12)- Pharmacology Flashcards
(83 cards)
1
Q
What are agonists
A
Drugs that activate receptors and causes biological response
2
Q
What are antagonists
A
Drugs that block receptors
3
Q
What are the different types of drug targets
A
Agonists, antagonists, interact with ion channels, activate enzymes, inhibit enzymes, inhibit transporters / pumps, interact with DNA
4
Q
Characteristic feature of a non competitive agonist
A
Decrease in maximum response
5
Q
Define affinity
A
Ability of drug to bind to receptor
6
Q
Define efficacy
A
The ability of a drug, once bound, to activate the receptor by a conformational change
7
Q
What is Kd
A
Concentration of drug needed to occupy 50% of receptors
8
Q
4 main classes of receptor
A
Ligand gated ion channels
G protein coupled receptors
Receptor tyrosine kinases
Nuclear receptors
9
Q
What is the difference between affinity, efficacy and potency
A
Affinity is the ability of a drug to bind to its receptor (KD)
Efficacy is the intrinsic ability of a drug to activate its receptor once bound
Potency is an empirical measure of the concentration- dependence of drug response.
10
Q
What are partial agonists
A
They cannot elicit the maximal possible receptor response even when all receptors are occupied because they have lower efficacy
11
Q
What is pain for
A
Tissue protection
Alerting the organism to potentially fatal or serious tissue damage
Genetic mutation can result in inability to detect pain which has major consequences
12
Q
What can dysfunction of sensory transduction produce
A
Loss of sensation (loss of function)
Acute pain
Chronic pain (phantom limb pain)
13
Q
6 sensory systems
A
1) visual
2) auditory
3) vestibular (balance)
4) olfactory (smell)
5) gustatory (taste)
6) somatosensory
14
Q
What is modality
A
Receptors respond to specific ‘energy’ or modality
- electromagnetic spectrum eg light, thermal
- mechanical eg vibration, pressure
- chemical eg pheromones
15
Q
Properties of receptor potential for sensory neurones
A
- transduction event occurs at naked nerve terminal
- always involved changes in ion channel activity
- receptor potential also called the generator potential
16
Q
How do we detect pain / water getting hotter
A
By AP frequency increasing (not amplitude)
17
Q
What is sensitivity
A
Ability to encode and detect a wide range of stimuli strengths (high sensitivity )
- max AP freq limited by refractory period (3ms, maximum at best 1ms)
18
Q
How is sensitivity increased
A
- use neurons with different AP thresholds
- low threshold (merkel discs) respond to light touch
- intermediate threshold (pacinian corpuscle) vibration
- high threshold (ruffini corpuscle) respond to pressure
- highest threshold nociceptors (pain) respond to hard knock
Population encoding (range fractionation) : use a larger number of. neurons to detect small stimuli. Grater chance of detection of small stimuli, larger stimuli excite more neurones
19
Q
How do we detect stronger stimuli
A
Sensory adaptation process
20
Q
What do pain nerve fibres respond to
A
Noxious stimuli:
- stimuli above normal range
- stimuli capable of causing damage
- withdrawal and aversion behaviour
21
Q
What is the process of nociception
A
Encoding and processing of noxious stimuli
22
Q
Structure of pain nerve fibres
A
Myelinated A
- fast sharp, pricking acute pain
- mainly mechanical
Unmyelinated C fibres
- slow, dull ache
- polymodal eg mechanical, thermal
23
Q
Difference between TRPV1s and meissners corpuscles
A
TRPV1s is associated with burning and heat
Meissners corpuscles are asssocited with tingling and numbness
24
Q
What do local anaesthetics do
A
- block nervous conduction at the level of the AP
- unmyelinated > small myelinated > large myelinated (pain blocked first)
Block voltage gated Na+ channels
- act internally at inner face of channel
- block AP conduction
Ionised at physiological pH
- polar molecules are membrane impermeable : action is pH dependent
Used mainly:
- dental
- minor surgery
- injection sites
- mild inflammatory pain eg teething gel
25
Examples of local anaesthetics
Weak bases in acidic solutions eg lidocaine, prilocaine, cocaine
They act on the internal side of voltage- gated Na+ channels (they access the cytosol by being packaged in an acidic solution)
26
What is the autonomic nervous system
Involuntary
Functions we have no control over eg heart function, saliva secretion
Smooth and cardiac muscle
27
What is somatic nervous system
Voluntary control of skeletal muscle
28
2 divisions of the ANS
Sympathetic: stress- fight or flight
Also shuts down non essential systems: heart inotropy and chronotropy, vasoconstriction in gut, vasodilation in skeletal muscle, increases sensory awareness
Parasympathetic: rest, growth, maintenance, digestion, relaxation
29
Tissues with only sympathetic innervation
```
Adrenal medulla
Piloerector muscles (hair follicles)
Sweat glands
Spleen
Many blood vessels
```
30
Tissues with only parasympathetic innervation
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Ciliary muscle (eye)
Constrictor pupillae (eye)
```
31
Autonomic innervation of the eye
Controls pupil size
| Controls shape of the lens
32
What are radial muscles
Muscles supplied by the sympathetic ANS
| Contraction of radial muscle pulls the open increasing pupil diameter
33
What are circular muscles
Muscles supplied by the Parasympathetic NS
| Contraction of these muscles constricts the pupil, decreasing pupil diameter
34
What are parasympathomimetic drugs
Agonists of the parasympathetic systems eg pilocarpine and physostigmine
Effects:
- miosis: constriction of the pupil
- decrease in near point (able to focus on near objects)
- decrease in intraocular pressure
35
What are parasympatholytic drugs
```
Blockers of parasympathetic systems eg muscarinic receptor antagonists
Effects:
- mydriasis (dilation of pupil)
- cycloplegia (loss of accommodation)
- increased IOP
```
36
What are the 4 subtypes of the adrenoreceptors
- a1, a2, B1, B2
37
What is the location, effect and endogenous ligands associated with the a1 adrenoreceptor subtype
Location: smooth muscle, arteries and veins and anal sphincter bladder
Effect: contraction
Endogenous ligand: noradrenaline: postganglionic sympathetic nerves
38
What is the location, effect and endogenous ligand of the a2 adrenoreceptor subtype
Location: sympathetic nerves varicosities, CNS
Effect: inhibition of noradrenaline release in sympathetic nerves and inhibition of sympathetic nervous system in CNS
Endogenous ligand: noradrenaline: postganglionic sympathetic nerves, noradrenaline from central nerves
39
What is the location, effect and endogenous ligand of the B1 adrenoreceptor subtype
Location: heart
Effect: increases HR, conduction, velocity and contractility
Endogenous ligand: noradrenaline: postganglionic sympathetic nerves
40
What is the location, effect and endogenous ligand of the B2 adrenoreceptor subtype
Location: smooth muscle arteries and veins
Bronchial smooth muscle
Effect: relaxation
Endogenous ligand: adrenaline: adrenal medulla
41
Therapeutic uses of directly acting sympathomimetics eg adrenaline
( cardiac arrest)
Cardiac arrest
- B1 stimulation tachycardia (inc HR) & (inc cardiac output)
- start or increase HR via stimulation of B1
- adrenaline administered intravenously, or intra cardiac
- also used to treat symptoms of sepsis and septic shock
42
Therapeutic uses of directly acting sympathomimetics eg adrenaline (anaphylactic shock- hypertensive immune response)
Symptoms due to degranulation of mast cells - histamine released
- bronchospasm (constriction of the airways by histamine)
- resp distress- death by airway obstruction
Peripheral vasodilation - hypotension: fainting and unconsciousness
Intravenous adrenaline (epipen):
- bronchodilation via B2 - restoration of airway potency
- increased heart rate & cardiac output via B1- increased blood pressure
- peripheral vasoconstriction a2 - inc blood pressure
43
Therapeutic uses of directly acting sympathomimetics eg adrenaline on bronchial asthma
- inflammation of the air passages in the lungs (airflow to lungs reduced)
- 5M people in Uk get treatement
- short term medication: dilate bronchi, mimics sympathetic bronchodilation, inhalation of B2 adrenoreceptor
44
Indirectly acting sympathomimetics: noradrenaline (NA) reuptake inhibitors
* tricyclics antidepressant (TCA): clomipramine, imipramide, amitriptyline, reboxetine: enhances function of NA and 5-HT in brain
- long term action reduced depressive disorders
* TCAs also block reuptake of NA by varicosity
- elevates and prolong NA at target receptors
- heightened sympathetic excitation
- tachycardia, vasoconstriction, hypertension
45
Indirectly acting sympathomimetics: cocaine and amphetamine
- cocaine : addictive CNS stimulates
Blocks neuronal reuptake of noradrenaline at varicosity
- elevates and prolong NA at postsynaptic receptors
- heightened sympathetic excitation : tachycardia, vasoconstriction, hypertension
Amphetamine: taken up via neuronal uptake and causes exocytotic NA
46
Use of adrenoreceptor antagonists : ischaemic heart disease and failing heart
* ischaemic heart disease:
- genetic and environment: diet, exercise, smoking, alcohol, obesity, diabetes
- atherosclerosis of coronary blood vessels
* angina : increased risk of heart attack
* aim to reduce cardiac load during heart beat
- block sympathetic tone, input, to heart
- B1 adrenoreceptors on heart -> B1 antagonist
(Propranolol, non-selective B blocked)
47
Difference between atenolol and propranolol
Propranolol is non selective so can cause bronchospasms as can affect any part of the body. Atenolol however is cardiac specific
48
Use of B adrenoreceptor antagonists: B blockers
Propranolol is also an antagonist at B2
| - B2 stimulation by salbutamol- bronchodilation
49
What happens is asthmatics take beta blockers and how can it be overcome
B blockers can be fatal in asthmatics due to bronchospasm
This can be overcome by an antagonist selective at B1 only (atenolol if essential- cardiac selective but not cardiac specific)
50
Role of parasympathetic activation
Rest and digest- wide range of physiological changes
- pupil constriction
- near point accommodation
- bronchiole constriction and secretion
- decreased HR and BP
- increased GI motility and secretions (digestion)
- contraction of bladder
- exocrine secretions (salivation and lacrimation)
51
Characteristics of muscarinic receptors
```
Activated by muscarinic not nicotine
- act via metabotropic not ionotropic events
- family of at least 3 members :
M1 brain ‘neural’
M2 heart ‘cardiac’
M3 smooth muscle / exocrine ‘glandular’
```
- utilise different 2nd messengers
- act on different effector / target proteins eg contractile proteins, ion channels
52
Describe the parasympathetic control of bladder function
1) projection fibres from thalamus (brain) deliver sensation to cerebral cortex
2) interneuron relays sensation to thalamus
3) postganglionic neuron in intramural ganglion stimulates smooth muscle tissue
53
Therapeutic uses of a muscarinic receptor antagonist (oxybutynin)
- non selective parasympatholytic or anti-muscarinic
- prevents unwanted bladder contractions
- side effects same as atropine : blurred vision, tachycardia, dry mouth
54
Opthalmic uses of a muscarinic antagonist : tropicamide
* facilitates ocular examination
| - mydriasis: relaxation of circular muscle of iris, also relaxation of ciliary muscle
55
What is the role of physostigmine
Increases miosis in the treatment of glaucoma (alternative to pilocarpine)
- stimulates bladder in urinary retention
- treatment of atropine poisoning
56
Define xenobiotic
Any foreign substance to our body (opposite to endobiotic)
57
Define poison
Agents that produce toxicity or even death, generally at low doses
58
Define toxin.
Toxic compound produced by biological systems eg phytotoxins of plants, mycotoxins of fungi
59
Define toxic syndrome/ toxic Rome
Constellation of toxic effects comprising of a set of clinical fingerprints for a group of toxic chemicals
60
What is idiosyncratic induced liver injury
Rare adverse drug reaction
- can lead to jaundice, liver failure or death
- antimicrobials, herbal, dietary supplements are among most common therapeutic classes to cause this
- acute liver failure is rare but 13-17% of all acute liver failure cases are due to this
61
What is ED, TD and LD50
ED = effective dose
TD = toxic dose
LD = lethal dose
The ‘50’ indicates it is the case for 50% of the population eg if everyone took something that was LD50, half of them would die
62
What is IC 50
Inhibitory concentration 50
- conc necessary to inhibit 50% of a measured response in an in vitro system
- analogous to LD50 or TD50 in animal testing but allows comparison
63
What is threshold dose
The point at which toxicity first appears - highest conc behind which adverse effects are witnessed
64
What is NOAEL
No observed adverse effect level
65
What is LOAEL
Lowest observed adverse effect level (lowest conc or amount of substance that causes an adverse effect)n
66
What are toxicokinetics
Considers at what rate the chemical enters the body, what storage and metabolism ensues and subsequent excretion
67
What is pharmacokinetics
The time course of a drug from absorption to elimination.
Determine the drug regimen for a drug:
- dose
- how often
68
What does ADME stand for
Absorption
Distribution
Metabolism
Excretion
69
Drug route abbreviations
```
Po: oral
Im: intramuscular
Iv: intravenous
Sc: subcutaneous
Neb: nebuliser
```
70
Why is less drug absorbed by oral than IV
IV all goes into body whereas oral some stomach acid could digest it, GI tract absorption can be incomplete, liver can break it down before proper circulation
71
What is bioavailability
Fraction of drug administered that gets into circulation (IV, IM and sub is almost 100%, oral can be anywhere between 1-99%) also can vary between patients eg if they’ve eaten recently
72
Some other routes of administration
Topical:
- eye drops
- nasal sprays
- creams
Transdermal:
-patches
Inhalation:
- asthma drugs
- general anaesthetics
Rectal
Sublingual:
- glycerol trinitrate spray
73
Difference between zero order and first order
First order is dependent on conc of drug, zero order is not conc dependent
Zero order processes occur when the system is saturated
74
What is a salt factor (S factor)
Proportion of medicine which is the active drug
75
What is volume of distribution
The apparent volume in which a drug is dissolved in the body
76
How do you calculate volume of distribution (Vd)
Vd = amount in body / conc =
| Dose / conc at t=0
77
What is clearance
The volume of plasma cleared of a drug in unit time
Clearance = renal clearance + hepatic clearance
78
First order kinetics
Rate of elimination is proportional to conc of drug
Ct = C0e-kt
```
Where Ct = conc at t=t
C0 = conc at t=0
K = rate constant (per min or hour)
-t= time
-e= 2.718
```
79
Rate constant equations
K is fraction eliminated per unit time
Eg is k = 0.1/day then there is 10% eliminated per day
Therefore k = clearance / Vd or
CL = k x Vd
80
What is t1/2
Time for conc to decrease by 50%
So t1/2 = 0.693/k = loge 2/ k
81
Equation for working out loading dose
Loading dose = Css x Vd / F
82
What is the idea of competitive antagonism
Antagonists bind at the same site as the agonist and so reduce the action of the same agonist by competition
- antagonists lack efficacy. The competition may be overcome by increasing the conc of the agonist
83
How can anticholinesterase poisoning be treated
Use anti-muscarinic (parasympatholytic)
- decreases availability of mAChR and alleviates muscarinic symptoms
- use atropine which blocks mAChR
* dephosphorylate acetylcholinesterase
- treatment with oximes
