Module 4 Pharmacology

Pharmacy
Board Exam Review

Pharmacology (Pharmacotherapeutics)

Pharmacotherapeutics
-‐ rational use of drugs in the management of
disease
AUTONOMICS
Sympathetic
ANS Parasympathetic
Auerbach
Enteric
Meissner

Receptor Location Response
Synaptic neurotransmission Alpha (α)
Pre-‐synapse α1 (Gq) Smooth muscle
-‐ synthesis of neurotransmitter Vasculature Vasoconstriction
-‐ storage and release of neurotransmittter Prostate Urinary retention
Synapse
Radial muscle Mydriasis
-‐ interface between a neuron and another
of Iris
neuron
Pilimotor Goose bumps
-‐ where neurotransmitters are released
smooth
-‐ neurotransmitters are metabolized or
muscles
taken up again by pre-‐synaptic cells
α2 (Gi) Presynaptic ! sympathetic
Post-‐synapase
tone
-‐ receptor
Blood vessels Vasoconstriction
Ganglion – collection of neurons outside the spinal
cord Beta (β)
β1 (Gs) Heart Chronotropism
Sympathetic (" heart rate,
-‐ fight or flight tachycardia)
-‐ thoracolumbar in location (neurons are Inotropism
taken beside the spinal cord) (" strength of
-‐ ganglionic receptors: Ach, Nicotinic contraction)
-‐ End-‐organ receptor: Norepinephrine Dromotropism
Parasympathetic (" conduction
-‐ rest and digest velocity in the
-‐ craniosacral in location hear)
-‐ ganglionic receptors: Ach, Nicotinic β2 Smooth muscle
-‐ End-‐organ receptor: Acetylcholine Bronchial Bronchodilation
Uterus Tocolysis
SYMPATHETIC DRUGS Skeletal Muscle
A. Biosynthesis/ Fate of Catecholamines muscle contraction
Inward movement
!"#$%&'( !"!!"#
𝑃ℎ𝑒𝑛𝑦𝑙𝑎𝑙𝑎𝑛𝑖𝑛𝑒 → 𝑇𝑦𝑟𝑜𝑠𝑖𝑛𝑒 𝐿 − 𝐷𝑂𝑃𝐴 of K+
→ 𝐷𝑜𝑝𝑎𝑚𝑖𝑛𝑒 → 𝑁𝐸 Blood vessels Vasodilation
→ 𝐸𝑝𝑖𝑛𝑒𝑝ℎ𝑟𝑖𝑛𝑒 (𝑎𝑑𝑟𝑒𝑛𝑎𝑙 𝑚𝑒𝑑𝑢𝑙𝑎) β3 Adipose Lipolysis
“Pare, True Love Does Not Exist” Dopamine
D1 Splanchnic Vasodilation
blood vessels
D2 # D4 CNS

1
Pharmacy Board Exam Review

B. Drugs
I. Direct-‐acting Isoproterenol
-‐ acts on adrenergic receptors -‐ used for heart failure
1. Non-‐selective agonist (α, β, D) -‐ Bronchial asthma
Natural catecholamines Direct acting AE:
NE: α1 = α2 = β1 >>> β2 -‐ receptors -‐ Tachyphylaxis on β2 effects
E: α = α2 β1=D1 Indirect-‐acting
D: D >> β >> α -‐ NT in the cleft
3. β1-‐selective agonists
Kinetics: poor oral BA because they are Dobutamine
metabolized to: -‐ DOC for cardiogenic shock
• Vanillyl-‐Medellic Acid – final product of E,
NE metabolism by MAO & COMT 4. β2-‐selective agonists
• Homovanillic acid SABA (Short-‐acting β-‐agonists)
• Metanephrine -‐ relievers
-‐ E.g. salbutamol

Clinical uses: LABA (Long-‐acting β-‐agonists)
Epinephrine – cardiac stimulant -‐ controllers
• Advanced Cardiac Life Support -‐ Formoterol
-‐ Dose: 1-‐3 mg of 3-‐5 minutes
Uses:
• Anaphylactic shock – caused by histamine • Bronchial Asthma
-‐ Epinephrine has actions that is opposite to • Management of hyperkalemia
that of histamine but binds to a different • Tocolytic – premature labor (give steroids to
receptor (physiologic antagonist) buy time to allow the lungs to mature)
-‐ Dose: 0.3-‐0.5 mg SC every 15-‐20 minutes up Additional use:
to 3 doses -‐ Symptomatic bradycardia (although this is
a β1 effect, e.g. terbutaline)
• Local vasoconstriction
-‐ to prevent wash-‐off of Lidocaine, e.g. 5. α1-‐selective agonist
Lidocaine-‐epinephrine preparations Phenylephrine
Propylhexidine
Norepinephrine Oxymetazoline
-‐ DOC for septic shock Tetrahydrozoline

Dopamine Uses:
Dose Receptor Response • Decongestant
1-‐3 mcg/kg/min D1 Renal vasodilation • Local vasoconstriction
3-‐5 mcg/kg/min β1 Tachycardia AE:
Inotropism -‐ Exacerbate HTN
> 5 mcg/kg/min α1 Vasoconstriction -‐ Urinary retention
Uses: -‐ Tolerance
-‐ Management of septic shock, cardiogenic -‐ Rhinitis medica mentosa (for locally
shock (shock due to a cardiac cause), heart applied decongestant)
failure, complications by anuria o Rebound congestion
AE: o Happens when using nasal
β1 – tachycardia, tachyarrhythmia decongestant for > 3 days
α1 – hypertension, digital necrosis
6. α2 agonist
Uses:
2. β-‐non-‐selective agonist • Tx of HTN (! sympathetic tone)
-‐ stimulates β receptors
2

Phenylpropanolamine (PPA)
Clonidine
-‐ Transient " in blood pressure – due to Uses:
peripheral vasoconstriction • Management of ADHD
Uses: • Appetite suppressant
• Management of HTN • Management of narcolepsy
• Decongestant (nasal spray) SE:
• Management of ADHD -‐ PPA # " risk for stroke
AE: -‐ Phentermine # " risk for pulmonary HTN
-‐ Rebound hypertension upon withdrawal
o Remedy: reinstitute Clonidine or IV. Sympatholytics/ Adrenergic antagonist
give Labetalol α blockers – effect: relieves urinary retention

Methyldopa Types:
-‐ α-‐methyl DOPA Non-‐selective blockers
-‐ 𝑝𝑟𝑜𝑑𝑟𝑢𝑔 → Phentolamine – reversible
!"#$ !"#$%&'()*$+"
𝑐𝑟𝑜𝑠𝑠 𝐵𝐵𝐵 𝛼 − Phenoxybenzamine – irreversible
𝑚𝑒𝑡ℎ𝑦𝑙 𝑑𝑜𝑝𝑎𝑚𝑖𝑛𝑒 Uses:
α-‐methyl dopamine – stimulates α2 receptor • Pheochromocytoma – 1st give α blockers then β
AE: blockers
-‐ sedation
-‐ Hepatotoxicity (>2 g/day) Selective α1 blockers
-‐ (+) Coombs test – hemolytic anemia -‐ Prazosin, Terazosin
SE:
Guanfacine -‐ First-‐dose phenomenon (syncope) # give
Guanabenz at bed time

Selective α2 blockers
7. D1 agonist Yohimbine
Fenoldopam Rauwolfscine
Use: vasodilator
• Adjunct in the management of hypertensive Uses:
crisis (DOC: sodium nitroprusside) • BPH with HTN (DOC: α1 blocker)
• Hyperplasia
• Raynauld’s phenomenon
II. Indirect-‐acting
-‐ " NE in the synapse β blockers:
Based on selectivity
Ephedrine – “Ma Huang” β1 selective Bisoprolol
MOA: Esmolol
-‐ Releases NE into the synapse Atenolol
-‐ Agonist at α1, β1, β2 Metroprolol
Use: Non-‐selective All others
• Decongestant Based on intrinsic sympathomimetic activity (ISA)
• Acute hypertension Carteolol Acebutolol
SE: Labetalol Pindolol
-‐ Exacerbation of HTN Based on membrane-‐stabilizing activity (MSA)
-‐ Tachyarrhythmia Propranolol Pindolol

Acebutolol Metoprolol
III. Centrally-‐acting Sympathomimetics
Labetalol
Amphetamine
Based on presence of α blocking activity
Methyl phenidate
Labetalol Carvedilol
Phentermine
3

Uses: GIT
• Used in HTN (! CO, ! renin secretion) Walls " peristalsis
• Angina pectoris Sphincter Retention
• Stable CHF Urinary bladder
o CI: Px with unstable CHF Detrusor Contraction
• Management of glaucoma (! aqueous humor Urethral Relaxation
production) sphincter
• Management of hyperthyroidism Exocrine glands
• Prophylaxis for migraine Lacrimal Lacrimation
• Familiar tremors glands
AE: Salivary Salivation
-‐ Mask S/Sx of hypoglycemia (tachycardia, glands
diaphoresis, tremors) – monitor glucose! Bronchial " mucus
-‐ Bradycardia/ Heart Block (! firing in the production
SA node, ! rate of conduction in the AV
Sweat glands Sweating
node)
Nicotinic
o CI: Px with heart block
o NN CNS
PARASYMPATHETIC DRUGS NM Skeletal
A. Biosynthesis/Fate muscle

Parasympathomimetics
I. Direct-‐acting
-‐ stimulates cholinergic receptors

Choline esters Alkaloids
Acetylcholine (N,M) Pilocarpine (M)
Betacholine (M) Muscarine (M)
Methacholine (N,M) Nicotine (N)
Carbachol (N, M) Lobelline (N)
II. Indirect-‐acting
-‐ inhibits acetylcholinesterase

Short-‐acting – Edrophonium (Tensilon)
Intermediate/Long-‐acting – Carbamates
Very long-‐acting – Organophosphates (Tabun,
Receptor Location Response Sarin, Soman)
Muscarinic
M1 (Gq) Stomach " gastric secretion Clinical uses:
linked • Dx of Myasthenia Gravis (antibodies for NM)
Heart (-‐) Dromotripism • Neuromuscular blocker toxicity
M2 (Gi) (-‐) Chronotropism • Management of glaucoma # Echothiopate,
(-‐) Inotropism Carbachol
Smooth muscles • Management of atropine toxicity #
Eyes Miosis Neostigmine
(circular • Smoking cessation # Nicotine, Lobelline
muscles) • Urinary retention # Betacholine
Ciliary Accomodation • Treatment of Alzheimer’s disease #
M3 (Gq) Rivastigmine, Tacrine, Doneprazil
muscle (adapted to near
vision)
Bronchial Bronchoconstriction
smooth
muscle
4

Cholinergic Side effects 3. Mydriatic-‐cycloplegics
Muscarinic Nicotinic a. Atropine
Diarrhea Muscle weakness b. Homatropine
Urination Adrenal medulla c. Tropicamide
Miosis (stimulation) d. Cyclopentolate
Bradycardia Tachycardia
Bronchoconstriction Cramping 4. Bronchodilators
Emesis Hypertension a. Ipratropium
Lacrimation b. Tiotropium
Salivation c. Oxytropium
Treatment: Use: 1st line in COPD
Atropine -‐ anticholinergic # for -‐ Adjunt in BA
Poisoning:
carbamate and organophosphate Carbamate
poisoning ANTI-‐NICOTINIC DRUGS
– temporary
Pralidoxine # specific for Organophosphate
1. Neuromuscular blocker (NM blocker)
organophosphate poisoning – permanent a. Depolarizing
-‐ Succinylcholine
Parasympatholytics Succinylcholine – difference with ACh: not as
quickly metabolized
I. Antimuscarinics
1. Atropine -‐ Effect: initially causes muscle contraction,
-‐ prototypical antimuscarinic but this is not sustained. Impulse does not
propagate.
Effects:

“Blind as a bat”
Normal Propagation of AP
“Hot as a hare” – no thermoregulatory sweating
“Red as a beet”-‐ flushing (cutaneous vasodilation)
“Mad as a hatter” – Psychosis
“Dry as a bone” -‐ ! secretion
-‐ Constipation/ ileus
-‐ Urine retention
-‐ Mydriasis
o CI: glaucoma
-‐ Bronchodilation
-‐ Tachycardia
-‐ ! secretions
Uses:
• Topical – cycloplegic, mydriatic
• Symptomatic bradycardia
• Added in diphenoxylate
DHPR – dihydropyridine receptor
2. Centrally-‐acting SR – sarcoplasmic reticulum
a. Scopolamine -‐ sedatives
Uses:
• Antimotion sickness
• “Twilight sleep”
-‐ Scopolamine + morphine

b. Biperiden, Benztropine, Trihexylphenidyl
Uses:
• Adjunct in Parkinson’s Disease
• Management of extrapyramidal symptom

5

Succinylcholine
Phase I – non-‐surmountable (no muscle contraction)
Phase II – surmountable (! sensitivity to Ach)

b. Non-‐depolarizing # blocks NM receptors
(surmountable block – reversed if you give
enough Acetylcholine)
2 classes:
1. Isoquinoline (-‐curium)
-‐ Mivacurium, Atracurium
2. Steroidal (-‐uronium)
-‐ Pancuronium, Vecuronium

AE:
-‐ Myositis or rhabdomyolysis
(succinylcholine)
o Myogloblinutis
o Muscle pain
o Hyperkalemia
-‐ Malignant hyperthermia
o Antidote: Dantrolene – inhibits
ryanodine receptor
-‐ Tubocurarine: anaphylactoid reaction
-‐ Atracurium: metabolism to landanosine #
seizures

2. Ganglionic blocker (NN blocker)
Hexamethonium
Mecamylamine
Trimethaphan

Effects: mixed
-‐ Mydriasis
-‐ Constipation
-‐ Tachycardia
-‐ Urinary retention
-‐ Anhidoris
-‐ Vasodilation # hypertension
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AUTACOIDS
-‐ Histamine e. Alkylamines
-‐ Serotonin Brompheniramine
-‐ Eicosanoids Chlorpheniramine
-‐ Bradykinin and other kinins
f. Phenothiazines
Histamine Promethazine
!"#$"%"&' !"#$%&'()*$+" -‐ Additional use: used in the induction of
𝐻𝑖𝑠𝑡𝑖𝑑𝑖𝑛𝑒 𝐻𝑖𝑠𝑡𝑎𝑚𝑖𝑛𝑒 anesthesia (! secretions, i.e. saliva to
prevent aspiration)
Smooth muscle g. Cyproheptidine
Vascular Vasodilation -‐ Management of serotonin syndrome
Bronchial Bronchoconstriction
Sensory Itch Non-‐sedating/ Less sedating/ 2nd generation
H1 nerve Less sedating # Cetirizine, Acrivastine
ending Non-‐sedating # Loratidine, Deslovatidine,
Capillary " capillary Fexofenadine
endothelial permeability
cells # fluid transudation Clinical use:
# swelling
• Management of allergic conditions (allergic
Parietal cells " acid secretion rhinitis, atopic dermatitis)
H2
(stomach)
NOTE: 1st generation is more effective
Triple Response of Lewis
-‐ intradermal injection of histamine • H2 Antagonists
o Redness Cimetidine (Tagamet)
o Itch
Ranitidine (Zantac)
o Swelling
Famotidine (H2 bloc)

Nizatidine (Axid)
Histamine Antagonists
Uses:
1. Physiologic epinephrine
• GERD (frequent irritation of esophagus due
2. Pharmacologic
to gastric contents # adenocarcinoma)

• Peptic ulcer disease (PUD)
• H1 blockers
AE:
Sedating/ Classical/ 1st generation
-‐ Cimetidine: enzyme inhibitor
Classification:
o Inhibits estradiol metabolism
a. Ethanolamine
# anti-‐androgenic effects
Diphenhydramine -‐ Ranitidine/ Famotidine: not associated
Dimenhydrinate w/ anti-‐androgenic effects
Carbinoxamine
Doxylamine
Uses:
• Most sedating: significant anti-‐cholinergic Serotonin – 5-‐HT
effects -‐ in GIT, platelets, CNS
• Additional uses: sleeping aids
• Adjuncts in the management of Parkinson’s !!"#$%!&'()$*, !"#$%&'()*$+,'-
𝑇𝑟𝑦𝑝𝑡𝑜𝑝ℎ𝑎𝑛 5
Disease
− 𝐻𝑇

b. Ethylene diamines – pyrolamine

tripelenamine

c.
d. Meclizine, cyclizine
-‐ Meclizine: used for motion sickenss
7

5HT1A Presynaptic cell Inhibits further
release of 5-‐HT
5HT1D Blood vessels Vasoconstriction
5HT2A Smooth muscles
Blood vessels Vasoconstriction
Uterus Uterine
contraction
5HT3 Chemoreceptor Vomiting
trigger zone (impt in chemo-‐
(CTZ) therapy px)
5HT4 GIT Peristalsis

Drugs
I. 5HT1A agonists Effects:
Partial agonist Leukotrienes
Buspirone # anxiolytic LTBa # chemokine
LTCa, LTDa # slow reacting substances of
Full agonist anaphylaxis (SRSA)
Triptans (Zolmitriptan, Sumatriptan,
Naratriptan) # migraine Blood vessels
SE: exacerbate HTN in patients with CAD # -‐ Vasodilation is caused by prostacyclins
angina (PGI2)
-‐ Vasoconstriction is caused by PGE2,
II. 5HT2A thromboxane (TXA)
Agonist -‐ NSAIDs # decrease renal perfusion #
Ergotamine, Ergonovine decrease diuretic efficacy # exacerbate
Use: migraine CKD
Uterus
Antagonist -‐ Contraction is caused by PGF, PGE
Methysergide Platelets
Use: prophylaxis for migraine -‐ Aggregation (TXA)
-‐ Inhibit aggregation (PGI2)
CI: pregnancy IOP reduction
-‐ PGE series, PGF2-‐α
III. 5HT3 antagonist
Ondansetron, Granisetron, etc.
Use: anti-‐emetics Prostacyclin Analogs
1. Epoprosterol – PGI2 analog
IV. 5HT4 agonist Use: primary pulmonary HTN (increased
Tegaserod pressure in right ventricle causing cardiac
Use: Irritable bowel syndrome remodeling and decompensation # HF)
2. Alprostadil – PGE1 analog
Eicosanoids Use: erectile dysfunction, prevent closure of
-‐ from arachidonic acid ductus arteriosus
3. Misoprostol (Cytotec) – PGE1 analog
Phospholipase A2 Use: cytoprotectant and abortifacient
(-‐): glucocorticoids 4. Dinoprostone – PGE2 analog
Cyclooxygenase Use: abortifacient
(-‐) NSAIDS, paraaminophenols 5. Latanoprost – PGF2-‐α analog
Lipooxygenase Use: Management of glaucoma
(-‐) Zileuton
Biosynthesis:
8

Drugs for Rheumatologic disorders/ Arthtitides Saturation kinetics -‐ phenytoin, alcohol,
Rheumatoid Arthritis theophylline
Genetic susceptibility + environmental factors
# reaction of T cells to self-‐antigens in the Effects: (4A)
synovium # inflamed joints (redness, • Anti-‐thrombotic # < 325 mg/d
heat/warmth, swelling, loss of function) # • Analgesic # < 600 mg/d
pannus • Antipyretic # 300 mg – 1200 mg/d
Osteoarthritis • Anti-‐inflammatory # 3.2 – 4 g/d
-‐ few signs of inflammation
-‐ due to overuse or change of dynamics AE:
of moving joints -‐ NSAID-‐induced gastritis

Systemic Lupus Erythematosus CNS Manifestations
Serum salicylate S/Sx
Genetic susceptibility Environmental Factors
levels
Salicylism (tinnitus,
vertigo)
Lymphocytes reactive e.g. UV radiation
To nuclear antigens 50-‐80 mg/dL (low) Hyperventilation #
Respiratory alkalosis
!"
Apoptosis 𝐻! 𝑂 + 𝐶𝑂! 𝐻! 𝐶𝑂!
Production of Metabolic acidosis
antibodies against 80-‐100 mg/dL (high)
Hyperthermia
nuclear antigens Nuclear 100-‐160 mg/dL Hypoprothrombinemia
material in (severe) # bleeding
Antibodies-‐antibody circulation > 160 mg/dL Respiratory depression
complex
Uric acid excretion
Non-‐selective COX < 2 g/d # hyperuricemic
Inflammation inhibitors > 3 g/d # uricosuric
-‐ Common SE: NSAID-‐induced gastritis CI: Aspirin in px with gout (anything
that can increase or decrease uric acid
Selective COX-‐2 inhibitors levels can exacerbate gout)
-‐ Adv: ! risk for NSAID-‐induced gastritis Common to non-‐selective NSAIDs:
-‐ Disadvantage: " risk for stroke -‐ ! GFR # ! perfusion of kidney #
“Selective” exacerbate CKD
-‐ Meloxicam Hypersensitivity reaction
-‐ COX-‐2 >>> COX-‐1 -‐ COX is inhibited; arachidonic acid is
“Specific” COX-‐2 inhibitors diverted to LOX pathway # LT
-‐ Celecoxib synthesis
-‐ Etoricoxib Reye’s Syndrome – only for aspirin

A. NSAIDS 2. Pyrazolone derivatives
-‐ inhibit cyclooxygenase Phenylbutazone
COX-‐1 # housekeeper Oxyphenbutazone
COX-‐2 # home wrecker; inducible -‐ Withdrawn from the market
COX-‐3 # CNS AE:
-‐ Agranulocytosis
1. Aspirin and other salicylates -‐ Aplastic anemia
Kinetics: -‐ Acute tubular necrosis
-‐ absorbed in the stomach and small -‐ Nephrotic syndrome
intestine
-‐ Excretion: < 600 mg/d = 1st order
>600 mg/d = Zero order
9

3. Indole derivatives SE:
Indomethacin -‐ Hepatotoxcity (dose-‐related)
Use: o Remedy: Leucovorin (Folinic
• Closure of patent ductus arteriosus (PDA) acid)
• 1st line in the management of acute gout
AE: 2. Anti-‐malarial agents
-‐ Compared to other NSAID, " risk for PUD Chloroquine
Hydroxychloroquine
SE:
4. Pyrolle, alkanoic acid derivatives -‐ Cinchonism (Tinnitus, optic neuritis)
Tolmetin 3. Gold compounds # no longer widely
AE: Hyperuricemia available
Oral: Auranofin
5. Oxiram derivatives Parenteral: Aurothiomalate, Aurothioglucose
Peroxicam SE:
-‐ COX-‐1 >>> COX-‐2 -‐ Hypersensitivity
AE: highest risk for PUD -‐ Nephrotic syndrome

6. Phenylacetic acid derivatives 4. Sulfasalazine
Sulindac, Diclofenac, and Nabumetone Metabolites:
Sulfapyridine # RA
Sulindac -‐ sulfa drug (prodrug) 5-‐aminosalicylate # IBD (i.e. Crohn’s Disease,
-‐ may cause hypersensitivity reactions (e.g. ulcerative colitis)
SJS – 10% of skin has rash, TEN -‐ >10% has
rash) 5. Biologic Agents
-‐ inhibits tumor necrosis factor (TNF)
7. Fenamates Adalimumab
Mefenamic acid – little anti-‐inflammatory/ Infliximab
antipyretic, analgesic Etanercept
Flufenamic acid Use:
Meclofenamic acid • RA that does not respond to other drugs
Caution: SE:
-‐ should not be used for > 5 days -‐ " risk for infection
-‐ should not be used in children (no
safety data) C. Glucocorticoids
a. Systemic (PO or IV)
8. Propionic acid derivatives Methylprednisolone – Methylprednisolone
Ibuprofen Pulse Therapy (MPPT) for SLE
Naproxen
Ketoprofen b. Intrasynovial
Flurbiprofen
D. Drugs for gout
Use: Hyperuricemia # deposition of sodium urate in
• Effective for fever due to malignancy joints and elsewhere # inflammation of the
(naproxen test) joints (podagra), subcutaneous tissue (tophi),
uters/ kidney (ureteral stones)

B. DMARDS Acute gout
1. Methotrexate -‐ may be the initial manifestation of gout;
-‐ first line DMARD in RA may be an exacerbation of chronic gout
MOA:
-‐ Inhibit folate synthesis (Dihydrofolate
reductase)
10

Treatment: b. Uricosuric
1. Colchicine –1st line Sulfinpyrazone
MOA: Probenecid
-‐ inhibits microtubule synthesis # ! Penicillamine
macrophage function SE:
Dose: -‐ Formation of ureteral stones
-‐ 1 tab/hr until significant toxicity Prevention:
appears or 600 mg 1-‐2 tab q 6-‐8 hrs -‐ alkalinize urine # K+ citrate hydration
SE:
-‐ watery diarrhea E. Analgesics
-‐ neuropathy Classification:
2. NSAIDs 1. Non-‐opioids/ Non-‐narcotics
3. Glucocorticoids (Prednisone – PO) NSAIDs
Para-‐aminophenols (Paracetamol)
Chronic Gout
Treatment: MOA: Inhibits COX-‐3
1. Colchicine – for 6 weeks to 6 months AE: Hepatotoxicity (N-‐acetyl-‐p-‐
• Hyperuricemic therapy after 2-‐3 weeks on benzoquinonimide)
colchicine

2. Hypouricemic therapy
a. Uric acid synthesis inhibitor
Allopurinol
Febuxostat
MOA: Inhibits xanthine oxidase

NAPQI # hepatocellular proteins # hepatic
necrosis

2. Opioids
Opioids – synthetic/ semi-‐synthetic
Opiates – natural

Opioid triad:

(1) pinpoint pupils
Uses:
(2) resp. depression
• 1st line hypouricemic agent in gout (3) coma
• Management of tumor lysis syndrome
o " K+– hyperkalemia MOA: Stimulates opioid receptors
o " PO34-‐ – hyperphosphatemia #

hypocalcemia
o " Uric acid – hyperuricemia

11

2. Codeine
Endogenous Effects -‐ activity is less than morphine
opioids Use: moderate pain antitussive
Endorphin Analgesia, euphoria, sedation, 3. Phebaine
resp. depression, bradycardia, -‐ precursor for the synthesis of naloxone
constipation, miosis,
dependence Semi-‐synthetic Compounds
Dynorphin Additional analgesia 1. Hydromorphine,
Efficacy-‐ maximum effect
Enkephalin Additional analgesia, oxymorphine
Potency-‐ mathematical
dysphoria, seizures -‐ Same efficacy as term, position in dose-‐
Effects: morphine but is 10-‐ response curve
CNS # (see table above) 12x more potent
Cardiovascular # bradycardia, peripheral
venodilation 2. Oxycodone/ hydrocodone
-‐ Same efficacy as codeine but is 10-‐12x more
Biliary # contraction of the gall bladder (except
Meperidine) potent
GIT # ! motility in the ileus# constipation
Mast cells # release of histamine 3. Heroin – common drug of abuse

4. Apomorphine
Uses:
-‐ Not an analgesic
• Management of pain states -‐ Management of Parkinson’s Disease # !
o Tramadol – moderate pain off periods
o Morphine – severe pain

• Acute pulmonary edema
Synthetic Compounds
o Morphine
1. Methadone
• Anesthetic adjuncts
-‐ same efficacy as morphine
• Antidiarrheals -‐ Adv: " oral bioavailability, longer duration
SE: of action
-‐ CNS # sedation, respiratory Use: wean patients off opioids
depression
-‐ Tolerance (minimal) 2. Meperidine
o Seizures -‐ same efficacy as morphine
o Constipation -‐ Adv: no biliary side effects
o Miosis
-‐ Dependence 3. Diphenoxylate, Loperamide
-‐ " Intracranial pressure -‐ antidiarrheals
o Due to respiratory depression -‐ Diphenoxylate is combined with atropine #
(accumulation of CO2) alice in wonderland effects (to prevent
CI: dependence)
-‐ Partial agonist is contraindicated in
those using full agonist # precipitation 4. Fentanils
of withdrawal symptoms (seizures, Alfentanil
hyperexcitability) or reduced effect of Fentanyl
full agonist Flufentanil
-‐ Head injuries # increased risk of
-‐ same efficacy as morphine but is ~100x
herniation
more potent
-‐ good oral bioavailability
Natural Opium Alkaloids
1. Morphine 5. Tramadol – weak μ opioid agonist
Bioavailability: ~25% 6. Pentazocine –κ partial agonist
Use: severe pain states

12

Classification according to strength Drugs for coagulation disorders
Strong full agonist Hemostasis – physiologic
Morphine Thrombosis – pathologic
Hydromorphone 1. Hypercoagulability
Oxymorphone 2. Stasis
Fentanils 3. Endothelial injury
Levorphanol
Meperidine Primary Hemostasis – formation of platelet
Mild-‐moderate full agonist plug
Codeine
Hydrocodone
Etc.
Partial agonist
Betorphanol
Buptenorphine
Nalbuphine
Pentazocine
Antagonist
Naloxone
Naltrexone
Nalorphine
Levallorphan

Secondary Hemostasis – clotting cascade;

formation of fibrin (acts like a glue; makes the
plug more cohesive) # clot formation

Activation of counter-‐regulatory mechanism
-‐ antithrombin
-‐ Protein C and S
-‐ Tissue plasminogen activation

13

Coagulation pathway -‐ Heparin-‐induced thrombocytopenia
o Heparin binds to platelet factor 4
(PF4) # production of antibodies #
antibody-‐heparin-‐PF4 complex #
platelet activation # ! platelet #
bleeding
-‐ Alopecia
-‐ Osteoporosis
CI:
-‐ Bleeding risk/ active bleeding
-‐ Thrombocytopenia (induce HIT)

b. Fondaparinux
-‐ synthetic pentasaccharide related to
heparin

-‐ Adv: ! risk for HIT

Uses: same as heparin

2. Direct thrombin inhibitors

a. Hirudin, Lepirudin – from medicinal leeches
Extrinsic pathway – if injury is outside the BV
(hirudis medicinalis)
Intrinsic pathway – if injury is inside the BV
• Used in the management of HIT

Anticoagulants
b. Bivalirudin
1. Indirect thrombin inhibitors
• Used in post percutaneous transluminal
MOA:
coronary angioplasty (PTCA) to prevent
-‐ forms a complex with antithrombin III -‐ thrombosis
" activity

-‐ degrades IXa, Xa, XIa, XIIa
c. Argatroban

• Used in the management of HIT
a. Heparin

-‐ Sulfated mucopolysaccharides
3. Oral Anticoagulants

1. Historical drugs:
Types:
1. Regular Heparin a. Dicoumarol # rodenticide
b. Indanediones – Anisidione, Phenindion
Dose Indication
SE: thrombocytopenia, hypersensitivity
80 units/kg bolus then 18 Thromboembolism
reaction
units kg/hr infusion
c. Phenprocoumon # long half-‐life (~ 6
50 units/kg then Acute coronary days)
15 units/kg/hr infusion syndrome (heart attack)

2. Warfarin
Monitoring: activated partial thromboplastin time MOA:
aPTT = 50-‐85 second delay compared to control -‐ inhibit vit. K dependent clotting factors
(1972) by inhibiting vit. K epoxide
2. LMW Heparin reductase (6-‐60 hours)
Enoxaparin
Fraxiparine
Dalteparin
Clinical uses:
• Anticoagulation (DVT, ACS, stroke)
• Initiation of anticoagulant therapy
SE:
-‐ Bleeding (antidote: protamine sulfate
from Scylliorhinus caniculus)
14

2. ADP inhibitors
a. Ticlopidine
AE:
-‐ Neutropenia # " risk for infections
-‐ Thrombotic thrombocytopenic purpura
(TTP)

b. Clopidogrel
-‐ not associated with neutropenia and
thrombocytopenia
Use:
• Prevention of acute thrombotic events

3. Phosphodiesterase inhibitors
Vit K is required in γ-‐carboxylation of -‐ " concentration of cAMP
clotting factors rendering them active
a. Dipyridamole
-‐ inhibit Protein C & S – vitamin K-‐ Use:
dependent activation # 6-‐24 hours • antithrombotic but only w/ other
o Procoagulant state – prevented antithrombotics
by overlapping with heparin SE:
-‐ Coronary steal phenomenon
Monitoring: o Used in pharmacologic stress
Prothrombin time/ international normalized testing
ratio; PT-‐INR = 2-‐3
𝑃𝑇!"#$%&#
b. Cilostazol
𝑃𝑇!"#$%"& Use:
Clinical uses: • Intermittent claudication (narrowed BV in
• Chronic anticoagulation necrosis # AF the lower extremities due to accumulation
• Prosthetic heart valve of lactic acid)
• Rheumatic heart disease
SE: 4. GP IIb/IIIa inhibitors
-‐ Bleeding (Antidote: Vitamin K) -‐ inhibits cross-‐linking of platelets
-‐ Cutaneous necrosis within 1st week of Abciximab
treatment Eptifibatide Angina
-‐ Teratogenic (CI: pregnancy; give -‐ no cellular death
Tirofiban
heparin) MI
Use: -‐ cellular necrosis
o 1st trimester: abnormal bone • Acute coronary syndrome
development o unstable angina
o 3rd trimester: hemorrhagic disease o MI (ST-‐elevation, non ST-‐elevation)
of the newborn
-‐ Necrotizing enterocolitis Fibrinolytics/ Thrombolytics
DI:
-‐ often an object drug (elicits the AE)
-‐ Pharmacokinetic # enzyme inhibitors
-‐ Pharmacodynamic # ASA, heparin,
chronic liver disease

Antiplatelets
1. Aspirin
MOA: ! TXA2 synthesis
Clinical use:
• Prevention of acute thrombotic events (ACS,
CVD)
15

1. Streptokinase Clinical uses:
-‐ protein derived from β-‐hemolytic • Prophylaxis for hemorrhagic disease of the
streptococci newborn
AE: • Management of bleeding disorders
-‐ Hypersensitivity reaction associated with vit. K deficiency
o Remedy: Pre-‐medicate w/ • Antidote for warfarin
diphenhydramine
2. Epsilon aminosalicylic acid
2. Anisoylated plasminogen-‐streptokinase Analog: Tranexamic acid
activator (APSA) MOA:
-‐ same with streptokinase -‐ Inhibits conversion of plasminogen to
plasmin
3. tissue plasminogen activator (rtPA -‐ Clinical uses:
recombinant, tPA) -‐ Used to minimize post-‐surgical
-‐ Alteplase bleeding
-‐ Adv: ! risk of hypersensitivity -‐ Minimize post-‐surgical bleeding

Uses:
• Pulmonary embolism (thrombus enters the
lungs)
• Deep vein thrombosis (underlying cause of
PE)
• Acute MI

Indications for fibrinolytic use:
1. STEMI
2. In patients w/ angina chest pain
unrelieved by nitrates (30 mins – 12
hrs)

Absolute CI:
-‐ presence of active internal bleeding (except
menses)
-‐ Intracranial neoplasm
-‐ Aortic dissection
-‐ Previous hemorrhagic stroke at any time or
other cerebrovascular events within 1 year
Relative CI:
-‐ Previous surgery

Prothrombotics
1. Vitamin K
Vit. K 1 – phytonadione
-‐ found in green leafy vegetables,
cruciferous vegetables
Vit. K2 – menaquinone
-‐ produced by intestinal bacteria
Vit. K3 – menadione
-‐ not clinically important
-‐ water-‐soluble

16

Drugs for Lipid Disorders Drugs for Dyslipidemia
Cholesterol From Dietary Lipids 1. Statins – given hs (maximal cholesterol
production occurs at night)
MOA: Inhibit HMG-‐CoA reductase
-‐ Short-‐acting # Fluvastatin, Simvastatin
-‐ Long-‐acting # Atorvastatin, Rosuvastatin
Clinical Use:
• 1st line in the management of
hypercholesterolemia
• in CAD, to stabilize atherosclerotic plaques
SE:
-‐ Hepatotoxic # " liver enzymes
o Obtain baseline ALT, AST before
starting statin therapy
Acceptable ALT on treatment:
ALT < 3x the upper limit of normal,
or ALT < 3x the baseline (whichever is lower)
-‐ Muscle pain # myositis #
rhabdomyolysis

2. Fibrates
Gemfibrozil
Fenofibrates
De Novo Synthesis
Clofibrate
-‐ primary source of cholesterol
-‐ fibric acid derivatives
-‐ Mevalonic acid pathway (HMG-‐CoA
reductase – rate-‐limiting step) MOA: stimulates lipoprotein lipase
Use:
Pathogenesis of Atherosclerosis • 1st line in the management of
1. Endothelial damage hypertriglyceridemia
-‐ Turbulence (blood flow is not laminar) SE:
-‐ Oxidized lipids -‐ " risk of gallstone formation
2. Inflammatory response -‐ " risk for rhabdomyolysis (esp. when
Macrophage engulfs oxidative lipids # foamy used with statins)
macrophages # release of inflammatory
mediators # platelet aggregation # migration 3. Nicotinic acid
of more inflammatory cells MOA: unclear; inhibit hepatic release of VLDL,
3. Smooth muscle proliferation may stimulate lipoprotein lipase
Clinical use:
Dyslipidemia -‐ alternative to fibrates in the hyperTG
a. Hypertriglyceridemia – TG ≥ 150 mg/dL SE:
b. Hypercholesterodemia – based on serum -‐ Hepatotoxicity (at >2g/d)
LDL levels and patient risk for a CV event -‐ Flushing
Risk Normal LDL o Remedy: co-‐administer w/
Very high < 70 mg/dL NSAIDS
-‐ Body odor
(ACS, CAD+DM)

High < 100 mg/dL
4. Bile acid-‐binding resins
(CAD, DM)
Cholestyramine
Intermediate < 130 mg/dL
Cholestipol
(2 or more risk
MOA:
factors)
-‐ Binds bile acid/salts in the intestine so
Low < 160 mg/dL
the liver uses more cholesterol to
(0-‐1 risk for CV
produce new bile acid/salts
events)
17

Use:
• Add on to statins
SE:
-‐ " risk for gall stone formation
-‐ steatorrhea
-‐ inhibit absorption of fat-‐soluble
vitamins

5. NPC1L1-‐like transporter inhibitors
Ezetimibe
MOA:
-‐ inhibits cholesterol transport in the
intestine (dietary cholesterol)
Use:
• Add on to statins

Lipid-‐lowering effect

18

Hypertensive Classification (JNC)
Cardiovascular Drugs Systole Diastole
Hypertensive Drugs Normal < 120 and < 80
-‐ " blood pressure Pre-‐HTN 120-‐139 or 80-‐89
Stage 1 140-‐159 or 89-‐99
Determinants of BP: Stage 2 ≥ 160 or ≥ 100
𝐵𝑃 = 𝐶𝑂 𝑥 𝑆𝑉𝑅
Systemic vascular resistance (SVR) Hypertensive Crises
-‐ tone of arterioles 1. Hypertensive urgency
-‐ “primary resistance vessels” -‐ DBP > 120
-‐ -‐ No organ damage
Determinants of cardiac output (CO): 2. Hypertensive emergency
𝐶𝑂 = 𝑆𝑡𝑜𝑘𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 𝑥 𝐻𝑅 -‐ Hypertensive BP
-‐ + end organ damage
Determinants of stroke volume: o Renal damage
-‐ Cardiac contractility o Papilledema
-‐ Preload # amount of blood returning to the o Encephalopathy
heart
o Blood volume Gestational HTN – HTN in pregnant patients
o Tone of peripheral veins Pre-‐eclampsia # HTN + proteinuria in pregnant
patients > 20 wks age of gestation (Tx: MgSO4)
Mechanics of BP regulation Eclamptia # HTN + proteinuria + seizure
1. Baroreceptor reflex arc
-‐ short-‐term regulation of BP Treatment goals:
-‐ Baroreceptors: sensitive to changes in BP Systole Diastole
then sends signals to brain Most cases < 150 and < 90
-‐ Carotid baroreceptor: detects stretch DM or CKD < 140 and < 80
DM + CKD ≤ 125 and ≤ 75
2. Renin-‐Angiotensin-‐Aldosterone system

RAAS is stimulated by ! GFR, e.g. ! BP
Combination Therapy:

19

Antihypertensive drugs Clinical use:
• 1st line management of open angle glaucoma
Diuretics -‐ ! blood glucose, ! CO • Acute mountain sickness
o Hastens acclimatization process by
eliminating more bicarbonate ions #
makes blood more acidic #
chemoreceptors: breathe faster
• Management of metabolic alkalosis
o Spilling bicarbonate ions
• Acetazolamide: useful in the management of
catamenial seizure (associated w/ menses)
CI:
-‐ COPD (may cause respiratory acidosis)
SE:
-‐ metabolic acidosis
-‐ Sulfonamide SE (SJS)
-‐ Hematologic abnormalities
o Aplastic anemia
o Hemolytic anemia
o Neutropenia

II. Osmotic Diuretics
Mannitol
MOA:
-‐ creates osmotic gradient between the
renal tubule and the surrounding areas
Uses:
I. Carbonic Anhydrase Inhibitors • ! intracranial pressure
Acetazolamide SE:
Brinzolamide -‐ Dehydration
Dorzolamide -‐ Pulmonary edema
Dichlorphenamide
MOA: III. Loop Diuretics
Furosemide
Ethacrynic acid
Bumetanide
-‐ acts on the thick ascending limb of the
loop of Henle
-‐ “high-‐ceiling diuretics”
MOA:
-‐ inhibits Na+-‐K+-‐2Cl-‐ co-‐transporter

• also happens in ciliary bodies (where
aqueous humor is produced)
20

Clinical use: o Paradoxical effect of thiazide diuretics
• CHF SE:
• Acute pulmonary edema -‐ Electrolyte imbalance
• Management of hyperkalemia and o Hypokalemia
hypercalcemia o Hyponatremia
SE: -‐ Hypersensitivity reactions
-‐ Electrolyte abnormalities
o Hyponatremia V. K+-‐sparing diuretics
o Hypokalemia 2 groups:
o Hypocalcemia 1. Aldosterone antagonists
o Hypomagnesemia Spironolactone
-‐ Hyperuricemia Eplerenone
-‐ Hyperglycemia 2. Direct Na-‐Cl transport inhibitors in the
-‐ Hypersensitivity reaction (sulfonamide-‐ collecting duct
like reactions Amiloride
-‐ Ototoxicity Triamterene

IV. Thiazide diuretics Clinical use:
Structure: • Prevent hypokalemia in the use of diuretics
• Benzothiadiazides • Adjunct in the management of CHF (Class
o Hydrochlorothiazide III)
o Chlorthiazide • Management of hypertension due to
• Thiazide-‐like compounds aldosterone-‐secreting tumors (Conn’s
o Indapamide syndrome)
o Chlorthalidone SE:
o Metolazone -‐ Hyperkalemia
MOA: -‐ Anti-‐androgenic effects
-‐ inhibits Na-‐Cl co-‐transporter (NCCT) (Spironolactone)
-‐ Renal stone (Triamterene)

Sympathoplegics -‐ ! renin, vasodilators,
! TPR, ! contractility, ! SV, ! CO

I. Centrally-‐acting
Clonidine
Methyldopa
Guanfacine
Guanabenz
MOA:
2 phases of effects:
-‐ ! NE release, ! sympathetic tone
1. Diuretic effect # lasts for 2 weeks
“Diuretic brake” phenomenon – kidneys II. Ganglionic blocker
counteracts diuretic effect through RAAS Hexamethonium
-‐ TZD diuretics and loop diuretics Trimethaphan
2. Vasodilating Effect # seen beyond 2 -‐ block sympathetic tone (predominant
wks
in the BV) # vasodilation

Clinical Use:
III. Adrenoreceptor blockers
• 1st line in the management of HTN α-‐receptor blockers
• Adjunct in the management of CHF β blockers
• Idiopathic nephrocalcinosis (Ca2+ out, Na+
in)
• Management of nephrogenic diabetes
insipidus
21

IV. Other drugs c. Diazoxide
Reserpine # inhibit catecholamine storage -‐ thiazide-‐related
Guanethedine Use:
• Management of hypertensive crisis
SE:
Vasodilators -‐ ! TPR, ! venodilation, -‐ Reflex tachycardia
! preload, ! SV, ! CO -‐ Hyperglycemia
-‐ Dyslipidemia
1. Arteriolar vasodilation -‐ Hyperuricemia
a. Hydralazine
MOA: 2. Mixed arterial and venous vasodilators
-‐ unclear, " K+ channel opening, " NO Sodium nitroprusside
release MOA:
Clinical use: -‐ Na nitroprusside # NO # " cGMP #
• Management of hypertensive crisis vasodilation
• Adjunct in the management of CHF Use:
• HTN in pregnancy -‐ 1st line for HTN emergencies
SE: Caution:
-‐ Reflex tachycardia -‐ Use only freshly prepared solutions
-‐ Drug-‐induced lupus (also -‐ Protect from light
Procainamide) -‐ When using at high doses, observe the
limit of duration
b. Minoxidil o ≥ 2 mg/kg/min – < 72 hrs
MOA: o Rationale: Sodium
-‐ outward movement of K+ from the nitroprusside produces CN-‐
smooth muscle cell #
hyperpolarization # vasodilation Calcium channel blockers -‐ ! blood volume
I. Dihydropyridine (DHP)
-‐ higher affinity to vascular smooth
muscles; low activity in heart
-‐dipines
Nifedipine
Nicardipine
Felodipine
MOA:
-‐ blocks ligand-‐gated Ca2+ channels #
smooth muscle relaxation #
vasodilation

II. Non-‐dihydropiridine (Non-‐DHP)
-‐ greatest effect on the heart
Verapamil
Diltiazem

Based on duration of action:
1. Most are short-‐acting

2. Long-‐acting
SE: a. Lacidipine
-‐ Reflex tachycardia b. Lercamdipine
-‐ Hypertrichosis/ Hirsutism c. Amlodipine
3. Modified long-‐acting
a. Plendil XR®
b. Versant XR®
c. Nifedipine GITS®
22

Clinical Uses:
• HTN
• Alternative anit-‐anginal circulation
• Non-‐DHPs # antiarrhythmics

SE:
-‐ Reflex tachycardia (DHP)
-‐ Peripheral edema

Angiotensin modifiers
(-‐) vasoconstriction (-‐) aldosterone
1. ACEIs
-‐pril
Captopril
Enalopril
MOA:
-‐ Inhibits angiotensin-‐converting enzyme
(kininase) # ! angiotensin II
SE:
-‐ Idiosyncratic dry cough
o ACE degrades bradykinin

2. Angiotensin I Receptor Blockers (ARBs)
-‐sartan
Losartan
Irbesartan
Candesartan
Adv: No dry cough

Clinical uses (ACEI and ARB)
• HTN (1st line: ACEI, 2nd line: ARB)
• HTN caused by CKD
o ! GFR # " renin secretion #HTN;
o constriction of efferent arteriole #
" hydrostatic pressure # " GFR #
! renal perfusion)
SE:
-‐ Dry cough (ACEI)
-‐ Hyperkalemia
-‐ Angioedema
CI:
-‐ Bilateral renal artery stenosis
-‐ Pregnancy (causes renal agenesis)

3. Renin inhibitors
Aliskiren
MOA:
-‐ binds to renin
Use:
• Add on to ARBs or ACEI
SE:
-‐ Dry cough
-‐ Rashes
-‐ Angioedema
23

Anti-‐anginal Drugs Nitric oxide – stimulates guanylyl cyclace (GC)
!"
Angina Pectoris 𝐺𝑇𝑃 𝑐𝐺𝑀𝑃
-‐ chest pain due to cardiac cause • cGMP – causes dephosphorylation of CHONs
-‐ Atherosclerosis # CAD # Ischemia and enzymes # relaxation of smooth
(lack of O2 in the blood) muscles of BV # vasodilation
Coronary Artery Disease (CAD)
1. Chronic stable angina pectoris Effects:
-‐ chest pain/ dyspnea on exertion Low dose: peripheral venodilation
𝐵𝑃 = 𝐶𝑂 𝑥 𝑆𝑉𝑅
2. Acute coronary syndrome
a. Unstable angina
-‐ no necrosis
HR SV
-‐ crescendo pattern
-‐ unrelated to exertion CC VR

b. NSTEMI FC TV
-‐ walls of the heart only partially affected TV – venous tone
VR – venous return
c. STEMI o “Cardiac preload”
-‐ walls of the heart are wholly affected o End diastolic ventricular volume
-‐ thrombolytic therapy CC – cardiac contractility
! venous tone # peripheral venodilation
3. Prinzmetal angina/ Vasospastic angina/ ! TV = ! VR = ! SV (! O2 demand)
Variant angina
-‐ vasospasm of coronary arteries High dose: arteriolar venodilation
-‐ " O2 supply (give coronary artery
Goals of Therapy: vasodilator)
1. Increase O2 supply
-‐ " blood delivery # vasodilators SE:
-‐ " O2 content of blood # supplemental O2 -‐ Reflex tachycardia
o Most common SE of rapid-‐acting
2. Decrease O2 demand arteriolar vasodilator
-‐ ! cardiac workload o Prevention: β blockers
o ! preload -‐ Peripheral edema
o ! afterload
o ! HR Examples:
a. Very short-‐acting
Approaches to Management Amyl nitrite (via inhalation)
1. ! demand (O2) -‐ Duration of action: < 5-‐10 minutes
-‐ drugs that ! SV, HR, SVR
b. Short-‐acting (SL – to prevent first-‐pass met)
2. " supply (O2) Nitroglycerin (glyceryl trinitrate)
-‐ CABG (Coronary Artery Bypass Graft) ISDN (SL)
-‐ PTCA (Percutaneous Transluminal -‐ Duration of action: 10-‐30 minutes
Coronary Angioplasty)
• Use Bivalrudin c. Intermediate-‐acting
Nitroglycerin sustained-‐release tab
Drugs for Angina ISDN (PO tab)
1. Nitrovasodilators -‐ Duration of action: 5-‐8 hours
-‐ stimulate ENOs (endothelial nitric oxide
synthase) d. Long-‐acting
-‐ Mixed vasodilator – both arteries and NTG Transdermal patch
veins ISDN SR tab
ISMN oral tab (BA ~ 100%)
-‐ Duration of action: 10-‐24 hours
24

Uses: Drugs for Heart Failure
• Management of angina pectoris Heart failure – pump failure
ACS: NTG IV infusion -‐ CO – 2.2-‐3.5 L/min/m2
CSAP (chronic stable angina pectoris): SL, TD -‐ """ demand
Prinzmetal angina: IV infusion high dose
nitrovasodilators + β blockers S/Sx:
-‐ Dyspnea on excretion
• Alternative in the management of -‐ Orthopnea
hypertensive crisis -‐ Paroxysmal nocturnal (PND)
-‐ Peripheral edema
• Management of acute pulmonary edema -‐ Neck vein engorgement
-‐ also opioids and furosemides (due to -‐ Hepatomegaly
peripheral venodilation) -‐ Third heart sound (S3)

• Management of HF New York Heart Association
ISDN + hydralazine Functional classes of HF:
Class I (+) S/Sx > ordinary exertion
• Management of CN poisoning Class II (+) S/Sx ordinary exertion
Amyl nitrite (+ NaNO2 and sodium thiosulfate) Class III (+) S/Sx < ordinary exertion
-‐ CN binds to cytochrome oxidase Class IV (+) S/Sx at rest
(important for cellular respiration)
-‐ Nitrites cause oxidation of hemoglobin Drugs:
(Fe2+) to methemoglobin (Fe3+) A. Inotropic agents
o Methemoglobin binds to CN # 1. Cardiac glycosides
cyanomethemoglobin (! toxic than CN) Digoxin (D. lanata)
-‐ Sodium thiosulfate: CN # SCN (! toxic) Digitoxin (D. purpurea)
-‐ Methemoglobinemia – SE of amyl MOA:
nitrite -‐ inhibition of Na+-‐K+-‐ATPase pump
↑ 𝐶𝑎 → ↑ 𝑓𝑜𝑟𝑐𝑒 𝑜𝑟 𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ (+ 𝑖𝑛𝑜𝑡𝑟𝑜𝑝𝑖𝑐 𝑑𝑟𝑢𝑔)
SE:
-‐ Headache (due to vasodilatory effect) Effects:
o Throbbing -‐ (+) inotropism
o Monday sickness – common in factory -‐ (-‐) chronotropism
workers -‐ (-‐) dromotropism
$ Due to tolerance because of the Digoxin Digitoxin
depletion of sulfhydryl groups -‐ more toxic; not
$ Tolerance – provide –SH group used anymore
(NAC, glutathione, captopril) Serum t1/2 36-‐40 hours 168 hours
• Provide 10-‐14 hours of nitrate-‐free BA 70-‐75% ≥ 90%
Normal flora
period
inactivates digoxin

Protein 20-‐40% ≥90%
-‐ Hypotension
binding

Vd 6.3 L/kg 0.6 L/kg
2. β blockers
Elimination Renal Hepatic
-‐ 1st line drugs in the management of
" risk of toxicity: (check for electrolyte levels)
CSAP
-‐ Hypokalemia

-‐ Hypomagnesemia
3. CCBs
-‐ Hypoxia
-‐ 1st line drugs in the management of
-‐ Hypercalcemia
CSAP (in patients with asthma)

-‐ Non-‐DHP type (due to its effect in the
Uses:
heart)
• Management of HF
• Management of AF

25

SE: 1. ACEIs/ ARBs
-‐ Cardiac bradycardia -‐ Part of the core treatment
o Arrhythmias (ventricular -‐ Balanced unloaders (both preload and
tachycardia) afterload)
-‐ Extracardiac: -‐ Mixed vasodilators
o GI: NVD (most common) o A: ! SVR – afterload unloaders
o Visual: blurring of vision & o V: ! VR – preload unloaders
xanthopsia (yellow vision) -‐ Maximum allowable dose or maximum
o Diuretic effect tolerable dose, whichever is lower – for the
Toxicity management: patient to benefit
-‐ Digifab, Digibind -‐ Maximum tolerable dose (MTD): highest
o Contains antibody fragments dose that produces an SBP ≥ 100 mmHG
against digoxin -‐ “start low, go slow”
o Correction of electrolyte o Titrate dose every 1-‐2 weeks
imbalance
2. Diuretics
2. β-‐agonists Loop diuretics
Dopamine TZD diuretics
Dobutamine Aldosterone antagonists
Use: o Spironolactone
• Management of acute HF (DOC) o Eplerenone
o Management of acute HF and acute • ! mortality rate in patients with HF
exacerbation of chronic HF o ACEIs/ ARBs
• Cardiogenic shock o Aldosterone antagonists
• Pharmacologic stress testing (also o β blockers
dipyridamole) o ISDN + hydralazine
MOA: -‐ Preload unloaders (cause ! VR by ! fluid
β1-‐Gs content of blood)
-‐ stimulates adenyl cyclase
!"#$%! !"!#$%& 3. β blockers
𝐴𝑇𝑃 ↑ 𝑐𝐴𝑀𝑃
Metoprolol
(+) dromotropism
Carvedilol
(+) chronotropism
Bisoprolol
(+) inotropism
• For stable HF (vs. β-‐agonists for acute HF)

3. Bipyridines/ PDE3 inhibitors
4. Vasodilator combination
Milrinone
ISDN + hydralazine
Inamrinone
(PDE4 inhibitors – Theophylline) • Alternative to ACEIs/ ARBs
MOA: -‐ African descent
ISDN: preload unloader
-‐ inhibit cAMP # AMP
Hydralazine: afterload unloader
(+) dromotropism

(+) chronotropism
5. Nesiritide
(+) inotropism
-‐ brain natriuretic peptide analogue (BNP) -‐
Use:
" cGMP
-‐ same with β-‐agonists
-‐ IV infusion
SE:
-‐ Management of decompensated HF
-‐ Hypersensitivity reaction
-‐ Arrhythmia
-‐ Thrombocytopenia

B. Unloaders
-‐ Preload
-‐ Afterload

26

Drugs for Arrhythmia Class Ib: shorten the AP
“Too Much Love
Tocainide
can lead to
SA node – pace Mexiletine
Pregnancy”
maker Lidocaine
Normal: 60-‐100/ min Phenytoin
(also the N HR)
AV node
Class Ic: no effect on the AP
Left Moricizine

Flecainide “More Fries
Bundle of
Propafenone PleasE”
His
Right 1. Encainide
2.
Purkinje fibers
• Procainamide – NAPA (N-‐acetylprocainamide)
3.
4. -‐ ! risk DILE
5. -‐ " NAPA # torsades de pointes
6.
7. Class II: β blockers (2nd letter of the Gk alphabet)
Proparanolol
Esmolol (shortest t1/2)
Acebutolol

Class III: K+ channel blockers (K = three strokes)
Amiodarone (32% of MW is I2)
1. Atrial fibrillation Bretyllium
-‐ No P wave Sotalol
-‐ No atrial depolarization Dronedarone (De-‐iodinated)
-‐ No atrial contraction Defetilide
-‐ Stasis of blood in some parts of the atrium Ibutilide

2. Ventricular tachycardia (V-‐Tach) • Amiodarone
-‐ Digoxin-‐induced SE: thyroid abnormalities
-‐ Post-‐MI -‐ Wolff-‐Chaikoff effect
DOC: Lidocaine, Phenytoin o 7-‐10 days: an excess of iodide inhibits
organification (impt step in the
3. Supraventricular tachycardia (SVT) biosynthesis of thyroid hormones)
-‐ " HR: 180 bpm o > 7-‐10 days: “escape phenomenon”;
DOC: Adenosine loss of inhibitory effect #
DOC for prevention: Verapamil hyperthyroidism
-‐ Carotid massage (to decrease HR) Pulmonary fibrosis
o Baroreceptors in the aortic arch and carotid -‐ Pulmonary function test before tx
arteries # detects stretch # (-‐) central Hepatotoxicity
vasomotor area (CVA) # no sending of -‐ Liver function tests (ALT)
sympathetic signals in the HR and BV # !
HR and vasodilation # ! BP Class IV: Ca2+ channel blokers (Ca++ = 4 figures)
-‐ Non-‐DHP
Drugs
Vaughan-‐Williams-‐Singh Classification: Miscellaneous:
Class I: Na+ channel blockers 1. Magnesium sulfate
“Double Quarter
Class Ia: prolong the AP Pounder”
DOC for torsades de pointes
Quinidine 2. Adenosine
Procainamide – acetylation (HIP); SLE-‐like DOC: SVT
Disopyramide -‐ Rapid IV bolus
-‐ t1/2: 15-‐20 secs
-‐ SE: bronchospasm (administer with SABA)

27

Use:
Respiratory Drugs • Management of chronic bronchitis
Drugs for Cold
Common colds – caused by viral infection Emphysema: ê elasticity
-‐ Self-‐limiting COPD
• Rhinovirus
• Adenovirus Chronic bronchitis: é mucus production
• Coronavirus
• ! elasticity – CO2 is trapped in the alveoli (air
Nasal decongestants trapping # respiratory acidosis)
α1 agonists
PO IV. Antitussive
-‐ SE: -‐ Cough suppressants
o Vasoconstriction a. Centrally-‐acting
o Urinary retention (BPH) -‐ Hyperpolarize the cough centers
o HTN i. Narcotics: codeine, noscopine
o Tolerance (used only for 5 days) ii. Non-‐narcotic: dextrometorphan
Topical
-‐ SE: b. Peripherally-‐acting
o Rebound congestion (rhinitis Butamirate citrate (Sinecod)
medicamentosa) – used only for 3 MOA:
days -‐ ! sensitivity of cough receptors

Phenylephrine – most common Drugs for Bronchospastic Disorders
Tetrahydrozoline – ophthalmic decongestant
Oxymetazoline – ophthalmic decongestant
(BA, COPD)
Based on effect:
Allergic colds A. Relievers – treat acute attacks
Nasal decongestants + antihistamines (1st gen (exacerbations)
is preferred) B. Controllers – prevent chronic attacks

Based on MOA:
Drugs for Cough and Mucus Production Bronchial tone:
I. Mucoregulators " !
Ambroxol Bronchoconstriction Bronchodilation
Bromhexine ✓ Acetylcholine ✓ cAMP
Carbocisteine ✓ Adenosine
MOA:
-‐ " the H2O portion of mucus A. Bronchodilators
-‐ Not better than placebo 1. β-‐agonists
-‐ Gs-‐linked # stimulates AC
II. Mucolytics SABA
N-‐acetylcysteine Salbutamol/ albuterol
MOA: Terbutaline – Used for pre-‐term labor via SC
-‐ Breaks disulfide bonds between mucus Uses:
molecules • 1st line relievers (BA)
-‐ Effective route: direct instillation into • Alternative relievers (COPD)
the tracheobronchial tree SE:
-‐ tremors (β2 stimulation causes skeletal
III. Expectorant muscle tremors)
Guaifenesin (glyceryl guaiacolate) LABA
MOA: Formeterol – rapid onset (F = fast)
-‐ Stimulates the bronchial glands to Slameterol – slow-‐onset (S = slow)
increase the secretion of the H2O portion Bambuterol (PO)
of mucus Indacaterol (COPD)
28

Uses: Use:
• Controllers + inhaled corticosteroids – • Controllers/ Prophylaxis
for BA and COPD o Given 3-‐4 weeks before clinical event
becomes evident
2. Anticholinergic SE:
Ipratropium – Short-‐acting -‐ Bronchospasm (irritates bronchi)
Tiotropium o Prevention: pre-‐medication of SABA
Long-‐acting
Oxitropium
C. Anti-‐inflammatory drugs
-‐ via inhalation (will not observe Alice in 1. Leukotriene modifiers
wonderland effects because it does not MOA:
have systemic effects) -‐ 5-‐lipoxygenase inhibitor (Zileuton) #
Uses: for the formation of leukotrienes
• 1st line relievers in COPD -‐ LTD4 antagonists (Zafirlukast,
• Alternative relievers in BA Montelukast) # bronchoconstriction
Uses:
3. Methylxanthines • Management of NSAID-‐induced bronchial
Theophylline asthma
Aminophylline – ethyldiamine salt of SE:
theophylline (80%); IV -‐ LTD4 antagonist: unmask the symptoms
MOA: of Churg-‐Strauss Syndrome
1° -‐ antagonism of adenosine receptors
2° -‐ PDE4 inhibition (bronchodilation, anti-‐ 2. Corticosteroids
inflammatory) a. Inhaled
Uses: Budesonide
• Alternative reliever in severe asthma Fluticasone
exacerbation (bronchodilation) Use:
• Alternative controller in severe persistent BA • 1st line controllers (BA/COPD)
• Respiratory stimulant in COPD (anti-‐ SE:
inflammatory) -‐ Oral thrush (oral candidiasis) – due to
-‐ ! TI (therefore not first-‐line) deposition of large droplets in the oral
-‐ TDM (tedious, costly) cavity # infection
SE: -‐ Vocal cord nodules # hoarseness of
Cardiac voice
-‐ tachycardia
-‐ Arrhythmia b. Oral
CNS (stimulation) Prednisone (prodrug)
-‐ Agitation Prednisolone (active form)
-‐ Confusion Use:
-‐ Seizures (≥ 40 mg/dL) • Short course treatment of severe acute
Diuretic effect asthma exacerbations (tx should not be more
-‐ therapeutic level: 5-‐15 mg/L than 10 days)
Severe acute asthma exacerbation
Early phase – give bronchodilators
B. Mast cell stabilizers Late phase (2-‐8 hrs after exposure to
Cromolyn sodium IV antigen) – give anti-‐inflammatory
Nedocromil
c. Parenteral (IV)
MOA: Hydrocortisone
-‐ Opening of Cl-‐ channels # influx of Cl-‐ Methylprednisolone
# Hyperpolarization of mast cells Use:
(inactivation to prevent release of • Management of severe asthma exacerbation
histamine) (if PO can’t be given)
• Management of status asthmaticus

29

ii. Positive feedback
Endocrine Drugs Ex.
Basic physiology of Endocrine System

Hypothalamus Pituitary Target End Organ
Gland Organ
TRH TSH Thyroid Thyroid
thyrotropin RH thyroid-‐ SH/ gland hormone
thyrotropin T4, T3
CRH ACTH Adrenal Cortisol
Corticotropin RH Adenocortico-‐ cortex
tropic H/ (Zona
cotricotropin fasciculata)
GHRH GH Liver Somatomedins
Somatotropin IGF-‐1
GHIH Somatostatin Liver Somatomedines
GnRH Gonadotropins F: Ovaries Estrogen,
FSH M: Testes Progesterone,
LH Testosterone
PIH Prolactin Mammary -‐
Prolactin IH glands
Dopamine
Adrenal gland b. Intrinsic mechanism
-‐ Adrenal medulla – where 𝑁𝐸
!"#$%
𝐸𝑝𝑖𝑛𝑒𝑝ℎ𝑟𝑖𝑛𝑒 i. Local – Wolff-‐Chaikoff effect (in Amiodarone)
PENMT – phenylethanolamine-‐N-‐methyltransferase ii. Central
(!)
-‐ Adrenal cortex 𝑃𝐼𝐻 𝑃𝑅𝐿
Zona glomerulosa (!)
-‐ synthesis of mineralocorticoids 𝐺𝐻𝐼𝐻 𝐺𝐻
-‐ stimulated by RAAS # aldosterone
Zona fasciculata 2. Patterns of secretion
-‐ synthesis of glucocorticoids a. Secretion of hormones is entrained to
Zona reticularis sleep
-‐ synthesis of sex hormones E.g.
GH: peak is during sleep
Anterior pituitary gland (synthesize hormones) Cortisol/ ACTH: peak is upon waking up
TRH
CRH b. Pulsatile
GHRH
GHIH
GnRH
PIH
E.g. GnRH, Insulin (basal insulin)
Posterior pituitary gland
Oxytocin c. Large oscillations
Vasopressin
-‐ synthesized by hypothalamus; stored in
posterior pituitary gland

1. Regulation
a. Feedback mechanism E.g. Demand insulin
i. Negative feedback
-‐ more common
-‐ H1 # H2 (an excess of H2 inhibits Hypothalmic-‐Pituitary Hormone
secretion of H1) GH deficiency
-‐ Ex. Hyperthyroidism Onset: pre-‐puberty – pituitary dwarfism
o " T4/T3 post-‐puberty – obesity; " risk of CV
o Have to ! TSH and ! TRH disease (normal stature)
30

Diagnosis: Other uses:
-‐ Child: short stature • Management of neuroendocrine tumors
1. Baseline level of GH • Management of Zollinger-‐Ellison Syndrome
2. Induce hypoglycemia (thru insulin) o Gastrinoma -‐ " gastric acid
-‐ body will secrete counter-‐regulatory o Also PPIs
hormones • Management of esophageal varices
Epinephrine, glucagon – secreted rapidly
Cortisol, GH – secreted slowly 2. Dopamine agonists
3. GH -‐ GH is co-‐secreted with PRL
If " GH: (-‐) GH deficiency Bromocriptine
If no change GH: (+) GH deficiency Cabergoline
4. Give GHRH/ GHRP (peptide)
5. Give GH 3. GH receptor antagonist
If " GH: problem is in the hypothalamus Pegvisomant
-‐ Give GHRH/ GHRP or GH
If no change in GH: problem is in the pit. GnRH analogues
gland Gonadorelin
-‐ Give GH Goserelin
Buserelin
1. Cadaveric GH (somatropin) Nafarelin
Creutzfelt Jakob Disease (same manifestations Leuprolide
with mad cow disease) 2 effects:
-‐ cause: jumping proteins/ prions 1. Stimulatory
-‐ Hypothalmic hypogonadism
2. Recombinant GH
-‐ Somatrem
-‐ SE: hyperglycemia

3. Mecasermin
-‐ IGF-‐1 analogue 2. Inhibitory
-‐ In px not responsive with GH (!)
-‐ Continuous (IM): 𝐺𝑛𝑅𝐻 ↓ 𝐹𝑆𝐻/𝐿𝐻
Use:
-‐ Breast cancer (estrogen receptor-‐
• Management of cachexia in patients with HIV
positive breast CA)

-‐ Prostate CA
GH excess
-‐ Endometriosis # severe dysmenorrhea
Onset: pre-‐puberty – gigantism/giantism
during menstruation # X
post-‐puberty – acromegaly

-‐ Thickened lips

-‐ Broadened nose

-‐ Prominent forehead

-‐ Large jaw

-‐ Macroglossia (large tongue)
SE:
-‐ Large joints
Females:
-‐ Organomegaly
-‐ Masculinizing effects
Treatment: (acromegaly)
-‐ Acne formation
1. Somatostatin analogues
-‐ Hirsutism
-‐ general inhibitory hormone:
Males:
TSH Glucagon
-‐ Feminizing effect (gynecomastia)
Insulin Gastrin
-‐ Decreased libido
GH 5-‐HT
-‐ Infertility
ACTH

-‐ Octreotide

-‐ Lanreotide

31

Posterior Pituitary Gland Hormone Thyroid Hormones
1. Oxytocin Deficiency: Hypothyroidism
Effects: -‐ ! T3/T4
-‐ Uterine contraction -‐ " TRH/ TSH (effect)
-‐ Milk letdown Causes:
Uses: -‐ Iodine deficiency
-‐ Induction of labor -‐ Post-‐procedural
-‐ Management of post-‐partum bleeding o Radioacive iodine therapy
-‐ Initiation of lactation o Thyroidectomy
Best stimulus: nipple stimulation -‐ Autoimmune
o Hashimoto’s thyroiditis
2. Vasopressin/ ADH -‐ Drug-‐induced
a.k.a. Arginine vasopressin (AVP) o Amiodarone
-‐ 2 receptors S/Sx:
a. V1: blood vessel # vasoconstriction -‐ Hypometabolic
b. V2: kidneys # H2O reabsorption -‐ Hyposympathetic state
Renal tubule/ collecting duct -‐ Cold intolerance
-‐ " sleeping time
ADH excess -‐ Slow movement/ speech
• SIADH (Syndrome of Inappropriate ADH -‐ Weight gain
secretion) Emergency state: myxedema coma
Effects: Tx:
-‐ Hypervolemia -‐ Levothyroxine (T4)
-‐ HTN -‐ Liothyronine (T3) – for myxedema coma
-‐ Concentrated urine -‐ Liotrix (4 I4: 1 T3)
Causes:
-‐ Neurologic disorder Biosynthesis of Thyroid Hormones
-‐ Lung CA • Site: follicular cells of the thyroid gland
-‐ Trauma
Treatment: Calcium homeostasis:
-‐ Demeclocycline (tetracycline) (1) Parafollicular cells
-‐ Antidiuretic hormone receptor -‐ synthesize calcitonin (! Ca, ! PO4)
antagonist (-‐vaptan) (2) Parathyroid hormone: (" Ca, ! PO4)
o Tolvaptan (3) Vitamin D (" Ca, " PO4)
o Cornivaptan
• Steps
ADH deficiency 1. Uptake of iodide
• Diabetes insipidus (DI) -‐ Na+-‐I-‐ symporter
Types: -‐ Peroxidase-‐mediated (thyroid peroxide
a. Central DI: ! ADH oxidase
Tx: Vasopressin (V1/V2) – SE: HTN -‐
Desmopressin (V2) – (-‐) HTN 2. Peroxidation
b. Nephrogenic DI: normal/ " ADH -‐ I-‐ # I0
V2 receptors: ! sensitivity
Tx: TZD diuretics 3. Organification
NSAIDs -‐ Iodination of the tyrosyl residues of
Manifestations: thyroglobulin
-‐ Polyuria MIT: Monoiodotyrosyl (TG-‐MIT)
-‐ Polydipsia DIT: Diiodotyrosyl (TG-‐DIT)
-‐ Diluted urine
4. Coupling
TG-‐MIT + TG-‐DIT # TG-‐T3
TG-‐DIT + TG-‐DIT # TG-‐T4

32

5. Proteolysis PTU Methimazole
-‐ Enzyme protease Onset Rapid Slow
TG-‐T3 # TG + T3 Duration Short Long
TG-‐T4 # TG + T4 Use Thyroid storm Maintenance
Pregnancy Aplasia cutis
6. Release (does not cross (if given in
-‐ 4:1 (T4:T3) the placenta) pregnancy)
T4 T3 SE Hepatitis Cholestatic
t1/2 7 days 1.5 days jaundice
% protein 99.96% 99.6% Agranulocytosis
binding -‐ ! formation of
10x more granulocytes
active (neutrophils,
eosinophils, basophils)
7. Peripheral conversion of T4 # T3 -‐ " risk of bacterial
-‐ by 5-‐deiodinase infection
Monitoring;
Thyroid hormone excess -‐ Fever, sore throat, oral
-‐ " T3/T4 – thyrotoxicosis ulcers
-‐ ! TRH/TSH (effect)
2. Inorganic anions
Hyperthyroidism – hyperconditioning of the Thiocyanate
thyroid gland Perchlorate
Causes: Pertechretate
-‐ Autoimmune (Graves’ disease) MOA:
o Antibodies targeting TSH -‐ inhibition of the uptake of iodide
receptors Use:
o Thyroid-‐stimulating antibodies • Management of amiodarone-‐induced
o Triad of GD: hyperthyroidism
$ Hyperthyroidism SE:
$ Ophthalmopathy -‐ Aplastic anemia
$ Dermopathy Goitrogenic vegetables: legumes, cabbage
-‐ Hyperfunctioning of the thyroid nodule
-‐ Drug-‐induced (Amiodarone) Thiocarbamide (progoitrin)
S/Sx:
Hypermetabolic/ Hypersympathetic state Thiocyanate (goitrin) – goitrogenic
-‐ Heat intolerance
-‐ Tremors 3. Iodides
-‐ Diaphoresis (heavy sweating) SSKI (Saturated solution of KI)
-‐ Palpitations/ tachycardia Lugol’s solution
-‐ Frquent diarrhea MOA:
-‐ Weight loss -‐ Inhibition of organification and release
-‐ " irritability -‐ ! size and vascularity of the thyroid
gland (firmer)
Drugs: Use:
1. Thionamides • Adjunct in surgery (thyroidectomy)
1st line: propylthiouracil (PTU) o 7-‐10 days administration
methimazole CI:
Carbimazole (prodrug) -‐ Pregnancy (lead to fetal goiter)
MOA: -‐ Radioactive iodine therapy
-‐ inhibition of thyroid peroxide oxidase SE:
-‐ PTU: inhibition of the peripheral -‐ Iodism
conversion of T4 # T3 o Rhinitis
o Conjunctivitis
o Sialadenitis
33

4. Radioactive I2 therapy (90% effective) Diabetes Mellitus
131I – for therapy
-‐ state of chronic hyperglycemia
125I – for diagnosis

Diagnosis:
If the patient is symptomatic (3P):
MOA: -‐ RBS: Random Blood Sugar (≥ 200 mg/dL)
-‐ releases β particles # oxidation of the If the patient is asymptomatic:
thyroid gland cells (destruction) -‐ FBS: Fasting Blood Sugar (≥ 126 mg/dL)
SE: o 2 determinations, separate occasions
-‐ Hypothyroidism (80% of px in RAI o 8-‐12 hours
therapy) -‐ OGTT: Oral Glucose Tolerance Test
o 4-‐6 months – max. effect is seen o 75g of anhydrous glucose load
o Quarantine: 48-‐72 hrs (to prevent o 2-‐hr post-‐prandial glucose
transmission of radioactive o ≥ 200 mg/dL
compound) -‐ HbA1c-‐Glycosylated Hgb (≥ 6.5%)
o Management: levothyroxine (for life)
CI: Types:
-‐ Pregnancy Type 1 DM
-‐ Lactation -‐ Absolute lack of insulin
-‐ Patients < 21 y.o. -‐ Destruction of β cells of the pancreas
b. Type 1A -‐ autoimmune (more common)
5. β blockers c. Type 1B -‐ idiopathic
Propranolol – prevents conversion of T4 # T3 -‐ young onset (< 30 years old)
-‐ At onset: not obese
6. Dexamethasone -‐ Tx: insulin
-‐ prevents conversion of T4 # T3 Type 2 DM
-‐ Relative lack of insulin
7. Radiocontrast dyes o ! insulin secretion
Ipodate o ! insulin receptor sensitivity
Iopanoic acid o " gluconeogenesis, " glycogenolysis
-‐ adult onset (≥ 30 years old)
-‐ At onset: obese
-‐ Tx: Antidiabetic agents, insulin
Type 3 DM
-‐ Others
o Chronic Pancreatitis
o Cushing’s syndrome
Type 4 DM
-‐ Gestational

Drugs for DM
Insulin
-‐ secreted by the β cells
-‐ stored as a hexamer (Zn)
-‐ active: monomer
Insulin receptor – enzyme-‐linked receptor
-‐ tyrosine kinase
Effects:
-‐ translocation of glucose transporters
into the cell membrane
34

Duration of action:
1. Short-‐acting agents
-‐ Control post-‐prandial hyperglycemia
Insulin Lispro, Aspart, Glulisine
Regular Insulin
Onset: 15-‐30 min
Duration: 3-‐4 hours

2. Intermediate-‐acting
NPH (Neutral Protamine Hagedorn)
Protamine Lispro, Aspart, Glulisine
Use: To provide basal insulin requirement

Onset: 1-‐4 hours
Forms of Insulin
Source:

1. Animal-‐sourced insulin
3. Long-‐acting
-‐ porcine/bovine
Insulin Glargine – “peakless”
-‐ highly immunogenic
Insulin Detemir

Insulin Zinc Suspension
2. Recombinant insulin
Use: To provide basal insulin requirement
-‐ less immunogenic
Onset: 1-‐4 hours

Duration: ≥ 24 hours
Structure:
SE:
1. Native
-‐ Hypoglycemia
-‐ no modifications were done in the
-‐ Weight gain
structure of insulin
-‐ Lipodystrophy (rotate site of injection)
Regular insulin – SQ, IV

NPH (Neutral Protamine Hagedorn) – isophane
Antidiabetic Drugs
A. Insulin secretagogues (OHAs)

-‐ " insulin secretion
2. Modified
MOA:
-‐ Modification of the amino acid sequence
-‐ block voltage-‐gated K+ channels #
-‐ Addition of fatty acid in the structure of
depolarization of β cells # insulin
insulin
secretion
SE: hypoglycemia, weight gain

Insulin Glargine
1. Sulfonylureas
Insulin Detemir – (+ myristic acid)
A. First generation

-‐ more AE, less potent
Use:
Chlorpropamide – longest t1/2
1. Basal insulin
Tolbutamide – most cardiotoxic
-‐ Important blood glucose level for 24 hrs
Tolazamide
Acetohexamide
Insulin Glargine
B. Second generation
Insulin Detemir
-‐ less AE, more potent
NPH (Neutral Protamine Hagedorn)
Glyburide (glibenclamide)
Glipizide

Glimepiride
2. Demand insulin

-‐ Prevent post-‐prandial hyperglycemia
2. Meglitinides
Repaglinide
Regular Insulin
Nateglinide

Use:
• to prevent post-‐prandial hyperglycemia
35

B. Biguanides Incretin
Metformin -‐ secreted in response to oral glucose load
Phenformin – X: " risk of lactic acidosis -‐ Effects:
MOA: unknown o " insulin secretion
Effects: o ! glucagon secretion
-‐ ! gluconeogenesis o Maintain normal GET (2-‐3 hrs)
-‐ ! glycogenolysis Exenatide (SQ)
Uses: Liraglutide (SQ)
• 1st line in newly-‐diagnosed DM patients Use:
• 1st line for pre-‐diabetes • Given with insulin for Type 2 DM patients
• Management of polycystic ovarian syndrome
(PCOS) – to counteract insulin resistance G. DDP4 inhibitors
SE: Dipeptidyl peptidase 4 inhibitors
!"!!
-‐ Does not cause hypoglycemia when 𝐺𝐿𝑃 − 1 𝑖𝑛𝑎𝑐𝑡𝑖𝑣𝑒
given as a single agent Sitagliptin (Januvia)
-‐ Diarrhea (goes away with chronic use) Saxagliptin (Onglyza)
-‐ N/V Linagliptin
-‐ Weight loss (Biguanide)
-‐ Lactic acidosis
o Risk factors: dehydration, chronic
liver disease, chronic renal failure,

chronic heart disease

C. Thiazolidinediones
-‐ “insulin sensitizers”
MOA:
-‐ stimulates PPAR-‐γ receptors # adipose
break down into smaller globules

Pioglitazone
-‐ associated with bladder CA
Rosiglitazone
-‐ CV event

D. Alpha-‐glucosidase inhibitors
Alpha-‐glucosidase -‐
complex CHO # simple CHO (absorbable)
• metabolism of complex CHO by normal flora
# short-‐chain carbon compounds #
formation of gas (flatulence)
Acarbose
Miglitol

E. Amylin analogue
Amylin – co-‐secreted with insulin (β cells)
-‐ enhances the effect of insulin
Pramlintide (SQ)
Use:
• Given with insulin for Type 1 DM patients
SE:
-‐ " risk of hypoglycemia

F. GLP-‐1 analogues
Glucagon-‐like peptide-‐1 # incretin

36

Glucocorticoids Respiratory: BA, COPD
GI: Inflammatory Bowel Disease
Anterior pituitary -‐ Sulfasalazine (5-‐aminosalicylate)
gland • Autoimmune Diseases
• Cancer
• Dermatologic D/O
(+) Adrenal cortex
ACTH (zona fasciculata) 1. Short-‐acting (-‐pred)
Methylprednisolone
Prednisone
Cortisol Prednisolone
ACTH Hydrocortisone
-‐ Starts to " before waking up 2. Intermediate-‐acting
-‐ Peaks upon waking up Fluprednisolone
Cortisol Paramethasone
-‐ Starts to " upon waking up Triamcinolone
-‐ Peaks 2 hours after ACTH peak 3. Long-‐acting
Dexamethasone
Effects: Glucocorticoids Betamethasone
1. Physiologic
Cortisol dose < 10-‐20 mg/day Mineralocorticoid activity (MA)
-‐ Metabolism of CHO, CHON, and fats -‐ salt-‐retaining
-‐ Enhancement of smooth muscle Note: " duration of action # ! MA
Response to catecholamines " potency
SE:
2. Pharmacologic -‐ HTN
Cortisol dose ≥ 10-‐20 mg/day -‐ Peripheral edema
-‐ Anti-‐inflammatory effect
-‐ Inhibition of cell division Mineralocorticoids
-‐ Catabolism of proteins in the bones -‐ zona glomerulosa (adrenal cortex)
o Proximal myopathy – muscle Aldosterone
weakness -‐ RAAS (Angiotensin II # " synthesis of
-‐ Adverse effects aldosterone)
o Cushing’s Syndrome (! risk: give dose
q other day) • Mineralocorticoids:
$ Moon facies o Pharmacologic = physiologic effects
$ Buffalo hump Effects:
$ Easy bruising -‐ Reabsorption: Na, H2O, HCO3-‐
$ Truncal obesity -‐ Excretion: K+, Cl-‐, H+
$ Thinning of the skin
$ Osteoporosis Hyperaldosteronism
o " risk of infection -‐ Conn’s Disease
o Poor wound healing o Hypertension
o HPA (hypothalamic-‐pituitary-‐adrenal) o Edema
axis suppression (≥ 7-‐10 days) o Hypokalemia
$ Prevent: give for NMT 7-‐10 days o Hypochloremic metabolic alkalosis
$ BID (AM: "dose; PM: !dose) Hypoaldosteronism
$ Taper the dose before DC o Hypotension
• Abrupt DC # adrenal insufficiency o Hyperkalemia
Adrenal crisis – adrenal insufficiency + stress o Hyperchloremic
-‐ Abdominal pain o Metabolic acidosis
-‐ HTN
-‐ Death Preparations:
Use: # Fludrocortisone
• Inflammatory Diseases # Desoxycorticosterone acetate
37

Gonadal Hormones E + P # constant D1-‐D21
Estrogen b. Biphasic
Forms: D1-‐D10
1. Natural D11-‐D21
Estone (E1) c. Triphasic
Estradiol (E2) – major and most effective D1-‐D7
Estriol (E3) D8-‐D14
D15-‐D21
2. Synthetic 2. Injectable Contraceptive
Ethinyl estradiol DepoProvera®
Quinestrol -‐ Medroxyprogesterone acetate (MPA)
Methallenestril -‐ IM q 3 months
3. Implantable Contraceptives
3. Non-‐steroidal Intradermal implants
DES: diethylstilbesterol -‐ Etonogestrel (Implanon®) q 3 years
-‐ " risk of clear cell adenocarcinoma 4. Intrauterine Devices (IUD)
o Cervix Mirena®
o Uterus -‐ Leonorgestrel
o Vagina -‐ q 5 years
Chlorotrianisene 5. Morning After Pills
Effects: -‐ emergency contraception
-‐ Development of 2° sexual characteristics -‐ within 72 hours after coitus
-‐ Metabolic effects
o ! LDL, " HDL MOA of contraceptives:
-‐ " synthesis of procoagulants
(" thrombosis)

Progestins
Endogenous Progestins

1. Progesterone derivatives (-‐progesterone)
Medroxyprogesterone acetate (MPA)

2. Testosterone derivatives Effect: " GnRH
-‐ highly androgenic ! FSH – ✗ maturation of egg
Dimethisterone ! LH – ✗ ovulation

3. 19-‐nortestosterone derivatives Testosterone
-‐ highly androgenic !!!!"#$%&'("
𝑇𝑒𝑠𝑡𝑜𝑠𝑡𝑒𝑟𝑜𝑛𝑒 𝐷𝑖ℎ𝑦𝑑𝑟𝑜𝑡𝑒𝑠𝑡𝑜𝑠𝑡𝑒𝑟𝑜𝑛𝑒 (𝑎𝑐𝑡𝑖𝑣𝑒)
Levonorgestrel
Norethindrone 1. 5α-‐reductase inhibitors
Finasteride
4. 13-‐ethyl-‐19-‐nortestosterone derivatives Use: Management of BPH
-‐ less androgenic
Desogestrel FERTILITY DRUG
Norgestimate Clomiphene citrate
-‐ partial agonist of estrogen citrate
Effects: -‐ MOA: inhibition of binding of estrogen to
-‐ Development of 2° sexual characteristics its receptor (no negative feedback # "
-‐ Thermogenic effects GnRH # "FSH, "LH)
AE:
FORMS OF CONTRACEPTIVES -‐ Multiple pregnancy
1. Combined oral contraceptives (E + P) -‐ Ovarian hyperstimulation syndrome
Recommended: NMT 50 mcg/day estradiol
a. Monophasic
38

CNS Drugs Clozapine
I. Psychotropics Olanzapine
-‐ "/! the concentration of Risperidone
neurotransmitters in the brain Paliperidone
Neurotransmitters Zipralidone
Excitatory: NE, 5-‐HT-‐glutamate Quetiapine
Inhibitory: GABA, glycine Aripiprazole
Both: dopamine Loxapine

A. Antipsychotics Most efficacious: Clozapine
Psychosis (e.g. Schizophrenia)
Symptoms: SE: Dopamine blockade
• Positive -‐ EPS: extrapyramidal symptoms
Hallucinations – altered sensory perception -‐ NMS: neuroleptic malignant syndrome
-‐ Most common: auditory, visual o Tx: Bromocriptine + Dantrolene
Delusions – altered thought processing -‐ Hyperprolactinemia
-‐ Most common: paranoid/ persecutory -‐ Dopamine hypersensitivity
Disorganized speech or behavior -‐ Tardive dyskinesia – most severe –
potentially irreversible
-‐ Antihistamine # sedation
• Negative
-‐ α-‐blocking effect # orthostatic HTN
Alogia – no verbal output
-‐ Anticholinergic effects # ! potency (1st gen)
Flattening of affect
-‐ Agranulocytosis (Clozapine)
Anhedonia – inability to feel/experience pleasure
o Weekly monitoring of WBC count x 6
Avolition – lack of drive
months q 3 weeks thereafter

-‐ Seizures
Receptors Involved:
-‐ Cadiotoxicity
-‐ " dopamine, " 5-‐HT
QT prolongation

o Thioridazine
1. First Generation/ Typical antipsychotics
o Ziprasidone
MOA: block D2 receptors
Myocarditis
Examples:
o Clozapine (" risk of DM/ prediabetes)
i. Phenothiazines
-‐ Corneal/ lens deposits: Chlorpromazine
Aliphatics: Chlorpromazine
-‐ Retinal deposits:
Piperidines: Thioridazine
Thioridazine # blindness (Love is blind)
Piperazines: Fluphenazines
-‐ Weight gain, except:

o Aripiprazole
ii. Butyrophenones – most potent
o Amisulpride
Haloperidol

Droperidol
Types of EPS:

1. Akathisia
iii. Thioxanthenes
-‐ uncontrolled restlessness
Thiothixene
2. Acute dystonia – IV diphenhydramine

-‐ spastic retrocolitis/ torticollis
Potency:
3. Pseudoparkinsonism
Butyrophenones = Piperazines > Piperidines ≥
Tremors
Thioxanthines >>> Aliphatic
Rigidity
Note:
Akinesia
" potency, " affinity to D2 receptor, ! affinity to
Postural instability
histamine, α, and muscarinic receptors
Tx: Anticholinergics
! potency, ! affinity to D2 receptor, " affinity to
Trihexyphenidyl (Artane®)
histamine, α, and muscarinic receptors
Benztropine (Cogentin®)

Biperiden (Akineton®)
2. Second Generation/ Atypical
Dantrolene – Malignant Hyperthermia
MOA: block 5-‐HT2, D4 receptors

39

II. Mood Disorders 4. Trazodone, Nefazodone
(NE, 5-‐HT)
MOA:
-‐ inhibits 5-‐HT re-‐uptake blocks 5-‐HT2A/2C
receptor
AE:
-‐ Hepatotoxicity (Nefazodone)
-‐ Sedation (Trazodone)
-‐ Priapism (Trazodone)
Mixed D/O

Bipolar disorder – Mania + Depression
5. SNRI (Serotonin-‐NE reuptake inhibitors)
Cyclothymia – Hypomania + Dysthymia
Duloxetine – AE: hepatotoxicity

Venlafaxine – AE: cardiotoxicity
Antidepressants
Desvenlafaxine
1. TCA – tricyclic antidepressants

MOA: inhibition of NE/ 5-‐HT re-‐uptake
6. SSRI (Selective Serotonin reuptake
-‐ antihistamine, α, muscarinic
inhibitors)
Imipramine
Fluoxetine
Despiramine
Paroxetine
Doxepin
Sertraline
Amitriptyline
Citalopram
Nortriptyline
Escitalopram

Fluvoxamine
Other uses:
AE:
• Neuropathic pain -‐ Serotonin syndrome
Postherpetic neuralgia – phantom limb
o 5-‐HT excess
Herpes zoster
o Tx: Cyproheptadine
• Insomnia
• Eneuresis (Imipramine) 7. RIMA (Reversible Inhibitor of MAOA)
Moclobemide
2. Tetracyclic
Maprotiline 8. NaRI (Noradrenaline Reuptake
Mianserin Inhibitor)
Amoxapine Reboxetine

3. Non-‐selective MAO inhibitors 9. NaSSA (Noradrenergic Specific
Moclobemide – MAOA Serotonergic Antidepressant)
Phenelzine Mirtazapine – inhibits pre-‐synaptic α2 receptors
Isocarboxazid (stimulation: inh. of NE release;
Tranylcypromine inhibition: inc. NE release)
Selegiline – MAOB
10. Bupropion
Drug-‐Food Interaction MOA:
MAOI – tyramine-‐rich food # hypertensive crisis -‐ inhibits the re-‐uptake of NE and dopamine
-‐ Cheese (aged)
-‐ Fermented meat Drugs for Mania
o Salami 1st line: Lithium
o Pepperoni MOA:
-‐ Chicken liver -‐ inhibits recycling of phosphoinositides
-‐ Wine Drug Interactions:
-‐ Pickled vegetables ! serum level " serum level
MAOI # tyramine # “releaser” -‐ " NE release # Acetazolamide ACEIs
(α1,β1) " BP
Xanthines NSAIDs

Osmotic diuretic Thiazide diuretics

Sodium supplements Sodium loss

40

SE: No metabolites:
-‐ Nausea -‐ Clonazepam
-‐ Diarrhea -‐ Oxazepam
-‐ Polyuria -‐ Lorazepam
-‐ Polydipsia -‐ Alprazolam
-‐ Fine tremors SE:
o Coarse tremors (toxicity) Anterograde amnesia
-‐ Idiosyncratic o “Roofies” – Flunitrazepam – date rape drug
o Nephrogenic DI
-‐ More toxic Barbiturates
-‐ Not as effective as other drugs in the Phenobarbital – Management of neonatal
management of rapid cycling hyperbilirubinemia
Bilirubin
2. Valproic acid -‐ Direct # conjugation
-‐ as effective as Li -‐ Indirect # unconjugated
-‐ > effective for rapid cycling -‐ Phenbarbital induces the enzyme
-‐ Safer than Li needed for glucoronidation of bilirubin

3. Carbamazepine 2. Buspirone
-‐ Management of acute mania (prophylaxis) -‐ Partial agonist of 5-‐HT1A
-‐ no sedation
(check supplement) -‐ no anticonvulsant
-‐ no addictive
III. Anxiety D/O -‐ no dependence
GAD # Generalized Anxiety Disorder -‐
PD # Panic Disorder 3. β blockers
PTSD # Post-‐traumatic Stress Disorder 4. TCA
SP # Social Phobia
OCD # Obsessive-‐Compulsive Disorder Drugs for Seizures
Types of seizures:
Anxiolytics I. Partial – 1 hemisphere
1. Sedatives/ Hypnotics Simple # no loss of consciousness
Benzodiazepines Complex # loss of consciousness
Barbiturates Tx:
MOA: 1st line: Phenytoin, Carbamazepine
-‐ act on the GABAA receptor complex Others: Lamotrigine, Oxcarbazepine,
(composed of 5 subunits # Cl-‐ channel) Valproic acid

II. Generalized – both hemispheres
Generalized Tonic-‐Clonic (Grand mal)
-‐ DOC: valproic acid
-‐ CI: < 2 year old (hepatotoxicity)

Absence (petit mal)
-‐ “blank stares”
-‐ DOC: ethosuximide
-‐ Alternative: valproic acid

Myoclonic
(Examples & SE: see supplement p.92) -‐ Tx: valproic acid, lamotrigine,
Benzodiazepines topiramate
2 active metabolites:
1. Nordiazepam – N-‐desmethyldiazepam Atonic (frequent falls)
2. Oxazepam -‐ Tx: valproic acid, lamotrigine,
topiramate
41

Status epilepticus Apomorphine
-‐ DOC: Lorazepam (initial) -‐ Derivative of morphine that is a non-‐
-‐ Phenytoin (maintain) narcotic
-‐ D2 agonist
Acute seizures -‐ Used as an adjunct in the management of
-‐ DOC: Diazepam parkinsonism
-‐ Also used as an emetic
Drugs for Parkinson’s Disease
! dopamine, " ACh Anesthetics
S/Sx: General anesthetics
-‐ TRAPS (shuffling gait) Stages of anesthesia:
Tx: (1) Cortical (analgesia)
-‐ Dopamine agonists (2) Delirium (excitation)
-‐ Anticholinergics (3) Surgical
(4) Medullary (respiratory failure)
1. Levodopa
-‐ dopamine: catecholamine # cannot Routes of administration for general anesthetics:
cross BBB 1. Inhalational
-‐ dopamine precursor # will be Minimum alveolar concentration (MAC)
converted to dopamine when it reaches -‐ relationship with potency: inverse
the brain (DOPA decarboxylase) Nitrous oxide – least potent
-‐ To prevent premature metabolism of Desflurane
levodopa jn the periphery: + Carbidopa Sevoflurane Decreasing
Isoflurane MAC
SE:
-‐ “Wearing off phenomenon” after 3-‐5 Enflurane – least hepatotoxic
years of use Halothane – most potent that is currently used;
most hepatotoxic
2. Direct dopamine agonists
Ergot derivatives:
Bromocriptine
Cabergoline
Pergolide – X: valvular heart disease

Non-‐ergot derivatives:
Pramipexole
Ropinirole
Rotigotine

3. Indirect dopamine agonists
-‐ Does not bind to dopamine receptors but
still " concentration of dopamine
MAOB inhibitors:
Selegiline
Rasagiline

COMT inhibitors Methoxyflurane – most potent
Entacapone
Tolcapone # AE: hepatotoxicity 2. IV
Benzodiazepines – balanced anesthesia
Amantadine Midazolam
-‐ Used also for tx of Influenza A Lorazepam
-‐ " secretion, ! reuptake of dopamine Diazepam

42

Barbiturates
-‐ Thiopental
Etomidate
-‐ no analgesic activity, (+) sedative
Propofol
-‐ emulsion
-‐ rapid onset
Ketonamine
-‐ dissociative anesthesia
Phencyclidine (PCP)
-‐ “angel dust”
Opioids
Fentanyl
-‐ (+ Droperidol) # neurolept analgesia
-‐ (+ Droperidol + 65% N2O in O2) #
neuroleptanesthesia
Morphine

Local Anesthetics
Ester-‐type (1 i)
Amide-‐type (2 i)

Procaine
Benzocaine
Cocaine – only local anesthetic with
vasoconstricting effects
-‐ inhibits the reuptake of NE
Lidociane
Bupivacaine – most cardiotoxic local anesthetic
43

Cancer Chemotherapy Multiple Drug Use
Cancer cells Rationale:
-‐ rapidly-‐dividing cells -‐ To prevent tolerance/ resistance
-‐ out of control -‐ For more effective killing of cancer cells
-‐ metastasis -‐ To minimize SE
o ! dose for each drug
Antineoplastic drugs
-‐ target rapidly-‐dividing cells Drugs:
-‐ target cells in the cell cycle A. Cytotoxic Drugs
1. Direct DNA-‐interacting
Cell Cycle a. Alkylating agents
G1 – preparation (40%) Cyclophosphamide/Ifafimide
S – DNA synthesis (39%) Pt-‐containing compounds
G2 preparation (19%) o Cisplatin
M – cell division/ mitosis (2%) o Carboplatin
o Oxaliplatin
Phase-‐specific Antineoplastics Carmustine, Lomustine
M phase – antimitotics Mechlorethamine
S phase – antimetabolites Busulfan
G1 phase – etoposides Procarbazine/ Dacarbazine
G2-‐M phase – Bleomycin
Non-‐phase-‐specific Antineoplastics MOA:
-‐ the rest -‐ Incorporates an alkyl group to cell
constituents
Tumor kinetics SE:
-‐ tumor growth rate follows a -‐ myelosuppression
Gompertzian curve -‐ alopecia
o after the peak the tumor already -‐ N/V
outgrows the blood supply -‐ Cyclophosphamide/ Ifosfamide:
# of cancer cells Clinical manifestation hemorrhagic cystitis
o Prodrug; converted to phosphoramide
< 109 Asymptomatic (subclinical)
mustard + acrolein (causes
109 Symptomatic (1 cm)
hemorrhagic cystitis)
10 12 Fatal size (1 kg)
o Prevention: Mesna

(mercaptoethanesulfonate) # rescue
Intermittent chemotherapy:
drug
Rationale:
-‐ Oxaliplatin – peripheral neuropathy
-‐ To give time for normal cells to recover
-‐ Busulfan – adrenal failure; pulmonary
-‐ To give time for normal cells to recover
fibrosis
-‐ To recruit cells in the Go phase back to

the cell cycle
b. Topoisomerase inhibitors

DNA topoisomerase 1: 1 strand
# of cycles: 5-‐6
DNA topoisomerase 2: 2 strands
Interval between cycles: 3-‐4 weeks
-‐ forms a break/ nick in the DNA strands

1° goal: to reduce the cancer cell number to ≤
# DNA damage

0.01 cells
1. Antineoplastic antibiotics

Mitomycin # AE: HUS (hemolytic uremic
For every cycle of chemotherapy:
syndrome)
3 log kill hypothesis
o First seen in E. coli 0157:H7
10!" → 10! → 10! → 10!
Bleomycin # pulmonary fibrosis (Busulfan)

-‐ only phase-‐specific antineoplastic
antibiotics
Dactinomycin

44

2. Anthracycline antibiotics Vinca alkaloids
-‐rubicin Vinca rosea; Catharanthus roseus
Doxorubicin Vinblastine
Daunomycin Vincristine # AE: neurotoxicity
Idarubicin Vinorelbine # AE: vasculitis
Epirubicin
AE: B. Hormonal Agents
-‐ Cardiotoxicity 1. Tamoxifen
MOA: partial agonist of estrogen receptor
3. Podophyllotoxin derivatives
Etoposide 2. Aromatase inhibitors
Teniposide MOA: converts androstenedione # estrogen
Exemestane
4. Camptothecin derivatives Letrozole
-‐tecan Anastrozole
Irinotecan
-‐ Diarrhea Use of Tamoxifen and Aromatase Inhibitors:
o Subacute: w/in 24 hours; Tx: Atropine • Management of estrogen receptor positive
o Delayed: w/in 1-‐10 days; Tx: breast CA
Loperamide
Topotecan 3. Androgen receptor antagonists
Bicalutamide
Flutamide
2. Indirect DNA-‐interacting Use:
a. Antimetabolites • Management of prostate cancer
Folic acid antagonists
MOA:
-‐ inhibit dihydrofolate reductase C. Targeted therapy
Methotrexate Mab – monoclonal antibody
SE: Mumab: murine
-‐ Hepatotoxicity Zumab: humanized
-‐ Mucositis Ximab: mixed
o Rescue drug: Leucoverin/ Folinic acid
Pemetrexed Bevacizumab
-‐ Rescue drug: vitamin B12 -‐ VEGF-‐R (vascular epithelial growth
factors)
Purine/Pyrimidine analogues Cetuximab
5-‐Fluorouracil -‐ EGF-‐R (epithelial growth factor)
-‐ + folinic acid (" effect) Trastuzumab
MOA: -‐ her2/neu-‐R
-‐ Inhibit DNA and RNA synthesis
Capecitabine – PO form of 5-‐FU -‐Nib # tyrosine kinase receptor
Sorafenib – VEGF-‐R-‐tk
b. Antimitotics Sunitinib -‐ VEGF-‐R-‐tk
Taxanes Erlotinib -‐ EGF-‐R-‐tk
Paclitaxel # AE: hypersensitivity reaction (esp in Gefitinib -‐ EGF-‐R-‐tk
1st and 2nd cycles)
-‐ albumin-‐bound Paclitaxel # less
hypersensitivity reactions
Docetaxel
Cabazitaxel

45

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