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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)
↓ acid, ↑ mucus,
↑ blood↓ tone
Kidney: ↑ blood,
↑ diuresis, ↓ ADH
↑ body temp
↓ NE
Misoprostol
AlprostadilPGE2 ↓ intraocular
pressure↓ plt aggregation
vasodil + vasocx
(↑ IP3 & ↑ Ca2+)
bronchodilation
(↑ cAMP)
↓ acid, ↑ mucus,
↑ 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)
↓ acid, ↑ mucus,
↑ 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
β1 ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin
β2
α1
α2 ↓ SNS outflow ↓ BP
α1 Reflex bradycardia ↑ DBP (vasocx)
β1 ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin
α1
α2
β1
Ephedrine
Clonidine α2 ↓ SNS outflow ↓ BP HTN
Brimonidine α2 ↓ SNS outflow ↓ BP OA glaucoma
Tizanidine α2 ↓ SNS outflow Multiple sclerosis
β1 ↑HR, ↑CX, ↑CO ↑ SBP (indirect) Kidney: ↑ renin
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 β1 ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin
Anti β2 bronchocx
Anti β1 ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin
Anti β2 bronchocx
Anti β1 ↓HR, ↓CX, ↓CO ↓SBP Kidney: ↓ renin
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
Ciliary muscle CX → widens trabecular network → ↑ drainage of aqueous humor
Ciliary muscle CX → widens trabecular network → ↑ drainage of aqueous humor
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
Adverse cardiac events
Diltiazem Ca2+ channel
blocker
Initial: ?
Eventual: ?Similar to Verapamil…but less ↓ HR & ↓ CO
Little reflex tachycardia
Adverse cardiac events
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)
Administer: oral or IV
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.)
Bind transpeptidase & prevent
cross-linking
Allergy
(5-10% PCN-allergy cross-
hypersensitivity)
Bind transpeptidase & prevent
cross-linking
1) Altered transpeptidases
2) ↓ permeability
3) β-lactamases
Administer: oral or IV
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
Administer: oral or IV
Distribution: good bioavailability
Crosses BBB
Allergy
(Can be desensitized)
Administer: oral or IV
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
Administer: oral or IV
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
Administer: oral or IV
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)
Block protein synthesis by bacterial
ribosomes
Block protein synthesis by bacterial
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
Administer: oral or IV
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
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
Nausea
ProcarbazineInhibits DNA/RNA/protein synthesis
Hodgkin/Non lymphoma
SCLC, Melanoma
Brain tumors
Bone marrow (immunosupp)
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.)
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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
Hodgkin/Non-H lymphoma
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.)
Bone marrow (immunosupp)
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.)
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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
Bone marrow (immunosupp)
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.)
Bone marrow (immunosupp)
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
(Post-men; in ER+ tumors)
CNS depression
(drowsiness, blurry vision, ataxia)
Post-menopause women
produce estrogen in adrenal
cortex….. Medical
Anastrozole Breast cancer
(Post-men; in ER+ tumors)
GI, weakness, headaches, bone/back
pain
Reduced incidence of blood clots
& vaginal bleeding compared to
Tamoxifen
Letrozole Breast cancer
(Post-men; in ER+ tumors)
Nausea
Musculoskeletal pain
Prednisone Converted to prednisolone → binds
receptor
ALL, CLL
Hodgkin/Non-H lymphoma
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
(prolong inactive state)
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
Gen. tonic-clonic seizures
Trigeminal neuralgia
Bipolar Disorder
(not absence)
Phenobarbital
Block Na+ channel
(prolong inactive state)
Prolongs GABA-A channel activity
Block AMPA receptor
Sedation, ataxia, respiratory depression, rash,
nystagmus, porphyria, tolerance, withdrawalCongeners (mephobarbital & primidone)
Partial seizures
Gen. tonic-clonic seizures
(not absence)
Vigabatrin Enhance GABA
LamotrigineBlock Na+ channel
(prolong inactive state)
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
(prolong inactive state)
Enhance GABA activity
Somnolence, dizziness, fatigue, cognitive slowing,
weight lossUsed for weight loss
Partial seizures
Gen. tonic-clonic 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
(prolong inactive state)
↑ 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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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)
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Gastric/duodenal ulcers
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
Gastric/duodenal ulcers
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Ventricular 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 tachycardia
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Different structure from thiazides
Chlorthalidone Longer actingSame potency as HCT
Different structure from thiazides
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Contraind: anti-coagulants
(may inhibit platelet aggregation)
As effective as antihistaminics in
nausea
Motion sickness
Morning sickness
Ginseng Many have NO donor capability
Contraind: anti-coagulants
(may inhibit platelet aggregation)
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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 anti-inflammatory
5x topical
DexamethasoneLong-acting
30x anti-inflammatory
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Half-life: 3-4 hours
↑albumin bound
PioglitazoneMetabolized to weak metabolites
Half-life: 3-7 hours
↑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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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
Half-life: 6-12 hours
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.
Drug Mechanism Metabolism Toxicity What makes it unique Treats
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