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Flashcards in Pharmacology Deck (232)
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1
Q

Give 3 enteral and 3 parenteral drug administration routes.

A

Enteral - oral, rectal, sub lingual

Parenteral - IV, IM, subcutaneous, intrathecal, transdermal

2
Q

What is meant by the volume of distribution?

A

The amount of the available drug that is trapped in muscle or fatty tissue compared with the amount that is active in the plasma.

3
Q

If a drug is lipophilic, will it have a low or high VoD? Give an example of such a drug.

A

High VoD
Because it is able to cross the cell membrane and enter lots of different types of tissue. Not much will be in the plasma.

Eg haloperidol

4
Q

If a drug is lipophobic, will it have a high or low VoD?

A

Low VoD
It is unable to cross the cell membrane so lots will be densely packed in the plasma.

Eg. Paracetamol

5
Q

If the same dose of a drug is given to a fat person and a thin person, who will have the higher VoD?

A

Fat person because they have proportionally more fat/muscle:plasma. More fat/muscle to spread into means a higher VoD

6
Q

The equation to calculate loading dose is VoD x kg x target plasma conc. Why is it adjusted for weight?

A

Fatter people will have a larger VoD so need a higher loading dose for the same effect.

7
Q

What 3 factors affect the clearance of a drug?

A

Liver function, kidney function. If they are poor, clearance is slowed.

Diahorrhoea/ GI dysfunction. Clearance is sped up.

8
Q

Why might you use a loading dose?

A

Reach the therapeutic range quicker. Or if the therapeutic range would be impossible to reach in 4-5 half lives of the maintenance dose.

9
Q

How long does it take to reach a steady state of a drug?

A

4-5 half lives

10
Q

What is the half life of a drug?

A

Time taken to lose half of drug activity

11
Q

What is the effect of CYP 450 inducers on plasma levels of a drug?

A

Induce metabolism of drug so decrease plasma levels.

12
Q

What is the effect of CYP 450 inhibitors on plasma levels of a drug?

A

Inhibit metabolism of the drug so increase plasma levels.

13
Q

What are 1st and zero order kinetics?

A

1st - linear - constant fraction eliminated so increase the drug, increase rate of elimination. Linear on a log scale.

Zero - nonlinear - constant rate eliminated because CYP enzymes are saturated

14
Q

What are the drug targets of the contraceptive pill?

A

Nuclear oestrogen and progesterone receptors

15
Q

What are the mechanisms of action of the combined and progesterone only pills?

A

Combined - negative feedback on anterior pituitary. Decreases production of LH and FSH. This prevents ovulation.

POP - modified gene expression in the cervix. Increased thickness of cervical mucus.

16
Q

What is the mechanism of action of tamoxifen? What is it used for?

A

Weak competitive agonist of oestrogen receptors.
Decreased negative feedback on anterior pituitary
Increased oestrogen

Used for breast cancer and to induce ovulation.

17
Q

What type of drug interactions occur with the contraceptive pill? What is the effect?

A

CYP inducers decrease plasma levels and decrease efficacy

18
Q

What is the main ADR with the contraceptive pill that needs to be monitored? How is it monitored?

A

Increased coagulability - monitor bp and ask about coagulation events

19
Q

Why can’t you usually give oestrogen alone? Who can have oestrogen only?

A

Unopposed oestrogen leads to excessive proliferation of endometrium and increased risk of cancer.

Women with a hysterectomy can have unopposed oestrogen for HRT

20
Q

What is the mechanism of action of statins?

A

Inhibits HMG coA reductase which is involved in cholesterol synthesis
Decrease in cholesterol
(Increase in LDL removal from plasma)

21
Q

Give an example of a drug with low bioavailability

A

Statins

22
Q

Why is atorvastatin the current recommended 1st choice?

A

Half life of 20 hours compared to 1-4 could be why it is slightly more effective.

23
Q

When is simvastatin given during the day? Why?

A

Nocte because short half life of 1-4 hours so given to coincide with the most cholesterol biosynthesis

24
Q

What are the 2 main ADRs with statins?

A

Myopathy and rhabdomyelysis

25
Q

What is monitored when on a statin?

A

Plasma lipid levels (total cholesterol and triglycerides) and liver function tests

26
Q

What combination of drugs increases the effect of a statin? What is the drawback?

A

Ezetimibe plus statin
Ezetimibe decreases absorption of cholesterol.

But increases risk of rhabdomyelysis

27
Q

When would you give a fibrate?

A

When triglycerides are high as well as cholesterol

28
Q

What is meant by bioavailability? What is it affected by?

A

The amount of drug that survives absorption and first pass metabolism and reaches the systemic circulation.

Affected by the route of administration and health of GI tract and liver function.

29
Q

How is oral bioavailability calculated?

A

We want to know how much gets in the system orally compared to the most efficient method.

Do it by - (area under curve oral route)/ (area under curve IV)

Because area under the curve represents the total amount of drug in the system.

30
Q

Drug A has a long half life. What variables in the prescription can be altered to keep it within the therapeutic interval?

A

Decrease dose size
Increase dose interval

Because if it has a long half life it is staying longer in the system

31
Q

What is the treatment for type 1 diabetes?

A

Straight to insulin therapy

32
Q

What is the first line of treatment for type 2 diabetes?

A

Improve diet and exercise

33
Q

What is the target HBA1C for a diabetic?

A

6.5-7.5%

34
Q

What are the risks if a diabetic is maintained at a low or high hba1c?

A

Low - risk of hypos

High - risk of long term damage to peripheral vessels and nerves

35
Q

What is the first line of treatment for type 2 diabetes which can’t be maintained on diet and exercise changes?

A

Metformin

36
Q

What is the mechanism of action of Metformin?

A

Increases insulin receptor sensitivity

Decreases gluconeogenesis

37
Q

Does Metformin change the levels of insulin in the blood? What effect does this have on the weight of the patient and risk of hypo?

A

No change
Weight neutral
Low risk of hypo

38
Q

What is an important contraindication for Metformin? Why?

A

Chronic renal disease - GFR

39
Q

Give 2 ADRs for Metformin.

A

GI dysfunction

Potential for lactic acidosis

40
Q

What is the NICE recommended second drug (on top of Metformin) for a diabetic who is a) skinny b) fat?

A

A) sulphonylureas

B) DPP 4 inhibitors or pioglitazone

41
Q

What is the NICE recommended third drug (on top of Metformin and sulphonylureas/ DPP4/pioglitazone) for a diabetic who is a) skinny b) fat?

A

A) DPP 4 inhibitor or pioglitazone

B) Exenatide

42
Q

What is the mechanism of action of sulphonylureas?

A

Stimulation of beta cells in islets of langerhans in the pancreas.
Leads to an increase of insulin

Antagonises ATP dependent K channel, depolarises, ca influx. Increase in release of insulin granules.

43
Q

What is a benefit of sulphonylureas?

A

Can be used in chronic kidney disease

44
Q

Do sulphonylureas change the levels of insulin in the blood? What effect does this have on the weight of the patient and risk of hypo?

A

Yes - increases by stimulating beta cells

Can cause weight gain and risk of hypo

45
Q

What are 2 major barriers to adherence to diabetic medication?

A

Weight gain or fear of weight gain
Risk of hypo and fear of hypo
(sulphonylureas and insulin therapy)

46
Q

What is the mechanism of action of pioglitazone ?

A

Same as Metformin
Increases insulin sensitivity
Decreases gluconeogenesis

47
Q

What are 2 important ADRs of pioglitazone?

A

Risk of hepatitis and liver failure

Risk of bladder cancer

48
Q

Give an example of a DPP-4 inhibitor. What is its mechanism of action?

A

Sitagliptin

Increases GLP-1 hormone which decreases glucagon (therefore the effects of insulin are more heavily felt)

49
Q

Do DPP-4 inhibitors change the levels of insulin in the blood? What effect does this have on the weight of the patient/risk of hypo?

A

No
Weight neutral
Low risk of hypo

50
Q

What is the mechanism of action of Exenatide? When is it considered?

A

Injectable GLP-1 so like a potent DPP-4 inhibitor, heavily decreases glucagon.
Considered for a fat person before you put them on insulin because it is not anabolic. In fact because it is injectable and potent it can even cause weight loss.

51
Q

What is the mechanism of action of SGLT 2 inhibitors ?

A

Decrease glucose reabsorption in proximal tubule
Causes glycosuria - you wee out sugar
For diabetes

52
Q

Give 2 ADRs of SGLT 2 inhibitors.

A

UTI and thrush because glycosuria

53
Q

Describe 2 possible insulin regimes and who they would be suitable for

A

Good control - first intermediate acting only, second add short acting around meals
Poor control - biphasic preparation (mixture of short acting and intermediate acting)

54
Q

Give 2 TYPES of antibiotic that act by inhibiting cell wall synthesis. Then give a drug name for each.

A

Beta lactams - penicillin, cephalosporins

Glycopeptides - vancomycin

55
Q

Give 2 TYPES of antibiotic that act by inhibiting protein synthesis.Then give a drug name for each.

A

Macrolides - erythromycin

Amino glycosides - gentamicin

56
Q

Give 3 TYPES of antibiotic that act by inhibiting DNA synthesis. Then give a drug name for each.

A

Quinolones - ciprofloxacin

Folic acid antagonists - trimethoprim

Rifampicin

57
Q

What is vancomycin useful for treating? Why is it saved for these infections?

A

MRSA (methicillin resistant staph aureus) and endocarditis

Narrow therapeutic window so levels need to be monitored to prevent hepatotoxicity

58
Q

What are cephalosporins useful for treating? Why are they saved for these infections?

A

Generally broad for gram positive but extra good at getting into CSF so used for meningitis.

Risk of c diff.

59
Q

Why is penicillin so great? What is bad about it? What would you use as an alternative?

A

Broad spectrum against gram positive and some gram negatives.
Can be allergic so use erythromycin as an 2nd choice alternative.

60
Q

Which 2 types of antibiotic have to be monitored to check for hepatotoxicity ?

A

Glycopeptides - vancomycin

Amino glycosides - gentamicin

61
Q

What are time dependent and concentration dependent killing? Give an example of an antibiotic which uses each.

A

Time dependent - Work best when exposed to a low dose IV infusion for long period eg beta lactams

Concentration dependent - work best when exposed to a high dose once per day eg gentamicin.

62
Q

What is meant by the MIC of an antibiotic?

A

Minimum Inhibitory Concentration.

In antibiotics which use concentration dependent killing this will be high.

63
Q

What is rifampicin used for? What is significant about its pharmacokinetics?

A

Treating mycobacteria such as TB and leprosy.

Major CYP inducer so will decrease efficacy of other drugs such as the pill

64
Q

Describe 2 ways in which antibacterial resistance can be transferred between bacteria.

A

Chromosomal transfer - natural selection

Horizontal transfer - plasmids, transposons and bacteriophages.

65
Q

Give 3 mechanisms a bacteria might use to resist an antibiotic.

A

Beta lactamase secretion

Penicillin binding protein

Reduced intracellular concentration - Decreased permeability to drug or active reflux of drug

66
Q

What is the mechanism of action of M2 ion channel blockers?

A

Antiviral drug. Blocks ion channel which pumps H+ into the virus and allows it to burst and release its DNA/RNA into the cell.

67
Q

Give 2 examples of m2 in channel blockers. Which is preferable and why?

A

Amantidine and rimantidine.

Rimantidine preferable because amantidine has a worse side effect profile with confusion, hallucination, dizziness and insomnia. (Side effects of “a man”….) it is also completely really excreted and inappropriate for use in CKD

68
Q

What is the proper name for Tamiflu? What is its mechanism of action?

A

Oseltamivir

Inhibits neuramidase which is the enzyme that allows the virus to be released from the infected cell and go on to infect other cells.

69
Q

During what time frame is Tamiflu effective? Why?

A

First 48 hours.

Because it’s action is to prevent spread throughout the body. After this time the damage is done.

70
Q

What is a prodrug? Give 3 benefits of prodrugs and for each give an example of a drug which utilises this benefit.

A

Drug which is given in the inactive form and uses the natural metabolism of the body to change into its active state.

  1. Increase bioavailability if normally poorly ABSORBED - Tamiflu
  2. Improve DISTRIBUTION - Enter the CSF - L-DOPA
  3. To slow release - codeine to morphine
71
Q

Give an example of an on target ADR and an off target ADR.

A

On target - too much of the correct response eg ACE inhibitor causing hypotension

Off target - lack of specificity causing an ADR in an unrelated location eg Beta blocker exacerbating asthma via b2 receptors

72
Q

Why should trimethoprim be avoided in the first trimester of pregnancy?

A

Folic acid antagonist so will lower levels. This could potentially affect notochord fusion and lead to spina bifida or anencephaly.

73
Q

What is the therapeutic window of a drug? What is the therapeutic index/ratio?

A

Window - The range of doses which lie between the minimum effective dose and the toxic dose for a specific side effect.

Index/ratio - expresses the range as a fraction. Toxic dose 50/ effective dose 50. The larger the window the larger the number and the rarer the side effect.

74
Q

Give two inflammatory cytokines and two anti inflammatory cytokines.

A

Inflammatory - IL 1, IL 6, TNF

Anti - IL 4, TGF

75
Q

What is the mechanism of action of corticosteroids?

A

Bind to nuclear receptor, inhibit gene expression and prevents release of inflammatory cytokines from macrophages. (IL 1 and 6)

76
Q

Give some side effects of corticosteroids.

A

Cushingoid - weight gain, fat redistribution, striae, thin skin and bruising

Increased risk of infection
Cataracts and glaucoma
Osteopenia

77
Q

Why can’t corticosteroids be stopped suddenly?

A

Adrenal suppression so risk of adissonian crisis.

78
Q

What drug can be given as an immunosuppressant to spare steroids?

A

Azathioprine

79
Q

What is the mechanism of action of Azathioprine?

A

Inhibition of purine metabolism leads to a decrease in DNA and RNA synthesis. Slows inflammation and prevents fast dividing immune cells.

80
Q

Why is Azathioprine a prodrug? What is it metabolised into? When is the active substance given instead?

A

Because it is metabolised into 6-MP which doesn’t get past the bowel.
Given as active 6-mp in IBD.

81
Q

What are the pharmacogenetic implications of Azathioprine ?

A

Eliminated by tpmt. This enzyme has high genetic variation.
If high levels - under treat
If low levels - over treat

82
Q

What are the key ADRs of Azathioprine?

A

Bone marrow suppression

Increased risk of infection

83
Q

What is the mechanism of action of calcineurin inhibitors?

A

Ciclosporin - binds to cyclophilin protein
Tacrolimus - binds to tacrolimus binding protein

Both inhibit calcineurin which normally activates IL-2 transcription in T cells. Therefore immunosuppressant.

84
Q

Why can patients sometimes struggle to get along with taking cyclosporin?

A

Strongly affected by CYP inducers and inhibitors - no grapefruit!!

Gum hyperplasia
Increased risk of infection .

85
Q

What is the mechanism of action of methotrexate in malignancy?

A

High affinity for DHFR enzyme that synthesises folate and therefore purines and therefore DNA and RNA.

Specific to s phase so attacks quickly dividing cells.

86
Q

Why must methotrexate be given weekly?

A

Metabolites are also active in binding to DHFR and they have a long half life.

87
Q

Why can’t NSAIDs be given with methotrexate?

A

NSAIDs displace methotrexate from plasma proteins which it it highly bound with.

88
Q

What are the key ADRs for methotrexate?

A
Abortive
Bone marrow suppressant
Risk of infection
Mucositis
Hepatitis
89
Q

What must be monitored with methotrexate? How often?

A

Baseline - chest x Ray, LFTs, u&es creatinine

Bloods must be monitored monthly.

90
Q

What is the mechanism of action of methotrexate in non- malignant disease?

A

Unknown but possibly due to increase in adenosine.

91
Q

What is the mechanism of action of sulphasalazine?

A

Prodrug reaches colon where it is metabolised to 5 ASA

The rest is unknown.

92
Q

Why is sulphasalazine so great?

A

Reaches colon so works for IBD.

Few ADRs, safe in pregnancy.

93
Q

When can sulphasalazine not given?

A

Aspirin allergy

94
Q

What substances are released at the site of tissue damage?

A

Bradykinin and cytokines

Membrane phospholipids pinch off - arachidonic acid - prostaglandins

95
Q

What enzymes catalyse arachidonic acid to prostaglandin e?

A

COX1 and COX2

96
Q

What are 2 differences between COX 1 and COX 2?

A
  1. Cox 1 is everywhere to ensure local perfusion. Especially gastric mucosa, myocardium and renal parenchyma. Cox 2 is only in inflammation.
  2. Cox 1 has a narrow binding site and cox 2 has a wide one.
97
Q

What do COX 1 and 2 catalyse?

A

Synthesis of prostaglandins (especially prostaglandin e and thromboxane)

98
Q

How do prostaglandins cause inflammation, pain, fever and vasodilation?

A

PAIN
PGe - EP1 receptor - Gq - increase Ca - increase c fibre firing
- EP2 receptor - Gs -decrease glycine inhibition
INFLAMMATION AND PERMEABILITY
- increase effects of bradykinin and histamine
FEVER
PGe - EP3 receptor - Gi - hypothalamus increase temperature
VASODILATION, DECREASED COAGULATION
Thromboxane

99
Q

What is the mechanism of action of NSAIDs?

A

Competitive antagonism of COX 1 and 2 enzymes. Therapeutic effect is COX2.

100
Q

Why do NSAIDs interact with a number of different drugs?

A

Heavily bound to plasma

101
Q

What drugs do NSAIDs interact with? Give three examples.

A

Highly protein bound - sulphonylureas, methotrexate, warfarin

102
Q

What are the common ADRs for NSAIDs? Why?

A

Gastric - bleeding, ulcers, infection. Because COX1 produces PGe which normally increases mucus, decreases acid.

Decreased GFR - PGe normally enhances perfusion

Bronchospasm in asthma

103
Q

What happens in paracetamol OD?

A

Phase 2 conjugation saturated - shift to phase 1 which produces NAPQI - glutathione saturated - further build up of NAPQI.

NAPQI is hepatotoxic

104
Q

What should be given in paracetamol OD?

A

0-4 hours activated charcoal

0-36 hours N acetylcysteine. Binds with NAPQI and stops it reacting with hepatocytes

105
Q

What are the three types of opiate receptor? What are their actions?

A

Mu - k efflux - decreased ca
Kappa - decreased ca influx
Delta - decreased cAMP

Overall decreased ca in neuron. Decreased release of substance p

106
Q

Which opiate receptor is acted on by opiate drugs?

A

Mu

107
Q

Give 2 examples of morphine pro drugs. Why do they have such different effects?

A

Codeine and diamorphine

Codeine has a low affinity for CYP enzymes giving it a low bioavailability
Diamorphine crosses the blood brain barrier so has a huge VoD

108
Q

What are the main ADRs of opiates?

A

Low dose- nausea and vomiting, constipation, itching, dependence and tolerance……leading to…..

High dose - respiratory depression, hypotension and arrhythmia

109
Q

What is the antidote for opiate overdose? Why must it be used carefully?

A

Naloxone

Shorter half life than morphine so may wear off before the OD. May need to give multiple doses.

110
Q

What is the mechanism of action of b2 agonists?

A

Act on b2 adrenergic receptor - Gs - adenyl cyclase - camp - pka - relax smooth muscl

111
Q

Give 2 long and 1 short acting b2 agonist?

A

Salbutamol - short
Salmeterol - long
Formoterol - long and potent

112
Q

What are some common ADRs of b2 agonists?

A

General adrenergic responses (particularly acting on b1)
Tachycardia, arrhythmia
Tremor
Hypokalaemia

113
Q

What factor is most important in determining bioavailability Of b2 agonists?

A

Technique with inhaler. Swallowed component is metabolised by first pass.

114
Q

What is the mechanism of action of a corticosteroid inhaler for asthma?

A

Long term prevention by:

Decrease cytokines, decrease COX2, decrease mast cells and eosinophils AND upregulates b2 receptors

115
Q

Why is theophylline not the first line treatment for asthma?

A

Narrow therapeutic window

Lots of ADRs - GI, headache, psychomotor, tachycardia

116
Q

Which types of drugs are used to treat venous thrombosis versus arterial thrombosis?

A

Venous - anti coagulant

Arterial - anti platelet and thrombolysis

117
Q

What is the mechanism of action of warfarin?

A

Inhibits vitamin k reductase which limits vitamin k recycling. Vitamin k is needed to carboxylate effective clotting factors - 7, 9, 10 and 2 (prothrombin). So it creates ineffective clotting factors.

118
Q

Why are there so many drug interactions with warfarin?

A

Metabolised by CYP 450 enzymes - so can be induced or inhibited
Heavily protein bound so can have binding interactions

119
Q

Why does heparin need to be given at the start of a course of warfarin?

A

It has a slow onset until all of the clotting factors are diminished. Heparin given as cover.

120
Q

Why does warfarin need to be stopped 3 days before surgery?

A

Slow offset - risk of bleeding in surgery. Heparin can be given as cover for these few days.

121
Q

What are the main ADRs with warfarin.

A

Massive risk of bleeding and bruising

122
Q

Give 4 types of drugs which will increase the effects of warfarin (increase INR)

A
  1. CYP inhibitors
  2. Heavily bound to albumen - NSAIDs
  3. Decrease availability of vit k from gut bacteria - cephalosporins
  4. Decrease platelet function - aspirin
123
Q

Name as many CYP inducers as you can

A

If you drive your CAR up the RAMP through the BARBed wire into St. John’s woods, you will be chronically attacked by an oPHENder.

Carbamazepine
Rifampicin
Barbiturates
St. John's wort
Chronic alcohol
Phenytoin
124
Q

Name as many CYP inhibitors as you can

A

Big MAC acutely drinks alcohol with grapefruit juice and ICE - then he needs cimetidine for Stomach Ache.

Macrolides
Acute alcohol - binging
Grapefruit juice
Isoniazid
Cimetidine
Sulphonamides
Amiodarone
125
Q

Give a type of drugs which will decrease the effects of warfarin (decrease INR)

A

CYP inducers

126
Q

What must be closely monitored when on warfarin? What is the target range?

A

INR - 2.5-3.5 but longer if there is an increased risk of clots eg prosthetic heart valve.

127
Q

Why must pregnant women not take warfarin?

A

Crosses placenta - Teratogenic and causes brain haemorrhage in the birth canal.

128
Q

What is the mechanism of action of unfractionated and LMW heparin?

A

Unfractionated - attaches anti thrombin 3 to thrombin to inactivate it
LMW - attaches anti thrombin 3 to factor X to inactivate it

129
Q

Why is LMW heparin preferable?

A
  1. No loading dose
  2. Longer half life
  3. More predictable - no aptt monitoring
  4. Lower risk of thrombocytopenia
130
Q

What are the ADRs of heparin?

A

Bleeding and bruising. Risk of thrombocytopenia

131
Q

What is the mechanism of action of aspirin as an anti platelet?

A

Irreversibly inhibits COX1 - decreases thromboxane - decrease ca in platelet - decrease cross linking and aggregation .

132
Q

What is the mechanism of action of streptokinase?

A

Binds to plasminogen to form plasmin.

This is a natural thrombolytic which is selective to clots.

133
Q

When would you give the following drugs for anti coagulation?

Warfarin
Heparin
Aspirin
Streptokinase

A

Warfarin - venous, chronic
Heparin - venous, acute/cover
Aspirin - arterial, chronic
Streptokinase - arterial, acute

134
Q

Give 6 drug types which are nephrotoxic (and therefore should not be mixed)

A
ACE inhibitors
Metformin
Cyclosporin
NSAIDs
Lithium

Penicillin
Gentamicin

135
Q

Give 3 drugs that are ototoxic and therefore should not be given together?

A

Gentamicin
furosemide
Cisplatin

136
Q

Give 2 drug types that can cause hyperkalaemia and therefore should not be given together

A

ACE inhibitors

K sparing diuretics

137
Q

Give 4 drug types that can cause Hypokalaemia and therefore should not be given together

A

Digoxin
Steroids
Thiazide diuretics
Loop diuretics

138
Q

Which types of people have an active RAAS? What is the first line treatment for their hypertension?

A

Under 55 years, diabetics

ACE inhibitors or angiotensin receptor blockers

139
Q

Which types of people have a slower RAAS? What is the first line treatment for their hypertension?

A

Over 55 years, black, pregnant, ckd,

Ca channel blocker

140
Q

What is the mechanism of action of an ACE inhibitor?

A
  1. Stops angiotensin 1 being converted to angiotensin 2. Therefore decreases vasoconstriction, aldosterone secretion and sympathetic tone.
  2. Prevents inactivation of bradykinin. Therefore increases vasodilation.
141
Q

What are the common ADRs of ACE inhibitors?

A

Dry cough
Angio oedema (black)
Renal failure
Hyperkalaemia

142
Q

What are the benefits of an angiotensin receptor blocker over an ace inhibitor?

A

Stops effect of angiotensin 2 therefore no effect on bradykinin.

No bradykinin related ADRs - dry cough or angio oedema

143
Q

What is the mechanism of action of ca channel blockers for hypertension?

A

Stops ca surging into cells.

  1. Decreases contractility of heart - decrease cardiac output - decrease bp
  2. Arterial vasodilation
144
Q

What are the common ADRs of ca channel blockers?

A

Baroreflex mediated - tachycardia, palpitations

Hypotension - dizziness and nausea

145
Q

What is the mechanism of action of thiazide diuretics/thiazide like diuretics?

A

Block the Na cl co transporter in the DCT. So less water reabsorption

146
Q

What are the ADRs of thiazide and loop diuretics? Which are more marked?

A

Hyper - glucose, urea, lipid
Hypo - k, Na, mg, calcium
Polyuria

Worse in loop

147
Q

Which drug types are used for prognosis improvement in heart failure and which are used for acute symptom relief?

A

Prognosis - ACE inhibitors (X RAAS and decrease plasma volume)
- beta blockers (X myocardial demand for O2 by lowering heart rate and cardiac output)

Acute. - loop diuretic

148
Q

What is the mechanism of action of beta blockers in heart failure? Why do they have to be titrated carefully?

A

Decrease myocardial O2 demand by lowering hr (b1 receptor) and lowering cardiac output (vasodilation)

Be careful because cardiac output is already low. Can exacerbate.

149
Q

What are the main ADRs of beta blockers?

A

Hypotension, dizziness, nausea

150
Q

What is the mechanism of action of loop diuretics? What two diseases may they be used in?

A

Heart and kidney failure

Blocks nak2cl in thick ascending limb, so cancels the cortico medullary gradient and massively decreases h2o reabsorption. Decrease in blood volume.

151
Q

What is the mechanism of action of k sparing diuretics? When are they used?

A

Block ENaC in DCT - amiloiride
Block aldosterone receptor in CD, decrease effect of ENaC - spironolactone

Used synergistically with loop diuretics to minimise risk of Hypokalaemia

152
Q

What are the ADRs of spironolactone?

A

Gynaecomastia and loss of masculine characteristics

153
Q

What is the ideal particle size for an inhaled drug? Why?

A

1 micrometer

Too big - stays in the throat
Too small - mist exhaled back out

154
Q

Why is poly pharmacy a big problem in anaesthetics?

A

A number of different drugs are necessary to perform different tasks.
Eg induction, analgesia, paralysis etc.

155
Q

What is meant by MAC in anasethesia?

A

Minimum alveolar concentration of inhaled drug required for 50% off population to be unresponsive to pain stimulus.

156
Q

What factors increase MAC?

A

Young
Hyperthermia
Pregnancy
Alcohol

157
Q

What factors decrease MAC?

A

Other anaesthetic - especially nitrous oxide
Opioids
Hypothermia
Old

158
Q

What is the mechanism of action of propofol?

A

Anaesthetic inducer.

Potentiates (increases) effect of GABA receptor which is inhibitory.

159
Q

Which 3 anaesthetics do not act on GABA receptors? What do they act on instead?

A

Xenon, nitrous oxide, ketamine

Block excitatory NMDA glutamate receptors

160
Q

What is the mechanism of action of lidocaine as a local anaesthetic?

A

Blocks Na channel, decrease excitability of local nerve endings.

161
Q

What is the mechanism of action of lidocaine as an anti arrhythmic?

A

Class 1b Na channel blocker.
1. Slows influx of Na at start of av action potential - decreasing conduction velocity.

2.Decreases excitability at AV - increasing refractory period.

162
Q

What type of arrhythmia is lidocaine best for?

A

Ventricular tachycardia (not supra)

163
Q

What is the mechanism of action of Amiodarone?

A

Class 3 k channel blocker

Powerful shit

  1. Slows av action potential - decreasing conduction velocity.
  2. Decreases excitability at AV - increasing refractory period.
  3. Decreases excitability at SA - decreasing heart rate and cardiac output
164
Q

What type of arrhythmia is Amiodarone best for?

A

Any arrhythmia but lots of side effects so rarely first choice except in wolf Parkinson white

165
Q

What are the ADRs of Amiodarone?

A

Pro arrhythmia
Lung fibrosis
Hypothyroid
Reversible liver damage

166
Q

What drugs does Amiodarone interact with?

A

Warfarin and digoxin

Especially important because all cardiac drugs.

167
Q

What types of arrhythmia are caused by abnormal conduction? What type of drugs are required?

A
Heart block
Ventricular tachycardia (not supra)
Re entry loops - from MI scar or wolf Parkinson white 

Need class 1 or 3 to increase refractory period and decrease conduction velocity

168
Q

What types of arrhythmia are caused by abnormal generation of activity? What type of drugs are required?

A

AF
Flutter
Supra ventricular tachycardia - eg from MI scar
After depolarisation

Need to decrease excitability at sa node. "Av blockers"
Class 2 (b blockers) class 4 (ca channel blockers) digoxin or adenosine.
169
Q

What is the mechanism of action of beta blockers as an anti arrhythmic?

A

Block HCN Na channels - slow funny current - slow hr and decrease excitability at sa node

170
Q

What is the mechanism of action of ca channel blockers as an anti arrhythmic?

A
  1. Slow ca entry at sa node - decrease hr and excitability at sa node
  2. Also decrease contractility by slowing ca induced ca release
171
Q

What is the mechanism of action of digoxin?

A

Block Na k atpase. Stop action of Na c exchange. Increase intracellular ca and increase contractility.
Also increase vagus activity and act as a beta blocker

172
Q

What are the main ADRs of digoxin?

A

Pro arrhythmic
Hypokalaemia
Narrow therapeutic index
Xanthopsia (yellow vision)

173
Q

What is the mechanism of action of atropine?

A

Muscarinic antagonist blocks vagus activity for vagal bradycardia

174
Q

What is the mechanism of action of ipratropium?

A

Anticholinergic actions on the M3 receptor in the lung.
Acts to block contraction.

Given in nebuliser as part of (O SHIT) for asthma attack

175
Q

What are the three main factors that determine whether a patient will be offered chemotherapy?

A

Stage of tumour
Performance score (0-5)
Molecular markers

176
Q

Give 6 key ADRs of any chemotherapy.

A
Neutropenia
Thrombocytopenia 
GI mucosa damage
Buccal mucosa damage
Hair follicle damage
Acute kidney injury - tumour lysis syndrome
177
Q

Which phase of the cell cycle is targeted by methotrexate?

A

S phase where chromosomes are dividing and most DNA synthesis is taking place.

178
Q

What is the mechanism of action of vincristine? Which phase of the cell cycle is affected?

A

Blocks the binding of spindle subunits during mitosis so that there is no spindle formation. Cell stuck in metaphase and causes apoptosis of rapidly proliferating cells.

M phase

179
Q

What is the mechanism of action of taxanes? Which phase of the cell cycle is affected?

A

Stabilises spindle subunits during mitosis so that there is no spindle pulling apart. Cell stuck in metaphase and causes apoptosis of rapidly proliferating cells.

M phase.

180
Q

What is the mechanism of action of alkalating agents such as cisplatin? Which phase of the cell cycle is most affected?

A

Form covalent crosslinks with base pairs and blocks replication fork. Therefore blocks DNA replication at s phase as well as translation throughout g1.

181
Q

What is the mechanism of action of the anthracycline antibiotics such as doxorubicin? Which phase of the cell cycle is most affected?

A

Intercalates between base pairs and blocks topoisomerase 2 which checks and fixes DNA. Therefore inhibits DNA synthesis.
Also generates free radical Fe2+ which destroys the cell

Non specific to any phase in the cycle

182
Q

Why is chemotherapy given in pulsed doses?

A

To allow the bone marrow to recover in between. Otherwise there is a high risk of neutropenia and thrombocytopenia

183
Q

What is the treatment for status epilepticus?

A
1. Benzodiazepines 
If doesn't work
2. Phenytoin infusion 
If doesn't work
3. Theopentone (anaesthetic inducer)
184
Q

What is important about the treatment of epilepsy during pregnancy?

A

Most anti-epileptics are teratogenic with a risk of neural tube defect.

Give folate supplement and aim to use lamotrigine alone. (Avoid sodium valproate)

185
Q

What is the treatment pathway for partial seizures?

A
  1. Lamotrigine
  2. Carbamezepine
  3. Sodium valproate
186
Q

What is the treatment pathway for generalised seizures?

A
  1. Sodium valproate
  2. Lamotrigine
  3. Carbamazepine
187
Q

What is the mechanism of action of carbamazepine?

A

Voltage gated Na channel blocker.
Decreases the excitability of neurons and prolongs inactivation by hyper polarising cell.
Voltage dependent so only binds during depolarisation. Therefore tends to detach when rate returns to normal.

188
Q

What is the mechanism of action of phenytoin?

A

Voltage gated Na channel blocker.
Decreases the excitability of neurons and prolongs inactivation by hyper polarising cell.
Voltage dependent so only binds during depolarisation. Therefore tends to detach when rate returns to normal.

189
Q

What is the mechanism of action of lamotrigine?

A

Voltage gated Na channel blocker.
Decreases the excitability of neurons and prolongs inactivation by hyper polarising cell.
Voltage dependent so only binds during depolarisation. Therefore tends to detach when rate returns to normal.

190
Q

Give some drugs which are commonly affected by CYP inducers or inhibitors.

A
Warfarin
Antidepressants
Antiepileptics - phenytoin
Statins
Contraceptive pill and steroids
Cyclosporin (anti inflammatory)
191
Q

Why do we have to be careful with carbamazepine?

A

Cyp450 inducer

Few ADRs except cvs - contraindicated in heart block

192
Q

Why do we have to be careful with phenytoin?

A

Cyp450 inducer
90% plasma bound
Zero order kinetics
Narrow therapeutic index!!!

Monitor drug levels and interactions.

193
Q

Why is lamotrigine the preferred treatment in partial seizures?

A

Few side effects - ataxia, GI, dry mouth
No CYP induction unlike other voltage gated Na channel blockers.
Least teratogenic

194
Q

Why do we have to be careful with lamotrigine?

A

Pill lowers lamotrigine levels in plasma.

195
Q

Why is sodium valproate the preferred treatment in generalised seizures?

A

Effective and minimal ADRs - GI, drowsiness

196
Q

Why do we have to be careful with sodium valproate?

A

Highly teratogenic

Sudden hepatotoxicity

197
Q

What is the mechanism of action of sodium valproate?

A

Agonises the GABA receptor, causes increase in cl current and increases the thresh for action potential. (Generalised inhibition)

198
Q

What is the mechanism of action of benzodiazepines?

A

Agonises the GABA receptor, causes increase in cl current and increases the thresh for action potential. (Generalised inhibition)

199
Q

Why do we have to be careful with benzodiazepines?

A

Dependence, tolerance, sedation, aggression.

200
Q

Name 4 drugs which can cause pulmonary fibrosis.

A

Methotrexate
Bleomycin
Nitrofurantoin
Amiodarone

201
Q

What is the mechanism of action of SSRIs?

A

Selective inhibition of SERT enzyme that reuptakes serotonin out of the synaptic cleft.
Increases effect of serotonin

202
Q

What is the most common ADR of SSRIs? What are the most dangerous ADRs of SSRIs?

A
Most common is general GI symptoms
Most dangerous is 
1. Increase in suicidality by increasing motivation first 
2. Precipitate mania
3. Citalopram increases QT interval
203
Q

What is the mechanism of action of tricyclic antidepressants?

A

3 mechanisms (hence the number of ADRs)

  1. Inhibition of NA reuptake
  2. Alpha 1 adrenoceptor block
  3. Muscarinic block
204
Q

Give 4 ADRs of tricyclic antidepressants.

A

Sedation
Seizures
Tachycardia
Postural hypotension

205
Q

Which two types of antidepressants can be dangerous in overdose?

A

Tricyclics and MAOIs

206
Q

What is the mechanism of action of venlafaxine?

A

Dose dependent selective reuptake inhibition of NA and 5HT

NA only at high dose

207
Q

What are the main ADRs of venlafaxine?

A

Adrenergic eg hypertension, dry mouth, sleep disturbance

208
Q

How is anxiety usually treated?

A

Either cbt or antidepressants. Try to avoid benzo prescription.

209
Q

What is the antidote to benzodiazepine overdose?

A

Flumazenil

210
Q

What is the general mechanism of action of antipsychotics?

A

Block d2 dopamine receptors in mesolimbic pathway

211
Q

Why do antipsychotics produce so many side effects?

A

D2 receptors are present in a number of pathways in the brain leading to on target side effects.

  1. Mesocortical - increases negative symptoms
  2. Nigrostriatal - Parkinsonism
  3. Tuberoinfundibular - pituitary endocrine eg lactation and sexual dysfunction
  4. Mesolimbic - positive symptom treatment target
212
Q

What are the ADRs of typical antipsychotics?

A

Eg haloperidol
Sedation, Parkinsonism, Tardive dyskinesia
Lactation and pigmentation

213
Q

What is neuroleptic malignancy syndrome?

A

Medical emergency caused by antipsychotics

Rigidity, labile blood pressure and hyperthermia.

214
Q

What is the main ADR of olanzapine?

A

Weight gain

215
Q

What is the main ADR of risperidone.

A

Lactation

216
Q

What is the main ADR of clozapine?

A

Neutropenia and agranulocytosis - monitor bloods

217
Q

What are the 4 main dangers with lithium?

A

Nephrotoxic
Narrow therapeutic window
OD risk
Hyponatraemia

218
Q

Give some common ADRs with lithium.

A
Thirst
Polyuria
Tremor
Memory loss
Drowsy
Hypothyroid
219
Q

What is the first line drug treatment for dementia?

A

Ach esterase inhibitors (same as myaesthenia gravis) to increase effect of synaptic connections and slow down progression.

220
Q

What are the main ADRs of ach esterase inhibitors?

A

Too much parasympathetic-
Bradycardia
SLUDGE
Salivation, sweating, lacrimation, urinary dysfunction, diarrhoea, GI, emesis

221
Q

What is the pathophysiology of Parkinson’s?

A

Loss of dopaminergic neurons in the substantia nitrate leads to a lack of inhibition in the neostriatum and cortex

222
Q

What is the mechanism of action of l dopa?

A

Pro drug that crosses the bbb. Converted to dopamine by DOPA decarboxylase to agonise the remaining dopaminergic receptors.

223
Q

Why must l dopa be given with carbidopa?

A

Peripheral decarboxylase inhibition.

Prevents the l dopa being converted to dopamine before crossing the bbb.

224
Q

What is the mechanism of action of bromocriptine? When is it used?

A

Dopamine receptor agonist. Add on therapy for Parkinson’s

225
Q

What are the main ADRs of bromocriptine?

A

Gambling, addiction, hyper sexuality, psychosis.

226
Q

What is the mechanism of action of COMT inhibitors?

A

Prevents peripheral breakdown of L DOPA

227
Q

What are the symptoms of myaesthenia gravis?

A

Fluctuating fatiguable weakness of skeletal muscle

Ptosis
Double vision
Bulbar dysfunction (dysphagia, dysphonia)

228
Q

What is the first line treatment for myaesthenia gravis?

A

Ach esterase inhibitors (same as dementia)

229
Q

What are the two main types of diarrhoea drugs? Give an example of each.

A

Anti motility eg codeine, loperamide

Bulk forming eg ispaghula (fybogel)

230
Q

Why is loperamide usually the drug of choice for your average diarrhoea? Why is it avoided in IBD?

A

Doesn’t cross the bbb like codeine and much more potent than the others.

Avoid in IBD due to risk of toxic mega colon

231
Q

What are the two best drugs for IBS? Why?

A

Mebeverine - smooth muscle relaxant without anti cholinergic side effects

Ispaghula (fybogel) - treats both constipation and diarrhoea.

232
Q

Give two examples of tyrosine kinase receptors.

A

Growth factor receptor

Insulin receptor