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