Pharmacology Flashcards
1
Q
Inheritance of acute intermittent porphyria
A
Autosomal dominant (defect in porphobilinogen deamine - enzyme involved in biosynthesis of haem)
2
Q
Presentation of acute intermittent porphyria
A
Neuropsychiatric/abdominal symptoms in 20-40 year olds
3
Q
Sedation in someone with acute intermittent porphyria
A
Chlorpromazine - NOT diazepam
4
Q
Drugs that could precipitate acute intermittent porphyria
A
Barbiturates, benzos, alcohol, OCP, sulphonamides
5
Q
Management of accidental adrenaline injection
A
Phentolamine (short acting alpha blocker)
6
Q
Effects of adrenaline
A
Very similar to DKA - hyperglycaemia (mostly alpha adrenergic response), inhibits insulin secretion, increased lactate by adipose tissue
7
Q
What is used for alcohol abstinence?
A
Disulfuram (inhibition acetaldehyde)
8
Q
Contraindication to disulfuram use
A
Psychosis, IHD
9
Q
What can be used to reduce alcohol cravings
A
Acamprostate - weak antagonist of NMDA
10
Q
MOA allopurinol
A
Inhibits xanthine oxidase
11
Q
What drugs used in acute gout attack
A
Clochicine/NSAIDs/steroids
12
Q
Who is at increased risk of gout?
A
Ethnic minotirites
13
Q
What allele should be screened for in gout in ethnic minorities?
A
HLA B 5801
14
Q
Key drug interactions allopurinol
A
Azathioprine (25% dose reduction - allopurinol increases active compound due to 6-mercaptopurine), cyclophosphamide (decreased renal clearance), theophylline (inhibits breakdown)
15
Q
Adrenoreceptor agonists acting on alpha-1
A
Phenylephrine eg eyedrops, hypotension
16
Q
Adrenoreceptor agonists acting on alpha-2
A
Clonidine (menopause, HTN)
17
Q
Adrenoreceptor agonists acting on beta-1
A
Dobutamine eg inotrope
18
Q
Adrenoreceptor agonists acting on beta-2
A
Salbutamol
19
Q
Adrenoreceptor agonists acting on beta-3
A
Being developed, role in obesity
20
Q
Key roles alpha 1 adrenoreceptors
A
Vasoconstriction, salivary secretion, hepatic gluconeogenesis
21
Q
Key roles alpha 2 adrenoreceptors
A
Mainly pre-synaptic inhibition, inhibits insulin, platelet aggregation
22
Q
Key role beta adrenoreceptors
A
Mainly located in heart - increase HR and force, vasodilation, lipolysis
23
Q
Adrenoreceptor antagonists acting on alpha
A
Alpha 1 - doxazosin, 1a tamsulosin, 2 yohimbine, non selective - phenoxybenzamine, carvedilol, labetalol
24
Q
Adrenoreceptor antagonists acting on beta
A
B1 Atenolol, non selective propranolol
25
Cellular pathway of all adrenoreceptors
G coupled
26
What adrenoreceptors activate phospholipase C
Alpha 1
27
What adrenoreceptors inhibit phospholipase C
Alpha 2
28
What adrenoreceptors stimulate phospholipase C
Beta 1,2,3
29
What class of anti-arrhythmic is amiodarone
III
30
How does amiodarone work
Blocks potassium channels, which inhibits repolarisation therefore prolonging action potential. Also blocks Na.
31
Half life amiodarone
20-100 days
32
Monitoring of amiodarone
TFT, LFT, Us+Es, CXR prior to tx
TFT, LFT, every 6 months
33
Adverse effects amiodarone
(Amiodarone is a Bitch)
Bradycardia/Blue man (slate grey)
Interstitial Lung Disease
Thyroid (hyper and hypo)
Corneal (ocular)/photosensitivity
Hepatic(liver fibrosis, hepatitis)/Hypotension when IV (due to solvents)
Lengthens QT, peripheral neuropathy
34
What is Wolff-Chaikoff effect
An autoregulatory phenomenon, whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis (leading to hypothyroidism)
35
What is type 1 amiodarone induced thyrotoxicosis
Increased iodine induces thyroid hormone synthesis, goitre present, managed with carbimazole or potassium perchlorate
36
What is type 2 amiodarone induced thyrotoxicosis
Destructive thyroiditis, goitre absent, managed with corticosteroids
37
Draw chemotox man
https://www.google.co.uk/search?q=+chemotox+man&tbm=isch&ved=2ahUKEwih8-DXi8j9AhUtpCcCHWx7AgMQ2-cCegQIABAA&oq=+chemotox+man&gs_lcp=CgNpbWcQAzIECAAQQ1DgCVjgCWDLC2gAcAB4AIABQ4gBeJIBATKYAQCgAQGqAQtnd3Mtd2l6LWltZ8ABAQ&sclient=img&ei=FkYGZKGQLK3InsEP7PaJGA&bih=969&biw=1920#imgrc=okRVfISvxNK2RM
38
MOA propofol
GABA receptor agonist
39
What is propofol used for
Rapid onset anaesthesia, pain, antiemetic
40
Risk of propofol
Moderate myocardial depression
41
What is sodium thiopentone used for
Extremely rapid onset anaesthetic agent (rapid sequence induction), little analgesic effects
42
Risk of sodium thiopentone
Marked myocardial depression
43
MOA Ketamine
NMDA receptor antagonist
44
What is ketamine used for
Anaesthetic induction, strong analgesic. Used in those who are haemodynamically unstable - little myocardial depression
45
What is etomidate used for
Anaesthetic induction - not used in maintenance due to adrenal suppression, good cardiac profile, post op vom common
46
List antiarrhythmic drug classifications
Son of a Bitch is Potentially Correct
I - Blocks Na
II - Beta-blocker
III - Blocks K
IV - Calcium channel blockers
47
List class I antiarrhythmics
Double Quarter Pounder, Lettuce Mayo, Fries Please:
1. Class IA = Disopyramide, Quinidine, and Procainamide
2. Class IB = Lidocaine and Mexiletine
3. Class IC = Flecainide and Propafenone
48
List class 2 antiarrhythmics
MANBABE:
Metoprolol
Acebutolol
Nebivolol
Betaxolol
Atenolol
Bisoprolol
Esmolol
49
List class 4 antiarrhythmics
Verapamil, diltiazem
50
List class 3 antiarrhythmics
AIDS:
A = amiodarone
I = ibutilide
D = dofetilide
S = Sotalol
51
What antibiotics inhibit cell wall formation (petidoglycan cross linking)
Penicillins, cephalosporins, carbopenems
52
What antibiotics inhibit cell wall formation (peptidoglycan synthesis)
Glycopeptides (vanc)
53
What antibiotics inhibit protein synthesis (50S subunit) (ribosomal)
Macrolides, chloramphenicol, streptogrammins, clindamycin, linezolid
54
What antibiotics inhibit protein synthesis (30S subunit) (ribosomal)
Aminoglycosides, tetracyclines
55
What antibiotics inhibit DNA synthesis
Quinolones (ciprofloxacin)
56
What antibiotics damage DNA
Metronidazole
57
What antibiotics inhibit folic acid formation
Sulphonamides, trimethoprim
58
What antibiotics inhibit RNA synthesis
Rifampicin
59
How does aspirin work
Blocks cox 1+2 (responsible for prostaglandin, prostacycline and thromboxane synthesis).
Blocking of thromboxane A2 decreases ability of platelets to aggregate
60
What does aspirin potentiate?
Oral hypoglycaemics, warfarin, steroids
61
What is the exception to U16 use of aspirin
Kawasaki
62
How does clopidogrel work?
inhibits P2Y12
63
Features of beta blocker overdose
Bradycardia. hypotension, heart failrue, syncope
64
Treatment of beta blocker overdose
If bradycardia - atropine, in resistant cases glucagon. HAEMODIALYSIS IS NOT EFFECTIVE
65
How does botox work
Blocks release of acetylchloride
66
Indications botox
Blepharospasm, hemifacial spasm, focal spasticity, spasmodic torticollis, severe hyperhidrosis, achalasia
67
Classes of calcium channel blocker
Centrally acting - focus on heart rhythm (non-dihydropyridines), eg verapamil, diltiazem.
Members of the other class (dihydropyridines) all end in -dipine (e.g., nicardipine, amlodipine).
68
Side effects verapamil
HF, constipation, hypotension, brady
69
Side effects diltiazem
Hypotension, brady, HF, ankle swelling
70
Side effects dihydropyridines
Flushing, headache, ankle swelling
71
Features of CO poisoning
Headache, confusion, N+V. subjective weakness, vertigo
Severe - pink skin, hyperpyrexia, extrapyramidal features
72
Investigations CO poisoning
Pulse oximetry may be high, carboxyhaem levels <3% in non smokers, <10% in smokers
73
Management CO poisoning
100% O2 for minimum 6 hours, treat until symptoms resolve
74
Indications for hyperbaric oxygen CO poisoning
LOC, neurology, MI/arrhythmia
75
Management of corrosive substance ingestion
Gen surg if perf, IV PPI, if symptomatic needs endoscopy
If asymptomatic - fluids and observation
76
MOA ciclosporin
DMARD - ecreases clonal proliferation of T cells by decreasing IL2 release
77
Side effects of ciclosporin
Increases everything (fluid, BP, hair, gums, glucose). Increased susceptibility to severe infection.
78
Indications cuclosporin
Following organ transplant, RA, psoriasis, UC, red cell aplasia
79
Risks COCP
VTE, breast and cervical cal, stroke and IHD, temproary SE
80
Contraindications COCOP
UKMEC 4 -
BMI >35, smoking > 15/day
Migraine with aura
VTE
Stroke
Breast feeding <6 weeks postpartum
Uncontrolled htn
BReast ca
Major surgery
SLE
UKMEC 3-
Gallbladder disease, controlled HTN, BMI >35
81
What decreases COCP efficacy
Vomit within 2 hours, liver enzyme inducing drugs eg rifampicin
82
MOA cocaine
Blocks uptake of dopamine, noradrelaine, serotonin
83
Rare SE cocaine
Ichaemic colitis, hyperthermia, metabolic acidosis, rhabdomylosis
84
Management of cocaine toxicity
Benzos
85
Management of HTN in context of cocaine
Benzos and sodium nitroprusside
86
Physiology of cyanide poisoning
Inhibits enzyme cytochrome C, resulting in cessation of mitochondrial electron transfer chain
87
Presentation of cyanide poisoning
Brick red skin, smell of bitter almonds:
- Acute: hypoxia, hypotension, headache
- Chronic: ataxia, peripheral neuropathy, dermatitis
(metabolic acidosis due to increased lactate)
88
Management of cyanide posioning
100% Oxygen, IV hydroxycoblamain, inhaled amynitrate, sodium nitrate, sodium thiosulphate
89
MOA digoxin
Decreases conduction through AV node, increased force of cardiac muscle contraction due to inhibition of Na/K/ATPase pump
90
When is digoxin level taken
Within 8-12 hours of last dose
91
Features of digoxin toxicity
Lethargy, nausea, green/yellow vision, gynaecomastia
92
Precipitating factors of digoxin toxicity
Hypokalaemia, hypomagnesmia, hypercalcaemia, hypernatraemia, acidosis, hypothyroidism
93
What drugs can precipitate digoxin toxicity
Amiodarone, CCB, spironolactone, ciclosporin, any drugs causing decrease in K eg loop diuretics
94
Management of digoxin toxicity
Digibind, correct arrhythmias, monitor K
95
Indications dopamine receptor agonists
Parkinsons, cyclical breast disease, acromegaly, prolactinoma
96
What must be checked before starting bromocriptine
Associated with pulmonary, retronperoneal and cardiac fibrosis so ESR, CXR and Cr obtained prior to treatment
97
Adverse effects dopamine agonists
N+V, daytime solomence, postural hypotension, hallucinations
98
Triad dress syndrome
Dermatitis, high fever, inflammation in 1 or more organs
+ eosinophilia, abnormal LFT
99
When does rash normally commence DRESS syndrome
2-8 weeks following commencement of drug
100
Drug precipitants of dress
Allopurinol, anti epileptics, Abu, immunosuppressants
101
Management of dress syndrome
Stop cause, antihistamines, topical steroids, emollients. Occasionally immunosupressants, IVIG, plasma
102
Drug monitoring statins
LFTs 3 months, 12 months
103
Drug monitoring ACEi
Prior, after dose change, annually
104
Drug monitoring amiodarone
TFTs, LFTs, Us+Es, xray prior to Tx
TFT and LFTs 6 monthly
105
Drug monitoring methotrexate
FBC, LFTs, Us+Es before, weekly until stabilised, 2-3 monthly
106
Drug monitoring azathioprine
FBC, LFTs, before treatment, weekly first 4 weeks, every 3 months
107
Drug monitoring lithium
TFTs, Us+ES prior to, weekly until stabilised then 6 monthly
108
Drug monitoring sodium valproate
LFT, FBC before treatment. LFTs periodically during first 6 months
109
Drug monitoring glitazones
Before treatment and regularly
110
Drug causes agranulocytosis (WBC most commonly neutrophils)
Drugs can cause pretty major collapse to granulocytes:
Dapsone
Clozapine
Carbamazepine
Propylthiouracil, penicillin
Mirtazapine, methotrexate
Colchicine, chloramphenicaol
Co-Trim
Ganciclovir
111
Drug causes urticaria
Penicillins, aspirin, NSAIDs, opiates
112
Drug causes impaired glucose tolerance
Thiazides, furosemide, steroids, tacrolimus, cilosporin, interferon alpha, nicotinic acid, antipsychotics.
BB used in caution in diabetics
113
Drugs causing thrombocytopenia
ABCDE - HI
anti- Arrhythmics: quinidine, beta-blockers
antiBiotics: Penicillins, cephalosporins, sulphonamides, rifampicin
anti- Coagulants: Heparin, abciximab
Diuretics - furosemide
anti- Epileptics: Valproic acid, carbamazepine
-
anti- Histamines: cimetidine
anti- Inflammatory: Aspirin, Indomethacin, NSAIDs
Quinine
114
Drugs causing urinary retention
Tricyclic antidepressants, anticholinergics, opioids, NSAIDs, Disopyramide (class 1A anti-arrhythmic)
115
Drugs causing lung fibrosis
amiodarone, cytotoxic, anti-rheumatoid, nitrofurantoin, dopamine receptor agonists
116
Drugs causing ocular problems
Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy
117
Drugs causing cataracts
Steroids (ster-eye-ds)
118
Drugs causing corneal opacities
Amiodarone, indomethacin
119
Drugs causing optic neuritis
Ethambutol, amiodarone, metronidazole
120
Drugs causing retinopathy
Chloroquine, quinine
121
What causes blue discolouration and non aretritic anterior ischaemic neuropathy?
Sildenafil
122
Can hydroxychloroquinine cause eye problems
Yes lol
123
Drugs causing photosensitivity
Thiazides, tetracyclines, sulphonamides, ciprofloxacin, amiodarone, NSAIDs, sulphonylureas
124
Name agonists of 5-HT system (migraine mx)
Sumatriptan, ergomatine (partial)
125
Name antagonists of 5-HT system (prophylaxis migraine)
Pizotifen (migraine), cyproheptadine (diarrhoea in carcinoid), ondansetron (5HT3)
126
Features of ecstasy poisoning
Tachy, hypertension, agitation, hyperthermia, rnhabdomylosis
127
Management ecstacy poisoning
Supportive, dantrolene for hyperthermia if simple measures fail
128
Stages of ethylene glycol toxicity (coolant, anti-freeze)
1. Confusion, slurred speech, dizziness
2. Metabolic acidosis with high anion gap + high osmolar gap
3. AKI
129
Management of ethylene glycol toxicity
Fomepizole (alcohol dehydrogenase inhibitor)
130
How does ethanol work in management of ethylene glycol toxicity
Competes with ethylene glycol for alcohol dehydrogenase enzyme therefore limiting formation of toxic metabolites (glycoaldehyde and glycolic acid)
131
Is haemodialysis used in ethylene glycol toxicity?
Only in refractory cases
132
MOA finasteride
Inhibitor of 5 alpha reductase - enzyme testosterone
133
Indications finasteride
BPH, male pattern baldness
134
Adverse effects finasteride
Decreased libido, gynaecomastia, impotence, can decrease PSA
135
MOA flecanide
Na channel blocker - slows conduction of action potential widening of QRS, prolongs PR
136
Indications flecanide
AF, SVT with accessory
137
Contraindications flecanide
Post MI, structural heart disease, sinus mode dysfunction, atrial flutter
138
Adverse effects flecainide
Neg inotrop, bradycardia, oral parasthesia, visual disturbance
139
What type of antibiotic is gentamicin?
Aminoglycoside
140
Nephrotoxicity in gentamicin toxicity is caused by
Renal tubular necrosis
141
Contraindication to gentamicin use
Myasthenia gravis
142
Drugs that can be cleared with haemodialysis
Barbiturate, lithium, alcohol, salictyes, theophyllines
143
Is heparin allowed in pregnancy?
Yes, but no DOACs
144
How does heparin work?
Activates antithrombin 3
145
Adverse effects heparin
Bleeding, thrombocytopenia, osteoporosis, increased K
146
Standard heparin - MOA
Activates antithrombin 3, forms a complex that inhibits thrombin, factors Xa, IXa, XIa, and XIIa
147
Standard heparin - monitoring
APTT
148
LMWH - MOA
Activates antithrombin 3 - forms a complex that in habits factor Xa (monitor this)
149
When is standard heparin used
Renal failure, contexts where may need reversed rapidly
150
Mechanism in heparin induced thrombocytopenia
Antibodies form against complexes of platelet factor 4 (PF4) and heparin. These antibodies bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors
151
Reversal of heparin overdose
Protamine sulphate, although this only partially reverses the effect of LMWH
152
When does heparin induced thrombocytopenia occur?
5-10 days after treatment. Also remember it is a prothrombotic state despite the low platelets
153
Statins MOA and adverse effects
HMG CoA reductase inhibitors,
Myositis, deranged LFTs
154
Ezetimibe MOA and adverse effects
Decreases cholesterol absorption in the small intestine,
Headache
155
Nicotinic acid MOA and adverse effects
Decreases hepatic VLDL secretion,
Flushing and myositis
156
Fibrates MOA and adverse effects
Agonist of PPAR-alpha therefore increases lipoprotein lipase expression,
Myositis, pruritus, cholestasis
157
Cholestyramine MOA and adverse effects
Decreases bile acid reabsorption in the small intestine, upregulating the amount of cholesterol that is converted to bile acid
GI side-effects
158
Causes of low Mg
Diuretics, PPI, TPN, low K, high Ca (2ndary to hyperparathyroidism), metabolic disorders - bartters, gitelmans
159
Features low Mg
Parasthesia, tetany, decreased PTH secretion so decreased Ca, also exacerbates digoxin toxicity, seizures
160
What is the half life of immunoglobulins (IgG)?
3 weeks
161
What is the therapeutic range of lithium?
0.4-1 (toxicity >1.5)
162
Precipitants of lithium toxicity
Dehydration, renal failure, drugs = DAMN: diuretics, ACEi, metronidazole, NSAIDs
Or remember it as less water, kidneys, met
163
Features of lithium toxicity
Coarse tremor (fine in therapeutic levels), hyperreflexia, polyuria, seizure, coma
164
Management lithium toxicity
Mild - fluid resuscitation, severe - haemodialysis. Limited evidence for NaHCO3 (supposed to increased alkalinity of urine)
165
What type of drug is lidocaine?
An amdie
166
Management of lidocaine toxicity
IV 20% lipid emulsion
167
Key drug interactions of lidocaine
Beta blockers, ciprofloxacin, phenytoin
168
Features of lidocaine toxicity
Initial CNS over activity then depression as lidocaine initially blocks inhibitory pathways then blocks both inhibitory and activating pathways. Cardiac arrhythmias.
169
When is cocaine mostly used?
As a paste in ENT surgery (great vasoconstriction)
170
MOA bupivicaine
Binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization - long duration of action
171
Why is bupivocaine not used in regional blockage?
Cardiotoxic and is therefore contra indicated in regional blockage in case the tourniquet fails
172
What local anaesthetic can be used as regional blockage?
Prilocaine - because far less cardiotoxic
173
How would an abscess affect efficacy of local anaesthetic?
All local anaesthetic agents dissociate in tissues and this contributes to their therapeutic effect. The dissociation constant shifts in tissues that are acidic e.g. where an abscess is present, and this reduces the efficacy.
174
Max doses lignocaine
Lignocaine 1% plain - 3mg/ Kg - 200mg (20ml)
Lignocaine 1% with 1 in 200,000 adrenaline - 7mg/Kg - 500mg (50ml)
175
Max doses bupivicaine
Bupivicaine 0.5% - 2mg/kg- 150mg (30ml) (adrenaline does not allow increased dose)
176
Contraindication to adrenaline use with local anaesthetic
MAOI's or tricyclic antidepressants
177
Name macrolides
Erythromycin, clarithromycin, azithromycin
178
MOA macrolides
Inhibit bacterial protein synthesis by blocking translocation. Bacteriostatic
179
Mechanism of resistance macrolides
Post-transcriptional methylation of the 23S bacterial ribosomal RNA
180
SE macrolides
prolongs QT interval
GI SE - nausea is less common with clarithromycin than erythromycin. Also promotes gastric emptying!
Cholestatic jaundice
P450 inhibitor
Azithromycin is associated with hearing loss and tinnitus
181
What drug should be stopped if starting macrolide?
Statin - increased risk of myopathy and rhabdomylosis
182
Features of mercury poisoning
paraesthesia
visual field defects
hearing loss
irritability
renal tubular acidosis
183
Treatment of motion sickness
Hyoscine > cyclising > promethazine
184
MOA metformin
Biguanide. Activation of AMP-activated protein kinase:
Increases insulin sensitivity
Decreases hepatic gluconeogenesis
Decreases gastrointestinal absorption of carbs
185
Adverse effects metforin
Diarrhoea, lactic acidosis in severe liver disease/renal failure. Can cause decrease vit B12
186
CI to metformin use
CKD - dose review if eGFR <45, stop if <30
Alcohol abuse relative contraindication
187
When should you withhold metformin?
Recent MI, sepsis, AKI, severe dehydration
188
If someone cant tolerate metformin due to GI upset what's the next step?
Try reduced dose and MR before switching to second line
189
Over what time period is metformin titrated
1 week
190
What are monoclonal antibodies?
Manmade proteins that bind to antigens
191
How are monoclonal antibodies made?
Somatic cell hybridisation - fusion of myeloma and spleen cells from a mouse that has been immunised with the desired antigen --> hybridoma --> can produce myoconal antibodies
192
What is humanising (monoclonal antibodies)?
A process that decreases immunogenicity of non human derived monoclonal antibodies
193
What is infliximab used for?
Anti-TNF - Rheumatoid arthritis and Crohn's
194
What is rituximab used for?
Anti-CD20 - used in non-Hodgkin's lymphoma and rheumatoid arthritis
195
What is cetuximab used for?
Epidermal growth factor receptor antagonist - used in metastatic colorectal cancer and head and neck cancer
196
What is trastuzumab used for?
(HER2/neu receptor antagonist): used in metastatic breast cancer
197
What is alemtuzumab used for?
(anti-CD52): used in chronic lymphocytic leukaemia
198
What is abciximab used for?
(glycoprotein IIb/IIIa receptor antagonist): prevention of ischaemic events in patients undergoing percutaneous coronary interventions
199
What is OKT3 used for?
(anti-CD3): used to prevent organ rejection
200
Other uses monoclonal antibodies? In terms of diagnosis
medical imaging when combined with a radioisotope
identification of cell surface markers in biopsied tissue
diagnosis of viral infections
201
Features of methanol poisoning?
Intoxication, nausea, blindness
202
Mechanism of blindness methanol poisoning?
Thought to be caused by a form of optic neuropathy, formed by accumulation of formic acid
203
Management methanol poisoning
Fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
Haemodialysis
Cofactor therapy with folinic acid to reduce ophthalmological complications
204
MOA suxamethonium
Depolarising neuromuscular blocker (only depolarising of muscle relaxants!)
Inhibits action of acetylcholine at the neuromuscular junction
205
Adverse effects suxamethonium
Hyperkalaemia, malignant hyperthermia and lack of acetylcholinesterase
Fastest onset and shortest duration of all muscle relaxants
206
MOA atracurium
Non depolarising neuromuscular blocking drug
207
Adverse effects atracurium
Generalised histamine release on administration may produce facial flushing, tachycardia and hypotension
208
MOA vecuronium
Non depolarising neuromuscular blocking drug
209
MOA pancuronium
Non depolarising neuromuscular blocker
210
What is used to reverse non depolarising muscle relaxants?
Neostigmine (pancuronium only partially)
211
What are novel psychoactive susbtances (legal highs) chemically similar to?
MDMA and cannabis (so side effect profile similar - serotonin syndrome)
212
What are hallucinogenics similar to?
Ketamine
213
When taken with alcohol Gamma-hydroxybutyric acid (GHB) can cause what?
Life threatening respiratory depression
214
What is octreotide?
Long-acting analogue of somatostatin
somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin
215
Uses of octreotide
Acute treatment of variceal haemorrhage
Acromegaly
Carcinoid syndrome
Prevent complications following pancreatic surgery
VIPomas
Refractory diarrhoea
216
Adverse effect ocreotide
gallstones (secondary to biliary stasis)
217
What is oculogyric crisis?
Dystonic reaction to certain drugs
218
Features of oculogyric crisis
Restlesness, involuntary upward deviation of eyes
219
Causes oculogyric crisis
Antipsychotics, metaclopramide, postencephalitic Parkinson's disease
220
Management of oculogyric crisis
Intravenous antimuscarinic: benztropine or procyclidine
221
Those with a penicillin allergy might also be allergic to
cephalosporins.
Also remember - co-amox, co-fluampicil, tazocin, timentin
222
Can POP be used when breastfeeding
Yes, also used in smoking and increased BMI
223
Adverse effect POP
Increased incidence of functional ovarian cysts
224
Describe physiology of paracetamol overdose
Liver normally conjugates paracetamol to glnucaronic acid. Saturation -> oxidation by p450 -> toxic metabolite (NAPQI).
Non toxic normal production forms mercaptopuric. If glutathione runs out toxins form covalent bonds with cell proteins leading to cell death.
Note low threshold for treating those taking P450 meds)
225
Whats N-acetyle cystine
Precursor of glutathione so can increase hepatic glutathione production
226
Criteria for liver transplant paracetamol OD
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy
227
Who may benefit from activated charcoal in paracetamol OD?
Those who present within 1 hour
228
Increased risk of hepatotoxicity in paracetamol OD
Liver enzyme inducing drugs
Malnourished
Note acute alcohol may be protective!
229
Management of paracetamol OD
<1 hour activated charcoal
NAC if staggered regardless of plasma conc (Staggered is taking >1 hour)
Or if above line at 4 hours
patients who present 8-24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available
patients who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal acetylcysteine should be continued if the paracetamol concentration or ALT remains elevated whilst seeking specialist advice
230
Adverse reaction of NAC
Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.
Watch for delayed nephrotoxicity
231
MOA rifampicin
inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
232
SEs rifampicin
potent liver enzyme inducer
hepatitis, orange secretions
flu-like symptoms
233
MOA isoniazid
inhibits mycolic acid synthesis
234
SE isoniazid
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
235
MOA pyrazinamide
converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
236
SE pyrazinamide
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
237
MOA ethambutol
inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
238
SE ethambutol
optic neuritis: check visual acuity before and during treatment
dose needs adjusting in patients with renal impairment
239
What are phosphodiesterase type V inhibitors used for?
Erectile dysfunction, pulmonary hypertension
240
MOA phosphodiesterase type V inhib
Vasodilation through increased cGMP leading to smooth muscle relaxation in blood vessels supplying corpus callous
241
Contraindication to phosphodiesterase type V inhib
Those taking nitrates and related drugs
Recent stroke/MI - need to wait 6 months
242
SE phosphodiesterase type V inhib
Blue discolouration of vision
Non arteric anterior ischaemic nephropathy
Nasal congestion
Flushing
Headache
Priapism
243
Risks of fluid overload post pic (acidosis)
Hyperchloraemic acidosis
Note if oedematous treat hypovolaemia first
244
What are the groups for potassium sparing diuretics?
Epithelial Na channel blockers - amiloride, triamterene
Aldosterone antagonist - spironolactone, eplerenone
245
How is amiloride normally given?
With a thiazide as an alternative to K supplementation
246
Where do aldosterone antagonists work?
Cortical collecting duct
247
Indication aldosterone antagonists
Ascites - patients with cirrhosis develop 2ndary hyperaldosteronism
HF
Nephrotic syndrome
Conns
248
What abx should not be given in pregnancy
Tetracyclines, aminoglycosides, sulphonamides and trimethoprim, quinolone
249
Can ACEi/ARBs be used in pregnancy
No
Neither can warfarin, sulphonylureas or statins
250
What medications can exacerbate HF?
thiazolidinediones - pioglitazone is contraindicated as it causes fluid retention
verapamil - negative inotropic effect
NSAIDs/glucocorticoids - should be used with caution as they cause fluid retention. Low-dose aspirin is an exception - many patients will have coexistent cardiovascular disease and the benefits of taking aspirin easily outweigh the risks
Class I antiarrhythmics
flecainide (negative inotropic and proarrhythmic effect)
251
Key drugs to avoid in renal failure
antibiotics: tetracycline, nitrofurantoin
NSAIDs
lithium
metformin
252
Drugs needing dose adjustment in CKD
most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
digoxin, atenolol
methotrexate
sulphonylureas
furosemide
opioids
253
Mechanism of st johns wort
Shown to be as effective as tricyclic antidepressants in the treatment of mild-moderate depression
mechanism: thought to be similar to SSRIs (although noradrenaline uptake inhibition has also been demonstrated)
254
Adverse effects st johns wort
Profile in trials similar to placebo
Can cause serotonin syndrome
Inducer of P450 system, therefore decreased levels of drugs such as warfarin, ciclosporin. The effectiveness of the combined oral contraceptive pill may also be reduced
255
Tamoxifen MOA
Tamoxifen is a Selective oEstrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor positive breast cancer
256
Adverse effects tamoxifen
menstrual disturbance: vaginal bleeding, amenorrhoea
hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects
venous thromboembolism
endometrial cancer
257
How long is tamoxifen typically used for?
5 years following removal of the tumour.
Note - Raloxifene is a pure oestrogen receptor antagonist, and carries a lower risk of endometrial cancer
258
MOA tacrolimus
decreases clonal proliferation of T cells by reducing IL-2 release
binds to FKBP forming a complex which inhibits calcineurin, a phosphotase that activates various transcription factors in T cells
259
MOA ciclosporin
Same as tacrolimus but binds to cyclophilin rather than FKBP
260
What type of drug is tacrolimus
Calcineurin inhibitor
261
Adverse effects tacrolimus
Nephrotoxicity and impaired glucose tolerance (more common than cyclosporin because more potent and risk of organ rejection is therefore less)
262
Monitoring of lithium
range = 0.4 - 1.0 mmol/l
take 12 hrs post-dose
263
Montioring ciclosporin
trough levels immediately before dose
264
Monitoring digoxin
at least 6 hrs post-dose
265
When should phenytoin levels be checked
Trough level immediately before dose if:
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
266
Whats the other name for trastuzumab and what's its MOA
Herceptin - monoclonal antibody directed against the HER2/neu receptor
267
Adverse effects trastuzumab
flu-like symptoms and diarrhoea are common
cardiotoxicity - more common when anthracyclines have also been used, an echo is usually performed before starting treatment
268
MOA organophosphate insecticide poisoning
Inhibits acetylcholinesterase - leads to up regulation of nicotinic and muscarinic cholinergic neurotransmission
(Sarin gas) (accumulat acetylechloride)
269
Features organophosphate insecticide poisoning
SLUD
Salivation
Lacrimation
Urination
Defication/diarrhoea
Bradycardia, hypoT, small pupils, muscle fasciculations
270
Management organophosphate insecticide poisoning
Atropine
271
Management of salicyte overdose
Urinary alkalinization with IV bicarbonate
haemodialysis
272
Management opiod overdose
Naloxone
273
Management of benzodiazepine overdose
Flumazenil
The majority of overdoses are managed with supportive care only due to the risk of seizures with flumazenil. It is generally only used with severe or iatrogenic overdoses.
274
Management tricyclic antidepressant OD
IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity - priority is to correct the acidosis over direct correction of arrhythmias (class 1a and 1c contraindicated)
Dialysis ineffective
275
Management of lithium toxicity
Mild-moderate toxicity may respond to volume resuscitation with normal saline
haemodialysis may be needed in severe toxicity
sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion
276
Management warfarin OD
Vitamin K, prothrombin complex
277
Management heparin OD
Protamine sulphate
278
Management beta blocker OD
if bradycardic then atropine
in resistant cases glucagon may be used
279
Management of ethylene glycol OD
Ethanol has been used for many years
works by competing with ethylene glycol for the enzyme alcohol dehydrogenase
this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
haemodialysis also has a role in refractory cases
280
Management methanol OD
fomepizole or ethanol
haemodialysis
281
Management of organophosphate insecticide OD
atropine
282
Management digoxin OD
Digoxin-specific antibody fragments
283
Management iron OD
Desferrioxamine, a chelating agent
284
Management lead OD
Dimercaprol, calcium edetate
285
Management OD poisoning
100% oxygen
hyperbaric oxygen
286
Management cyanide poisoning
Hydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate
287
What is P450 enzyme?
Haem protein that plays a role in drug metabolism. Mainly found in liver and gut. Main effect is to catalyse oxidation, making the substrate more water soluble so can be excreted by kidneys
288
p450 inducers
CRAPGPs:
Carbemazepines
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbitone
Sulphonylureas, St Johns Wort, Smoking (affects CYPIA2)
289
p450 inhibitors
SICKFACES.COM:
Sodium valproate, SSRI
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Acute alcohol & Grapefruit juice, amiodarone , allopurinol
Chloramphenicol
Erythromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
290
Features tricyclic overdose
Early - dry mouth, dilated pupils, agitation, sinus tachy, blurred vision
Severe - acidosis, arrhythmia, seizures, coma
291
ECG changes tricyclic overdose
Sinus tachy, widening QRS (>100 risk of seizures, >160 risk of ventricular arrhythmias), prolong QT
292
Why might IV lipid emulsion be used in tricyclic overdose?
Bind free drug and reduce toxicity
Remember dialysis ineffective in tricyclic
293
Effect on fetus of ACEi
Renal dysgenesis
Craniofacial abnormalities
294
Effect on fetus aclohol
Craniofacial abnormalities
295
Effect on fetus aminoglycosides
Ototoxicity
296
Effect on fetus carbamazepine
Neural tube defects
Craniofacial abnormalities
297
Effect on fetus chloramphenicol
Grey baby syndrome
298
Effect on fetus cocain
IUGR, preterm labour
299
Effect on fetus diethylstilbestrol
Vaginal clear cell adenocarcinoma
300
Effect on fetus lithium
Ebstein anomaly (atrialized right ventricle)
301
Effect on fetus maternal diabetes
Macrosomia
Neural tube defects
Polyhydramnios
Preterm labour
Caudal regression syndrome
302
Effect on fetus smoking
Preterm labour, IUGR
303
Effect on fetus tetracyclines
Discoloured teeth
304
Effect on fetus thalidomide
Limb reduction defects
305
Effect on fetus valproate
Neural tube defects, craniofacial abnormalities
306
Effect on fetus warfarin
Craniofacial abnormalities
307
Other name for quinine toxicity
Cinchonism
308
Signs/symptoms cinchonism
Tinnitus, visual blurring, flushed dry skin, abdo pain. Similar to salivate.
Hypoglycaemia - stimulates pancreas insulin secretion
309
Cardiac arrhythmias associated with cinchonism
Prolonged QT due to blockade of Na and K channels --> v fib/v tach
310
Management cinchonism
Fluid, inotropes, bicarbonates, PPV - pulmonary oedema
311
SE metformin
Gastrointestinal side-effects
Lactic acidosis
312
SE sulphonylureas
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
313
SE glitazones
Weight gain
Fluid retention
Liver dysfunction
Fractures
314
SE gliptins
Pancreatitis
315
SE CCB
Headache
Flushing
Ankle oedema
316
SE verapamil
Constipation
317
SE Beta blocker
Bronchospasm (especially in asthmatics)
Fatigue
Cold peripheries
Sleep disturbance
318
SE Nitrates
Headache
Postural hypotension
Tachycardia
319
SE Nicorandil
Headache
Flushing
Anal ulceration
320
Causes of serotonin syndrome
Monoamine oxidase inhibitors
SSRIs (St John's Wort can interact with SSRIs to cause serotonin syndrome)
Tramadol may also interact with SSRIs
Ecstasy
Amphetamines
321
Features of serotonin syndrome
Neuromuscular excitation - hyperreflexia, myoclonus, rigidity
Autonomic nervous system excitation - hyperthermia, sweating
Altered mental state
confusion
322
Management of serotonin syndrome
Supportive including IV fluids
Benzodiazepines
More severe cases are managed using serotonin antagonists eg cyproheptadine and chlorpromazine
323
Difference between serotonin syndrome and neuroepileptic syndrome
Neuroepileptic tends to be slower onset, decreased reflexes not increased, no dilated pupils. Also more associated with a raised CK (though both might)
324
Management of severe neuroepileptic syndrome
Dantrolene
325
MOA quinolones
Inhibiting DNA synthesis and are bactericidal in nature. inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
326
Mechanism of resistance quinolones
mutations to DNA gyrase, efflux pumps which reduce intracellular quinolone concentration
327
Adverse effects quinolones
Lower seizure threshold in patients with epilepsy
Tendon damage (including rupture) - the risk is increased in patients also taking steroids
Cartilage damage has been demonstrated in animal models and for this reason quinolones are generally avoided (but not necessarily contraindicated) in children
Lengthens QT interval
328
Contraindications quinolones
Pregnancy
G6PD
329
Salicyte overdose acidosis or alkalosis?
Mixed respiratory alkalosis and metabolic acidosis.
Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis.
In children metabolic acidosis tends to predominate.
330
Features salivate overdose
hyperventilation (centrally stimulates respiration)
tinnitus
lethargy
sweating, pyrexia (increased O2 consumption and increased CO2 and heat production)
nausea/vomiting
hyperglycaemia and hypoglycaemia
seizures
coma
331
Management salicyte overdose
gGneral (ABC, charcoal)
Urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
Haemodialysis
332
Indications for haemodialysis
Serum concentration > 700mg/L
Metabolic acidosis resistant to treatment
Acute renal failure
Pulmonary oedema
Seizures
Coma
333
Drug receptor decongestants (e.g. phenylephrine/oxymetazoline)
Alpha 1 agonist
334
Drug receptor glaucoma (e.g. topical brimonidine)
Alpha 2 agonist
335
Drug receptor benign prostatic hyperplasia (e.g. tamsulosin)
Alpha antagonist
336
Drug receptor hypertension (e.g. doxazosin)
Alpha antagonist
337
Drug receptor inotropes (e.g. dobutamine)
Beta 1 agonist
338
Drug receptor non-selective & selective beta-blockers (e.g. atenolol, bisoprolol)
Beta 1 antagonist
339
Drug receptor bronchodilators (e.g. salbutamol)
Beta 2 agonist
340
Drug receptor non-selective beta-blockers (e.g. propranolol, labetalol)
Beta 2 antagonist
341
Drug receptor parkinson's disease (e.g. ropinirole)
Prolactinoma
Dopamine agonist
342
Drug receptor schizophrenia (antipsychotics e.g. haloperidol), anti-emetics (e.g. metoclopramide/domperidone)
Dopamine antagonist
343
Drug receptor benzodiazepines eg baclofen
GABA agonist
344
Drug receptor Flumazenil
GABA antagonist
345
Drug receptor antihistamines (e.g. loratadine)
Histamine 1 antagonist
346
Drug receptor antacids (e.g. ranitidine)
Histamine antagonist
347
Drug receptor glaucoma (e.g. pilocarpine)
Muscarinic agonist
348
Drug receptor:
Atropine (e.g. for bradycardia)
Bronchodilator (e.g. ipratropium bromide, tiotropium)
Urge incontinence (e.g. oxybutynin)
Muscarinic antagonist
349
Drug receptor:
Nicotine
Varenicline (used for smoking cessation)
Depolarising muscle relaxant (e.g. suxamethonium)
Nictonic agonist
350
Drug receptor: Non-depolarising muscle relaxants (e.g. atracurium)
Nictonic antagonist
351
Drug receptor Inducing labour (e.g. Syntocinon)
Oxytocin agonist
352
Drug receptor Tocolysis (e.g. atosiban)
Oxytocin antagonist
353
Drug receptor Triptans (for acute migraine, e.g. zolmitriptan)
Serotonin agonist
354
Drug receptor anti-emetics (e.g. ondansetron)
Serotonin antagonist
355
Adrenaline dose anaphylaxis
anaphylaxis: 0.5ml 1:1,000 IM
356
Adrenaline dose cardiac arrest
cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV
357
Management of accidental injection e.g. resulting in digital ischaemia
local infiltration of phentolamine
358
Where is adrenaline released from
adrenal glands
359
Effects of adrenaline in CO, pulse pressure and total peripheral resistance
Increases cardiac output and total peripheral resistance
causes vasoconstriction in the skin and kidneys causing a narrow pulse pressure
360
Actions of adrenaline on alpha adrenergic receptors
Inhibits insulin secretion by the pancreas
Stimulates glycogenolysis in the liver and muscle
Stimulates glycolysis in muscle
361
Actions of adrenaline on beta adrenergic receptors
Stimulates glucagon secretion in the pancreas
Stimulates ACTH
Stimulates lipolysis by adipose tissue
362
What receptors does adrenaline act on
acts on α 1 and 2, β 1 and 2 receptors
acts on β 2 receptors in skeletal muscle vessels-causing vasodilation
363
What is pharmacodynamics?
What drugs do to the body
364
What is pharmacokinetcis?
What the body does to the drugs
365
What is an ion channel? (pharmacodynamics)
Simplest form of receptor. Channel either opened or closed (agonist or antagonist). Eg most local anaesthetics work on voltage gated Na channels
366
Give an example of a drug that works via ion channel
Zolpidem
367
What are G-protein coupled (pharmacodynamics)
When drugs bind to a target it causes a sequence of events with G protein subunits - production of secondary messengers eg cyclic AMP or protein phospholyration cascade
368
Give an examaple of a drug that works via G protein coupled
Adrenaline
369
What are tyrosine kinase receptors (pharmacodynamics)
Series of steps. Phosphorylation causing effects eg cell growth and differentiation
370
Example of a drug that works via tyrosine kinase receptors
Insulin like growth factor, cytokines like IL-2
371
What are nuclear receptors (pharmacodynamics)
Increased or decreased gene transcription. Lipid soluble because penetrate cell membrane. Then forms a complex with receptor protein before exhibiting effect
372
Give and example of a drug that works via nuclear receptors
Steroids, levothyroxine
373
What are agonists
drugs which activates the receptor.
374
What are antagonists
Those which block a receptor preventing activation, it is important to note they do not deactivate a receptor
375
What are competitive antagonists
Binds at same site as agonist
376
What are non competitive antagonists
Binds at another site causing change at site where agonist would otherwise bind
377
What is binding affinity
How readily the drug will bind to a specific receptor
378
What is efficacy
How able an agonist is to produce a response once bound
379
What is potency
Concentration at which drug is effective
380
What is therapeutic index
Ratio of the dose of a drug resulting in an undesired effect compared to desired effect
381
What is first order kinetics
The rate of drug elimination is proportional to drug concentration
382
What is zero order kinetics
Rate of excretion is constant despite changes in plasma) conc (saturation of metabolic process)
383
Example of drugs exhibiting zero order kinetics
Phenytoin and salicylates
384
What are phase 1 reactions?
Oxidation, reduction, hydrolysis. Mainly p450 enzymes.
Other enzymes eg alcohol dehydrogenase and xanthine oxidase
385
What are phase 2 reactions?
Conjugation eg Glucuronyl, acetyl, methyl, sulphate
386
What is first pass metabolism
Conc of drug greatly reduced before it reaches the systemic circulation due to hepatic metabolism (so higher dose have to be given orally)
387
Example of drugs undergoing first pass
aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone
(its important you know these!!)
388
Whats zero order kinetics?
Describes metabolism which is independent of concentration of metabolism. Because metabolic pathway saturated so constant amount eliminated eg failing a breathalyser test the morning after!
389
Examples of drugs exhibiting zero order kinetics
phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol
390
Drugs affected by acetylator status
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
(DHIPS)
