pharm & toxico all chpts

Pharmacology

the study of the effects of chemical substances on living systems

drug

- a chemical substance of known structure, other than essential nutrient which when administered produces biological effect

- can be synthetic, obtained from plants / animals, or genetic engineering

Toxins

has same definition of drugs, not usually administered in clinic but very important tools

Biotech

- emerged in 1980's major source of therapeutic agents such as antibodies, enzymes and regulatory proteins (hormones, growth factors and cytokines)

Physiology and Pharmacology link

- Chemical communication plays a role in almost every physiological process

Chemical communication

mainly the interaction between chemicals and proteins

Receptors

a very important part of chemical research

Pharmacogenetics

study of genetic influence on response to drugs

Pharmacogenomics

individual genetic info guides choice of drug therapy

Pharmacoepidemiology

the study of drug effects on a population level

Pharmacoeconomics

health economics, quantifies cost of drugs and benegfits of its usage

The concentration of a drug required to occupy 50 percent of its receptor sites is

the concentration required to produce the maximum physiological effect

directly proportional to the drugs affinity for its receptor

inversely proportional to the drugs affinity for its receptor

directly proportional to the drugs intrinsic efficacy

usually determined with the Schild equation

inversely proportional to the drugs affinity for its receptor

The magnitude of the response to a drug is related to the

total number of receptors for the drug

number of receptors occupied by the drug

number of vacant receptors in the tissue

number of spare receptors in the tissue

number of phosphorylated receptors in the tissue

number of receptors occupied by the drug

A partial agonist is typically a drug that

has low affinity for its receptor

can only occupy a small fraction of its receptors

can only produce a submaximal response

requires high doses to produce a maximal response

increases the number of spare receptors

can only produce a submaximal response

A type of drug that reduces the slope and maximum response of an agonist is

a non-competitive antagonist

a competitive antagonist

a physiologic antagonist

an inverse agonist

a partial agonist

a non-competitive antagonist

A gradual decrease in the number of drug receptors is most likely to result from exposure to

a competitive antagonist

a non-competitive antagonist

an agonist

an inverse agonist

an antimetabolite

an agonist

Receptor desensitization typically results from

endocytosis of receptors

exposure to an inverse agonist

irreversible agonist binding

spare receptors

phosphorylation of receptor protein

phosphorylation of receptor protein

In the presence of a competitive antagonist, the agonist log-concentration effect curve is

shifted to the right without a change in slope or maximum effect

shifted to the left without a change in slope or maximum effect

shifted to the right with a decreased slope and maximum effect

shifted to the left with a decreased slope and maximum effect

not shifted right or left but shows a decreased maximum effect

shifted to the right without a change in slope or maximum effect

An agonist for a ligand-gated ion channel typically

a) increases channel conductance

b) increases the number of open channels

c) increases the rate of channel closing

d) alters channel ion selectivity

e) alters the open channel conformation

b) increases the number of open channels

The opening of chloride ion channels by gamma-amino butyric acid is facilitated by

a tricyclic antidepressant drugs

b benzodiazepine drugs

c local anesthetics

d opioid analgesics

e central nervous system stimulants

b benzodiazepine drugs

The most rapid response is produced by activation of

kinase-linked receptors

G-protein coupled receptors

receptors activating gene transcription

ionotropic receptors

insulin receptors

ionotropic receptors

Which second messenger in a G-protein coupled receptor signal transduction cascade typically increases intracellular calcium?

cyclic GMP

cyclic AMP

diacylglycerol

arachidonic acid

inositol triphosphate

inositol triphosphate

Coupling of a G-protein alpha subunit to an agonist-occupied receptor initially leads to

activation of the beta-gamma complex

hydrolysis of GTP

activation of adenylate cyclase

exchange of bound GDP with GTP

dissociation of the alpha-subunit from the receptor

exchange of bound GDP with GTP

The nicotinic receptor is an example of a

G-protein coupled receptor

ligand-gated ion channel

tyrosine-kinase linked receptor

cytokine receptor

transport protein

ligand-gated ion channel

he opening of chloride ion channels by gamma-amino butyric acid is facilitated by

tricyclic antidepressant drugs

benzodiazepine drugs

local anesthetics

opioid analgesics

central nervous system stimulants

benzodiazepine drugs

The most rapid response is produced by activation of

kinase-linked receptors

G-protein coupled receptors

receptors activating gene transcription

ionotropic receptors

insulin receptors

ionotropic receptors

Which type of receptors contains seven transmembrane helices?

nicotinic acetylcholine receptors

sodium channels

steroid hormone receptors

insulin receptors

G-protein-coupled receptors

G-protein-coupled receptors

A calculated volume of distribution greater than total body water is most likely to occur with drugs that are

highly ionized

highly lipid soluble

subject to a high degree of first-pass inactivation

highly bound to plasma proteins

very large molecules

highly lipid soluble

Concerning the effect of pH on the urinary excretion of drugs, it can be correctly stated that

urinary acidification accelerates excretion of weak acids and bases

urinary alkalinization accelerates excretion of weak acids and bases

urinary acidification accelerates excretion of weak acids

urinary alkalinization accelerates excretion of weak acids

urinary alkalinization has no effect on excretion of weak bases

urinary alkalinization accelerates excretion of weak acids

The rectal route of administration

provides nearly 100 percent bioavailability

is only used for localized effects

is suitable for persons with nausea and vomiting

is subject to a high degree of first-pass metabolism

is used for administration of nitroglycerin

is suitable for persons with nausea and vomiting

The passage of drugs across the blood-brain barrier

is facilitated by a high degree of drug ionization

is most rapid for drugs with low lipid solubility

occurs more readily in the chemoreceptor trigger zone

is reduced by inflammation of the meninges

is rapid with aminoglycoside antibiotics

occurs more readily in the chemoreceptor trigger zone

The binding of drugs to plasma albumin

is usually irreversible

is saturable

is most important for basic drugs

accelerates drug metabolism

accelerates drug excretion

is saturable

Most drugs are absorbed across cell membranes of the gut by the process of

diffusing through lipid

pinocytosis

diffusing through aqueous pores

carrier-mediated transport

ion trapping

diffusing through lipid

In first-order drug elimination

drug half-life is directly proportional to drug concentration

the rate of elimination is directly proportional to drug concentration

drug clearance is directly proportional to plasma drug concentration

the rate of elimination is constant

the rate of elimination is unpredictable

the rate of elimination is directly proportional to drug concentration

Hepatic cytochrome P450 drug-metabolizing enzymes are primarily found in

cell nuclei

plasma membranes

the cytoplasm

the smooth endoplasmic reticulum

mitochondria

the smooth endoplasmic reticulum

Phase II drug metabolism

includes hydrolytic reactions

produces low molecular weight products

usually forms inactive metabolites

takes place mainly in the kidneys

requires NADPH as a cofactor

usually forms inactive metabolites

If a drug is administered repeatedly at the same dose and dosage interval, the time required to reach the steady-state plasma drug concentration is proportional to the

dose

route of administration

dosage interval

bioavailability

elimination half-life

elimination half-life

If a drug exhibits saturation (zero-order) kinetics, then

the rate of drug elimination is constant

drug half-life is constant

drug clearance is constant

plasma drug concentration is constant

plasma drug concentration falls exponentially

the rate of drug elimination is constant

In the two-compartment pharmacokinetic model, orally administered drugs are

absorbed into the peripheral compartment

distributed from the central to the peripheral compartment

metabolized in the central compartment

excreted in the peripheral compartment

none of the above

distributed from the central to the peripheral compartment

The volume of plasma from which a drug is eliminated in a unit of time is known as the

volume of elimination

volume of distribution

clearance

elimination rate constant

kinetic volume

clearance

Inactive prodrugs have been developed to

reduce drug toxicity

increase drug half-life

decrease hepatic drug metabolism

increase drug absorption

slow drug excretion

increase drug absorption

1. The release of acetylcholine from cholinergic nerve terminals is stimulated by

nitric oxide

norepinephrine

acetylcholine

prostaglandins

endothelin

nitric oxide

1. Constriction of bronchi is typically produced by activation of

adrenergic beta-1 receptors

adrenergic beta-2 receptors

muscarinic M1 receptors

muscarinic M2 receptors

muscarinic M3 receptors

muscarinic M3 receptors

1. The enteric nervous system is primarily concerned with the regulation of

the urinary tract

gastrointestinal motility

male sex organs

respiration

vascular smooth muscle

gastrointestinal motility

1. The final step in the release of norepinephrine from sympathetic neurons is

docking

loading

diffusion

synthesis

exocytosis

exocytosis

1. Activation of adrenergic beta-2 receptors produces

contraction of the iris sphincter muscle

relaxation of the iris sphincter muscle

relaxation of the ciliary muscle

contraction of the ciliary muscle

lacrimal gland secretion

relaxation of the ciliary muscle

Activation of muscarinic M2 receptors

increases calcium conductance

increases potassium conductance

increases cardiac rate and force

causes central nervous system excitation

produces vascular smooth muscle relaxation

increases potassium conductance

The second messengers formed by activation of muscarinic acetylcholine receptors include

inositol triphosphate

cyclic AMP

cyclic GMP

eicosanoids

guanosine triphosphate

inositol triphosphate

Pilocarpine lowers intraocular pressure by

decreasing aqueous humor formation

contracting the iris sphincter muscle

contracting the ciliary muscle

relaxing the iris sphincter muscle

relaxing the ciliary muscle

contracting the ciliary muscle

Pyridostigmine enhances neuromuscular transmission in myasthenia gravis patients by

increasing release of acetylcholine

inhibiting degradation of acetylcholine

causing up-regulation of nicotinic receptors

reactivating cholinesterase

blocking autoantibodies

inhibiting degradation of acetylcholine

Activation of muscarinic M3 receptors leads to

smooth muscle relaxation

cardiac slowing

central nervous system stimulation

vasoconstriction

exocrine gland secretion

exocrine gland secretion

The release of acetylcholine from cholinergic nerve terminals is blocked by

atropine

bungarotoxin

botulinum toxin

batrachotoxin

tetrodotoxin

botulinum toxin

Transient muscle fasciculations followed by paralysis typically occur after administration of

succinylcholine

tubocurarine

vecuronium

gallamine

atropine

succinylcholine

The reuptake of norepinephrine by presynaptic nerve terminals (uptake 1) is inhibited by

guanethidine

reserpine

methyldopa

methyltyrosine

cocaine

cocaine

The adverse effects of beta-adrenoceptor antagonists include

hyperglycemia

cardiac arrhythmias

myocardial ischemia

anxiety

bronchoconstriction

bronchoconstriction

Persons with acute thyrotoxicosis are often treated with propranolol because it

reduces peripheral vascular resistance

increases cardiac output

decreases cardiac stimulation

decreases blood glucose levels

inhibits thyroid hormone secretion

decreases cardiac stimulation

Which drug inhibits the transport of norepinephrine into synaptic vesicles, thereby leading to neurotransmitter depletion?

reserpine

methyldopa

bretylium

6-hydroxydopamine

guanethidine

reserpine

Delayed after-depolarizations in cardiac tissue typically result from an increased influx of

sodium

potassium

calcium

chloride

sodium and potassium

calcium

Verapamil is indicated for the treatment of

supraventricular tachycardia

ventricular tachycardia

atrial fibrillation

ventricular fibrillation

cardiac asystole

supraventricular tachycardia

Dobutamine is useful in treating acute heart failure because of its ability to

increase heart rate more than contractile force

increase contractile force more than heart rate

produce a negative dromotropic effect

cause cardiac stimulation and vasoconstriction

inhibit phosphodiesterase

increase contractile force more than heart rate

Digoxin slows AV conduction and decreases heart rate by

activating cardiac muscarinic receptors

blocking cardiac adrenergic beta-1 receptors

antagonizing cardiac calcium channels

increasing vagal outflow from the CNS

increasing cardiac contractile force

increasing vagal outflow from the CNS

Delayed after-depolarizations in cardiac tissue typically result from an increased influx of

sodium

potassium

calcium

chloride

sodium and potassium

calcium

The re-excitation of cardiac tissue prior to the next cardiac impulse occurs in the process known as

re-entry

ectopic automaticity

atrioventricular block

atrial fibrillation

bradycardia

re-entry

Drugs that increase serum digoxin levels include

furosemide

cholestyramine

amiodarone

enalapril

hydrochlorothiazide

amiodarone

Verapamil is indicated for the treatment of

supraventricular tachycardia

ventricular tachycardia

atrial fibrillation

ventricular fibrillation

cardiac asystole

supraventricular tachycardia

Dobutamine is useful in treating acute heart failure because of its ability to

increase heart rate more than contractile force

increase contractile force more than heart rate

produce a negative dromotropic effect

cause cardiac stimulation and vasoconstriction

inhibit phosphodiesterase

increase contractile force more than heart rate

Nitroglycerin relieves typical angina pectoris in part by

increasing cardiac stroke volume

dilating coronary arterioles

decreasing cardiac oxygen consumption

constricting collateral vessels in the heart

increasing blood pressure

decreasing cardiac oxygen consumption

Nitroglycerin and other organic nitrates produce their vasodilator effect by

increasing formation of cyclic AMP

increasing formation of cyclic GMP

blocking calcium channels

blocking adrenergic alpha receptors

activating potassium channels

increasing formation of cyclic GMP

Which vasoconstrictor substance is produced by vascular endothelial cells?

nitric oxide

bradykinin

prostacyclin

natriuretic peptide

endothelin

endothelin

Captopril is a structural analog of the terminal dipeptide of

renin

nitric oxide synthase

endothelin

angiotensin converting enzyme

angiotensin I

angiotensin I

The adverse effects of terazosin and related drugs typically include

hypokalemia

drowsiness and dry mouth

urinary retention in older men

postural hypotension and edema

bradycardia and syncope

postural hypotension and edema

Which drug inhibits phosphodiesterase and blocks adenosine receptors?

salmeterol

budesonide

zileuton

cromoglycate

theophylline

theophylline

In the treatment of asthma, glucocorticoids

increase secretion of interleukin-4

up-regulate adrenergic beta-2 receptors

increase microvascular permeability

increase formation of vasodilator prostanoids

are usually administered orally

up-regulate adrenergic beta-2 receptors

Tremor and tachycardia are common side effects of

theophylline

salbutamol

montelukast

fluticasone

cromoglycate

salbutamol

The 5-hydroxytryptamine 5-HT2 receptors are

primarily inhibitory

chiefly found in the area postrema

mostly presynaptic

abundant in the cortex and limbic system

predominantly presynaptic autoreceptors

abundant in the cortex and limbic system

Fast neurotransmitters in the central nervous system include

glutamate

dopamine

substance P

prostanoids

nerve growth factor

glutamate

Activation of AMPA (a-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid) receptors for excitatory amino acids leads to

fast inhibitory neurotransmission

fast excitatory neurotransmission

modulation of postsynaptic excitatory neurotransmission

slow excitatory neurotransmission

slow inhibitory neurotransmission

fast excitatory neurotransmission

Slow neurotransmitters and neuromodulators act mainly through

ligand-gated ion channels

G-protein-coupled receptors

enzymes

transcription factors

release of nitric oxide

G-protein-coupled receptors

The relationship between the biochemical and cellular effects of a drug and its behavioral and therapeutic effects are best understood for drugs used in treating

mood depression

epilepsy

Parkinson's disease

schizophrenia

mania

Parkinson's disease

The N-methyl-D-aspartate receptor for excitatory amino acids is positively modulated by

g-amino butyric acid

tyrosine

glycine

phenylalanine

alanine

glycine

The pathway leading to long-term potentiation of neuronal activity includes

inhibition of nitric oxide synthase

sustained blockade of N-methyl-D-aspartate receptors

feedback inhibition by nitric oxide

activation of protein kinase C by calcium

inhibition of metabotropic receptors

activation of protein kinase C by calcium

The glycine receptor blocked by strychnine is a

ligand-gated chloride channel

ligand-gated calcium channel

voltage-gated calcium channel

G-protein-coupled receptor

protein kinase receptor

ligand-gated chloride channel

The binding of g-amino butyric acid (GABA) to the GABA receptor is increased by

flumazenil

picrotoxin

diazepam

baclofen

gabapentin

diazepam

Which substance blocks ion channels of N-methyl-D-aspartate (NMDA) receptors for excitatory amino acids?

ketamine

cycloserine

kynurenic acid

cyclothiazide

kainite

ketamine

Activation of metabotropic excitatory amino acid receptors leads to

opening of chloride ion channels

opening of cation channels

formation of inositol triphosphate

formation of cyclic AMP

activation of protein kinase A

formation of inositol triphosphate

Agonists at 5-hydroxytryptamine 5-HT2A receptors typically cause

sleep

vigilance

hallucinations

hyperphagia

euphoria

hallucinations

The 5-hydroxytryptamine 5-HT3 receptors are

excitatory ligand-gated cation channels

inhibitory ligand-gated cation channels

G-protein-coupled receptors

inhibitory ligand-gated chloride channels

presynaptic autoreceptors

excitatory ligand-gated cation channels

A deficiency of dopamine in the nigrostriatal pathway contributes to the development of

drug dependence

Parkinson's disease

obesity

schizophrenia

insomnia

Parkinson's disease

Functions associated with noradrenergic pathways in the central nervous system include

feeding behavior

induction of sleep

control of mood

pleasure and reward

release of hormones

control of mood

Cumulative dose-related cardiac toxicity typically results from administration of

doxorubicin

bleomycin

vincristine

imatinib

irinotecan

doxorubicin

Vincristine inhibits mitosis of cancer cells at metaphase by

inhibiting telomerase

increasing tubulin degradation

inhibiting synthesis of tubulin

inhibiting polymerization of tubulin

stabilizing microtubules

inhibiting polymerization of tubulin

Cytarabine is converted to an active triphosphate metabolite that inhibits

DNA polymerase

adenine deaminase

dihydrofolate reductase

telomerase

thymidylate synthetase

DNA polymerase

Folinic acid can be administered to counteract the toxic effects of

fludarabine

gemcitabine

cytarabine

fluorouracil

methotrexate

methotrexate

Reactive carbonium ions that attack guanine bases of DNA and lead to crosslinking of DNA strands are formed in the body from drugs such as

cisplatin

bleomycin

doxorubicin

etoposide

cyclophosphamide

cyclophosphamide

Thymidylate synthetase is inhibited by the active metabolite of

pentostatin

fluorouracil

doxorubicin

gemcitabine

fludarabine

fluorouracil

Trastuzumab is useful in treating breast cancer because of its ability to bind

telomerase

human epidermal growth factor receptor 2

DNA transcription factors

insulin-like growth factor

calcium channel forming proteins

human epidermal growth factor receptor 2

Ivermectin is believed to kill filarial roundworm parasites partly by

blocking glutamate-gated chloride channels

opening glutamate-gated chloride channels

blocking voltage-gated calcium channels

opening voltage-gated calcium channels

inhibiting oxidative phosphorylation

opening glutamate-gated chloride channels