Therapeutics Flashcards
Should you stop a drug for chronic disease in pregnancy?
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
How is absorption altered in pregnancy?
N + V –> increased gastric pH, reduced gastric emptying, increased gut transit time
Increased absorption from IM injections + inhalation due to increased bioavailability
Pharmocokinetics - 4 areas
Absorption, distribution, metabolism, elimination (ADME)
Pharmacokinetic changes in pregnancy
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
Teratogenicity
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
2nd and 3rd trimester of pregnancy
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
Do drugs cross the placenta?
Assume all drugs cross the placenta unless they have a high molecular weight e.g. heparins
1st trimester drugs
Avoid if possible! Only prescribe if expected benefit to mother outweighs risk to fetes e.g. AEDs
Drugs to avoid in 1st trimester
Androgens, cytotoxic drugs, lithium, quinolone abx, retinoids, sodium valproate, thalidomide, warfarin
Drugs to avoid in 2nd and 3rd trimester
ACEi + ARBs, aminoglycosides, NSAIDs + aspirin, opiates + bendodiazepines, sulphonamides, tetracyclines
Does adjustment in pregnancy
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
Drugs when BF?
Drugs can be excreted in milk - greater risk if neonate/premature as immature excretory functions so drugs may accumulate.
What drug characteristics make them better for BF?
High MW e.g. insulin, heparin
High protein binding e.g. warfarin, NSAIDs
Low lipid solubility e.g. loratadine
Lower pH e.g. amoxicillin
Drugs to avoid during BF
Amiodarone, antithyroid drugs, benzodiazepines, lithium salts, radioactive iodine, statins, sulphonamides
AABILSS
Drug effects on lactation?
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
Absorption in children
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
Distribution in children
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
Dosing in children
3 different ways:
Age - for low therapeutic index drugs
Weight - lots
Body surface area - for narrow therapeutic index drugs e.g. chemo
Drugs to avoid in children
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
First pass metabolism in elderly
In elderly - reduced hepatic BF - reduced 1st pass metabolism + greater drug effect. Significant increase in drug bioavailability e.g. nitrates, verapamil
Distribution of drugs in elderly
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
Elimination of drugs in elderly
Really excreted drugs require does adjustment as renal elimination decreases e.g. digoxin, gentamicin, lithium salts, opiates
What problems do pharmacodynamic changes lead to in the elderly?
- 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
Drugs to avoid in renal impairment
NSAIDs - cause nephrotoxicity (interstitial nephritis)
Vancomycin - renally eliminated
Gentamicin - both of above!
aminoglycosides, metformin, nitrofurantoin, potassium, lithium
MANPLN - metformin, aminoglycosides, nitrofurnatoin, potassium, lithium, NSAIDs
Causes of raised troponin apart from ACS
Sepsis
PE
CKD
CCF
3 features of opiate overdose
miosis
coma
respiratory depression
Features of salicyclate overdose
N + V, tinnitus, deafness, sweating + hyperventilation
Features of ecstasy/cocaine overdose
Mydriasis, hyperthermia, tachycardia, arrhythmia and agitation
Drink driving limit for alcohol
Blood - 80mg/100ml
Breath - 35mg/100ml
Drugs to avoid in hepatic impairment
NWSSD - NSAIDs, warfarin, steroids, sedatives, diuretics
Weight changes in AEDs
Valproate, gabapentin - weight gain
Topiramate - weight loss
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
Classes of non-opioid analgesics
Paracetemol
NSAIDs
Antidepressants - amitryptline - SEs = dry mouth, constipation, reduced UO, cardiotoxicity
AEDs - gabapentin, pregabalin
Side effects of morphine
Euphoria, constipation, respiratory depression, euphoria, low BP
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
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
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
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)
Alcohol metabolism
Ethanol (ADH) –> acetylaldehyde (ALDH –> acetate
How does alcohol effect the CNS?
GABA - potentiates (inhibitory)
NMDA - antagonises (excitatory)
Effects 5HT, opioid + DA NT (reward centres)
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
CAGE questionairre
C - cut down amount of drinking
A - annoyed by criticism
G - guilty feelings about drinking
E - eye opener in the morning
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
What is pabrinex?
High potency vitamin B complex - contains high dose thiamine (B1), riboflavin (B2), B6, nicotinamide and vit c
Principles of management of alcoholism
Recognition
ABCDE
Prevent/tx encepalopathy - thiamine + other Bs
Prevent/tx withdrawal - chlordiazepoxide
Paracetemol OD likelihood in amounts
mg/kg
<75 - extremely unlikely
75 - 150 - rare
>150 - possible
How does paracetemol cause toxicity?
Glutathione depletion
Direct oxidising and arylating effects
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
What is a staggered OD?
If a pt takes paracetamol spread over <60mins = staggered
Pharmacological tx of orthostatic hypotension
Fludrocortisone
Midodrine
CHA₂DS₂-VASc
Score for AF stroke risk
- Age
- Sex
- Congestive HF
- HTN
- Stroke/TIA/thromboembolism
- Vascular disease
- DM
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)
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
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
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
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
ARB
e.g. losartan, candesaratan, valsartan
Do not cause cough
same contra-indications as ACE
Also used: HF, CKD
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
Thiazide like diuretics
bendroflumethiazide
Blocks Na-Cl channels in DCT - Na and water loss
SEs: gout, ED, hypercalcaemia
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
K sparing diuretics
Aldosterone antagonists e.g. spironolactone . Low doses in HTN
Also used for: hyperaldosteronism, Conn’s
SEs: hyperkalemia, gynaecomastia, ED
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
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
Why does HF lead to oedema?
Reduced renal BF –> activates RAAS –> Na and water retention –> oedema
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
Treatment for HF with preserved EF
BP control
Symptomatic tx
Categories of arrythmias
Fast/slow
Narrow complex/broad complex
Regular/irregular
Treatment of SVT
Defib pads
Vagal manoeuvres
Carotid sinus massage
Adenosine 6mg IV
If ineffective: verapamil IV slow injection
DC cardioversion if haemodynamically unstable
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
Digoxin
Inhibits Na/K ATPase in cardiac myocytes
SEs: N + V, diarrhoea, fatigue, arrhytmias, confusion
Amiodarone
Prolongs AP duration + effective refractory period in all cardiac tissues
SEs: fibrosis, hepatitis, thyroid dysfucntion, photosensitivity, optic neuritis, orchitis
Drugs that increase INR from warfarin interaction
Cranberry juice
Ciprofloxacin
Clarithromycin
Metronidazole
Warfarin interaction - drugs that decrease INR
Dietary vit K
Rifampicin
Carbamazepine
St Johns wort
Orlistat
Lipase inhibitor - prevents breakdown of dietary fats
SEs: abdo cramps, faecal urgency/incontinence, steatorrhoea
Drugs to help obesity
Orlistat
In DM: GLP1 agonists, SGLT2 inhibitors
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
Main strategies for pharmacotherapy in angina
Slow HR and reduce metabolic demand
Improve blood supply (coronary vasodilatation)
Reduce preload
Reduce afterload
Stable angina drugs
Rate limiting drugs e.g. bblockers, verapamil, diltiazem Nitrates e.g. isosorbide mononitrate CCBs e.g. amlodipine nicorandil ranolazine
Antiplatelet agents
Aspirin
Clopidogrel (prodrug) - requires conversion by CYP450 - used for 1yr post MI but aspirin lifelong
Ticagrelor
Secondary prevention following diagnosis of IHD
Dual antiplatelet therapy - aspirin + clopidogrel B blocker ACEi Statin Smoking cessation
