8-1 Pharmacology

q123456's version from 2016-06-01 19:52


Question Answer
Sulfa allergiescelecoxib,
sulfonamide loop diuretic (furosemide)
malignant hyperthermiahypersensitivity of skeletal muscles to inhalation anesthetics. ryanodine receptor release large amount of Ca after exposure to anesthetic. fever and muscle rigidity soon after surgery

muscle relaxant: intracelluar calcium release in skeletal muscles. used for malignant hypertheria soon after surgery
tachyphylaxistachyphylaxis (tachypnea: rapid breathing, tachycardia: high HR)
decreased durg responsiveness with repeated administration
additivewhen combined effect of two drugs is equal to the sum of the effects expected from the individual drugs
synergisticwhen combined effect exceeds the sum of the individual effects
permissivethe drug does not have a direct effect on vascular reactivity, but it augments the effect of other drug
electric stimulation of the musculocutaneous nerve causes a rapid twitch of the bicep muscle. electron microscopy shows numerous vesicles within the musculocutaneous nerve terminals. in order for these vesicles to release their contents into the synaptic cleft, which of the following substances in required?calcium
oral bioavailability area under the oral curve divided by area under the IV curve
potency=affinity of the drug for its receptor>>>ED50
treatment with competitive antagonist
lower the potency (low affinity)
efficacy=maximum ceiling of activity of a drug
treatment with noncompetitive antagonist
lower the efficacy (maximum effect)
higher potency=cause the same effect with lower con.c of drug
CYP450 InducersCYP450 Inducers
rifampin KA24-22

Chronic alcohol consumption and smoking induce the P450 system in SER of the liver. KA34-17

CYP450 Inhibitors KA35-6
CYP450Most drugs deactivated by P450. some drugs activated by P450 (e.g primidone>>>phenobarbital, clopidogrel)
inhibit warfarin metabolism leading to a high serum level and an increased bleeding riskcimetidin, SSRIs, amiodarone, trimethoprim, isoniazid and azole
a new drug has been developed that inhibits one of the steps in fatty acid oxidation. it is condidered promsing for the treatmnet of stable angina. which of the followin is the most likely mechanism explaining the potentially beneficial effect of the drug in patients with this condition?less oxygen use per one ATP synthesized
volume of distributionamount of drug/plasma con.c.
a higher VD indicates a greater amount of tissue distribution.

the volume of distribution of the drug is low:
The smaller the volume of distribution, the more likely that the drug is confined to the circulatory system.
3-5liters, large mw, bound to plasma protein, highly charged

the volume of distribution of the drug is high
The larger the volume of distribution, the more likely that the drug is found in the tissues of the body.
14-16 liters
small mw
high lipid solubility
low plasma binding capabilities
uncharged (>>>41 liters)
steady stateInfusion dose/CL KA23/12
first order kineticsconstant fraction or proportion of drug is metabolized per unit time based on the serum concentration.
zero order kineticsa constant amount of drug is metabolized per unit time, independent of concentration
Acetylation of durgisoniazid, dapsone , hydralazine procainamide
methylation of drugsazathioprine, 6-mercaptopurine
glucuronidation of drugsbilirubin,
high first pass metabolismwhen a drug is absorbed by the GI tract after oral administration, it first enters the portal circulation before gaining access to the systemic circulation. if the drug is metabolized extensively by the liver, the mount that reaches the systemic circulation and therefore the bioavailability will be LOW!
a drug has a volume of distribution of 10L and clearance of 7L/h for a healthy 70 kg man, how long would it take for 75% of this drug to be excreted after a single dose?2 hours, t1/2=VX0.7/Clearance=10x0.7/7=1 hours
75%=2 hours,
89%=3 hours
CKD patients use the drugs with high intrinsic hepatic clearance high lipophilicity and high volume of distribution>>>enter hepatocytes
the mechanisms of n-acetyl cysteine on acetaminophen overdoseNAC acts as a glutathione substitute and binds to the toxic metabolite NAPQI which causes hepatocelluar injury, provides sulfhydryl groups to enhance the non toxic sulfation elimination of acetaminophen.
activation of cGMPnitric oxide and antrial natriuretic peptide

Immunosuppressive theapy

Question Answer
Immunosuppressive theapy1 glucocorticoids

2 cyclosporine and tacrolimus:
inhibit calcineurin activition>>> inability to dephosphorylates NFAT>>> inability to enter the nucleus and bind to IL2 promoter>>>growth and differentiation of T cells
SE: kidney toxicity!!!, hirsutism

3 sirolimus(rapamycin):
blocks mTOR>>>inhibition of IL driven T cell proliferation
SE: hyperlipidemia and thrombocytopenia/leukopenia

4 mycophenolate mofetil: purine synthesis

5 thalidomide: block TNFa, increase IL10

6 daclizumab: IL-2 receptor

7 muromonab-cd3: binds to CD3

8 Purine analogs azathioprine (6-mercaptopurine's precursor)


Question Answer
chemotherapeutic drugfirst order kinetics KA34-47
the drug will kill a constant proportion of tumor cells (rather than a constant number).
a specific dose kills a specific fraction of tumor cells regardless of the population.
methotrexatedihydrofolate reductase
hydroxyurearibonucleotide reductase
purine analogs A/G6-mercaptopurine
cladribine (Adenosine):hairy cell leukemia
pyrimidine analogs C/T/U5-FU
alkylating agentchlorambcil (CLL) KA35-13

cyclophosphamide (also used for Wegener's)

cisplatin (Testicular and ovarian)

dacarbazine (metastatic malignant melanoma and Hodgkin)
vinca rosea (vincristine, vinblastine, vinorelbine)
bind to tubulin and prevent formation of microtubules>>>unable to form mitotic spindle
used for Hodgkin
SE: neurotoxicity-->finger numbness and tingling

paclitaxel (ovarian, breast and non small cell lung cancer)
bind to tubulin and promote the assembly of microtubules and prevent depolymerization.
both has a cardiotoxicity

bleomycin (pulmonary fibrosis)

etoposide (bone marrow suppression, used for testicular cancer)

1) eukaryotic type II topoisomerase inhibitors ***bacterial type II topoisomerase inhibitors (gyrase): fluoroquinolones

2) toxic oxygen free radicals (cardiac toxicity)
hormone therapyestrogen antagonists
tamoxifen (1st line for advanced breast cancer, but increases endometrial carcinoma)

aromatase inhibitors
exemestane KA35-20

GnRH analogs
leuprolide (prostate cancer)

Antiandrogens "mide"
monoclonal antibodytrastuzumab

binds to CD20
B-cell NHL

inhibits Bcr-AbL

inhibits phosphorylation of tyrosine kinases>>>EGFR
locally advanced or metastatic non–small cell lung cancer.

inhibit the 26 S proteasome>>>disrups cell proliferation and apoptosis
multiple myeloma

NE, Epi, Acetycholone

Question Answer
Cardiovascular changes when a persion sits or stands from a supine positionKA37-25
blood pressure tends to fall>>>baroreceptor mechanisms>>>increased HR, increased contractility, constriction of arterioles(increased TPR)
___use acetycholine as a neurotransmitter?sympathetic innervation of the sweat gland and adrenal glands
parasympathetic output to the heart and bronchi is mediated by muscarinic receptors
a 26 year old caucasian woman presents to the offcie with progressive fatigability and diplopia. she is currently receiving neostigmine for treatment and clains good compliance. physical examination reveals bilateral ptosis. infusion of low dose edrophonium elicits a significant improvement in her muscle strength. which of the following is the best next step in the management of this patient?infusion of the short acting cholinesterase inhibitor edrophonium
1) diagnosisi of myasthenia gravis
2) increases neuromuscular tranmission and provides temporary improvement in symptoms>>>myasthenic crisis>>> increase neostigmine dosage

cholinergic crisis: too high doses of cholinesterase inhibitor>>>muscle weakness
gardener's mydriasisjimson weed>>>toxins>>>anticholinergic. jimson weed=atropine. treatment: physostigmine (anticholinesterase)
Atropine (High HR, BP, dry mouth/eye, constipation and no urine)anticholinergic:
high HR
muscarinic antagnist: decreased nitric oxide>>>elevated BP
decreased GI motility.
***muscarinic agonist increase motility and secretion in GI tract.
anticholinergic drugs relax the GI wall and increase the contraction of the sphincters, casing constipation
urinary retention
dry eye/mouth

can causes acute closed angle glaucoma>>>unilateral servere eye pain and visual disturbances
treatment: timolol: decreased secretion of aqueous humor produced by the epithelial cells of the ciliary body.

aqueous humor is produced by the epithelial cells of the cilary body. glaucoma is a chronic eye disease characterized by increased intraocular pressure. it develops due to diminished outflow or increased secretion of the aqueous humor.
muscarinic AGONIST (M3 agonist)1) release of endothelium-derived relaxation factor>>>binds to muscarinic receptor>>>NO release>>>cGMP>>>vascular SM relaxation>>>lower BP>>>Baroreceptor reflex>>>HR is increased

2) increase GI motility not GI sphincter contraction (relax)!!
3) bronchoconstriction>>>

e.g flushing , diaphoresis and nausea, BP 100/70, HR 55/min, pupils are constricted but reactive to light
M1M3H1A1V1Gq-phospholipase C-IP3/DAG-Ca2+/PK C "C"
B1B2H2D1V2Gs-Adenylyl cyclase-cAMP-PK A "A"
a1 KA24-36------------------------------
vascular SM contraction, mydriasis, GI and bladder contraction
methyldopa, used for pregnancy and CKD patients with hypertension
nonselective a blockersphentolamine
phenoxybenzamine KA36-17
elevated HR
renin release
decreased uterine tone
insulin release

d1 renal vascular SM relax
h1nasal bronchial mucus production
h2gatric acid secretion
prevent the severe nausea and vomiting------------------------
1)antimuscarinic: scopolamine
2)antihistamine 1st generation: meclizine and dimenhydrinate
3)5-HT3 antagonists: ondansetron and tropisetron
4)dopamine D2 antagonist: metoclopramide block D2R in the chemoreceptor trigger zone in CNS, used for vomiting
SE: Parkinson disease KA8-47, contraindicated with bowel obstruction KA9-14
5) Aprepitant: NK1 antagonist, KA31-32
prevent the degradation of acetylcholine within the synaptic cleftorganophosphates
epinephrinea1+b1>>>increased contractility, HR, SBP+low renin
anaphylactic shock
a1 receptor>>>increase BP
b1>>>cardiac contractility
epinephrine low dose>>>b2>a1
epinephrine high dose>>>a1>b2
NE has a predominantly a1 effect, no b2 effect>>>no bronchodilator action
phenylephrinea1>>>hypertension+low renal blood flow
dopamine low doseb1+D1>>>increase contractility/reanl blood flow/SBP/HR
NEa1+b1 no b2
Stimulation of a1>>>vasoconstriction>>>IP3 KA36-17
Stimulation of b1>>>cAMP increase in cardiac muscle cells>>>contractility, HR
NE iv >>>tissue surrounding the IV site become cold and palephentolamine (a1 blocker) KA24-32
treated with streptokinase, morphine , IV fluids and a low dose beta-blocker. several hours later, the patient is comatose with asymmetric pupils and an irregular breathing pattern, caused by?streptokinase>>>hemorrhage>>>comatose with asymmetric pupils and an irregular breathing pattern (intracerebral hemorrhage)
vasoconstriction by a-adrenergic agonistsdecongestant>>>treatment of allergic rhinitis (congestion and rhinitis)
tachyphylaxis of a-adrenergic agonists
rapidly diminishing response to successive doses of a drug
decreased production of endogenous NE due to a negative feedback>>>relative vasodilation
fenolDOPAmfenoldopam IV Injection>>> relax renal vasuclar SM>>>improve renal perfusion/lower blood pressureselective

dopamine-1 receptor agonist>>>actives adenylyl cyclasee>>>raises intracellular cAMP>>>Vasodilation of renal

stimulation of dopamine receptors in the kidney
improves renal blood flow/increases sodium and water excretion
bethanecholpostoperative urinary retention
pilocarpinesjogren's syndrome (stimulator of sweat, tears and saliva)
methacholinetest for diagnosis of asthma
Stigmine (anticholinesterases)myasthenia gravis
benztropineparkinson's disease
Oxybutyninreduce urgency
pirenzepine propanthelinepeptic ulcer treatment
antagonism of ___affects bladder contraction?a1: benign prostatic hyperplasia. M3: urge incontinence
NE vs epinephrineNE has no affect on B2>>>no affect on vasodilation and bronchodilation