Pharmacology Flashcards
1
Q
Name the structures of the blood brain barrier
A
- astrocyte end feet
- tight junctions
- adherens junctions
- pericytes
- endothelial cell
2
Q
Which areas of the brain are not enclosed by the blood brain barrier
A
- Vascular organ of the Lamina terminalis
- pineal gland
- subfornical organ
- medial eminence and posterior pituitary
- area postrema
3
Q
Name a drug that competes with choline re-uptake in presynaptic neurones thus inhibiting synthesis of ACh
A
Hemicholinium
4
Q
Which drug breaks down SNARE proteins and prevents release of acetylcholine?
A
Botulinum toxin
5
Q
Name a toxin that promotes exocytosis/release of ACh resulting in depletion of it
A
Black widow spider (alpha latrotoxin)
6
Q
What is the action of tubocurarine ?
A
tubocurarine
Prevents access of ACh to its Nm receptor thus preventing depolarisation of the motor end plate
7
Q
Name an example of a depolarising neuromuscular blocking drug
A
suxamethonium
Causes excessive depolarisation of the motor end plate due to excessive stimulation of Nm receptor
8
Q
which drug reverses the effects of tubocurarine?
A
pyridostigmine
9
Q
how is tubocurarine administered?
A
intravenously
10
Q
what are the advantages and disadvantages of intravenous administration?
A
advantages:
- rapid onset
- instant plasma peak concentration
- can be stopped or adjusted if necessary
- all dose enters systemic circulation
disadvantages:
- skills needed/training
- sterile equipment necessary
11
Q
name something that is administered subcutaneously ?
A
insulin
12
Q
what is the difference between subcutaneous and intramuscular administration?
A
subcutaneous is under the skin whereas intramuscular is in the muscle.
generally intramuscular is faster due to a greater blood supply.
13
Q
which administration routes avoid first pass metabolism?
A
buccal/sublingual
transdermal
intramuscular
inhalation
14
Q
when is a drug administered rectally?
A
when person cannot swallow the drug due to vomiting or in children suffering from epilepsy and intravenous cannot be used.
15
Q
which drug is not administered rectally?
a) diazepam
b) aminophyline
c) indomethacin
d) hyoscine
e) prochlorperazine
A
d) hyoscine
16
Q
give an example of a drug inhaled
A
salbutamol or halothane
17
Q
list advantages and disadvantages of oral administration
A
advantages:
- easy
- no sterile preparations
- no special skills
- convenient, generally accepted by patients
disadvantages:
- not all drugs can be given this way
- goes through first pass metabolism
- has to withstand stomach acid
- withstand enzymes
- has to be lipophilic to be absorbed well
18
Q
give an example of a drug administered siblingually
A
trinitrin
19
Q
what is Evans blue?
A
evans blue is a dye that binds strongly to albumin and is used to determine the plasma volume
20
Q
what does a low volume of distribution of a drug suggest?
A
low Vd = high plasma concentration = low dose needed
21
Q
true or false;
CNS drugs have high volume of distribution
A
true
22
Q
what does a apparent high volume of distribution suggest?
A
Vd greater than total body water amount suggests that the drug is highly lipophilic and has distributed into the extravascular spaces
23
Q
what are the two phases of drug metabolisation?
A
phase 1: ‘functionalisation’
- involves, oxidation, reduction or hydrolysis of the drug to produce a more polar molecule
phase 2: ‘conjugation’
- involves joining of the phase 1 product to another substance such as glucuronic acid producing a more soluble product more easily excreted in the urine.
24
Q
what factors determine the concentration of the drug in plasma?
A
absorption distribution metabolism excretion rate of elimination
25
when does a drug dose reach 'steady state'?
when the concentration of drug administered is equal to concentration of drug being eliminated
26
what methods are used to administer drugs to reach steady state?
-loading dose
(a large amount is given, which then lowers to the required concentration)
-multiple dosing
(added to reach therapeutic window)
27
describe the differences between long and short half-life drugs in multiple dosing
long half life: - small fluctuations
- easy to maintain within therapeutic window
- takes longer to reach steady state
short half life: - large fluctuations
- difficult to maintain within therapeutic window
- rapid onset EG MORPHINE
28
why are somatic motor reflexes faster than autonomic reflexes?
somatic motor neurones are myelinated whereas the post ganglionic motor neurones of ANS are non myelinated
29
which division of the ANS is related with the cranio-sacral outflow?
parasympathetic
cranial nerves 3 (oculomotor), 7 (facial), 9 (glossopharyngeal) and 10 (vagus)
sacral nerves S1-S3
30
what are the anatomical differences between symp and parasymp divisions?
parasympathetic:
long preganglionic fibres + short postganglionic fibres
their autonomic ganglia are located nearer the target organs
release of Ach from post ganglion
fewer branches
sympathetic:
short preganglionic + long postganglionic
release of NA from postganglion
many branches
31
what neurotransmitter do the preganglionic neurones in the ANS release?
Ach
32
name an organ with dual innervation from both para and symp NS which have antagonistic control
the heart
sympathetic NS : releases NA = increase HR
parasympathetic NS: release of Ach = decrease HR
33
what is the enteric nervous system?
the plexus of nerves controlling the GIT
34
how is acetylcholine synthesised?
acetyl Co A and choline join together. catalysed by acetyl choline transferase
35
what is pseudocholinesterase?
enzyme in plasma made by liver that breaks down Ach but much more slowly
36
how is Ach broken down?
by acetylcholinesterase
enzyme has two sites on active site: anionic site (-ve) and ester site that has a serine protein (OH group)
attracts the positive choline and acetic acid (hydrogen bond)
37
name an irreversible acetylcholinesterase inhibitor
dyflos
38
name a reversible antagonist of AchE
neostigmine
| physostigmine
39
what are the receptors that Ach can bind to and what are their subclasses?
nicotinic : Nm= skeletal muscles
Nn= neuronal type
muscarinic :
M1 - Gq - GIT motility + acid secretions, CNS
M2 - Gi - cardiac (decrease rate and force)
M3 - Gq - smooth muscle contraction and increase gland secretions
40
which one is NOT a muscarinic antagonist?
a) hyoscine
b) ipratropium
c) pilocarpine
d) benzhexol
e) tropicamide
c) pilocarpine is an agonist
41
name a nicotinic antagonist
hexamethonium
| mecamylamine
42
list some nicotinic antagonist effects
- vasodilation
- dilation of pupils
- decreased HR
- dry mouth
- reduced sweating
- reduced GIT motility
- urinary retention
43
what are the main sympathetic ganglia ?
celiac
superior mesenteric
inferior mesenteric
inferior hypogastric
44
to which structure in the body does the sympathetic innervation not pass an autonomic ganglion?
adrenal medulla
45
list the enzymes needed in synthesis of adrenaline
tyrosine hydroxylase
dopa decarboxylase
dopamine beta decarboxylase
phentolamine N-methyltransferase
46
how is catecholamine neurotransmitter production modulated?
tyrosine hydroxylase is modulated by end product inhibition
depolarisation activates TH activity
activation of TH involves reversible phosphorylation
47
which enzyme is found in the vesicle during neurotransmitter synthesis?
a) tyrosine hydroxylase
b) dopa decarboxylase
c) dopamine beta decarboxylase
d) phentolamine N-methyltransferase
c) dopamine beta decarboxylase
48
which enzymes metabolise catecholamines?
```
monoamine oxidase (MAO)
catechol-O-methyl transferase (COMT)
```
49
name a non specific MAO inhibitor
phenelzine
50
name a MAO(B) inhibitor
selegilin - used in Parkinsonism
51
name a COMT inhibitor
tolcapone - long acting
| entacapone - short acting
52
name a 5-HT uptake blocker
fluvoxamine
53
name a NA and dopamine reuptake blocker
imipramine
54
what is the action of guanethidine?
taken up by uptake 1 =depletes NA stores in neurone
55
which drug blocks tyrosine hydroxylase?
metyrosine
56
which drug blocks uptake of dopamine into vesicles?
reserpine
57
which adrenoreceptors cause renin release from kidneys?
beta 1
58
which adrenoreceptors stimulate insulin release from pancreatic cells?
beta 2
| alpha 1 inhibit release
59
what does stimulation of beta 3 receptors cause?
lipolysis
60
in the eye what does stimulation of alpha 1 and beta 2 receptors cause?
alpha 1 = contraction of pupil
| beta 2 = relaxation for far vision
61
what effects does beta 1 and beta 2 stimulation have in the cardiac system?
beta 1 = increase HR
| beta 2 = bronchodilation
62
name a beta 2 agonist
salbutamol
63
what effects do Beta 2 stimulation have?
```
urinary bladder wall relaxation
uterus relaxation when non-pregnant
insulin release
decreased GIT motility
bronchodilation
vasodilation
```
64
name a drug used for hypotention
phenylephrine - alpha 1 agonist = vasoconstriction
65
what is the difference between alpha 1 and 2 adrenoceptors?
alpha 1: post-synaptic
Gq coupled
alpha 2: pre-synaptic
Gi coupled
66
what does beta 3 stimulation cause?
lipolysis
67
what does alpha 2 stimulation cause to pancreatic beta cells?
inhibition of insulin release
68
what does beta 1 receptor stimulation cause in the kidneys
renin release
69
which receptor stimulation causes decrease in GIT motility?
alpha 2 and beta 2
70
which receptor types in the eye control the ciliary muscle and the radial muscle?
radial : alpha 1
| ciliary : beta 2
71
which drug is a non selective beta adrenoceptor antagonist
propanolol
72
where is acetylcholinesterase found?
synaptic basal lamina of post synaptic neurone
73
which drug inhibits reuptake of choline?
hemicholinium
74
which drug prevents Ach transport into a vesicle?
vesamicol
75
what is the difference between tubocurare and suxamethonium
both are agents that prevent Ach depolarisation of the motor end plate
tubocurarine: non depolarising antagonist
flaccid paralysis
tetanus contraction is not maintained
suxamethonium: depolarising agonist
spastic paralysis
tetanus contraction sustained
76
how can you reverse the effects of tubocurarine?
neostigmine
AchE inhibitor = more Ach levels therefore more Ach competes for Nm receptor (tubocurarine is a competitive antagonist)
77
explain the mechanism of action of suxamethonium
phase 1
binds to receptor causes opening of Na+ channels = depolarisation
depolarisation does not stop
phase 2
continuous depolarisation causes desensitisation of receptor
78
can neostigmine be given to reverse the effects of suxamethonium ?
no, neostigmine is a AchE inhibitor = more Ach
suxamethonium is a depolarising agonist therefore increasing Ach levels will make it worse
the action is terminated by plasma cholinesterase (pseudocholinesterase)
79
what is a partial agonist?
only produces an effect if no full agonist is present
| if full agonist is present, acts as an antagonist
80
what are spare receptors?
if a maximal response is being elicited but not all the receptors are occupied
81
low dose of a non-competitive irreversible antagonist causes a shift in the concentration curve to the right, without changing the Emax and EC50. why?
because of spare receptors
82
what is the 'potency' and 'efficacy' of a drug?
potency is the concentration needed to produce half of the drugs maximal effects (EC50)
efficacy: the maximal effect produced once drug is bound to its receptor
83
what is the therapetuic index?
the difference between LD50 and ED50
LD50 =lethal dose
ED50= effective dose to produce 50% of maximal response
84
what is physiological antagonism?
two drugs producing opposing effects, cancelling each other out
85
what is pharmacokinetic antagonism?
one drug affecting the absorption, metabolism or excretion of another how does
86
in a dose response curve, how does addition of a competitive antagonist affect the curve?
shifts to the right without change to EC50 and Emax
| takes more [agonist] to reach Emax
87
in a dose response curve, how does the addition of a non competitive irreversible antagonist affect the curve?
small dose = shift to the right without change to EC5 or Emax
large dose: decrease in EC50 and Emax
88
why is salbutamol used in treating asthma?
salbutamol is a Beta 2 agonist.
beta 2 stimulation of lungs causes bronchodilation
it also reduces mediator release,
and reduces vascular leakage
89
which drug inhibits the enzyme 5-lipoxygenase in treatment of asthma?
zileuton
90
which drug binds to IgE on mast cells?
omalizumab
91
what is the role of sodium cromoglycate in asthma treatment?
prevents mediator release by stabilising membranes
92
which drug inhibits phospholipase A in treating asthma?
beclamethasome diproprionate
93
what causes bronchial hyperresponsiveness in asthma?
a) release of LTC4 by inflammatory cells
b) Release of LTD4 by inflammatory cells
c) release of neuropeptides by PAF
d) damage of epithelial lining by eosinophiles
d) damage of epithelial lining by eosinophiles
94
what is the action of ipratropium bromide
a) decrease cGMP
b) decrease cAMP
c) decrease PIP2 levels
d) decrease IP3
decrease PIP2
because it blocks M3 receptors that are Gq coupled
95
why is ipratropium not absorbed well?
quaternary ammonium = charged ion
96
which antimicrobial inhibits RNA polymerase?
a) Erythromycin
b) Metronidazole
c) Penicillin G
d) Rifampicin
e) Vancomycin
d) Rifampicin
97
what causes resistance to beta-lactams such as penicillin?
bacteria have enzymes called beta-lactamases that break down beta-lactum ring
98
name a compound that can inhibit beta-lactamase enzymes in bacteria
clavulanic acid
99
how can microorganisms develop resistance to antimicrobial agents?
- alter target (where drug attaches)
- alter uptake (altered entry into cell or efflux mechanism)
- drug inactivation (eg beta-lactamases)
100
what to dilution tests determine for antibiotics?
- minimum inhibitory concentration
| - minimum cidal concentration
101
which one is NOT an antifungal agent?
a) nystatin
b) amphotericin B
c) aciclovir
d) itraconazole
e) miconazole
c) aciclovir - this is an antiviral agent
102
which antibacterial agent inhibits DNA replication?
a) Erythromycin
b) Metronidazole
c) Nalidixic acid
d) Rifampicin
e) Vancomycin
c) Nalidixic acid
103
which antibacterial contain a beta-lactam ring ?
all penicillins
| and cephalosporins
104
what are the consequences of uncontrolled hypertension?
- stroke
- coronary heart disease
- cardiac failure
- progressive renal failure
- retinal vascular disease
105
what does stimulation of alpha2 adrenoceptors in the CNS cause?
decrease in sympathetic tone = vasodilation and reduction in heart rate
106
what does stmulation of beta receptors cause?
increase in blood pressure
| because increase in HR, increase renin release
107
what does production of cGMP cause in smooth muscles?
vasodilation
108
how do hydralazine and sodium nitroprusside work to reduce blood pressure?
they stimulate the production of cGMP = vasodilation
109
how do inhibitors of RAAS reduce blood pressure?
```
- reduce production of angiotensin II
=
↓ ADH secretion
↓ Na+/Cl- reabsorption
↓ aldosterone
↓ sympathetic tone
↓ vasoconstriction
```
110
which drug is not a RAAS inhibitor?
a) captopril
b) propanolol
c) atenolol
d) hydrochlorothiazide
c) losartan
d) hydrochlorothiazide
works by reducing Na+/Cl- reabsorption at the DCT and collecting duct
111
how does clonidine act to treat hypertension?
alpha 2 agonist = ↓ sympathetic tone
↓ HR
- vasodilation
112
how does propanolol act to treat hypertention?
beta receptor antagonist= ↓ renin release
| ↓ sympathetic tone
113
when does coronary perfusion occur?
at diastole
114
describe plaque formation
damage to endothelium cells causes lipids and cholesterol to accumulate at site
↓
the cholesterol oxidises
↓
inflammatory response triggered = release of cytokines from endothelial cells attract Monocytes
↓
monocytes differentiate into macrophages upon activation by oxidised cholesterol
↓
macrophages engulf the cholesterol = becoming foam cells
↓
foam cells accumulate and form plaque
↓
smooth muscle cells multiply and migrate to the plaque surface, forming a fibrous cap
115
what does atherosclerosis result in?
- development of collateral vessels
- angina (pain due to limited blood flow to cardiac muscle)
- myocardial infarction = heart attack
116
what are the types of angina?
- stable
- unstable (pre-infarction)
- variant (Prinz Metal) = spasm of coronary arteries
- intractable/refractory =persists after treatment
- silent ischemia
117
what does the work load of the heart depend on?
- preload (venous return)
- afterload (peripheral resistance)
- sympathetic stimulation
118
define heart failure
a state in which the heart cannot provide sufficient cardiac output to satisfy the metabolic needs of the body
119
list the symptoms of heart failure
- tiredness
- coughing
- swelling in ankles/legs
- swelling in abdomen
- pleural effusion (excess fluid around lungs)
- pulmonary oedema
120
what are the body's response to heart failure?
- drop in arterial pressure = baroreceptor reflex = vasocontriction
```
- ↓ blood flow to kidneys = ↑ renin production
= renin = angiotensin II
= ↑ ADH
↑ aldosterone
=(↑ water reabsorption)
```
- ↑ catecholamines in blood cause structural remodelling of the heart
- oedema
121
how does heart failure cause oedema?
decrease in cardiac output = ↓ BP
↓ blood flow to kidneys = ↑ renin release
= ↑ angiotensin II = ↑ water reabsorption = oedema
also cardiac remodelling = left ventricle hypertrophy = pulmonary oedema
122
what is the difference between GABAa and GABAb receptors?
GABAa
= ionotropic
= open Cl- channels allowing Cl- to go into cell = hyperpolarisation = no action potential
GABAb
=metabotropic (G protein coupled)
= cause K+ channels to open , K= moves out of cell = hyperpolarisation = no action potential
123
what is the mechanisms of action of benzodiazepines?
positive allosteric modulator
binds to allosteric site on GABAa receptor
increased affinity for GABA for its receptor
increased frequency of Cl- channels opening
124
what are benzodiazepines used for ?
muscle relaxant
anxiolytic
sedative
anticonvulsant
125
how are most benzodiazepines excreted?
in the urine as glucuronides or oxidised metabolites
126
which drug antagonises the effects of benzodiazepines?
a) triazolam
b) chlordiazepoxide
c) flumazenil
d) flurazepam
e) temazepam
c) flumazenil
127
what are the two steps that drugs undergo during metabolism?
- hydroxylation
| - conjugation (usually with glucaronic acid to make it more polar)
128
which part of the brain do benzodiazepines work on?
limbic system
129
which dopaminergic pathway is associated with positive symptoms of schizophrenia?
mesolimbic pathway
130
which dopaminergic pathway is associated with negative symptoms of schizophrenia?
mesocortical
131
name some of the positive symptoms of schizophrenia
- hallucination
- delusions
- disorganised thoughts + speech
132
list some of the negative symptoms of schizophrenia
blunt emotions
poor focus
loss of pleasure
social withdrawal
133
why does chlorpomazepine cause extra pyramidal side effects?
it is a neuroleptic that blocks D2 receptors which means theres a block in the nigrostriatal pathway and so the decreased dopamine stimulus to the striatum increases Ach release causing n increase of stimulation of extra pyramidal tracts
