Drugs, Chemicals & Health Flashcards
What are the known regulatory protein targets involved in drug action? What is the exception? i.e. not a regulatory protein.
1 Carriers/ transporters 2 Enzymes 3 Ion channels 4 Receptors The exception: DNA
Describe carriers/transporters
- sit in cell lipid membranes
- carry molecules into the cell because the permeating molecules are often insufficiently lipid soluble to penetrate lipid membranes on their own
Give examples of a transporter/carrier aided reaction
- ions and many organic molecules across the renal tubule, the intestinal epithelium and the blood-brain barrier
- the transport of Na+ and Ca2+ out of cells, and the uptake of neurotransmitter precursors (such as choline) or of neurotransmitters themselves (such as noradrenaline, 5-hydroxytryptamine [5-HT], glutamate and peptides) by nerve terminals
- transport of drug molecules and their metabolites across cell membranes and epithelial barriers
Describe enzymes
- used for reaction or inhibition, mostly inhibition using substrate equivalent that acts as a competitive inhibitor of the enzyme
- regulate protein concentrations and producing bioactive products
- Drugs may also act as false substrates, where the drug molecule undergoes chemical transformation to form an abnormal product that subverts the normal metabolic pathway
Give examples of enzyme aided reaction
- competitive inhibitor: captopril, acting on angiotensin-converting enzyme
- false substrate: anticancer drug fluorouracil, which replaces uracil as an intermediate in purine biosynthesis but cannot be converted into thymidylate, thus blocking DNA synthesis and preventing cell division.
Describe ion channels
- gateways in cell membranes, which selectively allow the passage of particular ions
- induced to open or close by a variety of mechanisms.
- 2 important types are ligand-gated channels and voltage-gated channels.
Describe LG and VG channels
- LG open only when one or more agonist molecules are bound since agonist binding is needed to activate them.
- VG channels are gated by changes in the trans-membrane potential rather than by agonist binding.
How do drugs affect ion channel function?
- by binding to the channel protein itself via the ligand-binding site (of LG channels), or to other parts of the channel molecule
- or they may affect channel function by an indirect interaction, involving a G-protein and other intermediaries
Use of drugs on ion channels
- local anesthetics affects VG sodium channels by plugging the channel physically, therefore blocking ion permeation.
- systems where drugs target ion channels: Nerves, brain, kidney and the cardiovascular system
- A competitive antagonist does which of the following?
a) shifts the dose response curve to the right
b) shifts the dose response curve in a parallel fashion
c) has no effect on the maximum response
d) all of the above
d.
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor. Sufficient antagonist will displace the agonist from the binding sites, resulting in a lower frequency of receptor activation.
Presence of a competitive antagonist will shift an agonism dose-response curve to the right
A competitive antagonist can be reversible competitive antagonist or irreversible competitive antagonist.
A G-protein coupled receptor has the following trans membrane domains: a) 5 b) 4 c) 6 d) 7
d.
(GPLR), constitute a large protein family of receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. They are called transmembrane receptors because they pass through the cell membrane, and they are called seven-transmembrane receptors because they pass through the cell membrane seven times.
There are two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.[6] When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G-protein by exchanging its bound GDP for a GTP. The G-protein’s α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type
A ligand gated ion channel responds to a ligand in:
a) milliseconds
b) minutes
c) hours
d) days
a. milli seconds
Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl- to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand),[1] such as a neurotransmitter
The potency of a drug is best estimated on a concentration response curve when the response is:
a) 25% of maximum
b) 50% of maximum
c) 75 % of maximum
d) 100% of maximum
b. 50%
potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug (e.g., morphine, alprazolam, chlorpromazine) evokes a larger response at low concentrations, while a drug of lower potency (ibuprofen, acetylsalicylic acid) evokes a small response at low concentrations. It is proportional to affinity and efficacy.
Affinity is the ability of the drug to bind to a receptor. Efficacy is the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level. The response is equal to the effect, or (E), and depends on both the drug binding and the drug-bound receptor then producing a response; thus, potency depends on both affinity and efficacy.
G-protein coupled receptors are linked via their G-proteins to enzymes which produce 2nd messengers in the cell. Which of these is such an enzyme?
a) monoamine oxidase
b) catechol -O-methyl transferase
c) adenylate cyclase
d) Cyclic AMP
c.
The vast majority of targets for drugs are: (circle CORRECT option)
a) lipids
b) ions
c) proteins
d) DNA
c. protein
A drug is 80% ionized at pH 7.4, and 20% ionized at pH 2, this means that it will be predominately absorbed via: (circle CORRECT option)
a) the mouth
b) the stomach
c) the intestine
d) the stomach and intestine equally
b. the stomach
In the stomach, drugs that are weak acids (such as aspirin) will be present mainly in their non-ionic form, and weak bases will be in their ionic form. Since non-ionic species diffuse more readily through cell membranes, weak acids will have a higher absorption in the highly acidic stomach.
Which of the following body compartments is the smallest in terms of drug distribution? (circle CORRECT option)
a) plasma
b) intercellular fluid
c) transcellular fluid
d) interstitial fluid
c.
Vd= A/C (amount of drug divided by concentration)
Oxidation is an enzymic reaction which occurs: (circle CORRECT option)
a) prior to Phase I metabolism
b) as part of Phase II metabolism
c) as part of Phase I metabolism
d) as part of entero-hepatic circulation
c. phase 1
Drug metabolism is divided into three phases. In phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are then conjugated to polar compounds in phase II reactions. These reactions are catalysed by transferase enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be further processed, before being recognised by efflux transporters and pumped out of cells.
Certain antidepressants can act at which of the following cellular target sites to increase synaptic catecholamine concentrations:
a) adrenoreceptor
b) nicotinic receptor
c) acetylcholinesterase
d) uptake 1 transport
d.
Noradrenaline \_\_\_\_\_\_\_\_\_\_ cardiac pacemaker cells via the \_\_\_\_\_\_\_\_ receptor: a) activates, a1 b) activates, b1 c) inhibits, b1 d) activates, M3
b.
b1-adrenoceptor agonists are most useful in the treatment of:
a) heart failure
b) diabetes
c) incontinence
d) none of the above
a.
Give an example of down regulation
Cellular decrease in number of receptors to the molecule
Ie increased number of cytochrome P450 enzymes in liver cells when xenobiotic molecules such as dioxin are administered
Which of the following IS NOT an opioid peptide?
a) endorphin
b) enkephalin
c) dynorphin
d) morphine
d.morphine.
Opioid peptides are short sequences of amino acids that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Opioid peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble opiates.
Which of the following statements about antiepileptic drugs is INCORRECT?
a) carbamazepine blocks voltage-dependent Na+ channels
b) phenytoin blocks voltage-dependent Na+ channels
c) carbamazepine is an inducer of hepatic enzymes
d) phenobarbital increase the effects of the excitatory neurotransmitter
glutamate
d.
The vinca alkaloids are anticancer drugs that prevent tubulin polymerisation, this results in: (circle CORRECT option)
a) cells being trapped in anaphase
b) failure to leave prophase
c) failure to enter anaphase
d) cells being trapped in metaphase
d. Vinca alkaloids are used in the treatment of cancer. They are a class of cell-cycle-specific cytotoxic drugs that work by inhibiting the ability of cancer cells to divide: Acting upon tubulin, they prevent it from forming into microtubules, a necessary component for cellular division.
One key target for anticancer drugs Is: (circle CORRECT option)
a) DNA-dependent RNA polymerase
b) DNA polymerase
c) thymidine Kinase
d) the 30S ribosome
b.
Drugs which inhibit proteases are most likely to be used against: (circle CORRECT option)
a) gram negative bacteria
b) influenza Viruses
c) human Immunodeficiency Virus
d) chronic myeloid leukaemia cancer
c.
Which of the following statements about dopamine is CORRECT?
a) it is present at high concentrations within the regions of the limbic
system
b) its reduction within the nigrostriatal pathway is associated with
schizophernia
c) it can only have excitatory effects within the central nervous system
d) its hyperactivity in the nigrostriatal pathway is associated with
Parkinson’s disease
a.
Which of the following is blocked by a local anaesthetic?
a) calcium channels
b) potassium channels
c) sodium channels
d) opioid receptors
c.
All local anesthetics are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Though many other drugs also have membrane stabilizing properties, not all are used as local anesthetics (propranolol, for example). Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited.
Some people especially in Asia have a genetic intolerance to alcohol.
Which of these enzymes is deficient in these people?
a) alcohol dehydrogenase
b) acetaldehyde dehydrogenase
c) monoamine oxidase
d) catechol-O-methyltransferase
b.
The neurotransmitter mainly associated with drug dependence is:
a) acetylcholine
b) 5HT
c) noradrenaline
d) dopamine
d.
The active ingredient of stimulant plant Khat is:
a) cocaine
b) heroin
c) opium
d) cathinone
d.
cathine and cathinone
Which one of these is least commonly associated with administration of opioid drugs: a) constipation b) nausea c) respiratory depression d) paralysis
d.
Which of the following statements about gamma-aminobutyric acid
GABA) is CORRECT?
a) it is a major excitatory neurotransmitter in the central nervous system
b) it is formed from aspartate by the enzyme glutamic acid decarboxylase
c) it activates GABAB receptors which are found mainly at postsynaptic sites
d) it activates GABAA receptors which leads to Cl- influx
[End
d.
- Explain what the terms affinity and efficacy mean in pharmacology.
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Using a brief sketch, show the basic pharmacokinetic phases of drug entry into
the body.
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Opioids are the most effective analgesic drugs. Describe how they work and
what their major limitations are in long term treatment of chronic pain.
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Compare the mechanism of action of cocaine and amphetamine.
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Describe the components of the Biopsychosocial model of addiction.
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How does an indirectly acting sympatho-mimetic work at a cellular level? List two examples of an indirectly acting sympatho-mimetic
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Briefly describe how cholinesterase inhibition would affect the function of the respiratory system (airways).
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Briefly describe how you would pharmacologically (i.e. with drugs) counter
or reverse the effects of exposure to an organophosphate poison (eg. Dyflos).
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Describe briefly the evidence which supports the 5-hydroxytryptamine (5-HT) hypothesis of schizophrenia.
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Describe briefly the mechanisms of action and adverse effects of drugs used to treat nausea and vomiting.
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Using brief notes compare and contrast the mechanisms of resistance to anticancer drugs and antiviral drugs.
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Give a brief definition of complementary medicine
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Describe the mechanisms of action and main side effects of THREE major
classes of antidepressant drugs.
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Specify the mechanisms of action and main side effects of THREE major
classes of antiepileptic drugs.
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Briefly describe the main criteria used to classify an endogenous substance
as a central nervous system neurotransmitter.
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Regulation of the concentration of neurotransmitters in the synaptic cleft is important for normal brain function. Discuss how this is achieved and how drugs commonly used to treat neurological and psychological illness act upon these mechanisms.
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List one potential clinical use for an antagonist of the i) muscarinic receptor and ii) b1 adrenoceptor. Explain how they achieve their therapeutic effect in both instances and list one example of a selective drug for each of these receptors
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Draw a representative schematic illustration demonstrating the main anatomical and pharmacological differences between the sympathetic and parasympathetic nerve pathways, using the heart as your innervating target organ. Include the major transmitters produced at each neuron and the main class of receptors for those transmitters. Include receptor subtypes where appropriate.
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Specify the main use of non-steroidal anti-inflammatory drugs (NSAID) and describe the differences between non selective cyclo-oxygenase (COX) inhibitors and selective cyclo-oxygenase inhibitors.
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Bacteria are described as “target rich environments” for drug therapy. Is this comment justified? Give examples of major antibacterial drug classes and their mechanisms of action to illustrate your answer.
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Describe the early (immediate) and late phases of an asthma attack and the mechanisms of action of THREE drugs used to treat asthma.
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Which of the following is not a part of the pharmacokinetic phase of a drug?
a. Absorbtion
b. Receptor site
c. Metabolism
d. Elimination
b. Receptor site
Which of the following factors may have an effect on drug absorption? I. Rout of administration II. Metabolic degradation III. Inactivation by stomach acids IV. Blood flow to absorption sitea a. I only b. I and II only c. I and IV only d. I,II,III, and IV d. I,II,III, and IV
d. I,II,III, and IV
Which of the following routs of drug aadministration help to reduce the firtst-pass effect? I. Oral administration II. Injection III.Sublingual tablets IV. Rectal administration a. I and III only b. II and IV only c. II,III, and IV only d. I,II, and IV only
c. II,III, and IV only
The mechanism of drug action by which drug molecule causes its effect in the body is known as the:
a. Pharmacodynamic phase
b. Elimination phase
c. Pharmacokinetic phase
d. Administration phase
a. Pharmacodynamic phase
Given the following information, which drug is more potent? Drug........... ED50 A ................10mg B .................5mg C .................1mg D .................15mg a. Drug A b. Drug B c. Drug C d. Drug D
c. Drug C
The drug albuterol binds to its corresponding receptor in order to initiate response of bronchodilation. By definition, albuterol is known as a:
a. Agonist
b. Antiagonist
c. Both a and b
d. Neither a nor b
a. Agonist
Pharmacokinetics
Body’s effect on the drug
Ion Trapping or Ph Partitioning
Ionization of drugs is Ph dependant, drug molecules will acumulate on the side of the membrane where the ph most favors ionization. Acidic drugs accumulate on the alkaline side and basic drugs accumulate on the acidic.
4 Factors of Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
Absorption effected by
Rate of dissolution, Surface Area available for drug absorption, blood flow to where drug is absorbed, lipid solubility, ph partitioning
First Pass Effect
Concentration of a drug is greatly reduced before it reaches the systemic circulation.
Pharamcodynamics
drug’s effect on the body
Simple occupancy theory
1) intensity of a response is proportional to the number of receptors occupied by the drug
2) maximal response occurs when all drug-receptors are occupied by the drug
Agonist
molecules that activate receptors
Antagonist
molecules that block receptors
non-competetive antagonist
binds irreversibly to receptors, and therefore reduces the total number of receptors available for activation by agonist
Look at [] of agonist v. non comp antagonist - the one that has more [] will win
competetive antagonist
typically binds reversibly to receptors. Only will block if higher concentration than the compound is trying to block.
Look at [] and Affinity –> Analogy holiday shopping and aggression for parking spot
Partial agonist
agonist with moderate intrinsic activity. Can act as antagonists and agonists.
Loading dose
large initial dose given to establish a therapeutic drug level
Drug Receptors - 4 primary
- Cell membrane - embedded enzymes [fast]
- Ligand gated ion channels [fast]
- G-protien-coupled receptor systems [fast]
- Transcription factors [slow]
