Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 3 - Script > Clinical Pharmacology > Flashcards

Clinical Pharmacology Flashcards

1
Q

in most drugs in clinical use the active agent of a drug is…

A

a small molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why are small molecules the active agent of a drug

A
  • more easily enter the body

- reach there site of action before being metabolised or cleared

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the advantages and disadvantages of medicines using anitbodies and gene therapies

A

Advantge
- designed to have greater specificity than small molecules

Disadvantage
- can be more difficult to deliver to their targets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the usual sites of drug action within the body

A
  • usually on proteins

- protiens are key and ubiquitous functional elements in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is an affinity of a drug

A
  • the affinity of a drug for its receptors is a measure of how well it binds a chemically sensitive site or receptor
  • drugs bind to receptors at a rate proportional to the drug concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the proportion of receptors occupied by a drug equal to

A

p = [D]/[D] + Kd

  • square brackets are short hand for concenration
  • Kd is ratio K-/K+
  • K+ is the foward rate constant
  • K- is the reverse rate constant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

increasing competitive antagonist concentration causes …

A

right shift in the relationship between drug concentrations and receptor binding so there is a lower proportion of receptors bound at a higher drug concentration due to the antagonist effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is an agonist

A
  • An agonist is a chemical that binds to its target to increase its activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is an antagonist

A

An antagonist is a chemical that opposes the action of another chemical
- this means that antagonists have no action on their targets in the absence of an agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can an antagonist act without an agonist

A
  • in the body it is common for an endogenous agonist to be continuously present so antagonists like propranolol will cause physciological effects by themselves
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does the effect of an antagonist depend on

A
  • Depends on the level of activation of the target by the agonist which can vary with the physiological state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two main classes of antagonists

A
  • Competitive

- non competitive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are competitive antagonists

A
  • the binding of the antagonists prevents the binding of the agonists usually by comepting for the same binding site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

increasing competitive antaognist concenration..

A

right shifts the curve, decreasing binding for a fixed agonist concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the efficacy of a drug

A
  • this is a term that is used to define how well an agonist achieves a response, it can encompass a complex pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

two drugs acting on the same target can have identical affinities…

A

but very different efficacies, producing different clinical effects for the same concentrations
- therefore different drugs acting at the same receptors can be given at very different concentrations to achieve the same effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What drug target most commonly used for drugs

A

G protein coupled receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what kind of drug measures the concentration of the drug and the response in percentage

A
  • logarthmic scale
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the potency of the drug

A
  • this is the input output relationship - how much goes in and what do you get out
  • potency of a drug is often described by the concentration (or dose) that is able to elicit 50% of the maximal response (ED50)
  • a drug that has a higher potency achieves that size of response at a lower concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

A drug that has a higher potency achieves …

A

that size of response at a lower concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is a partial agonist

A
  • A partial agonist is a drug that has a lower maximal response resulting from lower efficacy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe an example of how parital agonists can be used

A
  • Many of the beta blockers are actual partial agonist
  • this property means that they can compete with endogenous full agonists blocking their effect but nevertheless partially stimulating the receptors to avoid the symptoms that can arise from complete loss of receptor stimulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are allosteric modulators

A
  • The bind to proteins at sites other than the binding site for the principal agonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do allosteric modulators work

A
  • Alter the affinity of binding site for its agonists
  • change the efficacy of the response when the agonists binds

Action can be:

  • positive (to increase the potency of the agonists)
  • negative (to decrease the potency of an agonist)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is advatnages for allosteric modulators

A
  • they dont directly activate (or inactivate) cell signalling but rather they change the set-point for normal activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Members of the same drug class can have…

A

Different potencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is desensitisation

A

This it the process that diminishes a response by a drug after repeated exposure to it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Drugs can have longer term effects…

A
  • that are different from their initial action at receptors which can result in altered levels of the drug or its target thereby changing its potency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Describe how patches cause plasma concentration

A
  • patches - supply a relatively steady, sustained rate of nicotine delivery
  • a fall is ot predicted to occur during a constant rate of drug delivery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

agonists can differ in their efficacy …

A

even if they have the same receptor affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

peripheral desensitisation to the effect of drugs…

A

does not require that the activity of the receptors change
- there are other ways that the response can desensitise such as the adaptation of hte intracellular second messenger pathways or changes outside

32
Q

What is tolerance

A

Tolerance is a person’s diminished response to a drug, which occurs when the drug is used repeatedly and the body adapts to the continued presence of the drug.

33
Q

What is tachyphylaxis

A
  • this is a general term that describes a decline in the response to repeated doses of an agonist but doesnt imply a particular mechanisms
34
Q

How is tolerance associated with the long term use of opioid drugs

A
  • Tolerance associated with the long term use of opioid drugs is a biochemical response that involves increased production of mediators in the pathway affected by the drug
35
Q

Name two drugs from the same drug class that have different lipid solubility

A
  • Simvastatin = lipophilic

- Pravastatin = Hydrophilic

36
Q

describe how the chemical structure of drugs in the same class can have a major effect on how they are metabolised and excreted

A
  • for example not all statins are metabolised by the cytochrome P450 enzyme system in the liver therefore drug interactions can be different for different statins
37
Q

What are the two main types of ion channels

A
  • voltage dependent

- ligand gated

38
Q

describe voltage dependent ion channels

A
  • enable a cell to be excitable and to generate action potentials
  • named according to what ion they conduct
  • open in response to depolariation of the cell membrane
39
Q

What is the pore forming subunit in voltage dependent ion channels

A
  • the pore forming subunit is called the alpha subunit
40
Q

Describe the structure of calcium voltage dependent ion channels

A
  • 10 different alpha subunit genes
41
Q

Describe the structure of potassium voltage dependent ion channels

A
  • 40 different alpha subunits and because the channel is assembled from 4 subunits different subunits can form channels with different properties producing complexcity
  • very few drugs that target this channel type
42
Q

Describe the structure of sodium voltage dependent ion channels

A
  • 9 different alpha subunit genes

- targeting sodium channels is clearly important for local anaesthetics, antidysrhythmic and antiepileptic agents

43
Q

What do calcium voltage dependent calcium channels do

A
  • in neurones they are invovled in the release of neurotransmitter at a synapse
  • in smooth and cardiac muscle cells, the increase in intracellular caclium leads to contraction
44
Q

What calcium channel is targeted in cardiac and vascular smooth muscle

A
  • L type channel
45
Q

Name dihydropyridine calcium channel blockers

A
  • Nifedipine

- amlodipine

46
Q

What are dihydropyridine calcium channels blockers use for

A
  • vasodilators and are prescribed for the treatment of hypertension adn prophylaxis of angina
47
Q

What part of the calcium channel do dihydropyridine calcium channel blockers bind to

A
  • bind to the alpha subunit of L type calcium channels, reducing calcium channel opening
  • lowering intracellular caclium leads to relaxation of smooth muscle and vasodilation
48
Q

Where is the Cav1.2 variant expressed

A
  • It is exporessed in both vascular smooth muscle and cardiac muscle but there are molecular differences
49
Q

What part of the calcium channel does verapamil and dilitiazem bind to

A
  • Bind to the L type calcium channels, but these drugs act on the Cav1.2 splice variant expressed in cardiac muscle
  • thereofre it has a more ionotropic effect on the heart and is useful for the treatment of angina
50
Q

Name some monoamine transporter molecules at the synapse

A
  • Noradrenaline
  • 5-HT
  • dopamine
51
Q

Each monamine has there own …

A

transporter

  • DAT (dopamine)
  • NET (nroadrenaline)
  • SERT (serotonin)
52
Q

What inhibits NET and DAT

A
  • cocaine
53
Q

What activates NET, DAT, SERT

A
  • amphetamines are actually substrates for all three transporters
  • cause the release of monoamines at the synapse
54
Q

What drug is more selective for SERT

A
  • Ecstasy (MDMA)
55
Q

What are the euphoric effects of the drugs of abuse

A
  • they are due to the increased levels of doapmine at the synapse
56
Q

Why dont antidepressants lead to abuse

A
  • many antidepressant drugs inhibit the transporters (tricyclics, selective serotonin reuptake inhibitors) but they have little abuse potential probably because they have little effect on DAT
57
Q

what does methylphenidate inhibits

A
  • inhibits both DAT and NET

- used for the treatment of narcolepsy and attent deficit hyperactivity disorder

58
Q

What is the drug modafinil used for

A

= has some amphetamine like effects
- thought to act on mnay targets including DAT and has been used for the treatment of narcolepsy and other sleep disorders but its use is not widespread

59
Q

Describe the mechanism of action of TCAs

A
  • inhibit both NET and SERT
  • side effects of the TCAs can result from antagonism of muscarinic ACh receptors causing cardiac dysrhythmias, dry mouth, blurred vision and constipation
60
Q

Describe the mechanism of action of SNRIs

A
  • Venlafaxine
  • non selective for NET and SERT
  • do not have antimuscarinic effects
61
Q

Describe SSRIs

A
  • most commonly prescribed antidepressant in the UK -

- effectivness in itreating moderate depression is not different from TCAs but they do not have antimuscarinic effects

62
Q

What are the types of enzyme inhibition

A
  • Competitive = the drug binds to the same site on the enzyme as the substrate
  • Non-competitive - the drug-bound enzyme can still bind the substrate

can also be

  • Reversible
  • Irreversible - causing permanent loss of function
63
Q

Describe the mechanism of action of aspirin

A
  • irreversible, non competitive inhibitor of COX
  • COX is an important enzyme involved in the formation of prostaglandins and thromboxanes which are important mediators of the inflammatory response
64
Q

Describe the mechanism of action of captopril

A
  • reversible
  • competitive inhibitor of ACE
  • prevents the formation of angiotensin II, this acts to retain fluid and cause vasoconstriction
  • example of rational drug desgin where the drug has a similar chemical structure ot that part of the normal substrate that binds to the enzyme
65
Q

describe the different areas that enzymes can be affected by drugs in

A
  • Intracellular - e.g. COX usually requiring that the drugs are lipid soluble
  • Extracellular such as ACE - enzyme can be membrane bound or fully extracellular
66
Q

some drugs require…

A

enzyme action for their activity
- for example zidovudine (AZT) and other nucleoside reverse transcriptase inhibitors must be activated by host cell kinases to produce the triphosphate form

67
Q

How else can enzymes be used with drugs

A
  • antoher therapeutic approach is to provide novel enzyme susbtrates for the correction of faulty metabolic pathways
  • for example in dopamine beta hydroxylase deficiency the faulty synthesis of noradrenaline can be corrected by supplying a synthetic substrate for a different enzyme giving dihydroxyphenylserine (L-DOPS) which increases noradrenaline synthesis wihtout the need for the dopamine beta-hydroxylase enzyme
68
Q

How do statins reduce the risk of heart attacks and strokes

A
  • they reduce the risk by reducing cholesterol levels and thereby reducing atherosclerosis and thrombus formation
69
Q

What do statins inhibit

A
  • they inhibit the enzyme HMG-CoA reductase that catalyses the rate limiting step in liver cells for synthesis of cholesterol
70
Q

When are statins more beneficial

A
  • the enzyme HMG-CoA reductase are more active at night and therefore statins with a shorter half life are most benefiical when given at bedtime
71
Q

What tool is used to assess the formal CVD risk for the primary prevention of CVD

A
  • QRISK 3
72
Q

What drugs act on receptors that are located in the nucleus

A
  • steroid hromones act on receptors that are located in the nucleus
73
Q

what drugs act on things inside the cell

A
  • lipophilic receptors
74
Q

What are the concerns regarding gene therapy

A
  • induction of immune response by viruses

- cancer caued by random insertion of a replacement genes into the genome

75
Q

Name a disease that can be targeted by monoclonal antibodies

A
  • antibody against TNF alpha can be used in rhumatoid arthritis

Year 3 - Script (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions