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Flashcards in Pharmacology Deck (94):
1

what is pharmacodynamics

what a drug does to the body
biological effect and mechanism of action

2

what is pharmacokinetics

what the body does to the drug
How the drug gets from site of insertion to various tissues - absorption, distribution, metabolism and excretion of drugs and their metabolites

3

what is an agonist

a drug that binds to a receptor to produce a cellular response

4

what is an antagonist

a drug that block the action of an agonist

5

what represents affinity

the binding step

6

what represents efficacy

the activation step

7

what is the binding step

the strength of association between ligand and receptor

8

what is the activation step

the ability of an agonist to evoke a cellular response

9

what is an agonist mechanism of action

bind to receptors to activate them
they posses both affinity and efficacy

10

what is an antagonist mechanism of action

bind to receptors but do not activate them
posses affinity but lack efficacy
block receptor activation by agonist

11

what is the relationship between agonist concentration and receptor occupancy

low conc - very low no. of receptors occupied
moderate conc - more receptors occupied
high conc - nearly all occupied
saturated - all occupied

12

what is EC50

the concentration of agonist that elicits a half maximal response

13

what is the relationship between concentration and response

sigmoidal

14

what is competitive antagonism

Binding of agonists and antagonist occur at the same (orthosteric) site

15

what is non-competitive antagonism

Agonist binds to orthosteric site and antagonist binds to separate allosteric site

16

how does competitive antagonists affect the graph

causes a parallel rightward shift of the agonist concentration response curve with no depression of the maximal response.

17

how does non-competitive antagonists affect the graph

depress the slope and maximum of the concentration response curve, but do not cause a rightward shift

18

4 possible fates of drugs in the body

Absorption
Distribution
Metabolism
Excretion

19

3 physicochemical factors controlling drug absorption

Solubility
Chemical stability
Lipid to water partition coefficient

20

how does the lipid to water partition coefficient affect absorption

rate of diffusion increases with lipid solubility

21

what is a weak acid and a weak base

weak acid - substance that donates protons
weak base - substance that accepts protons

22

what is the difference between an acid and alkaline environment

Acid environment - proton dissociates more readily replaces
Alkaline environment - proton dissociates less readily replaces

23

what does degree of ionisation depend on

pKa of the drug and local pH

24

what is the pKa

the pH at which 50% of the drug is ionised and 50% is unionised

25

what is the relationship between acidic drugs in acid environments and basic drugs in basic environments.

Acidic drugs become less ionised in an acid environment; Basic drugs become less ionised in a basic environment.

26

what is oral availability

fraction of the drug that reaches the systemic circulation after oral ingestion

27

what is systemic availability

fraction that reaches the systemic circulation after absorption

28

routes of drug administration

oral, inhalation, sublingual, subcutaneous, intravenous, rectal intramuscular

29

advantages and disadvantages of oral administration

Adv - convenient, non-sterile route, good absorption for most drugs
Disadv - inactivation of some drugs by acid/enzymes, variable absorption, first pass metabolism, GI irritation

30

advantages and disadvantages of sublingual administration

Adv - by-passes portal system and avoids first pass, avoids gastic acid
Disadv - infrequent route, few sublingual preparations available

31

advantages and disadvantages of rectal administration

Adv - as for sublingual, used for nocturnal administration of some drugs
Disadv - infrequent route, variable absorption, aesthetically unacceptable in UK

32

advantages and disadvantages of IV administration

Adv - rapid onset (emergency) route, continuous infusion, complete availability, route for drugs that cause local tissue damage
Disadv - sterile preparation required, risk of sepsis or embolism, high drug levels at the heart

33

advantages and disadvantages of subcutaneous administration

Adv - rapid onset of lipid soluble drugs, depot injection for slow prolonged release possible
Disadv - painful, tissue damage with some drugs, absorption variable

34

advantages and disadvantages of inhalational administration

Adv - lungs ideally suited due to huge surface area, good for volatile agents (anaesthetic gases), aerosols etc, ideal for local effect
Disadv - few disadvantages

35

what are the possible ways from drugs to exist in compartments and which form can move between compartments

bound or free forms
only free form can move

36

what is volume distribution (Vd)

the apparent volume in which a drug is dissolved

37

what is the equation for drug administered IV

Vd = dose/plasma concentration

38

what does Vd 15L suggest

< 5L implies that the drug is retained in the vascular compartment
< 15L suggests that the drug is restricted to extracellular water
> 15L indicates distribution throughout total body water

39

what are the two sections of the nervous system

CNS and PNS

40

what is the ANS responsible for

- regulates visceral functions that are involuntary and don't require conscious effort

41

what does the parasympathetic ANS do

coordinates the body’s basic homeostatic functions

42

what does the sympathetic ANS do

coordinated the body’s response to stress, associated with fight/flight/fright reactions.

43

what is the transmitter in the preganglionic neutrons of both parasymp and symp ANS

Acetylcholine

44

what is the postganglionic transmitter for the sympathetic division

Noradrenaline

45

what is the postganglionic transmitter for the parasympathetic division

Acetylcholine

46

what cranial nerves are responsible for parasympathetic outflow

3, 7, 9 and 10

47

how does the parasympathetic and sympathetic system affect the heart

P - decreases HR
S - increases HR and force of contraction

48

how does the parasympathetic and sympathetic system affect the lungs

P - constrict bronchi, stimulate mucus production, increases airway resistance
S - relaxes bronchi, decreases mucus production, decreases airway production

49

how does the parasympathetic and sympathetic system affect the GI tract

P - increases motility, relaxes sphincters
S - reduced motility, contracts sphincters

50

how does the parasympathetic and sympathetic system affect the skeletal muscles

P - no effect
S - relaxes in skeletal muscle

51

how does the parasympathetic and sympathetic system affect the adrenal gland

P - no effect
S - release of adrenaline from adrenal gland

52

how does the parasympathetic and sympathetic system affect the male genitals

P - erection
S - ejaculation

53

what is the overview of neurochemical transmission

1 - Uptake of precursor
2 - Synthesis of transmitter (T)
3 - Storage of transmitter (T)
4 - Depolarisation by action potential
5 - Calcium ion (2+) influx through voltage-activated Calcium 2+ ion channels
6 - Calcium 2+ ion induced release of transmitter (exocytosis)
7 - Receptor activation
8 - Enzyme-mediated inactivation of transmitter
OR
9 - Reuptake of transmitter

54

what are the two type of signals in neurochemical transmission

electrical signal from transmitter gated ion channel
biochemical signal from G protein coupled receptor

55

what is the role of action potential in chemical transmissions in ANS

travels to the presynaptic terminal of the preganalionic neuron triggering calcium 2+ion entry and the release of ACh or noradrenaline

56

what does ACh do in the sympathetic division

opens ligand-gated ion channels (nicotinic ACh receptors) in the postganglonic neurone, causing depolisation and the generation of action potentials

57

what does noradrenaline do in sympathetic division

activates G-protein-coupled adrenoceptors in the target cell membrane to cause a cellular response

58

what activates G-protein-coupled muscarinic acetylcholine receptors in parasympathetic division

ACh

59

what is the mechanism for cholinergic transmission

1- Uptake of choline via transporter
2- Synthesis of ACh via choline acetyltransferase (CAT)
3 - Storage of ACh via transporter (concentrates)
4 - Depolazization by action potential
5 - Ca2+ influx through voltage-activated Ca2+ channels
6 - Ca2+- induced release of ACh (exocytosis)
7 - Activation of ACh receptors (nicotinic or muscarinic) causing cellular response
8 - Degradation of ACh to choline and acetate by acetylcholinesterase (AChE) – terminates transmission
9 - Reuptake and reuse of choline

60

what drug blocks ganglionic transmission and what was it mechanism of action

hexamethonium
open channel block - a form of non-competitive antagonism

61

overview of cholinergic transmission at parasympathetic neuroeffector junctions

1 - Depolarization by action potential
2 - Calcium ion influx through voltage activated calcium ion channels
3 - Ca2+- induced release of ACh (exocytosis)
4 - Activation of muscarinic ACh receptor subtypes (M1 – M3) causing cellular response (tissue dependent)
5 - Degradation of ACh to choline and acetate by acetylcholinesterase (AChE) – terminates transmission
6 - Reuptake and reuse of choline

62

what are the G-protein Coupled Muscarinic ACh Receptor Subtypes at Parasympathetic Neuroeffector Junctions

M1 Gq - stimulation of phospholipase C (increase in acid secretion in the stomach)
M2 Gi (i-inhibitor) - cause the inhibition of adenylyl cyclase; opening of potassium ion channels (decreases heart rate)
M3 Gq - causes the stimulation of phospholipase C (increased saliva secretion and contraction on bronchi smooth muscle)

63

Overview Noradrenergic Transmission at Sympathetic Neuroeffector Junctions

1 - Synthesis of NA
2 - Storage of NA by transporter
3 - Depolarization by action potential
4 - Ca2+ influx through voltage-activated Ca2+ channels
5 - Ca2+-induced release of NA
6 - Activation of adrenoceptor subtypes causing cellular response (tissue dependent)
7 - Reuptake of NA by transporters uptake 1 (U1) and uptake 2 (U2)
8 - Metabolism of NA by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)

64

what does noradrenalin bind to

adrenoreceptors

65

G-Protein Coupled Adrenoceptor Subtypes at Sympathetic Neuroeffector junctions

beta1 Gs (stimulatory)
beta2 Gs
alpha1 Gq
alpha2 Gi

66

what does beta1 Gs (stimulatory) do

causes stimulation of adenylyl cyclase. Increases rate and force of heart rate.

67

what does beta2 Gs do

causes stimulation of adenylyl cylase. Relaxation of bronchial and vascular smooth muscle.

68

what does alpha1 Gq do

causes Stimulation of phospholipase C. Leads to contraction of vascular smooth muscle (increases blood pressure)

69

what does alpha2 Gi do

inhibition of adenylyl cyclase. Leads to inhibition of NA release.

70

how do agonist and antagonist affect release of neurotransmitter

Presynaptic autoreceptors mediate negative feedback inhibition of transmitter release. Agonists decrease release, antagonists increase release.

71

how does cocaine affect the ANS

Blocks U1, increases conc of NA resulting in increased adrenoceptor stimulation

Causes vasoconstriction [α1 stimulation] and cardiac arrhythmias [β1 stimulation]

72

how does amphetamine affect the ANS

Substrate for U1, inhibits MAO, displaces noradrenaline into the cytoplasm.
Noradrenaline accumulates causing increased adrenoceptor stimulation.

73

how does prazosin affect the ANS

Selective, competitive, antagonist of α1. Vasodilator used as an anti-hypertensive agent.

74

how does atenolol affect the ANS

Selective, competitive, antagonist of β1. Used as an anti-anginal and anti-hypertensive agent

75

how does salbutamol affect the ANS

Selective agonist at β2. Used as a bronchodilator in asthma

76

how does atropine affect the ANS

Competitive antagonist of muscarinic ACh receptors, does not block nicotinic ACh receptors.
Blocks all muscarinic ACh receptors with equal affinity (1, 2, 3)
Used to reverse bradycardia following MI

77

what is the minimum effective concentration

drug must reach a critical concentration in the plasma to give the affect we want

78

what is the maximum effective concentration

the level where the drug starts to give unwanted (toxic) effects

79

what is the therapeutic ratio

TR = MTC/MEC

80

what is Kabs and Ket

Kabs - the rate the drug is added to the compartment
Ket - the rate the drug is eliminated from the body

81

what is first order kinetics

where the rate of elimination is directly proportional to drug concentration

82

what does doubling the dose of the drug do

prolong the duration of its action by one more half life.

83

what is the clearance rate

the volume of plasma cleared of drug in unit time - a constant that relates the rate of elimination to plasma concentration

84

when does the rate of drug administration = rate of drug elimination

at steady state

85

what is the volume of distribution

the volume into which a drug appears to be distributed with a concentration equal to that of the plasma

86

what is a loading dose

initial higher dose of a drug given at the beginning of a course of treatment before stepping down to a lower maintenance dose

87

why is a loading dose employed

to decrease time to steady state for drugs with long half lives (e.g. digoxin, phenytoin)

88

how do we estimate loading dose

by the Vd of the drug

89

what is the half life (t1/2)

The time for the concentration of drug in plasma (or the amount of drug in the body) to halve

90

what is the half life dependant on

Vd and Cl

91

what does voltage-activated sodium channels cause

depolarising

92

what does voltage-activated potassium channels cause

hyperpolarising and repolarisating

93

what is the cycle for self-reinforcing sodium channels

1 - increase in sodium ion conductance
2 - inward sodium ion current
3 - depolarisation
repeat

94

what is the cycle for self-limiting potassium channels

1 - depolarisation
2 - increase in potassium conductance
3 - outward potassium current
4 - repolarisation