Gobind rai general pharmacology
Drug transport mechanisms include: (a) Active transport (b) Passive transport (c) Lipid solubility (d) Bioavailability (e) Distribution
(a) Active transport; (b) Passive transport Drugs are transported across the membranes by: (a) Passive diffusion and filtration (b) Specialized transport Specialized transports are of two types: 1. Active transport 2. Facilitated diffusion
High first pass metabolism is seen in (A) lignocaine (B) propranolol (C) salbutamol (D)dipyridamole (E) erythromycin
(a) Lignocaine ; (b) Propanolol; (c) Salbutamol
Which one of the following is a prodrug? (a) Dopamine (b) Epinephrine (c) Levodopa (d) Prednisolone
Levodopa
Which of the following antiplatelet drugs is aprodrug? (a) Clopidogrel (b) Tirofiban (c) Aspirin (d) Dipyridamole
Clopidogrel • ADP receptor antagonists, ticlopidine and clopidogrel are prodrugs
Which of the following is a prodrug? (a) Enalapril (b) Clonidine (c) Salmeterol (d) Acetazolamide
Enalapril All ACE inhibitors are prodrugs except captopril and lisinopril.
Volume of distribution of drugs is altered in : (A) obesity (B) athletes (C) pregnancy (D) old age ( e) neonate
(a) Obesity; (c) Pregnancy; (d) Older age; (e) Neonate • In elderly patients, the Vd is more because of increased total body fat content and decreased plasma protein bindingof drugs. • In paediatric patients also, there is greater volume of extracellular fluid and this provides a larger volume of distribution of highly ionized drugs. Therefore, a larger initial dose may be required to achieve the desired blood level.ghly ionized drugs. • In obese patients because of greater than normal adipose content, Vd is increased. • In Pregnancy also blood volume increases about 30-40%. Although the total protein is increased, but plasma proteinconcentration is decreased, thus altering Vd.
Drug distribution is influenced by (a) plasma protein binding (b) lipid solubility (C) degree of blood flow (D) age
(a) Plasma protein binding; (b) Lipid solubility; (c) Degree of blood flow; (d) Age
High hepatic extraction ratio is seen in: (a) Propanolol (b) Lidocaine (c) Ampicillin (d) Imipramine (e) Theophylline
(a) Propanolol; (b) Lidocaine; (d) Imipramine; (e) Theophylline (Ref: KDT 6/e p28) • High hepatic extraction ratio means that most of the drug reaching the liver (via blood vessels) is removed by liver. These drugs have either high first pass metabolism or high systemic metabolism. • Propranolol and lidocaine undergo high first pass hepatic metabolism. • Theophylline is extensively metabolized in liver by demethylation and oxidation. • TCAs (tricyclic antidepressants) are extensively metabolized in liver; the major route for imipramine and amitriptyline is demethylation whereby active metabolites-desipramine and nortriptyline respectively are formed. • Ampicillin is partly excreted in bile and enterohepatic circulation occurs. However, primary channel of excretion is kidney.
In hepatic metabolism, phase II reactions are: (a) Dealkylation (b) Sulfation (c) Methylation (d) Glucuronidation (e) Deamination
(b) Sulfation; (c) Methylation; (d) Glucuronidation
CYP- 450 inducers are: (a) Cimetidine (b) Ketoconazole (c) Phenobarbitone (d) DDT (e) Theophylline
(c) Phenobarbitone; (d) DDT • P-450 inducers are:- Phenobarbitone, rifampicin, phenytoin, chloral hydrate, phenylbutazone, griseofulvin, DDT, and chronical cohol ingestion.- Ketoconazole and cimetidine inhibit the drug metabolizing enzymes.
Which of the following is an enzyme inhibitor? (a) Ketoconazole (b) Rifampicin (c) Tolbutamide (D) phenobarbitone
Ketoconazole
Ram Prashad is admitted to Guru Teg BahadurHospital with respiratory infection for which antibiotictobramycin is ordered. The clearance and Vd oftobramycin in him are 160 ml/min and 40 L, respectively.If you wish to give Ram Prashad an intravenous loadingdose to achieve the therapeutic plasma concentration of4 mg/L rapidly, how much should be given?g/L rap (a) 0.1 mg (b) 10 mg (c) 115.2 mg (d) 160 mg
160 mg (Ref: Katzung 10/e p45) Loading dose = V d × target plasma conc.
Rate of elimination of a new drug is 20 mg/hr at asteady state plasma concentration of 10 mg/L, then itsrenal clearance will be:(a) 0.5 L/hr (b) 2.0 L/hr (c) 5.0 L/hr (d) 20 L/hr
2.0 L/hr Clearance = rate of elimination/plasma concentration
A drug following first order kinetics is beingadministered by constant i.v. infusion at a rate of 10 mg/min. Its steady state plasma concentration is 2 mg/min.If the dose rate is increased to 20 mg/dl, what will be thenew steady state plasma concentration? (a) 6 mg/dl (b) 4 mg/dl (c) 3 mg/dl (d) 1 mg/dl
4 mg/dl (Ref: Katzung 10/e p44) Dose Rate = Clearance × Steady state plasma concentration • This means plasma concentration at steady state is a direct function of the dose rate, if clearance is constant. In first order kinetics (clearance is constant), plasma concentration attained is directly proportional to the dose rate. Thus, doubling of dose rate from 10 to 20 mg/min, will double the steady state plasma concentration (from 2 to 4 mg/dl).
Amount of a drug X administered to a patient is 4.0 g and its plasma concentration is found to be 50 mg/ml,what will be the volume of distribution of drug X? (a)100L (b) 80L (c) 60L (d) 50L
80 L (Ref: Katzung 10/e p34) V d = Amount administered/ Plasma concentration
True statement regarding first order kinetics is: (a) Rate of elimination is independent of plasmaconcentration (b) A constant proportion of plasma concentration iseliminated per unit time (c) Half life increases with dose (d) Clearance decreases with dose
A constant proportion of plasma concentration is eliminated per unit time (Ref: KDT 7/e p30-31) In first order kinetics, rate of elimination is proportional to plasma concentration of the drug. Half life and clearance are constant in first order kinetics.
Sulphonamide is conjugated with: (RJ 2001) (a) Acetylation (b) Methylation (c) Hydroxylation (d) None
Acetylation
All of the following reactions are catalyzed bymicrosomal enzymes EXCEPT: (a) Glucuronidation (b) Acetylation (c) Oxidation (d) Reduction
Acetylation Most of the phase I reactions and glucuronide conjugation (Phase II reaction) are catalyzed by microsomal enzymes. These enzymes can be induced or inhibited by drugs. Acetylation is carried out by N-acetyl transferase, a non-microsomal enzyme.
Which of the following is an inducer of microsomalenzymes: (a) Phenobarbitone (b) Paracetamol (c) Digoxin (d) Penicillin
Phenobarbitone
Duration of action of i.v. administered drug depends on: (a) Protein binding (b) Clearance (c) Distribution volume (d) Lipid solubility (e) Half life
All • High protein binding of a drug make it restricted to vascular compartment and thus has tendency to lower volume ofdistribution. It behaves as a long acting drug as bound fraction is not available for metabolism or excretion. Other factors that affect duration of action of IV drugs are: - Clearance - Half Life - Volume of distribution which depends on lipid solubility, ionization at physiological pH, protein bindingaffinity of tissues and regional blood flow.
Alkalinization of urine is required to treat toxicity of allexcept: (a) Sulfonamides (b) Amphetamine (c) Salicylates (d) Barbiturates
Amphetamine
Alkalinization of urine is required for decreasing thepoisoning due to: (a) Barbiturates (b) Amphetamine (c) Alcohol (d) Morphine
Barbiturates For acidic drug poisonings (like barbiturates, salicylates and methotrexate), urinary alkalinizing agents are prescribedwhereas for basic drug poisonings, (morphine, amphetamine, atropine etc.) urinary acidifying agents are administered.
Which of the following is true? (a) As the concentration of the drug increases overthe therapeutic range, only the bound form of thedrug increases (b) The bound form is not available for metabolismbut is available for excretion (c) Acidic drugs binds to beta globulin and basicdrugs bind to albuming (d) Binding sites are non-specific and one drug can displace the other
Binding sites are non specific and one drug can displace the other Acidic drugs bind to albumin whereas basic drugs bind to α1 acid glycoprotein. • It is the free form of the drug that is metabolized or excreted. Bound form is not available for either metabolismor excretion.• Many drugs can bind to the same plasma protein binding site resulting in the displacement reactions. • When plasma concentration increases, both free as well as bound drug will increase in plasma.
Which of the following statements is correct? (a) Most drugs are absorbed in ionized form (b) Basic drugs are generally bound to plasma albumin c) Microsomal enzymes are located in the mitochondriaof hepatic cells (d) Blood brain barrier is deficient at the chemoreceptortrigger zone
Blood brain barrier is deficient at the chemoreceptor trigger zone
Cytochrome P450 most commonly involved in drugmetabolism: (a) CYP 3A4 (b) CYP 1AI (c) CYP 2E1 (d) CYP 2D6
CYP 3A4
The mitochondrial enzyme involved in the metabolismof clopidorgel and proton pump inhibitors is: (a) CYP 2A (b) CYP 2B (c) CYP 2C10 (d) CYP 2C20
CYP2C10 Clopidogrel and proton pump inhibitors are metabolized mainly by CYP2C19 and by CYP3A4. Due to this reason there is potential of interaction between these two drugs but none of these enzymes were given in the options. We have no idea what the examiner want a student to learn. Whether student should know the clinically important things or they shouldgo for the most rarest of things.go for the most rarest of thing Anyways, some of these drugs are also metabolized by CYP2C9. On searching a lot, we came to know that this enzyme(CYP2C9) was previously known as CYP2C10. ......... So the answer among the given options should be CYP2C10. But again we will suggest to remember about 2C19 which isclinically more relevant.
Which of the following is a prodrug (A) captopril (B)cimetidine (C) carbimazole (D) carbamazepine
Carbimazole
A factor that is likely to increase the duration of action9 - U of a drug D that is partially metabolized by CYP3A4 inthe liver is:99 (a) Chronic administration of phenobarbital with thedrugr99 (b) Chronic administration of cimetidine with the drughir99 (c) Displacement from tissues binding sites by anotherdrugh (d) Chronic administration of rifampicin
Chronic administration of cimetidine with the drug • Cimetidine is a microsomal enzyme inhibiting drug. It increases the duration of action of the drugs metabolized by these enzymes. on the other hand, rifampicin and phenobarbitone are enzyme inducers and will decrease the duration of action of such drugs. • Displacement from binding sites increases the free drug that can be quickly metabolized.
Which does not induce microsomal enzymes ? (A) cimetidine (B) griseofulvin (C) rifampicin (D) phenobarbitone
Cimetidine
Which of the following drug acts as microsomal enzymeinhibitor: (a) Rifampicin (b) Cimetidine (c) Phenobarbitone (d) Phenytoin
Cimetidine
Which of the following parameters signifies the effective drug removal from the body ? (A) clearance (B) bioavailability (C) safety (D) volume of distribution
Clearance (Ref: KDT 7/e p30) Clearance of a drug is the theoretical volume of plasma from which the drug is completely removed in unit time
Loading dose depends on the following factors except: (a) Drug concentration to be achieved (b) Volume of distribution (c) Clearance of the drug (d) Bioavailability of drug
Clearance of the drug
In metabolism of xenobiotics, all of the followingreactions occur in phase one except? (a) Oxidation (b) Reduction (c) Conjugation (d) Hydrolysis
Conjugation Metabolic reactions may be classified into phase I (non-synthetic) and phase II (synthetic) reactions. Phase I reactions include oxidation, reduction, hydrolysis, cyclization and decyclization etc. whereas phase II reactions include glucuronidation, acetylation, methylation, sulfation and glycine conjugation etc.
Metabolism of a drug primarily results in: (a) Activation of the active drug (b) Conversion of prodrug to active metabolite (c) Conversion of lipid soluble drugs to water soluble metabolites (d) Conversion of water soluble drug to lipid solublemetabolites
Conversion of lipid soluble drugs to water soluble metabolites After metabolism most of the drugs become inactive and are excreted through the kidney. Lipid soluble drugs will be reabsorbed whereas water soluble drugs are easily excreted. Thus, metabolism of drugs helps in the conversion of lipid soluble drugs to water soluble metabolites.
All of the following results in detoxification of drugsEXCEPT: (a) NADPH cytochrome P450 reductase (b) Cytochrome P450 (c) Cytochrome oxidase (d) Monooxygenase
Cytochrome oxidase Drugs can be metabolized by cytochrome P450 dependent oxidations and cytochrome P450 independentoxidations (i.e., by monooxygenases) • NADPH cytochrome P450 reductase is same as flavin monooxygenase • Cytochrome oxidase is involved in respiratory chain and not in drug metabolism.• CYP3A4 is responsible for the metabolism of 50% of prescription drugs metabolised by the liver.
Which of the following drugs is commonly administeredby intranasal route? (a) Adrenaline (b) Desmopressin (c) Ganirelix (d) Insulin
Desmopressin
Which of the following drugs has maximum chances ofabsorption from gastric mucosa? (a) Morphine sulfate (b) Diclofenac sodium (c) Hyoscine hydrobromide (d) Quinine dihydrochloride
Diclofenac sodium Diclofenac is an acidic drug and is non-ionized in the acidic medium of stomach. Therefore, it has the maximum chances of absorption from the stomach. other drugs given in the options are basic drugs that are ionized at gastric pH.
Volume of distribution of drug is given by
Dose administrated by I.V. route/ Plasma concentration
The most general term for the process by which theamount of active drug in the body is reduced afterabsorption into the systemic circulation is:
Elimination
Which one of the following is a prodrug? (a) Dopamine (b) Enalapril (c) Ampicillin (d) Prednisolone
Enalapril
The process by which the amount of a drug in the bodydecreases after administration but before entering thesystemic circulation is called:
First pass effect Reduction in the amount of drug before it enters the systemic circulation is called first pass metabolism (also known as first pass effect) whereas if the amount of drug decreases after entry into the systemic circulation, it is called elimination. Latter includes excretion and metabolism.
Most common phase II drug metabolizing reaction is: (a) Glucuronidation (b) Acetylation (c) Oxidation d) Glutathione conjugation
Glucuronidation
Which of the following is NOT an oxidative type ofdrug metabolism? (a) Deamination (b) N-oxidation (c) N-dealkylation (d) Glucuronidation
Glucuronidation
Regarding termination of drug action: (a) Drugs must be excreted from the body to terminatetheir action (b) Metabolism of drugs always abolishes their pharmacologic activity (c) Hepatic metabolism and renal excretion are the twomost important mechanisms involved (d) Distribution of a drug out of blood stream terminatesthe drug's effects
Hepatic metabolism and renal excretion are the two most important mechanisms involved (Ref: KDT 6/e p23) • Action of a drug can be terminated either by hepatic metabolism or by renal excretion. Most of the drugs are inactivated by metabolism. However, some drugs may be activated from inactive form (pro-drugs) and others may produce active metabolites. • Some drugs may act away from blood e.g. digoxin leaves blood stream and enters the heart to produce its action.
Causes for reduced bioavailability include:y (a) High first pass metabolism (b) Increased absorption (c) IV drug administration (d) High lipid solubility (e) Non-ionization
High first pass metabolism • The causes of low bioavailability are: 1. Reduced absorption 2. High first pass metabolism
All of the following factors tend to increase the volumeof distribution of a drug EXCEPT: (a) High plasma protein binding (b) Low ionization at physiological pH values (c) High lipid solubility (d) High tissue binding
High plasma protein binding (Ref: Katzung 10/e p34, 35) • If a drug is highly bound to plasma proteins, it is more likely to stay in the blood. Thus, its V d will be less. • Low ionization favors the distribution of a drug because unionized molecules can cross the membranes of blood vessels and the tissues. • More lipid soluble drugs can easily cross the membranes and are more likely to be highly distributed.
Which of the following statements about a drug havinghigh plasma protein binding is true? (a) Volume of distribution of the drug is very high (b) This drug will be filtered quickly by glomerulus (c) This drug is likely to have minimum chances of drug interactions (d) High plasma protein binding decreases the volumeof distribution
High plasma protein binding decreases the volume of distribution When a drug is highly bound to plasma proteins, it is more likely to stay in blood and thus V d is less. Glomerular filtration depends on renal blood flow and plasma protein binding. Highly protein bound drugs are less likely to be filtered by the glomerulus. Due to non-specific binding sites on plasma proteins these drugs are subjected to several drug interactions.
Thiopentone is used for induction of anaesthesia. Itshows marked redistribution which is a characteristicof: (a) Highly lipid soluble drugs (b) Highly water soluble drugs (c) Weak electrolytes (d) Highly plasma protein bound drugs
Highly lipid soluble drugs
Which of the following is a Phase I metabolic reaction? (a) Hydroxylation (b) Conjugation (c) Glucuronidation (d) Sulfation
Hydroxylation
Which of the following drugs is an inhibitor ofcytochrome p450 enzymes? (a) Ketoconazole (b) Rifampicin (c) Phenytoin d) Phenobarbitone
Ketoconazole • Ketoconazole is a powerful microsomal enzyme inhibitor whereas rifampicin, phenobarbitone and phenytoin areenzyme inducers.
Which of the following is a prodrug? (a) Ampicillin (b) Captopril (c) Levodopa (d) Phenytoin
Levodopa
True statement about route of drug administration is: (a) 80% bio availability by iv injection (B) i.m administration needs sterile techniques (C) i.d injection produces local tissue necrosis and irritation ( d) inhalation produces delayed systemic bioavailability
I.M. administration needs sterile technique; I.D. injection produces local tissue necrosis and irritation 100% bioavailability is seen in case of IV route. • Sterile technique is needed in case of I.V. and I.M. administration. • Irritation and local tissue necrosis is seen in case of intradermal (ID) route. • In inhalational route, absorption of drugs takes place from vast surfaces of alveoli-so bioavailability is high and actionis very rapid.
Which of the following is NOT a prodrug? (a) Enalapril (b) Imipramine (c) Sulphasalazine (d) Cyclophosphamide
Imipramine
Titration of the dose of a drug with the responsecan be done with which of the following routes ofadministration: (a) Sublingual (b) Transdermal (c) Inhalational (d) Subcutaneous
Inhalational Inhalational anesthetic agents like halothane are used in the clinical practice by titration of dose with response.
High hepatic first pass metabolism is seen in all except (A) insulin (B) propranolol (C) lignocaine (D) nitroglycerin
Insulin
Which one of the following drugs does not undergo hepatic first pass effect? (A) propranolol (B) lidocaine (C)insulin (D) Morphine
Insulin
A highly ionized drug: (a) Is excreted mainly by the kidney (b) Can cross the placental barrier easily (c) Is well absorbed from the intestine (d) Accumulates in the cellular lipids
Is excreted mainly by the kidneys Ionized molecules cannot cross the biological membranes. Therefore, these are less likely to be absorbed. Entry of thesemolecules through blood brain barrier and blood placental barrier is also restricted. These drugs cannot be reabsorbed inthe nephron, thus are excreted by the kidneys
Factors affecting drugs distribution:
Lipid solubility of drugs. - Regional blood flow .- Ionization at physiological pH. - Fat: lean body mass ratio (changes with age) .- Degree of plasma protein binding. - Disease like CHF, uremia, cirrhosis.- Affinity for different tissues.
After I.V. drug administration, elimination of a drug depends on: (a) Lipid solubility (b) Volume of distribution (c) Clearance (d) Drug concentration
Lipid solubility; (b) Volume of distribution; (c) Clearance; (d) Drug concentration (Ref: KDT 7/e p30-31) • Elimination of a drug depends upon: - Volume of distribution - Clearance • Volume of distribution is more with highly lipid soluble drugs. • In case of drugs following first order kinetics; rate of elimination is directly proportional to plasma concentration
Which of the following drugs do not produce activemetabolites? (a) Enalapril (b) Lisinopril (c) Prednisone (d) Sulfasalazine
Lisinopril
Which one of the following drugs does not have active metabolite (A) diazepam (B) propranolol (C) allopurinol (D) lisinopril
Lisinopril (Ref: KDT 6/e p485) • Captopril and lisinopril are ACE inhibitors that are not prodrugs. • Diazepam produce many active metabolites like oxazepam. • Propranolol can produce 4-hydroxypropanolol which has b-antagonist activity. • Allopurinol gives rise to oxypurinol which can inhibit xanthine oxidase.
All of the following statements regarding bioavailabilityof a drug are true except: (a) It is a fraction of administered drug that reaches thesystemic circulation in unchanged form (b) Bioavailability of an orally administered drug can becalculated by comparing the Area Under Curve afteroral and intravenous administration (c) Low oral availability always and necessarily meanspoor absorption (d) Bioavailability can be determined from plasma concentration or urinary excretion data.
Low oral bioavailability always and necessarily mean poor absorption • Low oral bioavailability can also be due to high first pass metabolism.
Drugs with high plasma protein binding have (a) Short duration of action (b) Less drug interactions (c) Lower volumes of distribution (d) All Of the above
Lower volumes of distribution • The clinically significant implications of plasma protein binding are: 1. Plasma protein binding causes restriction of drugs in the vascular compartment and thus lower volume of distribution. 2. Longer duration of action - as the protein-bound fraction is not available for metabolism or excretion. 3. Plasma protein bound drugs tend to have more drug interactions due to displacement of a drug with lower affinity by a drug with higher affinity for plasma proteins. 4. Hypoalbuminemia can lead to high concentration of free drug and thus drug toxicity.
Which of the following are prodrug (A) mercaptopurine (B) dipivefrine (C) enalapril (D) phenytoin (E) linezolid
Mercaptopurine; (b) Dipivefrine; (c) Enalapril Enlapril-Enalaprilat Dipivefrine-Epinephrine Mercaptopurine-Methylmercaptopurine
Alkaline diuresis is done for treatment of poisoningdue to: (a) Morphine (b) Amphetamine (c) Phenobarbitone (d) Atropine
Phenobarbitone Phenobarbitone is a barbiturate which is a derivative of barbituric acid (weakly acidic drug) and its excretion can be enhanced by making the urine alkaline. Morphine, atropine and amphetamines are basic drugs
A drug X is secreted through renal tubules, tubularsecretion of this drug can be confirmed if renal clearanceof drug X is: (a) More than the GFR (b) Equal to the GFR (c) Less than the GFR (d) More than volume of distribution
More than the GFR (Ref: KDT 6/e p30) After filtration from glomerulus, a drug may undergo two processes (tubular reabsorption and tubular secretion) before going out from the body i.e. renal clearance. - Suppose 100 mg of a drug is filtered by glomerulus and the renal clearance is 150 mg, it means 50 mg is coming from somewhere else, i.e. tubular secretion must be present. However, we cannot say that reabsorption is not occuring because if 20 mg is reabsorbed and 70 mg is secreted, same thing can happen. Suppose, 100 mg of a drug is filtered but renal clearance is 50 mg. Therefore, 50 mg must have gone somewhere i.e. tubular reabsorption must be occuring, Again, we cannot say that tubular secretion is not present.
In a patient with nephrotic syndrome and hypoalbu minemia, protein binding of which drug will not be affected: (a) Tolbutamide (b) Morphine (c) Diazepam (d) Valproate
Morphine All drugs listed in the options are highly plasma protein bound (>90%) whereas morphine has only 35% binding to plasmaproteins.
Nonsynthetic phase I reaction for drug detoxification is: (a) Glucuronidation (b) Acetylation (c) Methylation (d) Oxidation
Oxidation
Major mechanism of transport of drugs across biological membranes is by: (a) Passive diffusion (b) Facilitated diffusion (c) Active transport (d) Endocytosis
Passive diffusion
Which of the following drugs binds to albumin? (a) Penicillin (b) Lidocaine (c) Propanolol (d) Verapamil
Penicillin (Ref: KDT 6/e p20) • Acidic drugs bind to albumin whereas basic drugs bind to a 1 acid glycoprotein. • Penicillin is an acidic drug, so it binds to albumin.
In drug metabolism, hepatic cytochrome P-450 systemis responsible for: (a) Phase I reactions (hydrolysis, oxidation, reductionetc.) only (b) Phase II reactions (conjugation, synthesis etc.) only (c) Both phase I and II reactions (d) Converting hydrophilic metabolites to lipophilic metabolites
Phase I reactions (hydrolysis, oxidation, reduction etc.) only Cytochrome P450 enzymes are responsible for phase I reactions only whereas microsomal enzymes can be involved in phase II also (glucuronide conjugation)
Ritonavir inhibits metabolism of the following drugsexcept: (AIIMS May 2013) (a) Amiodarone (b) Phenobarbitone (c) Cisapride (d) Midazolam
Phenobarbitone Ritonavir is a powerful inhibitor of CYP3A4, thus the metabolism of substrates of this enzyme will be inhibited by ritonavir.Important substrates of CYP3A4 are: • Amiodarone• Terfenadine, Astemizole, Cisapride• Cyclosporine, Tacrolimus• Lovastatin and other statins• Calcium channel blockers• Midazolam• Protease inhibitors
CYP 3A4 enzymes are affected by: (a) Fexofenadine (b) Phenytoin (c) Carbamazapine (d) Azithromycin (e) Penicillin
Phenytoin; (c) Carbamazepine • CYP3A4 cary out biotransformation of large number of drugs. The inhibition of this isoenzyme by erythromycin,clarithromycin, ketoconazole, itraconazole etc. is responsible for important drug interactions with terfenadine, astemizole and cisapride. Rifampicin, barbiturates and other anticonvulsants are important inducers
Which of the following factors has maximum effect onfiltration of a drug by the glomerulus? (a) Lipid solubility (b) Plasma protein binding (C) degree of ionisation (D) rate of tubular secretion
Plasma protein binding As discussed in question no. 121, glomerular filtration is dependent on renal blood flow and plasma protein binding. It does not depend on the lipid solubility.
Very high first pass metabolism is seen in: (a) Digoxin (b) Dicoumarol (c) Propranolol (d) Practalol
Propranolol
A new drug is found to be highly lipid soluble. It ismetabolized at a slower rate of 10% per hour. Onintravenous injection it produces general anaesthesiathat lasts only for 15 min. This short duration ofanaesthesia is due to: (a) Metabolism of the drug in liver (b) High plasma protein binding of the drug (c) Excretion of drug by kidney d) Redistribution
Redistribution Highly lipid soluble drugs like thiopentone are quickly distributed to the tissue having high blood supply (like brain). If the target organ is also having high blood supply, drug action will be very quick. This is the case with general anaesthetics like thiopentone. Now, the drug will be distributed to less vascular tissues like fat and muscle. Movement of the drug outside the brain results in the termination of its action. This is called redistribution.
One of the potent microsomal enzyme inducer drug is: (a) Captopril (b) Erythromycin (c) Rifampicin (d) Cimetidine
Rifampicin
Which of the following drugs should be removed bydialysis? (a) Digoxin (b) Salicylates (c) Benzodiazepines (d) Organophosphate
Salicylates Salicylates stay in the blood whereas digoxin, diazepam and organophosphates are distributed widely
Apparent volume of distribution (Vd) of a drug exceeds total body fluid volume, if a drug is: (a) Sequestrated in body tissues (b) Slowly eliminated from body (c) Poorly soluble in plasma (d) Highly bound to plasma proteins
Sequestered in body tissues (Ref: KDT 6/e p18-19) • Apparent volume of distribution (V d ) is more for drugs sequestered in tissues. • Lipid insoluble drugs do not enter cells, Vd approximates ECF volume.
Identify the wrong statement: (a) Acidic drugs bind to albumin in plasma (b) Basic drugs bind to alpha-1 acid glycoprotein in plasma (c) Drugs having higher affinity for a plasma proteincan displace the other drug from the same protein (d) Sex steroid hormones do not bind to any protein inplasma
Sex steroid hormones do not bind to any protein in plasma Acidic drugs mainly bind to albumin and basic drugs to alpha-1 acid glycoprotein. Drugs having high PPBlike sulfonamides can displace other drugs bound to same site and may result in toxicity.place other drugs bound to same site and may • Sex steroids bind to steroid hormone binding globulin as well as albumin.
Which of the following is wrongly matched regardingdrug elimination? (a) Calcium channel blockers: CYP3A4 (b) Carvedilol: CYP2D6 (c) Digoxin: P-glycoprotein (d) Simvastatin: Glucuronide conjugation
Simvastatin: Glucuronide conjugation Table 7-3 in Goodman and Gilman 12/e p159 clearly writes that CYP2D6 is involved in metabolism of beta blockers andCYP3A4 in calcium channel blockers' metabolism. P-glycprotein polymorphism decreases AUC of digoxin. Pg 1976 of Goodman and Gilman writes that ' irreversible oxidative metabolites of simvastatin are produced by CYP3Aenzymes.' Another important thing that a student may get confused with is that simvastatin metabolites can be glucuronide conjugated. This is true but the drug no longer remains simvastatin. Clinical importance of this is that if another drugor substance induces UGT glucuronyl transferase, it will not affect the activity of simvastatin. On the other hand if a drugis directly conjugated with glucuronide molecules, the inducers of UGT enzyme will affect the plasma concentration of thedrug
The extent to which ionization of a drug takes placeis dependent upon pKa of the drug and the pH of thesolution in which the drug is dissolved. Which of thefollowing statements is NOT correct? (a) pKa of a drug is the pH at which the drug is 50%ionized (b) Small changes of pH near the pKa of a weak acidicdrug will not affect its degree of ionization. (c) Knowledge of pKa of a drug is useful in predictingits behaviour in various body fluids. (d) Phenobarbitone with a pKa of 7.2 is largely unionizedat acid pH and will be about 40% nonionized inplasma.
Small changes of pH near the pKa of a weak acidic drug will not affect its degree of ionization pKa is the pH at which half of the drug is in the ionized form. There is maximum variation in the ionization of a drug at pH near its pKa value. • Phenobarbitone is an acidic drug having pKa of 7.2. Therefore, at pH = 7.2, 50% of drugis ionized and 50% un-ionized. In acidic medium, more of it will be unionized (becauseit is acidic in nature). In plasma (pH = 7.4), more will be ionized (60%) and less (40%)un-ionized.
Removal of acidic drugs from body is done by using: (a) Ammonium chloride (b) Sodium bicarbonate (c) Hydrochloric acid (d) Citric acid
Sodium bicarbonate
One of the potential microsomal enzymes inhibitorhir9 drug is: (a) Phenobarbitone (b) Griseofulvin (c) Sodium valproate (d) Phenytoin
Sodium valproate
Pharmacokinetics is:
Study of absorption, distribution, binding/storage/biotransformation and excretion of the drug (
A patient, Rajesh with a history of wheezing, coughingand shortness of breath is being evaluated in the asthmaclinic. Several drug treatments with different routes are under consideration. Which of the following statementsabout routes of administration is most correct? (a) Administration of a bronchodilator drug by inhaledaerosol is usually associated with more adverseeffects than administration of this drug by mouth. (b) The first pass effect is the result of elimination ofa drug after administration and before it enterssystemic circulation. (c) Bioavailability of most drugs is greater with rectaladministration than with sublingual administration (d) Administration of a drug by transdermal patch is of ten faster but is associated with more first pass metabolism than oral a
The first pass effect is the result of elimination of a drug after administration and before it enters systemic circulation • Inhalational route provides localized delivery to respiratory system and thus is associated with lesser adverse effects than the systemic routes like oral. option (a) is thus false. • option (b) is the definition of first pass metabolism as given in the text. • When a drug is administered by rectal route, first pass metabolism is less than oral route. But sublingual administration completely avoids first pass metabolism. Therefore, option c is also wrong. Transdermal route is associated with slower absorption of a drug because the pore size is smaller. However, first pass metabolism is avoided because the drug directly enters the systemic circulation.
Bioavailability
The percentage of drug that is detected in the systemic circulation after its administration
Time for peak plasma concentration (T max) indicates: (a) The rate of elimination (b) The rate of absorption (c) The duration of effect (d) The intensity of effect
The rate of absorption
True statement about first order kinetics is (a) A constant amount of a drug is eliminated in unittime (b) The half-life increases with an increase in dose (c)the rate of elimination is constant (D) the rate of elimination is proportional to the plasma concentration
The rate of elimination is proportional to the plasma concentration Drugs may follow zero order or first order kinetics. It depends on the following formula: Rate of Elimination α {Plasma Concentration} order • Thus, if a drug follows zero order kinetics, {Plasma Concentration} 0 is equal to one, in other words rate of elimination is independent of plasma concentration or rate of elimination is constant. • From the above formula, rate of elimination is proportional to plasma concentration for the drugs following first order kinetics.
True statement about weakly basic drugs is: (a) These are bound primarily to plasma albumin (b) These are excreted faster in acidic urine (c) Are highly ionized in the intestinal juice (d) These are absorbed mainly from stomach
These are excreted faster in acidic urine
Redistribution phenomenon is seen in: (a) Halothane (b) Ether (c) Thiopentone (d) All
Thiopentone
Loading dose of a drug is given: (a) To achieve steady state concentration in short time (b) For drugs with short t½ (c) To reduce complications (d) All of these
To achieve Steady State concentration in short time
Maintenance dose rate of a drug depends primarily on :(a) Volume of distribution (b) Half life (c) Lipid solubility (d) Total body clearance
Total body clearance (Ref: KDT 6/e p34) • Maintenance dose is determined by clearance. Maintenance dose = CL × Plasma concentration required
A three year old child is brought to the emergencytah department having just ingested a large overdoseta of an antihistaminic drug. This drug is a weak baseta capable of entering most tissues including the brain.t On physical examination the heart rate is 100/ minute,blood pressure is 110/60 mm Hg and the respiratory rateis 20/ minute. In this case of poisoning:/ minute. In this case of poisoning (a) Urinary excretion would be accelerated by administration of NH4Cl, an acidifying agent (b) Urinary excretion would be accelerated by administration of NaHCO 3, an alkalinizing agent (c) More of the drug would be ionized at blood pH thanat stomach pH (d) Absorption of the drug would be faster from thestomach than from the small intestine.
Urinary excretion would be accelerated by administration of NH 4 Cl, an acidifying agent (Ref: Katzung 10/e p7, 8) This question can be solved by the knowledge that basic drugs are ionized in the acidic medium and vice-a-versa. This antihistaminic drug is a weak base and will be highly ionized in the acidic urine. As ionized drugs cannot be reabsorbed in the nephron, urinary acidifying agents like NH 4 Cl will accelerate the excretion of this agent. on the other hand, NaHCo 3 will decrease its excretion by increasing the unionized form. Blood pH is slightly alkaline (7.4) whereas gastric pH is highly acidic. Basic drugs are ionized more in the acidic pH, therefore option (c) is false. only unionized molecules can cross the membranes, therefore more drug will be absorbed by the small intestine (alkaline pH) than by the stomach.
Loading dose of a drug primarily depends on: (A) volume of distribution (B) clearance (C) rate of administration (D) half life
Volume of distribution (Ref: KDT 6/e p34) • Loading dose is given to saturate the tissue stores so it is mainly dependent on volume of distribution; Whereas maintenance dose depends on the clearance. Loading dose is used for drugs having very long t½ (or high V d ). It is calculated as LD = V d × Target PC • Volume of distribution and clearance are primary pharmacokinetic parameters. All other parameters (e.g. half-life) can be calculated from these.
Urinary alkalinizing agents are administered in case ofpoisoning due to drugs which are: (a) Weak bases (b) Weak acids (c) Strong bases (d) Strong acids
Weak acid Strong electrolytes (strong acid and strong base) are ionized in all media, whether it is acidic or basic. Weak acids are ionized in the alkaline medium and are easily excreted.
Alkalinization of urine is done for: (a) Weak acid drugs (b) Weak basics drugs (c) Strong acidic drugs (d) Strong basic drugs
Weak acid drugs
Which of the following drugs is having the least oral bioavailability? (a) d-tubocurarine (b) Morphine (c) Ampicillin (d) Phenytoin
d-tubocurarine Tubocurarine is not absorbed orally whereas oral bioavailability of morphine, ampicillin and phenytoin are 24%, 62% and 90% respectively.
Which of the following is not true: (a) If a drug is administered rectally it follow 1st orderkinetics (b) If a drug is administered I.M. it follows zero orderkinetics (c) If a drug is administered I.V. it follows 1st orderkinetics (d) Bio availability is usually lower after oral administration than i.v. administration
f a drug is administered rectally it follow 1st order kinetics; (b) If a drug is administered I.M. it follows zeroorder kinetics; (c) If a drug is administered I.V. it follows 1st order kinetics • The order of kinetics of drugs does not depend upon the route of administration. It depends upon the type of drugs. • In case of i.v. injection bioavailability is 100%, but is frequently lower in oral ingestion.
A 70 kg man was given a drug in a dose of 100 mg/kg body weight. Its t1/2 is 10 hours, initial plasma concentration is 1.9 mg/ml. True statement is: (a) CL is 0.02 litre/hr (b) CL is 20 litre/hr (c) k is 0.0693 (d) k is 6.93 (e) CL is 0.2 litre/hr
k is 0.0693 and (e) CL is 0.2 L/hr (Ref: KDT 7/e p31-32) • In this patients total dose of drug administered = 70 × 100 mg = 7000 mg Plasma concentrations = 1.9 mg/ml Ve= total dose administratered/plasma concentration =7000/1.9 T1/2= 0.693 X Vd / clearance Clearance = 0.693 X V / t1/2
