GSS Past Paper Qs Flashcards
Excess acid in the stomach can cause
Heart Burn
Indigestion
Acid Reflux
name key sells found in the gastric glands
- Chief Cells
- Parietal Cells
- Mucus secreting cells
- Hormone secreting Cells
what does stomach acid do?
deactivates ingested bacteria and denatures ingested proteins to allow for efficient protease reactions
Here is a picture of histamine conformers. Which of the two conformations bind to H1 and H2?
The trans conformer. It has les steric hinderance than gauche
What is the name of this molecule and what is its pka, and shape in space
Guanidine - pKa = 14.5, planar shape
Here are some groups. What is their pKa values? Additionally, what is the pKa value of aliphatic amines, and what is the pka of an aromatic amine?
H
Ph
Ch3CO
NH2CO
MeO
CN
NO2
aromatic amines have pH of 4
Aliphatic amine has a pKa of 10
H = 14.5
Ph = 10.8
Ch3CO = 8.33
NH2CO = 7.9
MeO = 7.5
CN = -0.4
NO2= -0.9
What groups are critical for H2 receptor antagonist activity
Sulfur introduced an inductive effect on the side chain and also the CH3 introduced an inductive effect at C5, resulting in increase in electron densitiy at N1 and a decrease in electron density at N3. This facillitates the dissociation of the N3-Hydrogen to predominate the desired tautomer that characterises antagonist activity.
What is this structure and what is the pKa of the ring? and What makes it a successful drug?
Cimetidine - it has an imidazole ring which has a pKa of 14.5. if present the ‘t’ tautomer will predominate and it will be selective to H2 receptors.
what is this structure suggest why it lasts longer than cimitedine
Ranitidine - The tertiary amine side chain allows the formation of salts
what is this structure and how does it work, what is it’s pKa and why is it so goddamn specific
Omeprazole - Proton Pump Inhibitor. It is a prodrug that is tranformed within the acidic canaliculi of the parietal cells to its active form, a sulfenamide.
The sulfenamide reacs with thiol groups in the ATPase enzyme, forming a disulfide link which inactivates the enzyme.
it has a pKa of 4.0 and is a weak base. Thus it is ionised in the stomach into its active species. Specific because This active species is a permanent cation and cannot escape the canaliculi.
Provide the mechanism for Omeprazole that forms this the active sulfenamide
what determines the extent to which the PPI accumulates in the canalicular lumen?
the pKa and the hydrophobicity
How do glucose meters work?
- The meter is first calibrated to match the test strip
- When blood is placed onto the test strip, it reacts with a glucose oxidase producing gluconic acid from the glucose in the blood.
- At the other end of the test strip, the meter tranfers a current to the test strip.
- The Test strip has electric terminals which allow the meter to measure the current between the terminals
- At the electrode surface, the current is detected. Measures the amount transferred.
- can take up to 5-60 seconds depending on model
state the key liver enzymes and how they function
Alanine aminotransferase (ALT)
Aspartarte aminotransferase (AST)
Alkaline phosphatase (ALP)
Gamma glutamyl transferase (GGT or ‘Gamma GT’)
how does the liver influence drug metabolism
- Distribution of drugs may be altered:
- ↓ protein binding in cholestasis as bile is diverted from hepatocytes to blood + competes for protein binding sites
- Ascites - drugs may deposit in peritoneal cavity
- Elimination may be reduced in cholestasis reduced formation of water-soluble conjugates that can be excreted.
- For high extraction ratio drugs (i.e drugs that face high first-pass metabolism) they may experience increased bioavailablility
- varices formation may mean drugs can bypass liver alltogether.
Senna Calculates the percentage content of hydroxyantracene glycosides expressed as sennoside B. Rather than sennoside B itself. Why?
It is very difficult to separate the individual sennosides in Senna (A,B,C,D)
In order to calculate the extinction coefficient, the molecular weight of each sennoside is required
All the sennosides have the same biological activity
Sennosides: A + B = same molecular weight
Sennosides C + D = give same UV absorption as A and B
state how the skin is involved in temperature regulation
- Blood vessel innervation to dermis
- Heat exchange regulates body temperature via regulation of heat gain and heat loss
- Heat loss is regulated by altering blood flow through the capillaries in the dermal papillae
- Vasodilation stimulated by local production of bradykinin
- arrector pili muscle contracts and relaxes.
state antiemetic drugs and their mechanisms
5HT3 Antagonists: Ondansetron (post-op nausea and vomiting)
D2 Antagonists: Domperidone, Prochloperazine
Inhibitors of the Vomiting Centre: Hyoscine, Promethazine
Dexamthazone: Anti-emetic corticosteroid (post-op nausea and vomiting)
5 conditions for topical steroids
- Insect Bite and Sting Reactions
- Atopc Eczema
- Atopic Dermatitis
- Psoriasis
- Inflammation of the external ear (Otitis Externa)
cold sores. what is it and otc treatment
caused by herpes simplex virus - treated with aciclovir antiviral agent.
can also give Anaesthetics for symptomatic relief e.g lidocaine
what is psoriasis and how to treat
- Chronic inflammatory skin disease
- Increased epidermal cell turnover thickening and scaling
- Inflammatory cell infiltration
- Relapsing
Can be caused by:
- Stress
- Drugs (b-blockers, lithium, antimalarials, withdrawal of systemic steroids)
- Streptococcal infection
- Hormonal events
what is eczema and how does it differ from dermatitis
Impaired barrier function
- Maybe due to defect in lipid production that normally holds keratinocytes firmly together
- Causes great water loss, dry cracked skin
- Easier entry of irritants and allergens cause an inflammatory
response
• Acute Vs Chronic
mechanisms of drugs to increase their absorption into skin
Penetration enhancers (e.g Urea)
Pro-drugs to enhance lipophilicity
Ion pairing - pairing up the drug with an ion e.g lidocaine hcl to cross stratum corneum
Changing the thermodynamic activity of drug (super saturated systems),
vesicles (liposomes)
what are the phases of acid secretion
ten key points about skin physiology
- Largely there as a protective barrier against external forces; protects against loss of moisture, microbial infection etc.
- Stabilises blood pressure and temperature (site of heat loss for the body)
- Mediates sensitisation of Temperature, touch and pain
- HYPODERMIS (subcutaneous tissue - fatty insulating layer; at the very base of the skin)
- DERMIS (The middle layer of the skin of which contains blood vessels, hair follicle and sweat glands)
- EPIDERMIS (The top layer of the skin)
The epidermis provides one of the major barriers to drug absorption through the skin.
- Stratum corneum is the site for suncreens, antimicrobials and antiseptics
- Lower epidermis is the site for corticosteroids, cytotoxics and antiviral and antihistamines.
- appendages - sites of antimicrobials, acne and infection of follicle treatment
- deeper tissues/systemic - site of hormones and nicotine
what is the importance of bile salts and what mechanisms are fats absrobed across the small intestine
alcohol withdrawal signs and treatment
Potts and Guys Equation
RTS Acne. What drugs could make it worse?
high progestogen oral contraceptives, lithium
Treatments:
Salicylic acid & salicylates
Mode of action: antifungal property of salicylic acid helps promote shedding of cells from skin surface. It is effective against non-inflammatory acne lesions as it unclogs pores
Benzoyl peroxide
- Mode of action: antibacterial & removes dead skin cells
- Over 12 Years old
- Start on lower strengths
- ok in pregnancy
Light therapy
Oxy Clearlight
light therapy at a specific and safe wavelength to trigger a biological reaction that kills the P.acnes bacteria which in turn leads to reduced inflammation and healing
Self care
- Do not wash more than twice a day.
- Use a mild soap / cleanser + lukewarm water
- Do not scrub / use abrasive soaps, cleansing granules, astringents, or exfoliating agents (advise use of a soft
- wash-cloth and fingers instead).
- Should not attempt to ‘clean’ blackheads. Scrubbing or picking acne is liable to worsen the condition.
- Ideally, should avoid excessive use of make-up and cosmetics (non-comedogenic, water-based product
- should be used sparingly)
- Remove makeup at night.
- Use a fragrance-free, water-based emollient if dry skin is a problem (several topical acne drugs dry the
- skin). The use of ointments or oil-rich creams should be avoided as these can clog pores.
5 local side effects and 2 systemic side effects of topical corticosteroids
- Spread and worsening of untreated infection
- thinning of the skin
- Reddening of skin
- stretch marks
- contact dermatitis
Systemic:
Adrenal suppression; cushings syndrome
5 examples of steroids and doses
Hydrocortisone cream 1% - mild inflammatory skin disorders e.g eczemas and nappy rash 1-2bd
Clobetasone Butyrate 0.05% - more potent, for Eczema and dermatitis of all types. 1-2bd
Bethamethasone Valerate 0.025% - severe inflammatory disorders such as eczemas that were unresponsive. 1-2bd
Clobetasol Propionate 0.05% - Psoriasis 1-2bd for 4weeks max 50g per week
classes of steroids and their uses
Adrenal Corticoids e.g Prednisolone
Estrogens e.g transdermal delivery of estradiol
Androgens - Testosterone gel to increase testosterone
Progesterones
Anabolic steroids
Outline the two proposed mechanisms of corticosteroids
Genomic action and Non Gemonic action (faster)
Genomic:
Specific binding to cytoplasmic nuclear receptors occurs. Other transcription factors may be involved.
Gene activation or repression occurs by direct DNA binding of the steroid-receptor complex to recognition sites in the promoter regions associated with up-regulation or down-regulation.
Gene repression can occur through protein-protein cross talk.
Non-Genomic:
Involves Membrane bound steroid receptors, Intracellular receptors and other non-specific actions. Glucocorticoids at @ gene level to reduce inflammation by promoting transcription of some genes and inhibiting transcription of others.
what are the 5 key LFTs
Test Parameters:
Albumin
Hypoalbuminaemia = feature of advanced chronic liver disease (LD)
Bilirubin
An increase means a blockage in bile flow
Aminotransferase (AST and ALT)
An increase means hepatocellular damage
Gamma-glutamyltransferase (γGT)
Sensitive to drugs and alcohol
Alkaline phosphatase (ALP)
An increase means blockage of bile flow
