antagonists shift the dose response curve?

downward

Potency vs Efficacy vs Affinity?

Potency = amt of drug req to produce an effect

Efficacy = effect of drug once bound

Affinity = how well drug binds to receptor site

T/F - A partial agonist may have higher affinity than a full agonist but never a higher efficacy or potency

True

Pilocarpine

direct acting cholinergic agonist, act on CB, pulling on scleral spur and open TM for incr aqueous outflow in glaucoma pts. Also works on sphincter for miosis

Acetylcholine

direct acting Cholinergic agonist, acts on nicotinic receptors on symp AND parasymp and only acts on postganglionic receptors in parasymp.

Bethanechol

direct acting Cholinergic agonist, act on smooth muscles of bladder in tx for pts w/ urinary retention

"Bethanechol Bladder"

Carbachol

direct acting Cholinergic agonist, same MOA as pilo. More side effects vs pilo, used if pt allergic to pilo.

Demecarium

indirect acting chol agonist, an Acetylcholinesterase agent

Edrophonium

indirect acting chol agonist, Dx MG, immediately stimulates muscle and improve strength in pt w/ MG (Tensilon Test)

Echothiophate

irreversible indirect acting chol agonist, no longer used for glaucoma

Pyridostigmine

indirect acting chol agonist, used for Tx MG

Isofluorophate

irreversible indirect cholinergic agonist, similar to echothiophate but more ocular ADEs

Neostigmine

reversible indirect cholinergic agonist, stim intestinal and bladder motility, Tx MG

What is SLUD?

Salivation, Lacrimation, Urination, Defecation = parasympathetic effects

Anticholinergics prevent these...thus dry mouth, dry eyes, urinary retention, constipation

Succinylcholine

cholinergic antagonist, Block nicotinic receptors at NMJ and used for muscle paralysis prior to surgery

Tubocurarine

cholinergic antagonist, Block nicotinic receptors at NMJ and used for muscle paralysis prior to surgery

Atropine

muscarinic antagonist; for dilation, cycloplegia, amblyopia, posterior synechiae

Scopolamine

cholinergic antagonist, for preventing motion sickness, same ADEs as atropine

recall = scopolamine patch

Clonidine

A2 agonist, decr symp outflow, Tx HTN (decr vascular resistance and decr HR)

Cocaine

adrenergic agonist, block reuptake of norepi in reward centers of brain, local anesthetic (block Na channels), vasoconstrictor (stop nose bleed), mood elevator (drug abuse), topical anesthetic, Dx horner's

Albuterol

adrenergic agonist (bronchodilator), for cases of constricted airways = asthma, COPD, emphysema.

ADEs = tachycardia (beta 1 effect), heart palpitations, nervousness, tremor, nausea

Methyldopa

A2 adrenergic agonist, in CNS to Tx HTN. Negative feedback loop in periph NS and CNS leadign to decr total peripheral resistance and cardiac output

Phenylephrine

adrenergic agonist (A1 more so than A2, recall dilator has more A1 receptors). Also used systemically as nasal decongestant and incr BP

Dobutamine

adrenergic agonist (B1>B2), incr contractility and cardiac output, used for CHF and shock

Isoproterenol

adrenergic agonist, potent bronchodilator (B2 activity), for asthma

Norepinephrine

adrenergic agonist (A1, A2, B1), for shock and hypotension

NOT B2 like epi - hence no such thing as "NorEpiPen"

Recall Epi-Pens are used for anaphylactic shock i.e. bronchospasm thus use epi pen to bronchodilate

Epinephrine

adrenergic agonist (acts on all - A1, A2, B1, B2).

A1 = vasoconstrict periph arterioles to incr blood to core organs (thus incr BP)

B1 = Incr HR (used in cardiac arrest - Epi-Pen)

Mixed w/ local anesth to incr local anesthetic bioavailability

Dopamine

adrenergic agonist, acts on dopamine receptors more than beta receptors, least on alpha receptors. Does not cross BBB (vs derivative, L-Dopa). used for shock and heart failure (incr HR and BP).

Tyramine

adrenergic agonist, fermented from food products e.g. turkey and promotes serotonin release

Ephedrine

adrenergic agonist, CNS stimulant acts on Alpha and Beta receptors; similar to Epi but less potent. Incr BP by incr periph resistance; als used for local and nasal decongest.

Key = wt loss drug that speeds up metabolism (recall ephedra controversy)

Metraraminol

adrenergic agonist, similar to norepi, used for shock and acute hypotension, enhance cardiac activity, produces mild vasoconstriction

Prazosin

adrenergic antagonist, A1 selective receptor blocker, Tx HTN and BPH

Terazosin

adrenergic antagonist, A1 selective receptor blocker, Tx HTN and BPH

Doxazosin

adrenergic antagonist, A1 selective receptor blocker, Tx HTN and BPH

Bisoprolol

cardioselective adrenergic antagonist (B1 selective)

Lopressor

cardioselective adrenergic antagonist (B1 selective)

Propranolol

noncardioselective adrenergic antagonist (act on both B1 and B2)

Pindolol

noncardioselective adrenergic antagonist (act on both B1 and B2)

Labetolol

noncardioselective adrenergic antagonist (act on both B1 and B2)

Carvedilol

noncardioselective adrenergic antagonist (act on both B1 and B2)

Beta blocker effects on heart, BP, kidneys, glaucoma? ADEs?

Heart = inotropic (change in contractility), chronotropic (decr HR)
BP decr
Kidney = decr renin, incr Na retention
Glaucoma = decr aqueous
ADEs = depression, impotence, bradycardia, exacerbate asthma

Why do noncardioselective Beta Blockers exacerbate asthma?

Asthma = bronchoconstriction Sympathetic B2 action = bronchodilation
Block B2 = block bronchodilation therefore worsen bronchoconstriction (bad!)

Prostaglandin class? Precursor?

eicosanoids, from precursor Arachiodonic Acid

Prostaglandins (systemic)

eicosanoids, from precursor Arachiodonic Acid

Released when cells damaged, promote inflam response incl pain and fever. Also produced by stomach and intestines to inhibit gastric secretions and influence gastric motility. Also bronchoconstriction.

Inhibitors of prostaglandin synthesis?

aspirin, NSAIDs, Steroids

Serotonin

NT derived from L-tryptophan; fxns = vasoconstriction, mood variations, temp and BP regulation, pain, platelet aggregation; Tx migraine HAs

Histamine is released by

Mast cells, basophils, gastric endocrine cells, histaminergic neurons (stress hives)

MOA of histamine H1 receptors

incr intracellular Ca (intestinal and bronchial smooth muscle, cardiac muscle, endoth cells, CNS, periph nerve endings)

MOA of histamine H2 receptors

incr cAMP (vascular smooth muscle, cardiac muscle, gastric parietal cells, CNS, mast cells)

MOA of histamine H3 receptors

Feedback inhibitors - for histamine, ACh, Dopamine, NE, serotonin

Effects of histamine on lungs, heart, arterioles

Bronchoconstrict smooth and cardiac muscle; vasodilation of smooth muscle in arterioles.

Think of allergy side effects = tight airway (bronchoconstriction), redness/hives (vasodilation)

Gastric acid secretion, wakefulness, appetite, and body temp is controlled by...

histamine - recall it's in the stomach/intestine and CNS (hypothalamus)

What is the importance of histamine at nerve endings?

powerful stimulant of sensory nerve endings for mediating pain and itching

T/F - Epinephrine is an effective histamine antagonist

True - recall epi pen used for bee sting rxn

What histamine receptor type is in the stomach? In the intestine? In the lungs?

H2 = stomach
H1 = intestine
H1 = lungs

T/F - 1st generation antihistamines cross the blood-brain barrier

True

Common applications & drugs of H1 blocker class?

These are your typical antihistamines incl benadryl, dramamine, claritin, allergra; for allergic rhinitis, nausea/motion sickness relief, sleep aid

Common applications & drugs of H2 blocker class?

Stomach! Incl stomach ulcers, heartburn

Which antihistamine class induces sedation?

1st gen H1 blockers

Diphenhydramine (Benadryl, Dramamine)

1st gen H1 blockers for allergic rhinitis, sleep aid, motion sickness, itching; ADE = sedation (vs H1 2nd gen)

Azelastine

Nasal spray for allergic rhinitis; 1st gen H1 blocker

Promethazine

1st gen H1 blocker for nausea, vomiting, motion sickness

Loratadine (Claritin)

2nd gen H1 blocker; limited CNS access (not cross BBB) so less sedative effect; for allergic rhinitis and chronic urticaria; ADE = cardiac arrhythmias

Fexofenadine (Allegra)

2nd gen H1 blocker; limited CNS access (not cross BBB) so less sedative effect; for allergic rhinitis and chronic urticaria; ADE = cardiac arrhythmias

Ranitidine

aka Zantac; H2 blocker (decr acid secretion from parietal cells), for gastric ulcers, heartburn, urticaria (hives)

ADEs = diarrhea

Cimetidine

aka Tagamet; H2 blocker (decr acid secretion from parietal cells), for gastric ulcers, heartburn, urticaria (hives)

ADEs = gynecomastia and loss of libido

B2 agonists are useful for the lungs by

bronchodilation - Tx asthma, COPD

Formoterol

MAINTENANCE (long acting) B2-agonist - for chronic Tx, not acute; Tx bronchospasm due to Asthma or COPD

Salmeterol

MAINTENANCE (long acting) B2-agonist - for chronic Tx, not acute; Tx bronchospasm due to Asthma or COPD

Advair Diskus

MAINTENANCE (long acting) B2-agonist (salmeterol) in combo w/ steroid (fluticasone) - for chronic Tx, not acute; Tx bronchospasm due to Asthma or COPD

Theophylline

MAINTENANCE (long acting) B2-agonist - for chronic Tx, not acute; Tx bronchospasm due to Asthma or COPD

Albuterol

Short-acting B2-agonist for ACUTE Tx; for Asthma, COPD, Emphysema; ADEs = tachycardia (due to B1 effects)

Terbutaline

Short-acting B2-agonist for ACUTE Tx; for Asthma, COPD, Emphysema; ADEs = tachycardia (due to B1 effects)

Cromolyn Sodium

Mast cell stabilizer for lungs; mild to moderate anti-inflammatory

MOA = stabilize mast cell memb, prevents mediator rel by blocking Ca gates. Not indicated for acute Sx or asthma

ADEs = bronchospasm, throat irritation, nasal congestion, anaphylaxis

Beclomethazone

Corticosteroid for lungs; *stops inflammation by inhibiting phospholipase A2. Reduces inflam due to bronchal irritants. For mod to severe asthma. No effect on bronchial smooth muscle. PO or inhaled.

ADEs = oral thrush (steroid causes decr immune rxn)

Triamcinolone

Corticosteroid for lungs; *stops inflammation by inhibiting phospholipase A2. Reduces inflam due to bronchal irritants. For mod to severe asthma. No effect on bronchial smooth muscle. PO or inhaled.

ADEs = oral thrush (steroid causes decr immune rxn)

Fluticasone

Corticosteroid for lungs; *stops inflammation by inhibiting phospholipase A2. Reduces inflam due to bronchal irritants. For mod to severe asthma. No effect on bronchial smooth muscle. PO or inhaled.

ADEs = oral thrush (steroid causes decr immune rxn)

Omeprazole

aka Prilosec; Proton Pump inhibitor, irreversibly block H+/K+ ATPAse pump. Used for stomach ulcers and acid reflux

ADEs = GI distress, skin rash, gastrin-dependent hyperplasia

Esomeprazole

aka Nexium; Proton Pump inhibitor, irreversibly block H+/K+ ATPAse pump. Used for stomach ulcers and acid reflux

ADEs = GI distress, skin rash, gastrin-dependent hyperplasia

Colloidal bismuth compounds

aka Pepto-bismol; binds to ulcer craters, inhibits pepsin activity, stimulate mucous secretion. Used for H. pylori infections, prophylaxis for traveler's diarrhea

ADEs = black staining of tongue, black stools, tinnitus

Alkylating agents (for chemotherapy) MOA?

modify DNA, RNA, and protein by transferring a reactive alkyl group to them, resulting in disruption of fxn and cell death

Cisplatin

aka Platinol; Alkylating Chemotherapeutic agent; causes interstrand DNA crosslinking, used for various cancers

ADEs = kidney and ototoxicity

Cyclophosphamide

aka Cytoxan; Alkylating Chemotherapeutic agent; covalently x-links DNA; for Non-Hodgkin's lymphoma, breast, and ovarian carcinoma

ADEs = bladder cystitis, alopecia, myelosuppression

Antimetabolite (for chemotherapy) MOA?

close structural relationships to endogenous substances, interfere w/ formation of essential cellular components

Methotrexate

aka Mexate, Folex; Antimetabolite (for chemotherapy); folic acid analog inhibits dihydrofolate reductase, which inhibits DNA synth; used for RA, psoriasis, leukemia, lymphoma

ADEs = myelosuppression

5-Fluorouracil

aka 5-FU; Antimetabolite (for chemotherapy), similar to methotrexate; for colon cancer, *trabeculectomy, *basal cell carcinomas, and prevent wound healing after surgery

Adriamycin

aka doxorubicin; Antibiotic (for chemotherapy); non-covalently intercalates in DNA thus break DNA producing free radicals; for various cancers incl *breast cancer

ADEs = cardiotoxicity*, alopecia, myelosupp

Vincristine

Plant alkaloid (for chemotherapy); inhibits cell mitosis by inhibiting microtubule formation; use for lymphoma, wilms' tumor, choriocarcinoma

ADEs = neurotoxicity, bone marrow suppression

Vinblastine

Plant alkaloid (for chemotherapy); inhibits cell mitosis by inhibiting microtubule formation; use for lymphoma, wilms' tumor, choriocarcinoma

ADEs = neurotoxicity, bone marrow suppression

Paclitaxel

aka Taxol; Plant alkaloid (for chemotherapy); promotes microtubule polymerization; for *breast and ovarian cancer

ADEs = myelosupp, hypersensitivity

Tamoxifen

Estrogen antagonist (for chemotherapy); competitive partial agonist inhibitor of estradiol which *inhibits estrogen effects; used for active and remission of breast cancer

ADEs = *crystalline retinopathy, fatty liver, thromboembolism, hot flashes, incr chance of uterine cancer

Disinfectant vs Antiseptic?

Antiseptics = used on people, low toxicity for humans
Disinfectants = inhibits or kills microorganisms

"Auntie-septics can be used on your Aunties" - used on people

Silver sulfadiazine

Bacteriocidal antiseptic

Rifampin

mRNA synthesis blocker; used in combo w/ Isoniazid to Tx TB

Describe the nucleotide synthesis pathway in context of nucleotide synthesis blockers (antimicrobials)

Sulfonamides inhibit Dihydropteroate synthase. DS causes:
PABA + Pteriding → Dihydrofolic acid

Trimethoprim inhibits Dihydrofolate reductase. DS causes:
Dihydrofolic acid → THF

THF is used in making parts of DNA, RNA, and some proteins

Sulfamethoxazole

nucleotide synthesis blocker; inhibit *dihydropterate synthase; used for G+ & G-, UTIs.

ADEs = toxic to CSF (gout), CI in preg, Steven Johnson's syndrome, kernicterus in infants, nephrotoxicity

Trimethoprim

nucleotide synthesis blocker; inhibits *dihydrofolate reductase; used for UTIs in add'n to sulfonamides, bacteriostatic

ADEs = bone marrow toxicity (megaplastic anemia), leukopenia, granulocytopenia

Prim sounds like "trim" - reduce - reductase

Fluconazole

Fungal membrane blocker; inhibit ergosterol synth which inhibits plasma memb formation; for yeast infections, cryptococcal meningitis

Amphotericin B

Fungal membrane blocker; "tears holes" by binding to ergosterol and cause ions to leak out and disrupt homeostasis

ADEs = nephrotoxicity, reversible normocytic anemia, neurotoxicity

Bacitracin

Peptidoglycan synthesis blocker; for *G+ only; for blepharitis

Vancomycin

Peptidoglycan synthesis blocker; binds to D-ala & disrupts cell wall; used for serious G+ infections e.g. pseudomembranous colitis, MRSA; mainly IV form

ADEs = Red Man's syndrome, ototoxicity, nephrotoxicity

Ciprofloxacin, Norfloxacin, Ofloxacin

Fluoroquinolones; DNA Topoisomerase blocker; inhibits both *DNA gyrase and *topoisomerase II, bacteriocidal, mostly G- but 3rd & 4th gen covers both G+ & G-

used in eyes for ulcers, bacterial infections; used PO for UTIs, respiratory infections, GI tract infections

ADEs = *PO quinolONES affect the BONES causing tendonitis; CI in preg and kids due to dmg cartilage and bone

Penicillin

Cell wall synth blocker; inhibit peptidoglycan cross-links; used for strep, syphillis, meningitis, pneumococcal inf.

G type for IM or IV, V type for PO

What needs to be considered as far as taking penicillin w/ food?

Oral absorption of most penicillins is poor, and impaired by presence of foods - take 30 mins before or 2 hrs after meals

Methicillin

Cell wall synth blocker, MOA same as penicillin, but resistant to penicillinase b/c bulkier R group; narrow spectrum, targets Staph aureus

ADEs = *interstitial nephritis

Nafcillin

Cell wall synth blocker, MOA same as penicillin, but resistant to penicillinase b/c bulkier R group; narrow spectrum, targets Staph aureus

Dicloxacillin

Cell wall synth blocker, MOA same as penicillin, but resistant to penicillinase b/c bulkier R group; narrow spectrum, targets Staph aureus

Acid stable - other penicillins degraded quickly by stomach

Augmentin

Amoxacillin + Clavulanic Acid (this fights some penicillin resistant bacterial strains)

Amoxicillin

Penicillin (cell wall synth blocker); not resistant to penicillinase, but wider spectrum w/ incr activity vs G-.

ADEs = *hypersensitivity rxn

Cefaclor

aka Ceclor; a Cephalosporin (Cell wall synth blocker, related to penicillin); bacteriocidal, less susceptible to penicillinase; used for more G- at higher generations

ADEs = rashes, hypersens, nephrotoxicity

Cefalexin

aka Keflex; a Cephalosporin (Cell wall synth blocker, related to penicillin); bacteriocidal, less susceptible to penicillinase; used for more G- at higher generations, skin infections esp around eye - dacryadenitis/cystitis, preseptal cellulitis

ADEs = rashes, hypersens, nephrotoxicity

Ceftrioxone

aka Rocephin; a Cephalosporin (Cell wall synth blocker, related to penicillin); bacteriocidal, less susceptible to penicillinase; used for more G- at higher generations, meningitis, gonorrhea

ADEs = rashes, hypersens, nephrotoxicity

Cephalosporins are primarily for gram (neg/pos).

positive, but later generations have increased use for G-

Aminoglycoside MOA

block initiation of protein synth at 30S ("AT 30")

Tetracycline MOA

block initiation of protein synth at 30S ("AT 30")

Name some of the aminoglycosides

Aminoglycosides = Gentamycin, Neomycin, Tobramycin, Streptomycin

"AGeNTS"

Aminoglycosides are ineffective vs...

anaerobes, strep

What antibiotics are generally taken w/o food?

"PAT an empty stomach"

Penicillin, Azithromycin, Tetracycline

Aminoglycoside toxicity?

*Nephro and Ototoxicity

"amiNO"

Minocycline use?

Long term management of acne

Tetracycline coverage/use?

wide spectrum - for respiratory infections (pneumonia), genital infections, Lyme dz, rickettsia

Doxycycline use?

commonly for MGD & acne rosacea

T/F - You must take tetracyclines with milk.

False - inhibited by milk (also by antacids, iron containing compounds)

T/F - Tetracyclines can be used w/ pregnant females

False - also CI in kids

Tetracycline ADEs

Retards bone growth (CI preg, kids), discolor teeth, photosensitivity, GI distress, *pseudotumor cerebri

Chloramphenicol MOA?

block protein synth at 50S

Chloramphenicol ADEs?

*Aplastic anemia, *optic neuritis, *grey baby syndrome

Macrolide MOA?

block protein synth at 50S (bacteriostatic)

Name the Macrolides

Macrolides = Azithromycin, Clarithromycin, Erythromycin

"MACE"

Macrolide coverage?

G+ cocci and bacilli (bacteriostatic)

Macrolide ADEs

*Hard on the stomach...

Nausea, diarrhea, abdominal pain

Macrolides are the drug of choice for...

Mycoplasma pneumonia, chlamydia

Erytrhomycin ung often used for blepharitis

Lincomycin & Clindamycin use...

for methacillin resistant strains and anaerobic infections above diaphragm

Metronidazole

aka Flagyl; disrupts DNA & nucleic acid synth; used for bacterial infections below diaphragm e.g vaginosis, colon infections; also for giardia,

*ADEs = nausea, diarrhea, metallic taste, CNS effects, GI upset w/ alcohol

trichomonas

*Note that name has -azole but this is not an antifungal!!!

What antibiotics are used for TB?

Rifampin, Isoniazid, Pyrazinamide

"TB can Rest In Peace"

Rifampin MOA?

inhibit RNA polymerase (TB drug)

Orange-pink saliva, tears, sweat, and urine are characteristic ADEs of this antibiotic...

Rifampin (TB drug)

Isoniazid MOA?

Bactericidal, interfere w/ synth of mycolic acids and disrupt cell wall (TB drug)

What is the only drug that can be used by itself as prophylaxis for TB?

Isoniazid

"ISOniazid ISOlation"

Isoniazid ADEs?

periph neuritis , thus often Tx concurrently w/ Pyridoxine (Vit B6) for prevention

Pyrazinamide

Part of the 3 TB drugs ("RIP" = Rifampin, Isoniazid, Pyrazinamide)

Imadazoles

Antifungal; Interferes w/ synth or permeability of fungal cell wall

ADEs = GI distress, HAs, rash, hepatoxicity

Triazoles

Antifungal; Interferes w/ synth or permeability of fungal cell wall

Ketoconazoles

aka Nizoral; antifungal, used for fungal skin infections (ringworm) and PO for systemic fungal infections

Itraconazole

aka Spronox; fungal infections, esp of the nails; take while fasting

Griseofulvin

aka Grifulvin; antifungal; inhibits fungal mitosis by interacting w/ microtuble formation during cell wall development; used for fungal infections of scalp and skin

Terbinafine

aka Lamisil; inhibits ergosterols; used only for superficial fungal skin infections

Amantadine

aka Symmetrel; antiviral; inhibits viral entry into cell, limited activity only to RNA viruses (influenza A); used for influenza A and *Parkinson's

Rimantadine

aka flumadine; antiviral; inhibits viral entry into cell, limited activity only to RNA viruses (influenza A); used for influenza A and *Parkinson's

Oseltaminivir

aka Tamiflu; antiviral; inhibit influenza A and B virus neuraminidase; used for prophylaxis of influenza A, B, avian flu

What antivirals are used for Parkinson's?

Amantadine, Rimantadine

What antiviral is useful for both Influzena A and B? How about Influenza A only?

Oseltaminivir = A and B
Amantadine, Rimantadine = A only

Trifluridine

aka Viroptic; antiherpes; Inhibits viral DNA synth; gtt used for HSV in eye

What preservative is in Trifluridine?

Thimerosal

Acyclovir

antiherpes; inhibit viral DNA synth (selectively acting on DNA poly); used for oral, genital herpes and HZV.

ADEs = local irritation, renal dysfxn, neurotoxicity

Valacyclovir

aka Valtrex; prodrug of acyclovir but better oral availability and less freq administration; used for genital herpes, cold sores, HZV

Gancyclovir

aka Cytovene; antiviral; similar to acyclovir (inhibit DNA poly); used for *CMV infections, thru IV (AIDS patients)

ADEs = bone marrow supp, renal insufficiency

Foscarnet

aka foscavir; antiviral; inhibits viral DNA poly of herpesvirus and reverse transcriptase of HIV; used for CMV retinitis for AIDS pts when gancyclovir fails, also for HSV, HZV

"Foscarnet is the safety net"

Zidovudine

aka Retrovir, AZT; anti-HIV; inhibit rev transcriptase; used to Tx AIDS

*Resistance a huge problem

Didanosine

aka Videx; anti-HIV; used w/ AZT for AIDS pts

Ivermectin

ant-helminth (worm); inhibit microtubule formation during cell wall synth; for river blindness (onchocerciasis)

"IVER rIVER"

Chloroquine

aka Plaquenil; anti-malarial; causes *heme build-up which is toxic to parasite, also *inhibits phospholipase-A; used for malaria (heme buildup), SLE, RA (inhibit PLA).

ADEs = *Bulls-eye maculopathy (irrev); also GI upset, HAs, reversible visual disturbances

Prednisone (incr/decr) blood glucose?

incr

T/F - Prednisolone decr mast cell accumulation.

True

Steroids decr leukotrienes and prostaglandins by...

inhibiting phospholipase A2, which is an enzyme that creates arachidonic acid.

Arachidonic acid is a precursor to lipoxygenase and COX, which make leukotrienes and prostaglandins, respectively

Steroids cause vaso(dilation/constriction)?

constriction (decr blood flow, swelling, edema)

How do steroids interfere w/ healing?

decr fibrin and collagen synth which normally promotes healing following inflammation

This anti-inflammatory agent can promote diabetes or promote insulin resistance.

Steroids

Aspirin MOA?

IRREVERSIBLY Inhibit COX-1 pathway, thus decr prostaglandin (hence anti-inflam and analgesia) and thromboxane (hence blood thinner)

Aspirin ADEs?

Gastric ulcers & bleeding, cardiovascular effects (clotting inhibition), Reye's syndrome (post-infectious encephalopathy)

What common pain reliever does NOT have anti-inflammatory action?

Acetaminophen (Tylenol)

Ibuprofen and Naproxen fall under this drug category...

Propionic Acid Derivative, NSAID

What pain med is a reversible inhibitor of COX?

Ibuprofen, Naproxen (Propionic Acid derivatives)

Ibuprofen ADEs?

Nausea, vomiting, epigastric pain, GI bleeding, kidney damage; does NOT cause Reye's syndrome

Tylenol uses?

Pain and fever ONLY (NOT an anti-inflammatory!)

T/F - Celecoxib is a COX-1 inhibitor.

False - COX-2

What is special about COX-2 inhibitors vs COX-1 inhibitors?

COX-2 inhibitors don't affect gastric mucosa

COX-2 inhibitor use?

For osteoarthritis, RA

(Celecoxib aka Celebrex)

T/F - Celecoxib interferes w/ bleeding time.

False - no effect, vs ibuprofen and aspirin

Morphine MOA?

opioid; *acts on Mu, Kappa, and Delta receptors

T/F - Morphine causes pupillary constriction

True

T/F - Morphine is safe for pregnant females

False

Temazepam

aka Restoril; sedative hypnotic (help people fall asleep); acts on GABA receptor

Benzodiazepine uses

anti-convulsant, anti-anxiety, sedative hypnotic (help sleep), status epilepticus (extended brain seizure)

Zolpidem

aka Ambien; acts on GABA receptor; to help sleep

Alprazolam

aka Xanax; Anxiolytic (anti-anxiety); act on GABA; used for anxiety, insomnia, agoraphobia, panic attacks, sedative, alcohol withdrawal

ADEs = drowsiness, sedation

Fatal if combined w/ alcohol

Diazepam

aka Valium; act on GABA; used for anxiety, insomnia, agoraphobia, panic attacks, sedative, alcohol withdrawal, muscle spasticity

ADEs = drowsiness, sedation

Fatal if combined w/ alcohol

Schizophrenia = (excess/not enough) dopamine?

Parkinsons = (excess/not enough) dopamine?

Schizo = too much
Parkinsons = not enough

Chlorpromazine

Antipsychotic; inhibits D2 receptor (lower affinity vs Haloperidol thus lower side effects)

ADEs = too much causes Parkinson-like effects (hence reduces Dopamine effect)

Ocular ADEs = RPE and outer retinal degeneration, pigment deposits throughout eye, and cataracts

Haloperidol

Antipsychotic; inhibits D2 receptor (higher affinity vs Chlorpromazine thus lower side effects)

ADEs = too much causes Parkinson-like effects (hence reduces Dopamine effect)

T/F - D2 receptor antagonists are effective vs. Parkinson's.

False - you want to increase dopamine, not inhibit for parkinson's!

Parkinson's can be treated with this drug that can cross the BBB...

Levodopa (converts into dopamine)

"Levitate Dopa" - raise dopamine

This anti-Parkinson's drug can cause acute angle closure glaucoma...

Levodopa

Too much dopamine results in ___-like Sx. Too little results in ___-like Sx.

Schizo, Parkinson's

Prominent symptoms of Parkinson's?

TRAP = Tremor at rest, Rigidity, Akinesia, Postural reflex loss

Carbidopa MOA, use?

anti-Parkinson's; incr levels of dopamine but does not cross BBB

Bromocryptine

aka Parlodel; anti-Parkinson's; D2 receptor agonist, helps incr dopamine levels

Selegeline

aka Eldepryl; MAOI, reduce metabolism of levadopa/dopamine; Tx parkinson's

MAOIs have tons of drug interactions

Benztropine

aka Cogentin; block muscarinic ACh receptors; reduce tremor and rigidity

ADEs = anti-parasymp so think stop SLUD...dry mouth, dry eyes, urinary retention, constipation

Phenelzine

aka Nardil; MAOI - block major breakdown paths of NE and Serotonin, thus incr these NTs; used for depression, panic attacks

Amitriptyline

Trycyclic Antidepressant (TCA); inhibits NE and Serotonin reuptake thus incr these NTs; used for pain, fibromyalgia, migraines, sedation

*ADEs = TCA OD is life threatening! Do NOT give to suicidal pt!

Fluoxetine

aka Prozac; SSRI (Selective Serotonin Reuptake Inhibitor); for depression, panic disorder, OCD, bulimia

MAOIs cannot combine with...

lots of drugs, especially other antidepressants

Buproprion

aka Wellbutrin; inhibit NE and Dopamine uptake; for depression, hypersomnia, adhd

ADEs does NOT include sexual dysfxn

What antidepressant involves inhibition of dopamine uptake?

Buproprion (Wellbutrin) - also inhibits uptake of NE

What antidepressant does not include sexual dysfxn?

Buproprion (Wellbutrin)

Sertraline

aka Zoloft; SSRI (Selective Serotonin Reuptake Inhibitor); for depression, panic disorder, OCD, bulimia

Carbamazeprine

aka Tegretol; enhances GABA (inhibitory) transmission and inhibit reuptake of NE, blocks Na channels; anticonvulsant, for partial seizures

ADEs = diplopia

Phenytoin

aka Dilantin; enhances GABA (inhibitory) transmission and inhibit reuptake of NE, blocks Na channels; anticonvulsant, for partial seizures

ADEs = diplopia, nystagmus

GABA in general has what kind of effect?

Important inhibitory NT; relaxing effect - anti-anxiety and anti-convulsant

Phenobarbital use?

seizures

Gabapentin

aka Neurontin; Incr GABA in synaptic cleft; for nerve pain (esp DM pts), restless legs syndrome

Valproic Acid use?

aka Depakene; used for seizures, migraines, bipolar dz

Baclofen

aka Lioresal; GABA agonist; decr spasticity due to MS and spinal cord injury

Cyclobenzaprine

aka Flexeril; depress polysynaptic reflexes, for muscle spasms

Nicotine MOA

Mimics ACh at preganglionic synapses in both parasymp and symp (hence nicotinic receptors in both systems), acts on pleasure centers in the brain (hence causing dependence)

Tx alcohol withdrawal with...

Chlodiazepoxide (Librium), Lorazepam (Ativan), Clonidine (Catapres)

Chronic alcoholism leads to this severe thiamine deficiency...

Wernicke's Syndrome

Cocaine MOA?

Blocks dopamine and NE uptake in the reward receptors in the brain (floods dopamine and NE in the synapse)

Morphine (dilates/constricts) pupils?

constricts - "pin point pupils" with morphine

Cocaine (dilates/constricts) pupils?

dilates

Local anesthetic MOA?

*Block flow of voltage gated sodium channels along nerve axons

Procaine is aka

Novacaine

Procaine = Amide or Ester?

Ester

Cocaine = Amide or Ester?

Ester

Benoxinate = Amide or Ester?

Ester

Lidocaine = Amide or Ester?

Amide

Bupivacaine = Amide or Ester?

Amide

What is often added w/ local anesthetics to improve its effect?

Vasoconstrictors e.g. Epi to concentrate drug in affected area

Levothyroxine Sodium MOA, use

aka Synthroid, Levothyroid, Levoxyl; T4 hormone; used for hyperthyroidism and pseudotumor cerebri

Methimazole MOA, use

Antithyroid agent (thioamide); prevent hormone synth and the addition of iodine to T4 and T3; used for hyperthyroidism

Propothiouracil MOA, use

Antithyroid agent (thioamide); prevent hormone synth and the addition of iodine to T4 and T3; used for hyperthyroidism

Radioactive Iodine MOA, use

Antithyroid agent; inhibit/destroy thyroid cells that have iodine receptors; used for hyperthyroidism

Insulin MOA

Cell surface receptor causes activation of *tyrosine kinase and a phosphorylation cascade

For pregnant DM pts, you must administer insulin by...

IV (cannot give oral)

Sulfonylurea MOA

Incr secretion of insulin by beta cells, decr glucagon release, incr sensitivity to insulin

recall that glucagon incr blood glucose (opposite of insulin)

glipizide class, MOA, use

Sulfonylurea; Incr secretion of insulin, decr glucagon release, incr sensitivity to insulin; for DM Type 2

glyburide class, MOA, use

Sulfonylurea; Incr secretion of insulin, decr glucagon release, incr sensitivity to insulin; for DM Type 2

glimepiride class, MOA, use

Sulfonylurea; Incr secretion of insulin, decr glucagon release, incr sensitivity to insulin; for DM Type 2

gliclazide class, MOA, use

Sulfonylurea; Incr secretion of insulin, decr glucagon release, incr sensitivity to insulin; for DM Type 2

Metformin class, MOA, use, CI, ADEs

aka Glucophage; Biguanide; decr liver glucose production and incr glucose uptake; for DM Type 2

CI = renal insuff

ADE = Lactic acidosis

Miglitol class, MOA, use

aka Glyset; Alpha-glucosidase inhibitor; inhibit carbohydrate breakdown and intestinal uptake (therefore less glucose in blood); for DM2

Acarbose class, MOA, use, ADEs

aka Precose; Alpha-glucosidase inhibitor; inhibit carbohydrate breakdown and intestinal uptake (therefore less glucose in blood); for DM2

ADEs = "Acarbose Caboose" - rear end issues (gas, diarrhea)

Pioglitazone class, MOA, use, ADEs

aka Actos; Thiazolidinediones ("glitazones"); enhance insulin receptors to incr glucose intake in fat and muscle tissue; used for DM2

ADEs = wt gain, edema, upper respiratory tract infection

Rosiglitazone class, MOA, use, ADEs

aka Avandia; Thiazolidinediones ("glitazones"); enhance insulin receptors to incr glucose intake in fat and muscle tissue; used for DM2

ADEs = wt gain, edema, upper respiratory tract infection

Sitagliptin class, MOA, use

aka Januvia; Dipeptidyl peptidase-4 inhibitor; inhibit glucagon release, help incr insulin secretion, decr gastric emptying; for DM2

ADEs = Upper respiratory tract infection, hypersensitivity rxn

Estrogen uses

*Oral contraceptive, Tx hypogonadism, hypopituitarism, *post-menopausal Sx, osteoporosis, dysmenorrhea, premenstural Sx

Progestins used w/ Estrogens to prevent endometrial cancer

Estrogen ADEs

Nausea, dry eyes, edema, breast tenderness, hyperpigmentation, migraines, HTN, endometrial hyperplasia (if not used w/ progesterone), incr risk of deep venous clots

MOA of oral contraceptives

inhibit ovulation by disrupting cyclical release of gonadotropins

T/F - Testosterone is used to Tx osteoporosis

True

Recall that Estrogen can cause osteoporosis

T/F - Testosterone ADE includes testicular atrophy

True

Spironolactone MOA, use

Inhibits mineralcorticoid receptors, androgen receptors, aldosterone; used alone or w/ birth control to Tx hirutism (male hair growth) in women

Hydrochlorothiazide class, MOA, use, ADEs

Diuretic; Acts on *Early distal tubule, inhibits NaCl reabs and decr Ca excretion into loop; used for HTN, CHF, Hypercalciuria

ADEs = *HYPOkalemia, metabolic acidosis, hyperglycemia, hypernatermia, hyperlipidemia, sulfa allergy

Aldactone class, MOA, use, ADEs

aka Spironolactone; K sparing diuretic; works on *Late distal tubule and collecting duct, blocks aldosterone, incr excretion of water and Na and decr passive excretion of K; used for hyperaldosteronism, K depletion, CHF

ADEs = HYPERkalemia, gynecomastia, antiandrogen effects

Lisonopril class, MOA, use, ADEs

ACE inhibitor ("prils"); Prevent formation of Angiotensin II by inhibiting ACE, blocks metabolism of Bradykinins (vasodilator); used to lower vascular resistance (anti-HTN) and decr aldosterone secretion

ADEs = *COUGH, angioedema, proteinuria, taste changes, hypotension, rash, incr renin

Enalapril

Prodrug converted into ACE inhibitor

Losartan class, MOA, use, ADEs

Angiotensin II receptor agonist (ARBs = "sartans"); antiHTN; inhibits Angiotensin II contraction of vascular smooth muscle, reducing blood pressure

ADEs = hypotension, GI effects, *NO COUGH (this drug is used as an alternative for CAIs which induce cough)

T/F - Beta blockers can increase blood glucose

True

Propranolol = cardioselective or nonselective?

non

Labetalol = cardioselective or nonselective?

non

Carvediolol = cardioselective or nonselective?

non

Pindolol = cardioselective or nonselective?

non

Metoprolol = cardioselective or nonselective?

cardioselective

Atenolol = cardioselective or nonselective?

cardioselective

Nebivolol = cardioselective or nonselective?

cardioselective

Bisoprolol = cardioselective or nonselective?

cardioselective

The "zosins" are used for ___. Name some examples. MOA?

BPH and HTN (Terazosin aka Hytrin, Prazosin aka Minpres)

A1 receptor blockers, prevent periph vasoconstriction

Terazosin MOA, use

aka Hytrin; A1 receptor blockers, prevent periph vasoconstriction; for BPH and HTN

Prazosin MOA, use

aka Minpres; A1 receptor blockers, prevent periph vasoconstriction; for BPH and HTN

Nifedipine class, MOA, use

aka Adalat, Procardia; Ca channel blocker; decr Ca in cells thus decr contraction force of heart (neg inotrope); used for angina, HTN

Verapamil class, MOA, use

aka Calan, Isoptin; Ca channel blocker; decr Ca in cells thus decr heart contractility (neg inotrope) and also *dilates coronary arteries; used for HTN, angina, arrhthmias

Clonidine class, MOA, use

aka Catapres; A2 adrenergic agonist; decr vascular resistance and decr HR; used for HTN, analgesia, opioid or tobacco withdrawal

Hydralazine class, MOA, use

vasodilator; incr cGMP to cause smooth muscle relaxation, vasodilates arterioles; for severe HTN and CHF

Sodium Nitroprusside class, MOA, use

vasodilator; dilates arteries and veins; for HTN emergency

Guanethedine class, MOA, use

adrenergic neuronal blocking drug; stim NE release from postsynaptic nerve ends then enhances reuptake, also blocks adrenoreceptors; used formerly for HTN, but can be used w/ Grave's to narrow palpebral fissure & elim "stare"

What three main classes are used to Tx CHF?

Beta-blockers (decr HR to allow more blood in heart)
ACE inhibitors
Diuretics

Digitalis class, MOA, use, ADEs

aka Digoxin; cardiac glycoside; *inhibits Na/K ATPase enzyme leading to incr Ca in cells (neg inotrope), parasymp effects leading to decr HR (decr AV conduction); used for CHF, atrial fibrillation

ADEs (ocular) = B/Y color defects, pain on eye mvt

Antiarrhythmic drug classes?

Class 1 = Na channel blockers
Class 2 = Beta blockers
Class 3 = K+ channel blockers
Class 4 = Ca channel blockers

"No Bears Kiss Cats"

Procainamide and Qunidine are used as...

Antiarrhythmics (Class IA, Na Channel Blockers)

Lidocaine class, MOA, use

Na Channel Blocker (Antiarrhythmic Class IB), blocks Na channels (open and deactivated thus better effect on unhealthy depolarized tissue); for ventricular tachycardias and arrhythmias after MIs

Amiodarone class, MOA, use, ADEs

K channel blocker (Antiarrhythmic class III)

*ADEs = fatal pulmonary toxicity, thyroid dysfxn, OPTIC NEUROPATHY (vision loss), WHORL KERATOPATHY