Here are some drugs that prolong the QT (With a simple introduction/reference).

I hope that it can help

you in some way:

Class III antiarrhythmic: inhibition of potassium channels, can lead to ventricular tachyarrythmias.

Erythromycin: macrolide antibiotic, and is often used for people who have an allergy to penicillins.
Better coverage of atypical organisms, including mycoplasma and Legionellosis.

Clarithromicin: macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute
bacterial exacerbation of chronic bronchitis, pneumonia (especially atypical pneumonias associated with
Chlamydia pneumoniae or TWAR), skin and skin structure infections. In addition, it is sometimes used to
treat Legionellosis, Helicobacter pylori, and lyme disease.

Pentamidine: Pentamidine is an antimicrobial medication given for prevention and treatment of

Pneumocystis pneumonia (PCP). Also the mainstay of treatment for stage I infection with Trypanosoma
brucei gambiense (West African Trypanosomiasis).

Moxifloxacin: is a fourth-generation synthetic fluoroquinolone antibacterial agent. This drug can lead to
spontaneous tendon ruptures and worsening of myasthenia gravis symptoms, including muscle
weakness and breathing problems. It is used to treat respiratory tract infections, cellulitis, anthrax,
intraabdominal infections, endocarditis, meningitis, and tuberculosis.

Levofloxacin: is a fluoroquinolone used to treat infections including: respiratory tract infections,

cellulitis, urinary tract infections, prostatitis, anthrax, endocarditis, meningitis, pelvic inflammatory
disease, and traveler's diarrhea. Can also cause spontaneous tendon ruptures.

Imipramide: is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group.

Imipramine is mainly used in the treatment of major depression and enuresis.

Desipramine: is a tricyclic antidepressant (TCA). It inhibits the reuptake of norepinephrine and to a

lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the
introduction of SSRI antidepressants. Desipramine is an active metabolite of imipramine.

Amitriptyline: is a tricyclic antidepressant (TCA). It is the most widely used TCA and has at least equal
efficacy against depression as the newer class of SSRIs. As well as reducing depressive symptoms, these
type of tricyclics also ease migraines, tension headaches, anxiety attacks and some schizophrenic
symptoms.

Doxepin: is a psychotropic agent with tricyclic antidepressant and anxiolytic properties. Doxepin is used
to treat depression, anxiety disorders, and as a second line treatment of chronic idiopathic urticaria. It is
also used to treat insomnia.

Thioridazine: is an antipsychotic drug belonging to the phenothiazine drug group. Due to concerns
about cardiotoxicity and retinopathy, this drug is reserved for patients who have failed to respond to, or
have contraindications for, more widely used antipsychotics. A serious side effect is the potentially
fatal neuroleptic malignant syndrome. It exerts its actions through a central adrenergic-blocking, a
dopamine-blocking, and minor anticholinergic activity.

Haloperidol: is a typical antipsychotic. Haloperidol is an older antipsychotic used in the treatment of

schizophrenia and, more acutely, in the treatment of acute psychotic states and delirium.

Risperidone: is a second generation or atypical antipsychotic. It is used to treat schizophrenia (including

adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar
disorder, and irritability in people with autism. It is associated with significant weight gain and metabolic
problems, as well as tardive dyskinesia and neuroleptic malignant syndrome. Risperidone and other
antipsychotics also increase the risk of death in patients with dementia.

Ziprasidone: is an atypical antipsychotic approved for the treatment of schizophrenia and acute
agitation in schizophrenic patients. Ziprasidone has also received approval for acute treatment of mania
and mixed states associated with bipolar disorder.

Quetiapine: is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar
disorder.

Fluconazole and itraconazole are known to inhibit drug metabolism, leading to large increase in
plasma drug concentration.

Doxorubicin acts by hindering DNA replication and transcription by intercalating DNA. It also generates
free radicals and inhibits topoisomerase II. Dexrazoxane can be used to decrease the incidence of
doxorubicin cardiotoxicity

paclitaxel inhibits microtubule depolymerization.

Vincristine inhibits microtubule/spindle formation (choice E) and causes peripheral neuritis, areflexia,
muscle weakness, paralytic ileus, and mild bone marrow depression.

Doxorubicin and daunorubicin are known to cause cardiotoxicity.

A patient with cardiotoxicity secondary to doxorubicin may present with a persistently reduced
voltage of the QRS complex, a prolonged systolic time interval, and a reduced ejection fraction.

These agents can cause congestive heart failure and/or cardiomyopathy for several weeks after the
discontinuation of therapy.

Doxorubicin hinders DNA replication and transcription by intercalating DNA. It also generates free
radicals.

Propranolol, a nonselective beta-adrenergic receptor antagonist, and primidone, a barbiturate

anticonvulsant, are effective first-line therapies. Second-line therapies for Essential tremors include
gabapentin, topiramate, and alprazolam. Benign essential tremor is a progressive, bilateral, largely
symmetric postural tremor of the upper extremities that is not associated with other neurologic
symptoms.
Benign essential tremor can be successfully treated by propranolol, a nonselective beta-antagonist, and
primidone, a barbiturate analog.

Pharmacokinetic parameters of a new antimicrobial agent are being determined during Phase I clinical
trials. It has recently been determined that the half-life of this new agent is 9 hours, and studies to
determine the safe limits of the clinical dose range are now being performed. One subject given a high
drug dose began to seize when the drug reached steady state levels. The drug was immediately
discontinued. How long will it take until his plasma drug levels are approximately 6% of steady state
levels? A. 9 hours
B. 18 hours
C. 27 hours
D. 36 hours
E. 45 hours
F. 54 hours

The correct answer is D. The rule of thumb is that the levels decrease by half every half-life. Therefore,
50% will remain after one half-life, 25% will remain after two half-lives, 12.5% will remain after three
half-lives, and 6.25% will remain after four half-lives. The half-life of this drug is 9 hours, so it will reach
approximately 6% of steady state levels in 36 hours.

A 15-year-old boy presents to the emergency room with agitation, mydriasis, and hot, dry skin. Physical
examination reveals decreased bowel sounds and tachycardia. Assuming that he is suffering from a drug
overdose, which class of drugs is most likely responsible for his symptoms?

A. Anticholinergic
B. Cholinomimetic
C. Opioid
D. Salicylate
E. Sedative-hypnotic
F. Stimulant

The correct answer is A. This patient is most likely suffering from an anticholinergic overdose,
which would produce the symptoms described in the question. The probable culprit is Jimson
weed, a naturally growing plant that contains antimuscarinic agents. This plant is often
cultivated or field-collected and its leaves brewed in a tea.
Cholinomimetics (choice B), such as those in insecticides, can cause miosis, excessive salivation
and sweating, hyperactive bowel sounds with abdominal cramping and diarrhea, anxiety,
agitation, seizures, and coma. Muscle fasciculations may occur, followed by flaccid paralysis.
Death may result from flaccid paralysis of respiratory muscles.

Opioids (choice C) can cause sleepiness, lethargy, or coma, miosis, cool skin, hypoventilation,
hypotension, bradycardia, and decreased bowel sounds.

Salicylates (choice D) can cause hyperventilation, hyperthermia, anion gap metabolic acidosis,
dehydration, potassium loss, and confusion, lethargy, or coma.

Sedative-hypnotics (choice E) can cause disinhibition at low doses, and increasing central
nervous system depression (lethargy, stupor, coma) with higher doses.

Stimulants (choice F) can cause agitation, mydriasis, and tachycardia. The best way to distinguish
stimulant overdose from anticholinergic overdose is the skin, which is sweaty with stimulants
and dry with anticholinergics. Stimulants can also cause arrhythmias, seizures, psychosis, and
hyperthermia.

Leflunomide: Dihydroorotate Dehydrogenase (DH) [Carbamoyl phosphate --> Orotic Acid]

Mycophelonate: Inositol Monophosphate (IMP) DH
Ribavirin: IMP DH [IMP --> GMP]
Hydroxyurea: Ribonucleotide Reductase [UDP --> dUDP]
6-MP (& Azathioprine): PRPP Amidotrasnferase (de novo purine synthesis) [PRPP --> 5-
phopsphoribosylamine --> IMP]
Allopurinol: non-competitive inhibitor of Xanthine Oxidase [Xanthine --> Uric Acid]. Allosteric
Inhibitor of PRPP Amidotrasnferase
5-FU: Thymidylate synthase [dUMP --> dTMP]
Pyrimethamine: Dihydrofolate (DHF) Reductase
Trimethoprim: DHF Reductase
Methotrexate: DHF Reductase [DHF --> THF = no dUMP --> dTMP]
Rifampin: DNA dependant RNA polymerase [inhibits sigma (promoter) and rho (terminator)] in
RNA transcription
Actinomycin: RNA polymerase 2, RNA polymerase 2
-amanitin (amanita phalloid mushroom): RNA polymerase 2
Quinolones: DNA topoisomerase II (DNA gyrase
Fomepizole: alcohol dehydrogenase
Disulfiram: acetaldehyde dehydrogenase
Beta-lactams: peptidoglycan cross-linking in cell wall
Glycopeptides: peptidoglycan formation by binding D-ala-D-ala portion on cell wall
Aminoglycosides: initiation complex in protein synthesis & translocation
Linezolid: initiation complex in protein synthesis
Streptogramins: aminoacyl-tRNA (aa incorporation) in protein synthesis
Tetracylins: aminoacyl-tRNA (aa incorporation) in protein synthesis
Cloramphenicol: peptide bond formation in protein synthesis
Macrolides: translocation in protein synthesis
Lincosamides: translocation in protein synthesis
Fluoroquinolones: DNA topoisomerase II (DNA gyrase) & DNA topoisomerase IV
Sulfonamides: dihydropteroate synthase
Trimethoprim: dihydrofolate reductase
Rifampin, Rifabutin (rifamycins): DNA-dependant RNA-polymerase
Ethambutol: arabinosyltransferase, inhibits synthesis of arabingalactan, no cell wall.
INH: synthesis of mycolic acids, need bacterial catalase-peroxidase, encoded by KatG gene.
Resistant if deletion of KatG gene
Azoles: 14alpha-demethylase, thus inhibits ergosterol synthesis from lanosterol
Flucytosin: DNA/RNA synhesis, active metabolite inhibits thymidilate synthase (5-FC --> cytosine
deaminase --> 5-FU --> 5- Fd-UMP)
Echinocandins (-fungin): beta glucan, thus inhibit cell wall synthesis
Terbinafine: squalene epoxidase, thus inhibit the formation of squalene epoxide from squalene
Griseofulvin: mitosis, interferes microubule fx.
Chloroquine: detoxification of heme into hemozoin; heme accumulates, heme toxic for
plasmodia.
The immunosuppressive drug that inhibits de novo purine synthesis and interacts with
allopurinol, subsequently requiring a dose reduction of the immunosuppressant agent. The first
step is to determine which of the answer choices listed inhibits de novo purine
synthesis. Azathioprine is an immunosuppressant that ultimately inhibits T-lymphocyte
proliferation. This agent is converted to 6-mercaptopurine (see figure), which inhibits DNA
purine synthesis and subsequent T-cell proliferation. Xanthine oxidase is instrumental in the
metabolism of azathioprine metabolites, and coadministration with allopurinol (an inhibitor of
xanthine oxidase) can result in azathioprine toxicity. Because azathioprine interacts with
allopurinol.

Azathioprine, a purine antimetabolite and an imidazolyl derivative of 6-mercaptopurine, is

converted to additional metabolites that inhibit de novo purine synthesis.
Xanthine oxidase, a primary enzyme involved in the catabolism of azathioprine metabolites, is
blocked by allopurinol.
The major side effect of azathioprine is bone marrow suppression, which includes leukopenia,
thrombocytopenia (less common), and anemia (relatively uncommon)
A 68-year-old woman is taking L-dopa and carbidopa for Parkinson's disease. She presents to her
physician
complaining of a worsening tremor. Her neurologist decides to add trihexyphenidyl to her drug
regimen but warns
her about the potential side effects of this drug. Which of the following side effects will this
patient most likely
experience?
A. Diaphoresis

B. Diarrhea

C. Dry mouth

D. Miosis

E. Urinary incontinence
The correct answer is C. Trihexyphenidyl is a muscarinic antagonist used as adjunctive therapy in
Parkinson's
disease. It can improve tremor and rigidity, but has little effect on bradykinesia. Trihexyphenidyl
is given to block
cholinergic tone in the striatum, and therefore, helps to maintain the dopamine/acetylcholine
balance in this
region. However, this drug and similar agents that block muscarinic receptors also block
parasympathetic tone
to peripheral end organs, producing a number of side effects. One such side effect is a reduction
of salivation,
leading to a dry mouth.

Trihexyphenidyl would cause decreased sweating, not diaphoresis (choice A), by blocking
sympathetic
cholinergic (muscarinic) tone to sweat glands.

Trihexyphenidyl would cause constipation, not diarrhea (choice B), by blocking parasympathetic
tone to the gut.

Trihexyphenidyl would cause mydriasis, not miosis (choice D), by blocking parasympathetic tone
to the pupillary
sphincter muscle of the eye.

Trihexyphenidyl would cause urinary retention, not urinary incontinence (choice E), by blocking
parasympathetic
tone to the bladder.
A 54-year-old man is admitted to the hospital with chest pain. Based on serial enzyme
determinations and his
electrocardiogram, he is diagnosed with a myocardial infarction. He is hospitalized for three
days and recovers,
but left ventricular dysfunction remains. He is prescribed several medications on discharge. A
week later, he
complains to his doctor about a dry, non-productive, persistent cough. Which of the following
medications is most
likely responsible for the appearance of this symptom?
A. Aspirin

B. Captopril

C. Metoprolol

D. Procainamide

E. Warfarin

Explanation:

The correct answer is B. Captopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor),

reduces the
mortality associated with myocardial infarction. ACE inhibitors decrease the amount of
ventricular remodeling
after infarction and reduce the risk of congestive heart failure; they may also diminish the risk of
a second heart
attack. ACE inhibitors are known to frequently cause a dry cough. They also cause headache,
diarrhea, fatigue,
nausea, and dizziness. All of the other agents might be prescribed in this setting, but dry cough
is only
associated with captopril.

Aspirin (choice A) is a nonsteroidal anti-inflammatory drug associated with increased bleeding

time,
gastrointestinal bleeding, and tinnitus.

Metoprolol (choice C), a beta-1 antagonist, can cause hypoglycemia, peripheral

vasoconstriction, and CNS side
effects.

Procainamide (choice D) is a group IA antiarrhythmic that can cause antimuscarinic and direct
depressant
effects on the heart, and may produce a reversible syndrome similar to lupus erythematosus.

Warfarin (choice E) is an oral anticoagulant that can cause bleeding at therapeutic doses, and
bone defects in
the developing fetus.
A 68-year-old woman is taking L-dopa and carbidopa for Parkinson's disease. She presents to her
physician
complaining of a worsening tremor. Her neurologist decides to add trihexyphenidyl to her drug
regimen but warns
her about the potential side effects of this drug. Which of the following side effects will this
patient most likely
experience?

A. Diaphoresis

B. Diarrhea

C. Dry mouth

D. Miosis

E. Urinary incontinence

Explanation:

The correct answer is C. Trihexyphenidyl is a muscarinic antagonist used as adjunctive therapy in

Parkinson's
disease. It can improve tremor and rigidity, but has little effect on bradykinesia. Trihexyphenidyl
is given to block
cholinergic tone in the striatum, and therefore, helps to maintain the dopamine/acetylcholine
balance in this
region. However, this drug and similar agents that block muscarinic receptors also block
parasympathetic tone
to peripheral end organs, producing a number of side effects. One such side effect is a reduction
of salivation,
leading to a dry mouth.

Trihexyphenidyl would cause decreased sweating, not diaphoresis (choice A), by blocking
sympathetic
cholinergic (muscarinic) tone to sweat glands.

Trihexyphenidyl would cause constipation, not diarrhea (choice B), by blocking parasympathetic
tone to the gut.

Trihexyphenidyl would cause mydriasis, not miosis (choice D), by blocking parasympathetic tone
to the pupillary
sphincter muscle of the eye.

Trihexyphenidyl would cause urinary retention, not urinary incontinence (choice E), by blocking
parasympathetic
tone to the bladder.

A 48-year-old woman goes to her dermatologist to have a mole removed. The patient tells her
physician that she
had an allergic reaction to a local anesthetic the last time she had dental work performed.
Examination of her
dental records by her dentist reveals that the patient received procaine for a tooth extraction.
Which of the
following drugs would be appropriate for the present procedure?

A. Benzocaine

B. Chloroprocaine

C. Cocaine

D. Mepivacaine

E. Tetracaine

Explanation:

The correct answer is D. There are two classes of local anesthetics: esters and amides. The rule
of thumb is
that if you are allergic to one drug in a given class (usually the ester class), you also will be
allergic to other
drugs of the same class. The proper course of action would be to switch over to the other drug
class. In this
question, the patient received procaine, which is an ester. Therefore, you need to identify the
amide in the list
of answers. The only amide listed is mepivacaine. Other amide local anesthetics include
lidocaine, bupivacaine,
etidocaine, prilocaine, and ropivacaine.
A 48-year-old man presents with a complaint of nonbloody diarrhea and right lower quadrant
pain with a palpable
mass and tenderness. He states that this "flare-up" is one of the worst he has ever experienced.
Radiographic
examination reveals evidence of ulceration, stricturing, and fistula development of the colon
and small bowel.
Which of the following drugs would be most useful for treating this patient?

A. Diphenoxylate and atropine

B. Hydrocortisone suppositories

C. Hyoscyamine

D. Mesalamine

E. Prednisone

Explanation:

The correct answer is E. The patient is presenting with signs and symptoms suggestive of Crohn's
disease,
which is an idiopathic inflammatory process that can affect any portion of the alimentary tract.
This condition is
often characterized by intermittent bouts of low-grade fever, diarrhea, malaise, and weight loss,
as well as focal
tenderness and a palpable tender mass in the lower abdomen. There is radiographic evidence of
ulceration,
stricturing, or fistulas of the small intestine and colon. Nonpharmacologic therapy can be
efficacious in some
cases, but more severe cases may require corticosteroids, such as prednisone, which
dramatically suppress
the clinical signs and symptoms.

Antidiarrheal agents (eg, diphenoxylate with atropine (choice A) or loperamide) should be used
very cautiously
in these patients since there is a very high risk of toxic megacolon.

Hydrocortisone suppositories (choice B) are indicated for the treatment of distal ulcerative
colitis, not Crohn's
disease.
Hyoscyamine (choice C) is an anticholinergic agent that may alleviate the postprandial
abdominal pain of a
patient with irritable bowel syndrome when administered 30-60 minutes before a meal.

Mesalamine (choice D) is a 5-aminosalicylic acid derivative indicated for the treatment of

ulcerative colitis.
Although this agent may provide some benefit in the treatment of Crohn's disease, prednisone
is the drug of
choice for treatment of acute "flare-ups" seen in patients with this disease.

A research scientist is studying calcium fluxes in cultured cells using confocal laser scanning
microscopy. The
magnitude of the signal (brightness) is proportional to the strength of the calcium flux.
Stimulation of which of the
following receptor types would be expected to produce the strongest signal?

A. Alpha-1 adrenergic receptor

B. Beta-1 adrenergic receptor

C. Dopamine-1 receptor

D. Muscarinic-2 acetylcholine receptor

E. Nicotinic acetylcholine receptor

Explanation:

The correct answer is A. Alpha-1 receptors activate phospholipase C via the G protein Gq.
Phospholipase C
cleaves the membrane phospholipid phosphatidylinositol 4,5-bisphosphate to produce the
products, inositol
triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium from the
endoplasmic reticulum,
and would therefore generate a robust signal. DAG activates protein kinase C.

Beta-1 adrenergic receptors (choice B) stimulate adenylate cyclase via the G protein Gs, leading
to an increase
in intracellular cAMP. All beta adrenergic receptors share a common mechanism of action.
Dopamine-1 receptors (choice C) stimulate adenylate cyclase via the G protein Gs. This leads to
an increase in
intracellular cAMP.

Muscarinic-2 acetylcholine receptors (choice D) inhibit adenylate cyclase via the G protein Gi.
This leads to an
decrease in intracellular cAMP. Muscarinic receptors also stimulate the opening of potassium
channels in the
heart, via the beta and gamma subunits of Gi.

Nicotinic acetylcholine receptors (choice E) are ligand-gated ion channels. When stimulated,
they allow sodium
ions to enter the cell.

A 69-year-old woman develops an atrial tachyarrhythmia. Which of the following agents could
be used to slow
conduction through the AV node?

A. Atropine

B. Digitalis

C. Nicotine

D. Norepinephrine

E. Quinidine

Explanation:

The correct answer is B. Digitalis is a cardiac glycoside that slows conduction through the AV
node via
parasympathomimetic actions, which can be blocked by atropine.

Atropine (choice A) blocks cardiac muscarinic receptors, thereby increasing conduction through
the AV node.

Nicotine (choice C) increases conduction by stimulating sympathetic autonomic ganglia and the
adrenal
medulla.
Norepinephrine (choice D) increases conduction by stimulating cardiac receptors.

Quinidine (choice E) acts centrally to decrease vagal tone, thereby increasing AV conduction.

A 41-year-old woman presents with chronic widespread musculoskeletal pain, fatigue, and
frequent headaches.
She states that her musculoskeletal pain improves slightly with exercise. On examination,
painful trigger points
are produced by palpitation of the trapezius and lateral epicondyle of the elbow. If objective
signs of inflammation
are absent and laboratory studies are normal, this patient would most likely be responsive to
which of the
following drugs?

A. Amitriptyline

B. Cefaclor

C. Naproxen

D. Oxycodone

E. Prednisone

Explanation:

The correct answer is A. The patient is presenting with signs and symptoms of fibrositis
(fibromyalgia). This
disorder is most commonly seen in women between the ages of 20 and 50, and is associated
with widespread
chronic musculoskeletal pain that improves with exercise, chronic fatigue, and sometimes,
severe headaches.
Examination typically reveals painful trigger points produced by palpation of the trapezius and
the lateral
epicondyle of the elbow. Objective signs of inflammation are absent and laboratory studies are
normal. Patients
with this disorder are likely to respond to treatment with tricyclic antidepressants or skeletal
muscle relaxants
with strong anticholinergic side effects, such as cyclobenzaprine. One of the most effective
agents in the
treatment of this disorder is amitriptyline, a tricyclic antidepressant commonly used in the
treatment of
depression, and as an adjunctive pain medication.

Cefaclor (choice B) is a second generation cephalosporin. Since fibromyalgia is not an infectious

disorder, this
agent would be ineffective in this patient.

Naproxen (choice C) is a non-steroidal anti-inflammatory drug indicated for the treatment of

mild-to-moderate
pain. NSAIDs are generally ineffective in the treatment of this disorder.

Oxycodone (choice D) is an opioid analgesic indicated for the treatment of moderate to severe
pain; opioids
are ineffective in the treatment of fibromyalgia.

Prednisone (choice E) is a corticosteroid indicated for the treatment of a variety of disorders

caused by
inflammation. Since this disease is not an inflammatory condition, prednisone would be not be
indicated for this
patient.

A 72-year-old patient presents complaining of shaking in his right hand and trouble starting
movements. On
physical examination, the patient has a resting tremor of the right hand that decreases with
active movement.
The man's face is expressionless, and his voice is very soft. Cogwheel rigidity is noted in both
arms. He also has
a slightly stooped posture, and a slow, shuffling gait. Which of the following treatments for this
disease works by
inhibiting the metabolism of dopamine?

A. Benztropine

B. Bromocriptine

C. Levodopa

D. Pergolide
E. Selegiline

Explanation:

The correct answer is E. This clinical vignette is classic for Parkinson's disease and all the answer
choices are
drugs used in the treatment of this disorder. Selegiline (deprenyl) inhibits monoamine oxidase B
(MAO-B). This
form of MAO preferentially metabolizes dopamine, whereas MAO-A preferentially metabolizes
norepinephrine
and serotonin. Selegiline slows the breakdown of dopamine, thereby prolonging the clinical
effects of levodopa.
Some studies show that selegiline may slow the progression of Parkinson's disease.

Benztropine (choice A) is an antimuscarinic drug that may improve the tremor and rigidity of
parkinsonism,
although it has little effect on the bradykinesia. It is thought to help maintain the balance of
cholinergic and
dopaminergic neurotransmission in the neostriatum.

Bromocriptine (choice B) and pergolide (choice D) are both dopamine receptor agonists. If you
did not know
how these drugs worked, but you knew that they belonged to the same drug class, you could
have still
eliminated both answers as wrong.

Levodopa (choice C) is the most effective drug for the treatment of Parkinson's disease and is
the mainstay of
treatment. Levodopa is a dopamine precursor that increases circulating dopamine levels in the
striatum.
Parkinson disease and has the classic symptoms ofbradykinesia, a resting tremor, gait
difficulty, and rigidity. This disease is caused by the degeneration of nigrostriatal dopamine
neurons, leading to decreased levels of dopamine in the striatum. This leads to an imbalance of
dopamine (DA) and acetylcholine (ACh) in the striatum (DA is too low and ACh is too high). As a
result, increasing dopaminergic tone (primarily) and decreasing cholinergic tone is the goal of
pharmacotherapy.
Increasing dopaminergic tone can be achieved by levodopa/carbidopa (dopamine precursor and
peripheral dopa decarboxylase inhibitor), dopamine agonists (e.g., bromocriptine, pramipexole,
ropinirole, apomorphine), MAO B inhibitors (e.g., selegiline, rasagiline), COMT inhibitors
(tolcapone, entacapone), and amantadine (increases DA release). Decreasing cholinergic
tone by using muscarinic antagonists (trihexyphenidyl, benztropine) provides the most benefit
for tremor, but is less effective for treating bradykinesia or rigidity. Antimuscarinics can be used
as monotherapy for patients who have primarily have a tremor or as part of combination
 therapy for those whose tremor is not adequately controlled by agents such as levodopa and
dopamine agonists.
Trihexyphenidyl has side effects common to other drugs that also block muscarinic receptors,
and includes:
hyperthermia (dry, flushed skin)
tachycardia
mydriasis and cycloplegia
urinary retention
constipation
dry mouth
sedation
Another drug with well-known antimuscarinics side effects is amitriptyline, a tricyclic
antidepressant. Other drugs that can produce antimuscarinics side effects include
antihistamines (e.g., diphenhydramine), antipsychotics, quinidine, amantadine, meperidine, and
other antimuscarinics (e.g., oxybutynin, tolterodine).

porphyria Cutanea tarda->

most Common cause of porphyrias

will cause Cutaneous problems (photosensitivy, and cutaneous lesions)
enzyme in the Cytosol
enzyme is uroporphrinogen decarboxylase
The drug of choice for localized cutaneous leishmaniasis is either sodium stibogluconate or
meglumine antimonate.
Second-line drugs, e.g., amphotericin B and pentamidine, are potentially more toxic, so they are
used in the treatment of visceral leishmaniasis cases that are unresponsive to the antimonials.
Amphotericin B is the drug of choice for severe diffuse cutaneous and visceral leishmaniasis.

The diagram shows changes in blood pressure and heart rate in an animal with intact reflexes in
response to drug X (agonist) and drug Y (antagonist). Assume that the antagonist's effects will
last for the duration of the experiment and that the agonist's effects are transient. Drug X and
drug Y are most likely to be which of the following?
A. X=Isoproterenol/Y=Atropine
B. X=Isoproterenol/Y=Phentolamine
C. X=Isoproterenol/Y=Propranolol
D. X=Norepinephrine/Y=Atropine
E. X=Norepinephrine/Y=Phentolamine
F. X=Norepinephrine/Y=Propranolol
The correct answer is D. A good approach for such questions is the process of elimination.
Important point to remember: when looking at drug traces, always think about blood
pressure first and then heart rate second. Changes in blood pressure will be due to a direct
effect on blood vessels and changes in heart rate may be due to either a baroreceptor effect or
a direct effect on the heart.
Because the agonist raises arterial blood pressure, it must be a pressor, such as norepinephrine
(NE). Isoproterenol, a beta agonist, would cause a decrease in blood pressure by vasodilation;
therefore, choices A, B, and C can be immediately eliminated. The decrease in heart rate is due
to a baroreceptor reflex. The increased blood pressure leads to increased parasympathetic and
decreased sympathetic tone to the heart.
The next step is to see if any antagonists can be eliminated. Drug Y alone causes no change in
blood pressure but an increase in heart rate. Phentolamine (choice E), an alpha antagonist, can
be eliminated because this should decrease blood pressure by blocking sympathetic tone to
arterioles. Propranolol (choice F), a beta antagonist, would be expected to cause a small
decrease in blood pressure and a decrease in heart rate. So choices E and F can be eliminated.
Every option except choice D has been eliminated, but working through choice D would still be a
good idea. Atropine blocks muscarinic receptors, but has virtually no effect on blood
pressure because the muscarinic receptors in the vasculature (M3 receptors) are not innervated
and therefore have no tone. However, blocking M2 receptors on the SA node results in
an increase in heart rate due to the removal of the dominant parasympathetic tone that
normally slows the heart. Administration of NE after atropine would still lead to the alpha-1
receptor-mediated vasoconstriction, thus increasing blood pressure. However, because
atropine is still blocking muscarinic receptors in the SA node when NE is administered the
second time, there is no slowing of the heart rate because it was primarily mediated by
increased parasympathetic activity. Therefore the direct beta-1 adrenergic effects of NE on the
SA are unopposed and the heart rate increases. This is consistent with the drug trace in the
question.

Drugs Y and X are infused into an experimental animal and the effects on systemic vascular
resistance (SVR) and heart rate (HR) are measured. The entire experiment is completed over 10
minutes. Assume that the effects of the antagonist (drug Y) persist throughout the experiment.
The graph shows the results of the experiment. Which of the following are the most likely
identities of drugs Y and X?
Which of the following are the most likely identities of drugs Y and X?

A.
B.
C.
D.
E.
F.
The correct answer is C. First, a general rule about drug traces. You must always consider the
effects on blood pressure (BP) BEFORE the effects on heart rate (HR). This is because it is
sometimes unclear at first whether the changes in HR are a direct effect of the drug or the result
of a baroreceptor reflex.
The table below summarizes the mechanism of action of all the drugs in this question.
Drug Y has to either be an (phentolamine) or (propranolol) antagonist, and Drug Y clearly
decreases systemic vascular resistance (SVR) or blood pressure (BP). Of the two, phentolamine
would have the more profound and immediate effect. Blood pressure is directly regulated by
the sympathetic nervous system stimulating -adrenergic receptors on blood
vessels. Stimulation of receptors causes vasoconstriction and an increase in BP and blockade
of these receptors leads to vasodilation and a decrease in BP. The decrease in BP by
phentolamine would elicit a baroreceptor reflex, thus increasing heart rate, which is consistent
with this trace.
Propranolol, a -adrenergic receptor antagonist, would not have much effect on systemic
vascular resistance in the time frame of the experiment. (The mechanism of how propranolol
decreases BP is not completely clear, but likely has to do with decreasing heart rate and cardiac
output, inhibiting renin release, and central mechanisms.) Also, propranolol lowers heart rate
directly by blocking 1 receptors on the heart. Therefore, choices D, E, and F can be eliminated.
Now that we know the answer is either A, B, or C, we need to start eliminating Drug X. We
know that Drug Y is present when Drug X is administered. So, we need to subtract effects from
Drug X. (Note that in the discussion that follows, 2receptors are mentioned for completeness,
but these receptors contribute little in terms of drug traces and can be ignored.)
Choice A: Epinephrine (EPI) is a 1, 2, 1, 2 agonist. So, in the presence of phentolamine, it only
stimulates 1 and 2receptors (acting like isoproterenol). This should cause a decrease in
BP because 2 stimulation causes vasodilation. However, Drug X has no effect on BP, and
therefore, EPI can be eliminated.
Choice B: Isoproterenol (ISO) is a 1, 2 agonist. This is very similar to epinephrine in the
presence of phentolamine. Again, it should decrease BP because of 2-induced vasodilation,
and ISO can be similarly eliminated.
Choice C: Norepinephrine (NE) is a 1, 2, 1 agonist. In the presence of phentolamine, its effects
on systemic vascular resistance (via 1 receptors) would be blocked. However, since it also
has 1 adrenergic activity, 1 receptors in the heart are stimulated, and HR increases. This is
consistent with the graph, and choice C is the correct answer.
Sirolimus inhibits T-cell activation and proliferation by binding mTOR, a serine-threonine
kinase that is instrumental in cell cycle progression. This agent also inhibits antibody production.
Remember that one of theprimarily differences between sirolimus and both tacrolimus and
cyclosporine is that sirolimus hasminimal nephrotoxicity and neurotoxicity, which is the key
point needed to correctly answer this question.
The most common reactions associated with the agent include peripheral edema,
hypertension,hypercholesteremia, and hypertriglyceridemia. Other common side effects
include thrombocytopenia and leukopenia. Additional serious adverse effects associated with
sirolimus include atrial fibrillation, heart failure, interstitial pneumonitis, hypervolemia, and
palpitations
Tamoxifen: Estrogen antagonist in Breast, agonist in bone and agonist in endometrium, thus
chance of endometrial cancer

Raloxifen: similar to Tamoxifen, however antagonist in endometrium / uterus as well. Thus

better than tamoxifen

Captopril (an ACE inhibitor): side effects

CAPTOPRIL

Cough
Angioedema / Agranulocystosis
Proteinuria / Potassium excess
Taste changes
Orthostatic hypotension
Pregnancy contraindication / Pancreatitis/ Pressure drop (first dose hypertension)
Renal failure (and renal artery stenosis contraindication) / Rash
Indomethacin inhibition
Leukopenia / Liver toxicity

SPANCEL
Sulfa drugs
Phenobarbital/Phenytoin/Penicillin
Allopurinol
NSAIDs
Carbamazepine
Ethosuximide
Lamotrigene

P450 Inducers induce me to madness!!

Griseofulvin
Phenobarbitone
Sulphonylureas,St John;s wort
Carbemazepines
Rifampicin
Alcohol (chronic)
Phenytoin

P450 Inhibitors

Don't join this group it will make your spirit go down...

SICKFACES.COM Group
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol..binge drinking
Chloramphenicol
Erythromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Grapefruit juice

infliximab,adalimumab,eternercept,alifacept,efalizumab...........anti TNF
palivizumab.........anti RSV
oprelevkin...........anti IL11 (use in thrombocytopenia)
omalizumab.........anti igE
bevacizumab,ranibizumab,sorafenib,sunitinib,pegaptanib.........anti VEGF
tratsuzumab...........anti HER2neu
rituximab........anti CD20
abciximab,tirofiban,eptifibatide........anti Gp2b3a
dacliximab.......anti IL2
muromonab(OKT3)........anti CD3
bortezomib.......inhibit 28s proteosome, decrease NFKB, use in multiple myeloma, 2 line in
mantel cell
lymphoma
tocilizumab....anti IL6 (use in chrohn ) (anti IL12 can be use in chrohn)
Basiliximab...higher affinity for IL2 receptor
Hypertension Best initial therapy= Thiazide
*Excellent treatment of systolic HTN= CCB
*HTN + Recurrent stroke= ACEI, Thiazide
*HTN + Migraine = CCB
*HTN + Raynaud's phenomena= CCB
*HTN + Essential tremor= BB
*HTN + Glaucoma= BB
*HTN + Hyperthyroidism= BB
*HTN + Depression= avoid BB
*HTN + Asthma= avoid BB
*HTN + CHF + AF from ischemia= BB
*HTN + LVH= BB, CCB
*HTN + CAD= BB, ACEI, ARB
*HTN + Heart failure= ACEI, ARB, BB, Spironolactone
*HTN + Osteoporosis= Thiazide
*HTN + ADPKD= ACEI
*HTN + Pregnancy= M.dopa , nifedipine
1. Phrmacology A 28-year-old woman presents to a court-ordered drug treatment center
because of methamphetamine abuse. She tells the drug counselors that she initially started
taking methamphetamine because she was trying to work two jobs and needed to try to stay
awake and remain productive. She found that she liked the euphoric effects of the drug and
kept taking methamphetamine to reexperience the "high." Which of the following mechanisms
of action is most likely responsible for the reinforcing effects of methamphetamine?

A. Blocks the metabolism of both dopamine and norepinephrine

B. Directly stimulates dopamine receptors
C. Directly stimulates adrenergic receptors
D. Induces dopamine release
E. Induces norepinephrine release
 Explanation: The correct answer is D. Methamphetamine (and amphetamine) acts by gaining
entrance to dopamine and norepinephrine (and serotonin) nerve terminals, causing the release
of these neurotransmitters via the uptake carriers. Dopamine is believed to play an important
role in the reward system of the brain, and is thought to be a significant factor in the reinforcing
effects of stimulants. One area of the brain that is thought to be involved in this reward system
is the dopaminergic projection from the ventral tegmental area of the midbrain to the nucleus
accumbens of the forebrain. Although methamphetamine is a weak inhibitor of monoamine
oxidase (MAO), and would therefore weakly block the metabolism of catecholamines (choice A),
this is not the primary mechanism of action of this drug. Methamphetamine acts as an indirect-
acting agonist, via the release of neurotransmitter, not as a direct agonist (choices B and C).
Methamphetamine does induce norepinephrine release (choice E), but this plays a role in the
production of systemic side effects (e.g., hypertension), rather than in the central effect of
reinforcement.

A 24-year-old migrant farm worker is rushed to a nearby emergency room after an accidental
exposure to parathion. He is in respiratory distress and is bradycardic. Which of the following
drugs can be given to increase the activity of his acetylcholinesterase? A. Atropine B.
Deferoxamine C. Dimercaprol D. N-acetylcysteine E. Physostigmine F. Pralidoxime

The correct answer is F. Pralidoxime (2-PAM) is an acetylcholinesterase (AChE) reactivating agent. It is

only useful for counteracting AChE inhibitors which act by phosphorylating the enzyme
(organophosphates). Pralidoxime can remove the phosphate group from AChE, thus regenerating the
enzyme. This must be done in a timely fashion because normally after the phosphate group is bound
to the enzyme, it undergoes a chemical reaction known as "aging." Once this bond ages, pralidoxime
will no longer be effective. Atropine (choice A) is a nonselective muscarinic antagonist. Although
atropine would be an appropriate agent for this patient, it acts by preventing the excess ACh from
stimulating muscarinic receptors rather than altering the activity of AChE. Deferoxamine (choice B) is
a chelator used for iron poisoning. Dimercaprol (choice C) is a chelator used alone for arsenic,
mercury and gold poisoning, and also in conjunction with edetate calcium disodium (EDTA) for the
treatment of severe lead poisoning. N-acetylcysteine (choice D) is used to treat acetaminophen
overdose. Physostigmine (choice E) is a carbamylating acetylcholinesterase inhibitor that can be used
to treat antimuscarinic overdose. This drug would certainly exacerbate this patient's symptoms.

A clinical pharmacologist is gathering pharmacokinetic data during clinical trials of a new

antimicrobial agent. He has already determined that the half-life of this drug is 4 hours. He began a
continuous intravenous drip 24 hours ago at a rate of 10 mg/min. Blood tests after 24 hours reveal
that the patient's drug plasma concentration is 20 mg/L. What is the clearance of this agent? A. 0.5
L/min B. 2 L/min C. 10 L/min D. 50 L/min E. 200 L/min Explanation: The correct answer is A. You must
be familiar with the maintenance dose equation to answer this question: M.D. = Cl x Cpss/F, where
M.D. = maintenance dose Cl = clearance Cpss = plasma concentration at steady state F =
bioavailability In this case, M.D. is 10 mg/min; F, or how much drug is absorbed, is 1 (100%) because
drugs administered I.V. are completely absorbed. (F becomes important when drugs are given orally.)
Cpss = 20 mg/L; it takes 4 -5 half-lives to achieve steady state, so this drug has been administered for
a time period equaling 6 half-lives. Solving, 10 mg/mL = Cl x 20 mg/mL 189
 3. Cl = 0.5 L/min

A 57-year-old man presents to the emergency department with a nosebleed for the past 2 hours. The
patient received a prosthetic heart valve 5 months ago and is currently taking warfarin (7.5 mg per
day) and oral antibiotics. Laboratory evaluation reveals an INR (international normalized ratio, the
ratio of patient to normal prothrombin times) of 6.4. Which of the following antibiotics is the patient
most likely taking? A. Ampicillin B. Cephalexin C. Nitrofurantoin D. Norfloxacin E. Phenazopyridine
Explanation: The correct answer is D. The patient is most likely experiencing a potentiation of the
effects of warfarin by norfloxacin, which decreases the metabolism of the warfarin. The increased
warfarin effect produces an increase in the INR. (The target INR for patients with prosthetic heart
valves is usually 1.5-4, depending on the type of valve.) Although norfloxacin is the most likely drug
among the choices given to cause this effect in this patient, the antibiotics most commonly
associated with this type of interaction are the macrolides, such as erythromycin, metronidazole, and
the sulfonamide antibiotics. Oral doses of penicillins, such as ampicillin (choice A), are generally not
associated with a potentiation of warfarin's effect, although large IV doses of penicillin may be.
Cephalexin (choice B) is a first-generation cephalosporin that can be used in the treatment of acute
cystitis. Although this agent is generally not associated with an increased hypoprothrombinemic
effect when given with warfarin, the cephalosporins with a methyltetrazolethiol side chain, such as
cefazolin, cefmetazole, and cefoperazone, are known to increase warfarin's therapeutic effect.
Nitrofurantoin (choice C) is a urinary anti-infective agent that does not interact with warfarin.
Phenazopyridine (choice E) is a urinary tract analgesic that does not interact with warfarin, although
it commonly changes the color of urine to a bright orange/red color, which the patient may mistake
as blood in the urine.

Which of the following antihistamines would be the most appropriate treatment for an airline pilot
with hay fever? A. Chlorpheniramine B. Diphenhydramine C. Meclizine D. Pyrilamine E. Terfenadine
190

Explanation: The correct answer is E. Terfenadine is the only drug listed that does not cross the
blood-brain barrier and therefore does not cause sedation (a bad thing for someone flying an
airplane). Other drugs from the same class (piperidines) include astemizole and loratadine. All of the
other choices have some degree of sedation as a side effect and therefore would not be
recommended for someone who is flying an airplane or operating any kind of machinery.

A 35-year-old male with a history of hypertension presents to the emergency room with fever,
left flank pain, dysuria, and hematuria. He had one episode of calcium oxalate nephrolithiasis in
the past. Family history is significant for a mother with diabetes mellitus, hypertension, and
end-stage renal disease (ESRD). The examination is otherwise normal. Urine culture is positive
for gram-negative bacilli. Renal ultrasound is significant for enlarged kidneys and more than
five renal cysts bilaterally without any hydronephrosis or evidence of stones. The most likely
underlying diagnosis is determined to be autosomal dominant polycystic kidney disease-1.
What is the recommended treatment?

A. Ciprofloxacin
B. Ampicillin
C. Vancomycin
D. Gentamicin
E. Clindamycin

During an investigational study, blood pressure is monitored in an anesthetized experimental

animal. The animal is given an intravenous dose of epinephrine, which produces an increase in
blood pressure. After the blood pressure returns to baseline 3 minutes later, an unknown drug is
given, followed by the readministration of epinephrine 15 minutes later. Readministration of
epinephrine produces a decrease in blood pressure. To which of the following classes does the
unknown drug most likely belong?
A. Indirect-acting sympathomimmetic

B. Nicotinic ganglionic blocker

C. Nonselective alpha-receptor agonist

D. Nonselective alpha-receptor antagonist

E. Nonselective beta-receptor antagonist
Explanation & ReKaps
The correct answer is D. This classic drug response, called epinephrine reversal, is a favorite
topic in pharmacology classes and on the USMLE. Epinephrine, a nonselective alpha- and beta-
adrenergic agonist, increases blood pressure. The unknown drug is an alpha-adrenergic
antagonist, such as phentolamine, which blocks epinephrine's vasoconstrictive action on
arterioles. Subsequent administration of epinephrine produces only beta-receptor stimulation,
causing vasodilation in skeletal muscle and leading to a decrease in blood pressure.
Epinephrine, for all practical purposes, now acts like the nonspecific beta agonist isoproterenol.
This effect is called epinephrine reversal because of the fact that epinephrine originally
increases blood pressure and then produces the opposite effect after phentolamine
administration.
Note about drug experiments: You can assume that the effects of an agonist stop fairly quickly.
You can also assume that the effects of an antagonist remains for the length of the experiment.
Notice that the effect of epinephrine, an agonist, is transient and baseline blood pressure
returns. When epinephrine is readministered 15 min after the second drug and the effects of
epinephrine are altered, you can assume this drug is an antagonist, narrowing the options
to choices B, D, and E.
An indirect-acting sympathomimetic (choice A), such as amphetamine or cocaine, would not
prevent the epinephrine-induced increase in blood pressure. In fact, if any residual indirect-
acting sympathomimetic remained prior to the second dose of epinephrine, the blood pressure
would be expected to rise even higher than with the first dose.
A nicotinic ganglionic blocker (choice B) may prevent a potential decrease in heart rate due to
baroreceptor reflexes, but epinephrine would still cause an increase in blood pressure because
its access to end-organ receptors would be unaltered.
A nonselective alpha-receptor agonist (choice C) might not affect a second administration of
epinephrine 15 minutes later because the agonist effect would probably be gone. But if some
agonist was still "on board" at the time of the second administration, it would only serve to
enhance epinephrine's increase in blood pressure.
A nonselective beta-receptor antagonist (choice E) would enhance epinephrine's increase in
blood pressure. After administration of a beta-antagonist such as propranolol, epinephrine
would only produce alpha-receptor stimulation. This would increase blood pressure to a greater
extent than epinephrine alone.

Warfarin is stereoselectively metabolized by hepatic cytochrome P450 (CYP) isoenzymes.

Enhanced risk for hemorrhage in patients receiving oral anticoagulants is caused by decreased
metabolism resulting from CYP2C9 inhibition by other drugs such as azole antifungals,
cimetidine, cotrimoxazole, fluoxetine, fluoroquinolones (such as norfloxacin), macrolides (with
the exception of azithromycin), metronidazole, and sulfinpyrazone.

Podophyllum resin in tincture of benzoin, which binds to microtubules and causes mitotic arrest
in metaphase
A 37-year-old man is brought to the emergency department after a motor vehicle collision in
which he sustained blunt abdominal trauma. His blood pressure is 95/52 mm Hg. An ultrasound
shows rupture of the spleen. Which of the following would most likely be the predominant
intracellular compensatory mechanism in his arteriolar smooth muscle cells in response to his
hypotension?
You switched answers: E G
A. Decrease in cAMP
B. Decrease in cGMP
C. Decrease in IP3
D. Decrease in Na+
E. Increase in cAMP
F. Increase in cGMP

G. Increase in IP3
H. Increase in Na+
Explanation & ReKaps
The correct answer is G. Low blood pressure is sensed as reduced stretch by both aortic arch
and carotid sinus baroreceptors, which convey afferent signals via the vagus and
glossopharyngeal nerves respectively. A resulting baroreceptor reflex compensates for a
 decrease in blood pressure by increasing sympathetic outflow and decreasing
parasympathetic outflow.
Increased sympathetic activity at arterioles causes greater norepinephrine release from
postganglionic sympathetic neurons, leading to increased 1-adrenergic receptor
stimulation on arterioles.
1 receptors are linked to Gq, which causes phosphatidylinositol 4,5-bisphosphate (PIP2)
hydrolysis (via phopholipase C), forming two second messengers: inositol 1,4,5-triphosphate
(IP3) and diacylglycerol (DAG).
DAG travels in the membrane to activate protein kinase C.
IP3 is water-soluble and causes the release of Ca2+, increasing intracellular Ca2+.
Ca2+ then binds calmodulin to form a complex that activates myosin light chain kinase (MLCK).
The activated form of MLCK phosphorylates myosin light chains, leading to the interaction of
myosin with actin to cause arteriolar smooth muscle contraction, increasing blood pressure.
Vasopressin and angiotensin II would also increase IP3; these contribute to the pressor response
to hemorrhage.
Note in the figure below, avoid confusing myosin light chain kinase (MCLK, the enzyme that
phosphorylates myosin light chain) with myosin light chain:
MLCK: active when dephosphorylated; inactive when phosphorylated
Myosin light chain: active when phosphorylated; inactive when dephosphorylated
A decrease in IP3 (choice C) would decrease, not increase, smooth muscle contraction, further
lowering blood pressure. This could be caused by blocking 1 receptors.
Changing intracellular levels of Na+ (choices D and H) is not the mechanism by which
the 1 receptors acts. An example of a receptor that increases intracellular levels of Na+ is the
nicotinic cholinergic receptor (nAChR), a ligand-gated ion (Na+) channel receptor.
An increase in cAMP (choice E) would lead to muscle relaxation; this is why epinephrine causes
vasodilation via the 2 receptor. The increase in cAMP leads to phosphorylation of MLCK,
inactivating it and preventing myosin/actin interaction. A decrease in cAMP (choice A) might
aid in smooth muscle contraction by allowing more MLCK to be activated; however, this is not
the mechanism by which the 1receptor acts.
An increase in cGMP (choice F) would cause relaxation and vasodilation by dephosphorylating
(deactivating) myosin light chain. A decrease in cGMP (choice B) could reverse the relaxation,
 but this is not the mechanism by which the 1 receptor acts, nor is cGMP the dominant
controller of vascular smooth muscle under basal conditions; therefore, its decrease is not the
dominant mechanism of hemorrhage-induced vasoconstriction

NaCl delivery to macula densa will result in constriction of afferent arteriole. Based on this data
which of the following diuretics will cause afferent arteriole constriction?
A. Acetazolamide
B.Amiloride
C.Furosemide
D.Hydrochlorthiazide
E.Spironolactone

Glucocorticoids can cause hypocalcemia, fluid retention, hypokalemia, hyperglycemia,

hypertension, and (with chronic use) osteoporosis and avascular necrosis.

A new investigational drug is undergoing Phase I clinical trials. The half-life of this drug is 9
hours. A healthy volunteer has an adverse reaction and the drug is immediately discontinued.
How long will it take until the plasma drug level is approximately 6% of the initial steady state
level?

Answer selection is incorrect. A. 9 hours

B. 18 hours
C. 27 hours
This is the correct answer. D. 36 hours
E. 45 hours
F. 54 hours
Explanation & ReKaps
The correct answer is D. The rule of thumb is that the levels decrease by half every half-life.
Therefore, 50% will remain after one half-life, 25% will remain after two half-lives, 12.5% will
remain after three half-lives, and 6.25% will remain after four half-lives. In this case the half-life
of this drug is 9 hours, so it will reach approximately 6% of steady state levels in 36 hours:

1 half-life: 50% drug left, time = 9 hrs

2 half-lives: 25% drug left, time = 18 hrs
3 half-lives: 12.5% drug left, time = 27 hours
4 half-lives: 6.25% drug left, time = 36 hours

During an investigational study, intravenous administration of Drug X to an anesthetized

experimental animal causes an increase in blood pressure. After administration of Drug Y,
readministration of Drug X causes a decrease in blood pressure. Which of the following pairs of
drugs will most likely produce this sequence of events?
 A.

B.
C.

D.
E.
Explanation & ReKaps
The correct answer is B. Drug X originally increases blood pressure (BP). Therefore, first
eliminate all answers in which Drug X does not produce an increase in blood pressure (BP).
Choice A should be eliminated because acetylcholine stimulates the noninnervated muscarinic
(M3) receptors that are located on endothelial cells of the vasculature. Stimulation of these
receptors releases nitric oxide, which produces a relaxation of the neighboring smooth-muscle
cells, leading to a decrease in BP. Choice C should be eliminated because isoproterenol (a
nonspecific beta agonist) decreases BP by stimulating beta-2 receptors in the vasculature.
Epinephrine, norepinephrine, and phenylephrine all increase BP, so the remaining answers must
be eliminated by examining the effects of Drug Y on Drug X.
Start with choice B: Epinephrine is an agonist at alpha-1, alpha-2, beta-1, and beta-2
receptors; phentolamine is an antagonist at alpha-1 and alpha-2 receptors. Therefore, after the
administration of phentolamine, epinephrine can stimulate only beta receptors, which would
produce a decrease in BP. Epinephrine is now acting like isoproterenol. This is
called epinephrine reversal (the name stems from the fact that epinephrine originally
increases BP and then produces the opposite effect after phentolamine administration).
Therefore, choice B is correct.
Choice D: Norepinephrine is an agonist at alpha-1, alpha-2, and beta-1 receptors; propranolol is
a nonselective beta antagonist. After administration of propranolol, norepinephrine can
stimulate only alpha receptors, which will still cause vasoconstriction (primarily via alpha-1
stimulation in the vasculature) and therefore increase BP.
Choice E: Phenylephrine is an alpha-1 agonist; hexamethonium is a nicotinic ganglionic
blocker. Hexamethonium administration would be predicted to eliminate the baroreceptor
response after the second phenylephrine administration by blocking the peripheral ganglia.
However, phenylephrine will still reach the alpha-1 receptors on the vasculature to produce an
increase in BP.
POISON- ANTIDOTE
acetaminophen-acetylcysteine

organophosphorous poisoning-atropine and pralidoxime

iron and iron salts-deferoxamine

methanol and ethylene glycol-ethanol

benzodiazepenes-flumazenil

anticholinergics,antiparkinsonians-physostigmine

heparin-protamine

leadpoisoning backupdrug-EDTA
. Flumazenil
benzodiazepines antagonist

A. Acetylcysteine
used acetamenophen toxicity

B. Atropine
can be used in organo-phosporus poisoning

C. Bicarbonate
cause alkalanization of urine ==> enhance urinary excretion of acidic drugs (by increasing the
ionization ==> decrease reabsorption
eg. acetly salcylic acid (ASA)

D. CaNa2EDTA chelation
used for chelation in heavy metal toxicity (eg. lead toxicity)

E. Deferoxamine
used to chelate Iron (Iron toxicity)

F. Ethanol
will enhance diazepam toxicity.

H. Physostigmine
Parasympathomimetic by reversibly inhibiting choline esterase enzyme
I. Pralidoxime
used early in organophosphorus poisoning to free cholinesterase enzyme before permenantly
damaged.

J. Protamine
Protamine sulfate (derived from fish sperm or testis )used in heparin toxicity

A study is conducted to measure the effects of drugs added to an isolated uterus preparation on
the strength of muscle contraction in response to an electrical stimulus. The control consists of
delivering an electrical stimulus without adding any drugs. An unknown drug X is added to the
isolated uterus, and the effects on contraction strength in response to the electrical stimulus are
recorded. Drug X is then thoroughly washed out prior to the addition of a receptor antagonist.
Drug X is then added again in the presence of the antagonist, and the contractions are recorded
again. The graph shows the results of the experiment. Which of the following are the most likely
identities of drug X and the antagonist?

A.

B.

C.
 D.

E.

Explanation & ReKaps

The correct answer is B. It is important to keep in mind the experimental procedures. The
contraction seen at each point is elicited not by the drug or the antagonist, but by electrical
stimulation. The figure shows the response to electrical stimulation in four conditions: control
(electrical stimulation without drug); electrical stimulation with the Drug X; electrical stimulation
with the antagonist only; electrical stimulation with Drug X and the antagonist.
The uterus smooth muscle contains 1 and 2 adrenergic receptors.
Stimulation of 2 receptors stimulates Gs, increases cAMP, and activates protein kinase A (PKA).
As a result of PKA phosphorylation and inactivation of myosin light-chain kinase (MLCK), uterine
smooth muscle contractions are reduced.
In contrast, stimulation of 1 receptors stimulates Gq, increases intracellular levels of IP3, and
increases intracellular calcium, causing greater smooth muscle contraction.
Because epinephrine (EPI) has higher affinity for 2 receptors than for 1 receptors, it initially
causes a decrease in contraction strength.
Because its effects are opposite the second time it is given, the antagonist must be
blocking receptors (propranolol). In the presence of propranolol, EPI acts only at 1 receptors,
leading to greater uterine contraction.

Acetylcholine (ACh) (choice A) acts on M3 receptors on the uterus and would increase calcium
to increase contractions. In the presence of a muscarinic antagonist such as atropine, there
should be no response when ACh is readministered.
Isoproterenol (choice C) stimulates 2 receptors on the uterus and would initially decrease
contraction strength. In the presence of the 1 -selective antagonist atenolol, its effects would
be largely unchanged
Norepinephrine and phenylephrine (choices D and E) act primarily on 1 receptors on the uterus
and would increase contraction strength. (Norepinephrine is a and a 1 agonist; phenylephrine
is an 1agonist). In the presence of an blocker such as phentolamine, neither norepinephrine
nor phenylephrine would produce a response after the second administration.
HIV is one of the tough topic and it is very high yield in the exam, so we can share the concept
about HIV , and at the end we can cover this topic, so please add any important concept.
Diagnosis:
*Best initial test= ELISA test.
*Confirmatory test= western blot (considered +ve if patient demonstrated the presence of
antibodies to at least 2 of 3 important HIV antigens which are gp120, gp41, and gp24).
*Early marker of infection is p24 Antigen.
* ELISA/Western blot are often falsely ve in first 1-2 mths of HIV infection.
*Viral load testing (detected by RT PCR) useful to:
1- Measure response to therapy
2- Detect treatment failure
3- Diagnose HIV in babies
*Diagnosis in babies of HIV +ve mother:
Test of choice is detect HIV-DNA by PCR
Can culture HIV with antigens detection
ELISA/Western blot are often falsely +ve in infant(anti-gp 120 cross the placenta)
In children> 18 mths can use ELISA(IgG Ab) and Westren blot
*Best single prognostic indicator is plasma viral load
*Evaluate progression of disease: CD4:CD8 ratio by flow cytometery.

HIV- associated infections and CD4 count:

Normal CD4 count 6001000
*CD4 >200: Increase risk of
VZ,TB, HSV, Oral and Vaginal Candidiasis, Bacterial pneumonia.
*CD4 < 200: Increase risk of
1- PCP: *Prophylaxis= TMP/SMX, and if patient allergy give Dapsone or Atorvoqine *treatment
=TMP/SMX is best initial therapy, add steroids if PCP is sever.
2- Cryptosporidiosis: *treatment= by increase CD4 count
3- Disseminated Coccidioidomycosis: *treatment= Amphotericin B
*CD4 < 100: Increase risk of
1- Toxoplasmosis:* prophylaxis= TMP/SMX , Dapsone *treatmen=Primethamine/sulfadiazine
2- Candida esophagitis: *treatment= fluconazole
*CD4 < 50: Increase risk of
1- Mycobacterium avium*Prophylaxis = Azithromycin *treatment = clarithromycin +
ethambutol+/-rifambutin
2- CMV:Prophylaxis and treatment by Valgancyclovir
3- Cryptococcal meningoencephalitis: treatment I.V amphotricin for 10-14 days followed by
fluconazole as mentinance
4- PML= caused by JC virus= No effective treatment
5- NHL= associated with EBV
*HIV with any cell count:
1- If patient PPD >5mm= INH for 9 mths
2- Pneumococal vaccine, influenza vaccine, and Hep B vaccine, Hep A vaccine

P450 Inhibitors
Don't join this group it will make your spirit go down...
SICKFACES.COM Group
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol..binge drinking
Chloramphenicol
Erythromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Grapefruit juice

P450 Inducers

CRAP GPS induce me to madness!!

Carbemazepines
Rifampicin
Alcohol (chronic)
Phenytoin

Griseofulvin
Phenobarbitone
Sulphonylureas