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Pharmacology S4 Flashcards

1
Q

Insulin Therapy

Fast acting native insulin

A

Actrapid, Humulin S

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2
Q

Insulin Therapy

Fast acting analogues

A

Novorapid, Humalog

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3
Q

Intermediate acting native insulin (NPH)

A

Insulatard, Humulin I

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4
Q

Insulin Therapy

Intermediate / long acting analogues

A

Levemir, Glargine

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5
Q

Different Insulin Regimens

Pre-mixed insulin regimen

A

Humalog Mix 25, Novomix 30, Mixtard 30

◼ ◼

Taken twice daily with or before meals Lacks flexibility but only twice per day

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6
Q

Basal Bolus regimen features

A

Intermediate or long acting insulin as background Fast acting insulin with meals Flexible but up to five times per day

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7
Q

Side effects of insulin therapy

A

Hypoglycemia

Lipodystrophy

  1. Allergy
  2. Weight gain
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8
Q

Symptoms of hypoglycemia

A 
Headache 
Vertigo 
Diaphoresis
Shaking
Inc appetite
Blurred vision 
Weakness/ fatigue 
Anxiety
Tachycardia 
Confusion
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9
Q

Metformin

Action?

A

Decreased hepatic glucose output

mitochondria

Increased glucose uptake in skeletal muscle and fat

GLUT 1 and GLUT 4

Special benefits in overweight patients

Weight-neutral or weight-reducing Improvement in cardiovascular outcomes

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10
Q

Metformin side effect

A

Side effects mitigated by slow dose titration (GI upset)

Usual maximum dose is 1g bd

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11
Q

Metformin contraindicated

A

Contraindicated in metabolic failure (renal failure, hepatic failure and acute heart failure)

Stop before radiocontrast media and surgery

Does not cause hypoglycaemia

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12
Q

Action of Sulphonylureas

A

Enhances insulin secretion (irrespective of ambient glucose level)

Specific receptor on beta cell Closure of ATP-sensitive potassium channel Influx of calcium and extrusion of secretory granules

Reduces fasting and postprandial glucose

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13
Q

Sulphonylureas half life

Give examples of drug with long Half life& which one is the preferred type of drug

A

Half-life important

Glibenclamide long half life

Can lead to prolonged hypoglycaemia, especially in elderly

Gliclazide short half-life and, therefore, preferred agent

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14
Q

Sulphonylureas side effect

A

Can cause hypoglycaemia

Associated with weight gain

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15
Q

Repaglinide action

A

Non-sulphonylurea insulin secretagogue Three receptors.

Similar action to sulphonylureas. Identical efficacy

Requires glucose to have effect

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16
Q

Repaglinide half life ?

A

Short plasma half-life

◼

0.5mg with meals, max 16 mg/day

◼

Weekly increase in dose if required

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17
Q

Good effect of Repaglinide

A

Weight neutral Less severe hypoglycaemia.

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18
Q

Acarbose action

A

a-glucosidase inhibitor

◼ ◼

Delays absorption of carbohydrates Allows beta-cell time to augment response

Decreases HbA1c by 1%, fpg by 1.5mmol/l No change in weight Modest decrease in triglyceride Dosage schedule

◼

With first bite. Start low, increase every 2 weeks.

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19
Q

Acarbose CI

A

Contraindicated in renal failure, IBD & cirrhosis

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20
Q

side effects of Acarbose

A

Rarely used owing to poor efficacy and significant GI side effects
Bloating
Constipation
Git distress

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21
Q

Thiazolidenediones actions

A

PPARg-agonists Improve insulin sensitivity

◼

Liver, skeletal muscle and adipocytes

22
Q

Thiazolidenediones side effect

A

Durable effect on glycaemia Associated with weight gain

◼

Part of action of these drugs

23
Q

Thiazolidenediones CI

A

Contraindicated in heart failure

Recent controversy about CV effects and increased risk of bone fractures

24
Q

Pharmacology of Type 2 Diabetes

A

Metformin

🌼
First choice in overweight or obese unless contraindicated

Sulphonylureas and their derivatives Thiazolidinediones

Insulins

Including inhaled insulin (no longer available)

Newer agents

◼

◼

◼ ◼

GLP 1 analogues

◼

GLP 1 is produced by L cells of the small intestine

DPP4 inhibitors

◼

DPP4 is the enzyme that breaks down GLP1

Sodium-glucose transporter inhibitors Colesevelam and bromocriptine

25
GLP1analogues?
Exenatide is An injectable GLP1 analogue
26
DPP4 Inhibitors
and the gliptins are oral DPP4 inhibitors
27
Adverse effects of GLP-1 analogues
All of the GLP-1 receptor agonists may increase the risk of pancreatitis Cases of renal impairment and acute renal injury have been reported in patients taking exenatide. Both exenatide and liraglutide stimulate thyroidal C-cell (parafollicular) tumors in rodents. The drugs, however, should not be used in persons with a past medical or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) syndrome type 2
28
GLP-1 analogues CI
The drugs, however, should not be used in persons with a past medical or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) syndrome type 2
29
SGLT2 inhibitors give examples
Canagliflozin and empagliflozin dapagliflozin
30
SGLT2 inhibitors side effect
The osmotic diuresis can also cause intravascular volume contraction and hypotension Canagliflozin and empagliflozin caused a modest increase in LDL cholesterol levels (4–8%) In clinical trials patients taking dapagliflozin had higher rates of breast cancer (nine cases versus none in comparator arms) and bladder cancer (nine cases versus one in placebo arm
31
SYNTHETIC AMYLIN ANALOGUE:give E
Pramlinitide
32
SYNTHETIC AMYLIN ANALOGUE: Mechanism
Pharmacological effects ◼ ◼ ◼ 1. 2. 3. Reduces glucagon secretion Slows gastric emptying rate Centrally decreases appetite
33
Bromocriptine adverse events
The main adverse events are nausea, fatigue, dizziness, vomiting, and headache
34
mechanisms of dopamine agonist lowering BG level
Bromocriptine the dopamine agonist, in randomized placebo-controlled studies lowered HbA1c by 0–0.2% compared with baseline and by 0.4–0.5% compared with placebo. The mechanism by which it lowers glucose levels is not known. The main adverse events are nausea, fatigue, dizziness, vomiting, and headache
35
Obesity Medication Three specific drugs
Orlistat ◼ Gastric and pancreatic lipase inhibitor ◼ Theoretical deficiency of fat soluble vitamins Sibutramine ◼ Norepinephrine and serotonin reuptake inhibitor ◼ ◼ Contraindicated in depression Blood pressure must be closely monitored Rimonabant ◼ ◼ Endocanabinoid antagonist - newest agent Contraindicated in depression
36
Side effect of metformin
Weight reducing GI upset Nausea & vomiting
37
Statins | Mechanism of action
Statins work by inhibiting the HMG~CoA reductase enzyme in the liver which would normally be used in the production of cholesterol. Decrease in the plasma concentration of cholesterol causes an increase in the number of LDL receptors, which in turn increases the rate of LDL removal from the plasma. Secondary importance of statins appear to be as acting as antiinflammatories, plaque reduction, and reduction in thrombotic risk.
38
Short acting statins give examples شوكت ننطي مثل هيج نوع من الأدوية وكذلك شنو الفرق عن ال longer half life
Short acting statins, such as simvastatin, can have t 1 / 2 of 1-4 hours and are usually given at night to coincide with peak cholesterol production in the early morning. Others have t 1 / 2 of around 20 hours so can be given at any time of day and have superior efficacy. Statins will show a non-linear pharmacokinetics.
39
Adverse Drug Reactions of statins
Statins appear to be well tolerated by the general population. The only significant ADRs seen involve increased transaminase levels and myopathies (more common with increasing age, can be checked by testing the CPK levels), yet only seen in 0.1% of individuals who take high doses. Other miscellaneous complaints reported include GI complaints, joint pain, and headaches.
40
Cholesterol Absorption Inhibitors
Cholesterol Absorption Inhibitors act by blocking the specific cholesterol transport protein NPC1L1 in the brush border. This causes a reduction in the amount of dietary cholesterol reaching the liver, which in turn causes a secondary upregulation of LDL transporter expression. Both of these combine to cause a lowered circulating cholesterol level
41
Cholesterol Absorption Inhibitors give examples
Ezetimibe can reduce LDL levels by around 15-20% and is normally given as a monotherapy is statin-intolerant patients; if used synergistically with statins, it can cause a 20% reduction in LDL levels (which is actually better than simply doubling the dose of a statin as it reduces the ADRs of the statin).
42
Fibrates | يستخدم بشكل رئيسي لتخفيض ؟
Fibrates act on the Peroxisome Proliferator-Activated Receptor-α (PPARα), which acts to significantly reduce triglyceride production, and also lowers LDL and raises HDL. Whilst they can be used in conjunction with statins, they are mainly used directly for hypertriglyceraemias.
43
Fibrates C.I.
They are not to be used with hepatic or renal dysfunction, as well as any pre-existing gall-bladder disease due to risk of cholelithiasis.
44
Nicotine’s acid give example
Niacin Inhibit hormone sensitive lipase in the adipose tissue so decreasing the levels of free fatty acids synthesized in adipose tissue & decreasing levels of free fatty acids reaching the liver which lead to decrease VLDL & LDL
45
Bile acids sequestrants | Mechanism of action
these drugs lead to increase excretion of bile acids by formation of insoluble complexes which lead to to increase synthesis of bile acids which made of cholesterol lead to increase expression of LDL receptors hence lowering LDL levels
46
Bile acid sequestrants | Give examples of
Colesevelan Colestipol Cholestyramin
47
Fibrates give examples
Fenofibrate | Gemfibrozil
48
Omega 3 fatty acids give examples
DHA & EPA | Icosapent ethyl
49
Omega 3 fatty acids mechanism of action
Inhibit VLDL &TG synthesis in the liver
50
PCSK9 INHIBITORS | Give examples
Evolocumab | Alirocumab
51
PCSK9 inhibitors | ميكانيزم
هذا أنزيم يكسر ال LDL رسبتورز فبالتالي مراح يبقى ريسبتور فهذا راح يثبطه ويبين الرسبترات لوقت اطول فيقل ال LDL

S6 (20 decks)

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