Absorption Distribution; Metabolism and Elimination

1. Cell membranes are composed of: a. b. c. d. e. 2. Phospholipids. Receptor proteins. DNA. a and b. All of the above are correct

All of the following tend to lower the plasma concentra tion of a drug except: a. b. c. d. e. Metabolic biotransformation. Renal tubular reabsorption. Binding to plasma proteins. Renal secretion. Biliary excretion.

3.

What is the approximate percentage of a weak acid (pKa 5.4) in the nonionized form in plasma having a pH of 7.4? a. b. c. d. e. 99% 90% 10% 1% 0.1%

4.

Passive diffusion of a drug across a lipid membrane is enhanced if: a. c. d. e.

b.

It is highly polar.

It contains a quaternary nitrogen.

A substantial gradient exists between extracellular and intracellular concentrations. The drug is water soluble and very lipid soluble. c and d are correct.

5.

Drug oxidations frequently involve all of the following except: a. b. c. d. e. Cytochrome P450 proteins. NADH or NADPH cofactors. Liver endoplasmic reticulum. Esterases. Molecular oxygen.

6.

Conjugation reactions: a. b. c. d. e. Occur with weak acids but not weak bases. Do not require the presence of drug-metabolizing enzymes. Need activation by high energy phosphate com pounds. Can involve amino acids. c and d are correct.

General Principles
1. The half-life of a drug: a. b. c. d. e. 2. Is an independent pharmacokinetic parameter. Depends on clearance. Depends on the volume of distribution. Must be known to calculate the loading dose. b and c only are true.

Drug clearance is: a. b. c. d. e. The volume of blood cleared of drug per unit time. Dependent on the volume of distribution. Dependent on half-life. Dependent on bioavailability. Characterized by all of the above.

3.

Which of the following statements concerning the binding of drugs to plasma proteins is/are correct? a. b. c. d. e. The rates of drug disappearance and the concentration of free drug available to the site of action are altered substantially, if a significant portion of the drug is bound. Many acidic drugs bind strongly to albumin. Many basic drugs bind strongly to a1-acid glycoprotein. Induction of metabolic enzymes by another drug can cause significant changes in the free concentration of a second drug. All of the above are true.

4.

Altered pharmacokinetics of a drug in the elderly may be attributable to: a. b. c. d. e. Decreased total body fat. Increased total body water content. Increased gastric acid secretion. Decreased glomerular filtration rate. Increased plasma albumin concentrations.

5.

The hepatic drug metabolism reaction most likely not to be decreased in the elderly is: a. b. c. d. e. N-Demethylation. Hydroxylation. Sulfoxidation. Glucuronidation. Deesterification.

Receptors and Concentration-response Relationships

1. Binding of a drug to a receptor generally: a. b. c. d. e. 2. Involves covalent binding between receptor and drug. Involves more than one type of weak bond between drug and receptor. Requires long-lasting stable bonds between drug and receptor. Has a similar affinity for the several stereoisomers of the drug. Is characterized by high KD values.

Long or continuous exposure of a receptor to an agent that is an antagonist can: a. b. c. d. e. Result in a phenomenon called supersensitivity. Desensitize the receptor. Produce tachyphylaxis. Cause downregulation of the receptor. b and c are correct.

3.

Which of the following is not a feature of receptors? a. b. c. d. e. By acting on receptors, drugs can enhance, diminish, or block generation or transmission of signals. The KD of drug binding to receptors is generally in the range of 1 to 100 micromolar. Specificity of drug binding to receptors is not absolute. It may require more than one drug molecule to bind to a receptor and elicit a response. Receptors are frequently glycosylated.

4.

Hormone signaling can occur by: a. b. c. d. e. Tyrosine phosphorylation. Receptor association with G-proteins. Formation of second messengers, such as cAMP. + Mobilization of Ca2 from endoplasmic reticulum. All are correct

5.

When added to an intestinal smooth muscle in a tissue bath, two different drugs both cause relaxation of the muscle but with different EC 50 values. Based on this information, which of the following statements are true? a. b. c. d. e. The two drugs have similar chemical structures. The two drugs have different potencies in causing relaxation. Both drugs activate the same receptor in the muscle. Both drugs are directly-acting agonists. The maximum relaxation caused by the two different drugs will be similar.

6.

The affinity constant of a drug for a receptor (KD) is: a. b. c. d. e. The concentration of drug that occupies half of the available receptor sites. The ratio of the reverse to forward rate constants for the drug-receptor interaction. Important in determining fractional occupancy of the receptor by the drug. Characterized by all of the above. Characterized by a and b only.

Drugs affecting the Autonomic Nervous System I

1. Which of the following is not a characteristic of the parasympathetic nervous system? a. b. c. d. e. 2. ACh is the neurotransmitter at parasympathetic ganglia. ACh is the neurotransmitter for postganglionic neurotransmission. The postganglionic neurons are long and unmyelinated. Cell bodies for preganglionic neurons originating in the brainstem and sacral region of the spinal cord. It is essential for life.

The sympathetic nervous system is characterized by all of the following except: a. b. c. d. e. Cell bodies for preganglionic sympathetic neurons originate in the brain. The neurotransmitter for preganglionic sympathetic neurons is ACh. Postganglionic sympathetic neurons are long. Postganglionic sympathetic nerve terminals have an active uptake process for NE called the NE transporter. Nicotinic cholinergic receptors are present at the paravertebral ganglia.

3.

Which of the following autonomic receptors results in the activation of adenylate cyclase as the major component of its signal transduction process? a. b. c. d. e. Nicotinic Muscarinic !1-Adrenergic receptor !2-Adrenergic receptor 1-Adrenergic receptor

4.

Stimulation of prejunctional or presynaptic a2-adrenergic receptors on postganglionic sympathetic neurons causes the following: a. b. c. d. e. Inhibition of ACh release. Stimulation of Epi release. Stimulation of NE release. Inhibition of NE release. Has no effect on neurotransmitter release.

5.

Which of the following signal transduction processes can be used by muscarinic cholinergic receptors? a. b. c. d. Inhibition of adenylate cyclase Stimulation of adenylate cyclase Activation of phospholipase C Stimulation of a sodium-hydrogen exchange system a and c

e.
6.

Activation of the parasympathetic nervous system results in which of the following responses? a. b. c. d. e. An increase in heart rate Vasoconstriction Bronchoconstriction Renin secretion Relaxation of the Gl tract

Drugs Affecting the Autonomic Nervous System II

1. A 60-year-old man complains of difficulty reading in artificial light. Lenticular opacities are diagnosed, and he undergoes cataract removal. After surgery, ACh chloride (Miochol) is administered to: a. b. c. d. e. 2. Relax the circular muscle of the iris. Ensure complete miosis. Decrease lacrimal secretion (tearing). Decrease the flow of aqueous humor. All of the above.

An elderly woman is found to exhibit elevated Intraocular pressure, and open-angle glaucoma is diagnosed. Her physician prescribes pilocarpine (Isopto Carpine) every 6 hours. The anticipated effect of pilocarpine eyedrops would be to: a. b. c. d. e. Relax the ciliary muscles. Improve accommodation. Relax the sphincter muscle of the iris. Inhibit the production of aqueous humor by the ciliary epithelium. Contract the longitudinal ciliary muscle, and pull on the trabecular meshwork to relieve pressure.

3.

An agricultural worker is accidentally sprayed with an insecticide. He complains of a tightness in the chest and difficulty with vision. In the hospital emergency room he is found to have pinpoint pupils and to be profusely salivating. It is assumed he has been exposed to an anticholinesterase. The most appropriate medication for treating his condition would be: a. b. c. d. e. Atropine sulfate. Physostigmine (Isopto-Eserine). Edrophonium (Tensilon). Propantheline (Pro-Banthine). Atropine plus pralidoxime.

4.

If anticholinesterase poisoning goes untreated, the expected cause of death would be: a. b. c. d. e. Hypertension. Hypotension. Congestive heart failure. Respiratory failure. b and c.

5.

The most toxic substance known that affects the cholinergic nervous system is an exotoxin secreted by the anaerobe Clostridium botulinum. There are several forms of botulinum toxin, all of which are highly toxic after they are ingested in contaminated food. The toxin produces respiratory paralysis by: a. b. c. d. e. Blocking nicotinic receptors. Blocking release of ACh from nerve endings. Blocking peristalsis. Causing circulatory collapse. Stimulating the vagal nerve.

6.

Bethanechol is administered subcutaneously to a patient with postoperative abdominal distention and gastric atony. The subcutaneous route of administration is chosen over the oral route because gastric retention is complete and there is no passage of gastric contents into the duodenum. Which of the following effects might be observed after the subcutaneous administration of bethanechol? a. b. c. d. e. Skeletal muscle twitching Decrease in heart rate Peripheral vasodilatation Constriction in the airways of the lung b, c and d

Drugs Affecting the Autonomic Nervous System

1. Metoprolol would be most effective in blocking the ability of Epi to: a. b. c. d. e. 2. Reduce secretion of insulin from the pancreas. Increase release of renin from juxtaglomerular ap paratus. Increase secretion of glucagon from the pancreas. Produce mydriasis (dilatation of pupil). Increase secretion of saliva.

Which of the following drugs is most likely to produce orthostatic hypotension? a. b. c. d. e. Propranolol Dobutamine Labetalol Nadolol Methoxamine

3.

Which of the following drugs would be most likely to increase airway resistance in a patient with pulmonary obstructive disease? a. b. c. d. e. Isoproterenol Atenolol Bitolterol Terbutaline Nadolol

4.

Systemic administration of which of the following drugs would most likely cause bradycardia? a. b. c. d. e. Dopamine Phentolamine Phenylephrine Prazosin Metaproterenol

5.

Terbutaline would be expected to cause all of the following effects except: a. b. c. d. e. Mydriasis. Reduced pulmonary airway resistance. Tachycardia. Hyperglycemia. Increased blood flow in skeletal muscle.

6.

The cardiovascular effects of Epi in a person treated with phentolamine will most closely resemble the responses after the administration of: a. b. c. d. e. Phenylephrine. Terbutaline. lsoproterenol. NE. Methoxamine.