Pharmacology Flashcards
1
Q
Define pharmacology
A
Study of drug effects
2
Q
Define pharmacokinetics
A
How the body affects the drug (ADME)
3
Q
Define pharmacodynamics
A
How the drug affects the body
4
Q
Define druggability
A
Ability of a protein target to bind to a small molecule (drug) with high affinity
5
Q
What are most drug targets?
A
Proteins
e.g. Receptors, enzymes, ion channels, transporters
6
Q
What are the 3 types of receptor targets?
A
NT receptors (e.g. mACHR) Autocoid receptors (e.g. cytokines, histamine) Hormone receptors (e.g. steroid)
7
Q
What are 4 receptor types?
A
Ligand-gated ion channels (e.g. nACHR)
GPCR (e.g. mACHR, beta-adrenergic receptors)
Tryptase kinase-linked (e.g. growth factors, insulin)
nuclear/cytosolic (e.g. steroid)
8
Q
Define potency
A
measure of how well a drug works (basically binding affinity)
e.g. a more potent drug would have a higher receptor response at EC50
9
Q
Define EC50
A
The concentration at half the maximum response (Emax)
10
Q
What is the difference between a full and partial agonist?
A
Full agonist can achieve 100% response
Partial agonist has an Emax
Partial agonists are less efficacious
11
Q
Define intrinsic activity of a drug
A
proportionality factor between the receptor occupacy and tissue response
(Emax/100% response)
Full agonist=1, antagonist=0
12
Q
what is the difference between selective/competitive antagonism and non-competitive antagonism?
A
Competitive antagonists bind to orthosteric sites so increasing the concentration of the agonist would eventually achieve Emax.
Non-competitive antagonists bind to allosteric sites so increasing the concentration of the agonist would have no effect on the tissue response
13
Q
What effect do irreversible antagonists have?
A
Permanently block the receptor so can no longer be stimulated. It can only then be endocytosed.
14
Q
Define affinity
A
How well a ligand binds to a receptor
Shown by both agonist and antagonist
15
Q
Define efficacy
A
How well a ligand activates a receptor
Only shown by agonists
16
Q
What equation is used to calculate the no. of available receptors?
A
Furchgott Equation
17
Q
What does an increase in receptors at a tissue mean for the drug dose?
A
A lower dose would achieve the same response
18
Q
What do many tissues have a receptor reserve for?
A
Full agonists
19
Q
Define allosteric modulation
A
Inactivates receptors
Affinity modulation: alters EC50
Efficacy modulation: alters Emax
20
Q
Define inverse agonism
A
When a ligand binds to orthosteric site causing the opposite effect e.g. propanolol + cimetidine
21
Q
Define tolerance
A
Down regulation of receptor with prolonged use. Require higher dose to achieve same effects.
22
Q
Define receptor desensitisation
A
This is when the receptor can’t interact with the G protein –> endocytosed + degraded
23
Q
Define specificity
A
Relates to the number of certain targets a drug binds to
no drug is completely specific
24
Q
Define selectivity and give examples of selective and non-selective drugs.
A
Relates to the different effects a drug can cause.
Non-selective: isoprenaline (beta 1 + 2 agonist)
Selective: salbutamol (beta 2 agonist) –> however with continual high doses it can lose its selectivity and activate both beta 1 + 2 receptors.
25
What are 3 enzymes as drug targets?
1. NSAIDS--> COX
2. ACEi --> ACE
3. Beta-Lactam Abs --> inhibit specific enzymes required for peptidoglycan cell wall biosynthesis
26
How does aspirin affect COX isotypes?
Irreversibly inhibits them (forms covalent bonds)
27
Describe the process of prostanoid synthesis
membrane phospholipid --PLA2--> Arachidonic acid --COX--> PGH2 --specific synthases-->
PGD2, (Mast cells)
PGI2, (vascular endothelial cells)
TXA2, (Platelets)
PGE2(Macrophages - mediates most body effects)
28
What are the 2 COX isotypes?
COX-1: Found widely in body
| COX-2: induced - by inflammation
29
What are 2 examples of ACEi?
Captopril
Enalapril
Both are peptides that mimic the final AA sequence of angiotensin I (preventing it from binding to ACE)
30
What are some transporters as drug targets? (4)
1) PPIs --> H+/K+ ATPase
2) H2 antagonists --> H2 receptor
3) Diuretics: Thiazides = NCC on DCT, Furosemide (loop diuretics) = NKCC2 on LoH)
4) Neuronal uptake inhibitors --> inhibit synaptic reuptake of NTs
31
What are 4 synaptic reuptake inhibitors?
1) Fluoxetine (prozac) = serotonin
2) Imipramine = serotonin + dopamine (non-selective)
3) Cocaine = dopamine
4) Tiagabine = GABA
32
Give 2 examples of ion channels as drug targets.
1) Calcium channel blockers e.g. amlodipine
| 2) Local anaesthetics = sodium channel blockers
33
What is amplodipine used to treat?
Calcium channel blocker used for angina, arrhythmias and hypertension
34
How do lidocaine and procaine work?
They inhibit post synaptic voltage gated sodium channels.
35
What are the 4 phases of pharmacokinetics
1) Absorption/uptake
2) Distribution
3) Metabolism
4) Elimination
36
What is the order of diffusion?
First order reaction
37
Give 5 forms of transport across membranes
1) Simple diffusion
2) Facilitated diffusion
3) AT (starts as 1st order --> 0 when fully saturated)
4) Via extracellular spaces (e.g. pores)
5) Non-ionic diffusion
38
Define non-ionic diffusion and give an example of a drug that utilises this transport mechanism.
When a molecule becomes less ionic when it diffuses across a membrane. E.g. ASPIRIN
39
How does pH effect the diffusion of weak acids across a membrane?
Higher pH: weak acid is MORE ionised, so rate of diffusion decreases.
Lower pH: weak acid is LESS ionised so rate of diffusion increases.
So weak acids are best absorbed in acidic environments where there is a lower pH outside cells than inside cells.
40
How does pH effect the diffusion of weak bases across a membrane?
Higher pH: weak base is LESS ionised, so rate of diffusion decreases.
Lower pH: weak base is MORE ionised so rate of diffusion increases.
41
Why do local anaesthetics not work on abscesses?
Because local anaesthetics are weak bases and abscesses have an acidic internal environment.
42
Define bioavailability (F)
The proportion of the volume of drug administered that is taken up by the plasma.
F = [drug uptake into plasma]/[drug administered]
43
What form of drug administration has a bioavailability of 1?
Intravenous
44
Give an example of a drug administration route
- ORAL
- SUBLINGUAL
- NASAL
- INHALATION
- TOPICAL
- TRANSCUTANEOUS
- SUBCUTANEOUS
- IV
- IM
- INTRATHECAL
- RECTAL
45
Why is oral administration the most unpredictable?
Because drug absorption depends on various factors including pH (most drugs HA/A-), surface area, diarrhoea.
46
What drugs can alter the uptake of aspirin?
Any drugs that increase the pH of the stomach e.g. PPIs H2 antagonists, antacids.
47
What effect do drugs decreasing gut motility have of drug absorption?
Decrease absorption
48
What properties affect drug distribution?
Drug size and molecular properties.
| pH of the compartment and membrane permeability.
49
Define volume of distribution (Vd)
Vd= (total amount of drug in body in body)/[drug in plasma]
Vd (L/kg)= (dose (mg))/[drug in plasma(mg/L)]
Finds how much of the drug is required in the body to get a certain concentration in the plasma (can also be used to calculate dose if you have the Vd and concentration required in the plasma)
50
Give an example of a drug with a high Vd. What does this mean?
Amiodarone (anti-arrhythmatic).
The drug is highly lipid soluble and it can easily be taken up by most body compartments. So a high dose is required to get a certain response from the effect site.
Adjusting infusion rates + achieving steady state plasma levels takes long time.
51
Give an example of a drug found in the plasma compartment. (CAW)
Proteins and large molecules e.g.
- Crystalloids and colloids (plasma expanders)
- Antibodies
- Warfarin
52
Give an example of a drug found in the interstitial fluid compartment. (MAN)
Water soluble drugs e.g.
- NSAIDs
- Muscle relaxants
- Antibiotics
53
Give an example of a drug found in the ICF compartment. (COALS)
- CNS drugs Steroids
- Opiods
- Amiodarone
- Local anaesthetics
- Steroids
54
What 2 main organs are involved in elimination?
Liver and kidneys
55
Define clearance
clearance(ml/mg) = (rate of drug elimination (mg/min))/[drug]p (mg/L)
56
Define renal clearance and name the common marker used.
Renal clearance = [drug]U x urine volume/[drug]P
| Creatinine (Cr)
57
What properties do renally excreted drugs commonly have?
They are small water-soluble molecules
58
What can renal impairment lead to?
- Increased plasma urea and creatinine
- Hypoalbuminaemia
- Oedema in compartments - unpredictable drug reactions
- DECREASED CLEARANCE AND ELIMINATION
59
How should you treat patients with renal impairment? (4)
1) Avoid nephrotoxic drugs
2) Replace renal eliminated drugs by liver eliminated drugs.
3) Correct their drug dosage based of their creatinine clearance (normally ≈ 125ml/min)
4) Measure [drug]P if toxicity risk
60
What is the HER?
The proportion of a drug metabolised by 1 pass through the liver.
61
What does a high HER mean?
These drugs are cleared rapidly via liver first pass metabolism.
Perfusion limits rate of elimination.
E.g. Propanolol, Lidocaine
62
What does a low HER mean?
These drugs are inefficiently metabolised by first-pass metabolism in the liver.
Diffusion limits their rate of elimination.
Drugs with a low HER induce liver enzyme synthesis to increase clearance.
E.g. Warfarin, Erythromycin
63
How are large hydrophilic drugs excreted as opposed to large lipophilic drugs?
Large hydrophilic drugs are DIRECTLY removed via BILE.
Large lipophilic drugs are conjugated with UGT (+UDPGA) via phase II detoxification reactions to a hydrophilic glucuronide that can then be removed via BILE.
64
What happens to pro-drugs in the liver?
They are activated via phase I functionalisation reactions which may involve microsomal CYP450 enzymes which oxidise drugs via a heme cofactor.
65
What 4 main factors does an ideal drug have?
1) Low Vd
2) Low toxicity risk
3) Broken down regardless of hepatic/renal function
4) Predictable dose-response relationship
66
Define steady state plasma levels
When uptake rate is in equilibrium with rate of elimination
67
What is the difference between continuous and pulsatile GnRH delivery?
```
Continuous = contraception
Pulsatile = fertility treatment
```
68
What type of receptor is a nicotinic cholinergic receptor (nAChR) and where is it found?
It is a ligand gated ion channel.
Autonomic NS= post-synaptic neuron
Somatic NS= NMJ
69
What type of receptors are muscarinic cholinergic receptors (mAChR) and where are they found?
GPCRs
| Found at the autonomic NMJ.
70
What are the 5 stages of ACh action at the NMJ?
1) Synthesis (Acetyl CoA + Choline --> CoA + ACh)
2) Storage (vesicle)
3) Stimulation + release (Na+ IN, Ca2+ IN, vesicle + membrane fuse)
4) Receptor binding (ACh + AChR --> Na+ IN)
5) Inactivation (ACh --AChE--> Acetate + choline (taken up)
71
How does the botulinum toxin (BOTOX) work at the NMJ?
1) Uses proteases to degrade ACh vesicles
2) No ACh released on stimulation
3) Paralysis
72
What is curare?
A competitive nAChR antagonist.
| Causes paralysis.
73
What can be used to reverse the effects of curare?
SUGAMMADEX
74
What is the mechanism of action of suxamethonium?
DEPOLARISING BLOCKADE (anaesthetic)
1) Binds to nAChR
2) Desensitises it
3) Paralysis
75
What is an example of a reversible cholinesterase inhibitor?
NEOSTIGMINE (MG treatment)
76
What is an example of an irreversible cholinesterase inhibitor?
ORGANOPHOSPHATES (insecticides + sarin)
77
What effects do organophosphates have at different cholinergic receptors?
1) nAChR: twitching, seizures, muscle weakness, paralysis
2) mAChR: salivation, bradycardia, hypotension, urination, defecation
3) CNS: confusion, convulsions, coma, reflex loss
78
What are 4 therapeutic targets of muscarinic ligands?
1) Eyes: glaucoma - PLIOCARPINE
2) Lungs: asthma/COPD - TRIOTROPIUM (LAMAs)
3) GI: IBS - MEBEVERINE
4) Bladder: BETHANECHOL(agonist - contraction), OXYBUTININ (antagonist - relaxation)
79
What are some adverse effects of muscarinic ligands?
DUMBELS
1) Diarrhoea
2) Urinary incontinence
3) Miosis
4) Bradycardia
5) Emesis (vomitting)
6) Lacrimation (tearing)
7) Salivation + sweating
80
What is HEXAMETHONIUM and what effects does it have?
NEURONAL nAChR COMPETITIVE ANTAGONIST
- PSNS effects: less secretions, constipation, blurred vision urine retention
- SNS effects: Hypotension (anti-hypertensive)
81
Give 3 examples of AChR ligands in the CNS. (SBD)
1. SCOPOLAMINE (motion sickness) - inhibits ACh at mAChR in vomitting centre
2. BENZATROPAMINE (Parkinson's) - inhibits ACh stimulated DA reuptake
3. DONEPEZIL (Alzheimer's) - inhibits AChE
82
Describe the synthesis of catecholamines
Phenylalanine --> L-tyrosine --> L-DOPA --> dopamine --> adrenaline and noradrenaline (--COMT--> metadrenaline + normetadrenaline)
83
What are 2 enzymes that inactivate catecholamines release?
MAO (mono-amine oxidase)
| COMT (catechol-o-methyltransferase)
84
What type of receptor are adrenoceptors?
GPCRs
85
How do alpha-1 adrenoceptors work?
| exactly like M2
1) NAd binds to a1
2) Activates Gq protein
3) Activates PLC breakdown of a membrane phospholipid to DAG + IP3
4) DAG activates PKC
5) IP3 acts to increase intracellular Ca2+
VASOCONSTRICTION, PUPIL DILATION, BLADDER RELAXATION
Agonist: PHENYLEPHRINE
Antagonist: DOXAZOSIN
86
How do alpha-2 adrenoceptors work?
| like B2Ad
1) NAd binds to a2
2) activates Gi protein
3) activates AC (ATP --> cAMP)
4) activates PKA
INHIBITS PRESYNAPTIC NAd RELEASE (negative feedback)
Agonist: CLONIDINE
Antagonist: YOHIMBINE
87
How do beta adrenoceptors work?
1) NAd binds to a2
2) activates GS
3) activates AC (ATP--> cAMP)
4) activates PKA
88
What effects does B1 stimulation have? Drug examples?
HEART: +ve chronotropism, +ve inotropism, renin secretion
Agonist: DOBUTAMINE
Antagonist: ATENOLOL (beta-blockers)
89
What effects does B2 stimulation have? Drug examples?
LUNGS: Broncodilation, vasodilation, increased gut motility
Agonist: SALBUTAMOL (SABAs)
90
What effects does B3 stimulation have? Drug examples?
Bladder relaxation, lipolysis
Agonist: MIRABEGRON
91
Give an example of a non-selective adrenergic agonist
Adrenaline
Used in: anaphylaxis, acute hypotension, cardiac arrest
92
Give an example of a non-selective adrenergic antagonist
1) PROPANOLOL: beta non-selective
| 2) CARVEDILOL: beta and alpha-1 (decreases BP, VD)
93
What are certain features of PROPANOLOL?
Non-selective BAd antagonist.
| Membrane stabilising activity (MSA) - can inhibit AP propagation so treat arrhythmias.
94
What drug should you NEVER give to asthmatics?
BETABLOCKERS
95
What are some indirect adrenergic agonists?
- Amphetamines + cocaine
| - MAO + COMT inhibitors
96
Define pain and give 3 advantages.
An unpleasant sensory and emotional experience associated with actual/potential tissue damage
1) Warning of tissue damage
2) Immobilisation for healing
3) Memory establishment
97
How do nociceptive/neuropathic pain differ?
Nociceptive involves nociceptor stimulation, neuropathic involves neuronal tissue damage.
98
After how many weeks does acute pain become classed as chronic?
12 weeks
99
What are the 4 main stages of the ascending pain pathway?
1) Noxious stimuli
2) Tissue damage (PG synthesis)
3) Nociceptor stimulation (Ad/c fibres + substance P)
4) Lateral spinothalamic tract (3 order) (2nd ON decussates)
5) Pain sensation
100
Summarise the gate-controlled theory.
Non-noxious stimuli trigger larger A beta fibres, these override smaller pain fibres and 'close the gate' to pain transmissions to the CNS.
101
What is the descending pain pathway an example of and where does it take place?
An endogenous pain control system activated under extreme stress.
Periaqueductal grey matter
102
Summarise the descending pain pathway.
1) Serotonin + NAd neurons: inhibit the 1st ON (substance P release)
2) Opiod interneurons: release endogenous opiods (e.g. enkephalins and endorphins) which inhibit both the 1st and 2nd ON
3) These produce profound analgesia
103
What is the basis of pain treatment? (3)
1) Decrease excitatory NTs (e.g. Local anaethetics)
2) Decease PGs (e.g. NSAIDs)
3) Increase inhibitory NTs (e.g. Antidepressants)
104
What percentage can't metabolise morphine or codeine?
10%
105
Give 2 naturally occurring opiods.
Morphine
| Codeine
106
Give an example of an opiod which has had simple molecular modifications. (DOD)
Diamorphine (heroin)
Oxycodone
Dihydrocodeine
107
Give an example of a synthetic opiod.
```
Pithidine
Fentanyl (very potent)
Remifentanil (very potent)
Alfentanil (very potent)
Tramadol
```
108
What is a synthetic partial opiod that DOESN'T cause respiratory depression but isn't as potent?
Buprenorphine
109
What is an opiod antagonist?
NALOXONE!!
110
Why is it better to give morphine via IV infusion rather than orally?
Because morphine has a 50% oral bioavailability so only half the dose (5mg) is required via IV.
111
If respiratory depression is such a devastating side effect of opiod OD, why can inpatients control their own administration?
Because they would fall asleep before it occurs.
| Can only give 1mg every 5 minutes as well.
112
What makes diamorphine (heroin) more dangerous than morphine?
More potent and faster acting.
| Can cross the BBB
113
What does opiod induced sustained activation of the descending pain pathway cause?
TOLERANCE + DEPENDENCE + ADDICTION
114
What are the 4 types of opiod receptors
1) μ / MOP
2) delta / DOP
3) kappa / KOP
4) Nociceptin opiod-like receptor
115
Which receptor do all current opiod drugs target?
MOP
116
What is significant about the kappa / KOP receptor?
Causes depression instead euphoria
117
What dose of morphine, diamorphine and buprenorphine have the same efficacy but different potency?
10mg morphine
5mg diamorphine
100mg buprenorphine
118
How long do opiod withdrawal symptoms last?
Start within 24 hours and last ≈ 72
119
What drug can be used to slowly and safely decrease opiod dosage?
METHODONE
120
Give 3 side effects of opiods. (NICE SIR)
```
Nausea + vomiting
Immune suppression
Constipation
Endocrine effects
Sedation
Itching
Respiratory depression
```
121
What should you always do when starting IV opiods?
LOW DOSE + TITRATE UP
122
Quick, there's an opiod induced respiratory depression what do I do?
1) ABCDE
| 2) IV NALOXONE 400ug/ml - has a short half life so give DEPOT and titrate to effect
123
What microsomal enzyme metabolises codeine to morphine?
CYP2D6
124
What % of the population has less active CYP2D6?
10-15%
125
What % of the population has overactive CYP2D6?
5%
So banned in children + pregnant/breast feeding mums
Titrated to effect
126
What % of the population have no CYP2D6?
10%
127
Why should you not give opiod to a patient with <30% renal function?
It can accumulate in the nephron and cause respiratory depression
128
What is morphine metabolised by the liver?
Morphine-6-glucuronide
129
What is tramadol?
A weak opiod agonist and also inhibits 5-HT and DA reuptake
130
What is homeopathy?
'treating like with like'
Symptom causing substances in healthy people, used to treat ill patients.
They don't interfere with other meds but are prone to placebo effect.
131
Give an advantage and a disadvantage of medicinal herbalism.
Advantage: Can be effective.
Disadvatages: Can interfere with other medications + are usually produced by an unregulated industry.
132
What drug originates from the periwinkle plant and is used to treat cancer?
Vincristine
| Vinblastine
133
What drug originates from the poppy plant and is used as analgesia?
Morphine
| Codeine
134
What drug originates from the deadly nightshade and is used to treat scarlett fever?
Atropine
135
What drug originates from the Foxglove plant and is used to treat AF?
Digitalis/Digoxin
136
What are 2 forms of drug development?
```
Fermentation (e.g. penicillin)
Rational design (e.g. propanolol)
```
137
What are insulin analogues formed by?
Recombinant DNA
138
How are monoclonal Abs (-mab) formed?
1) Mouse immunised against specific An
2) B cells checked for specific Ab production
3) Spleen removed + specific B cell obtained
4) Specific B cell + myeloma cell --> HYBRIDOMAs
5) Clonal expansion of hybridomas (infinite Ab production)
6) mAbs extracted
139
What are the 3 forms of mAbs?
1) MURINE (mouse - derived) -mab
2) CHIMERIC (human + mouse mix) -ximab
3) HUMANISED (3 hyper-variable regions) -zumab
140
Briefly describe the process of gene therapy drug production.
1) Combinatorial chemistry + biosynthesis produces a huge library of compounds
2) Compounds go through HTS (High throughput screening)
3) Generates HITs
4) Generates LEADs
5) Long, expensive, ^ attrition rate process --> DRUG
141
What is the most common classification of ADRs (adverse drug reactions)?
Rawlin-Thompson ABCDE classification
142
What are Type A ADRs?
- Augmented
- Most common
- Dose-related extension of clinical effects
E.g.
PRIMARY: Anticoagulant --> bleeding
SECONDARY: B blocker --> bronchoconstriction
143
What are Type B ADRs?
- Bizarre
- Unexpected
- Mostly hypersensitivity reactions
- Idiosyncrasy
E.g. Heparin --> hair loss
144
What are Type C ADRs?
- Chronic
- After long-term use
E.g. Steroids--> hyperglycaemia(DMT2) / Cushing's syndrome
145
What are Type D ADRs?
- Delayed
- Occur months-years after treatment
E.g.
Chemotherapy --6 weeks--> leukopenia
Thalidomide + birth defects
146
What are Type E ADRs?
- End-of-use
- Occurs after treatment stopped
E.g. Opiod withdrawal symptoms
147
What are the 5 questions asked to identify the ADR?
1) Predictable? [A]
2) Allergic reaction? [B]
3) Long-term use? [C]
4) Drug history? [D]
5) Withdrawing? [E]
148
What can increase ADR susceptibility?
1) Pregnancy
2) Age >65
3) Female
4) Drug interactions
5) Diseases
6) Diet & alcohol
7) Genetics + hypersensitivity
149
What are the 2 types of anaphylaxis?
IMMUNE: IgE-mediated
| NON-IMMUNE: direct mast cell degranulation
150
Are Type A ADRs drug allergies?
No!!
151
What is used to report ADRs?
MHRA yellow-card scheme.
Strength: Continual safety monitoring
Limitation: Not all ADRs reported (only 10% severe reactions reported)
152
Give 4 drug interactions
1) Summation: 1 + 1 = 2
2) Synergism: 1 + 1 > 2
3) Potentiation: 1 + 1 = 1 + 1.5
4) Antagonism: 1 + 1 = 0 (E.g. beta blocker and beta-2 agonist)
153
What is the name for Amoxicillin + clavulonic acid
Augmentin (AB with less likely resistance)
154
What are patient risk factors for drug interactions? (PHOG)
Polypharmacy
Hepatic/renal impairment
Old age
Genetics
155
What are drug property risk factors for drug interactions?
1) Saturable metabolism (so low HER)
2) Steep dose/response curves
3) Narrow therapeutic index (between ED50 + TD50)
156
Give examples of pharmacokinetic mechanisms of drug interactions.
1) Alter gut motility
2) Alter pH
3) Alter solubility of the other drug
4) Form non-absorbed complexes
5) Directly alter enterocyte function
6) Alter active drug distribution
7) Alter liver metabolism
8) Alter excretion
157
Would a weak base be excreted faster if urine is acidic or alkali?
ACIDIC
158
Would a weak acid be excreted faster if urine is acidic or alkali?
ALKALI
159
What are 3 broad pharmacodynamic mechanisms of drug interactions?
1) Receptor based mechanisms (agonist etc)
2) Signal transduction (
3) Physiological system interactions (drugs affecting different receptors in same system)
160
What can beta blockers e.g. propanolol cause in diabetics?
Can prevent detection of fall in BGL.
Beta-2 blocker: inhibits hyperglycaemic response
Beta-3 blocker: inhibits adipocyte detection and alteration of BGLs.
161
What is the 'triple whammy' drug response? (DAN)
Diuretic
ACEi
NSAID
162
How does grapefruit juice affect drugs?
Grapefruit juice is a CYP4A3 inhibitor, and modulates PGP in enterocytes.
Increases the bioavailibility + effectiveness of drugs e.g. Ca2+ channel blockers and anti-transplant rejection drugs.
163
How does avocado affect the absorption of fat soluble drugs like warfarin?
It causes them to dissolve due to its high fat content, decreasing its effectiveness.
164
What are 3 actions of NSAIDs?
AAA
1) Anti-inflamatory
2) Analgesic
3) Anti-pyrexic
165
What is an adverse drug reaction?
A noxious and unintended response to a drug/combination of drugs
166
Describe how rational drug design works.
Focuses on developing an antagonist from an agonist. Looks at electrostatic charge, solubility and bulk.
167
Define a side effect.
An unintended effect of a drug related to its pharmacological properties. Can be beneficial.
168
How does the drug dose related to its therapeutic range determine its ADR effect type?
Above therapeutic index = TOXIC EFFECTS
Within therapeutic index = COLLATERAL EFFECTS
Below therapeutic index = HYPERSUSCEPTIBILITY EFFECTS
169
What is an example of a mild ADR?
Nausea, drowsiness, itchy rash
170
What is an example of a severe ADR?
Respiratory depression, neutropenia, anaphylaxis, catastrophic haemorrhage
171
What are some examples of time dependent reactions?
1) Rapid
2) First dose
3) Early
4) Intermediate
5) Late
6) Delayed
172
What is an example of a rapid reaction?
Red man syndrome.
| Due to histamine release on rapid admin of vancomycin
173
What is a common example of a first dose reaction?
Hypotension and ACEi
174
What type of reaction is Stevens-Johnson syndrome?
Intermediate - delayed immunological reaction e.g. to carbamazepine.
175
Other than the Rawlins Thompson ABCDE classification, how else can ADRs be classified?
DoTS
- Dose related? (toxic, collateral, hypersusceptibility)
- Timing? (e.g. fast infusion)
- Suceptibility of patient?
176
What are F type ADRs?
- Failure of therapy
| E.g. OCP failure in presence of enzyme inducers
177
Define idiosyncrasy.
Inherent abnormal drug response.
| E.g. Enzyme deficiency, abnormal receptor activity
178
Give 3 of the most common drugs to have ADR's.
1) Antibiotics
2) Anti-neoplastics
3) Cardiovascular drugs
4) Hypoglycaemics
5) NSAIDS
6) CNS drugs
179
What are the most common systems affected by ADRs? (ReGIMED)
```
Renal
GI
Metabolic
Endocrine
Dermatological
(+ haemorrhagic)
```
180
What are some common ADRs?
- Confusion
- Nausea
- Balance problems
- Hypotension
- Constipation/Diarrhoea
181
What % of ADRs are preventable?
30-50%
182
What are black triangle drugs?
A drug undergoing additional monitoring
183
What drugs MUST be reported on the Yellow card?
1) All suspected ADRs for: vaccines and black triangle drugs
| 2) All serious suspected reactions
184
What 3 factors determine a serious reaction?
1) Fatal/life threatening
2) Disabling/incapacitating
3) Result in/prolong hospitalisation
185
Define anaphylaxis.
Extreme allergic reaction
186
Are non-immune anaphylactoid reactions considered a type 1 HS?
NO!
They do not involve prior exposure and IgE antibodies, despite being clinically identical to immune acute anaphylaxis.
They involve direct mast cell degranulation.
187
Do anaphylactic reactions always involve urticaria?
NO!
| Absent 10-20% of the time.
188
What is the usual presentation of anaphylaxis?
- Immediate
- Swelling with central cyanosis
- Wheezing, SOB
- Urticaria
- Hypotension
- Cardiac arrest
- Anaphylactic shock (lose consciousness)
189
What is the alternative presentation of anaphylaxis?
- CARDIORESPIRATORY ARREST
190
What is the 4 step management of anaphylaxis?
1) ABCDE
2) Recovery position
3) Get help
4) ADRENALINE: 500ug IM
5) Establish airway (HIGH FLOW OXYGEN)
6) IV fluid, glucocorticoids + anti-histamines
7) Equipment: ECG, pulse oximetry, BP
191
What is the most common antihistamine used in anaphylaxis?
IM CHLORPHENAMINE 10mg
192
What is the most common glucocorticoid used in anaphylaxis?
IM HYDROCORTISONE 100-200mg
193
Why do you give IV fluids e.g. 500-1000ml colloids in anaphylaxis?
Because blood volume is greatly reduced due to increased vascular permeability and exudation.
194
Why is adrenaline given in anaphylaxis?
Non-selective adrenergic agonist.
| Can vasoconstrict, bronchodilate, inhibit mast cells, myocardial contraction.
195
Why might a second dose of adrenaline be required in anaphylaxis? And it what route must it be administered?
If there is no improvement in the patient.
| IV administration must be started.
196
What confirmatory blood test is taken to diagnose anaphylaxis?
MAST CELL TRYPTASE.
Ideally 3 timed samples.
1) Immediately
2) 1-2 hrs after symptom onset
3) <24 hrs post onset
