Flashcards in Pharmo Deck (392):
Black triangle = all
Established - serious
Legal requirements prescribing
Define slip, lapse, mistake, volation
First pass metb includes
Liver, gut wall and gut lumen
Describe protein binding of different drugs
Albumin = acidic drugs
Globulins = hormones
Lipoproteins = basic drugs
Acid glycoproteins = basic drugs
What is Vd affected by?
Receptor sites in tissues
Regional blood flow
St John's Wort
Hepatic disease (opiates in cirrhosis)
When should you monitor drugs?
Long half life
Risk of DDIS
What does BNF contain
Comprehensive list of all licensed drugs in the UK
Role of pharmacist in prescribing
No legal responsibility
Check prescriptions are correct
Pharmokinetics of Digoxin
Long half life = 40hrs
builds up in renal failure
How do you calculate Loading dose
Vd x [Drug at target}
Note that Vd = L or L/kg
How do you calculate the elimination rate constant?
=slope of the curve (k)
Calculation of T1/2
Vd (kg)/Cl log0.5/k
T1/2 in children
Higher as Vd is lower as more of their body is ECF
Comptments and drugs
Equilibrium in each compartment.
Describe drug specificity and selectivity
The more selective the less undesired effects elsewhere. Affinity for one receptor over another.
The more specific the more it can be used for a select organ. Specific basically means its so selective that no matter how much you give it wont work at another site
DDI absorption example
Gastric emptying - metaclopramide. Affects Fe and tetracyline absorption
Types of ADRs
A= augmented effect (dose)
B = Unpredicable off target
C = chronic
D = Delayed e.g. osteoporosis and steroids
E = End of treatment effects
Mild, moderate(additional treatment) or major
Preparations of testosterone?
Oral, IM, implant
Steroid hormones and distribution?
Steroid hormone binding globulin (not prog) and albumin
Use/ Actions of ostradiol
Prevent HRT symptoms - hot flushes, support bone structure.
Impair glucose tolerance
Improves mood and concentration
Side effects of oestradiol
Endometrial hyperplasia and cancer
Actions of prog
Increase Bone density
Secretory to endometrium
Side effects of Prof
Lack of conc
Actions/ Side effects of testosterone
Male secondary sexual characteristics
Metabolic adverse effect on lipids - increases LDL and decreases HDL
Preparations of COCP?
How does COCP work?
Suppresses ovulation (inhibit LH and FSH), effect on mucus and endometrium
MEtabolism of COCP?
Absorption of COCP DDI?
Broad spec on flora
Some COCP ADRS
Focal migranes (stroke)
Precipitate porphyria (skin sensitivity-dark urine-memntal disturb)
Use of POP?
Not as effective
Action on Cervical mucus and endometrium
Emergency contraception (72hrs) (120?)
Cu IUD - 5 days
Formulation of HRT?
Sequential or continuous
No shedding in continuous (Cx?)
Treat with lowest dose for shortest time
ADRs of HRT
Anti-oestrogens and action e.g. tamoxifen/ Clomiphene
Weak oestrogens - block receptors.
Induce ovulation by blocking oestrogen affect on put. More GnRH
Tamoxifen also acts at bone. Used in breast cancer.
Better for HRT as can reduce cancer risk, not be proliferative. But can increase hot flushes
Affects of anti-progs
Partial agonist again.
Sensitises uterus to prostaglandins (like increased O:P0)
Induction of labur
Terminaton of pregnancy
Effect of high LDL?
Toxic to endothelial. enhance platelet aggregation.
Affect of obesity on lipid profile
Increases Cholesterol, Triglycerices and decreases HDL
Action of simvastatin/ atorvastatin
Inhibit HMGCoA reductase
Used in CVS risk and hypercholesterolaemia
Decrease VLDL and LDL.
Anti-inflammatory, plaque reduction, improved endothelial cell function, reduce thrombotic risk, slow neurodegeneration.
ADR of simvastatin/ atorvastatin
Myopathy - CPK
Metab and elimination of Statins DDIS
OATP2 - fibrates and cyclosporin augment affect
Describe Benzafibrates action
More lipoprotein lipase
Reduce TG (espc Post prandial)
Not great LDL decrease
Increase LDL size
Nicotinic acid action
Increase HDL (best C)
Inhibits lipoprotein synthesis.
Reduce coronary events
ADRS/ contraindications for Nicotinic acid
Flushing, itching, headache
CIs: Liver, PUD
Ezetimibe action and uses
Cholesterol absorption. Circulates enterohepatically.
Lowers LDL (more hepatic receptors)
ADRs of Ezetimibe
Headache, abdo pain, diarrhoea
Give a statin?
CVS risk tables in BNF
Decrease insulin resistance and hepatic glucose production
Side effects metformin
Lactic acidosis (HRH)
Vit B 12 deficiency
No weight gain/hypos
K/ATP channel antagonist
Increase Ca release
Pioglatizone Rosiglatizone MoA
PPAR receptor. Decrease FAs. Increased muscle and adipose sensitivity
Pioglatizone Rosiglatizone ADRs
Fluid retention and CVS risk
More LDL and HDL
Repaglinide, Nateglinide MoA
Repaglinide, Nateglinide ADRs
Hypo (lower risk)
No Weight gain
Repaglinide, Nateglinide pharmacokinetics
Short half life so taken before meals
DPP4 inhibits/ GLP1 analogue
GLP released from distension of the stomach.
DPP4 breaks down GLP.
GLP increases insulin secretion and suppresses appetite
GLP1 agonist more effective
GLP1/ DPP4 inhibitor ADRs
Injected so pain
SGLT2 inhibitor action
Blocks in PCT
Acarbose/ a-glcosidase inhibitors ADRs
Criteria for treatment of Diab?
over 7% = sulphonylureas
over 7.5 = TZD or 3rd drug
Insulin (titrated upwards)
Physiological effects of Insulin
Glucose uptake in liver, muscle, adipose
Glycogesis in liver
Lipogenesis in Adiposites
Proteogensis in Muscle cells
Half live of insulin
Best indulin regime
Long acting with rapid acting`
Types of insulins
Animal porcine and bovine
Given 15-30 preprandial
Peaks at 2 hours
Examples of short acting insulins
Actrapid, Humulin , Novorapid
Examples of longer acting insulins
Rapid acting insulins
Peaks at 30-90
Intermediate acting inslins
Isophane intermediate actin (NPH)/ Humulin I.
Onset 1.5-3, peaks at 4-8. lasts 12-20.
Long acting basal analogue insulins
Slow onset 2-6hours, duration up to 24
Very long acting insulins
Fatty acid added so longer into blood stream. Lasts up to 50 hours (glargine)
Painful injection site
Sources of insulin error
Programme not written up
Name of insulin incorrect
Number/ dose unclear
Gastric and pancreatic lipase inhibitor. FA conversion decreased by 30%. Needs to be combined with diet
Soft, fatty stools, risk of flatus, faecal incontinence
What is pharmacovigilance
Process of identifying and then responding to safety issues about marketed drugs.
Withdrawral of drug results? (E)
Aims of pharmacovigilance
ID unrecognised safety hazards and quantify
Factors predisposing toxicity
Evidence for safety
False positive ADR
Why is pharmacovigilence needed?
PAtients in trials are restricted
Limited duration of drugs
Specialists giving drugs in trials
Not big enough sample
How are ADRs identified?
Spontaneously reported to the MHRA - Medicines and healthcare products regulatory agency. through yellow card. (licencing responsibility. Can report to pharmacological company (post marketing surveillance).
Cohort or case control
Advantages of spontaneous reporting
Can generate ADR hypothesis
ID risk factors
Limitations of spontaneous reporting
Delay in reorting
Misleading information given
No control group
Cant get incidence rate as no idea how many are treated
Controvosy in yellow card
Quality of patient reports?
Difference between pharmacogenetics vs genomics
Gene vs entire genome
Variability in ADRs. drugs
Some toxic, some not
Some effective some non responders.
Variability in ACEi
Better for whites as they have a higher RAS activity
Older and afrocarribean = CCB
Issues surrounding pharmacogenetics
Prednisolone also a glucocorticoid
More potent than cortisol?
Metabolic actions of glucocorticoids
Redistricubution of fat centrally
Slight mineralocorticoid activity
Mineralocorticoid deficiency and example
Fludrocortisone (a bit at GC)
Actions of hydrocortisone
Dexamethasone, Betamethasone, fludrocortisone at GC and MC
Pred more at GC
Dex and Bet +++GC no MC
Fludo --GC, +++MC
Pharmacokinetics of corticosteroids
All have high bioav
All metabolised in liver 1 & 2
Glucoronidation in liver for stage 2
Clearance affected by age
Kidney can metabolise too
Steroid action on immune repsonse
Inhibit B, T, cytokines, cell adhesion molecules, phagocytes
Steroid receptor (HSP dissociated)
Bind to hormone response element (HRE/ GRE) on DNA
Activates/ inhibits transcription = transactivation/ cis repression.
Transactivation = antiinflam
Cis repression = keratin, oesteo, POMC (side effects)
Trans repression (protein) = immune/ cytoknes
Some non genomic MoA via surface receptors
Some glucoorticoid ADRs
Adrenal crisis - hypogly, shock/ hypotension/ hypokalaemia/ hyponatraemia/ dehydration
Inhbits osteoblast, ca absorption.
Describe influenza A,B,C
A = Multiple host species, most severe, various.
B = No animal reservoir, lower mortality
C = not clinically important
Amantadine and Rimantadine MoA
Block M2 channel and inhibit uncoating. Proton channel that allows A to enter.
ADR amantadine and rimantadine
CNS nervousness, anxiety, agitation, insomnia think schitzo as similar to anticyclic
Give examples of neuroaminidase targetting drugs
Oseltamivir (Tamiflu) and Zanamivir
MoA of neuroaminidase targeting drugs
Neuroaminidase removes sialic acid bridges between virus particles so that particles can be exocytoses.
Blocking causes aggregation.
Earlier treatment the better.
High resistance - monitored by WHO
ADRs of neuroaminidase inhibitors
Vomiting, abdo pain, epistaxis.
Resp depression, bronchospasm
Folic acid antibitic examples and action
Trimethoprin and sulphonamides
What is an E test?
Sensitivity testing. Measures the minimum inhibitory concentration
What is the MIH?
The minimum concentration of antibiotic required to inhibt growth of a bacterium in vitro (mg/l). Antibiotic and isolate specific.
What are breakpoints?
Clinical testing data, wild type MIC, and antibiotic pharmacokinetics calulate breakponts.
Compare with MIC
Drug is effective when in microbiological terms?
Maximal concentration (Cmax) and MIC ratio.
MoA of antibiotics in terms of dependent killing
Time dependent killing - porlonged no at high conc e.g. beta lactams and glyco.
Concentration dependent killing e.g. aminoglycosides and quinolones
describe MDR, XDR PDR
MDR - Non-susceptibility to at least one agent in 3 or more categories
XDR NS to at least... in all but two or fewer
All microbial categories
Hypersensitity, C diff
Renal and ototoxicity
ADR Cloramphenical and MoA
Broad spec, protein
Renal, Bone marrow, ototoxoicity
Drugs that are monitored
Vancomysin and aminoglycosides.
Monitor FBC for clor
Renal and aud for gent
Common DDIs for antibiotics
Antiepileptics and carbapenems
Bisphosphonates (hypocal) and aminohlycosides
Digoxin in amino
blurred vision, confusion, drowsiness, dizziness, depression, psychosis, convulsions
Initially localised to synovium
Inflammatory change and proliferation leading to destruction of cart and bone
How is RA diagnosed
>3 joints (often hand)
Rheumatoid nodules (ripe fruit)
X ray (only late stage)
Describe SLE/ Vasculitis
Necrosis of distal vessels
Granulomatosis with certain types
What are DMARDs
Disease modifying antirheumatic drugs
Lead to clinical improvement unlike NSAIDs.
Active metabolite = 6MP (Mercaptopurine)
Decreases DNA and RNA synthesis.
TMPT metabolises but varying rate. Low rates = myelosuppression
Use of Azathioprine
Weak for RA
Bullous skin disease
Steroid sparing drug
non hodgkin lymphoma
Cacineurin inhibitors e.g. ciclosporin and Tacrolimys MoA
Against T helper cells and IL2
Cyclophilin protein/ TBP.
IL2 regulates WBCs
Cacineurin inhibitors e.g. ciclosporin and Tacrolimys ADRsa
eGFR - nephrotoxic
BP - hypertension
Does not supress bone marrow
Uses of Cacineurin inhibitors e.g. ciclosporin and Tacrolimys
Dermatis and psoriasis
Mycophenolate Mofetil (MMF) MoA
Inhibits monophosphate dehydrogenase and therefore guanosine synthesis.
Inhibits B/T cell proliferation. but highly selective
Uses Mycophenolate Mofetil (MMF)
Mycophenolate Mofetil (MMF) ADRs
Liver and kidney disease
Inhibits dihydrofolate reductase and purine and thymidine synhesis (malignant only).
In RA - inhibits T cells, cell adhesion and adenosine
One a week
Long half life
Highly bound - NSAIDs
BM (give folic acid)
Do baseline CXR, FBC, LFT, UE, Creatine
Sulphasalazine/ Masalazine MoA
Inhibit T cell proliferation and IL2
Uses of sulphasalazine/ masalazine
ADRs of sulphasalazine
Safe in preg
AntiTNF e.g. infliximab MoA
Inhibits cytokine cascade- adhesion, recruitment, less angiogenesis, less joint destruction e.g. MMP
Expensive so other DMARD must have been tried. Withdrawn if no effect in 6 months or any ADR.
Targets CD20 B cells. Induces apoptosis.
RA, especially with MTX
Alkylating - DNA cross links
Bladder cnacer, lymphoma, leukaemia
TH2 dirven inflammation
Neutrophilic or eosinophilic
Mast cells-IgE and leukocytes
Bronchospasm and congestion due to epithelial damage, thickening of BM
Basics of asthma treatment
Check compliance, technique
Severe asthma criteria
unable to comple sentences
RR>25 PF 33-50% of best
Life threatening asthma
If severe plus
Near fatal asthma
PaCo2 >6 = mechanical ventilation
Treatment of acute asthma
O2 high flow- sats >94
Nebulised salbutamol -continuous
Oral prednisolone 10-14 days
Nebulised ipratropium bromide
Consider IV aminophyhlline (methylxanthine)
Steps in asthma treatment
1 inhaled SABA
2 Inhaled steroid (when SABA 3x or waking 1 or exacerbation with oral steroid in last 2 years)
3 LAba, ca add steroid, consider other drug (some people are unresponsive to ICS
4 Increase steroid to 2000mg a day, forth drug
5 oral steroid, other e.g. antiIGe, specialist care
SABA e.g. salbutamine tolbutaline action
Inhibit mast cell degranulation
Increase cAMP, PKA, deacrease CA, more K currents.
Adrenergic, tachycardia, palpitations, termor
Why use LABA e.g. formoterol, salmeterol (slightly lipophilic)
Better at preventing exacerbation
Examples of inhaled cortico
Why CorticoS in asthma
Reduce exacerbations, ecrease eosinophils, imporve symptoms and function. Decrease inflam via transactivation and transrepression (cytokines)
Leukotriene receptor antagonist e.g. montelukast MoA
Blocks action of cytokine to prevent inflam and mucus
Angioedema, dry mouth, arthralgia, fever, GI, rare
Methylxanthines MoA e.g. theophylline
Antagonise adenosine receptor inhibit cAMP
LAMA e.g. ipotropoium bromide and tiotropium ADR
Glaucoma (esp neb)
Anti IgE MoA
blocks IgE receptor so limits mast cell activation
Expensive buyt good at steroid sparing
NSAIDs physiologic effects
What are autocoids and what do they do?
'Self-drugs' cause a local response in response to stimuli.
What are Eicosanoids?
20C phospholipid derivative.
Overlap with autocoids to ensure a robust inflamatory response. Localised release and short half lives allow fine control.
From arachidonic acid
Prostanoids and leukotrienes.
Prostanoids = prostaglandins (potent), prostacyclins and thromboxane
What are COX and reactions they catalyse.
Cyclo-oxygenase synthesis PGs.
Arachidonic acid to PGG
PGG to PGH
PGH to DEFI via PG enzymes
PGE most important in infalm
Isoform constitutionally expressed.
PG from COX1 in many places e.g. aid perfusion.
Half life of prostaglandins
Induced by injury
Expresses mediators e.g. bradykinin
Constitutionally expressed in parts of brain and kindey also.
Therapeutic effect of NSAIDs
How are prostaglandins produced in inflamation and how do they produce their effect
Autocoids increase COX2
PGs bind to GPCRS (EP1-4 receptors)
Pain modulation via:
Sensitisation of central nociception
Describe how prostaglandins cause vasodilation locally?
Describe how prostaglandins cause pain via afferent sensation
(EP2 binds to) EP1 receptor (Gq) causes peripheral nociception on C fibres resulting in sensitivity to bradykinin, inhibition of K channels and increased Na sensitivity (more APs)
Activates previously silent C fibres
Gq - increases Ca so more neurotransmittor release can = allodynia/hyperalgesia.
Describe how prostaglandins can cause pain via sensitation of central nociception
Increase cytokines from sustained nociception
Binds to Gs (EP2)
Increase in cAMP, PKA
Decrease in glycine receptor binding affinity
Increased pain/ sensitisation
Describe how prostaglandins can cause pyrexia
IL1 from macrophages from endotoxins tirggers PGE2 sythesis in the hypothalamus.
Triggers EP3 receptor (Gi)
Heat production and decrease heat loss.
Increase to assist bacterial killing.
Which COX inhibition reduces pain?
How do NSAIDS inhibit COX
Competitive inhbition of COX hydrophobic channel.
Extent of COX1/2 varies.
Variable half lives
ADRs of NSAIDS
Stomach/GI = pain, heartburn, ulceration as PGE2 creates mucus, increases BF and reduces acid.
Renal in HRH or hypovol as PGE2, PGI2 maintain BF. Na, K, Cl, H2O retention.
Incresed bleeding time (asprin)
Hypersensitivity e.g. Stevens Johnson/ Mucositis
Bronchial asthma (CI = asthma_
Reyes syndrome - brain/ liver injury
Describe COX2 specific drugs
Increased CVS e.g. hypertension
Short term only
DDIs of NSAIDS
Extends opiate action
Reduces opiate ADR
Interact with each other
Hughly bound drugs e.g sulphonylyrea, warfarin and MTX
Describe Aspirin use and pharmacokinetics
Long term then risk
Irreversibly inhibit COX via acetylation
Describe all about paracetamol
No anti inflammatory action -
Good ADR profile in TI
Long term = hearing loss and affect metab
T1/2 = 2-4 hours
Caution in alchol compromised
OD in paed and elderly risk
Mainly phase II
When saturated = zero order
0-4 OD = activated charcoal
MoA of Opioids
Central effects (psychoactive)
Peripheral effects (gate theory) to counter pain as it is caused by physiological and psychological factors.
Inhibits substance P release from nerve nerminals
Describe enkephalin precursor receptor, MoA Pre, location
(negative action on cAMP)
Decrease cAMP and Ca
Describe Dynorphin precursor receptor, MoA Pre, location
Ca2 direct channels (-ve)
Describe Endorphin precursor receptor, MoA Pre, location
K outward flux and decreased (+ve)excitability
KOP agonist and results
Dysphoria (confusion and disruption of thought)
MOP agonist ad results
Naloxone but t.5 = 1-1.5
Naltrexone is 4hpurs
Describe morphine kinetics
Lipophobic so not good at BBB
Metabolites also active
half life = 4 hours
Describe Diamorphine kinetics
t.5 = 5 mins
polar so can cross BBB
Metablised to morphine
More in brain
Describe uses of opiods
Analgesic (particularly visceral)
Morphine and clay/ Loperamide for diarrhoea
Methadone to maintain dependence
Tramadol = antidepressant as 5HT and NA
Fentanyl ADR not obvious
Puritis due to histamine release
Codeine use and kinetics
Metabolised to morphine
Some unaffected e.g. chinese as they lack CYP enzymes
Similar effect to tramadol
What are nociceptin and nocistatin
Nociceptin agonises ORL1 and nocistatin blocks
Gi so less cAMP
Describe schedule 2 and 5 controlled drugs
2 = storage, prescription and destruction conditions e.g. morphine and diamorphione
5= codeine- preparation regulations and keep invoice over the counter
Descrine caumarins MoA
Inhibit Vit K reduction so less active clotting factors II,VII,IX,X
Descriube caumarin ADRS
Bleeding (above 3.5)
Protein - NSAIDs, Sulphonylureas, MTX
Vit K from gut - cephalospoirn
Uses and kinetics warfarin
t=48hrs and slow offset
DVT, valves, PE, AF
Deactivate thrombin and Xa and IXa.
Activates antithrombin III
Reversal of Heparin and warfarin
Parenteral vit K
Kinetics of heparin
Rapid onset and offset
Thrombocytopenia - autoimmune activated platelets
Large enough to bind with IIa, Xa too
Must monitor as variable kinetics/ behaviour via APTT
Non linear dose respose
Variable bio av
Given IV (witha bolus)
Describe low molecule weight heparins
Only inhibits Xa (poorly ATIII)
No monitoring needed
Describe Xa inhibitors e.g. Dabigatran
Not really DDIs
Also get direct thrombin inhibitors
inhibits thromboxane A2 production (like asmirip
Also positive inotrope and vasodilatory (flushes headaches) prevention of stroke.
ADP antagonist so blocks action at P2Y12 receptor, less Gi so more cAMP, less aggregation.
In ACS, PCI, used with asprin only 1 year after NSTEMI
How does alteplase work
Works in presence of fibrin whereas streptokinase is general.
Better if earlier use
Bleeding brain and GI
Explain general types of anaesthetics
Describe Guedel's signs of anaesthetic
1 - Norm tone, breathing and eye movement, slight analgesia
2 - excitement - possible aggretion, everything increased/ erratic
3 surgical anaesthesia - everything slightly to extremely relaxed
4 resp paralysis, flaccid with no breathing or eye movement
Describe the thalamo-cortical switch
Sudden anaesthesia above a certain anaesthetic conc
Loss of which functions with increasing concentrations
What is the MAC
Minimum alveolar concentration at which 50% of patients fail to respond (move) to a surgical stimulus at 1atm.
Autonomic loss of of carbiocascular response =1.5MAC
Induction and recovery affected by what properties
Solubility/ partition oefficients blood to gas/ oil to gas
What factors affect MAC
NO (strongly reduces MAC)
Potential target sites of anaesthetics
Sensitise GABA e.g. propafol
Inhibit Ach (not sedation bu analgesia and amnesia)
NMDA inhitors e.g. N2O and ket. Depress RF system
Fast and slow IV anaesthetics?
slow = ket
How is TIVA monitored
Total intravenous anaesthesia
Plasma conc for end point e.g. loss of eyelash of BUS (cortical activity)
Normally just used as bolus for induction in mixed anaesthesia
Local anaesthetic describe
pKa = dissociation constant
If lower then faster onset
Describe regional anaesthetic
Often a nerve block
A local anaesthetic or opioid
ADRs of anaesthetics
post opiod nausea and ovmiting PONV, hypotension, POCD (cog dys) for 1-2days
Local- systematic spread and CVS toxicity
Fluranes - CS and resp depressin, arrhthmia, hypo, OCP, cough
NO2 - diffuse hypoxia
Propafol - CVS and resp depression
Classes of drugs used in anaesthetics
IV agents (induction)
Inhalational agents (maintainence
Anxiolytics/ hypnotics e,g, Benzos
Opiates (intraoperative analgesia_
NM blocking drugs
Describe Carbonic anhydrase inhibitor use and ADRs and MoA
Reduces HCO3 production and absorption so less NA, Cl in PCT.
Describe osmotic agent use and ADR
Loop diuretics ADR and use
DDIs Digoxin and steroids
Thiazide/ thiazide like Use and ADRs
DDIs steroids, carbamazepine, digoxin
Aldosterone antagonists use and ADR
Liver disease, hypertension and HF.
ADH antagonists e.g. demeclocycline/lithium moA
Reduces concentrating ability of CD
Amiloride vs spirono
Amiloride inhibits Nachannels in (ENAc)
Spirono = aldosterone receptor antagonist
ACE inhib/ ARB (affective in year 1)
NOT Ca channel
Explain diuretic resistance
NSAIDS/ poor renal perfusion
High Na intake
Explain hypertension drugs
CCB if over 65? or black
Decompensated liver disease drugs
As kidneys retain sodium
Describe physiological control of BP
ADH (a bit but more osmotic)
Atrial naturetic peptide - stretch = dilation
Describe the pathology of hypertension
Loss of compliance
Aim for hypertension
Dry cough (not with angiotensin receptor blocker)
Real failure hyperkalaemia
Not to be used in preggers
Examples of angiotension receptor blockers and receptor
AT1 to inhibt aldosterone and vasoconstriction
Examples of CCBs
Amlodipine, verapamil, diltiazem
Vasodilate and decrease contractility some more than others
HF and bradycardia
Alpha blockers example and action
antagonise a1 so vasoconstriction
Alpha blockers ADRs
Reduced exercise tolerance
Imaired glucose tolerance
Explain ventricular arrhyrhmias
Suddencause of death in people with no history
Stages of AP in a myocyte`
1 K+ Cl-
2 Ca++ K+
Stages of AP in SAN
4 = Naf
0 = Ca
3 = K
Describe WPW syndrome
Wolf parkinson White = reentry throught the bundle of Kent
Describe class 1
Na channell inhibitors
II= lidocaine- no change in phase O due to fast dissoc, decreased conduction
III = flecainide = phase 0 block, slowed conduction due to increased refractory beats
ADRs class 1
Proarrhythmic - ventricular response to atrial flutter
Describe class 2 action
BB e.g. propanol, atenalol, bisoprolol and sotalol
Diminised phase 4 depolarisation so increase refrat in AV.
Conduction and generation
Class 3 action
Increased stage 3 and refractory period/ AP duration.
Conduction and generation
Warfarin and digoxin
Sotalol moA and adrs
BB and III
Class IV action
Decrease inward Ca (conduction) and inotropy
Decreae slope of pacemaker potential at SA node
Conduction and generation
ADRs class 4
AV block and aystole (with BB)
Enhances K conductance and hyperpolarises cell to prolong RP
Drugs for AF
BB or CCB or Digoxin or amioderone
Vagal activity so more refrac
Re-entry SVT/ AV node?
Adenosine or B blocker or CCB.
Often re-entry at AV node
Ectopic atrial tachy or sinus tachy?
BB or CCB
Flutter vs fibrillation
Prepared loop/ route vs random
How are chemo agents discovered?
Serendipity e.g. platinum
Types of cells in a tumour
A = Dividing cells with adequate blood supply
B = cells which are not actively dividing but are able to
C - no longer able to divide but contribute to bulk
Target A (low in prostate)
What is the log kill ratio?
109 cells before detectable
Kill ratioe.g. 99.9. until 10 cells left
Compartment model disagrees
Fractional cell kill hypothesis?
BM harder hit than cancer but better recovery so given in 2-4 week doses.
MTX decreases folates- purine and thymidine
5Flurouracil inhibits thymidine
S phase only
Alkylating agents moA
Cross lnk DNA
Contain Cl- (DNA is positive/ nucleophillic)
Cl dissociates in cell leaving a postiive platinum ion/ molecule to bind
Intercalating agents moa
DNA transcription and dulication via topoisomerase II.
Anthracycline antibiotics e.. doxorubicin and daunorubici.
Intercalate between base pairs to prevent breaking/ re ligation during rapair and replication (topoisomerase II).
Generates free radicles
Spindle poisons moa
Inhibit microtubule polymerisation - vinva alkaloids e.g. vincristine
Inhibit microtubule depolymerisation e.g. taxanes e.g. paclitaxel
How does chemo resistance occur?
Increase exit/ entry
Inactivation in cell
Multidrugresistant protein (MDRP)- removes
Downreg of carriers
Side effects of chemo
Alopecia - scalp cooling
Mucositis and thrust
Dosing of chemo?
Performance score Who1-5 based on activity and co morbidities
Pharmokinetics of chemo
E = liver and renal
Monitor drug levels, organ damage and cancer
Non chemo options?
Episodic discharge of abnormal high frequency electrical activity in the brain leading to seizure
Diagnosis of epilepsy
Evidence of recurrent seizures unprovoked or by identifyable caues
Types of seizure
Tonic clonic/ grand mal = fit and loss of conscious
Absent/ petit mal = unconsoius often standing, no or little movement.
Simple = conscious
Can lead to secondary gene. one area (symptos depend on area)
Often with aura
Status >5mins or 2 back to back without any recovery in between. Convulsive or non convulsive may lead to SUDEP
How is status treated
IV benzo or phenytoin
NM blocking agent and ITU
Causes of epilepsy
2/3 idiopathic (age=RF)
Secondary = neurological condition, vascular disease, tumours
Symptoms ad consequences of epilepsy
Physical injury from fall
ADR to medication
Stigma/ loss of livlihood
Explain how votage gated sodium channel blockers work and list the types for epi
Inactive so reduce chance of abnormal firing.
prolongs inactivation stae and detatches
Explain how enhancing GABA mediated inhibitio can work for epilepsy
GABA receptor agonist
Increases Cl- and increases threshold
VGSC blockers use epi
Carbamazepine general, partial not absence
Phenytoin the same
Lamotrigene all 3
Valporate all 3
Dizziness, drowsiness, ataxia, numbness tingling
GI, BP, rashes, neutropeia, hyponatraemia
Loads of DDIs
Tyes As - nystag and nervousness
Gingival hyperplasia/ stevens Johnson
Not as tetratogenic
Kinetics of VGSC blockers epilepsy
C- linear PK but inducable (monitor)
P-NON linear half (monitor
E- Lear PK
Sodium valporate - Linear
Sodium valporate MoA
Inhib of inactivating enzymes of GABA
Stimulates synthesis of GABA
Weak Ca channel blocker
ADRs of valporate
Dependence withdrawral (seizure)
OD = resp and cns depression
First lie for primary generalised
OCP and antiepileptics
Carbamezepine and phenytoin interefere
Additional supplements to pregnant epileptic women
Vit K in last trimester
Briefly describe parkinsons and its symptoms
Motor and non-motor
Diagnosis of parkinsons
Exclude other forms of parkinsoniasm
Response to treatment - normal neuro imaging
Other forms of parkinsonism
Multi system atrophy
Drug induced (antipsychotics)
Pathophysiology of parkinsons
Loss of dopaminergic neurones in rthe substantia nigra so less inhibition of the neostriatum
More Ach in neostriatum
Management of parkinsons
Surgery e.g. lesions if ADR if ADR with L Dopa
L Dopa MoA
Active transport across BBB
Given with peripheral DOPA decarboxylase inhibitor to reduce systemic effects.
Loss of efficacy over time
ADRs of L DOPA
Schitzo/ psychosis, delusions, pananoia
DDIs e.g MAO (hypotension)
Not absorbed as well with protein
Kinetics of L dopa
Half life is 2 hours
Given orally so controlled release
Examples of Dopamine receptor agonists
Apomorphine, bromocriptine, Ropinirole
Use and ADRs of dopamine receptor agonists
Motor treatment, less efficacy than L-Dopa
Impulse control disorders e.g. gambling,
Exaple of MAOI type B and effect
Smooth motor response
COMT inhibitors examples and use
Entacapone - reduces peripheral breakdown of Dopa.
prolongs L dopa effect
Examples of anticholinergics and use in parkinsons
Ach antagonises dopamine.
Treats tremor thats it
Amatidine MoA and use
Unceartain but promotes dopamine release.
Tremor, few side effects
Cause of MG
Autoantibody blockage of postsyn
Symtoms of MG
Fluctuating, fatigueable weakness of skeletal muscles
Bulbar involvement - dysphagia, dysphonia, dysarthria
Overtreatment = cholinergic crisis
Exacerbating drugs of MG
BB, CCB, type 1
Management of MG
Plasmapheresis to remove AChR
How is depression diagnosed?
Tools e.g. PHQ 9
PAtient health questionnaire
2 of 3:
Anhedonia (lack of pleasure)
Secondary symptoms of depression
Pathophysiology of depression
Monoamine deficiency - 5HT and Na or binding sites but can be normal
Treatment of deression
Moderate - severe = SSRI and CBT
Example of SSRIs
Efficacy and ADRs of SSRIs
Best, responably safe
Diarrhoea(normal in first 2 weeks)
Suicide - energyt and conc first
TCA example and MoA
Inhibits Na uptake, muscurinic blockade and alpha 1 so sympthaolytic and mimetic
Lowers seizure threshold
AND- accomodation, glands
CVS - tac, hypo, imair contractility
OD= cardiac monitoring
Example of SNRI
Non-selective monamine uptake inhibitors e.g. Venlafaxine
Efficacy of DNRI and ADRs
Not as well tolerated as SSRIs
Describe paranoid schizophrenia
Psychoses (other causes include depression, mania, delerium, depression)
Psychosis = lack of context with reality
Unusual speech (thought)
Lack of insight
Negative symptoms include:
What are delusions
A fixed false blief that is out of keeping with someones culture or religious beliefs
Schitzophrenia increases risks of
Early death 20 years
Pathophysiology of schitzophrenia
Dopamine excess (not negative)
5HT excess/ glutamate excess possible
Describe the dopamine pathways in the brain
Nigrostriatal - motor/ extrapyradimal (results in tardive dyskinesia)
MEsocortical - enhanced negative and cognitive
Tuberinfundibular - hyperprolactinamia
Describe MOa and examples of typical antipsychotics
Uses and adrs of typical antipsychotics
Uses - haloperidol in emergencies
Can be iven depot
ADRs include sedation
Neuroleptic malignant syndrome (rigidity)
OD: CNS and CVS sidden death
Examples and Moa atypical antipsychotics
Same same but less side effects.
Defined as less likely to cause parkinsonism but not neccessarily better
ADRs atypical antipsychotics
Weight gain (saity)
ins and needles
Treatment of anxiety
CBT first line
Anxiolytics and antipsychotics in crises/ really severe
SSRI/NI first if stage 3/4
What is bipolar disorder
Mania and depression, hypomania (mild)for prolonged periods
Symptoms of mania
Poor judgement e.g. addiction/ spending
Psychotic symptoms- hallucinations, grandiose, delusions
Treatment of bipolar
VGSC anti epileptics
Lithium Moa and efficacy
Reduces certain other neurotransmittor effects
Best for lowering suicide in bipolar but only after 1 year
Augments antideprresants in unipolar depression
ADRs of lithium
give anticonvulsants and increas fluids/ dyalise.
monitor 3 months
Examples and effect of acetylcholinesterase inhibitors in Altzeimers
Prolongs progresion by one year. Increases arousal, memory, attention and mood (not if severe)
e.g. Donepezil and galantamine
ADRs of AChesterase inhibitors in alt
NMDA antagonist example and ARDS and use
Moderate/ sever dementia
Explain stomach acid secretion
HKATPase exchanger on apical
Becomes phiosphorylated as part of ccle which is stimulated by luminal K
Found in tubulovesicles (canalioicular membrane precursor)
Acid activated pro drug
Accumulate selectively in acid space
Only bind to active pumps so delayed action (2-3 days)
Restoration from de novo synthesis (covalent binding)
H2 receptor antagonist
Viscous layer over exposed layer
Diarrhoea, gastrinomas, TB, C diff, oesteoporosis
Step up or step down
symtoms vs healing
Not bothered about H pylori
Treatment of PUD
H pylori (lansoprazole
How does H pylori cause disease?
Produce lipopolysaccharides and peptides to stimulate chemotaxis and inflammation
Neurogenic control of guy
Intrinsic -local enteric system
instestino=intestinal -one segment distensioncauses intenstinal inhibition
Anointestinal reflex - distension of anus inhibits gut
Gastrocolic and duodenal colic
Causes and lifestyle factors for constipation
Medical cause e.g. DM, dehydration, preg, cancer, obstruction, drugs
Bulk laxatives example and MoA
Fibre, days to work
irritant moa and examples
stimulates gut motility - water and electroyte retentiona dn peristalsis -rapid. used if soft faeces
Colonic atony (constipation)
Osmotic agent, dissachoride broken down into lactose/ monomers.
Macrogols e.g. movical moa
Glycerol Supps moa
Safe not effectie
Glycerol suppos ADRs
Anal irritation, burning, dia, gas, nausea
Phosphate enema moa
Osmotic, quickly and severe
Phosphate enema adrs
dehydration, cramps, gas
Mechanism of emesis
pyloric sphincter closes
Cadia and oesophagus relac
Contraction of abdominal wall and diaphragm
Glottis closes with elevation of soft palate
Ach, H1, 5HT in medullary centre
Postrema = part of medullar on the floor of the fifth ventricle (dopamine)
Hyoscine MoA and ADRs
used in motion sickness and short lived
Antimuscurinic used in GI spasms and IBS.
Cyclizine MoA and ADRs
Used in acute N/V
QT prolongation sedative
Anti cholinergic blocks vagal afferent 5HT
Domperidone moa and adr
D2 antagonist, increase gastic empyting and in acute n/v. adrs prolactin and dystonia
Ondansetron moa adrs
Vagal stimulation blocked
Diarrhoea causes and treatmetn
Drugs treat symptoms not cause
Fluid and electrolytes
Loperamide moa and Adrs
reduce motility and increase anal tone and sensory defecation reflex, good for chronic
CI; IBD = toxic megacolon,
abdo pain, constipation, sleepiness, vomiting and dry mouth
Bulk forming moa in dia
Increase water absorption