Principles of General and Autonomic Pharmacology
Principles of General and Autonomic Pharmacology
Principles of General and Autonomic Pharmacology
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<strong>Principles</strong> <strong>of</strong> <strong>General</strong> <strong>and</strong><br />
<strong>Autonomic</strong> <strong>Pharmacology</strong><br />
Dr. Edward JN Ishac<br />
Pr<strong>of</strong>essor<br />
<strong>Pharmacology</strong> Course Director<br />
Department <strong>of</strong> <strong>Pharmacology</strong> &<br />
Toxicology<br />
Smith Bldg, Room 742<br />
eishac@vcu.edu, x82127<br />
Reference Material<br />
• Basic <strong>and</strong> Clinical <strong>Pharmacology</strong><br />
by Katzung, 11th ed., 2009,<br />
paperback (required text)<br />
(New: $65, Used: $49)<br />
• Goodman & Gilman’s<br />
Pharmacological Basis<br />
<strong>of</strong> Therapeutics, 11 th ed.<br />
2005 (optional text)<br />
(New: $170, Used: $127)<br />
Paperback manual ($58)<br />
<strong>Pharmacology</strong> Syllabus<br />
• Course material approx. 300 pages<br />
• Drug summary tables for available for<br />
<strong>Pharmacology</strong> instructors.<br />
- Drug summary tables also available for<br />
faculty in other courses<br />
- Drug summary tables are not a substitute<br />
for syllabus, but list the main points or<br />
features<br />
- Underst<strong>and</strong>ing the drug summary<br />
Requires knowledge <strong>of</strong> syllabus<br />
<strong>Principles</strong> <strong>of</strong> <strong>Pharmacology</strong> Faculty<br />
Dr. Ishac<br />
Dr. Ritter<br />
Dr. Welch<br />
Dr. Damaj<br />
Dr. Robinson<br />
Dr. Lichtman<br />
Dr. Cumpston<br />
<strong>Autonomic</strong> pharmacology & NMJ,<br />
human simulation modules (new)<br />
Absorption, distribution, metabolism,<br />
excretion (ADME), drug interactions<br />
pharmacokinetics<br />
Pain control, opioids, NSAIDs, PGs<br />
Mechanisms <strong>of</strong> drug action, dose<br />
response, pharmacogenetics, drug<br />
modification, FDA regulation<br />
Local anesthesia, CYP450<br />
Antihistamines, herbal products<br />
Toxicology introduction<br />
Additional learning resources<br />
• Micromedex <strong>and</strong> MD Consult<br />
These are drug <strong>and</strong> patient databases<br />
available through the VCU Library web<br />
• Rx List www.rxlist.com<br />
• Online Pharmacokinetics training module<br />
(Dr. Ritter)<br />
• Online Cardiovascular modules (Dr. Ishac)<br />
Alternate <strong>Pharmacology</strong> website<br />
• http://www2.courses.vcu.edu/ptxed/ptx<br />
• Contains: many practice questions (ANS),<br />
faqs, audio review <strong>of</strong> the cardiovascular<br />
system, online PowerPoint presentations,<br />
glossary. PDF <strong>and</strong> other downloads<br />
• https://ecurriculum.som.vcu.edu/<br />
1
Examinations <strong>and</strong> Grading<br />
Faculty<br />
• Final grade is determined by your<br />
performance on all pharmacology questions<br />
during the year 2010-11<br />
• <strong>Pharmacology</strong> questions are identified on<br />
each exam (Pharmtox). Questions will count<br />
as part <strong>of</strong> your grade in each course (GI,<br />
CNS, Renal, etc.,) <strong>and</strong> then combined to<br />
determine your final pharmacology grade.<br />
Name<br />
Balster<br />
Costanzo<br />
Damaj<br />
Gewirtz<br />
Hylemon<br />
Ishac<br />
Nicholson<br />
Course<br />
Behavioral<br />
Renal<br />
<strong>Principles</strong><br />
Hem/Oncology<br />
Microbiology<br />
<strong>Principles</strong><br />
Cardiovascular<br />
Microbiology<br />
Name<br />
Lichtman<br />
Cumpston<br />
Ritter<br />
Robinson<br />
Miles<br />
Akbarali<br />
Welch<br />
Course<br />
<strong>Principles</strong><br />
<strong>Principles</strong><br />
<strong>Principles</strong><br />
Cardiovascular<br />
<strong>Principles</strong><br />
Respiratory<br />
GI<br />
<strong>Principles</strong><br />
Womens Health<br />
M2 Course<br />
<strong>Pharmacology</strong> Questions (Pharmtox)<br />
<strong>Pharmacology</strong><br />
Pathogenesis<br />
Microbiology<br />
Hematology<br />
Endocrine<br />
Renal<br />
Respiratory<br />
Cardiovascular<br />
Central Nervous System<br />
Behavioral Sciences<br />
Women’s Health<br />
GI<br />
Musculoskeletal<br />
Total Questions<br />
2009-10<br />
99<br />
4<br />
42<br />
12<br />
17<br />
20<br />
9<br />
26<br />
14<br />
25<br />
19<br />
5<br />
10<br />
303<br />
(1FCM)<br />
2008-09<br />
100<br />
4<br />
39<br />
12<br />
15<br />
21<br />
8<br />
36<br />
13<br />
25<br />
19<br />
9<br />
10<br />
311<br />
2007-08<br />
100<br />
4<br />
46<br />
17<br />
20<br />
22<br />
8<br />
28<br />
24<br />
28<br />
17<br />
10<br />
15<br />
339<br />
2006-07<br />
104<br />
4<br />
39<br />
15<br />
17<br />
22<br />
8<br />
30<br />
22<br />
27<br />
18<br />
11<br />
15<br />
332<br />
Exam Results 2009-10<br />
Total pharmacology questions in various<br />
courses = 303 (class avg = 85.9)<br />
Total all M-II questions 1420<br />
(class avg = 84.2 – 89.8)<br />
<strong>Pharmacology</strong> % <strong>of</strong> total – 21.4%<br />
2009-10: Honors (33) High Pass (75)<br />
Pass (85) Marginal (0)<br />
Fail (0) Incomplete (1)<br />
<strong>Pharmacology</strong> Examination<br />
• Exam will be on Friday Aug. 6 th in MSB<br />
• Curriculum <strong>of</strong>fice will announce time & duration<br />
• It will be a paper exam not electronic<br />
• The test will be multiple choice questions<br />
• It will consist <strong>of</strong> 100 MCQs, no True/False<br />
• You should bring a calculator; PDAs not allowed<br />
• Contains reference value table (back)<br />
• Most questions in USMLE Step 1 format<br />
• Drug trade names not included nor required<br />
Pharmacokinetics & Cardiovascular Review<br />
Session (Optional)<br />
• Friday July 30th, 12 noon in Baruch (optional)<br />
• Dr. Ritter:<br />
• Review principles <strong>of</strong> Pharmacokinetics (ADME)<br />
• Online Pharmacokinetics self-learn module (access<br />
through eCurriculum)<br />
• Monday Aug. 2nd, 12 noon in Baruch (optional)<br />
• Dr. Ishac: Review autonomic agents <strong>and</strong> their effect<br />
on the cardiovascular system<br />
• http://www2.courses.vcu.edu/ptxed/ptx/cardiov<br />
ascular.htm<br />
2
Neuromuscular Blocking Agents - TBL<br />
• Dr. Ishac<br />
• Team-based Learning (TBL) session<br />
• Tuesday Aug 3rd, 9:40am-11am<br />
• Use <strong>of</strong> “Clickers”<br />
• Use M-I group assignments<br />
• Complete reading assignment before class<br />
• Individual MCQ (6) test<br />
• Group MCQ test (same 6 questions)<br />
• MCQ question discussion appeal<br />
• <strong>General</strong> discussion question by group<br />
• Review <strong>of</strong> material<br />
Human Simulation Module<br />
• Drs. Ishac & Cumpston (ANS & Toxicology)<br />
• Optional Manikin simulation modules<br />
• Sign-up online (see eBoard) by Wed Jul 28 th , 10pm<br />
• North Hospital, 2 nd Floor, B218 (staging area)<br />
• Held Tue Aug 3rd, 12:40pm-5pm (20 min<br />
simulation session followed by 15 min debriefing)<br />
• Team groups <strong>of</strong> 8 for simulation module<br />
• Bonus <strong>of</strong> 1 point towards your <strong>Pharmacology</strong><br />
examination for participation (sign-out)<br />
• Includes 1 Pharmacy student per group<br />
• Presented with 1 module <strong>of</strong> 10 for simulation<br />
• Reinforce concepts from class<br />
Tips for Drug Learning<br />
• Learn agents by drug classes<br />
ie. beta-blockers, Ca ++ -blockers etc<br />
• Key points:<br />
- Clinical application<br />
- Mechanism <strong>of</strong> action<br />
- Drug <strong>of</strong> choice (DOC)<br />
ie. epinephrine (anaphylaxis)<br />
- Prototype drugs, most common agents<br />
ie. propranolol, atenolol, metoprolol<br />
- Important drug/drug interactions<br />
ie. MAO inhibitors & tyramine rich food<br />
- Adverse drug reactions<br />
ie. beta-blockers – asthma, Raynaud’s D.<br />
- Do not focus on dosage, know high/low Rx<br />
Typical / Ideal Step 1 Exam Question<br />
A 42-old woman who is a biochemist is<br />
brought to the emergency department<br />
because <strong>of</strong> a 1-hour history <strong>of</strong> severe<br />
abdominal cramps, nausea, vomiting,<br />
sweating, <strong>and</strong> difficulty breathing due to<br />
bronchospasm <strong>and</strong> congestion. On<br />
physical examination her pulse is<br />
45/min, BP is 85/50 mm Hg <strong>and</strong> she<br />
exhibits generalized muscle weakness.<br />
Laboratory studies show no<br />
abnormalities. Exposure to which <strong>of</strong> the<br />
following is most likely?<br />
A. atropine<br />
B. bethanechol<br />
C. botulinum toxin<br />
D. is<strong>of</strong>lurophate<br />
E. phentolamine<br />
Stem order<br />
Patient details<br />
Presenting problem<br />
History<br />
Physical exam<br />
Laboratory findings<br />
Initial treatment<br />
Subsequent findings<br />
Option lead-in<br />
(No negative lead-in)<br />
Options<br />
Cover-up rule<br />
Homogenous (tests, Rx)<br />
Balanced (↑ or ↓)<br />
Plausible<br />
Similar length<br />
Alphabetical<br />
Typical / Ideal Exam Question Type F 1d<br />
A 52-old man undergoes a right<br />
total hip replacement. During the<br />
procedure, the patient experiences<br />
a flaccid muscle paralysis <strong>and</strong> a<br />
decrease in blood pressure<br />
following the administration <strong>of</strong> the<br />
neuromuscular blocking drug.<br />
Which <strong>of</strong> the following<br />
neuromuscular drugs was most<br />
likely administered in this patient?<br />
A. atracurium<br />
B. mivacurium<br />
C. pancuronium<br />
D. rocuronium<br />
E. succinylcholine<br />
F. tubocurarine<br />
Rules ?<br />
Two questions<br />
Same stem<br />
No return to 1 st MCQ<br />
No extra information<br />
Answers not dependent<br />
Different lead in<br />
Options<br />
Cover-up rule<br />
Homogenous (tests, Rx)<br />
Balanced (↑ or ↓)<br />
Plausible<br />
Similar length<br />
Alphabetical<br />
Typical / Ideal Exam Question Type F 1e<br />
A 52-old man undergoes a right total hip<br />
replacement. During the procedure, the patient<br />
experiences a flaccid muscle paralysis <strong>and</strong> a<br />
decrease in blood pressure following the<br />
administration <strong>of</strong> the neuromuscular blocking drug.<br />
At the end <strong>of</strong> the operation, a drug is administered<br />
to reverse the muscle paralysis. This drug was<br />
most likely which <strong>of</strong> the following?<br />
A. atropine<br />
B. dantrolene<br />
C. neostigmine<br />
D. pancuronium<br />
E. physostigmine<br />
F. succinylcholine<br />
3
Drug Extensions I<br />
Drug Extensions II<br />
Beta-blockers<br />
-olol<br />
propranolol<br />
atenolol<br />
Alpha1-blockers<br />
ACE inhibitors<br />
-azosin<br />
-pril<br />
prazosin<br />
captopril<br />
terazosin<br />
lisinopril<br />
Thrombolytics<br />
Corticosteroids<br />
-ase<br />
-plase<br />
-sone<br />
streptokinase<br />
prednisone<br />
reteplase<br />
dexamethasone<br />
A-II blockers (ARBs)<br />
NMJ blockers<br />
Ca Channel blockers<br />
HMG CoA reductase<br />
inhibitors (statins)<br />
-sartan<br />
-curium<br />
-dipine<br />
-vastatin<br />
losartan<br />
atracurium<br />
nifedipine<br />
atorvastatin<br />
valsartan<br />
rocuronium<br />
nicardipine<br />
simvastatin<br />
Protein pump<br />
inhibitors<br />
H2-blockers<br />
Benzodiazephines<br />
-prazole<br />
-tidine<br />
-zepam<br />
-zolam<br />
omeprazole<br />
cimetidine<br />
diazepam<br />
loprazolam<br />
lansoprazole<br />
ranitidine<br />
lorazepam<br />
alprazolam<br />
Antifungals<br />
Drug Extensions III –<br />
Antibiotics/Antifungal Agents<br />
Aminoglycosides<br />
Macrolides<br />
Fluroquinolones<br />
Tetracyclines<br />
Cephalosporins<br />
Penicillins<br />
-azole<br />
-micin,<br />
-mycin<br />
-thromycin<br />
-floxacin<br />
-cycline<br />
cef-, ceph-<br />
-cillin<br />
miconazole<br />
gentamicin<br />
erythromycin<br />
cipr<strong>of</strong>loxacin (2)<br />
doxycycline<br />
cefaclor (2)<br />
penicillin G<br />
itraconazole<br />
streptomycin<br />
azithromycin<br />
lev<strong>of</strong>loxacin (3)<br />
oxytetracycline<br />
cefdinir (3)<br />
penicillin V<br />
1A2<br />
2E1<br />
2C9<br />
2C19<br />
2D6<br />
3A4<br />
Main Cytochrome P450 Enzymes<br />
Inhibitors<br />
Amiodarone, cimetidine,<br />
cipr<strong>of</strong>loxacin, fluvoxamine<br />
Disulfirum<br />
Amiodarone, fluoxetine,<br />
metronidazole,<br />
trimethoprim/sulfamethoxazole<br />
Isoniazid, ritonavir,<br />
fluvoxamine<br />
Amiodarone, cimetidine,<br />
diphenhydramine, ritonavir,<br />
fluoxetine<br />
Diltiazem, grapefruit, verapamil,<br />
erythromycin, clarithromycin,<br />
ritonavir, ketoconazole<br />
Inducers<br />
Carbamazepine,<br />
smoking, rifampin,<br />
phenobarbital<br />
Alcohol, isoniazid<br />
Carbamazepine,<br />
phenytoin,<br />
phenobarbital, rifampin<br />
Carbamazepine,<br />
phenytoin, rifampin<br />
No significant inducers<br />
Carbamazepine,<br />
phenytoin,<br />
phenobarbital, rifampin,<br />
St. John’s wort<br />
Substrates<br />
Caffeine, tizanidine,<br />
theophylline,<br />
r-warfarin<br />
Acetaminophen<br />
Carvedilol, ARB,<br />
s-warfarin,<br />
fluvastatin<br />
Omeprazole,<br />
phenytoin,<br />
phenobarbital<br />
Carvedilol,<br />
amitriptyline,<br />
codeine, metoprolol<br />
CCBs, statins,<br />
zolpidem, r-warfarin,<br />
prednisone,<br />
saquinavir, estrodiolcontraceptives<br />
Agent<br />
Lead<br />
Arsenic<br />
Iron<br />
Mercury<br />
Carbon<br />
monoxide<br />
Copper<br />
Cyanide<br />
Symptoms<br />
Toxicity I<br />
Vomiting, nausea, diarrhea, gingival bluish line<br />
(Burton line), weakness extensor muscles (wrist<br />
drop), microcytic hypochromic anemia, ab. pain<br />
Vomiting, neuropathy, microcytic hypochromic<br />
anemia, diarrhea, alopecia, hyperpigmentation<br />
Vomiting with blood, lethargic, ab. pain, ↑ferritin,<br />
high anion gap metabolic a. (prenatal supp.)<br />
Vomiting, abdominal pain, hyperhydrosis, ataxia,<br />
↑HR, muscle weakness, ↑NE/EPI (↓metab.), red<br />
cheeks/fingers/toes, lethargy, renal toxicity<br />
Headache, blurred vision, nausea, fatigue, red<br />
lips/fingers, ↑carboxyhemoglobin, tachycardia<br />
Headache, tremor, rigidity, difficulty swallowing,<br />
irritable, confused, ↑AST/ALT, ↑ceruloplasmin<br />
(ferroxidase), renal toxicity, hemolysis, ab. pain<br />
Muscle weakness, hypotension, high anion gap<br />
metabolic acidosis, dysrhythmias, dyspnea,<br />
seizures, bitter almond odor, ↑plasma lactate<br />
Treatment<br />
Succimer<br />
(Ca-EDTA,<br />
Dimercaprol)<br />
Fluid replacement<br />
<strong>and</strong> Dimercaprol<br />
Deferoxamine<br />
Dimercaprol<br />
Hyperbaric oxygen,<br />
Oxygen<br />
D-Penicillamine,<br />
(Dimercaprol)<br />
Na nitrite/Amyl nitrite,<br />
Hydroxycobalamin,<br />
Na Thiosulfate<br />
Agent<br />
Organophosphate<br />
Belladonna<br />
alkaloids<br />
Nitrates<br />
Methanol<br />
Ethylene<br />
glycol<br />
Warfarin<br />
Amiodarone<br />
Symptoms<br />
Toxicity II<br />
sludgebam, muscle weakness, salivation<br />
sweating, miosis, lacrimation, urination,<br />
diarrhea, bronchospasm, bradyacardia, cramps<br />
Dry mouth, blurred vision, mydriasis,<br />
tachycardia, flushing, delirium, convulsions,<br />
urinary retention, constipation, confusion<br />
Headache, dizziness, chest pain, tachycardia,<br />
hypotension, methemoglobin, hemolysis<br />
Nausea, vomiting, intoxication, blurred vision,<br />
ataxia, ↑plasma formic acid, high anion gap<br />
metabolic a., ↑osmolality gap<br />
Slurred speech, nausea, vomiting, confusion,<br />
uncoordinated, lethargic, resting tremor, anion<br />
gap m. acidosis, ↑osmolar gap, intoxication<br />
Ecchymoses, easy bruising, hematuria, anemia,<br />
dark stools, bleeding gums, ↑PT/INR<br />
Diffuse crackles, wheezing, pulmonary fibrosis,<br />
↓HR, prolonged QT, wide QRS, hypothyroidism,<br />
cardiac depression, photosensitivity, bluish skin<br />
Treatment<br />
Atropine <strong>and</strong><br />
Pralidoxime (2-<br />
PAM)<br />
Cholinesterase<br />
inhibitor ie.<br />
Physostigmine<br />
Methylene blue<br />
Fomepizole<br />
Fomepizole<br />
Stop drug<br />
Stop drug<br />
4
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