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What are the methods of absorption of a drug?
- - Oral
- - 1st pass absorption - pass through the liver
- - IM and IV - Bypass the 1st pass metabolism - more potent
What are the 2 main components of the body that a drug is distributed?
- - Vascular system - proteins eg albumin
- - Tissues - fat & muscle
(occasionally in ascites and gut collections)
Which organs clear/metabolise drugs?
Liver and Kidney
What is maximum effect (Emax)?
Once this is reached, no further therapeutic effect is achieved by increasing the dose of the drug - due to saturation of receptor sites or exhaustion of metabolites.
Is 4 times the therapeutic dosage.
Increase above Emax = toxicity
- - Inhibits arachidonic acid pathways - COX pathways inhibited
- - Lacks anti-inflammatory effects
- - Inhibits COX pathways - Decrease in prostaglandin synthesis
- - Inhibits TXA2 in platelets and increases clotting time after 1 week.
- - Good for viral disease
NSAIDs (Non-Steroid Anti-Inflammatory Drugs)
- - Good for acute inflammation
- - NEVER give to 3rd trimester pregnant woman
- - Mild blood thinning effects
- - Severe GORD if used long term
- - Tightly controlled meds
- - morphine, fentanyl, oxynorm
- - works at CNS level
- - Side Effects: euphoria, dysphoria, restlessness, skin itch
Causes of muscle spasm?
Acute nerve compression or irritation
Acute injury eg: facet imbrication, sprain etc
Low sodium / hypocalcaemia (Chvostek’s sign)
Chvosteks sign: tapping the facial nerve: twitching
Can also be low in Mg and zinc
- - GABA agonist
- - Safe and effective
- - Addictive if long term
Side effects - falls, memory loss, drowsy
- - More peripheral effect than central
- - GABA agonist - hyperpolarises cell membranes
- - Used mainly with contractures
- - Less sedation than benzo diazapines
- - Rarely used
- - Works outside CNS but can depress it.
- - Inhibits the release of calcium from the sarcoplasmic reticulum of muscles
- - Usually occurs after a significant insult to the nervous system
- - Chronic in nature - > 6 weeks
- - Paresthesias, radiculopathy & dull aching
- - Predisposed by alcoholism, MS, diabetes, HIV, VZV
- - Usually co-morbid diagnosis.
- - Tricyclics - given in low doses
- - SSRI's
- - Opiates
- - Anti-epileptic drugs - best.
What is migraine believed to be a disorder of?
Serotonin and its balancing mechanisms.
4 phases of migraine
- Aura (vasospasm)
- Headache (vasodilation)
Migraine preventative drugs:
- Anti HTN - Propanolol, ACE - inhibitor: Peripheral vaso-constrictor, DONT give to asthmatics
- TCA's - reinforces serotonin dynsfunction theor
- Anti Epileptic Drugs: Valproate, topamax
- Botulinum toxin to cx muscles
What is the action of calcitonin?
Inhibits osteoclasts and blocks bone resorption.
Used in treatment of Pagets, hypercalcaemia and osteoporosis
Sumatriptan, a serotonin agonist, is an anti migraine preparation. It may be given orally (100 mg) or subcutaneously (6 mg). Why are the concentrations so different with the two different routes of administration?
a. oral administration is subject to a high hepatic first pass
b. most of the drug given orally is destroyed in the acid environment of the duodenum
c. higher subcutaneous doses result in potent local vasodilation and oedema
d. the oral form is a solid, the subcutaneous form is a liquid.
a. oral administration is subject to a high hepatic first pass??