Brainscape's Knowledge GenomeTM

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


See full index

Year 2 LCRS > Pharmacology 1 > Flashcards

Pharmacology 1 Flashcards

1
Q

Define pharmacology

A

The science of the properties of drugs and their side effects on the body

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

What are the autonomic actions to the eye?

A

S: Pupils dilate
P: Pupils and ciliary muscle constrict

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

What are the autonomic actions to the salivary glands?

A

S: Thick, viscous secretion
P: Copious, watery secretion

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

What are the autonomic actions to the trachea?

A

S: Dilates
P: Constriction

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

What are the autonomic actions to the skin?

A

S: Piloerection and Increased sweating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the autonomic actions to the liver?

A

S: Increased gluconeogensis and glycogenolysis

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

What are the autonomic actions to the heart?

A

S: Increased rate and contractility
P: Decreased rate and contractility

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

What are the autonomic actions to adipose tissue?

A

S: Lipolysis

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

What are the autonomic actions to the GI tract?

A

S: decreased motility and tone, also sphincter contraction
P: increased motility and tone and increased secretions

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

What are the autonomic actions to the kidney?

A

S: Increased renin secretion

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

What are the autonomic actions to the ureters and bladder?

A

S: Relaxes detrusor; constriction of trigone and sphincter
R: Constriction of detrusor; relaxation of trigone and spinster.

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

What arm of the autonomic nervous system is more dominant at rest?

A

Parasympathetic

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

Compare neurone length of the autonomic nervous system

A

Parasympathetic: Large pre-ganglionic neurones, small post-ganglionic neurones - often in the effector organ.

Sympathetic: Opposite

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

What neurotransmitters are used in the autonomic nervous system?

A

All pre-ganglionic neurones (sympathetic and parasympathetic) are cholinergic neurones releasing ACh.

Parasympathetic post-ganglionic neurones are also cholinergic.

Sympathetic post-ganglionic neurones release noradrenaline (apart from those synapsing with skin tissue to cause sweating, and those connected to the adrenal medulla which release ACh).

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

Which arm of the autonomic nervous system tends to have discrete and localised pathways, in comparison to divergent and mass-discharge pathways?

A

Parasympathetic tends to be discrete and localised.

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

What arm of the autonomic nervous system modulates the enteric nervous system?

A

Sympathetic

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

What are the functions of the enteric nervous system?

A

Maintaining lumen environment, blood flow, and epithelial cell function

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

What receptors respond to ACh

A

Nicotinic or Muscarinic (M1, M2 and M3 mainly, but also M4 and M5)

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

What type of receptors are Nicotinic and Muscarinic receptors?

A 
Nicotinic = ion channel linked
Muscarinic = G-protein linked
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the different adrenoreceptors, and their general action?

A

a1, a2, b1, b2. a1 has constricting effects while b2 has a dilatory effect.

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

What is the Acetylcholine synthesis pathway?

A

1) Acetyl CoA + Choline –> ACh + CoA by Choline Acetyl Transferase
2) ACh is packaged in a vesicle

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

What is the Acetylcholine release and metabolism pathway?

A

1) Calcium influx causes vesicles to merge with synaptic membrane, releasing ACh
2) ACh binds to nicotinic or muscarinic receptor
3) Acetylcholinesterase breaks down ACh into acetate and choline
4) Choline is re-absorbed into the pre-synaptic cell.

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

What is the Noradrenaline synthesis pathway?

A

1) Tyrosine –> DOPA by tyrosine hydroxylase
2) DOPA –> Dopamine by DOPA decarboxylase
3) Dopamine –> Noradrenaline inside a vesicle by Dopamine β hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the Noradrenaline release and metabolism pathway?

A

1) Calcium influx causes vesicles to merge with synaptic membrane, releasing NA
2) NA binds to adrenoreceptor
3) Uptake 1: NA is taken up by pre-synaptic neurone where it is either re-packaged into a vesicle or broken down in the mitochondria by monoamine oxidase A (MOA-A)
Uptake 2: NA is taken up by post-synaptic neurone and degraded by COMT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Define pharmacokinetics

A

The study of how drugs are handled within the body, including their absorption, distribution, metabolism and excretion.

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

Define pharmacodynamics

A

The interactions of drugs with cells and their mechanism of action on the body

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

What are the four drug target sites?

A
  1. Cell Receptors
  2. Ion channels
  3. Transport systems
  4. Enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the different types of receptors?

A

TYPE 1: Ionotropic
TYPE 2: Metabotropic (G-protein coupled)
TYPE 3: Kinase linked
TYPE 4: Intracellular steroid type

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

What are the main secondary messenger systems?

A
  • Adenyl Cyclase converts ATP to cAMP which up regulates Protein Kinase A (PKA)
  • Phospholipase C coverts PIP2 into DAG and IP3. IP3 increases [Ca2+], DAG activates Protein Kinase C (PKC)
  • Phospholipase A2 increases levels of AA which increases levels of Eicosianoids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Define Agonist

A

A drug of other substance that acts on the cell receptor to activate it, imitating a response

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

Define Antagonist

A

A substance that interferes with or inhibits the physiological action of another

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

What are the two types of ion channels?

A

Voltage sensitive and receptor-linked

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Give examples of two types of drugs that affect a transport systems.

A

TCAs (Tri-cyclic antidepressants) slow down the re-uptake of noradrenaline, prolonging its effect.
Cardiac glycosides slow down the Na/K ATPase, leading to an increase in intercellular Na+, which leads to increased force of contraction.

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

What are the ways drugs can interact with enzymes? Give examples of these drugs.

A

Enzyme inhibitors. E.g Neostigmine is an anticholinesterase
False substrates. E.g methyldopa subverts normal NA production
Prodrugs. E.g chloral hydrate which is converted to the active trichloroethanol.

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

Give examples of types of drugs that work by non-specific action.

A

General anaesthetics
Antacids (generally bases)
Osmotic purgatives/laxatives.

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

Define Affinity

A

the strength of drug binding to the receptor

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

Define Efficacy

A

the ability of the drug to induce a response in the receptor post-binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Define Potency

A

the powerfulness of a drug, depending on its affinity and efficacy

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

Define Full Agonist

A

an agonist which has the ability to induce a max response in the tissue post-binding

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

Define Partial Agonist

A

an agonist which can only produce a partial response in tissue

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

Define Selectivity

A

the preference of a drug for a receptor

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

Define Receptor Reserve

A

the fact that in many tissues, not all receptors need to be occupied to achieve the maximal tissue response

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

What are the mechanisms for antagonism?

A

1) Receptor blockade (competitive or irreversible)
2) Physiological antagonism (act on different receptors to induce opposite effect)
3) Chemical antagonism
4) Pharmacokinetic antagonism

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

What factors affect drug tolerance?

A

1) Pharmacokinetic factors (e.g increased metabolism when upregulation of enzymes)
2) Receptor down-regulation
3) Receptor desensitisation (receptor undergoes conformational change)
4) Exhaustion of mediator stores
5) Physiological adaption - homeostatic response

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

What is the acronym to describe the journey a drug makes through the body?

A

ADME

Absorption, Distribution, Metabolism and Excretion

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

Why are drug excipients added?

A

To improve biological/chemical stability, flavour, fragrance etc.

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

What are the different types of administration routes?

A

Enteral: Oral, rectal, sublingual and buccal
Parenteral: Inhalation, subcutaneous, intramuscular, intravenous, dermal and intraperitoneal.

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

What are the advantages and disadvantages of administration via the oral route?

A

ADV:

  • self-medication
  • does not require sterile preparation
  • incidence of anaphylactic shock is lower
  • capacity to prevent complete absorption

DIS:

  • requires patient compliance
  • inappropriate for drugs which are liable in stomach pH or undergo extensive first pass metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the advantages and disadvantages of administration via the IV route?

A

ADV:

  • rapid onset
  • avoids poor absorption/destruction in GI tract

DIS:

  • slow injection necessary
  • higher incidence of anaphylactic shock
  • medical professional required
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are the advantages and disadvantages of administration via the inhalation route?

A

ADV:

  • Ideal for particles, gases and volatile liquids
  • Large surface area of alveolar membranes
  • Simple diffusion mechanism

DIS:
- possible localised effects within lung

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

What are the advantages and disadvantages of administration via the intramuscular route?

A

ADV:
- high blood flow, increased during exercise

DIS:
- Possible infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are the two ways the drugs move around in the body?

A

Bulk flow transfer and Diffusional transfer

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

Why do most drugs exist in both ionised and unionised forms?

A

Ratio depending on pKa and pH of solution - most drugs are either weak acids or weak bases.

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

Describe the absorption journey of Aspirin

A

Aspirin has a pKa of 3.4. The pH of the stomach is 3, so aspirin remains unionised. Therefore aspirin is preferentially absorbed in the stomach. In contrast, the pH of the intestine is higher, therefore more aspirin exists in an unionised state, meaning a slower absorption.

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

How does slow-absorbing aspirin work?

A

It is enteric-coated and so is not absorbed in the stomach. The pH of the intestine is greater than the pKa of aspirin therefore more aspirin exists in an unionised state, meaning a slower absorption.

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

What factors affect drug distribution?

A

Regional blood flow
Extracellular binding (plasma protein binding)
Capillary permeability
Localisation in tissues

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

How do 50-80% of acidic drugs exist in the plasma?

A

Bound to a plasma protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Where are fat soluble drugs stored in the body?

A

Adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Describe the two routes of drug excretion:

A

Kidney: ultimately responsible for elimination of most drugs. In the glomerulus, drug-protein complexes are not filtered, but unbound drugs are. There is active secretion of acids and bases in the PCT. Lipid soluble drugs are reabsorbed in the distal tubules.

Liver: some drugs are concentrated in the bile, and them eliminated from the body via biliary secretion. This involves active transport systems into the bile. Enterohepatic cycling us where the drug/metabolite is excreted into the gut via bile but is reabsorbed again, leading to drug presistance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Define Bioavailability

A

The promotion of administered drug that is available within the body to exert a pharmacological effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What factors affect bioavailability when a drug is administered orally?

A
  • Ionisation in the gut may reduce absorption
  • Gastrointestinal pH
  • Whether drug is actively is passively or actively absorbed.
  • Gastrointestinal motility can reduce transit time, reducing absorption
  • Particle size (smaller drugs are absorbed better)
  • Physiochemical interaction between drug and gut contents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

When must we be careful of bioequivalent drugs?

A

When the drug has a narrow therapeutic index (window between amount needed to treat, and toxic amount)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

How can drug elimination be describe with kinetics?

A

Zero-order kinetics implies a saturable metabolic process. Applies to very few drugs.

First-order kinetics describes the rate of elimination of a drug where the amount of a drug decreases at a rate proportional to the concentration of drug in the body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Define Clearance

A

The volume of blood/plasma from which a drug is completely removed in time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is first-pass metabolism?

A

Usually hepatic, it is the lowering of the pharmacological material that is released in the general circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

How do Phase I and Phase II metabolism link?

A

Oxidation/reduction creates new functional groups. Hydrolysis unmasks them. Functional groups serve as a point of attachment for Phase II metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What are the Phase I metabolic reactions?

A

Oxidation, Reduction, Hydrolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What carries out Phase I reactions?

A

Cytochrome P450 enzyme system - found in theHo deliver, and is composed of 57 enzymes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

How does the Cytochrome P450 enzyme oxidise a drug?

A
  • RH (Drug) binds to the P450-Fe3+ forming P450-Fe3+-RH
  • An electron oxidises the iron. P450-Fe2+-RH
  • O2 binds to P450 forming: O2-P450-Fe2+-RH
  • The electron is unloaded to the oxygen: -O2-P450-Fe3+-RH
  • Another electron oxidises the iron. -O2-P450-Fe2+-RH
  • The electron is unloaded to the oxygen again: (2-)O2-P450-Fe3+-RH
  • The drug is oxidised and water is expelled: P450-Fe3+, ROH, H2O
70
Q

What enzyme, conjugating agent and target functional groups are needed for Glucoronidation

A

Glucoronyl transferase needs UDP-glucoronic acid. The target functional groups are: -OH, -COOH, -NH2, -SH

71
Q

What enzyme, conjugating agent and target functional groups are needed for Acetylation

A

Acetyl transferase needs Acetyl CoA. The target functional groups are: -OH, -NH2

72
Q

What enzyme, conjugating agent and target functional groups are needed for Acylation

A

Acyl transferase needs Glycine, Glutamine, Taurine. Target functional group is -COOH

73
Q

What enzyme, conjugating agent and target functional groups are needed for Methylation

A

Methyl transferase needs S-adenosyl-methioine. Target functional group are: -OH, -NH2

74
Q

What enzyme, conjugating agent and target functional groups are needed for Sulphation

A

Sulfotransferase needs 3’-phosphoadenosine-5’phosphosulfate. Target functional groups: -OH, -NH2

75
Q

What enzyme, conjugating agent and target functional groups are needed for the addition of glutathione

A

Glutathione-S-transferase needs glutathione. Targets electrophile.

76
Q

What are the Phase II reactions?

A
  • Glucoronidation
  • Acetylation
  • Acylation
  • Amino acid conjugation
  • Sulphating
  • Methylation
  • Glutathione conjugation
77
Q

Explain the metabolism of paracetamol

A

Phase 1: formation of a reactive intermediate NAPQI

Phase 2: Sulphation or Glucoronidation of OH group on paracetamol. Glutathione conjugation of NAPQI

78
Q

What is the reasoning behind the treatment for paracetamol overdose?

A

Administer N-Acetylcystine. This is because cystine is part of glutathione, which is needed to conjugate toxic NAPQI.

79
Q

What is a cholineomimetic drug?

A

A cholinomimemtic drug mimics the action of acetylcholine. in the body.

80
Q

What is Atropine?

A

A competitive muscarinic antagonist

81
Q

What are the different muscarinic receptor subtypes and where are they found?

A

M1: Salivary Gland, Stomach and CNS
M2: Heart
M3: Salivary Gland, Bronchial/Visceral SM, Sweat glands, Eye
M4 + M5: CNS

82
Q

Describe the structure and secondary messenger systems of muscarinic receptors

A

They have 7 transmembrane segments, and cytoplasmic loops with G-protein subunits. M1,3,5 use IP3 and DAG as secondary messengers, M2,4 use cAMP. They all have excitatory effects apart from M2 which is found in the heart.

83
Q

Describe the structure of nicotinic receptors

A

Ligand-gated ion channels with 5 subunits. Muscle receptors have 2(alpha), (beta), (delta) and (epsilon) subunits; Ganglion receptors have 2(alpha) and 3 (beta).

84
Q

What are the parasympathetic effects on the eye?

A

Contracts ciliary muscle and sphincter papillae to constrict pupil and improve the drainage of intraocular fluid. Also causes lacrimation.

85
Q

What is a consequence of M2 receptor activation?

A

M2 acetylcholine receptors in the atria and nodes decreases cAMP and consequently decreases Ca2+ entry into the cell, while increasing K+ efflux, leading to decreased cardiac output and heart rate. This is a negative ioniotropic/chronotropic effect.

86
Q

What is a consequence of M3 receptor activation in vasculature?

A

Most blood vessels do not have parasympathetic innervation. However, acetylcholine acts on vascular endothelial cells to stimulate NO via M3 receptors. This causes vascular smooth muscle relaxation and a decrease in TPR. [more relevant to clinical use of choliniminetics than normal physiology]

87
Q

How does activation of muscarninc receptors affect blood pressure?

A

The decrease in heart rate and cardiac output (M2) as well as fall in TPR (M3) leads to a sharp drop in blood pressure.

88
Q

What is a consequence of muscarinic receptor activation in smooth muscle?

A

Smooth muscle that has parasympathetic innervation CONTRACTS in response to ACh. E.g bronchoconstriction, increased peristalsis and gut motility, bladder emptying.

89
Q

What are the types of cholinomimetics?

A

Directly Acting (choline esters and alkaloids) and Indirectly Acting (reversible and irreversible anticholinesterases)

90
Q

What are the choline esters cholinomimetics and their use?

A
  • Acetylcholine: no therapeutic use as it does not differentiate between muscarinic and nicotinic receptors and degrades quickly.
  • Bethanechol: similar structure to ACh, but addition of methyl group making it more resistant to degradation. It is an M3 agonist with limited access to the brain. It is used to assist in bladder emptying or enhance gastric motility.
91
Q

What are the pharmacokinetics and side-effects of Bethanechol?

A

Orally active; Half-life 3-4 hours

Side effects: Sweating, impaired vision, nausea, bradycardia, hypotension + respiratory difficulty

92
Q

What are the alkaloid cholinomimetics and their use?

A
  • Nicotine: stimulates all autonomic ganglia, increasing sympathetic and parasympathetic activity. Not used clinically.
  • Muscarine: selective for muscarinic receptors, is why some mushrooms are poisonous.
  • Pilocarpine: non-selective partial agonist for muscarinic receptors. Useful in the local treatment for glaucoma.
93
Q

What are the pharmacokinetics and side-effects of Pilocarpine?

A

Administration: locally as eyedrops
Half-life: 3-4 hours
Side effects: Predicted by PNS actions:
Blurred vision, sweating, GI disturbance, hypotension, respiratory distress

94
Q

What is the general MOA of Indirectly acting cholinominetics?

A

Anticholinersterases increases the effect of normal parasympathetic nerve stimulation. A low dose will enhance muscarinic activity, a moderate dose will also increase transmission at all autonomic ganglia. A high dose can be toxic due to a depolarising toxic effect.

95
Q

What are the differences between the two cholinesterase enzymes?

A

Acetylcholinesterase: found in all cholinergic synapses. Highly specific for acetylcholine. Very rapid action
Butyrylcholinesterase: only found in plasma and most tissues (not synapses). Has broader substrate specificity and hydrolyses other esters. It is the reason for low plasma acetylcholine.

96
Q

List the indirectly acting cholinomimetics

A

Reversible anticholinesterases: Physostigmine, Neostigmine and Donepezil
Irreversible anticholinesterases: Ecothiopate, Dyflos, Sarin.

97
Q

What is the MOA of reversible anticholinesterases?

A

Physostigmine and neostigmine compete for active sites with acetylcholine. However, they donate a carbamyl group to the enzyme, blocking the active site. The carbamyl group is eventually removed by slow hydrolysis.

98
Q

What are the pharmacokinetics and use of Physostigmine?

A

Half-life 30 minutes (carbamyl group removed by slow hydrolysis)
Use in:
Treatment of glaucoma
Treat atropine poisoning (Ach antagonist)

99
Q

What are the uses of irreversible anticholinesterases?

A

Only ecothiopate is used clinically, others are pesticides and nerve gas. Ecothiopate is used as eye drops in the treatment of glaucoma with a prolonged duration of action.

100
Q

How can anticholinesterases affect the CNS?

A

Non-polar anticholinesterases can cross the blood-brain barrier. In low doses this can cause excitation with possible convulsions. In high doses, unconsciousness, respiratory depression and death. Donepezil is used to treat Alzheimer’s disease as ACh is important in learning and memory.

101
Q

Why are ganglion-blocking drugs technically not antagonists?

A

They block the ion channel and do not necessarily have affinity to the receptor.

102
Q

Define use-dependent block

A

A term used to describe the drug’s properties to work more effectively when the ion channels are open (and so more agonists are present)

103
Q

What is the general effect of nicotinic receptor antagonists / ganglion blocking drugs?

A

Dampening down of parasympathetic function (as parasympathetic arm usually more dominant). Exceptions include:

  • Liver: ganglion blockage would see a decrease of sympathetic function of glycogenolysis and gluconeogenesis
  • Kidney: decrease sympathetic release of renin -> hypotension
  • Blood vessels: sympathetic tone decreased -> vasodilation -> decrease in TPR -> hypotension
104
Q

List ganglion-blocking drugs and their use.

A
  • Hexamethonium - first anti-hypertensive - no longer in use.
  • Trimetaphan - only ganglion-blocking drug used today, but has much more pronounced antagonistic effect. Reserved for surgical hypertensive crisis administered I.V.
105
Q

What is the difference between receptor-blocking nicotinic antagonists and ganglion-blocking drugs?

A

Receptor-blocking nicotinic antagonists block the receptor but not the ion channel.

106
Q

What venom does the Common Krait use?

A

alpha-bungarotoxin binds to nicotinic receptor irreversibly.

107
Q

What are the muscarinic receptor antagonists?

A

Atropine, Hyoscine, Tropicamide and Ipratropium Bromide

108
Q

What is Atropine derived from?

A

The deadly Nightshade plant

109
Q

What are the CNS effects of muscarinic receptor antagonists?

A

M1 and M5 receptors found in CNS.

  • Normal doses of atropine has little effects on the CNS. A toxic dose will cause mild restlessness.
  • Normal dose of hyoscine causes sedation and amnesia. A toxic dose can cause CNS depression or paradoxical CNS excitation.
110
Q

What is the use of tropicamide

A

Muscarinic receptor antagonist given as eye drops. Blocking muscarine receptors in the iris, it causes pupil dilation, making it easier to examine the retina.

111
Q

What is the clinical use of Hyoscine?

A
  • Anaesthetic premedication. In surgery where intubation is required, the muscarinic antagonist will cause airways to dilate. Also reduce secretions in the mouth and trachea as well as reducing heart rate. Also has sedative effects.
  • Hyoscine patches used to treat motion sickness.
112
Q

How can muscarinic antagonists be used to treat Parkinson’s disease?

A

Nigrostriatal dopiminergic neurones are very important in fine control of movement. These neurones are lost in Parkinson’s disease. Muscarinic receptors normally have a negative effect on dopamine signalling, therefore antagonists allow the dopaminergic neurones to fire at a maximum rate.

113
Q

What is the use of Ipratropium bromide?

A

Muscarinic antagonist used to treat asthma by causing bronchodilation. The larger quaternary structure (in comparison to Atropine) makes it harder to cross membranes. This localises the effects to lungs.

114
Q

What are the side-effects of muscarinic antagonists?

A
  • Hot as Hell: decreased sweating and thermoregulation
  • Dry as a Bone: decreased secretions
  • Blind as a Bat: due to cyclopegia
  • Mad as a Hatter: high doses can cause CNS agitation, restlessness and confusion.
115
Q

What is used to treat Atropine poisoning?

A

Physostigmine

116
Q

What is the most deadly toxin the world and how does it work?

A

Botulinum toxin from Clostridium botulinum.

- It interferes with exocytosis preventing ACh from being released. Specifically the protein binding to SNARE complex.

117
Q

What muscles and their autonomic arms control the size of the pupil?

A
  • The sphincter pupillae parasympathetically innervated to cause constrict the pupil
  • The radial muscle sympathetically innervated to dilate the pupil.
118
Q

What is the normal intraocular pressure?

A

10-20 mmHg

119
Q

Explain the second messenger systems of adrenoreceptors

A

alpha-1 act through the phospholipase C system, producing IP3 and DAG.
alpha-2 DECREASE the levels of cAMP via the adenyl cyclase system
beta-1 and beta-2 result in an increase in cAMP via the adenyl cyclase system.

120
Q

What are the directly acting sympathomimetics and their selectivities?

A 
Adrenaline (non-selective)
Phenylephrine (alpha-1)
Clonidine (alpha-2)
Dabutamine (beta-1)
Salbutamol (beta-2)
121
Q

What are the indirectly acting sympathomimetics?

A

Cocaine and Tyramine

122
Q

Describe the distribution of adrenoreceptors

A

alpha-1: constriction of resistance vessels and large veins (also in the eye for sympathy innervation), relaxation of GI tract
alpha-2: pre-synaptic receptors, inhibiting release of noradrenaline, also in CNS
beta-1: found in cardiac muscle, where it produces a positive chronotropic and ionotropic effect. Also found in kidneys, where it leads to the release of renin, and found in GI tract.
beta-2: dilation of bronchi and skeletal muscle vasculature, relaxation of visceral smooth muscle and hepatic glycogenolysis.

123
Q

For what receptors are noradrenaline and adrenaline selective for?

A

Noradrenaline has a greater selectivity for alpha receptors, while adrenaline has a greater selectivity for beta receptors.

124
Q

Where is adrenaline synthesised?

A

Chromaffin cells in the adrenal medulla.

125
Q

How is adrenaline synthesised and broken down?

A

Noradrenaline is converted to adrenaline by enzyme phenylalanine methyltransferase. Adrenaline is broken down by MOA-A and COMT

126
Q

Describe the pathophysiology of anaphylactic shock

A

Mast-cell degranulation releases inflammatory mediators such as histamine.

  • Histamine receptors in blood vessels causes vasodilation -> decrease in TPR -> hypotensive crisis.
  • PRIMARY THREAT: histamine receptors in the bronchial smooth muscle causes bronchoconstriction.
127
Q

How does treatment for anaphylactic shock work?

A

Adrenaline is administered as treatment because the primary threat is ventilation:
- beta-2 activation will cause bronchodilation
- beta-1 activation causes tachycardia increasing CO and BP
- alpha-1 activation causes vasoconstriction of resistance vessels. Although beta-2 causes vasodilation of skeletal vasculature, still overall rise in BP.
Adrenaline also blocks release of inflammatory mediators from leukocytes.

128
Q

What sympathomimetic is preferable over adrenaline in the treatment of asthma and why?

A

Salbutamol as it is more beta-2 selective, minimising side-effects.

129
Q

How can adrenaline treat glaucoma?

A

Adrenaline decreases the production of aqueous humour via alpha-1 mediated vasoconstriction.

130
Q

What are the clinical uses of Adrenaline?

A
  • treat anaphylactic shock
  • glaucoma
  • cariogenic shock
  • myocardial infarction
  • cardiac arrest
131
Q

What are unwanted actions of Adrenaline?

A
  • Secretions reduced and thickened mucus

- CVS effects i.e tachycardia, palpitations arrhythmias, cold extremities and hypertensive.

132
Q

What are the properties of Phenylephrine and its use?

A

Phenylephrine has selective action on alpha1»alpha2»>beta1/beta2. Chemically related to adrenaline but resistant to COMT degradation. Used for:

  • vasoconstriction, useful when dealing with sepsis or hypotensive effects of anaesthesia
  • mydriatic eye drops
  • Nasal decongestants to decrease mucus production.
133
Q

What are the properties of Clonidine and its use?

A

Clonidine is selective to alpha2»>alpha1»>beta1/beta2. Used for the treatment for:

  • hypertension as it would lead to the reduction of sympathetic tone
  • migranes
134
Q

What are the properties of Isoprenaline and its use?

A

Isoprenaline is selective to beta1/beta2&raquo_space;» alpha1/alpha2. It is based on the chemical structure of adrenaline but is less susceptible to uptake 1 and MAO breakdown. This means it has a longer half-life of 2 hours. It is used to treat cariogenic shock when given IV. Also to treat acute heart failure and myocardial infarction.

135
Q

What are the properties of Dobutamine and its use?

A

Dobutamine is selective to beta1»beta2»>alpha1/alpha2. It has little beta2 action and so lack isoprenaline reflex tachycardia effect. Used to treat heart block and is administered by I.V infusion. It has a very short plasma life of 2 mins as it is rapidly metabolised by COMT.

136
Q

What are the properties of Salbutamol and its use?

A

Salbutamol is selective to beta2»beta1»»alpha1/alpha2. It is a synthetic catecholamine derivative withe relative resistance to COMT and MAO-A, so it has a much longer half-life than NA or adrenaline. Used in the treatment of asthma and threat of premature labour (as it relaxes smooth muscle).

137
Q

How does Cocaine work and what are its effects?

A

It prevents uptake 1 so there is more catecholamine at the synoptic cleft of noradrenergic and dopaminergic neurones. CNS effects include:
- Euphoria due to more dopamine action in midbrain
- Excitement and increased motor activity
- In high doses - activation of vomiting centre, CNS depression, respiratory failure and death
PNS effects include:
- tachycardia, vasoconstriction and raised blood pressure in low doses
- V-fib and cardiac arrest in large doses

138
Q

What are the sympathetic antagonists and their selectivities?

A 
Labetalol: alpha1 + beta1
Phentolamine: alpha1 + alpha2
Prazosin: alpha1
Propranolol: beta1 + beta2
Atenolol: beta1
139
Q

What are the clinical uses of SNS antagonists and false transmitters?

A

In the treatment of:

  • hypertension
  • cardiac arrhythmia
  • angina
  • modify plasma lipid levels
  • glaucoma
140
Q

Define hypertension

A

Sustained diastolic arterial pressure greater than 90 mmHg

141
Q

What are the main elements that determine blood pressure?

A

Blood volume (as determined by kidneys)
Cardiac Output
Peripheral vascular tone

142
Q

How do beta-blockers treat hypertension?

A

The sympathetic arm has an important role in blood pressure control while the parasympathetic has little effect. The long-term effect of beta-blockers is a reduction in TPR through blocking the renal nerve mediated release of renin. Although initially a fall in CO occurs, the beta1 receptors in the heart adapt over time in chronic treatment.

143
Q

What are the unwanted effects of Beta receptor antagonists?

A
  • Bronchoconstriction (beta2): little importance in the absence of airway disease, but can be life threatening in asthmatic patients.
  • Cardiac failure: patients with heart disease may rely on a degree of sympathetic drive to the heart to maintain an adequate CO
  • Hypoglycaemia: beta-antagonists may mask the symptoms of hypoglycaemia (sweating, palpitations and tremor). Non-selective beta-antagonists prevent glycogenolysis.
  • Fatigue: due to reduced CO and muscle perfusion
  • Cold extremities: due to loss of beta receptor mediated vasodilation in cutaneous vessels
  • Bad dreams due to CNS effects.
144
Q

What are the effects of Propranolol?

A 
non-selective beta antagonist. At rest causes little change in heart rate or CO, but reduces the effect of exercise. As it is non-selective it produces all typical unwanted effects.
Also is a class II anti arrhythmic as it reduces sympathetic drive and increases myocardial refractory period.
145
Q

What are the effects of Antenolol?

A

Atenolol is a beta-1 antagonist (cadioselective). It has less effect n airways than non-selective drugs but still not safe with asthmatics. Reduces TPR and CO.

146
Q

What are the effects of Labetalol?

A

Dual acting beta-1 and alpha-1 blocker. It lowers peripheral resistance through alpha-1 effects as well as beta1 effects to lower blood pressure.

147
Q

What are the effects of alpha adrenoreceotor antagonists?

A

Cause a fall in arterial pressure. However, also causes postural hypotension.
It also causes a reflex increase in heart rate as beta-receptors are unblocked.
It also increases blood flow through cutaneous and splanchnic vascular beds

148
Q

What are effects of Phentolamine?

A

non-selective alpha adrenoreceptor antagonist.
Causes a fall in arterial pressure. However, also causes postural hypotension.
It also causes a reflex increase in heart rate as beta-receptors are unblocked. Blockade of alpha-2 receptor prevents inhibition of NA release, enhancing reflex tachycardia.
Diarrhoea is a problem of increased gut motility.

149
Q

What are effects of Prazosin?

A

an alpha-1 antagonist that is increasingly used as an antihypertensive.

  • causes vasodilation -> fall in arterial pressure
  • less tachycardia than non-selevive alpha blockers
  • CO falls due to decrease in venous pressure
  • hypotensive effect without affecting cardiac function, although postural hypotension is still a problem
  • causes a modest decrease in LDL, and an increase in HDL, positively affecting cholesterol balance.
150
Q

How does Methyldopa work?

A

Methyldopa is an antihypertensive agent taken up by noradrenergic neurones. It is decarboxylated and hydroxylated to form a false transmitter - alpha-methyl-noradrenaline.
This is not deaminated by MAO and so tends to accumulate more than NA, displacing NA from synaptic vesicles. The false transmitter is less active on alpha1 receptors than NA, causing less vasoconstriction. Also more active on presynaptic alpha2 receptors - increasing auto-inhibitory feedback.
It also stimulates vasopressor centre in the brainstem to inhibit sympathetic outflow.

151
Q

What are the indications for Methyldopa?

A

Widely used in hypertensive patients with cardiovascular disease or renal insufficiency as CNS blood is maintained.
Recommended for pregnant woman as it has no adverse effects on developing foetus.

152
Q

What are the side-effects of Methyldopa?

A

Dry mouth, sedation, orthostatic hypotension and male sexual dysfunction,

153
Q

What is an Arrhythmia?

A

Abnormal or irregular heart beats. It is mainly caused by myocardial ischaemia due to ischaemic tissue allowing abnormal electrical circuits.

154
Q

How can adrenoreceptor antagonists help control arrhythmias?

A

An increase in sympathetic drive to the heart via beta-1 receptors can precipitate or aggravate arrhythmias. Particularly after myocardial infarction as there is a sympathetic tone as the body thinks the heart is not working properly. Blocking sympathetic activity will therefore reduces this.

Also, atrioventricular conductance depends on the refractory period, which is influenced by adrenoreceptor activity. Increasing the refractory period means that abnormal re-entrant impulses cannot trigger additional heartbeats reducing arrhythmias.

155
Q

What is Angina?

A

Tight chest pain that occurs when oxygen supply to the myocardium is insufficient for its needs. It is associated with the feeling of breathlessness. The pain is distributed across the left chest and radiates to the arm and neck.

156
Q

What are the three types of Angina?

A
  • Stable angina = pain on exertion
  • Unstable angina = pain with increasingly less excretion with time, culminating with pain at rest. Could be due to platelet-fibrin thrombus associated with ruptured atheromatous plaque, but without complete occlusion of vessel. It poses a serious risk of infarction.
  • Variable angina - occurs at rest. Caused by artery spasm but also associated with atheromatous disease.
157
Q

Why do beta blockers treat angina?

A

Beta blockers reduce myocardial oxygen demand by:

  • decreasing heart rate
  • decreasing systolic blood pressure
  • decreasing cardiac contractile activity
158
Q

When are beta-blockers contraindicated?

A

NOT USED in patients with bradycardia (heat beat of less than 55 beats/min), bronchospasm, hypotension (systolic pressure less than 90mmHg), AV block or severe congestive heart failure.

159
Q

How can Glaucoma be treated by beta-blockers?

A

Aqueous humour production is done by the blood vessels in the ciliary body via the actions of carbonic anhydrase. Beta1 receptors facilitate the action of carbonic anhydrase.

160
Q

What type of receptors are present on the motor end plate?

A

Nicotinic acetylcholine receptors (different structure to those in autonomic nervous system)

161
Q

What is the neuromuscular junction?

A

The location where the neurone activates the muscles to contract - the junction between an axon terminal and a motor end plate.

162
Q

Describe the events at a neuromuscular junction

A
  1. Action potential stimulates voltage-gated Ca2+ channels to open
  2. Ca2+ ions diffuse into the axon terminal, triggering acetylcholine containing vesicles to release ACh into the synaptic membrane.
  3. ACh binds to the nicotinic receptors, opening Na+ and K+ channels.
  4. More Na+ diffuses into the cell than K+ out, depolarising the membrane, producing an end-plate potential (EPP)
  5. If the EPP reaches the threshold potential, an action potential will be generated.
  6. ACh is metabolised by acetylcholinesterase. Choline produced by degradation is recycled by re-uptale, acetate diffuses away into the blood stream.
163
Q

Describe the structure of nicotinic acetylcholine receptors.

A

They are ligand gated ion channels with intracellular and extracellular domains.
The ANS ganglion type has 2 alpha and 3 beta subunits
The NMJ type has 2 alpha, beta, gamma and a delta subunit.
Two acetylcholine molecules bind at each alpha site causing a conformational change.

164
Q

What drugs interfere with the NMJ in the generation of AP in the neurone?

A

Spasmolytics such as diazepam and baclofen. They potentiate the action of GABA (inhibitory receptors) reducing action potentials generated.

165
Q

What drugs interfere with the NMJ in the conduction of AP in the motor neurone?

A

Local anaesthetics

166
Q

What drugs interfere with the NMJ in the release of ACh?

A
  • Hemicholinum blocks the re-uptake of choline.
  • Botulinum toxin inhibits release of ACh
  • Ca2+ entry blockers
167
Q

What drugs interfere with the NMJ in the depolarisation of the motor-end plate?

A

Tubocurarine, Atracurium (Non-depolarising) and Suxamethonium (depolarising)

168
Q

What drugs interfere with the NMJ in the propagation of the AP along the muscle fibre?

A

Spasmolytics such as Dantrolene reduces Ca2+ levels by reducing the release of Ca2+ from the sarcoplasmic reticulum in skeletal muscle fibres -> reduced force of contraction

169
Q

How does Suxamethonium work and what is it used for?

A

It is a compound that looks like two molecules of ACh attached, therefore only one molecule is necessary to activate the receptor. Although it is an agonist, it paradoxically acts as a blocker because it causes a depolarising block due to overstimulation of nAChR. This leads to a flaccid paralysis.

Used for Endotracheal intubation and muscle relaxant for electroconvulsive therapy.

170
Q

What are the pharmacokinetics and side-effects of Suxamethonium?

A

Given IV as highly charged. Duration of paralysis is 5 minutes. It is metabolised by a pseudo-cholinesterase in the liver and plasma. It causes initial fasciculations and again when the drug is being broken down.

Side effects include:

  • Post operative muscle pains due to fasciculations
  • Bradycardia mimicking ACh to slow heart down - atropine is often co-adminitered to prevent this.
  • Hyperkalaemia as K+ ions escape through ion channels when Na+ influx, causing leakage into blood.
  • Increases intra-oscular pressure.
171
Q

How does Tubocurarine work and what is it used for?

A

Tubocurarine is a competitive nAChR antagonist. Only a 70-80% block is necessary. It causes flaccid paralysis is a specific order:
Extrinsic eye muscles (causing double vision) -> Small muscles of face, limbs and pharynx -> Respiratory muscles. Recovery comes back in the opposite direction.

It is used as a muscle relaxant during surgeries so less anaesthetics are required. It permits artificial ventilation by relaxing our own respiratory muscles.

172
Q

What are the pharmacokinetics and side-effects of Tubocruanine?

A

Administered IV, taking 2-3 minutes to work, lasting for 40-60 minutes. Not metabolised. Excreted in urine (mostly) and bile.

At higher doses, effects overlap into the ANS nAChR:

  • Hypotension
  • Tachycardia
  • Bronchospasm
  • Apnoea

Year 2 LCRS (5 decks)

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