Board Review Flashcards
Buspirone, a drug with large first pass effect
Which of the following pharmacokinetic properties of the drug was most likely affected by this large first pass?
Oral bioavailability
Amount of concentration of the drug available at that particular time
First pass effect affects
Absorption
Bioavailability
Ability of drug to cross the placenta at fastest rate
Low molecular weight
Not bound to maternal plasma protein
Least ionized in maternal plasma
Measure that most reliably reflects the total amount of drug reaching the target tissue
Area under the curve
Factor that determines how long it will take for the drug to reach a steady-state concentration CSS in blood
Half-life
Phase II reaction
a. Glucoronidation
b. Deamination
c. Hydrolysis
d. Reduction
Conjugation reaction
Transferase
Glucoronidation
Elimination rate via metabolism catalyzed by alcohol dehydrogenase when the enzyme is saturated
Zero order kinetics
Ex. Phenytoin, Aspirin, Warfarin, Theophylline
Already saturated the enzyme
Plateau
Rate of elimination is not proportional to the concetration
Related to zero order kinetics
Toxicity
Narrow therapeutic index
Initial rates of drug distribution to different tissues depend primarily on which of the following parameter?
a. blood flow to the tissue
b. fat content of the tissue
c. degree of ionization of the drug un the tissue
d. active transport of the drug out of different cell type
INITIAL
blood flow
The pro-drug increases the expression of CYP450 that converts the pro-drug to its active form.
With chronic, long-term administration of the prodrug, which of the following will be observed
a. potency will decrease
b. potency will increase
Potency will increase
Antiseizure medication Phenobarbital
Diminished breathing
Low body temperature
Skin reddening
Barbiturate overdose
How does bicarbonate help overcome toxic effects of phenobarbital
Bicarbonate is a weak acid and there is overdose
We do not want it to recirculate
We want to trap weak acid (barbiturate) in the urine
It decreases distal tubular reabsorption
Vd
protein binding
The more protein-bound, the lesser the binding to tissue
What the drug can induce to body
Pharamcodynamics
Loraradine binding to H1 receptor is
Affinity
Selective drug
Mass action
Total amount of drug that comes in, it will bind to a receptor
After the drug binds to receptor, receptor activation
Full agonist
Maximal efficacy
Two drugs act on the same tissue or organ via activarion of different receptors, resulting in effects that are qualitatively the opposite of one another
An example would be the direct effects of norepinephrine and acetylcholine on heart rate. This represents which of the following types of antagonism?
a. Chemical
b. Competitive
c. Pharmacologic
d. Physiologic
Physiologic - yin and yang of pharmacology
Insulin vs Cortisol
Sympa vs Para
Pharmacologic
•Chemical - Heparin vs Protamine sulfate
• Competitive - enzyme not saturable, concentration-dependent
Dopamine, epinephrine and histamine interact with their cellular serpentine receptors
How do they mainly elicit their responses?
a. activating PLC
b. activating adenylate cyclase leading to inc cAMP
c. inducing or inhibiting synthesis of ligand-specific intracelualr proteins
d. opening or closing ligand-gated ion channels
e. regulating intracellular 2nd messengers through G protein-coupled receptors
Regulating intracellular 2nd messengers through G protein coupled recetors
Range of doses that have a high probability of therapeutic success
a. Efficacy
b. Potency
c. Therapeutic index
d. Therapeutic window
Therapeutic window
LD50/ED50
TILED
Therapeutic index = Lethal dose/ED50
If a drug has no intrinsic activity and bound reversible to B1 receptor, the drug is
a. Full agonist
b. Partial agonist
c. Competitive antagonist
d. Noncompetitive antagonist
Competitive antagonist
Non competitive antagonist = covalent, irreversible ex. aspirin (it will take you 7-10 days before aspirin will be eliminated)
Agonist = inherent power of 1 Antagonist = inherent power of 0
TMP-SMZ
Both are bacteriostatic when given alone but bactericidal effect is obtained when the two drugs are given in combination
What do you call this drug interaction?
a. Additive effect
b. Potentiation
c. Synergysm
d. Tolerance
Synergism
Potentiation
- no relationship with each other but when given together, they are effective
Co-Amox (beta lactamase) when given together can eliminate beta lactam ring of clavulanic acid instead of amoxicillin (clavulanic is like suicide drug) -
potentiation
Synergysm - both agonist 1 + 1 = 3
Drug with least amount that creates an effect (Potency) but it doesn’t mean that it is equally effective
At a dose of 2mg, it creates + 15 HR
Ar a dose of 10mg, it creates + 22
At a dose of 15mg, it creates + 30HR
At a dose of 20mg, it creates +55HR
Which is the most potent?
A dose of 2mg
Which is most effective?
A dose of 20mg
A 51-year old man reported to his physician that in the morning he noticed his urine was cloudy and red.
The man had been taking on oral anticoagulant for 3 weeks to treat a deep venous thrombosis. If the patient’s symptoms were caused by the anticoagulant, which adverse drug reactions as most likely involved?
a. Overdose toxicity
b. Autoimmune reaction
c. Idiosyncratic reaction
d. Hypersensitivity
e. Immediate allergic reaction
Overdose
Augmented type of allergic reaction
Non competitive antagonist
a. Alters the mechanism of action of an agonist
b. Alters the potency of an agonist
c. Shifts the dose-response curve of an agonist to the right
d. Decreases the maximum response to antagonist
e. Binds to the same site on the receptor as the agonist
Decreases the maximum response to antagonist
ED50 will not be affected by non competitive antagonist
ED 50 will be affected by competitive antagonist by increasing ED50
Mild asthma b2 agonist
Which of the following was most likely the immediate consequence of activation of B2 receptors?
a. conformational change of a G protein
b. Increased synthesis of cAMP
c. Decreased synthesis of cAMP
d. Phosphorylation of a G protein
Conformational change of a G protein
Parasympthetic receptors -
M1 - Brain, (Gq) PLC 2nd: IP3 DAG always Ca
M2 - Heart (Gi)
M3 - Bladder and all of the body not supplied by the parasympathetic (Gq) oPLC 2nd: IP3 DAG always Ca
Governs acid production
M1 (Gq)
Sympathetic
a 1 -Gq IP3 DAG, Ca, vasoconstrict, inc sphincter tone
a 2 - Gi (autoreceptor) in presynapse release of NE from cleft, stimulates autoreceptor creating negative feedback -> inhibition of NE release
Gs - beta receptors
Subfamily of CYP450 responsible for the highest fraction of clinically important drug interactions resulting from metabolism
CYP3A4 50%
CYP2D6 - prone to polymorphism
A japanese man had been receiving a standard dose of warfarin, which is an anticoagulant drug biotransformed by CYP2C9
Which is the most likely cause of the patient’s disorder?
a. Increased protein binding of warfarin
b. Decreased renal excretion of warfarin
c. Inherent polymorphism of CYP2C9
d. Increased metabolism of CYP2C9
Inherent polymorphism of CYP2C9
African American with weakness, fatigue, yellowing of skin and sclera and slight fever
He was given chloroquine as prophylaxis for malaria
Lab findings confirmed hemolytic anemia likely due to chloroquine use
Due to
G6PD deficiency
Patient has acute intermittent porphyria. If coma was caused by thiopental, which of the ff drug reactions is likely involved?
Idiosyncratic reaction
Which of the following drug may prevent absorption of Vit K?
a. Lovastatin
b. Cholestyramine
c. Niacin
d. Gemfibrozil
Cholestyramine
Niacin converts cholesterol to VLDL
Gemfibrozil stimulated PPAR-alpha gene transcription stimulating insulin and fat deposition
Succinylcholine was given and drug-induced paralysis lasted several hours
Which enzyme polymorphism is responsible to cause this problem?
a. acetylcholinesterase
b. Glucose-6-phosphate dehydrogenase
c. N-acetyltransferase
N-acetyltransferase
Non-depolarizing drugs - curare (tobucurarine)
Severe allergic reaction to procaine an ester-type local anesthetic provokes allergic or anaphylactic reaction.
Which will also provoke allergic or anaphylactic reaction?
a. Bupivacaine - longest amide
b. Lidocaine - intermediate
c. Mepivacaine -intermediate
d. Prilocaine -intermediate
e. Tetracaine - long acting, lipid solubility amide
Tetracaine
Esters - no “i” before caine
Amide - procaine, tetracaine, cocaine (least)
A pregnant woman with low RBC and positive direct Coombs test during regular visit
Woman had started treatment with methyldopa because of stage 1
Which most likely mediated the drug-induced reaction?
a. Deficiency of NADH-methemoglobin reductase
b. Product ion of autoantibodies against RBC
c. Drug-induced deficiency of folic acid
d. Drug-induced bone marrow supression
e. Deficiency of G6PD
Product ion of autoantibodies against red blood cell
Methyldopa is a good drug for pregnants because it is protein bound does not cross BBB
Peripheral neuropathy a known adverse effect of isoniazid, is caused by the patient’s symptoms and signs
a. Rifampin-ibduced inhibition if isoniazid
b. Deficiency of N-acetyltransferase
Deficiency of N-acetyltransferase
Palpitations, dry mouth, blurred visions and constipation
Depression with use of antidepressant therapy
a. a1 and a2
b. a1 and B1
c. M2 and M3
d. B1 and B2
M2 and M3 blockade
65 year old, open angle glaucoma underwent ocular surgery
Before the operation, opthalmologist instilled few drops of carbachol in conjunctival sac
Which of the following anatomical structures represents the primary site of action of this drug?
a. Ganglionic neurons
b. Ciliary muscle
c. Lens
d. Radial muscle of iris - dilate
Inc IOP, open angle glaucoma has too much aqueous production vs closed angle, there are ciliar muscles that impede canal of schlemm
You need a drug to cause miosis to constrict
Give Carbachol
Contraction of ciliary muscle lead to drainage of aqueous humor to canal of schlemm
Any drug that impede accomodation whether near or far (BOV) anticholinergic agents inhibits M3 receptor of ciliary muscle -> dilation with cyclopegia
Beta blockers can cancel radial muscle but cannot paralyze ciliary muscle since it is controlled by M3
Urinary retention neurogenic atonic bladder
Bethanechol was given
Which of the following most likely mediated the therapeutic effectiveness of the drug?
Increased tone of the bladder detrusor muscle
Neostigmine for MG caused bradycardia
Which molecular mechanism most likely mediated this adverse effect?
a. Opening of ligand-gated K channels
b. Opening of voltage-gated Na channels
c. Increased synthesis of IP3 DAG
Opening of ligand gated K channel
Ach slows the heart
Slowing down of the heart rate is caused by opening of K channels
GA was induced with thiopental maintained with halothane and nitrous oxide
Tubocurarine, a muscle relaxant
Which is most likely given to reverse muscle paralysis
a. Physostigmine
b. Edrophonium
c. Neostigmine
d. Bethanicol
e. Pralidoxime
Neostigmine
Quarternay compound, polar, ionized and water soluble canNOT cross BBB something that will act on peripheral receptor
Physostigmine can cross BBB because it is a tertiary compound
physostigmine c
Atropine can control diarrhea because it acts on the
a. histamine secretion by gastric cell
b. inositol triphosphate/diacylglycerol (IP/DAG)
c increase in cAMP
Inositol phosphate/DAG
Therapeutic effect of scopolamine is blockade of
a. B1 adrenergic
b. D2Dopaminergic
c. M1 cholinergic
M1 cholinergic
Accidental spraying of ipratropium will most likely cause the following anticholinergic side effect?
a. hallucination
b. increase salivation
c. AV block
d. Difficulty in near vision
Difficulty in near vision
Mechanism of botulinum toxin
a. Directly activated all muscarinic and nicotinic receptors
b. Inhibits Ach release from all cholinergic nerves
Inhibits Ach release from all cholinergic nerves
Epinephrine-induced increase duration of lidocaine effect was most likely mediated by activation of the ff adrenoreceptor?
a. B1
b. B2
c. a1
d. a2
alpha1
Molecular action of the therapeutic effect of dobutamine?
a. Activation of PLA2
b. Increased synthesis of IP3DAG
c. Increased cAMP
increased cAMP
Albuterol’s therapeutic efficacy is because of
a. Increased microvascular permeability
b. Decreased bronchial secretion
c. Release of histamine from mast cell
d. Increasef mucociliary clearance
Increasef mucociliary clearance
Acebutalol Type II antiarrythmic and Pindolol are classified as b blockers with intrinsic sympathomimetic activity (ISA)
this means
They are partial agonist (mixed agonist/antagonist)
submaximal effect
Therapeutic effect of phenoxybenzamine
a. Decreases peripheral vascular resistance
b. Increased cardiac output
c. Decreased epinephrine release from adrenal medulla
d. Increased heart rate
Decreased peripheral vascular resistance
Phenoxybenzamine - irreversible covalent binding to alpha receptors
So in a tumor, you need something that will bind permanently (covalently) despite release of tons of vasoconstrictors
Phentolamine is kicked off because it does not bind irreversibly (non-covalent)
Weakness
Drowsiness
Palpitation
Diagnosed with bladder obstruction due to BPH
has been taling a drug for 2 weeks
Which is the patient likely taking?
Tamsulosin
Block of a1 on trigone sphincter loosens them
Prazosin will cause
a. Mydriasis
b. Impaired micturition
c. Pale and cold skin
d. Bronchoconstriction
e. Postural hypotension
Postural hypotension
First dose syncope
Vasodilates capacitance vessels less blood going to brain
Timolol, open angle glaucoma for 3 months
Treatment stopped progression of optic nerve damage
Which of the following is the most likely site of action of timolol?
a. Uvoscleral vessel
b. Conjunctival vessel
c. Ciliary EPITHELIUM NOT MUSCLE
d. Retinal vessel
Ciliary epithelium
Parient has hyperthyroidism
Which of the ff drugs is likely included in the therapeutic management of this patient?
a. Albuterol
b. Propranolol
c. Labetalol
d. Prazosin
Propranolol
blocks 5’ deiodinade conversion of T4-T3
MSA membrane stabilizing effect highest MSA can cause sedation
Atenolol
Verapamil
Digoxin
Which best explains the therapeutic effectiveness of all these drugs in treating atrial fibrillation?
a. Decreased AV conduction
b. Increased intra-atrial conduction
c. Increased ventricular refractoriness
d. Increased myocardial contractility
d. Decreased cardiac preload
Decreased atrioventricular conduction
Atenolol - both atria and ventricle
Verapamil - on atria mostly
Digoxin - on atria blocks Na-KATPase; blocks K arm of ATPase no sodium coming in, no depolarization
58 MI
Ventricular tachycardia given IV Amiodarone
The therapeutic effect of the drug was most likely mediated by an increase in which of the following electrophysiologic parameter
a. Slope of phase 4
b. Slope of phase 0
c. Action potential duration
d. Length of phase 2
Amiodarone is a class III antiarythmic affecting Phase III
Block K channels
Delay depolarization of heart
Increase AP duration by blocking K channels
Dry disturbing cough from use of essential hypertension drug
Which caused the sign and symptom?
a. Captopril
b. Clonidine
c. Propranolol
d. Minoxidil
e. Nifedipine
Captopril
Safest drug to give on pregnant hypertensive patient
a. Captopril
b. Prazosin
Prazosin
Variant angina appropriate therapy
a. Propranolol
b. Furosemide
c. Verapamil
d. Captopril
Verapamil
Sublingual nitroglycerine oral isosorbide can cause a potential detrimental side effect of nitrate in prophylactic treatment of exertional angina?
a. Decreased ejection time
b. Increased heart rate
Increased heart rate
Prevents new stone production after operation?
a. Acetazolamide
b. Hydrochlorthiazide
c. Furosemide
d. Triamterine
e. Spironolactone
HCTZ inhibits Na-Ca exchange
Remove sodium reabsorption of Ca
Loop diuretic will aggravate condition, loose calcium too much calcium in tube
CHF drug that caused serious allergic reaction to (furosemide)
Which of the ff diuretics was most likely prescribed?
a. Spironolactone
b. Acetazolamide
c. Triamterine
d. Ethacrynic acid
e. Indapamide
Ethacrynic acid
Furosemide
HCTZ
sulfa-containing diuretics
Captopril for CHF delivers several benefits to CHF because
a. High affinitt for angiotensin II receptors
b. Promotes increased peripheral vascular resistance
c. Decreases CO and increases afterload
d. It causes venodilation and induces natriuresis
e. It increases preload
It causes venodilation and natriuresis
Drug that acts by multiple mechanism including inhibition of phosphodiesterase in inflammatory cells
a. Tiotropium
b. Albuterol
c. Theophylline
Theophylline inc cAMP (symp)
parasympathetic cGMP, inc cGMP ensures bronchodilation
Also acts on heart, inc cAMP goes to brain
Effect on adenosine receptors on heart Gs Beta 1
Effect on inflammatory cells deacetylation
