Brainscape's Knowledge GenomeTM

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


See full index

Drug Action > Drug Action > Flashcards

Drug Action Flashcards

0
Q

What is the difference between agonists and antagonists?

A

Agonist- Possess affinity and efficacy
Bind to a receptor and produce a response
Antagonist- possess affinity but not efficacy
Binds to a receptor but does not produce a response
Atropine blocks acetylcholine but not histamine
Mepyramine blocks histamine but not acetylcholine

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

List some drugs that work by their physiochemical properties

A 
Antacids- NaHCO3- basic
Bulk laxatives- methylcellulose- large and indigestible 
Osmotic laxatives- magnesium sulphate
Osmotic diuretics- mannitol
General anaesthetics- halothane
Alcohol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the Emax and EC50?

A

Emax is the saturation dose

EC50 is halfway to Emax- 50% response

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

What is the response equation?

A

P=bound receptors/total receptors= [drug]/(Kd+[drug]

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

Name some potential drug receptors

A

Enzymes- COX- aspirin
Ion channels- Ca channels blocked by nifedipine
Transporters- noradrenaline transporters blocked by cocaine
(Not meant to be bound to- no real agonists or antagonists)
Physiological receptors

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

Name the receptor superfamilies

A 
Integral ion channels- ligand gated
Nicotinic or glycine receptors
Integral tyrosine kinases- enzymes
Insulin receptors
Steroid receptors- inside the cell
Oestrogen receptor 
G protein coupled receptors- has no direct action- actives a G protein
Muscarinic or adrenoreceptors
Cytokines receptors- enzyme free in the cytosol
Prolactin and growth hormone receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the difference between the concept of spare receptors and partial agonists?

A

Spare receptors- highly efficacious agonists can produce a max response without binding to all the receptors
Partial agonists- low efficacy agonists cannot produce the max response even when bound to all the available receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give an example for the allosteric effects on receptors

A

The GABA-A receptor a ligand gated Cl channel
Benzodiazepines increases the affinity for GABA on the channel
Antagonist- flumazenil- no effect
Inverse agonists- betacarbolines- less likely

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

Give some examples of competitive antagonists

A

Atropine at muscarinic receptors
Propranolol at beta-adrenoreceptors
Nalixone used in opiate overdose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Give some examples of irreversible antagonists

A

Phenoxybenzamine at alpha-adrenoreceptors and decreases max response

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

Give examples of allosteric antagonists

A

Gallamine at the muscarinic receptor
Betacarbolines at the GABA-A receptor
Bind reversibly and decrease agonist affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name a channel blocker

A

Phencyclidine at the NMDA receptor

Binds inside the channel to block ions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is an example of a ‘physiological antagonist’?

A

Acetylcholine and adrenaline

Both agonists at their own receptors but produce opposite effects

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

Describe the phenomenon of desensitisation

A

Prolonged and repeated exposure to an agonist reduces the response to that drug
Eg tolerance to heroin- ⬆️adenyl cyclase activity in the brain in response to the decrease cAMP
Inactivation of nicotinic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the importance of ion trapping in drug delivery?

A

For weak acids and bases the degree of dissociation depends on the pH
Only the unionised form is sufficiently lipid soluble to diffuse through cell membranes
Drugs will tend to accumulate in area where ionisation is favoured

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

Name the advantages and disadvantages of drug administration routes

A

Oral- common, easy but strong acids and bases (>10 and <3 pKa)
Rectal- useful if patient is vomiting and cannot swallow but absorption is unreliable
Injections- fastest and most reliable, rate of absorption depends on the site of injection and local blood flow
Inhalation- high absorption SA that raises the chances of attentive side effects
Sublingual- absorbed directly into circulation also useful if the drug is too unstable to get to the intestine, helpful if the drug tastes nice
Topical/transdermal- local effects but most drugs are poorly absorbed through unbroken skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the factors that influence absorption?

A

Route of administration
Blood flow
Drug conc.
Drug solubility in lipids and aqueous body fluids

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

How do you calculate apparent volume of distribution?

A

Dose/plasma conc.

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

What is the basic structure of a local anaesthetic?

A

Benzene ring- linkage (amide or ester)-amine

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

List some examples of local anaesthetics, their linkage and duration

A

Procaine/cocaine-ester-short
Lidocaine-amide-medium
Prilocaine-amide-medium
Bupivacaine-amide-long

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the equilibrium of a local anaesthetic in solution

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

What does use dependent block mean in the context of local anaesthetics?

A

LA only block open voltage gated Na channels

⬆️nociceptors activity ⬆️block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does inflammation effect local anaesthetic?

A

Low pH ⬇️ the neutral form of the drug leading to poor anaesthesia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the different methods of administering local anaesthetic?

A 
1 topically
2 infiltration (surrounding the wound)
3 nerve block 
4 epidural
5 spinal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the possible unwanted effects of local anaesthetics ?

A 
Hypersensitivity to other components of the solution
Tremor, convulsions, respiratory failure
Decreased cardiac contractility
Vasodilation
⬇️blood pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What other drugs are administered with local anaesthetics?

A

Vasoconstrictors eg adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe the action of botulinum toxin

A

Has a heavy and light chain
To get into the cell and have it’s action once inside the cell
1 binds to presynaptic membrane and mediates endocytosis
2 peptidases cleave proteins involved in exocytosis (SNAP-25)
SNARE complex doesn’t work

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

Describe the action and name examples of non-depolarising neuromuscular blockers

A

Curare, pancuronim, vecuronium
Competitive antagonists at nicotinic acetylcholine receptors to decrease the end plate potential
Used as an adjunct to general anaesthetic as a muscle relaxant
Side effects include decreased blood pressure and histamine release

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

Describe the action and name an example of a depolarising neuromuscular blockers

A

Agonist at nicotinic acetylcholine receptors
Suxamethonium
1 causes end plate depolarisation
- action potential
- uncoordinated fine contractions
2 not broken down by acetylcholinesterase
- prolonged depolarisation
Type1 paralysis due to inactivation of voltage gated Na channels
Type2 desensitisation- longer action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Name the unwanted effects of depolarising blockers

A 
Bradycardia 
K release
- cardiac arrest
Increased intraocular pressure
Prolonged paralysis if there is a deficiency of plasma cholinesterase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe the action of cholinesterase inhibitors

List some examples

A

Interacts with AChE and plasma cholinesterase to prevent the breakdown of ACh
Enhances synaptic function
Affects other synapses where ACh is released
Edrophonium- ionic (minutes)
Neostigmine- covalent (hours)
Organophosphate- phosphorylation (irreversible) war gases and pesticides, reactive red by pralidoxmine

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

What are the uses of anti cholinesterase?

A

Reverses the effects of non depolarising NMJ blockers
Used at the end of an operation
⬆️ACh to compete with antagonist
Effects of depolarising blocker are made worse
️ACh acquires suxamethonium-like action
Used in the treatment of Myasthenia gravis
Edrophonium
Neostigmine
Pyridostigmine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Where are drugs metabolised and excreted?

A 
Liver- first pass metabolism 
Kidney- some enzymes but mostly excretory
Lungs
Skin
Plasma
Gut
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the difference between active and toxic metabolites?

A

Active- Pro-drugs eg cortisone, choral hydrate
Diazepam is metabolised to nordiazepam which is also active
Toxic- eg paracetamol, carcinogens- activated by metabolism to more active carcinogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe liver metabolism

A

Phase 1
Oxidation, reduction
Often introduces reactive groups- products may be more toxic
Phase 2
Conjugation- using the modification from phase 1
Products tend to be soluble and inactive
Secreted into bile and/or urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the importance of cytochrome P450?

A

Oxidise a range of drugs
Haem containing enzymes
>1 drug at a time can create competition for the active site
Substrate inhibition- phenytoin
Non-substrate inhibition- quinidine
Induction- barbiturates, rifampicin, brassica, tars

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the three processes of renal excretion that eliminate drugs?

A

Glomerular filtration- <20% passive filtration
Tubular secretion- active transport of substances into urine- unaffected by plasma binding
Two transporters- acids eg penicillin, probenicid, uric acid
Organic base eg pethidine, quinine
Reabsorption- water reabsorbed forced alkaline diuresis speeds elimination of acidic drugs- ion trapping

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Describe the process of adrenaline

A

Tyrosine➡️DOPA➡️dopamine➡️noradrenaline➡️adrenaline

  1. Tyrosine hydroxylase- rate limiting step, feed back inhibition by NAd
  2. DOPA decarboxylase
  3. Dopamine-beta-hydroxylase- inhibited by disulfiram
  4. PNMT- in A cells in the medulla
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

List some drugs that affect noradrenalin synthesis

A

Alpha-methyl tyrosine- inhibits tyrosine hydroxylase
Carbidopa- inhibits DOPA decarboxylase, works in the periphery, used in Parkinson’s disease
Methyldopa- taken up in sympathetic neurons, converted into alpha-methylnoradrenaline, acts as a ‘False transmitter’
6-OH dopamine- neurotoxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How is adrenaline and noradrenaline stored?

A

Sub cellular membrane-limited particles

Chromaffin granules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Name the transporters involved in noradrenaline storage in vesicles

A

H ATPase
VMAT (vesicular mono amine transporter) antiporter- H/dopamine
(Vesicle contains dopamine-beta-hydroxylase)
VNUT (vesicular nucleotide uptake transporter)- ATP in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Describe the autoregulation of noradrenaline release

A

Alpha-2 adrenoceptors in the presynaptic membrane which are negatively coupled to adenyl cyclase are involved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Name some mediators of noradrenaline release

A

Morphine
Acetylcholine- inhibits via muscarinic receptors
Adenosine- inhibits via (A1 receptors)
Opioids- inhibits via u-receptors
Angiotensin- facilitates release via AT1 receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Describe the neuronal uptake of catecholines

A

Secondary active transporter NET (norepinephrine transporter)
Relatively selective for noradrenaline (NAd>Ad>isoprenaline)
Co-transports Na, Cl (uses electrochemical gradient
Inhibitors- phenoxybenzamine
Desipramine- tachycardia and dysthymia
Cocaine- tachycardia, increased BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Describe the non-neuronal uptake of catecholamines

A

Low affinity for noradrenaline
Ad>NAd>isoprenaline
Inhibited by normetabephrine, steroid hormones, phenoxybenzamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Name some enzymes involved in the degradation of catecholamines

A

Monoamine oxidase (MAO)- bound to the surface of mitochondria converts catecholamines to aldehydes which are metabolised by aldehyde dehydrogenase (PNS) or aldehyde reductase (CNS)
Some antidepressants block MAO irreversibly to increase levels of NAd, dopamine and 5-HT eg phenelzine, tranylcypromine, iproniazid
Catechol-O-methyl transferase (COMP)
Converts catecholamines to methoxy derivatives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is VMA?

A

3-methoxy,4-hydroxylase mandelic acid

Final metabolite of adrenaline and noradrenaline excreted in urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

List the agonist potency order of adrenergic receptors

A

Alpha1- noradrenaline>=adrenaline&raquo_space;isoprenaline
Alpha2- adrenaline>noradrenaline»isoprenaline
Beta1- isoprenaline >noradrenaline>adrenaline
Beta2- isoprenaline>adrenaline>noradrenaline
Beta3- isoprenaline >noradrenaline=adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Describe the intracellular cascade from the alpha1 adrenoceptors

A

Coupled to a Gq protein that activates phospholipase C➡️IP3+DAG
IP3➡️IP3 receptor, Ca channel in the ER (➡️contraction in smooth muscle)
DAG➡️protein kinase C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Describe the intracellular cascade from alpha2 adrenoceptor

A

Couple to Gi protein which inhibits adenyl cyclase➡️ decreased cAMP➡️ decreased PKA activity➡️ decreased phosphorylation of certain intracellular proteins➡️ effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Describe the intracellular cascade from beta adrenoceptors

A

(All beta receptors stimulate AC)
Coupled to Ga protein➡️activates Adenyl cyclase➡️ increased cAMP➡️ increased PKA➡️ increased phosphorylation of certain intracellular proteins➡️ effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What are the functions of beta1 adrenoceptors?

A 
They are important cardiac adrenoceptors 
SA node- increased heart rate
AV node- increased conduction velocity
Atria- increased contractility 
Ventricles- increased contractility
- enhanced automaticity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are the functions of beta2 adrenoceptors?

A

Important in smooth muscle
Blood vessel dilation (alpha1+2 for constriction)
Bronchi dilation
GI tract relax (alpha1+2 contraction of sphincters)
Uterus relax (alpha1 contract)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Name a use of beta 3 adrenoceptors?

A

Adipose tissue- lipolysis and thermogenesis

Skeletal muscle- thermogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Name the selective agonists and antagonists of alpha1 receptors

A

Agonists- phenylephrine

Antagonists- prazosin and doxazosin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Name the selective agonists and antagonists of alpha2 receptors

A

Agonist- clonidine

Antagonist- yohimbine and idazoxan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Name the selective agonists and antagonists of beta1 receptors

A

Agonists- dobutamine

Antagonists- atenolol and metoprolol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Name the selective agonists and antagonists of beta2 receptors

A

Agonists- salbutamol, terbutaline and salmeterol

Antagonists- butoxamine

58
Q

Name a non selective agonist and antagonist of beta adrenoceptors

A

Agonist- isoprenaline

Antagonist- propranolol

59
Q

Name some uses for adrenoceptors agonists

A

Adrenaline- (alpha + beta) help restore cardiac rhythm & acute anaphylaxis and asthma & adjunct to local anaesthetics
Dobutamine- (beta1) cardiogenic shock
Salbutamol & Terbutaline- (beta2) asthma & delay of premature labour
Salmeterol- (beta2) asthma
Mirabegron- (beta3) prodrug for overactive bladder syndrome
Phenylephrine- (alpha1) nasal decongestion
Clonidine- (alpha2) hypertension and migraine

60
Q

Name some uses for alpha adrenoceptor antagonists

A

Hypertension- prazosin (short acting) doxazosin (long acting)
Benign prostatic hypertrophy- tamsolusin
Phaeochromacytoma- phenoxybenzamine

61
Q

Name some uses for beta adrenoceptor antagonists

A 
Cardiovascular- metoprolol and atenolol
Glaucoma- timolol
Thyrotoxicosis- pre-operatively
Anxiety States- propranolol 
Migraine prophylaxis 
Benign essential tremor
62
Q

How is the supply of choline kept at a sufficient level?

A

Choline is taken from the diet and the liver to nerve endings via high affinity carrier, Na dependent process

63
Q

How is acetylcholine synthesised?

A

Choline + acetylCoA➡️acetylcholine + CoA

Catalyses by choline acetyltransferase

64
Q

How is acetylcholine stored?

A

Energy dependent vesicular ACh transporter
Uptake mechanism is not very specific
Acetyltriethylcholine can be stored and released as a false transmitter

65
Q

Describe some of the feedback systems for cholinergic nerves

A

Muscarinic ACh receptors in the enteric nervous system inhibit ACh release
ATP is converted to adenosine which inhibits release via A1 receptors
Morphine- inhibits release via u receptor
Noradrenaline- inhibits release alpha2 adrenoceptors

66
Q

List the relative potency series of agonists for skeletal muscle and autonomic ganglia

A

Skeletal muscle
Nicotine>carbachol»DMPP»>methylcholine muscarine
Autonomic ganglia
Nicotine, DMPP>carbachol»>methacholine muscarine

67
Q

Autonomic ganglia are selectively antagonised by what?

A

Hexamethonium

68
Q

What is the mechanism of action of hexamethonium?

A

Blocks the ion channel

Use dependent block

69
Q

Which are the three most important subclasses of muscarinic receptor?

A

M1- found in stomach and salivary glands antagonist- pirenzepine
M2- found in cardiac muscle, antagonist- gall amine
M3- found in smooth muscle

70
Q

What are some clinical uses of muscarinic antagonists?

A

Asthma- iota tropism
Bradycardia- atropine
Decrease gut motility and secretions- pirenzepine

71
Q

Summarise the 3 main acetylcholine receptors

A 
Skeletal nicotinic- ligand gated, alpha1
Nicotine vs. decamethonium
Neuronal nicotinic- ligand gated, alpha2-7
DMPP vs. hexamethonium 
Muscarinic- G protein coupled, M1-5
Carbacol vs. atropine
72
Q

Name some weak base used as antacids

A

Sodium bicarbonate
Magnesium hydroxide
Aluminium hydroxide
Calcium carbonate

73
Q

Name two H2 antagonists and their action

A

Cimetidine and ranitidine
Inhibits resting and stimulated acid acid secretion
Used in peptic ulcer
Cimetidine inhibits P450

74
Q

Describe the muscarinic antagonists

A

Pirenzepine
Inhibits acid secretion at cons that do not produce marked anti-muscarinic side effects
Selective for M1 receptors

75
Q

Describe the action of omeprazole

A

Irreversibly inhibits H/K ATPase
Weak base, accumulates in the stomach, reduces acidity and increases its own absorption
Side effects- headache, diarrhoea, rashes, stomach stones and an increase in gastrin secreting cells

76
Q

Name and describe a prostaglandin analogue

A

Misoprostol
Inhibits acid (and mucous) secretion
Can be used to prevent ulcers
Side effects- diarrhoea and abortion

77
Q

Name and briefly describe the action of mucosal protectants

A

Carbenoxoline- increase secretion and salt/water retention
Sucralfate- forms a gel in acid and binds to ulcer craters and protects it
Bismuth chelate- antibacterial

78
Q

Name the H. Pylori antibacterial drugs

A

Amoxicillin

Clarithromycin or metronidazole

79
Q

What is the action of domperidone and metoclopramide?

A

Increased ACh release this increases tone of oesophageal sphincter, speed of gastric emptying and transit through the small intestine
Used in reflux oesophagitis, nausea, delayed gastric emptying

80
Q

What are the types, and name some examples of drugs used to treat constipation?

A

Bulk laxatives- methylcellulose
Saline purgatives- magnesium sulphate, lactulose (also decreases ammonia production by bacteria)
Irritant purgatives- Senna, bisacodyl
Faecal softeners- liquid paraffin, docusate sodium

81
Q

What are the types of drugs used in diarrhoea?

A

Oral rehydration therapy
Absorbents- kaolin, methylcellulose
Opiates
Antispasmodics- antimuscarinics, peppermint oil, mebeverine
Anti-inflammatory- steroids, mesalazine
Drugs which inhibit secretion- enkephalinase inhibitor

82
Q

What is the clinical significance of ️glucose-6-phosphate deficiency?

A

Is an X linked characteristic, more common in some races that confers protection against malaria
Causes haemolytic reactions to primaquine (malaria drugs)
Oxidative stress causes lysis
of RBCs

83
Q

Describe two polymorphisms in the cytochrome P450

A

CYP2D6 metabolised 25% of prescription drugs
5-10% of Caucasians have polymorphisms
-CYP2D65, entire gene deleted
-CYP2D62, multiple copies of gene
CYP3A5 75% of Caucasians and 50% blacks do not express functional enzyme with virtually no clinical significance as other enzymes are unregulated to compensate

84
Q

What are the relevant pharmacogenomics for Thiopurine S-methyl transferase?

A

Inactivates mercaptopurine and azothiaprine
Slow, intermediate and fast metabolisers
2 common SNPs associated with decreased enzyme levels that could be tested for before prescription

85
Q

What is the clinical significance of Her2?

A

Epidermal growth factor- increased cell growth
Over expressed in some forms of breadth cancer
Trastuzumab is a monoclonal antibody against Her2

86
Q

What is the clinical significance of Bcr-abl?

A

It’s an active tyrosine kinase
Keeps signalling to cells to grow in chronic myeloid leukaemia
Selectively inhibited by imatinib

87
Q

What is the clinical significance of B-raf?

A

A kinase involved in cell growth
V600E mutation leaves it permanently activated
Vemurafenib is a specific inhibitor, licensed for use in melanoma

88
Q

What is the clinical significance of hERG?

A

Encodes a cardiac K channel
Mutations with ‘long QT syndrome’
Many drugs bind to hERG and induce long QT EG. Erythromycin and terfenadine
Drugs that bind to hERG are not developed

89
Q

What is the triad of general anaesthetic?

A

Need for unconsciousness
Need for analgesia
Need for muscle relaxation

90
Q

Describe the protein theory of general anaesthetics

A

Proteins are the targets of action and lipid solubility is needed to access the binding domain
There is a cut off phenomenon; increased chain length and therefore lipid solubility only increases anaesthetic potency only up to a certain point
Plus there appears to be stereoselectivity

91
Q

What are the proposed molecular targets of general anaesthetics?

A

K channel activation ⬇️membrane excitability
Ligand gated channels excitatory
Glutamate, 5-HT, ACh inhibitory GABA-A, glycine

92
Q

What are the four stages of anaesthesia?

A
  1. Analgesia- drowsiness, reflexes intact, still conscious
  2. Delerium- excitement, deletion, loss of consciousness, unresponsive to painful stimuli, muscle rigidity, spasms, cardiac arrhythmias, vomiting, choking
  3. Surgical anaesthesia- unresponsive to pain, regular breathing, no reflexes, muscle relaxation, synchronised EEG
  4. Medullary paralysis- pupillary dilation, respiration/circulation ceases, EEG wanes➡️death
93
Q

What is the minimal alveolar concentration?

A

The concentration of anaesthetic in the alveoli required to produce immobility in 50% of patients when exposed to a noxious stimulus

94
Q

How is the MAC is related to lipid solubility?

A

The more lipid soluble the lower the MAC, the lower concentration needed to produce the anaesthetic effect

95
Q

What factors increase the speed of induction of general anaesthetic to the alveoli?

A

⬆️[anaesthetic]

⬆️rate and depth of breathing

96
Q

What are the factors involved in the transfer of general anaesthetics from the lungs to the blood?

A

Solubility in blood
(High solubility➡️blood has a large capacity ➡️more molecules needed to saturate blood and the blood needs to be saturated before it can get into the brain)
Rate of pulmonary blood flow
(High cardiac output=faster transfer)

97
Q

What are the factors that affect the transfer of general anaesthetic from blood to tissue?

A

Solubility in tissue (tissue:blood coefficient 1 in lean tissue much more than 1 in adipose-high capacity; accumulation
Tissue blood flow- high in lean tissue, low in adipose tissue

98
Q

What are the advantages and disadvantages of some general anaesthetics?

A

Halothane- potent, fairly fast; possible liver toxicity
Enflurane- less liver damage; potential seizures
Isoflurane- rapid acting, muscle relaxation; bad smell
Sevoflurane- pleasant odour, rapid recovery; metabolites could cause renal damage
Nitrous oxide- very rapid, good analgesic; low potency- normally combined with other agents

99
Q

What a possible adjuncts to general anaesthesia?

A

Premedication to decrease anxiety, pain and to induce amnesia- benzodiazepines, opioids, antimuscarinics
Muscle relaxants- benzodiazepines and neuromuscular blockers
Anti-emetics- metoclopramide

100
Q

Briefly name some corticosteriods

A 
Hydrocortisone, aldosterone
Prednisolone- anti-inflammatory
Dexamethasone- anti-inflammatory
Beclometasone- nasal spray 
Triamcinolone- injection into a joint
101
Q

What is the action of glucocorticoids?

A

Acts at nuclear receptors and effects the expression of genes involved in inflammatory and immune response with a delayed action

102
Q

What are the metabolic effects of steroids?

A 
⬆️conversion of protein into glycogen 
⬆️blood glucose
⬇️protein synthesis ⬆️breakdown
Fat redistribution
⬆️bone reabsorption
103
Q

What are the anti-inflammatory effects of steroids?

A

Suppress all phases of the inflammatory response

Decreases the production of inflammatory mediators

104
Q

Describe the production of inflammatory mediators

A

Membrane phospholipids➡️(via PLA2) arachidonic acid➡️(via COX) prostaglandins- increased expression of anti-inflammatory proteins
➡️(via LOX) leukotrienes- decreased expression of pro-inflammatory proteins

105
Q

What inhibits PLA2 in the production of inflammatory mediators ?

A

Annexin-1

106
Q

What are the immunosuppressant effects of steroids?

A

Decreased expression of genes for IL-2, TNF-alpha, TNF-gamma etc
Via inhibition of transcription factors such as AP1 and NFkappaB

107
Q

What are the uses of anti-inflammatory steroids?

A

Replacement therapy in Addison’s disease
Inflammatory disease- eczema, asthma, arthritis
Immunosuppression in organ transplantation or ⬇️lymphopoesis in some leukaemias

108
Q

What are the side effects of using steroids?

A 
Hyperglycaemia and diabetes
Muscle weakness and wasting
Central obesity
Osteoporosis
Thin skin and bruising
Increased appetite and weight gain
Mood changes
Infections
Glaucoma and cateracts
Peptic ulcers (inhibiting prostaglandin production)
Adrenal suppression and atrophy
109
Q

Where is the site of action of non-steroidal anti-inflammatory drugs?

A

Inhibit COX and therefore prostaglandin production

110
Q

What are the side effects of NSAIDs?

A

Gastric irritation and ulceration due to loss of the protective prostaglandins
“Hypersensitivity” increased leukotrienes production
Decreased renal function- trivial without an underlying problem
Prolonged gestation

111
Q

Describe aspirin

A

Irreversible COX inhibitor
Anti-platelet action
Side effects- high incidence of GI side effects
Salicylism- tinnitus, dizziness, deafness, acid-base disturbance,
Reyes disease

112
Q

Describe ibuprofen

A

Reversible COX inhibitor
Low incidence of side effects
5-15% experience GI side effects

113
Q

Describe paracetamol

A

Analgesic and anti-pyretic but not anti-inflammatory
Prevents peroxide a binding to COX competitively so under inflamed conditions the [peroxide] overwhelms the effect if paracetamol so it doesn’t work
No effect on the GI tract, acid-base balance, bleeding time or uric acid secretion

114
Q

Describe paracetamol toxicity

A

Paracetamol➡️(via conjugation) harmless
➡️(via P450) toxic
➡️via cells- cell death
➡️via glutathione- harmless

115
Q

What is the importance of COX2 inhibitors?

A

COX2 more associated with inflammation
Celecoxib
They have fewer side effects

116
Q

What is the action of osmotic diuretics?

A

Eg. Mannitol
Filtered by the glomerulus but not readily absorbed
⬆️osmolarity of tubular fluid
⬇️water reuptake
Used in acute glaucoma/eye surgery, cerebral oedema, oliguria produced by renal failure
Not on heart failure

117
Q

What is the action of loop diuretics?

A

Eg. Furosemide and ethacrynic acid
Stops the action of salt transporters in the ascending limb, reducing the salt concentration in the medulla and reducing water reabsorption
Side effects- dehydration and increased ion excretion, alkalosis and hypokalaemia
Used in heart and renal failure, hypercalcaemia/kalaemia and hypertension

118
Q

Describe the action of thiazides

A

Eg. Bendroflumethiazide
Acts in the DCT stops salt transporters
Side effects- ⬆️Mg, H, K excretion
⬇️Ca excretion
Disrupted electrical activity, kidney stones, erectile dysfunction
Used in hypertension, heart failure and oedema not used in kidney failure

119
Q

What is the action of spironolactone?

A

Potassium-sparing diuretics
Mineralocorticoid receptor anatagonist
Used in hypertension due to elevated aldosterone
Side effects- action at other steroid receptors- gynaecomastia and sexual dysfunction
Hyperkalaemia

120
Q

What is the action of amiloride/triamterene?

A

Potassium sparing diuretics
Blocks sodium channels in the collecting duct
Side effect- hyperkalaemia
Often used to counter the hypokalaemia from using thiazides

121
Q

What are the different ways of targeting viruses?

A

1 target viruses outside the cell
2 inhibition of genetic replication and integration
3 protease inhibitors

122
Q

How would you target a virus outside the host cell?

A

Vaccine
Neuraminidase- oseltamivir- Tamiflu
Breaks the sialic acid bond between the virus and the cell it was released from

123
Q

How do DNA polymerase inhibitors work to treat viruses?

A

Eg. Acyclovir used in the herpes viruses
-prodrug, an guanosine derivative with an altered ribose domain
Phosphorylated by viral thymidine kinase more than host TK➡️acyclo GTP- active form 40-100x higher in infected cells
Inhibits viral DNA polymerase and terminates viral DNA chain extension

124
Q

How do reverse transcriptase inhibitors work against viruses?

A 
Used in AIDS
Nucleoside analogues- lamivudine
Cytosine analogue
Phosphorylates to a triphosphate 
Inhibits RT and terminates viral DNA chain
Non-nucleosides- efavirenz
Denatures active site of enzyme
125
Q

How does integrase inhibition work against viruses?

A

For HIV
Raltegravir
Used in combination with nucleoside RT inhibitors
Viral DNA is incorporated into host DNA using viral integrase
Side effects- GI upset, rash and maybe hepatitis

126
Q

Describe the action of protease inhibitors

A

Used in AIDS
Eg. Saquinavir
Inhibits aspartate proteases- post translational modification of poly proteins into functional proteins by viral proteases

127
Q

What are the main forms of malaria?

A 
Pre-erythrocytic
Plasmodium falciparum- malignant malaria 
P. malariae- benign 
Exo-erythrocytic stage
P. vivax, P. ovale - benign
128
Q

List some anti-malarial drugs

A

Chloroguins- concentrated in parasite lysosomes- site of Hb metabolism
Prevents haem polymerisation
Used in chemoprophylaxis and in the acute phase of gametogenesis in erythrocytes
Quinine- same as chloroquine
Also used in the acute phase- used for P. falciparum
Artemisinin- activated by haem to form free radicals that bond to and modify proteins damaging the membrane- used in the acute phase
Primaquine- disrupts mitochondria and decreases pyrimidine synthesis
Used in liver for Exo-erythrocytic P. vivax and ovale
And used to prevent transmission

129
Q

What is the action of two drugs in bacteria folate metabolism and utilisation?

A

Bacteriostatic
Sulphonamides- competitive inhibit dihydrofolate synthase turns PABA➡️folate
Trimethoprim- inhibits dihydrofolate reductase turns folate into tetrahydrofolate which is necessary for DNA synthesis

130
Q

List antibiotics that inhibit peptidoglycan synthesis

A 
Penicillins
Cephalosporins
Cyclase run
Vancomycin
Bacitracin
131
Q

List antibiotics that increase the permeability of the cytoplasmic membrane

A

Polymixin B

Gramicidin

132
Q

List antibiotics that inhibit protein synthesis

A

Tetracyclins; competitive with tRNA for the A site in ribosomes- selective uptake into prokaryotes
Aminoglycosides- (streptomycin) anticodon recognition- misreading the message
Erythromycin- inhibition of translation

133
Q

Give examples of antibiotics that inhibit nucleic acid synthesis

A

Inhibiting DNA or RNA polymerase Rifampicin- TB
Inhibiting DNA gyrase
Quinolones- gram -ve infections

134
Q

What is the action of metronidazole?

A

Interferes with energy metabolism
Effective against anaerobic bacteria and Protozoa
Cytotoxic products destroy the cell

135
Q

What are the common side effects of anticancer drugs?

A 
bone marrow suppression 
Impaired wound healing
GI tract damage
Sterility
Hair loss
136
Q

Describe the action of cyclophosphamide

A

Alkylating agents
Binds irreversibly to both strands of DNA and prevents replication
Prodrug activated by P450
Side effects- nausea, vomiting, bone marrow suppression, harmorrhagic cystitis due to acrolein (mesna inactivates this)

137
Q

Describe the action of bleomycin

A

Cytotoxic antibiotics
Breaks up the DNA chains
Most effective in G2, will also work in non-dividing cells
Side effects- little bone marrow suppression
Pulmonary fibrosis
Allergies
Hyperpyrexia

138
Q

Describe vincristine and vinblastine

A

Inhibits tubulin polymerisation
Arrests cell division in metaphase
Also affects other cell functions
Side effects- relatively non-toxic
Vincristine- little myelosuppression but neurotoxicity is common
Vinblastine- less neurotoxicity but causes leukopenia

139
Q

Describe the action of methotrexate

A

Antimetabolites- inhibits mammalian dihydrofolate reductase
Decreases tetrahydrofolate production and thymidylate synthesis for DNA production
Side effects- bone marrow suppression
High doses- nephrotoxicity
Rescue with folinic acid to help with recovery

140
Q

How can you control the side effects of anticancer drugs?

A 
Drug combinations given intermittently 
Anti emetics- ondansetron 
Chilled skull caps
Harvesting bone marrow- haemopoetic factors
Management of infections
141
Q

Briefly describe anticancer drug resistance

A

P-glycoprotein- membrane transporter

Hydrophobic ‘Hoover’- drugs at often hydrophobic

142
Q

List some anti-fungal drugs

A

Nystatin- binds to ergosterole and creates holes in the cell membrane- cation leakage
Amphotericin- similar method as nystatin -anion influx
Ketoconazole- inhibits fungal cytochrome P450- lagosterole to ergosterole

143
Q

What are the different mechanisms of drug resistance?

A

Develop a method of drug resistance- beta-lactamase production
Expression of drug transporters- MDR family
Alter target- PBP polymorphism in MRSA
Alter metabolic pathway- PABA in folate metabolism
Decreased drug permeability- spore formation in fungi

Drug Action (1 decks)

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