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Year 3 > Therapeutics > Flashcards

Therapeutics Flashcards

1
Q

Should you stop a drug for chronic disease in pregnancy?

A

Usually better not to stop as disease may adversely affect the pregnancy e.g. epilepsy, DM, HTN

Less than 30 medicinal molecules are genuine human teratogens

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2
Q

How is absorption altered in pregnancy?

A

N + V –> increased gastric pH, reduced gastric emptying, increased gut transit time

Increased absorption from IM injections + inhalation due to increased bioavailability

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3
Q

Pharmocokinetics - 4 areas

A

Absorption, distribution, metabolism, elimination (ADME)

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4
Q

Pharmacokinetic changes in pregnancy

A

ADME picture is complicated but changes not clinically significant for most drugs. BEWARE drugs with narrow therapeutic index e.g. AEDs, enoxaparin - dosing may need to be altered

Drug effect may be delayed after oral doses but enhanced after IM injections

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5
Q

Teratogenicity

A

Potential for a drug to cause foetal malformations + affects the embryo 3-8wks after conception

3-8wks is period of highest risk as organs are formed

Pre-embryonic phase (days 0-14 after conception) = all or nothing effect = recovery or spontaneous loss

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6
Q

2nd and 3rd trimester of pregnancy

A

Can affect growth (IUGR) and functional development or have toxic effects on tissues

Adverse effects on neonate if given shortly before/during labour e.g. diazepam or pethidine

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7
Q

Do drugs cross the placenta?

A

Assume all drugs cross the placenta unless they have a high molecular weight e.g. heparins

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8
Q

1st trimester drugs

A

Avoid if possible! Only prescribe if expected benefit to mother outweighs risk to fetes e.g. AEDs

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9
Q

Drugs to avoid in 1st trimester

A

Androgens, cytotoxic drugs, lithium, quinolone abx, retinoids, sodium valproate, thalidomide, warfarin

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10
Q

Drugs to avoid in 2nd and 3rd trimester

A

ACEi + ARBs, aminoglycosides, NSAIDs + aspirin, opiates + bendodiazepines, sulphonamides, tetracyclines

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11
Q

Does adjustment in pregnancy

A

Maternal drug conc usually lower than non-pregnant when taking same dose. Foteal + placental metabolism also affects drug concn. Some drugs may need increasing e.g. lamotrigine or enoxaparin

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12
Q

Drugs when BF?

A

Drugs can be excreted in milk - greater risk if neonate/premature as immature excretory functions so drugs may accumulate.

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13
Q

What drug characteristics make them better for BF?

A

High MW e.g. insulin, heparin
High protein binding e.g. warfarin, NSAIDs
Low lipid solubility e.g. loratadine
Lower pH e.g. amoxicillin

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14
Q

Drugs to avoid during BF

A

Amiodarone, antithyroid drugs, benzodiazepines, lithium salts, radioactive iodine, statins, sulphonamides
AABILSS

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15
Q

Drug effects on lactation?

A

Drugs affecting DA activity cause main effect on lactation (through prolactin changes)
Early postpartum use of oestrogen may reduce milk vol - use progesterone contraception

Da agonists decrease milk production
Da antagonists promote lactation when inadequate

Some drugs may affect infant’s suckling reflex e.g. phenobarbital

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16
Q

Absorption in children

A

Oral - developmental changes in absorptive surfaces of gut, GI motility + intraluminal pH alter rate + extent
Absorption also affected by slower gastric emptying which takes 6-8m to reach adult levels
1st pass metabolism increased for some drugs

Percutaneous absorption increased the younger the pt due to thinner stratum corneum + increased skin hydration

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17
Q

Distribution in children

A

For water soluble drugs - higher doses per kg of bodyweight must be given to children than adults e.g. gentamicin (younger the child - greater their total body water as a % of weight)

For protein bound drugs - plasma proteins e.g. albumin reduced in neonates

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18
Q

Dosing in children

A

3 different ways:
Age - for low therapeutic index drugs
Weight - lots
Body surface area - for narrow therapeutic index drugs e.g. chemo

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19
Q

Drugs to avoid in children

A

IV chloramphenicol –> Grey baby syndrome (in neonates causing cyanosis, grey skin, reduced BP, CV collapse)

Aspirin –> Reye’s syndrome (mitochondrial damage leading to rash, vomiting + liver damage) <16yrs

Tetracycline –> growing teeth + bone so not given to <12yrs

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20
Q

First pass metabolism in elderly

A

In elderly - reduced hepatic BF - reduced 1st pass metabolism + greater drug effect. Significant increase in drug bioavailability e.g. nitrates, verapamil

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21
Q

Distribution of drugs in elderly

A

Increased body fat –> increased Vd of lipid soluble drugs so they accumulate e.g. diazepam

Decrease in total body water - decreased Vd for water soluble drugs so lower doses of water soluble drugs required e.g. digoxin

Reduced plasma protein conc –> reduction in plasma protein binding causes an increase in ‘free’ drug e.g. phenytoin so increased risk of toxicity

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22
Q

Elimination of drugs in elderly

A

Really excreted drugs require does adjustment as renal elimination decreases e.g. digoxin, gentamicin, lithium salts, opiates

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23
Q

What problems do pharmacodynamic changes lead to in the elderly?

A
  • Changes in R sensitivity
  • Reduction in R no.
    –> increases sensitivity to several drugs e.g. decreased Da Rs leads to increased risk of EPS SEs
    Reduced baron function leads to increased hypoTN on antiHTI therapy
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24
Q

Drugs to avoid in renal impairment

A

NSAIDs - cause nephrotoxicity (interstitial nephritis)

Vancomycin - renally eliminated

Gentamicin - both of above!

aminoglycosides, metformin, nitrofurantoin, potassium, lithium
MANPLN - metformin, aminoglycosides, nitrofurnatoin, potassium, lithium, NSAIDs

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25
Causes of raised troponin apart from ACS
Sepsis PE CKD CCF
26
3 features of opiate overdose
miosis coma respiratory depression
27
Features of salicyclate overdose
N + V, tinnitus, deafness, sweating + hyperventilation
28
Features of ecstasy/cocaine overdose
Mydriasis, hyperthermia, tachycardia, arrhythmia and agitation
29
Drink driving limit for alcohol
Blood - 80mg/100ml | Breath - 35mg/100ml
30
Drugs to avoid in hepatic impairment
NWSSD - NSAIDs, warfarin, steroids, sedatives, diuretics
31
Weight changes in AEDs
Valproate, gabapentin - weight gain | Topiramate - weight loss
32
Drug OD treatments
Paracetemol - N-acetylcysteine - 3 bags over 21h Stimulate OD - diazepam 10mg IV Sedative (heroin) - Naloxone Benzodiazepine - flumazenil Ethylene glycol/methanol - fomepizole (or ethanol!) bromocriptine - used in prolactinoma
33
Classes of non-opioid analgesics
Paracetemol NSAIDs Antidepressants - amitryptline - SEs = dry mouth, constipation, reduced UO, cardiotoxicity AEDs - gabapentin, pregabalin
34
Side effects of morphine
Euphoria, constipation, respiratory depression, euphoria, low BP
35
Classes of anti-psychotic drugs
Typical/1st gen = chlorpromazine, haloperidol - EPS side effects (D2 R antagonists) so due to reduced DA in nigro-striatal path Atypical/2nd gen = clozapine, risperidone - act on serotonine, NA, and DA to avoid parkinson like effects - cause weight gain and blurred vision
36
2 types of adverse drug reactions
Type A - 'dose-dependent' and predictable on the base of the pharmacology of the drug Type B - bizarre - not predictable
37
3 steps of the WHO pain ladder
Non-opioid analgesics e.g. paracetamol Mild opoiod e.g. codeine Strong opiod e.g. morphine Can add NSAIDs at any stage
38
Where is alcohol absorbed in the body?
Duodenum-jejunum = >80% Rate of absorption is conc dependent + related to gastric emptying W more affected by alcohol as have more fat + less h2o than men (alcohol is found in water component so they have less h2o so higher conc)
39
Alcohol metabolism
Ethanol (ADH) --> acetylaldehyde (ALDH --> acetate
40
How does alcohol effect the CNS?
GABA - potentiates (inhibitory) NMDA - antagonises (excitatory) Effects 5HT, opioid + DA NT (reward centres)
41
Alcohol - drug interactions
CNS drugs e.g. tricyclic ADs, benzos, phenothiazines - increased drowsiness + sedation AntiHTN drugs - enhanced hypotensive effect Warfarin - affects anticoagulant control Metronidazole/ketoconazole - inhibit aldehyde dehydrogenase causing accumulation of acetylaldehyde
42
CAGE questionairre
C - cut down amount of drinking A - annoyed by criticism G - guilty feelings about drinking E - eye opener in the morning
43
What is delirium tremens?
Occurs 48-72h after withdrawal of alcohol Chracacterised by agitation, confusion, paranoia, visual + auditory halluciantions *tonic clonic seizures occur 24-48h
44
What is pabrinex?
High potency vitamin B complex - contains high dose thiamine (B1), riboflavin (B2), B6, nicotinamide and vit c
45
Principles of management of alcoholism
Recognition ABCDE Prevent/tx encepalopathy - thiamine + other Bs Prevent/tx withdrawal - chlordiazepoxide
46
Paracetemol OD likelihood in amounts
mg/kg <75 - extremely unlikely 75 - 150 - rare >150 - possible
47
How does paracetemol cause toxicity?
Glutathione depletion | Direct oxidising and arylating effects
48
Timings to antidote in paracetemol OD
8hr rule Provided a pt is treated in 8hrs - not at risk of significant liver damage - worth waiting for plasma paracetamol conc if will be back before 8hrs
49
What is a staggered OD?
If a pt takes paracetamol spread over <60mins = staggered
50
Pharmacological tx of orthostatic hypotension
Fludrocortisone | Midodrine
51
CHA₂DS₂-VASc
Score for AF stroke risk - Age - Sex - Congestive HF - HTN - Stroke/TIA/thromboembolism - Vascular disease - DM
52
HAS-BLED
Score for major bleeding risk - estimates risk of bleeding for pts on anti-coag to assess risk benefit in AF care - HTN (uncontrolled or >160) - Renal disease - Liver disease - Stroke hx - Prior major bleeding or predisposition - Labile INR (unstable/high INRs) - Age (>65) - Medication usage predisposing to bleeding (aspirin, clopidogrel, NSAIDs) - Alcohol use (>8 drinks/wk)
53
Treatment of acute severe asthma
``` O2 Nebulised salbutamol Prednisolone 40-50mg PO or hydrocortisone 100mg IV if response poor.. Inhaled ipatropium IV Mg sulphate, aminophylline ```
54
HTN definitions
Stage 1: clinic of 140/90 or ABPM 135/85 Stage 2: clinic of 160/100 or ABPM of 150/95 Severe: 180/110
55
Anti HTN
Aged under 55 = ACEi (ARB if can't tolerate) >55 or Black-afro = CCB Then add on the opposite so A + C Then add on thiazide like diuretic A + C + D For resistant HTN - consider another diurectic, alpha blocker (doxazosine) or b-blocker
56
ACEi
e.g. ramipril, perindopril SE: dry cough (BK) Rare SE: angiodema, hyperkalemia Check U+Es 1 wk after commencing Contra-indications = pregnancy, BF Also used: post-MI, HF, CKD
57
ARB
e.g. losartan, candesaratan, valsartan Do not cause cough same contra-indications as ACE Also used: HF, CKD
58
CCB
Dihydropyridines e.g. amlodipine, felodipine Main SEs: ankle oedema, acid reflux, gingival hyperplasia Also used for: raynauds, angina Non-dihydropyridines e.g. diltiazem (heart/BVs), verapamil (heart) SEs: worsening HF, bradycardia, heart block Also used for: tachyarrhytmias, angina, migraine, cluster headache
59
Thiazide like diuretics
bendroflumethiazide Blocks Na-Cl channels in DCT - Na and water loss SEs: gout, ED, hypercalcaemia
60
Loop diuretics
e.g. furosemide block Na-K-Cl pump in thick ascending limb SEs: electyolyte disturbance, polyuria, dehydration used in: pulmonary oedema, CCF, nephortic syndrome, ascites
61
K sparing diuretics
Aldosterone antagonists e.g. spironolactone . Low doses in HTN Also used for: hyperaldosteronism, Conn's SEs: hyperkalemia, gynaecomastia, ED
62
Beta blockers
reduced HR and force of contraction reduce renin release B1: increased cardiac rate + force B2: vasodilation, bronchodilation, SM relaxation, hepatic glycogenolysis, muscle tremor cardioselective (B1) = bisoprolol, metoprolol non selective: propanolol SEs: tiredness, bracycardia, bronchoconstriction, ED, hypoglycaemia
63
Postural hypotension
>20mmHg drop in SBP or >10mmHg drop in DBP on standing Adrenal insuffiency, autonomic failure (DM, alcoholism, PD), drugs Pharamcological management includes fludrocortisone or midodrine
64
Why does HF lead to oedema?
Reduced renal BF --> activates RAAS --> Na and water retention --> oedema
65
Treatment for HF with reduced EF (systolic)
ACE/ARBs - reduce preload + afterload B-blockers - reduced symp overactivity Aldosterone antagonists - reduce mortality Diuretics - treat oedema - reduces preload Digoxin - increases force of contraction - useful when HF caused by AF
66
Treatment for HF with preserved EF
BP control | Symptomatic tx
67
Categories of arrythmias
Fast/slow Narrow complex/broad complex Regular/irregular
68
Treatment of SVT
Defib pads Vagal manoeuvres Carotid sinus massage Adenosine 6mg IV If ineffective: verapamil IV slow injection DC cardioversion if haemodynamically unstable
69
Atrial fibrillation
Paraoxysmal Persistent Permanent Tx: anticoagulant and rate control OR rhythm control Anti-coag: warfarin or DOACs Rate: b-blockers, diltiazem, verapamil, digoxin Rhythm: amiodarone, flecainide
70
Digoxin
Inhibits Na/K ATPase in cardiac myocytes SEs: N + V, diarrhoea, fatigue, arrhytmias, confusion
71
Amiodarone
Prolongs AP duration + effective refractory period in all cardiac tissues SEs: fibrosis, hepatitis, thyroid dysfucntion, photosensitivity, optic neuritis, orchitis
72
Drugs that increase INR from warfarin interaction
Cranberry juice Ciprofloxacin Clarithromycin Metronidazole
73
Warfarin interaction - drugs that decrease INR
Dietary vit K Rifampicin Carbamazepine St Johns wort
74
Orlistat
Lipase inhibitor - prevents breakdown of dietary fats SEs: abdo cramps, faecal urgency/incontinence, steatorrhoea
75
Drugs to help obesity
Orlistat | In DM: GLP1 agonists, SGLT2 inhibitors
76
Drugs for hyperlipidaemia
Statins - HMG CoA reductase inhibitor Ezetimibe - inhibits intestinal absorption of cholesterol Fibrates PCSK9 inhibitors - monoclonal AB which binds to R for LDL cholesterol
77
Main strategies for pharmacotherapy in angina
Slow HR and reduce metabolic demand Improve blood supply (coronary vasodilatation) Reduce preload Reduce afterload
78
Stable angina drugs
``` Rate limiting drugs e.g. bblockers, verapamil, diltiazem Nitrates e.g. isosorbide mononitrate CCBs e.g. amlodipine nicorandil ranolazine ```
79
Antiplatelet agents
Aspirin Clopidogrel (prodrug) - requires conversion by CYP450 - used for 1yr post MI but aspirin lifelong Ticagrelor
80
Secondary prevention following diagnosis of IHD
``` Dual antiplatelet therapy - aspirin + clopidogrel B blocker ACEi Statin Smoking cessation ```

Year 3 (14 decks)

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