Pharmacology/Toxicology Flashcards
Drug induced thrombocytopenia
Quinine
Abciximab
NSAIDs
Furosemide
Abx - penicilins, sulphonamides,
rifampicin
Anticonvulsants - Carbamazepine, Valproate
Heparin
Carbon monoxide affect on O2
Causes decreased O2 saturation of Hb - - > LEADS TO EARLY PLATEAU
Ciclosporin side effects
EVERYTHING INCREASED:
BP Gums Hair K+ Fluid
Pharmacokinetic terms :
Half life
Volume of distribution
Half life = time taken for plasma drug conc to decrease by half
Volume of distribution - calue that descibes the extent at which a drug is retained within circulation or distributed elsewhere.
Pharmacodynamic termsL:
Efficacy
Emax
Potency
a measure of drug effects in a particular symptom
Emax - maximal effect - partial agonist Emax < Full agonist
Potency: Expresses drug efficacy in relation to dose/conc.
Pharmacokinetics - Metabolism
2 types of biochemical rxn:
Phase 1:
- oxidation/reduction/hydrolysis.
- P450
- toxic/reactive product
Phase 2:
- Conjugation
- products less reactive
- typical groups - glucoronyl/acetyl/methyl/sulphate
1st pass metabolism:
- Drug is extensively etaboliused before reaching systemic circulation.
in LIVER
- ASA, verapamil, GTN, Propanolo, ISMN, hydrocortisone, testosterone
Zero-order kinetics:
- Metabolism is independent of drug conc.
- Metaboplic pathway= saturated
- Phenytoin, ASA, Heparin, Ethanol
Drug induced lupus
Assoc with Acetylation and HLA-DR4
Ft:
- butterfly rash
- myalgia
- pleurisy
Causes:
- PROCAINAMIDE
- HYDRALAZINE
- others: isoniazid, phenytoin, minocyclione
Inx:
- ANA +,/ dsDNA -
- anti-histone Ab
Liver inducers/inhibitors
inducers - stop warfarin - PCBRAS
- Pghenytoin/carbamezapine/barbituates/rifampicin/alcohol/St Johns wort
Inhibitors - inc warf - AODEVICES
- allopurinol/omeprazole/disulifram./erythromycin/valproate/isoniazid/ciproflox/ethanol/sulfonamide
Fx of COCP
decreased absopriton - e.g. diarrhoea
Liver inducers
Con-comitant broad-spec Abx
drugs to avoid in pregnancy
Earyl - teratogenics:
- Li - cardiac abnormalities
- ACEI/ARBs - oligohydraminos
- phenytoin - cleft lip/palate
- Na Valp - NT Defects/spina bifida
- Warfarin
Late preg –> X placents:
- Carbimazole –> neonatal goitre
- Gentamycin - CN8 deafness
prescribing in BReastfeeding
- Amiuodarone
- n Cytotoxics
- Gold
- Indometacin
- Li
- Iodides
- OEstrogens
Liver Fx
Increase susceptible to sedatives/ drugs taht cause encephalopathy
Thiazide/loop diuretics –> hypokalaemia –> Encephalopathy
Rifampicin - accumulates as excreted in bile
Hypoalbuminaemia –> Phenytoin toxicirty
Poor clotting –> Warfarin leads to bleed
NSAIDs - Inc NA/H2O retention
Cardiology drugs
Abciximab - glycoprotein 3a/2b inhibitor –| platelet aggregation
Adenosine - activates K+ in SAN/AVN - CI - Asthma
Aliskiren - Direct renin inhibitor - used in essential HTN
- S.e High K+
Amiodarone:
- prolongs refractory period
- long half life
- give IV - effect hrs
- PO effect = weeks
- it is the LEAST NEG INOTROPIC ANTIARRHYTHMIC
\s.e. - CHIPCHANGE - cutaneous photosensitivity/hep dysfn/inc LDL/pulm fibrosis/CNS/hypo/hyper-thyrid/asx corneal deposits/neuropathy/GI effect/ Enhanced warf and dig
ACEI:
- CI - BL RAS
- S.e. - dry cough/hyperkalaemia/hypersesnsitivity
Clopidogrel:
- Inhibits ADP bindiong site on platelet - stopp aggregation
- P2Y12
- longer anti-plt than ASA –> bleeding risk for 7/7
Digoxin:
- Slows AVN conduction –> Blsacks Na/K+ ATPasa pumo
- eliminated by KIDNEYS
- S.e. –> Gynaecomastia
Flecainide:
- class 1c anti-arrythmic
- avoid if IHD/structural heart dx
Statins:
- HMG CoA reductase inhib –> inhib RLS of cholesterol synth
- S.E. - myopathy/drug induced hepatitis
Ivabradine_
- Funny current blocker - inward NA-K channel - found in SAN
- S.e - visual effects, headache, bradycardia/HB
Nicorandil:
- V.D. used in angina
- activates K+ Channels –> inc. cGMP
- S.E. - headache, flushing, ulceration
- CI - LVF
Pasugrel/Tocagrelor:
- P2Y12 receptor inhibitor
- use Ticagrelor in ANY NSTEMI
s. e. - bleeding/ brady + inc SOB (ticagrelor)
Thiazide:
- hypo Na/K/Mg
- hypochloraemic acidossis
- postural hypotension
- agranulocytosis
- pancreatitis
- thrombocytopenia
Digoxin toxicity
- reverse tick
- arrythmias
- confusion
- yellow-green vision
precipitants:
- hypokalaemia - competively competes with dig
- low MG / High Ca
- Inc Age/ RFx/
- MI
- Drugs 0- amiodarone/verapamil/ dilitiazerm
Mx:
[- Digi-bind
- correct arrythmioa
- Monitor K+
Endocrinology - Drugs
Carbimazole:
- inhibits peroxidase enzyme
- Agranulocytosis
- X placenta –> neonatal goitre/hypothyrpoid.
HRT:
- reduces bone fracture
- inc breast Ca
NAteglinide/repaglinide:
- INCREASE INSULIN secretion
- similar mechanism as SU
- good for postprandial hyperBGL as short 1/2 line
- S.e> - GI Upset/hypersensitivity rxn
GAstro - drugs
S-ulfasalazine:
- S- afe in oregnancy ]- pro -drug of 5-ASA –> dec neutrophil chemotaxis/lymphocyte prolif/pro inflamm cytokines.
- cuation w/ G6PD deficiency or allergy to aspirin/sulkphonamides.
S.e. - oligospermia/SJS/ pneumonitis/lung fibrosis. myelosupression/heinz body anaemia/ coloured tears
Mesalazine/Osalazine:
- types of 5-ASA
- S>E - GI Distrubance / headache/pancretitis
Orlistat:
- Inhibits pancreatic lipase
- used ij obesity if BMI >30 or BMI > 28 + RF or cont WL
PArkinsons meds - See neuro notes
MAO-B inhib - Selegline
Amantadine - inhibit reuptake of DA
L-DOPA
- absorbed in prox. small bowel - decr. if AA present
- prodrug
- netabolised by COMT
- S.e. - Arrythmia/dyskinesia/post lowBP /psychosis/somnolescence
DA-R agonisst:
- Carbegoline/bromocriptine/apomorphine/ropinerole - less dyskinesia vs L-DOPA
- inc neuro psych s.e. ]
- pulm/retroperitoneal fibrosis
Epilepsy meds
lamotrigine
- inhibits glutamate
- s.e. mood change/mavulopapular rash/influenza symptoms/SJS
Gabapentin:
- GABA isomer
Leviteracetam
- presynaptic GABA release
Vigabatrin
- irreversible inhib of GABA transaminase –> inc GABA activity
BZD:
- inc affinity for GABA to bind to it’s receptor
Carbamezapine:
- derivative of TCA:
- HEadache/diplopia soon after starting ]
- morbilliform rash
- toxic epidermal necrolysis
- AGRANULOCYTOSIS
Valproate - S.e = V.A.L.P.R.O.A.T.E
- Vomitting/allopecia/liver toxicity/pancytopaenia or pulm fibrosis/ retention of fat = wG/ pedema/ataxia/ teratogenic or tremor/ enzyme inhib.
- AGRANULOCYTOSIS
5 HT - agonist:
- Triptans
- used in acute migraine
0- do not give in 24 hr of hemiplegic migraine or egotamine –> Vasospasm
- S.e. - chest paibn, flushing, drowsiness, vasospasm
Rheumatology drugs
MTX:
- Folate agonist - inhibits dihydrofolate mediators
- 1st kline in RA
- S.e. - Pulm fibrosis /mucositis/myelosupression.pneumonitis/liver fibrosis
- m Preg - avoid for 6/12
- monitor FBC/U+E/LFT - @ start –> wkly until stable –> every 2-3/12
- interactions - Trimethoprim/co-trimoxazole –> marrow supressionm
- ionteractions - high dose ASA –> inc toxicity
- MX toxicity with folic acid
Allopurinol:
- Inhibits xanthine oxidase –> stops purne synth
- inc risk of acute attach on commencent
- can cause accum of azathiprine
- decrease clearance of cyclophosphamide
Colchicine:
- Inhibits macrophage migration
- s.e. –> diarrhoea
Febuxostat:
- Xanthine oxidase inhibitor.
TOXICITY BEAR
LOOK UP PIC
Azathiprine - neurotoxic Cisplatoin - ototoxic and nephrotoxic Doxyrubicin - Cardiotoxic PSI - cyclophosphamide - bladdeer toxic MTX - Nephrotoxic/myelosupression Vincristine - periph neuropathy Vincristine 0- periph neuropathy
Retinoids
usewd in sev psoriasis/acne
Teratogenic --> NT Defect 0 S.e.: - Benign IHH - dry mucus memrban e - PHOTOSENSITIVITY - decreased night vision
Strontium
used in post-menopauesal osteoperosis
S.e.:
- Sev Allergy
DRESS - drug rash w/ eosinophillia and systemic sx
Spec drug adverse effects
Amennorhgea:
- DA block - chlorpromazine, cimetidine
- Na Valproate
Bronchospasm
- ASA
- BSAIDs
- Adenosine
- beta blkocker
Dyskineasia:
- L- DOPA > other antiparkinsons
Gynaecomastia:
- OEstrogen like - Dig/ spiro
- anti-androgen –> LHRH analogue/cimetidine
Drug induced liver dx
Heoatocellular:
- Paracetamol
- Valproate
- MAOI
- Halothane
- anti-TB - R.I.P
- statins
- Alcohol/amiodarone
Cholestasis: - COCP - Fluclox / erythomycin / co-amox - anabolic . steroids - chlorpromazine/promethazine -
Liver Cirrhosis
- MTX
- amiodarone
- methyldopa
drug provoked myasthenia
amenoglycloside beta block phenytoin penicillamine procaiamide lidocaine
drug induced photosensitivity
Amiodarione Tetracyclines RETINNOIDS PSoralen Cipro
drug induced vasculiuti s
allopurinol \Catopril Cimetidine LTRA penicillin
acute pancreatitis - drug causes
antiretrovirals azathiprine corticosteroidn fibrates statins thiazides
SIADH - derug causaes
Carbamazepine
chlorpropamide
cytotoxic
PAracetamol OD
liver normally conjugats paractamol + glutathione
in OD –> saturated –> all glutatjione used. Therefore get oxidation of P450 mixed fn oxidases. –> toxic metabolite = N- Acetly - B - Benziquinoneimine.
Mx:
- <1hr –> aCharcoal
- > 1hr/staggered –> NAC
- at 4hrs if level >100 –> NAC
- @15hrs >15 –> NAC
S.e of NAC:
- Anaphylactoid rxn –> STOP and restart @ SLOWER rate.
Kings college criteria:
- Arterial pH <7.3
or All of :
- Cr >300
- PT <100
- Encephalopath grade 3/4
TCA OD
Amitriptyline + dosulepin
Early sx:
- dry mouth
- blurred vision
- sinus tachy
- agitation
- blurred pupil
Ft of sev poisoning:
- Arrythmias
- Seizures
- Metabolic acidosis
- Coma
ECG Changes:
- Tachy
- Wide QRS - >100 - seizures >140 –> VT
- prolonged QT
Mx:
- IV NaHCO3-
- IV lipid emulsion
Throphylline toxicity
Sev acidosis
Tachy
Hypokalaemia
LOC/seizures/confusion
MX:
- Rpt aCharcoal
- IVI
- Electrolyte
- if level >60 !!! –> HAEMODYALISis
CO Poisoning
PX - >1 person from samew hosue px with flu-like sypmpotoms –> then get:
- pounding headache
- cherry red skin
- N.V
- Fatigue
- FALSELY HIGH PO2
CO + Hb –> Carboxyhaemoglobin = MEASURE
Carboxy-Hb ;evels:
- <3% normal
- 3-10% = smokers
- 10-30% = symptoms
- > 30% = severe
Mx:
- 100% O2
- Hyperbaric O2
indications for hyper baric OR:
- LOC
- neuro signs
- MI/arrythmia
- Pregnancy
Quinine toxicity
Anticholinergic + Direct neurotoxic –> BLINDNESS
prolonged QT
alpha blocjk –> HGYPOTENSION
TINNITUS
SEV METAB ACIDOSIS
Pb Poisoning
Think if ABDO PAIN + NEURO SIGNS
also get blue lines on lid margin
Inx:
- Blood Pb >10
- microcytic anaemia
Mx = chelating agent:
- DMSA
- D-penicillamine
- EDTA
Ecstasy poisoning
Agitation ]sweating ]tachy dilated pupils htn hypoNa hgih temp rhabdomyolysis
Tx:
- supportive
- if Temp very high depsirt supportive –> Dantrolene
Mercury poisoning
blindness hearing loss parasthesia RTA irritabilty
cyanide poisoning
inhibits Cytochrome C ocidase –> inhibits mitochondrial e- chain
Brick red skin + smell of bitter almonds
Mx:
- 100% O2
- HYDROXOCABALOMIN
Methanol poisoning
DRUNK + VISUAL problems
Mx:
- Fomepizole or ethanol
- Haemodialysis
insecticide poisoning
Inhibits scetylcholinesterase –> inc cholinergic side. effects
Ft - SLUD
- salivation
- lacrimation
- urination
- diarrhoea
Mx
- Atropine
Ethylene glycol toxicity
USed coolant/antifreeze
Ft of toxicirty:
- stage 1 - like being drunk
- 2 - metab H+ with inc anion gap
- 3 - ac ute renal fx
Mx:
1) Fomepizole
2) Ethanol/HD
Drug causes of photosensitivity
Thiazides Tetracycline, cipro, sukphonamides Amiodsrone Nsaids Psoralen Sulphonylureas
Which drugs are assoc wuth acetylator status
Procainamide Hydralazine isoniazid sulfasalazine dapsone
Drugs that exhibit Zero Order Kinetics
Phenytoin
Salicylates
Heparin
Ethanol
Kings collecge criteria for liver transplant in paracetamol OD
At 24 hours:
pH <7.3
or all of:
PTT >100 secs
Cr >300
Grade 3 or 4 encephalopathy
Causes of raised anion gap acidosis:
CAT MUDPILES
C - Cyanide/ CO
A - aminglyclosides
T- theophylline/toluene (glue)
M - MEthanol
U - Uraemia
D - DKA/ starvation KA/ Alcoholic KA
P - paracetamol/acetoaminophen
I - Isoniazid/inborn error of metab/ IRon
L - LActic acidosis
E - Ethanol/ethyene glycol
S - Salicylates/ASA/Aspirin
Drugs that cause photosensitvity:
SAT
Sulphonamides
Amiodarione
Tetracycline
Adrenoreceptor anatg
Apha - 1 = Doxazosin
Alpha - 1a = Tamsulosin
Alpha (non-selective) = phenoxybenzamine
beta - 1 = Atenolol (A for 1)
non-selective beta = propanolol
Drug induced impaired glucose tolerance
Thiazides/ Steroids tacrolimus/ciclopsotin IFN-alpha nicotinic acd antipsych
Contraindications to COCP
Migraine with Aura >35 and smoking >15/day BP persitent >160/95 maj surgery secondary raynauds SLE w/ Anti-phospholipid BReast Ca <6/12 Post-partum and breastfeeding.
When to check phenytoin levels after a dose change
2 Weeks.
Half life of phenytoin = 22 hours. Can take 5 - 14 days to reach a steady state.
10 - 20 = range for therapeutic
SIADH Drug causes:
SIADH Causes Poor Voiding
ssri/indomethacin/antidepressants (TCA)/diuretics - furos/bendro
C CARBEMAZAPINE/cyclophosphamide/chlorpromazine
P - phenothiazine
V- Vincristine/vinblastin
Pseudomembranous collitis
Cephlasporin >clinda >cipro
Drugs and Vision
1) Blue
2) Colour viision
3) haloes + Photosensitivity
4) Yelolow
5) Red/green affected
1) Viagra - blue pill
2) Chloroquine
3) Amiodarone
4) Dig
5) Isoniazid
Olyguric Crisis - causes and management
Neuroleptics - onlanzapine + haloperidol Metoclop Domperidone Carbamexapine chlrooquine
Mx:
- IV Procyclidine
others = benzhexol/benzadyle
Anti- HTN in preg
Methyldopa/labetolol/hyrdalazine
late pref –> Nifedipine
Acquired AIHA
methyldopa
penicillin
quinine
quinidine
Highly protein boudn drrugs
ASA/warf/phenytoin/digitoxin/valroate/nifedipine/propanolol/verapamil
Increased action in low alb states —> unbound drug leads to action
why do you get nitrate tolerance with GTN use?
formation of reaction oxygen species
Theophylline toxicity
Ft:
- Tachy/seizures/metabolic acidosis
- Tremor
- Vomit
- Insomnia
Mx:
- acute tachy –> Esmolol
- If arrythmia –< HAEMODYALISIS
Amitryptilline OD
Cant see pee spit or shit
Acidosis
Prolonged QT
Mx:
mild –> IVI
Sev –> IV NaHCO3
Fruit + Drug interation
Inhibitors - Grapefruit + Seville orange –> Simvastatin/amlodipine/diazepam/nifedipine
Inducers: Cranberry juice
- doesnt affect statisn
Drug induced oedema
intermittent facial oedema = moxonidine
PEripheral oedema = amlodipine
Angioneurotic oedema - ace-I
drug induced prolonged QT
Sotalol/quinidine/procainamide/amiodarone
Antipsych/domperidone/clarithromycin/erythromycin/cipro/trimethoprim/domperidone/cocaine
Hyper-PRL drugs
DA Antag - Phenothiazones/risperidone/metoclop
DA Depleting - MEthyldopa/isoniazid/TCA/ Verapamil/Oestrogens
Antiaeeythmics
Type 1 - Na channel (Double Quarter pounder/ with Lettuce Mayo and Tomato/ and More Fries Please
1a = quinidine/procainamie/disopyramdie
1b = lidocaine.moxeletine/tocainide
1c=flecainids/propefenanone
Type 2 - betablocker (Lol)
Type 3 - K+ blocker (this is SAD)
- Sotalol
- Amiodarone
- dofelitide
Type 4 - Ca-channel blocker ( I and V in IV)
- d-i-lt-i-azem
- V-erapamil
Drug precipitant of psoriasis
“NAAL man i don want psoriaisis
Nsaids/Atenolol/antimalarials/Li
BZD overdones
Managemengt - SUPPORTIVE +/- flumazenil (inc seizure risk)
Digoxin OD
Downlslope ST, Short QT and prolonged PR, U wave
Mx:
- HD unstable –> DC cardioverion
Otherwise DIGIBIND
Monitor K+ and renal fn
Warafrin in pregnancy
Stop in 1st 2/52 of preg and cover with lmwhh –> restart at 2/52 –> 3rd trimester stop and cover LMWH–> Start 2/52 psot=partum
Black triangle in BNF meaning
Recently added therefore must report advers affects = yellow card scheme
MEthanol poisoonig
Ft –> BLINDNESS
Mx = Ethanol/fumepazole
Drug cause of dupyterns contracture
PHENYTOIN
Chloroquine toxicity
NAusea, headache, visual disturbance, arrythmia coma
Hypoglycarmia
interferes with cardiac NA channels –> PROLONGED QRS
MTX Interatcion
Trimethoprim and co-trimoxazole–> myelo supressopm
Checl U+Es weekly –> sstable then every 2-3/12
Monoclonal Ab
Inrfliximab - anti-TNFa - RA/Crohns/CML Rituximab - CD20 - NHL/RA Cetuximab - EGFR - met colorectal ca/ Head + neck Ca Transtuzumab - HER2 - met breast Alemtuzumab - CD52 - CLL
Drug monitoring
Li - 12 hr post dose
Dig - 6hr post dose
Ciclosporin - immed b4 next dose
Phenytoin: - doesnt req reg monitor only if: ?toxicity ?compliance Dose change - Immed before next dose
Drugs that precipitate AIP
BArbituates BZD Halothanes EtOH OCP Sulphonamides
Heparin vs LMWH MOA
LMWH:
- Activates antithrombin 3 –> FXa inhibition
Heparin
- Activates antithrombin 3 –> inhibits F9,10,11,12
Indications for NA Bicarb in TCA OD
Reduced consciousness
QRS>100
Metabollic acidosis
