pharmacology - drug charts

Drug Charts

� Eicosanoids

� NSAIDs

� Immunopharmacology

� Adrenergic Agonists

� Adrenergic Antagonists

� PsNS Agents

� Anti-Hypertensives

� Antibiotics

� Cancer Drugs

� Movement Disorders

� Anti-Convulsants

� Anxiolytics

� Anti-Psychotics

� Anti-Depressants

� Alcoholism

� Opioids

� General Anesthetics

� Local Anesthetics

� GI Drugs

� Anti-Virals

� Anti-Virals: HIV

� Anti-Arrhythmics

� Cardiotonics

� Diuretics

� Alternative Medications

� Pituitary Hormones

� Estrogens/Progestins

� Thyroid/Parathyroid/Adrenal Hormones

� Anti-Malarials

� Anti-Parasitics

� Pulmonary Drugs

� Caloric Regulation

� Diabetes Drugs

� Lipid Drugs

� Dermatology Drugs

� Gout Drugs

S. Carr

Drug Eye Clotting Vasculature Lungs GI Reproductive Organs CNS TreatsPGI

↓ plt aggregationvasodilation

(↑ cAMP)

bronchodilation

(↑ cAMP)

↓ acid, ↑ mucus,

↑ blood↓ tone

Kidney: ↑ blood,

↑ diuresis

Primary pulmonary

HTN

PGE1 ↓ intraocular

pressure↓ plt aggregation

vasodilation

(↑ cAMP)

bronchodilation

(↑ cAMP)


↑ blood↓ tone

Kidney: ↑ blood,

↑ diuresis, ↓ ADH

↑ body temp

↓ NE

Misoprostol

AlprostadilPGE2 ↓ intraocular

pressure↓ plt aggregation

vasodil + vasocx

(↑ IP3 & ↑ Ca2+)

bronchodilation

(↑ cAMP)


↑ blood

↓ tone

(+ ↑ oxy CX)

Kidney: ↑ blood,

↑ diuresis, ↓ ADH

↑ body temp

↓ NEDinoprostone

PGF2α ↓ intraocular

pressure

vasocx

(↑ IP3 & ↑ Ca2+)

bronchocx

(↑ IP3 & ↑ Ca2+)

↑ CX

(↑ oxytocin)

Latanoprost

CarboprostTXA

↑ plt aggregationvasocx

(↑ IP3 & ↑ Ca2+)

bronchocx

(↑ IP3 & ↑ Ca2+) ↑ CX

Kidney: ↓ blood

LTC ↑ permeability

(↓ BP)

bronchocx

(↑ IP3 & ↑ Ca2+)

LTD ↑ permeability

(↓ BP)

bronchocx

(↑ IP3 & ↑ Ca2+)

Epoprostenol (PGI)

Treprostinil

vasodilation

(↑ cAMP)

Primary pulmonary

HTN

Misoprostol

(PGE1)


↑ blood

↑ CX

(↑ oxytocin)

NSAID-ulcer

Abortifacient

Alprostadil

(PGE1)

vasodilation

(↑ cAMP)

Impotence

Maintain PDA

Dinoprostone

(PGE2)

↑ CX

(↑ oxytocin)

Abortifacient

Labor induction

Latanoprost

(PDF2 α)

↓ intraocular

pressure

Open angle

glaucoma

Carboprost

(PGF2 α)

↑ CX

(↑ oxytocin)Abortifacient

Zileuton

(↓lipoxygenase)

bronchodilation

(blocks LT synth)Asthma

Zafirlukast (↓LTR)

Montelukast

bronchodilation

(blocks LT synth)Asthma

Indomethacin

(COX inh.)

vasocx

(↓ PG synth)Close PDA

(administered vaginally, uterine contractions & ↑ collagenase activity)

(GI = cytoprotective at low doses, ↓ acid at high doses) (during pregnancy = dinoprostone)

(male = erection injection)

(stable, long acting, SE: brown pigmentation, dry eyes)

(administered vaginally, uterine contractions & ↑ collagenase activity)

Zileuton

Zafirlukast

Montelukast

(NSAID indole derivative)

(Epopro = IV / Trepro = subQ)

(vasculature = vasodilates to maintain PDA until surgical correction)

(vasculature = vasoconstricts to close PDA in premies)

(vasculature = vasodilates to relieve pulmonary HTN)

(inhibits leukotrienes)

(blocks leukotriene receptors)

Drug Inhibits Metabolism Duration What Makes it Unique Side Effects Treats

Aspirin COX-1

COX-2

Low = 15 min

High = 4 h

↑ High = 13 h

1) binds serum proteins (depends on dose)

2) irreversibly acetylates COX-1&2, 3)

irreversibly inhibits platelet aggregation

1) salicylism, respirary alkalosis, met. acid

2) NSAID-asthma

3) Reyes syndome

RA

Chronic inflm

Non-acetylated

salicylates

COX-1

COX-2Less effective at COX inhibition than ASA

Less side effects, no renal toxicity,

no NSAID-asthma

RA

Chronic inflm

Ibuprofen COX-1

COX-2

Liver

CYP2C8

Short

(2hr)

Low dose = analgesic (no anti-inflam)

High dose = analgesic & anti-inflam

GI, rash, tinnitis, fluid retention

kidney failure, hepatitis

RA

Chronic inflm

Diclofenac COX-1

COX-2

Liver

CYP3A4

CYP2C9

Short

(2hr)

1)↑ serum aminotransferase activity in liver

2) Renal dysfx doesn't impair clearanceTypical NSAID

RA

Chronic inflm

Etodolac COX-1

COX-2

Intermediate

(5 hr)Affects COX-2 > COX-1 by 10:1 Less GI

RA

Chronic inflm

Indomethacin COX-1

COX-2Very potent indole derivative

30% have to discontinue

(psychosis & hallucination)

RA

Chronic inflm

Ketoprofen COX-1

COX-2

1) Short (2 hr)

2) Slow releaseAlso inhibits lipoxygenase Typical NSAID

RA

Chronic inflm

Naproxen COX-1

COX-2

Long

(12 hr)Free fraction is 40% higher in females Typical NSAID

RA

Chronic inflm

Sulindac COX-1

COX-2

Long

(12 hr)

1) ↑ serum aminotransferases

2) Treats familial intestinal polyposisCholestatic liver damage

RA

Chronic inflm

CelecoxibCOX-2

1) Least potent of COX-2 inhibitors

2) Does not affect platelet aggregation

Can interfere w/antihypertensive therapy

Still contraindicated in pts w/GI ulcers

RA

Chronic inflm

Rofecoxib

ValdecoxibCOX-2 Most COX-2 selective → CV problems Still contraindicated in pts w/GI ulcers

RA

Chronic inflm

Acetaminophen COX-1

COX-2

1) COX inhibitory effects primarily in CNS

2) Best anti-pyretic/analgesic in children

3) No anti-inflammatory or anti-coagulant

1) Less GI irritation & bleeding

2) Liver toxicity (↓ glutathione)

RA

Chronic inflm

NSAID EffectsAnalgesia

(low grade pain)

Anti-pyretic

(PG inhibition)

Anti-inflamatory

(MSK, RA, OA)

Anti-coagulant

(other NSAIDs can block long-lasting ASA)

COX-2 Pro-coagulant

(↓ COX-2 PGI but not COX-1 TXA)

NSAID Side EffectsGI irritation

(ASA espclly)

↑ bleeding time

(inhib. TXA)Kidney effects

Pregnancy

(delayed onset of labor from ↓ PGE & PGF)

Hypersensitivity

(↓ COX → arachidonate → ↑ lipoxygenase)

Drug Action Response What Makes it Unique Treats

Prednisone

PrednisoloneDown-regulate inflammation

Immunosuppression

Anti-inflammatory

Chronic use associated with: ↑infections, ulcers,

hyperglycemia, osteoporosis

Autoimmune disease

Transplantation inflm

Hypersensitivity

Cyclosporine

Tacrolimus

Inhibits calcineurin phosphatase

→ ↓ cytokinesImpairs T-cell response to antigen Tacrolimus is 100x more potent

GVHD (bone marrow trxpnt)

Aplastic anemia (ineligible)

Autoimmune disease

Sirolimus Inhibits T-cell activation

& proliferation↓ T-cell response

Renal transplant have surgical complications

May produce an immunosupp tolerance

Transplant rejection

GVHD

Autoimmune disease

AzathioprineConverted to thioinosinate

Competitive inhibition of inosinate

S phase inhibitor

Myelosuppression

Coadministration w/allopurinol is toxic

Transplant rejection

Rheumatoid arthritis

Mycophenolate Inhibits inosine monophosphate

dehydrogenase

Inhibits T-cell & B-cell cell cycle &

proliferation

Coadminister: cyclosporine & corticosteroids

Do not coadminister: antacidsTransplant rejection

FTY720Sphingosine 1-P receptor agonist

Reversibly sequesters lymphocytes in

2° lymph organs

Graft is protected from T-cell attack

↑ HR in 30% of patientsTransplant rejection

Antithymocyte IgIg against T-cells Removes T-cells from system Coadminister: azathioprine & corticosteroids Transplant rejection (kidney)

Immune globulinHuman plasma Ig Replaces missing Ig Toxicity: autoimmune hemolytic anemia

Immunodeficiencies

Lymphocytic leukemia

Kawasake disease

Anti-CD3 IgIg against CD3 on T-cells Blocks antigen recognition site Toxicity: cytokine release syndrome Transplant rejection

Basiliximab

DaclizumabIg against IL-2 receptor Blocks activation of T-cells by IL-2

Coadminister: cyclosporine & corticosteroids

Toxicity: none!Transplant rejection (kidney)

Infliximab

EtanerceptIg against TNF-α Blocks immune activation of TNF Coadminister: methotrexate for RA

Rheumatoid arthritis

Crohn's disease

Rho Immune IgIg against anti-D antibodies Blocks anti-Rh antibodies

Administered to Rh- mother pregnant with Rh+

fetus

Hemolytic disease of the

newborn (prevention)

Bacillis Calmette-

GuerinStrain of myobacterium bovis Stimulates T-cells & NK cells Toxicity: severe hypersensitivity & shock Bladder cancer

Thymic FactorsPromotes T-cell differentiation Enhanced T-lymphocytic function Stem cells rushed through boot camp SCID

Interleukin-2 Promotes T & B-cell proliferation,

differentiation↑T-cells, ↑B-cells, ↑NK cells Natural cytokine

AIDS

Cancer

GM-CSF

G-CSFStimulates clonal expansion

↑ WBC recovery

in pts with ↓ hematopoiesisNatural cytokine

Cancer

Congenital

T-c

ell

Inh

ibito

rC

yto

toxic

Imm

unoglo

bulin

sB

iolo

gic

al R

esp

on

se

Mo

difie

rs

Drug Receptors Heart Vasculature Lungs GI Reproductive Organs Treatsα1 [high] Reflex bradycardia ↑ DBP (↓ MSK) ↑ uterine CX

α2 [high] ↓ ACh (α2A)

β1 [low] ↑HR, ↑CX, ↑CO ↑ SBP (indirect) ↓ motility

β2 [low] ↓ DBP (↑ MSK) bronchodilation ↓ motility ↓ uterine CX

Phenylephrine α1 Reflex bradycardia ↑DBP & ↑SBP Nasal deconges.

Levarterenol Shock

α1 Reflex bradycardia ↑ DBP (vasocx)

α2

β1 ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin

D1 [low] vasodilation

β1 [high] ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin

α1 [↑ high] ↑ DBP (vasocx)

Amphetamine Narcolepsy

α1


β2

α1

α2 ↓ SNS outflow ↓ BP

α1 Reflex bradycardia ↑ DBP (vasocx)


α1

α2

β1

Ephedrine

Clonidine α2 ↓ SNS outflow ↓ BP HTN

Brimonidine α2 ↓ SNS outflow ↓ BP OA glaucoma

Tizanidine α2 ↓ SNS outflow Multiple sclerosis


β2 ↓ cardiac efficiency ↓DBP vasodilation bronchodilation ↓ motility

α1 [high] ↑ cardiac efficiency ↑ DBP (vasocx)

β1 [low] ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin

Metaproterenol β2 M = medium bronchodilation Bronchospasm

Salmeterol β2 S = steroid & slow bronchodilation Bronchospasm

Formoterol β2 F = fast bronchodilation Bronchospasm

Terbutaline β2 T = tachycardia bronchodilation Bronchospasm

Albuterol β2 A = acute bronchodilation BronchospasmShort-acting (inhalation) acute relief

(Experimental)

Initially potentiates NE effects, then eventually depletes NE

Medium duration (oral administration)

Long-lasting (inhalation) must be accompanied by steroid

Long-lasting (inhalation) fast-acting

Minimal tachycardia

Bronchodilator

Cardiac arrest

Decompensated

heart failure

Depletes NE in the SNS (but does not cross the BBB)

1) displaces NE from vesicles….2) competitively inhibts NE reuptake….3) inhibits MAO activity → NE lingers (acts like amphetamine)

↓ humor production & ↑ uveoscleral outflow

↓ MSK spasticity

If MAO inhib: 1) displaces NE from vesicles, 2) competes w/NE for reuptake

1) shock caused by

↓ CO & ↓ renal fxn

2) Parkinson's

HTN during

pregnancy

Asthma

Anaphylaxis

Cardiac arrest

1) displaces NE from vesicles….2) competitively inhibts NE reuptake….3) inhibits MAO activity → NE lingers

similar to EPI…potent vasoconstrictor used to treat hypotension & shock

↓ mucus congestion Eye: ↓ intraocular

pressure

Metabolism: ↑

some activity, but less effective than NE SE: hepatotoxicity & autoimmune hemolytic anemia

Epinephrine

Norepinephrine

Dopamine

Arbutamine

Dobutamine

α-methyl-DOPA

Tyramine

Guanethidine

Isoproterenol

Drug Receptors Heart Vasculature Lungs GI Reproductive Organs Treatsα-methyl-paratyrosine

Reserpine

Cocaine

Anti α1 Reflex tachycardia ↓ vasocx

Anti α2 ↑ SNS outflow

Anti α1

Anti β1

Anti β2

Anti α1 Reflex tachycardia ↓ vasocx smooth muscle RX

Anti α2B Reflex tachycardia ↓ vasocx

Tamsulosin Anti α1A Reflex tachycardia ↓ vasocx Hypertension

Alfuzosin Anti α1 smooth muscle RX BPH

Yohimbine Anti α2 Male impotence

Anti β1 ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin

Anti β2 bronchocx

Anti β1 [low] ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin

Anti β2 [high] bronchocx

Atenolol Anti β1 ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin Hypertension

Acebutolol Anti β1 ↓HR, ↓CX, ↓CO ↓SBP Hypertension


Anti β2 bronchocx


Anti β2 bronchocx


Anti β2 bronchocx

Carbachol ACh musc OA glaucoma

Pilocarpine ACh musc OA glaucoma

Physostigmine AChE inhib OA glaucoma

Echothiophate AChE inhib OA glaucoma

Brimonidine α2 OA glaucoma

Latanoprost PDF2α OA glaucoma

β1 specific, partial agonist → less exercise intolerance

Inhibits aqueous humor production

Enhance uveoscleral outflow

Ciliary muscle CX → widens trabecular network → ↑ drainage of aqueous humor




Long-lasting, specific, reduced CNS activity, no bronchocx

↓ intraocular pressure w/o affecting pupil or ciliary body

anti-arrhythmic, anti-atrial fibrillation

Heart failure

Hypertension

BPH

Hypertension

Migraine

Hypertension

Open angle

glaucoma

Hypertension

Arrhythmia

Atrial fibrillation

competitive inhibitor of tyrosine hydroxylase → depletes NE, EPI, DA pre-operatively in pheochromocytoma

binds VMAT-2 irreversibly inhibits vesicular concentration of NE & DA → transient ↑ at receptors → SNS depletion

reversibly inhibits NET & DAT (CNS) → anesthetic, CNS stimulant, sympathomimetic

PheochromocytomaPhenoxybenzamine

Carvedilol

Prazosin

Propranolol

Metoprolol

Timolol

Labetalol

Sotalol

Drug Mechanism Heart Vasculature Lungs GI GU Organs Treats

Bethanechol

Carbachol

Choline Ester

PsNS agonist

M1, M2, M3

M2

[Lo] = reflx tach

[Hi] = AV block

M3

vasodil (B & C)

↑ secretions

bronchoCX

M1

↑ motility (B)

↑ secretions

M1

Detrussor CX

(B & C)

Eye : M1

Circular M. CX

Ciliary M. CX

C: OA glaucma

B: GI/GU retentn

PilocarpineNatural alkaloid

M1, M2, M3

AtropineMuscarinic blockade

(M1, M2, M3)

M2 (ant)

[Lo] = brady

[Normal] = ↑ HR

ScopalamineMuscarinic blockade

(M1, M2, M3)

M2 (ant)

[Lo] = ↑brady

[Hi] = ↑ HR

Pirenzepine M1 antagonist Gastric ulcer

Tolterodine

Trospium

Oxybutynin

Anti-muscarinicOveractive

bladder

Ipratropium

Tiotropium

EdrophoniumReversible ChE

inhibitor

Diagnosis of MG

PAT

PhysostigmineAtropine toxicity

(crosses BBB)

NeostigmineParalytic ileus

Treatment of MG

Xerostomia

PralidoximeReverses ChEI

toxicity

Tacrine

Donepezil

TubocurarineNm (ant)

↑ HR

(↓PsNS + rx tach)

Nm (ant)

↓ BP

(↓SNS + hstmne)

Resp. paralysis

BronchoCX

(histamine)

Mivacurium

Vecuronium

Rocuronium

Isoquinoline

competitive NMJ

blocker (NmX)

SuccinylcholineDepolarizing NMJ

blocker

(↑ open freq. & dur.)

Nn

↓ HR

(↑PsNS + rx brad)

Nn

↑ BP

(↑SNS)

Resp. paralysis

Slight histamine

Ganglion blockersCompetitive /

Depolarizing Nn

blockers

Nn (ant)

↑ HR (PsNS)

↓ CX (SNS)

Nn (ant)

↓ BP

Nn (ant)

↓ motility ↓ secr

(PsNS)

Nn (ant)

Urinary reten

♂ impotence

Eye : mydriasis

Skin : ↓ sweat

Surg: ↓ bleeding

SCI: ↑ reflexia

Botulinum toxinPrevent ACh release

from the motor nerve

terminal

Dystonia

Spasticity

Hyperhidrosis

VareniclinePartial nicotine agonist

at α4β2 NnNicotine addictionMay help prevent rewarding aspects of nicotine administration

↓ cardiac effects (less tachycardia)...↑ histamine release (more bronchoCX)

↑ cardiac effects (more tachycardia)...↓ histamine release (less bronchoCX)

w/halothane + RyR defect → malig. Hyperthermia

(give sodium dantrolene)

Alzheimer's

disease

↑ AChE selectivity in CNS (minimal peripheral activity)…no hepatotoxicity

Irreversible ChE

inhibitor

(phosphorylate ChE)

Cleaves synaptobrevin & SNAP to prevent ACh vesicle fusion & release

Echothiophate

DFP

Malathion

Parathion

Soman

Steroid nucleus

competitive NMJ

blocker (NmX)Used during

procedures that

require muscle

paralysis

Drug intrx: aminoglycosides & tetracyclines

Contraind.: asthma, MG

Eye : M1

Circular M. CX

Ciliary M. CX

~

Skel Muscle :

Nm

↓

fasciculations

~

CNS :

Stimulation

↓

depression

Caused by

exposure to

toxins

*Atropine can

reverse

*Pralidoxime can

reverse

Splits covalent bond → forming oxime-phosphonate → splits off → leaves regenerated ChE

Also: (1) blocks DA, NE, 5-HT uptake (2) MAO inhibitor (3) block Na+ & K+ channels…hepatotoxicityNon-competitive

reversible ChE inhib.

(centrally-acting)

Reversible ChE

inhibitor (competitive)

Physo : block nACh?

M3

NO-cGMP

↓

vasodil

M1

↑ motility

↑ secretions

M1

Detrussor CX

Trigone RX

Ex. sphincter RX

↓

micturition

↑ secretions

bronchoCX

Direct:

M2

↓HR

Indirect:

M3

vasodil

↓

reflex tachy

GI spasms

Eye exams

ChEI toxicity

Anesth adjunct

Motion sickness

Overax bladder

Used w/H-2 blockers to reduce gastric acid secretion to promote gastric ulcer healing

Muscarinic blockade

(M1, M2, M3)

[No ↓ cilia motility]

COPD↓ secretions

bronchodil

Neuro

muscula

r Junction B

lockers

(nA

ChR

)C

holin

om

imetics

Treats OA glaucoma: (1) pupillary CX, (2) spasm of accom., (3) transient ↑ IOP → persistent ↓ IOP, (4) impaired night vision

Para

sym

path

etic A

nta

gonis

tsC

holin

este

rase I

nhib

itors

M3 (ant)

vasocx

Eye: M1 (ant)

Circular M. RX

Ciliary M. RX

M1 (ant)

↓ motility

↓ secretions

↓ secretions

bronchodil

M1 (ant)

Detrussor RX

Urine retention

Drug Mechanism Duration Renin What Makes it Unique Side Effects Treats

Guanethidine

Reserpine

Depletes NE

↓ SNS

Long lasting

w/residual

Initial: ↓

Eventual: ↑

Reserpine: central depletion of 5-HT, DA,

NE…Parkinsonism & depression

Nasal cong, ortho hypo, miosis, brady,

diarrhea, cramps, ♂ impHTN (?)

α-methyl DOPA Stimulate NTS

α2 receptors

Post-syn α2A

↑ NTS → ↓ SNS

Initial: ↓

Eventual: ?

Metabolized to α-methyl NE (false NT) and

acts mostly α2, little α1 centrally

Common…+...hemolytic anemia,

sedation, ♂ imp, ↑ lactation, EP signs

Moderate HTN

(LVH)

Clonidine Stimulate NTS

α2 receptors

Initial: ↓

Eventual: ~No DA problems (↑ lactation, EP signs) Less ortho hypo, rebound W/D HTN HTN (?)

Hydralazine ↑ NO

↑ K+ permeability

Initial: ↑

Eventual: ?Can produce a lupus-like syndrome

Tachycardia, fluid retention, edema,

headache, nauseaSevere HTN

Minoxidil ↑ K+ permeability

Initial: ↑

Eventual: ?

Preference for resistance (over capacitance)

vessels….↓ venous pooling

Same as hydralazine

(should use w/β-blocker & diuretic)

Severe HTN

w/ renal disease

Sodium

nitroprusside

Metabolized to NO

↑ cGMPVery short

Initial: ↑

Eventual: ?

Unstable: degrades → thiocyanate & CN

IV only: moment to moment controlNausea & headache HTN Crisis!

Th

iazid

e

Diu

retic Hydrochlorothiazide

Chlorthalidone

↓ Na+ reabsorption

in DCT → ↑ urine

Initial: ↑

Eventual: ~Ceiling effect of 15 mmHg

Hypokalemia, hyperglycemia,

hyperuricemia, ↑ chol & ↑ TAGMild HTN

K+

Sp

ari

ng

Diu

retic Amiloride

Spironolactone

Aldosterone

antagonist

Initial: ?

Eventual: ?

Used with thiazide diuretic to avoid

hypokalemia

Hyperkalemia (in renal disease)

Gynecomastia

Not anti-HTN by

themselves…

ProproanololInitial: ↓

Mild-Moderate

HTN

AtenololInitial: ↓

Mild-Moderate

HTN

Acebutolol Same as above

(+ partial agonist)Initial: ↓

Partial agonist activity:

less ↓ HDL & less exercise intolerance

Mild-Moderate

HTN

Labetalolα1/β1/β2 blocker Initial: ↓ HTN Crisis!

α1

Anta

g Prazosin Block α1

(& some α2B)t1/2 = 3-4 hr Initial: ↑ Could cause cardiac events

Syncope (initial trx), ortho hypo,

tachycardia, headache, depression

Mild-Moderate

HTN

Captopril

Enalapril

Prevent A1 → A2

conversion

(ACE inhibitors)

Short

Long (prodrug)

Initial: ?

Eventual: ?

Also inhibit bradykinin metabolism

…leads to PGI2 production → cough

Good in diabetics (renal)/CHF

Moderate HTN

(LVH)

Losartan Vasculature A-2

receptor blocker

Initial: ?

Eventual: ?Similar to ACE inhib. but no cough HTN (?)

Nifedipine DHP Ca2+

channel blocker

Initial: ?

Eventual: ?Good vasodilation w/ less cardiodepression

Reflex tachycardia

Adverse cardiac events

Verapamil L-type Ca2+ channel

blocker

Initial: ?

Eventual: ? Cardiodepression: ↓ HR & ↓ CO

Little reflex tachycardia


Diltiazem Ca2+ channel

blocker

Initial: ?

Eventual: ?Similar to Verapamil…but less ↓ HR & ↓ CO

Little reflex tachycardia


PD

E5

inhib Sildenafil PDE-5 inhibitor

→ ↑ cGMP

Initial: ?

Eventual: ?

Requires ACh to initiate process:

M3 → NOS → GMP cyclase → ↑ cGMP

Rx interaction: (in cardiac pts)

Nitrates → ↑ NO → hypotension

♂ impotence

Pulm. Art. HTN

SN

S I

nhib

itors

Direct

on V

SM

β B

lockers

Renin

-

Angio

tensin

Inhib

itors

HTN (?)

(Not first-line)

Ca

2+

Ch

an

ne

l B

locke

rs

↓ CX, ↓ CO, ↓ renin

↓ pre-syn. (+) fdbk

Recommended use: w/ CHF or angina

NSAIDs interfere w/anti-HTN effect

↓ Heart, bronchial CX, hypoglycemia,

W/D rebound, exercise intol.

↑ TAG & ↓ HDL

Cough, rash, leukopenia, renal,

ageusia, fetal ab, no ortho hypo,

K+ diuretic, BC, NSAID, lithium intaxn

Hypotension in volume-depleted pts

Less effective in Afr.Americans

Should use

long-acting

(short acting → ↑

toxicities)

Drug Action Resistance Pharmacodynamics Adverse Reactions

Ciprofloxacin

Levofloxacin

Rifampin Inhibit RNA polymerase

(Bactericidal)Target site mutation in rpoB subunit

Administer: oral or IV

Distribution: great, CNS, intracellular

Liver problems, induces cyt p450

(HIV meds), turns fluids orange

Metronidazole Produces compounds

toxic to DNA(Rare, unknown mechanisms)


Distribution: great, CNS

↓ elimination of lithium & ergot

derivatives...(no alcohol!)

Sulfanilamide PABA analog that binds DHP

synthetase → ↓ folic acid

Trimethoprim DHF acid analog that binds DNF

acid reductase → ↓ folic acid

Dapsone PABA analog that binds DHP

synthetase → ↓ folic acid

Penicillin G/V

Artificial penicillin

Ticaricillin-

Clavulanic Acid

Amoxicillin-

Clavulanic Acid

Piperacillin-

Tazobactam

Ampicillin-Sulbactam

Gly

co

peptide Vancomycin Binds D-alanine dimer in cross-

linking peptide in peptidoglycan

Transposon: enzymes use D-serine or

D-lactate to make cell wall

Administer: IV

Distribution: good, CNS (inflam.)

Red man syndrome: histamine

mediated w/rapid IV admin.

Poly

peptide Bacitracin Binds membrane lipid carrier

molecule → ↓ cell wall comp.

Administer: topical

(often w/neomycin & polymyxin B)Allergy (rare)

Cephalexin

Cefotaxime

Ceftazidime

Ceftriaxone

Mono

bacta

m Aztreonam Bind transpeptidase & prevent

cross-linking

No PCN-allergy cross-

hypersensitivity

Carb

a

penem Imipenem-Cilastatin

Ertapenem

Bind transpeptidase & prevent

cross-linking

Cilastatin = inhibits renal

dihydropeptidase I to prolong t1/2

Allergy

(PCN-allergy cross-hypersen.)


cross-linking

Allergy

(5-10% PCN-allergy cross-

hypersensitivity)


cross-linking

1) Altered transpeptidases

2) ↓ permeability

3) β-lactamases


Distribution: good bioavailability

Crosses BBB

Allergy

(Can be desensitized)

1) Bind transpeptidase & prevent

cross-linking

2) Bind & inhibit β-lactamase

1) Altered transpeptidases

2) ↓ permeability

3) β-lactamases


Distribution: good bioavailability

Crosses BBB

Allergy

(Can be desensitized)


Sulfa & trimethoprim given together

(TMX-SMX = Bactrim)

Sulfa given w/silver ions in cream

Target site mutation, up-regulation,

new genes, altered uptake/efflux

(Plasmid/Chromosomal)

Allergy

Not given to: G6P or folic acid

deficiency, or pregnant

HIV: prophylaxis → neutropenia &

exfoliative dermatitis

Inhibit DNA gyrase & topo IV

(Bactericidal)

1) Target modification

2) Altered uptake/efflux

3) Plasmid-mediated modification by

quinolone transacetylase


Drug Intrxn: antacids ↓ oral avail.

Arthopathy (no preg or children)

QT interval prolongation

Inhib

itors

of N

ucle

ic A

cid

Synth

esis

Cephalo

sporins

Inhib

itors

of th

e B

acte

rial C

ell

Wall

Flu

oro

qu

ino

lon

es

Sulfa

Dru

gs

Penic

illin

s

Penic

illin

s

w/β

-lacta

mase

inhib

itors

Drug Action Resistance Pharmacodynamics Adverse Reactions

Streptomycin

Neomycin

Gentamycin

Tobramycin

Tetracycline

Doxycycline

TigecyclineNot affected by resistance

ErythromycinMore nausea & ↑ QT prolongation

Azithromycin

Clarithromycin

TelithromycinSevere hepatotoxicity

Lin

co

sam

ide Clindamycin Block protein synthesis by bacterial

ribosomes

1) rRNA methylation/adenylation

2) altered ribosomal proteins

Administer: oral or IV or topical

Distribution: good, but no CNSAllergy

Oxazoli

din

one Linezolid Block protein synthesis by bacterial

ribosomes


Distribution: good

Thrombocytopenia

Contraindication: SSRI

Chloramphenicol Block protein synthesis by bacterial

ribosomes

1) acetylation (most common )

2) efflux pumpingAdminister: oral or IV

Aplastic anemia, BM suppression

Gray syndrome (shock, coma)

Str

epto

gra

min Quinupristin-

Dalfopristin

Block protein synthesis by bacterial

ribosomesOccurs if only one of the two is given Administer: IV

Arthralgias

Myalgias

PolymyxinsDisrupts bacterial membranes

Administer: Topical or IM or IV

(often w/neomycin & bacitracin)Few

Daptomycin Cyclic lipopeptide: interferes

w/bacterial membraneAdminister: IV

↑ liver fx tests

muscle weakness & pain (↑CPK)

Nitrofurantoin Radiomimetic

(IC enzymatic redctn required)Altered levels of reduction enzymes

Administer: oral

(drug concentrated in urine)

Turns urine brown

Lung problems w/chronic use

MupirocinDisrupts protein synthesis

Mis

cella

neous

Nephrotoxicity

Ototoxicity

(Particularly Streptomycin)


ribosomes


ribosomes

1) Efflux pumping (most common )

2) Altered ribosome bindingAdminister: oral or IV

Distribution: good, including CNS

Drug Intx: food → ↓ absorption

Antagonizes β-lactams

Nausea

Photosensitivity

Can discolor teeth

(not given to children or pregnant)

1) Methylation of ribosomes

(most common )

2) Efflux pumping


Distribution: good

Azithromycin: long intracellular

half-life, given to children, pregnant

1) Block protein synthesis by

bacterial ribosomes

2) Disrupt magnesium bridges in

LPS

1) Modifying enzymes (most com .)

2) Efflux pumping

3) Altered ribosome binding

Administer: IM or IV

Post-ABX Effect: persistent

suppression after drug removal

Conc.-Dependent Killing:

↑ concentrations → better killing

Inhib

itors

of B

acte

rial P

rote

in S

ynth

esis

Tetr

acyclin

es

Macro

lides

Am

inogly

cosid

es

Drug MOA Treats Toxicity What Makes it Unique Mnemonic

MechlorethamineHodgkin lymphoma

Bone marrow

GI

Interesting N-(CH2-CH2-Cl)2

structure activates to ring

Cyclophosphamide

Ifosfamide

Non-Hodgkin Lymphoma

Breast/Ovary Carcinoma

Bone marrow (immunosupp)

Alopecia

Hemorrhagic cystitis

Acrolein byproduct toxic but

rescued by MESNA

Tall lean cyclist has bladder

problems & needs a mens

room!

Carmustine

Lomustine↑ lipophilic → crosses BBB Brain tumors


Nephrotoxicity (long-term trx)

We must preserve the brain

to maintain life!

StreptozocinInhibits DNA synthesis

Pancreatic islet cell

carcinoma

Insulin shock

Nephrotoxicity

Hepatotoxicity

Retained in β cells of islets of

Langerhans

BusulfanCML Pulmonary fibrosis

Dacarbazine

Temozolomide

Active metabolite monomethyl triazeno

methylates DNA

Dcarb: Hodgkin lymphoma

Temozo: malignant glioma


Nausea

ProcarbazineInhibits DNA/RNA/protein synthesis

Hodgkin/Non lymphoma

SCLC, Melanoma

Brain tumors


Neurotoxic & leukemia

Contraindx: EtOH/Drugs

Drinking, driving, & drugs

don't mix!

Cis-platinum

Carboplatin

Forms intrastrand & interstrand DNA

cross-links → ↓ DNA/RNA synthesis

Produces DNA breaks

CURES: testicular tumor

Ovarian cancer

Also: SCLC & bladder CA

Ototoxicity

Nephrotoxicity

Electrolyte disturbances

Testes & ovaries are

precious, & platinum is a

precious metal!

Oxaliplatin Forms platinum-DNA cross-links →

↓ DNA synthesis

Colorectal cancer (malig.)

Ovarian cancer (adv.)


Nausea/diarrhea/fatigue

Neurotoxicity (glutathione helps)

CRC: w/5-FU & Leucovorin

Ovary C: w/Cisplatin & Paclitaxel

Good for ovaries & your

o-ring

Methotrexate Inhibits DHFR → ↓ thymidylate, ↓

purines, ↓ methionine, ↓ serine

CURES: osteosarcoma &

choriocarcinoma

ALL, Burkitt's, Non-H, Blad


GI

Nephro & Hepatotoxicity

Develops resistance via DHFR ,

transport, MPs

Also treats RA & psoriasis

Luke to the rescue

(meth lab)!

6-Mercaptopurine Converted to 6-MPRP by HGPRT →

↓ purine synthesisALL


6-MP can → gout (give Allopurinol)

Thiopurine methyltransferase

mutation → ↓ 6-MP metabolismMP controls ALL

6-Thioguanine Converted to nucleotide → inhibits

PRPP amidotrx → ↓ DNA synthesis

Fludarabine Unnatureal purine → incorporated into

DNA & RNA → ↓ synthesis & ↓ function

Pentostatin

5-Fluorouracil Converted to 5FdUMP →

↓ thymidylate synthetase →

↓ TMP → ↓ DNA synthesis

Breast cancer

Colorectal cancer

Basal cell carcinoma


GI

Mod: Cispt/IFN/Luke/MTX/PALA/Uridine

Patients on Cimetidine have

↑ survival rate

Cytarabine Converted to AraCTP → incoporated

into DNA → terminates elongation

Acute leukemia

(w/6-TG)Bone marrow (immunosupp)

Gemcitabine Converted to dFdCTP → incorporated

into DNA → terminates elongation

Pancreatic cancer (1st line)

Non-SC lung cancer


Flu-like syndrome

Elevated liver enzymes (transaminases)

Not S-phase specific

Vincristine ALL (1st line)

Hodgkin/Non-H lymphoma

Acute myelo leukemia

Peripheral neuropathy

Vinocristine = treats

children

Vinocristine = Christ PN

Vinblastine CURES: testicular tumor


Choriocarcinoma

Vinoblastine = bone marrow

supp.

Vinorelbine Non-SC lung cancer (adv.)

Breast cancer (adv.)

Vinorelbine = bone marrow

supp.

Paclitaxel Promotes microtubule formation &

stabilizes the polymer

Ovarian cancer (met.)

Breast cancer (met.)

Neutropenia (give G-CSF)

Hypersensitivity (give

dexameth/diphen/H2)

Abraxane = albumin-bound Taxol

(give ↑ doses)

Etoposide Testicular cancer

Prostate cancer

Oat cell lung cancer

Etoposide = topoisomerase

II

TeniposideALL

Teniposide =

topoisomerase II

Teniposide = ten year-olds

Topotecan

Irinotecan

Inhibit topoisomerase I →

↓ DNA replication

Colorectal cancer (met.)

Ovarian cancer (met.)

SC lung cancer (adv.)


Alopecia & skin bronzing & cholinergic sx

Nausea/vomiting/diarrhea/mucositis

Topotecan =

topoisomerase I

Both "tecans" do the same

Actinomycin D CURES: Wilm's tumor

& rhabdomyosarcoma

MTX-res. Choriocarcinoma

Bone marrow (immunosupp) Flat ring structure

Doxorubicin Myeloma

Sarcoma

Lymphoma

DaunorubicinAcute leukemia

Epirubicin

PlicamycinInhibits RNA synthesis Bone cancer (met.)


Hepatotoxicity

Nephrotoxicity

Specific to osteoclasts →

↓ [Ca2+] in hypercalcemic

patients

Bleomycin Glycopeptides that bind DNA →

produce free radicals → strand breaks

Inhibits DNA ligase → ↓ DNA repair

CURES: testicular cancer

Squamous carcinoma

Lymphoma

Pneumonitis & Pulmonary fibrosis

Hyperpigmentation, alopecia, stomatitis

Bleomycin = DNA breaks

Least myelosuppressive

activity

MitomycinCross-links DNA → ↓ DNA synthesis

Cervical cancer

GI cancer (stomach/anus)

Lung cancer


Nephrotoxicity

Interstitial pneumonia

Mighty Mitomycin is the one

treating cervical cancer!

Of the Rubicin sisters, Epi is

less likely to break your

heart (she is "above"

that….Epi)!

Inhibit topoisomerase II →

↓ DNA replicationBone marrow (immunosupp)

Intercalates between GC bp → binds

DNA → ↓ DNA/RNA synthesis Bone marrow (immunosupp)

Alopecia

Cardiotoxicity

Monofx: modify DNA base

Bifx: DNA cross-link or DNA-protein

Leukemia Bone marrow (immunosupp)

Binds tubulin to ↓ polymerization into

microtubules


Alk

yla

ting A

gents

(Phase n

on-s

pecific

)

Antim

eta

bolit

es

(S p

hase s

pecific

)A

ntim

itotics

Antibio

tics

Drug MOA Treats Toxicity What Makes it Unique Mnemonic

L-asparaginase Metabolizes L-asparagine required by

tumor cells with ↓ asparagine

synthetase

ALL

Hypersensitivity, hyperglycemia,

Coagulation defects, hypoalbuminemia

…due to ↓ normal protein

Sometimes interferes w/other

drugs activityALL disparaging

Tretinoin Stimulate transcription of retinoic acid

receptor genes

CURES: Prostate cancer

Leukemia

Nasty drug….retinoic acid syndrome:

fever, wt gain, SOB, heart, photosens.,

skin, hearing, diarrhea, liver enzymes,

Can become resistant

Imatinib mesylateBinds to Bcr-Abl kinase → ↓ activity CML

Nausea, diarrhea, edema, cramps, rash

Neutropenia, thrombocytopenia

↑ [Warfarin]

Itraconz & Erythro → ↑ [IM]

Phenytoin → ↓ [IM]

Gefitinib Inhibits EGFR tyrosine kinase →

↓ cell proliferation & survivalNon-SC lung cancer

(Well tolerated!)

Diarrhea, acne-like rash

EGFR mutations correlate with

drug's efficacy

Works best in Asian non-

Asian non-smokers Get fit

without lung cancer

SunitinibInhibits VEGFR & PDGFR kinase

RCC (adv.)

GI stromal tumors

Fatigue, anorexia

Nausea, diarrhea, mucositis, stomatitis

Ketoconz → ↑ [Sunitinib]

Rifampin → ↓ [Sunitinib]

Sunni are vegetarians &

pretty darn good

Sorafenib Inhibits cell surface & intracellular

kinasesRCC (adv.)

Fatigue, diarrhea, dermatologic

Hypertension, neutropenia, bleeding

Pro

tea

som

e

Inhib

. Bortezomib Reversible 26S proteasome inhibitor →

↓ activation of NFκBMultiple myeloma

Nausea, diarrhea, anorexia, fever, weak

Neuropathy, neutropenia,

thrombocytopenia

My llama is a bore, I've had

enough (NF)!

Trastuzumab Antibody that blocks (amplified)

HER2/neu receptor → ↓ growth signalBreast cancer (met.)

Fever & chills

Cardiotoxic (if given w/Adriamycin)

Respiratory problems

HER2/neu is overexpressed in

breast cancer

Adam Trask's wife broke his

heart with her new pistol

Rituximab Antibody that blocks CD20 antigen on

B-cells → ↓ B-cells in bloodNon-H B-cell lymphoma

Fever & chills

Nausea w/first infusion

Does not deplete stem cells

(which lack CD20)

Ritu has 20 CD's which will

be selled.

Cetuximab Antibody that blocks (amplified)

EGF receptor → ↓ growth signalColorectal cancer Acne-like skin rash

EGFR is overexpressed in

colorectal cancer

Can see (C) Colorectal

cancer in situ (Cetu)

Bevacizumab Antibody that blocks VEGF → prevents

binding to endothelium → ↓

angiogenesis

Colorectal cancer (met.)Nausea, constipation, GI bleed, abd. pain

Hypertension, ↓ wound healingIn combo w/ 5-FU & leucovorin

The color of a very good

beverage

Interferons 1) Stim. 5-oligoadenylate synthetase

2) ↓ c-myc 3) ↓ protein synthesis

4) Activates nuclease degrades dsRNA

Hairy cell leukemia

Kaposi's sarcoma

Melanoma (malig.)


Fever & chills

Neurotoxicity

Antiviral activityHarry interferes and should

mellow out.

Interleukin-2 Induce T-cell response → kill tumor

cells

Melanoma (malig.)

RCC

Nausea, diarrhea, fever, ↑ liver function

Anemia, hypotension, edema, arrhythmia

Thrombocytopenia

G-CSF Induce neutrophil & granulocyte

precursor formation

Chemotherapy-induced

neutropeniaBone pain Doesn't treat cancer

GM-CSF Rescue bone marrow graft failure

Speed bone marrow graft recovery

Bone marrow

transplantation

Fever

Bone pain

Diethylstilbesterol

Ethinyl Estradiol

Block production of LH →

↓ testosteroneProstate cancer (met.)

Hypercalcemia

Vaginal carcinomas in offsprings

Prostate cancer is still the

best.

Tamoxifen

Toremifene

Binds ER → estrogen antagonist

Depletes ER, EGF, IGF-1

Breast cancer

(Post-men; in ER+ tumors)

Nausea, hot flash, rash, vag bleed, ↑ Ca

May cause endometrial cancer

↓ osteoporosis

↓ serum & LDL cholesterol

↑ apolipoprotein A1

FulvestrantBinds ER → prevents dimerization

Breast cancer

(Pre-men; in ER+ tumors)Nausea, hot flashes, pain, headaches

Indicated for pre-menopausal

breast cancer

Aminoglutethimide Inhibits aromatase & desmolase →

↓ estradiol

Breast cancer


CNS depression

(drowsiness, blurry vision, ataxia)

Post-menopause women

produce estrogen in adrenal

cortex….. Medical

Anastrozole Breast cancer


GI, weakness, headaches, bone/back

pain

Reduced incidence of blood clots

& vaginal bleeding compared to

Tamoxifen

Letrozole Breast cancer


Nausea

Musculoskeletal pain

Prednisone Converted to prednisolone → binds

receptor

ALL, CLL


Breast cancer

Cushing's syndrome

Immunosuppression

ALL pretty girls should get

phone CaLLs

Leuprolide

Goserelin

LHRH analog that initially ↑ FSH & LH

secretion → desensitization → ↓ FSH &

LH → ↓ testosterone/estrogen

Prostate cancer Sexual dysfunction Transient flare w/initial dose

(give flutamide)

A goose named Lou was

sick with the flu, but still

showed flare at the pro state

Flutamide Converted to dihydroxyflutamide →

blocks DHT binding to receptorsProstate cancer GI distress

Dwight (DHT) plays the

flute but he's still a man

The breast way to treat

Tammy, Ethyl, Anna, and

Lenny is by aromatherapy.

Inhibits aromatase → ↓ estradiolHorm

ones

Mis

ce

llan

eo

us

Tyro

sin

e K

inase Inhib

itors

Specia

lty A

ntibodie

sB

iolo

gic

al R

esp

on

se

Mo

difie

rs

Drug Mechanism Metabolism Toxicity What makes it unique Treats

Levodopa

Carbidopa

Dopamine agonist (→ DA)

L-DOPA −(AADC)→ DA

↑ DA in striatum

C-DOPA: ↓ peripheral AADC

L-DOPA → DA (AADC)

DA (MAO-B, DBH, COMT)

Periph: N/V, OH, arrhythmia

CNS: On-off, wear-off, dyskin

Psych: hallucin, delusion, sleep

Peak-Dose: grimace/writhe

Neuroleptic malignant syndrome

↑ SNS tone peripherally

N/V/anorexia via CTZ stimulation

Tubero-infund DA → ↓ prolactin

Apomorphine Dopamine agonist

Used in "frozen" cases

(Reverses "off" state)

Advanced PD on ↑ dose L-DOPA

Bromocriptine

Pergolide

B: D2 agonist / D1 antagonist

P: D2 agonist / D1 agonist

B: short half-life

P: better w/L-DOPA (D1 & lipophilic)

Bromo only works in L-DOPA Pergolide

allows ↓ L-DOPA dose

Pramipexole

RopiniroleD2 agonist

Reduce on-off in late PD

Pramipexole can delay L-DOPA by 2

years

MA

O

Inh

ibito

rs

Selegiline

DeprenylInhibits MAO-B → ↑ striatal DA

Used when L-DOPA effects are starting to

decline

An

tich

olin

erg

ic

Amantadine

Treats influenza A & hepatits C

May: alter DA release/reuptake

Block NMDA receptors

Block mACh receptors

Restlessness, agitation, insomnia,

confusion, hallucinations, OHNo effect on tremor

CO

MT

Inh

ibito

rs

Tolcapone

EntacaponeInhibits COMT → ↑ DA in cleft

Produce 2x ↑ in bioavailability & half-life

of L-DOPA Tolcapone: fatal hepatoxicity

Competes w/L-DOPA → BBB May

cause "wear-off" / "on-off"

SSRI

Anxiolytics

Butyrophenone

Phenothiazine

Reserpine Deplete DA vesicles → ↓ chorea Hypotension, depression, sedation, GI

Clonidine

Guanfacineα2 agonists Tachycardia, sweating, restlessness

Don't w/d suddenly

Improve tics in 50% of childrenTourette's Syndrome

Antipsychotics

Bromocriptine

Block DA receptors (D2)

Some 5-HT receptor blockNeuroleptic malignant syndrome

↑ dose APD helps

Balancing DA agonist helpsTardive Dyskinesia

Primidone Anticonvulsant Abuse potential Congener of phenobarbital Benign Essential Tremor

Baclofen GABA-B receptor agonistDrowsiness, loss of coordination,

confusion, nausea, seizures

Riluzole Reduces glutamate release Dizziness, GI, pain, diarrhea, weakness

Parkinson's Disease

An

ti

De

pre

ssa

nt

An

ti

Psych

otics

Help with tics

Nausea, somnolence, dry mouth, edema,

insomnia, postural/OH

Peak-dose, on-off,

depr., anxiety, hallucinations

Do

pa

min

e A

go

nis

ts

Huntington's Disease

Block 5-HT reuptake

Block DA receptors (D2)

Amyotrophic Lateral

Sclerosis

Mis

ce

llan

eo

us

Fatigue, restlessness, hyperexcitability,

tardive dyskinesia

Prolong time before tracheostomy


PhenytoinBlock Na+ channel

(prolong inactive state)

Admin: oral / IV (status epilepticus)

90% protein bound

First order (low) → Zero order (high)

Displaced by other protein-bound Rx

Acute: nystagmus, diplopia, ataxia, GI, conf.

Chronic: Gingival hyperplasia, hirsutism,

osteomalacia, rash, agranulocytosis,

megaloblastic anemia

High IV: arrhythmia, CNS depression

Congeners (mepheny/etho-toin) more toxic

Phenacemide very toxic (refractory partial)

Fosphenytoin = more soluble (injection)

↓ BC effectiveness & birth defects

Partial seizures

Gen. tonic-clonic seizures

Status epilepticus

(not absence)

CarbamazepineBlock Na+ channel


Enhance GABA activity

Induces liver microsomes

Produces active 10,11 epoxide metabolite

Acute: stupor, coma, convulsions, irritability

Chronic: diplopia, ataxia, GI, sedation, fluid reten

Major: aplastic anemia, agranulocytosis

Accelerates metabolism: phenytoin,

primadone, ethosuximide, valproate, BC

Congener (oxcarb) less toxic, less potent

Partial seizures


Trigeminal neuralgia

Bipolar Disorder

(not absence)

Phenobarbital

Block Na+ channel


Prolongs GABA-A channel activity

Block AMPA receptor

Sedation, ataxia, respiratory depression, rash,

nystagmus, porphyria, tolerance, withdrawalCongeners (mephobarbital & primidone)

Partial seizures


(not absence)

Vigabatrin Enhance GABA

LamotrigineBlock Na+ channel


May block Ca2+ channel

Headache, diplopia, rash, nausea, dizziness, ataxia Life-threatening rash in 1-2% of patients

Partial seizures

Generalized seizures

Absence seizures

Myoclonic seizures

FelbamateNMDA antagonist

Enhance GABA

Aplastic anemia

Severe hepatitis

Partial seizures

(poorly controlled)

GabapentinGABA analog

(↑ release of GABA?)Renal excretion of unchanged drug Somnolence, dizziness, ataxia No liver involvement!

Partial seizures

Neuropathic pain

Alcoholism

TopiramateBlock Na+ channel


Enhance GABA activity

Somnolence, dizziness, fatigue, cognitive slowing,

weight lossUsed for weight loss

Partial seizures


Tiagabine GABA reuptake inhibitor

Pregabalin GABA analog

Can produce euphoria

Neuropathic pain: post-herpetic neuralgia &

diabetic neuropathy

Partial seizures

Neuropathic pain

EthosuximideBlock T-type Ca2+ channel (↓ threshold)

↓ rhythmic thalamic activity

Good absorption orally (stomach irritation)

75% liver metabolizedGI, lethargy, fatigue, rash, bone marrow suppression Phensuximide & methsuximide not as good Absence seizures

Valproic Acid

Block Na+ channel


↑ GABA (↑ GAD) ↓GABA-T activity

Block T-type Ca2+ channel

Well absorbed

90% protein bound

Liver metabolized

Nausea, vomiting, GI, hepatotoxicity, birth defects,

Sedation (w/phenobarbital)

Preferred over ethosuximide if absence +

generalized tonic-clonic seizures

Absence seizures

Myoclonic seizures

Atonic seizures

Partial seizures

Diazepam Status epilepticus

Clonazepam Sedation, tolerance, withdrawal

Absence seizures

Myoclonic seizures

Infantile spasms

Pa

rtia

l &

Ge

ne

raliz

ed

To

nic

-Clo

nic

Se

izu

res

Ge

ne

raliz

ed

Se

izu

res

Mis

ce

llan

eo

us


Alprazolam Short actingAnxiety

Depression

ChlordiazepoxideRapidly absorbed

Short acting

Anxiety

Alcohol withdrawal

TriazolamRapidly absorbed

Short acting (very )Insomnia

DiazepamRapidly absorbed

Long acting

Anxiety

Status epilepticus

OxazepamSlowly absorbed

Short actingAnxiety

LorazepamSlowly absorbed

Short actingAnxiety

Flurazepam Long acting Insomnia

MidazolamSteep dose-response curve

Short acting

Water soluble

Clonazepam Long acting Status epilepticus

Buspirone?: 5-HT1A or DA receptor

Major metabolite blocks α2

(Not GABA receptor)

Slowly developing anxiolysis

Palpitations, tachycardia

GI distress

Miosis, ↑BP

No sedation, dependence, abuse,

W/D, amnesia, CNS interx, motor

(w/MAOIs)

Generalized anxiety D/O

Anxiety w/MDD

Meprobamate

CarisiprodolMuscle relaxant

Zolpidem Short acting

Zaleplon Short acting

Eszoplicone Long acting

Thiopental

MethohexitalUltra short acting Thio huxtable was ultra short Anesthesia adjuct

Pentobarbital

SecobarbitalShort-intermediate acting Drugs of abuse

Phenobarbital Long acting Fennel seeds are long Anticonvulsant

RamelteonMelatonin-1 & 2 agonist →

↓ sleep onset

Insomnia

(sleep onset problems)

InsomniaGet some ZZZ's….

E-long-ate

Acts just like Benzos (BZ-1) but

structually unrelated

Bizarre night-time behavior

Less SE than benzos/barbs

Reversed by flumazenil

Bind α1γ2 on GABA-A receptor

→ ↑ GABA binding freq.

→ ↑ Cl- conductance

→ neuron hyperpolarizaiton

→ ↓ neuron activity

~

Anxiolytic-sedative

Hypnotic

Anesthesia

Anticonvulsant

Muscle relaxation

Alcohol withdrawal

Don't induce their own metabolism

(MDOS)

Difficult to produce respiratory arrest

alone

~

King Midas and Lora found a tri-

color ox on their short trip to the

Alps

~

Flur Diaz longed to be a clown

Propanediols indistinguishable from barbiturates in their drawbacks

Ba

rbitu

rate

sA

nxio

lytics

(No

n-B

en

zo

/No

n-B

arb

)B

en

zo

dia

ze

pin

es

Induce own metabolism (MDOS)

Excessive sedation, confusion,

lethargy, motor incoordination

Tolerance

Phys/Psych dependence → W/D

Respiratory arrest

↑ ALA synthase → AIP

Act at GABA-A receptor → prolong

Cl channel opening → inhibition

REM suppression

REM rebound upon W/D

Tolerance

~

Sedation, lethargy, fatigue, mental

clouding, fine motor incoord, ataxia,

W/D, convulsions

~

Physio/Psycho dependence

~

Anterograde amnesia

Paradoxical hostility

~

Toxicity reversed by flumazenil

-BZ-1 & BZ-2 antagonist

-Not effective w/other agents

-Short acting

-Must be given IV


ChlorpromazineBlocks: α1=5-HT2A > D2

mAChR, histamine receptors

High dose, low potency

Liver metabolized

Interax: produce sedation

DA: EPS, ↑ prolactin, wt gain

mACh: "anti-cholinergic effects"

α1: orthostatic hypotension

Jaundice, photosensitivity,

Parkinsonism, NMS, TD

Haloperidol

FluphenazineBlocks: D2 > 5HT2A Low dose, high potency Less CV & anti-cholinergic effects IM preparation

ClozapineBlocks: D4=α1 > 5-HT2A > D2

Weak agonist at M4 ACh receptor

Ortho hypotension, ~EPS

↓ seizure threshold

Agranulocytosis

Causes sialorrhea

Have to keep their mouth clozed

RisperidoneBlocks: 5-HT2A > D2

(potent @ D2…looks typical)

Low doses → ↓EPS

Therapeutic doses → EPS &

prolactin

DA: EPS, ↑ prolactin, wt gain

Olanzapine Blocks: 5-HT2A > D2 > αWeight gain prominent

(Metabolic syndrome)

Especially good for negative SX of

schizophrenia

Aripiprazole Partial agonist at: D2 & 5-HT2A Minimal or no weight gain

LithiumNa+ or Mg2+ replacement

↓IP3/DAG, ↓cAMP

↓NT release

Oral absorption

Kidney excretion (↑ in preggo)

Narrow therapeutic window

Acute: fatigue, weakness, tremor

Chronic: ↓thyroid, diabetes insipidus,

nephritis, edema

Only drug that ↓suicide

Breast milk (Ebstein anomaly)

↑ dietary sodium can ↓ effect

Mania

Valproic AcidUsed for early mania

Used as lithium adjunct

Sedation, GI

Hepatotoxicity

Birth defects

As effective as lithium in early maniaMania

(early)

CarbamazepineUse anti-convulsant dose

Used if lithium inadequate

Diplopia, ataxia, GI

Aplastic anemia, birth defects

Agranulocytosis

LamotrigineAnti-convulsant

Block Na+Used as lithium adjunct

Clonazepam Benzodiazepine

Sedation

Amnesia

Abuse, dependence

Mood S

tabili

zers

Typic

al

Antipsychotics

Aty

pic

al A

ntipsychotics

Schizophrenia

Schizoaffective D/O

Bipolar D/O

Mania

Tourette's syndrome

Schizophrenia

Schizoaffective D/O

Bipolar D/O

Mania

Tourette's syndrome

Less SE's

Anti-convulsant

Block Na+, enhance GABA

Mania


ImipramineInhibits NE & 5-HT reuptake

Blocks: α1, mAChR, histamineMetabolized to desipramine

AmitriptylineInhibits NE & 5-HT reuptake

(5-HT>NE)

Blocks: α1, mAChR, histamine

Metabolized to nortriptylinePronounced anti-ACh visual effects:

mydriasis & ↓accom.

Desipramine Inhibits NE reuptake Sudden death in children

Nortriptyline Inhibits NE & 5-HT reuptake

(NE>5-HT)

Buproprion Inhibits DA reuptake (?)

↓CV SE's

↓sexual complications

↓seizure threshold

Psychomotor activationDepression

Nicotine withdrawal

Venlafaxine Inhibits NE & 5-HT reuptake↓CV SE's

↑BPDepression

Trazodone

NefazodoneTrazodone: Sedation (in a tranz)

Nefazodone: Hypnotic

Trazodone can cause priapism &

orgasms w/yawning

Depression

(Nef>Traz)

FluoxetineLong acting

Active metabolite

Inhibits P450 system

↓ food intake → weight loss

Sertraline

Paroxetine

Fluvoxamine

Shorter acting (than fluox)

No active metabolites (like fluox)

No inhibition of P450 system

Phenelzine

TranylcypromineIrreversibly inhibit MAO-A & B →

↑NE & ↑5-HT & ↑DA

MoclobemideReversibly inhibit MAO-A →

↑NE & ↑5-HT

St. John's WortPartially inhibit NE & 5-HT reuptake

Bind GABA receptors

Interax: ↑ levels of…cyclosporine,

warfarin, indinavir, digoxin,

amitriptyline

Photosensitivity

Induces liver enzymesDepression?

Substance P

antagonistNeeds confirmation Depression?

Mifepristone Glucocorticoid receptor antagonistPsychotic major

depression

Mis

cella

neous

Tricycic

Antidepre

ssants

2nd &

3rd

Genera

tion

SS

RIs

MA

O Inhib

itors

Sedation

Orthostasis

Cardiotoxicity

Anti-cholinergic effects

Hypomania

Rash, photosensitivity

↓seizure threshold

α1: hypotension → reflex SNS

Tachycardia

Arrhythmia

Angina, infarct

Suicide

Impotence

Depression

~

Enuresis

(anti-ACh)

Pain

ADHD

Depression

OCD

Bulimia

Akathisia

Behaviorally activating

Nervousness, insomnia, N/V

Headache, anorgasmia

Suicide

MAOI Interax: serotonin syndrome

Inhibition of 5-HT reuptake

Inhibit SIF ganglion cells → ↓BP

Headache

Sexual dysfunction

Hypertension/hypotension

Interax: tyramine-containing foods →

hypertensive crisis

~

Mood elevations in depressed &

normal individuals

Depression

Narcolepsy

Phobia anxiety D/O

OCD


DisulfiramIrreversibly inhibit ALDH →

↑acetaldehyde

Converted to active metabolites

(which inhibit ALDH)

Acetaldehyde syndrome →

alcohol flush reaction

NaltrexoneOpiate µOR antagonist

Blocks alcohol reinforcement

Reduces craving

Reduces relapse rates by 50%

AcamprosateInteracts with NMDA & GABA-A

receptorsTaurine derivative

Reduces hyperexcitability during

withdrawal

TopiramateFacilitates GABA-A function

Blocks AMPA & kainate receptors

Tiapride D2 dopamine antagonist

Ondansetron 5-HT effectsAlcoholism

(early-onset)

MethanolMethanol −ADH→ formaldehyde

−ALDH→ formic acid

Headache, vertigo, vomiting,

abd/back pain, dyspnea, met.

Acidosis, coma, resp. failure

Can cause blindness (15mL) Toxic

Ethylene glycolEthgly −ADH→ glycoaldehyde

−ALDH→ glycolic acid →

glyoxylic & oxalic acid

Metabolic acidosis

Renal failure (oxalate deposits)

Treat with EtOH

Treat w/fomepizole: ADH inhibitorAntifreeze

Alc

oh

olis

m T

rea

tme

nt

To

xic

Alc

oh

ols

Alcoholism


Morphine30% absorbed in gut

90% first pass metabolism

Analgesia, sedation, euphoria,

dysphoria, miosis, N/V, OH,

resp. & cough suppression

Pinpoint pupils = opioid OD

Constipation

Mod-severe pain

Myocardial infarction

Dyspnea, anxiety

Fentanyl

Su & Alfentanil80x morphine potency Less nausea

Sufentanyl = ↑ fentanyl

Alfentanyl = ↓ fentanyl

Post-op pain

Anesthetic (w/droperidol)

Meperidine1/5 morphine potency

1/4 morphine duration

No cough suppression

Less constipation

No labor prolongation

OB/Surg analgesia

Mod-severe pain

MethadoneSame potency as morphine

↑bioavailability than morphine

Long acting

No euphoria

Prevents W/D signs

Mod-severe pain

Opioid addiction

CodeineMetabolized in part to morphine

Excellent bioavailabilityFew SE

Mild-moderate pain

Cough

Propoxyphene1/2 codeine potency

Given w/acetaminophen

Interax: alcohol/sedatives (fatal)

Oxycodone Given w/aspirin or acetaminophen Abuse

PentazocineGiven w/naloxone IV to avoid

analgesic & euphoric effects

Combined w/tripelennamine

("T's & blues") → heroin-likeModerate pain

Butorphanol30x pentazocine antagonism

20x pentazocine analgesia

Mod-severe pain

(acute)

NalbuphineSame potency as morphine

5x pentazocine potency

Less psychotomimetic effects

Less MOR antagonist activity

Buprenorphine 25-50x morphine potency (pain)

Worse sedation & resp. depression

than morphine

Binds MOR w/high affinity

Naloxone Fast onsetT-REX is bigger than an OX, and a

T-REX is more orally active!Precipitates opioid W/D Opioid overdose

Naltrexone3-5x naloxone potency

Long acting

Orally active (moreso)

Opioid addiction

(highly motivated)

TramadolWeak MOR agonist

Inhibits NE & 5-HT reuptake

1/10 codeine MOR affinity

6000x less morphine MOR affinity

Less potential for abuse &

respiratory depressionDual mechanism of action

Dental pain

Acute MSK pain

Cancer pain

Str

on

g O

pio

id A

go

nis

tsM

od

era

te O

pio

id

Ag

on

ists

Mix

ed

Op

ioid

Ag

on

ist-

An

tag

on

ists

Op

ioid

An

tag

on

ists

Competitive opioid antagonist

(MOR)

Mild-moderate pain

KOR agonist

MOR antagonist

Potent MOR agonist

Weaker MOR agonist

Sedation (KOR)

Sweating, dizziness

Psychotomimetic effects

Anxiety, nausea, vomiting

Mod-severe pain

Drug Mechanism Metabolism Toxicity What makes it unique Mnemonic

HalothaneSlow induction (↑ blood:gas)

Most potent (↓MAC)

Hepatotoxicity (free radicals)

Sensitizes myocardium to NE/EPI

↑cerebral blood flow

Halo = Heart

Enflurane

Isoflurane

Nitrous oxideFast induction (↓ blood:gas)

Least potent (↑MAC)NO potency

Thiopental Barbiturate

Ultra short acting

Rapid onset, short anesthesia

Diffuses out of brain

May produce "hangover"

Myocardial/Respiratory depression

↓cerebral/renal blood flow, ↓GFR

Thio huxtable is ultra short

Diazepam

Loraz/MidazBenzodiazepines

Slower onset

Long acting

Prolonged post-op. recovery

Anterograde amnesia

Morphine

FentanylHigh potency opioid Can be reversed w/naloxone Respiratory depression

Analgesic

Only anesthetic @ ↑ doses

PropofolRapid onset

Rapid recovery

Anti-emetic

Respiratory depression

Hypotension Most popular IV anesthetic Be proper, don't puke

Ketamine Blocks NMDA receptors

CV stimulation: ↑HR, ↑BP, ↑CO

↑cerebral blood flow, ↑ICP

Disorientation, illusions, vivid dreams

Analgesic

Amnesia

Catatonia

Ketamine = catatonic

Droperidol Antipsychotic Given w/opioid (fentanyl)

Analgesia

Pt. can respond to commands

(no loss of consciousness)

Can talk to the patient from

behind the drape

EtomidateRapid onset

Rapid recovery

Nausea & vomiting

Pain

(Minimal CV/repspiratory Depression)

Not analgesic He tummy ache

Not analgesic

Fluranes fluoride floppy

muscles

Nonspecific interactions w/ lipid bilayer

Block K+ channels → hyperpolarization

Activate or facilitate GABA

Intermediate induction

Intermediate potency

Fluranes (fluoride) can be nephrotoxic

↓minute volume

Muscle relaxation

Genera

l A

nesth

etics (

IV)

Genera

l A

nesth

etics

(Inhala

tion)

Drug Mechanism Metabolism Toxicity What makes it unique Use

CocaineAbsorb via mucous membranes

Topical useCNS stimulation & euphoria (abuse)

Produces vasoconstriction

(All other LA's produce vasodilation)Topical LA

ProcaineShort acting

(metabolized by plasma ChE)

Given w/EPI

Aunt Ester had allergies

…but she was a peach! (PChE)

Infiltration

Nerve block

Spinal anesthesia

TetracaineMore lipophilic than Pro/Coke:

Rapider onset, potenter

Longer acting

Most commonly used drug for SpinalsSpinal anesthesia

Topical LA

Benzocaine Poorly water solubleSo poorly water soluble that systemic toxicity

potential is zero.

Dusting powder

Ointment

(burns/ulcerations)

Lidocaine Drowsiness Used in ester-allergic individualsLA

Cardiac arrhythmias

Mepivacaine Lassitude in neonate OB LA

BupivacaineMore lipophilic than Mep/Lido:

Long acting

Highly plasma protein bound

Cardiotoxic

Particularly long acting

(some nerve blocks last 24+ hrs!)

Analgesia + abdominal muscle control

Epidural anesthesia (OB)

Nerve blocks

Procainamide Cardiac arrhythmias

Block V-G Na+ channels

in high frequency pain fibers

(spend lots of time "open")

~

Weak bases (pKa=8-9)

1) uncharged into axoplasm

2) ionized & trapped inside

3) binds open Na+ channel

More lipophilic than Pro/Coke:

Rapider onset, potenter

(Intermediate) Longer acting

Block V-G Na+ channels

in high frequency pain fibers

(spend lots of time "open")

~

Weak bases (pKa=8-9)

1) uncharged into axoplasm

2) ionized & trapped inside

3) binds open Na+ channel

~

Quickly metabolized by PChE

Local A

nesth

etics (

Este

rs)

Local A

nesth

etics

(Am

ides)


Cromolyn Sodium

Nedocromil

ChlorpheniramineRapidly absorbed orally

Metabolized by CYP3A4

Ineffective in bronchial asthma (mediated by

more than just ol' histamine)

Seasonal allergic rhinitis

Urticaria

Diphenhydramine

Promethazine

Strong sedation!

Ototoxicity

(newborns or ABX)

Allergies

Motion sickness

Sedation

TerfenadineDrug interax: cardiotoxic w/ conazoles or

macrolides

Metabolized to fexofenadine (not cardiotoxic),

if CYP3A4 inhibited, terfenadine accumulatesAllergies

Fexofenadine Lower risk of arrhythmia

Loratadine Long acting No significant side effects

Cyproheptadine Strong 5-HT blocking

CimetidineInhibits P450 system

Drug interax: ↑chlordiazepoxide, EtOH,

propranolol, theophylline, warfarin

Diarrhea, muscle pain

Headache, dizziness

Gynecomastia, impotence

Ranitidine4-10x more effective than cimetidine

Does not interfere with P450

Less side effects than cimetidine

No antiandrogenic effects

Famotidine Not metabolized by P450 Don't use in renal disease

Nizatidine Don't use with salicylates

Pro

ton

Pum

p

Inhib

itor

OmeprazoleActive form irreversibly binds & inhibits

proton pump in parietal cells

Absorbed in alkaline SI pH

Use >2 months not advisable

Diarrhea, nausea

Dizziness, headache

Heals duodenal ulcers more rapidly than H2

blockers

Gastric/duodenal ulcers

ZE syndrome

GERD

SucralfateAluminum salt of sucrose sulfate →

binds plasma proteins in crater →

protective barrier

Short acting

Drug interax: blocks tetracycline & PO4

absorption

Constipation

Nausea

Additionally: inhibits pepsin & bile aciton

Also: ↑ prostaglandin releaseDuodenal ulcer

Colloidal bismuthReact w/proteins in acid medium →

protective barrier in ulcer crater

Black stools, black tongue

Don't use in renal diseaseMay have ABX activity against H. pylori Gastric/duodenal ulcers

Cyto

Pro

tect

MisoprostolProstaglandin E1 analog → ↓ H+

↑mucus & ↑bicarbonate secretion

Nausea, diarrhea

Abortion in preggos


NSAID-induced damage

SulfasalazineBacteria split azo bond → 5-ASA (&

sulfapyridine) → ↓ inflammation

75% reaches colon

5-ASA = active metabolite

Sulfapyridine = SEs

Nausea, vomiting

Headache

Allergy

Can cause ↓ folate absorptionUlcerative colitis (85%)

Colonic Crohn's Dz

Hydrocortisone Corticosteroid → ↓ inflammation Acute episodes

Azathioprine

MercaptopurineUlcerative colitis

Crohn's disease

Cyclosporine Severe refractory IBD

InfliximabMonoclonal antibody against TNF-α → ↓

inflammatory actionSingle IV infusion → remission

Nausea

Serum sickness

Infections, autoimmunity, cancer

Crohn's disease

Cytotoxins Low dose used for prophylaxis Toxicity may limit chronic use Used in nonresponsive cases

Competitive inhibitor of histamine (H2)-

stimulated gastric HCl secretion


ZE syndrome

GERD

Ci me, I ran ti dine with my family & my nizce

Block H1 receptor → ↓ histamine ax

Allergies

Motion sickness

Sedation

Antiparkinsonian effects

Anti-cholinergic effects

Anti-serotonergic effects

α receptor blocking

Local anesthetic effects

Block H1 receptor → ↓ histamine ax AllergiesLittle to NO sedation

Degra

nula

tion

Inhib

itors

Bronchial asthma

(prophylaxis)

Inhibit immunologically triggered mast

cell degranulationIneffective after asthma attack has started

H2

Re

ce

pto

r A

nta

go

nis

tsM

uco

sa

l

Pro

tecta

nts

Infla

mm

ato

ry B

ow

el D

ise

ase

First G

enera

tion

H1 R

ecepto

r A

nta

gonis

ts

Second G

enera

tion

H1 R

ecepto

r A

nta

gonis

ts

Drug Mechanism Metabolism Toxicity What makes it unique Mnemonic Treats

Acyclovir

ValacyclovirValacyclovir −(rapidly)→ acyclovir

Nausea, vomiting, diarrhea

Headache, renal dysfx

Resistance: altered/deficient viral

thymidine kinase or

viral DNA polymerase

HSV

VZV

Ganciclovir

Valganciclovir

Myelosuppression, neutropenia vision

disturbances, carcinogenic

CNS effects

More toxic than acyclovir

CMVertables are fos

cars, cid so you ganci

the road fomi

CMV

(retinitis)

Famciclovir

Penciclovir

Guanine nucleoside analog

Inhibits viral DNA synthesis

Famciclovir is a prodrug metabolized to

active penciclovir

Nausea, diarrhea

Headache

Tumors, testicular toxicity

Acute herpes zoster

FoscarnetInorganic pyrophosphate analog

Reversibly inhibits viral DNA & RNA polymerases

Nausea, fever, headaches, hypocalcemia,

hypomagnesemia, nephrotoxicity, anemia,

genital ulcer

More toxic than gancyclovir

CMV (retinitis)

HSV

(acyclovir resist.)

Trifluridine Pyrimidine analog Cornea inflammationTri flurting w/Kera's

tits & HSV

HSV

(Keratoconjunctivitis)

(Epithelial keratitis)

CidofovirNephrotoxicity, neutropenia, metabolic

acidosisCMV (retinitis)

Fomivirsen Antisense oligonucleotideIritis, vitritis, ↑ intraocular pressure

Vision changes

Don't give to patients who have taken

cidofovir in past month

CMV (retinitis)

(in HIV patients unresp)

Docosanol Prevents viral fusion → ↓ viral entryOnly effective if given at first symptoms

(ineffective at papule stage)HSV

IdoxuridineIodinated thymidine analog

Incorporated into viral & cellular DNA →

susceptible to breaks & error in trx

Pain, inflammation, edema

of eyes or eyelids

HSV

(keratitis)

Amantadine Metabolized by kidney

Anorexia, nausea, peripheral edema

CNS effects

(in renal failure dz)

Reduces duration & severity of influenza

infection

90% of influenza is resistant!

Rimantadine Metabolized by liver

ZanamivirNasal/throat discomfort, headache,

bronchospasm (asthmatics)

Oseltamivir Nausea, vomiting, headache

Dexamethasone Croup

Adefovir Inhibits viral reverse transcriptase NephrotoxicityAde for viruses

makes me hep B!

Hepatitis B

(chronic)

InterferonsIFNα & IFNβ bind cellular receptors → activate JAK-

STAT → ↑ 2,5-oligoadenylate synthetase & kinase

→ ↓ protein syn

IM or SC injection

Flu-like symptoms, bone marrow

suppression, fatigue, infections, anorexia,

diarrhea, depr, anxiety

HPV

Hepatits B & C

Kaposi's sarcoma, MS

TelbivudineRenal dysfunction

Myopathy (↑ CK)

Tell bi he's a dead

hepatitis…..Hepatitis B

RibavirinSynthetic guanosine nucleoside analog

Alters nucleotide pool → ↓ viral mRNA syn

Conjunctiva irritation, wheezing, rash

Anemia, bone marrow suppression

Teratogenic

Ribavirin blocks RNA

of virin

Hepatitis C

RSV , Influenza, HIV

Parainflu, Paramyxo

ImquimodInduces IFNα & TNFα

(and other cytokines)

Local erythema, flaking, itching

(topical)I'm quiet about warts HPV

For herpes, tri giving

acyclovir, doc (or

dox)!

He

rpe

s / V

ari

ce

lla / C

MV

Vir

al R

esp

ira

tory

In

fectio

ns

Vir

al H

ep

atitis In

fectio

n

Guanine nucleoside analog

Viral thymidine kinase produces analog →

binds viral DNA polymerase & inactivates

Inhibits viral uncoating & blocks influenza A M2

protein (↓ dissociation of RNP complex in

replication)

Influenza A

Parkinson's disease

Inhibits neuraminidase → ↓ release of virus →

↑ viral aggregates & ↓ viral spreadInfluenza A & B

Orally inhaled

Used once taily to prevent flu

If taken within ~30 hrs of SX onset →

↓ duration & respiratory complications

Drug Mechanism Metabolism Toxicity What makes it unique Mnemonic Treats

ZidovudineConverted via human thymidine kinase → AZT-TP

→ incorporated into viral DNA → terminates chain

elongation

↑ toxicity w: probenecid, tylenol,

lorazepam, indomethacin, cimetidine

Anemia, leukopenia, headaches, lactic

acidosis, hepatic steatosis, lipoatropy,

central fat, ↑lipids

Protects fetuses from infection

Resistance: mutated RT w/↓ affinity for

AZT-TP

HIV

DidanosineOrally in buffered tablets

↑ toxicity w: stavudinePancreatitis, peripheral neuropathy

HIV

(AZT resistant)

ZalcitabineGiven w/AZT or alone

(if can't tolerate AZT)Stomatitis, peripheral neuropathy, rash HIV

StavudinePeripheral neuropathy

Lactic acidosis, hepatic steatosis,

lipoatropy, central fat, ↑lipids

HIV

Lamivudine Pancreatitis (pediatric patients)Resistance to AZT develops more slowly

if you add lamivudine

Emtricitabine Hyperpigmentation

AbacavirGiven w/AZT or Lamivudine or

protease inhibitorHypersensitivity, fever, GI, malaise, rash HIV

TenofovirDo not give w/didanosine, lamivudine,

abacavir

Flatulence

Renal toxicity

HIV

Hepatitis B

Efavirenz Given w/AZT & lamivudine Dizziness, headache, insomnia, rash

Nightmares, hallucinations

↓ [phenobarb, phenytoin, carbmzpne,

methadone, rifabutin]

Rifampin → ↓ efav

DelavirdineGiven w/AZT & didanosine

Least potentRash

↑ [rifampin, rigabutin, ergot, triazolam,

midazolam, cisapride]

Efavirenz Rx & SJW → ↓ dela

Nevirapine Given w/didanosine & stavudine Rash, fever, nausea, hepatotoxicity

↓ [rifampin, ketoconazole, ethinyl

estradiol (BC)]

SJW → ↓ nevir

Indinavir

Saquinavir

Ritonavir

Lopinavir

Nelfinavir

AmprenavirInhibits CYP34A (Rx toxicity)

Rifampin induces CYP3A4

Although HIV cross-resistance occurs,

most likely to still be Amprenavir

susceptible

Atazanavir

Fosamprenavir

Fusio

n

Inh.

EnfuvirtideBinds viral envelope glycoprotein to prevent

conformational change when binding host cell

membrane

Pain, erythema, nodules, cysts

(at injection site)Injected twice a day Binds enfulope HIV

No

n-N

ucle

osid

e

RT

In

hib

ito

rsP

rote

ase

In

hib

ito

rsN

ucle

osid

e R

eve

rse

Tra

nscri

pta

se

In

hib

ito

rs

Binds next to RT activation site → change

conformation → inhibit RT activity

Inhibits viral reverse transcriptase → terminates

DNA chain elongation

Resistance: mutated RT

HIV

Hepatitis B

Zitty Zal went nuclear

& did stab a baby

lamb he tends.

Interferes w/proteolysis of gag-pol viral protein

precursor → nonfunctional virions

Administered together:

Ritonavir inhibits CYP3A4 →

↑ Lopinavir

Diarrhea, nausea, fatigue, headache,

hyperlipidemia, hyperglycemia, altered

body fat

SJW lowers concentration

Diarrhea, nausea, vomiting, lipodystrophy,

hyperglycemia

Diarrhea, nausea, vomiting, lipodystrophy,

hyperglycemia

Nel is a LIAR. She is

a professional tease

and will inhibit or slow

your fost progress

Never ever tell a nun

a lie.HIV

HIV


QuinidineBlocks V-G Na+ channels

& K+ channels

Blocks α-adren. & vagus

↓ automaticity, prolonged QT, widened

QRS, ↑ SA & AV node conduction velocity

GI, hepatic granulomas, torsades, ↑ ventricular

rate w/A flutter, cinchonism, lupus-like

syndrome

Can cause paradoxical ↑ in heart rate in

atrial flutterChronic SVT

ProcainamideBlocks V-G Na+ channels

& K+ channels

(no ANS effects)

↓ automaticity

↑ refractory period

↓ conduction velocity

GI, hypotension, torsades,

heart block, agranulocytosis, lupus-like

syndrome

Converted to active metabolite NAPA →

no Na+ channel activity but blocks K+

channels

Ventricular tachycardia

SVT

LidocaineIV use only (↑ first pass metab)

↓automaticity, ↓ action potential,

↓ conduction velocity

Seizures

Nystagmus, tremor, dysarthria, altered

sernsorium

Mexiletine Same, but orally effective Nausea, tremor, CNS effects Orally active

FlecainideBlocks Na+ channels

Blocks K+ channels

Blocks Ca2+ channels

Proarrhythmic (after MI)

Exacerbate CHF by ↓ LV fxn

Heart block (in AV node dz)

Atrial arrhythmia

(if no other strx disease)

PropafenoneBlocks Na+ channels

Blocks K+ channels

Blocks β-adrenergic

Proarrhythmic (after MI)

Exacerbate CHF by ↓ LV fxn

Heart block (in AV node dz), torsades

Bradycardia & bronchospasm (β block) Atrial arrhythmia

PropranololNon-selective β blocker

Na+ blocker at ↑ dose

(membrane stabilization)

↓ AV conduction velocity, prolonged PR, ↓

automaticity in ectopic foci

Myocardial depression, heart block,

bronchospasm, ↑ insulin hypoglycemia,

depression, rebound SNS if w/d

Metoprolol β1 blocker

CarvedilolNon-selective β blocker

α blockerAntioxidant properties

Acebutolol Lupus-like syndromeIntrinsic SNS activity, but no membrane

stabilizing effects

Atenolol Longer acting Less polar → less CNS effects

EsmololUsed IV when immediate block is needed

Cleared quickly

Amiodarone Blocks K+ channels

Blocks Na+ & Ca2+ channels

Non-competitive SNS blocker

Prolonged QT, ↓ automaticity, ↓

conduction velocity,

widened QRS, prolonged PR

Corneal deposits (100%), liver dz, hypo &

hyperthyroidism, pulmonary fibrosis,

vasodilation, photosensitivity/skin color

First line agent in ACLS code

Active metabolite: desethyl-amio

Atrial tachycardia


SotalolBlocks K+ channels

Non-selective β blocker

↑ action potential, ↓ automaticity,

↓ conduction velocity (AV only), prolongs

AV refractory period

Torsades (especially in hypokalemia)

β blocker SE's

Renal excretion of unchanged drug

β blocker w/Class III effectsAtrial arrhythmias

(chronic)

IbutilideBlocks K+ channels

Non-selective β blocker

IV use only

Delays repolarization,

↓ action potential

Torsades

Contraindicated in hypokalemiaIV use only

Atrial arrhythmias

(acute)

DofetilideBlocks K+ channels

(rapid delayed rectifier K+ current)Greater effect on atria than ventricles Torsades

Rx Interax: ↑ [Dofetilide]

Interfere w/cation trx in kidney, prolong QT

interval, use liver metab.

Atrial arrhythmias

(chronic)

VerapamilGiven orally but IV is better

More active L-isomer first pass met.

DiltiazemLess negative inotropic effects

(less ↓ CX)

DigoxinDirect: Blocks Na+/K+ ATPase

Indirect: vagal stimulation

↑ CX (↑ Ca2+)

Vagal: ↓ atrial AP & ↑ AV refractory

Arrhythmias

Nausea

CNS effects

Rx Interax: ↑ [Digoxin]

quinidine & verapamil

SVT

(acute or chronic)

CHF (↑ CO)

AdenosineBinds adenosine receptors → opens

ACh-sens. K+ channels (in

SA/AV/atria)

Shortens atrial AP, ↓ automaticity,

↑ AV refractory period,

↓ AV conduction velocity

Transient: asystole, dyspnea, bronchoCX

Atrial fibrillation

Flushing

IV use only

Rx Interax: theophylline & caffeine block

adenosine receptors

Atrial tachycardia

Atrial fibrillation

Produce controlled hypotension

Cla

ss IV

-

Ca2+

channel

blo

ckers

Mis

ce

llan

eo

us

Cla

ss 1

A

Na

+ b

locke

r

(In

term

ed

iate

τ)

Cla

ss 1

B

Na

+ b

locke

r

(Ra

pid

τ)

Cla

ss 1

C

Na

+ b

locke

r

(Ve

ry lo

ng

τ)

Cla

ss I

I - β B

lockers

Blocks Na+ channels, ↑ gK in fast

fibers during phase 3 & 4


Ventricular fibrillation

↓ conduction velocity, widened QRS, ↑

action potential,

prolonged QT, prolonged PR

Cla

ss I

II -

K+

channel blo

ckers

β1 blocker

Atrial flutter

Atrial fibrilliation

Ventricular arrhythmia (post-MI)

Angina

SVT

(acute or chronic)

Hypotension → reflex tachy, neg. inotropy,

heart block (AV conduction dz), bradycardia

(SA conduction dz), GI

↓ HR, ↓ CX, ↓ conduction velocity (AV),

prolongs AV refractory periodBlocks L-type Ca2+ channels


Digoxin25% plasma protein bound

Renal elimination

2 day half-life

Digitoxin>90% plasma protein bound

Hepatic elimination

7 day half-life

Dopamine

DobutamineSimulate β1 receptors → ↑ CX

Dopamine: tachycardia, arrhymthia

Dobutamine: tolerance, vasodilation (via

β2 receptors)

Dopamine vasodilates renal vasculature via

D1 receptors

AmrinoneInhibits phosphodiesterase-III →

vasodilation & ↑ CX

PDE-III selectively found in cardiac & smooth

muscle

Nausea, vomiting

Thrombocytopenia, liver damage

Arrhythmia

Does more harm than good when used long-

term

Furosemide

Bumetamide

Diuresis & peripheral vasodilation →

↓ cardiac workload

Short acting

Very potent

Hyponatremia, hypokalemia,

hypocalcemia, hypomagnesemia,

hypophosphatemia

Heart failure

Hyrdochlorothiazide

Chlorothiazide Diuresis Synergistic with loop diuretics

Hyponatremia, hypokalemia,

hypocalcemia, hypophosphatemia

Kidneys can adapt

Ineffective at GFR < 30 ml/min

Heart failure

(mild)

Spironolactone DiuresisAdd to other diuretics

(to help w/diuresis & to spare K+)

Hyperkalemia, anti-androgenic effects

(gynecomastia)Avoids K+ wasting Heart failure

Captopril

Enalapril

Lisinopril

Venous & arterial vasodilation →

↓ preload & afterload

(+ ↑ bradykinin)

Abrupt ↓ in BP w/first dose (vol dep)

Rash, loss of taste, coughHeart failure

Sodium nitroprussideHypotension, coronary steal, angina,

cyanide toxicity, thiocyanate toxicity

Cyanide → thiocyanate

(eliminated kidneys)

No tolerance (different NOS from NG)

Heart failure

Angina

Isosorbide dinitrate

Nitroglycerin

Isosorbide 5-mononitrate

Flushing, headache, hypotension, reflex

tachycardia,

Fast first pass metabolism

Tolerance develops rapidly

CHF (acute & chronic)

Vasospastic Angina

(w/Ca2+ blockers)

HydralazineArterial vasodilation → ↓ afterload

↑ CX

renal dilation → ↑ renal blood flow

Hypotension

Reflex SNS activityHeart failure

Carvedilol

Metoprolol

Bisoprolol

Blocks β receptors in heart → counteracts

SNS input to heart

May allow gradual up-regulation of β receptors

to occur in the heart

Myocardial depression, bronchoCX,

hypoglycemia, fatigue, depression,

impotence, rebound SNS if W/D

Heart failure

Verapamil

Diltiazem

Nifedipine

Blocks L-type Ca2+ channel →

vasodilation & ↓HR & ↓CX

Highly protein bound (~90%)

Liver metabolized

Worsening angina, worsening HF, heart

block (in AV dz), bradycardia,

hypotension, edema, resp, GI

Not helpful for systolic dysfx

Helpful for diastolic dysfx (cardiac filling)

Heart failure / HTN

Reentry arrhythmia

Angina (vasospastic/exer)

Dig

ita

lis

Gly

co

sid

es

Diu

retics

Va

so

dila

tors

Mis

ce

llan

eo

us

Ino

tro

pe

s

Heart failure

(serious)

Metabolized to NO → venous & arterial

vasodilation → ↓ preload & afterload

Inhibit Na+/K+ ATPase binding

extracellularly on α subunit

Prefers E1-P form → stabilize to E2-P

form

Na & Mg favor binding

K favors release

Aglycone portion = for cardiac activity

Monosaccharide chain = metab.

Eubacterium lentum in gut inactivates

Fatigue, malaise, dizziness, confusion,

delirium, anorexia, N/V, abdominal pain,

color vision, halos, bradycardia, AV

block, ectopic beats, SA arrest,

ventricular arrhythmias, EKG changes

Heart failure


AcetazolamideInhibits CA in the PCT →

↓ Na & HCO3- reabsorption

Secreted into lumen via OA trx

Inhibits 85% of PCT HCO3 reabs

Inhibits 45% of total HCO3 reabs

Metabolic acidosis, renal CaPO4 stones,

hypokalemia, CNS, allergy

Contraind: cirrhosis (encephalopathy)

CHF edema, Glaucoma

Urine alkalinization

Mountain sickness

Dorzolamide Inhibits CA in the eye Topical application MinimalUsed more often for glaucoma than

acetazolamideGlaucoma

FurosemideSecreted into lumen via OA trx

Eliminated via kidney

Decrease luminal (+) potential

(↓ K+ pushed out) → ↓Ca2+ & Mg2+ reabs

BumetanideShorter acting

50% liver elimination

(50% kidney elimination)

40x more potent

TorasemideLonger acting

Faster absorption

80% liver elimination

Ethacrynic AcidNo sulfur group in its structure

Only if allergic to other loops

Worst ototoxicity

HydrochlorothiazideSecreted into lumen via OA trx

Absorbed orally

Low Na in cell sucks Na through basolateral

Na/Ca exchanger → ↑ Ca2+

reabsorption

Chlorothiazide Shorter acting 10x less potent than HCT

Metolazone Longer acting10x more potent than HCT

Different structure from thiazides

IndapamideLonger acting

Excellent oral absorption

Eliminated via liver

20x more potent than HCT


Chlorthalidone Longer actingSame potency as HCT


SpironolactoneCompetitive aldosterone receptor in DCT &

CT → ↓ in Na+ channels & ↓ out K+ channels (Princ.)

↓ Na+ reabsorption & ↓ K+ secretion

in Principal cells

↑ H+ secretion Intercalated cells

Hyperkalemia, metabolic acidosis, gynecomastia,

impotence, ↓ libido, GI, CNS effects

Also inhibits DHT receptor →

↓ testosterone

Only diuretic not acting in lumen

Cirrhosis (ascites)

Hyperaldosteronism

Hypertension

Eplerenone Epoxy-spironolactone derivativeLess anti-androgenic effects (less DHT &

progesterone receptor binding)Heart failure

AmilorideSecreted unchanged into lumen via

organic base transporter

Eliminated unchanged via kidney

Hyperkalemia (NSAIDs ↑ likelihood)

Nausea, vomiting, diarrhea, leg cramps, headache,

dizziness

TriamtereneShorter acting

Metabolized in liver → into kidney lumen

→ insoluble & ppts out

Photosensitivity 10x less potent than amiloride

MannitolFiltered & excreted exerting osmotic pull in

PCT & loop of henle

Must be given IV

↑ flow → ↑ urea excretion →

↓ ability to concentrate urine

Headache, nausea, vomiting,

hypernatremia/dehydration, pulmonary edemaInitial rapid expansion of plamsa volume

Intracranial pressure

Renal excretion of toxins

Demeclocycline Nephrotoxic Tetracycline antibiotic SIADH

Lithium Usually used to treat maniaBipolar disorder

(~SIADH)

NesiritideRecombinant form of ANF →

↑ Na+ excretionHypotension CHF

TolvaptanADH V2 receptor antagonist →

↑ free H2O excretion &

↓ urea & Na+ reabsorption

Heart failure

ConivaptanADH V1a antagonist →

↓ vasocx & ↓ smooth muscle growth

ADH V2 receptor antagonist →

↑ free H2O excretion &

↓ urea & Na+ reabsorption

Mis

ce

llan

eo

us

Inhibits Na+/K+/2Cl- trx in TAL →

↓Na & K & 2Cl reabsorption

Blocks Na+ channels in Principal cells in

DT & CT →

↓ Na+ reabs & ↓ K+ secretion

Carb

onic

Anhydra

se

Inhib

itors

Lo

op

Diu

retics

Th

iazid

e D

iure

tics

Po

tassiu

m-S

pa

rin

g D

iure

tics

Inhibits NaCl cotrx in DCT →

↓Na & Cl reabsorption

Hyponatremia/dehydration

Hypocalcemia

Hypokalemia

Metabolic alkalosis

Hypomagnesemia

Hyperuricemia

Ototoxicity

Allergy

Hyponatremia/dehydration

Hypokalemia

Metabolic alkalosis

Hypercalcemia

Hyperglycemia

Hyperuricemia

Allergy

Weakness

Blocks ADH action in the CT →

↓ aquaporins

Edema

Hypertension

Not very good

Pulmonary edema

Edema (CH, renal, cirrhosis)

Hypercalcemia

Hyperkalemia

Hypertension

CHF

Idiopathic hypercalciuria

(renal stones)

Nephrogenic diabetes insipidus


Echinacea Proposed immune stimulant Flu-like, hepatitis, asthma, rash,

nausea, urticaria, anaphyaxis

May contain organocholine

pesticidesURI or "Colds"

EphedraContains ephedrine

(sympathomimetic)Stroke, arrhythmias, hypertension

16x risk of hemorrhagic stroke

(w/phenylpropanolamine)

Weight loss

Energy

FeverfewMay inhibit PLA2 → arachadonic

acid

Contraind: anti-coagulants

(may inhibit platelet aggregation)

Dizziness, nausea, indigestion,

heartburn, oral ulcer, rash

Contains melatonin

Does work, but not better than

traditional treatment

Migraines

Arthritis

GarlicLowers blood pressure

Lowers cholesterol

(small & brief)

GI distress, allergy, dermatitis,

bleeding, odorCulture media for C. botulinum Hypertension

GingerEffective anti-nausea

Inhibit thromboxane synthase



As effective as antihistaminics in

nausea

Motion sickness

Morning sickness

Ginseng Many have NO donor capability



Phenelzine

Ginseng abuse syndrome:

CNS, arousal, HTN, nervous,

insomnia, vaginal bleeding

Dementia

Ginko biloba↑ACh activity

Effects 5-HT & NE

VasoRX….Antioxidant...↓coag

Contraind: anti-coagulants GI, headache, allergy, bleedingDementia

Circulatory disorders

Kava Enhances GABA activty

Dry flaking skin, puffy face, red eyes,

weakness, oral tingling, GI, SOB,

EKG abnormalities

Can cause serious cirrhosis & liver

failure!

Anxiety

Insomnia

Saw PalmettoInhibit 5α-reductase → ↓DHT

Block α1 receptorsHeadache, GI, hypertension, ↓libido Trad. > Saw palmetto > placebo BPH

St. John's WortContains hyperforin → activates

PXR → ↑CYP450

↑metabolism of: cyclosporine,

indinavir, digoxin, phenobarbital,

tamoxifen, BC

Photosensitivity Depression

Valerian Small hypnotic effectMorning drowsiness, headache,

excitability, cardiac, odorInsomnia

GlucosamineStimulate cartilage cells → GAG &

proteoglycans

Gi discomfort, nausea,

photosensitivity, systolic HTN,

proteinuria

Osteoarthritis

Wound healing

Creatine

Androstenedione

DHEA →androstenedione &

testosterone & androsterone

Creatine → phosphocreatine

Rash, dyspnea, N/V, diarrhea,

nervousness, fatigue, migraine,

myopathy, seizures, a-fib, testo

Athletic performance

Weight loss

Herb

al m

edic

ations &

Nutr

ient supple

ments


Growth Hormone Somatropin

Somatotropin

↑IGF-1, ↑ECM, ↑muscle, ↑soft

tissue, ↑urinary retention of nitrogen,

PO4, K+, anti-insulin

Administered daily in evening

(mimics normal pattern)

Children: few

Adults: per. edema, arthralgia,

myalgia, carpal tunnel syndrome

Childhood deficiency

Adult deficiency

IGF Mecasermin

Mitogenic & anti-apoptotic

Skeletal, muscle, organ growth

Should not be used after closure of

epiphyses or in neoplasiaMay induce hypoglycemia

SPIGFD: mutations in GH receptor,

post GHR defect, IGF-1 defects

Severe primary IGF

deficiency

GHRH Sermorelin

Hexa/Capromorelin

Binds GHRH receptor → ↑cAMP →

↑GH synthesis & release

40-80% of GH deficienct children

respond normally to GHRH

Hexorelin: ↑cardiac performance

(dilated cardiomyopathy)

Dx pituitary defect

Hypothalamic GH deficiency

Somatostatin Octreotide

Binds SRIF receptor → ↓cAMP →

↓GH release (synthesis intact)

Also inhibits TSH secretion

Synthetic SRIF is resistant to

enzymes (t1/2: 3min→2hr)

Selective for GH (vs. insulin)

↓GI motility & secretions, ↓bile

production, ↓gallbladder CX

PVR of hypothalamus = 14 AAs

δ cells of pancreas = 28 AAs

Acromegaly

Carcinoid tumors

VIPomas

PegvisomantGH lysine replaced by glycine → GH

antagonist

PEGylated to ↑t1/2,

↓immunogenicity…but ↓affinity

(8 AA substitutions fix that)

↑hepatic aminotransferase

(otherwise well-tolerated)

Does not reduce size of GH tumor or

lower GH levelsAcromegaly

Bromocriptine

Cabergoline

Pergolide

Paradoxical inhibitory effect on

somatroph adenomas (↓GH)Cabergoline > bromocriptine

Headache, N/V, dizziness, postural

hypotension, insomniaMost useful in ↑GH & ↑prolactin Somatroph adenomas

ACTH Cosyntropin

CRH (hypothalamus) → ACTH (ant.

pituitary) → cortisol & aldosterone &

sex hormones

Dx adrenal insufficiency

CRH Corticorelin

Binds CRH receptor → ↑cAMP →

↑POMC → ↑ACTH

Ovine CRH = ↑t1/2 & potency

(over synthetic)

Flushing, SOB, tachycardia,

hypotension

Blood drawn from inferior petrosal

sinus after CRH stimulation

Dx ACTH-secreting tumor

location

TSH Thyrotropin-α

Binds TSH receptor → ↑cAMP →

↑iodide uptake & TH syn/secr'n

Dx residual thyroid

carcinoma

TRH Protirelin

Binds TRH receptor → ↑Ca2+ →

↑TSH & ↑prolactin

Admin: IV over 15-30 seconds

(TSH → 2-5x basal in 30 min)

Transient nausea, hypo/HTN,

flushing, palpitations

Dx 2° hypothyroidism

Measure PRL reserves

hCG Choriogonadotropin-α

Used for LH activity (acts at same

receptor as LH, but longer t1/2)

Male infertility

Cryptorchidism

Dx Leydig cell failure

hMG Menotropin

Used for LH & FSH activity IMDerived from urine of

postmenopausal women

Male infertility

Female infertility

FSH Urofollitropin

rFSH

Used for FSH activity (merotropin

w/LH component removed)

Urofollitropin: IM/subQ

rFSH: subQ

Multiple births, ovarian

hyperstimulation syndrome, fluid

accumulation in cavities

Female infertility

ClomiphenePartial estrogen agonist (competitive

inhibitor of ER)Admin: oral x5 days

Ovarian enlargement, vasomotor

flushing, OHSS

↑amplitude (not frequency) of

pulsatile LH & FSH secretion

Induce ovulation

Dx gonadotropin secr'n

GnRH Gonadorelin

Leuprolide, Goserelin

Binds GnRH receptor → ↑Ca2+ →

PLC → ↑FSH & ↑LH

Long-acting agents (leuprolide,

histrelin, nafarelin, goserelin) have D-

AA's at cleavage site

Hypogonadism, ↓bone

mineralization, ↑lipids

Pulsatile: ↑LH & FSH release

Continuous: ↓LH & FSH release

GnRH deficiency

Delayed/precoc. Puberty

Gn-depen. Disease

Ganirelix

Cetrorelix

Competitive antagonists binding

GnRH receptor → ↓LH > ↓FSHsubQ

No transient rise in gonadotropin

secretion as with continuous GnRH

administration

Inhibit premature LH surge

in ovary stim.

Post.

Pituitar

y

Vasopressin

Desmopressin

Binds V1a receptors → GI/vasoCX

Binds V1b receptors → ↑ACTH

Binds V2 receptors → ↑aquaporins

Nasal spray, subQVasoCX

↑GI muscle, ↑uterine muscle

Desmopressin challenge: urine Osm

should ↑50% w/central DI

SIADH: Rx w/loop/demeclocycline

Central diabetes insipidus

Dx central/nephro DI

Post-op ileus...eso varices

Gro

wth

Horm

one A

ssocia

ted A

gents

HP

A A

xis

HP

T A

xis

Gonadotr

opin

s


17 β-estradiolAdmin: transdermal patch

Most potent natural steroid

Extensive first pass metabolism

Esterified estradiolConjugated & esterified natural

steroidsAdmin: IM

Hormone replacement

(Primary hyogonadism)

Prostate cancer

Ethinyl estradiol

MestranolAdmin: PO

↓ first pass metabolism (ethinyl)

Estradiol cypionateAdmin: IM (x1/month)

Insoluble in water

Diethylstilbesterol

MethallenestrilSynthetic non-steroidal estrogens

Admin: PO

As potent as estradiol

Longer t1/2 than estradiol

Advanced prostate

carcinoma

Progesterone

MedroxyprogesteroneAdmin: IM

>oral activity than progesterone

Endometriosis

Dys/amenorrhea

Norethindrone

Norgestrel

Levonorgestrel

Oral contraceptive

Suppress gonadotropins

FulvestrantPure estrogen receptor antagonist →

ER downregulation

Admin: IM (x1/month)

As effective as anastrozole

ER+ metastatic breast

cancer

TamoxifenBreast: estrogen antagonist

Lipids, bones, uterus: agonistER+ breast cancer

Raloxifene↓total cholesterol

↓risk of breast cancer

Osteoporosis

(in post-menopausal)

ExemestaneBinds irreversibly to aromatase →

inhibiting conversion to estrogenStructure similar to androstenedione

Anastrozole Nonsteroidal aromatase inhibitor

Anti

Pro

gestin

MifepristoneCompetitive binding to progesterone

receptor & ↓prostaglandin

dehydrogenase

Inh. prog receptor & ↑PG → uteroCX

Given w/misoprostol 2 days laterAlso blocks glucocorticoid receptor

Abortifacient

Cushing syndrome

The only role of the progestin

component of combination oral

contraceptives is to protect

endometrium from estrogen-induced

hyperplasia & cancer

Estr

ogen R

ecepto

r

Modula

tors

Estr

ogen

Synth

esis

Inhib

itors

Breast cancer

(unresponsive to

tamoxifen)

Pro

gestins ↑fat deposition & weight gain

Acne

Menstrual abnormalities

Uterine cramps

Hirsutism (androgenic preps)

↑risk of breast cancer

Ethinyl estradiol = #1 estrogen

Norethidrone = #1 progestin

Low-dose mono-triphasic = #1

~

Suppress ovulation by negative

feedback on gonadotropin release

~

Progestins = thicken cervical mucus

~

Thin endometrium

↓ ovum transport

~

↑hormone binding proteins

↑insulin secretion & resistance

Synthetic steroidal estrogens

Oral contraceptive

Hormone replacement

(Primary hypogonadism)

Estr

ogens

Endometrial hyperplasia

Endometrial cancer

Breast tenderness

Feminization in males

Cholestasis (GB disease)

Hepatic adenomas

↑plasma TAG

Thromboembolic disease/MI

Headache, migraine

BC Interax: ABX, phenytoin,

barbiturates


LevothyroxineIdentical to endogenous T4

Converted to T3

Intrx: steroids, tmxfn, opioid, 5-FU,

phenytoin, CPZ, salicylate, benzos

Contraind: adrenal insufficiency

Nervousness, arrhythmia, HTN,

SOB, N/V, diarrhea, heat intolerance,

↓reproductive fx

↑TBG in children & preggos →

↑doses required Thyroid hormone replacement

Propylthiouracil

Methimazole

Inhibit thyroid peroxidase →

↓TH synthesis

Propyl: Preggos

Methim: longer duration

Rash, agranulocytosis, arthralgia,

myalgia, hepatic necrosis (P),

cholestatic jaundice (M)

Propylthiouracil ↓T4→T3 conversion Graves disease

Thyrotoxicosis

Radioactive iodine Selectively destroys thyroid tissue

Coadmin: β-blockers or Ca2+

channel blockers for Sx

Contraind: preggo

HypothyroidismDoesn't increase cancer risk or

fertility or effect offspringHyperthyroidism

Sodium IodideTraps thyroid iodide & blocks thyroid

hormone release

Coadmin: β-blockers & Ca2+ channel

blockers & thionamideThyrotoxic crisis

PTH Teriparatide acetate

Binds PTH receptors → ↑Ca2+ bone

mobilization & ↑renal Mg & Ca (↓PO4)

reabsorption & ↑vit.D production

Daily intermittent admin ↑osteoblasts

& bone formation

(not bone resorption!)

Not used to treat hypocalcemia

Hypoparathyroidism

Dx pseudohyperPTH

Osteoporosis

Vitamin D Calcitriol

Binds VitD receptor + RXR →

↑calbindins & ↑osteocalcin &

↑osteoclast formation & ↑Ca2+

Stored for prolonged periods in fat Hypervitaminosis D: hypercalcemia

HypoPTH, pseudohypoPTH

Rickets, osteomalacia

Osteoporosis

CalcitoninBinds calcitonin receptors → ↑cAMP

→ ↓osteoclast-mediated Ca2+

mobilization & ↑ excretion

Nausea, facial flushing, hand

swelling, urticaria, resistance

Salmon CT is ↑potent and ↑t1/2

20% develop resistance

Hypercalcemia

HyperPTH, ↑VitD, Bone mets

Osteoporosis, Paget's Dz

Etidronate

Alendronate

Risedronate

Bisphosphonates (pyroPO4 analogs)

Bind OH-apatite → ↓osteoclasts

↑bone mass

Absorbed IV much better than PO

PO: take w/full glass of water

Hypocalcemia, hypophosphatemia

Upper GI distress

Paget's Dz

Osteoporosis

Malignancy ↑Ca2+

Hydrocortisone

CortisoneShort-acting

Prednisone

Prednisolone

Short-acting

4x anti-inflammatory

TriamcinoloneIntermediate-acting


5x topical

DexamethasoneLong-acting


10x topical

Dx of hypercortisolism

Congenital adrenal

hyperplasia

Betamethasone Inhaled Asthma

AC

TH

CosyntropinACTH analog w/complete biological

activity

Plasma cortisol measured 30-60 min

after IM/IV administration

Replaced therapeutically with steroid

hormonesDx of adrenal insufficiency

FludrocortisoneBinds mineralocorticoid receptor →

↑Na+ reabs. & ↑K+ secretion

Hypernatremia, hypokalemia

Metabolic alkalosis, hypervolemia

Hypertension

Primary adrenocortical

deficiency

Metyrapone Blocks cortisol synthesis

AminoglutethimideBlocks conversion of cholesterol →

pregnenalone

KetoconazoleInhibit P450 enzymes required for

steroid synthesis

Spironolactone

Drospirenone

Competitive mineralocorticoid receptor

antagonistPrimary hyperaldosteronism

Th

yro

id

Ca

lciu

m H

om

eo

sta

sis

Cushing's syndrome

Bind glucocorticoid receptors →

↑gluconeogenesis

↑glycogenesis

↑hormone-sensitive lipase

↑blood glucose

↓cytokines

↑vasoCX

demarginalized PMNs

↓vitamin D → ↓Ca2+ absorption &

↑Ca2+ clearance & ↑bone resorption

↑susceptibility to infx

Inhibits growth in kids

Myopathy

Osteoporosis

Cataracts

Adrenocortical atrophy

Iatrogenic Cushing's

Addison's disease

Glu

co

co

rtic

oid

sC

ort

ico

ste

roid

An

tag

on

ists


ChloroquineSchizonticide → terminates fever &

parasitemia

Buildup of free heme

Resistance: mutant PfCRT trx

(reversed by verapamil & desipramine)

Pruritus, nausea, anorexia, blurring

Hemolysis in G6PD, Wide QRS

Agranulocytosis, oto/retinopathy

PF malaria

Hepatic amebic abscess

Quinine

QuinidineUnknown

Metabolized by liver, excreted by kidney

Coadmin: doxycycline

Only used in chloroquin-resistant

Cardiotoxicity, hematologic

Cinchonism, hypersensitivity

Blackwater fever, ↓glucose, uteroCX

PF malaria

MefloquineSchizonticide

Used as prophylaxisLong half-life (~20 days)

GI

Neuropsychiatric

Cardiac & blood dyscrasias

PF malaria

(chloroquine resistant)

Primaquine Synthetic 8-aminiquinolineAbsorbed GI

Half-life: 3-8 hours

GI, methemoglobinemia

Hemolysis in G6PD

Cardiac & blood dyscrasias

Only agent active against dormant

hypnozoite liver form

(P. vivax & P. ovale)

Fola

te

Inhib

.

Pyrimethamine

Proguanil

Active against RBC forms

Inhibit DHF reductase → ↓folate

Coadmin: sulfa drugs

(inh. DHP synthase = synergy)

GI

Pruritus

AB

X

Tetracycline

Doxycycline

Clindamycin

Action is too slow to be used as

monotherapy

Doxycycline added to quinine trx

Clindamycin instead of doxy for

preggos

Atovaquone Combined w/proguanil (malarone) GINot to be used alone

(Resistance & toxicity)

Halofantrine

ArtemisinSesquiterpene lactone peroxide →

dihydroartemisin

PF malaria

(drug-resistant)

Malaria

Mis

cella

neous

Main

Dru

gs Does not eliminate liver forms

(P. vivax & P. ovale)

No P. falciparum gametocyte kill

Active against RBC forms


SuraminAdmin: IV

Does not cross BBB

GI

Neurological

Cardiovascular, blood dyscrasias

Adding pentamidine may increase

efficacy

Early hemolymphatic

African trypanosomiasis

Melarsoprol Trivalent arsenical compoundAdmin: IV

Does cross BBB

Reactive encephalopathy

Renal & cardiac toxicity

Hypersensitivity

EflornithineInhibits ornithine decarboxylase → blocks

conversion of ornithine → putrescineAdmin: IV

GI

Blood dyscrasias

Mammalian OC enzyme very short

half-life…trypanosome OC enzyme

much more stable

Nifurtimox Nitrofuran structure Admin: oralGI

CNS

Decreases severity of acute disease,

but many times fails to eradicate the

parasite

Acute American

trypanosomiasis

Stibogluconate Pentavalent antimonialAdmin: IM or IV

(daily)

GI

Fever, arthralgias

T wave changes, QT prolong

First line therapyCutaneous & visceral

leishmaniasis

MetronidazoleCauses multiple-strand breaks, disruption of

DNA replication & trx & inhibits DNA repairAdmin: oral

Nausea, headache, metallic taste

GI, CNS, hematologic

Disulfiram-like reaction

May potentiate oral anticoagulants

Giardiasis

Entamebiasis

Trichomoniasis

Iodoquinol Coadmin: metronidazoleGI

Pruritis

Contraind: Optic neuropathy

Renal or thyroid disease

Iodine intolerance

ParomomycinLittle GI absorption

Renal excretionGI

EmetineEffective against tissue E. hystolytica

trophozoites

Heart failure

Hypotension

Use limited to severe amebiasis

when metronidazole unavailable

Pentamidine Effective against trypanosoma & P. carinii

Admin: IM or IV

Half-life: ~6 hr

Accumulates in tissues (12 days)

Cardiovascular

Pancreatic, hepatic, renal, blood

Bronchospasm, dyspnea

Injectable (trypanosomatid)

Inhalation (pneumocystis)

Trypanosomes

P. carinii

NitazoxanideBlocks pyruvate:ferredoxin oxidoreductase

pathwayConverted to active tizoxanide

Useful in trx metro-resistant protozoa

& tapeworms

Giardiasis

Cryptosporidiasis

(+ tapeworms)

PiperazineDirect GABA agonist

Blocks ACh at NMJ to produce nematode

flacid paralysis

Admin: oral

Excretion: w/in 24 hrsGI Cure rate of ascariasis (>90%) Ascariasis

Pyrantel pamoateTetrahydropyrimidine derivative

NMJ blocking agent → paralyzes & expels

Admin: oral

Poorly absorbed from GI (good!)

GI

Insomnia

ACh release & AChE inhibition

Cure rates >90%

Ascariasis

Pinworm

Hookworm

Mebendazole Inhibits microtubule synthesis

Admin: oral

Poorly absorbed from GI

(effect ↑w/fatty meal)

Hypersensitivity reactions

AlopeciaWide-spectrum

Ascariasis

Trichuriasis

Pin & Hookworm

Albendazole Active albendazole sulfoxideAdmin: oral

Metabolized in liver to active form

Mild GI

Long-term use (hydatid):

↑liver enzyme & blood dyscrasia

Admin fasting: luminal parasite

Admin fatty meal: tissue parasite

Coadmin: corticosteroids (cyst)

Cysticercosis

Hydatid disease

Round, Pin, Hook

NiclosamideSalicylamide derivative

Inhibits oxidative phosphorylationAdmin: oral Mild GI Tapeworm

PraziquantelIsoquinoline-pyrazine derivative

↑cell membrane permeability to Ca2+ →

paralysis

Admin: oral

[↑]: cimetidine or carbs

[↓]: steroids or antiepileptics

Mild: headache, dizziness, GI,

myalgia, pruritis, feverBitter taste (don't chew)

Schistosomiasis

Hydatid disease

Neurocysticercosis

Trematodes & Cestodes

Bithionol Admin: oralGI

Skin rashFascioliasis

DiethylcarbamazepineSynthetic piperazine derivative

Immobilizes & alters microfilament surface

structure

Admin: oral

Half-life: 2-3 hrs (acidic urine)

10 hrs (alkaline urine)

Mild: headache, dizziness, GI, fever,

rash, blood dyscrasias

Give w/antihistaminics

(↓allergic reactions)Filariasis

CNS advanced

African trypanosomiasis

Effective against intraluminal E. hystolytica

(not tissue)

Entamebiasis

An

ti-T

rem

ato

de

sA

nti-H

elm

inth

sT

ryp

an

oso

mia

sis

& L

eis

hm

an

iasis

Oth

er

Pro

tozo

a


PhentermineAmphetamine derivative

Inhibits NE reuptake

Diethylproprion

Phendimetrazine

Benzphetamine

Inhibit NE reuptake

Phenylpropanolamine NE targetWithdrawn in 2000 due to

hemorrhagic strokes in women

Only approved OTC appetite

suppressant

Ephedra Appetite suppressant & weight loss ↑weight loss w/: caffeine & aspirinCardiac arrest, HTN, arrhythmia,

stroke, seizure, MIFound in the herb Ma Huang

Obesity

Asthma

URI

Mix

ed

Targ

et

s Sibutramine Inhibits NE, 5-HT, DA reuptake

Interax: MAOI, SSRI, triptans,

ergotamines, dextromethorphan,

opioids, lithium, tryptophan

Drug mouth, insomnia, constipation,

↑BP, ↑HR, abuse

Lose 10-15% of weight

Contraind: HTN, renal/liver impair,

addx, CAD, CHF, arrhythmia, stroke

Fat

Meta

b.

OrlistatInhibits GI lipases → ↓dietary fat

absorptionInterax: cyclosporine

Gas, oily stools, ↑defecation

↓absorption of ADEK & β-carotene

Lose 8-10% of weight

Improves H1Ac & sulfonylurea dose

Contraind: malabsorption, cholestitis

Obesity

Obesity

Nora

dre

nerg

ic T

arg

ets

Drug mouth, insomnia, constipation,

↑BP, ↑HR, abuse

Coadmin: fenfluramine

(Pulmonary HTN & valve problems)

Interax: MAOI, guaneth, stim, EtOH,

sibutramine, TCA

Fenfluramine releases 5-HT &

inhibits 5-HT reputake

Contraind: hyperthyroid, HTN, CVD,

glaucoma, anxiety


Lispro insulinAble to stay as monomer, because

proline & lysine AA's are swappedUltra-fast & short-acting

Regular insulinZinc insulin crystals in a neutral,

unbuffered suspension

Short-acting

Admin: IV or subQ

(30-60 min before meal)

NPH insulinInsulin(-) complexed w/protamine(+)

& zinc

Lente insulin30% semilente insulin + 70%

ultralente insulin crystals in acetate

buffer

Ultralente insulinExcess zinc (produces large

crystals) in acetate bufferLong-acting

Glargine insulinPeakless recombinant insulin that

precipitates in neutral subQ tissues

Ultra-long-acting

Delayed onset of action

PramlintideAmylin analog → ↓gastric emptying

& ↑satiety & ↓post-pran glucagon

Admin: subQ w/mealtime insulin

Don't use w/acarbose

↑Insulin-induced severe

hypoglycemia

Type 1 diabetes

Type 2 diabetes

ExenatideGlucagon-like peptide agonist →

↓gastric emptying & ↓post-pran

glucagon & ↑insulin secretion

GLP-1 secreted in response to food

to potentiate glucose-stim insulin

release

N/V, diarrhea Type 2 diabetes

TolbutamideFirst generation:

Shortest acting

Least potent

ChlorpropamideFirst generation:

Longest acting (60 hours)

Intermediate potency

May induce SIADH

or alcohol flush reaction

Recurring hypoglycemia

Glipizide Second generation: Extended release form does not

induce weight gain!

Glyburide Once daily dosingDoes not cross placenta

(can use for gestational diabetes)

GlimepirideHighest potency

Once daily dosing

Binds a site on K+ channel different

from all other sulfonylureas

↑muscle insulin sensitivity

RepaglinideMetabolized by liver

Half-life: 1 hour

NateglinideMetabolized by liver

Half-life: even shorter & rapider

Phenformin

Metformin

RosiglitazoneMetabolized to inactive metabolites


↑albumin bound

PioglitazoneMetabolized to weak metabolites


↑albumin bound

α

glc

sdase

inhib

. Acarbose

Miglitol

Competitive α-glucosidase inhibitors

→ ↓carbohydrate digestion/absorb

Blunted post-prandial glucose

Low systemic bioavailability

Taken with a meal

Flatulence, nausea, diarrhea

Contraind: IBS, obstruction, ulcer

Do not cause hypoglycemia, lactic

acidosis, or weight gainType 2 diabetes

Dip

ep

Pptd

ase

4 inhib

SitagliptinBlocks dipeptidyl peptidase IV →

↓GLP-1 & GIP → ↑post-pran insulin

With: diet & exercise

With: metformin or TZDType 2 diabetes

Diazoxide↑ open time of ATP-sensitive K+

channel → ↓insulin release

Metabolized in liver

Half-life: 48 hours

Nausea/vomiting

Fluid & salt retention

Does not inhibit the synthesis of

insulin, only the releaseInsulinoma

GlucagonBinds glucagon receptor → ↑cAMP

→ ↑(P) glycogen phosphorylase &

synthase

Admin: subQ, IM, IV

Half-life: 3-6 minutes

Metabolism: 25% first-pass

Nausea & vomiting

Inotropic & chronotropic

RX of GI smooth muscle

Release catecholamines & CT

Severe hypoglycemia

Shock & GI RX

Dx pheochr-cytoma

Type 2 diabetes

Severe hypoglycemia

(chlorpropamide & glyburide)

Weight gain

Skin reactions & erythema

Blood dyscrasias

Hepatic dysfunction

(All are liver metabolized)

GI disturbances

Bind SUR receptors associated w/

ATP-sensitive K+ channels (diff. site

from sulfonylureas) → ↓K+ current

→ ↑insulin secretion

Type 2 diabetesHypoglycemia

Weight gainUsed for post-pran hyperglycemia

TZ

Ds

Hyp

erg

lyce

mic

sIn

sulin

Peptides

Contraind: hypersensitivity,

gastroparesis, hypoglycemia

unawareness

Sulfonylu

reas

Meglit

inid

es

Big

uanid

es

Bind SUR receptors associated w/

ATP-sensitive K+ channels →

↓K+ current → ↑insulin secretion

↓ gluconeogenesis

↑insulin-stimulated GLUT4

trafficking to membrane

↑cAMP-act. protein kinase

(Increase tissue sensitivity to

insulin)

Lactic acidosis

(Even less with 2nd generation)

Cardiovascular disorders

Hypoglycemia

(Counter-reg. often impaired)

Mild: juice/glucose

Severe: glucagon

~

Allergy

(insulin or protamine)

~

Insulin resistance (IgG)

~

Lipohypertrophy

Insulin requirements ↑ during 2nd

half of pregnancy

~

If impaired renal fx: ↓insulin

clearance

Intermediate-acting Type 1 diabetes

Type 2 diabetes

(obese)

Do not cause hypoglycemia

(even at high doses)

↓TAG, ↓cholesterol, ↓LDL, ↑HDL

Weight loss & ↓BP

Not significantly metabolized

90% oral dose gone in 24 hours

Half-life: 2 hours

Low potency

Bind PPAR-γ receptor + RXR →

↑GLUT1 & GLUT4

↑lipoprotein lipase, FABPaP2

↓TNFα, ↓leptin

Troglitazone: hepatotoxicity

Heart failure

Angina, MI

Do not cause hypoglycemia

Current TZD's do not cause

hepatotoxicity

Type 2 diabetes


NiacinVitamin B3 → ↓hepatic TAG

synthesis & ↑lipoprotein lipase →

↓apoB → ↓VLDL → ↓LDL

Half-life: 1 hour

Used w/: bile acid binding resin

Used w/: HMG CoA reductase inh.

Flushing, pruritis

Nausea, diarrhea, peptic ulcer

Hepatotoxic, glucose intol., gout

Most effective agent to ↑HDL

Only agnet to ↓Lp(a)

HyperTAG

Familial hyperTAG

FC hyperTAG

Gemfibrozil

Fenofibrate

Clofibrate

Bind PPAR-α+ RXR → ↓apoC-III &

apoB & ↑lipoprotein lipase → ↓VLDL

→ ↓LDL & ↑apoA

Half-life: 1.5 hours

Highly albumin bound

GI disturbances

Rash, myopathy, arrhythmia

Fatigue

HyperTAG

Dysbetalipoproteinemia

FC hyperTAG

Cholestipol

Cholestyramine

(+) charged resins that bind bile

acids → ↓reabsorption of bile acids

→ ↓cholesterol & ↑LDL receptors

Taken with meals POHyperTAG

GI (constipation)

Negligible systemic bioavailability

Approved for use in children

Familial HyperTAG

FC hyperTAG

StatinsInhibit HMG CoA reductase (HMG

CoA → mevalonate) → ↓cholesterol

& ↑LDL receptors

First pass metabolism

Cytochrome P450 metabolized

Extensively protein bound

Myopathy (↑CK)

Renal dysfx (myoglobinuria)

Rhabdomyolysis (w/gemfribrozil)

↑BMP-2 → ↑osteoblasts →

↓fracture risk

Hypercholesterolemia

(& familial)

Ezetimibe↓cholesterol transport at brush

border in small intestine lumen →

↓cholesterol & ↓LDL-C & ↑HDL

Enterohepatic recycling

Half-life: 22 hours

Low systemic bioavailability

Cholesterol lowering effect limited

by ↑liver cholesterol synthesisHypercholesterolemia

Estrogen

replacement

↓lipid oxidation

↑TAG, ↑HDL

↓LDL, ↓cholesterol

Progestins have undesirable effects

on plasma lipids

(CAD & stroke)

Plant stanol

esters↓absorption of dietary cholesterol

Omega-3 fatty

acids

↓endothelial inflammation

↓LDL & ↓TAG

Monosaturated fatty acids (oleic):

↓LDL but not HDL

Ethanol ↑HDL & ↓LDL No association with beverage types

Trig

lyce

rid

es

Ch

ole

ste

rol


BacitracinOintment

Used w/neomycin or polymyxin

Absorbed through skin

Allergic contact dermatitisGram (+) bacteria

Anaerobes (cocci)

Mupirocin Effective against most gram (+) Intranasal preparationPEG vehicle can irritate nasal

mucosa

Impetigo

(S. aureus & S. pyogenes)

Polymyxin BP. aeruginosa

E. coli, enterobacter

Klebsiella

Neomycin

Gentamycin

Sensitization

Cross-sensitivity to streptomycin,

kanamycin, gentamycin

Clindamycin10% of topical application is

absorbed

Bloody diarrhea

Pseudomembranous colitis

ErythromycinBurning

Irritation

SulfacetamineTopical

Alone or with sulfur preparationContraind: sulfa allergy

Acne vulgaris

Acne rosacea

MetronidazoleEffective against Dermodex brevis

Anti-inflammatory

Possible carcinogen

Contraind: pregnancy & lactationAcne rosacea

AzolesEffective against dermatophyte

infection

Cream, shampoo, lotion, vagial

tablets, suppositories

Seborrheic dermatitis

Candidiasis

CiclopiroxolamineUse in onychomycosis only effective

in ~10% of patients

Dermatophytes

Candida

P. obiculare

Naftifine

TerbinafineAllylamines

Inhibit ergosterol synthesisDermatophytes

Tolfnaftate Well toleratedCessation of therapy generally

followed by infection recurrence

Amphotericin B

NystatinWell tolerated Superficial candidiasis

GriseofulvinEffective against growing cells

Inhibits fungal cell wall synthesisFine microcystal suspension

Diarrhea

Photosensitivity

Headaches

Contraind: porphyria, liver dysfx Tinea infections

KetoconazoleInterax: benzos → ↑sedation

statins → rhabdomyolysis

Gynecomastia

Hepatitis

Ventricular dysfx

Chronic gen. MC candidiasis

Dermatophytes

Acyclovir Decreases viral shedding OintmentPrimary cutaneous HSV

Limited MC HSV

PencyclovirDecreases viral shedding (time) &

↓time to healing

Cream

Applied at first sign of infectionRecurrent orolabial HSV

LindaneShampoo or lotion

~Absorbed via skin, ↑in fatty tissue,

excreted in urine in 5 days

Hematotoxicity

Neurotoxicity

Pediculosis capitis

Pediculosis pubis

Scabies

SulfurSkin staining

Unpleasant odor

Lack of systemic effects

(good for kids and preggos)Scabies

Hydroquinone

MonobenzoneInhibit tyrosinase → ↓melanin →

↓skin hyperpigmentation

Hydroquinone = temporary

Monobenzone = permanent

Local irritation

Allergy

Trioxsalen

Methoxsalen

Produce repigmentation of

depigmented macules

Psoralens intercalate w/DNA

Skin cancer

CataractsVitiligo

Retinoic acidTretinoin (ATRA)

↓epidermis cohesion

↑cell turnover

Admin: topical

Applied to dry skin only

Erythema

Dryness

Sunlight sensitivity

May appear worse in the first month,

as quiescent comedones emerge &

rupture

Acne vulgaris (comedones)

Light-damaged skin

Adapalene Naphtoic acid analogSimilar to retinoic acid but less

irritationMild to moderate acne

IsotretinoinSynthetic retinoid-like drug

Decreases sebaceous gland functionAdmin: oral

Similar to hypervitaminosis A:

dryness, itching, IBS

IBS, muscle pain, teratogen

Severe cystic acne

Benzoyl peroxideConverted to benzoic acid

Effective against P. acnesAdmin: topical Skin irritation Acne vulgaris

Acitretin Admin: oral

TazaroteneAnti-inflammatory

AntiproliferativeExtreme caution in young women

Calcipotriene Synthetic vitamin D3 Skin dryness

Itching

CorticosteroidsAnti-inflammatory

Antimitotic

Skin atrophy, rosacea

↑IO pressure

Cushing's syndrome, growth

Keloids, cystic acne, alopecia areata

= triamcinolone injection

Tar compoundsByproducts of petrol distillation

Antipruritic

Irritant folliculitis

Allergic contact dermatitis

Psoriasis

Chronic lichenified dermatitis

Salicylic acid Solubilize cell surface protein debris

Anaphylactic shock

Irritation & inflammation

Salicylism

Propylene glycolUsed for elimination of keratolytic

debrisAlone or with: salicylic acid Allergic contact dermatitis

Urea↑prekeratin & keratin solubility →

↑elimination

Xerosis

Hyperkeratosis

(palms & soles)

Pru

ritis

DoxepinPotent histamine receptor (H1 & H2)

antagonistAdmin: oral or topical Allergic contact dermatitis

SE's & contraindications similar to

anticholinergics

Atopic dermatitis

Lichen simplex chronicus

MinoxidilReverses progressive ↓ of terminal

scalp hairsAdmin: topical

Discontinuation causes continued hair

loss in 4-6 months

FinasterideBlocks 5α-reductase → inhibits

conversion of testosterone → DHTAdmin: oral

↓libido

Ejaculation disorders

Eretctile dysfunction

Pregnant women should not be

exposed (hypospadias)

An

ti-

infla

mm

ato

ryK

era

toly

tics

Tri

co

ge

nic

s

Psoriasis

Androgenic alopecia

An

tip

ara

site

sS

kin

Pig

me

nta

tio

nA

cn

eP

so

ria

sis

Acne vulgaris

To

pic

al A

ntifu

ng

als

Ora

l

An

tifu

ng

als

To

pic

al

An

tivir

als

Effective against most gram (-) TopicalBa

cte

ria

l In

fectio

ns

Acn

e V

ulg

ari

s

Effective against

Propionibacterium acnes


ColchicineBinds microtubule tubulin →

↓polymerization → ↓WBC migration

& urate phagocytosis

Admin: oral

Accumulates in WBCs

Deacetylated in liver

GI

Blood dyscrasias

CNS depression, shock

Gouty arthritis attacks

Pseudogout

Familial Med. fever

Indomethacin Anti-inflammatoryNot to be used in chronic gout or

prophylaxisAcute gouty attacks

ProbenecidInhibits proximal tubule reabsorption

of urate

Admin: oral


Interax: PCN, ASA, sulfa, allopurinol

GI

Dermatitis

Nephrotic syndrome

Not to be used in acute gout attacks

SulfinpyrazoneInhibits proximal tubule reabsorption

of urate

No anti-inflammatory or analgesia

Very highly plasma protein boundPotentiates insulin & oral

hypoglycemics

Ura

te

Inh

ib.

AllopurinolComp. inhibits xanthine oxidase

↓conversion of hypoxanthine →

xanthine → uric acid

Metabolized to oxipurinol (active)

Depletes purine precursors

(5'-PRPP)

Maculopapular rash (pruritus)

GI, hepatotoxicity

Fever, hypersensitivity

Not useful for acute gout attacks

Inhibits kidney reperfusion injuryChronic tophaceus gout

Hyperuricemia control

Urico

su

ric

Ag

en

tsM

isc.


Albuterol

Terbutaline

Metaproterenol

Admin: Metered dose inhaler

Nebulizers

Anxiety, tremor, restlessness, ↑HR,

hypokalemia

Albuterol is the most used

Metered dose inhaler is most

common

Acute asthma attack

Salmeterol

Formoterol

Long-acting

Salmeterol = slow-acting

Formoterol = fast-acting

Salmeterol is not useful in acute

asthma attacks!

(Slow onset of action)

Severe refract asthma

COPD

Chronic bronchitis

TheophyllineAntagonist at adenosine A1 receptor

→ ↓Gi → ↑cAMP & ↓PLC →

bronchoRX

Admin: IV

Low therapeutic index

Headache, CNS stimulation

N/V, epigastric pain

Arrhythmias, seizures

Nocturnal asthma

Ipratropium

TiotropiummACh receptor antagonist → ↓Gi →

↑cAMP & ↓PLC → bronchoRXAdmin: dry powder inhalation

Chronic bronchitis

Limited in asthma

Cromolyn No role in acute asthma!

NedocromilGreater potency than cromolyn

Additive therapeutic effects with

corticosteroids

Prednisone

MethylprednisoneAdmin: oral

Methylprednisone

Hydrocortisone Admin: IV

Beclomethasone

Flunisolide

Triamcinolone

Admin: inhalationReformulated as HFA inhaler

systems (+MDI)

Troleandomycin

Gold salts

Methotrexate

TAO = macrolide antibiotic → inhibit

corticosteroid metabolismSteroid-sparing therapy

MontelukastWeak anti-inflammatory &

bronchodilator actions

Best if added to ICS therapy

(allows lower doses)

Omalizumab Monoclonal anti-IgE antibodyAllowed lower doses of ICS &

↓hospitalizations & ER visits

Iodinated glycerolMucolytic that improves

expectoration, cough, chest

discomfort, duration of attack

Tumorigenicity forced removal from

the marketChronic bronchitis

Systemic corticosteroid effects

Hoarseness

Oropharyngeal candidiasis

Coughing, wheezing

HPA axis suppression

Long-term therapy (>3weeks) only if

refractory to other trx

Inhibit late-phase reactions of

inflammation

Decrease bronchial reactivity

Most potent anti-asthma agents

available

Acute asthma

Asthma

(maintenance)

β2-agonists → Gs → ↑cAMP →

bronchoRX

Asthma

(maintenance)

Admin: metered dose inhaler

Spinhaler

4x day regimen

Prevents mast cell degranulation

(asthma prophylaxis)Virtually no side effects

pharmacology - drug charts

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